Organ Donation in Ontario: a Guide for Critical Care Residents 1St Edition

Organ Donation in Ontario: A Guide for Critical Care Residents 1st Edition

NDD V025 Organ Donation in Ontario: A Guide for Critical Care Residents 1st. Edition

Edited by Pierre Cardinal MD FRCPC MScEpi

Contributors: Ian M Ball, Janice Beitel, Kim Bowman, Pierre Cardinal, Sonny Dhanani, Ronish Gupta, Mike Hartwick, Andrew Healey, Eli Malus, Edwin Poon, Louise Pope-Rhoden, Sam Shemie, Karim Soliman, Sabira Valiani, Alissa Visram, Lindsay Wilson

Produced by the Trillium Gift of Life Network and the Practice Performance and Innovation Unit of the Royal College of Physicians and Surgeons of Canada

Copyright © (2016) Trillium Gift of Life Network All rights reserved. This material may be reproduced in whole or in part for educational, personal or public non-commercial purposes only. Written permission from the Trillium Gift of Life Network is required for all other uses.

Disclaimer All material found in this guide, including text, images, audio and other formats, was created for informational purposes only. The content is not intended to be a substitute for professional medical consultation, diagnosis, treatment or care of actual patients. Always seek the advice of other qualified health providers with any questions you may have regarding a medical situation, medication or procedure described in this guide. Never disregard professional medical consultation or delay seeking it because of something you have read in this guide. The Trillium Gift of Life Network and the Royal College of Physicians and Surgeons of Canada do not recommend or endorse any specific tests, products, procedures, opinions or other information that may be mentioned within this guide or the content to which it links. The Trillium Gift of Life Network, the Royal College of Physicians and Surgeons of Canada, and the authors assume no responsibility for any circumstances arising out of the use, misuse, interpretation or application of any information within this material. Reliance on any information within the guide or associated web content is solely at your own risk.

ISBN: 978-0-9951644-0-6 Ian M Ball Eli Malus Contributors MD, FRCPC MD, FRCPC

This eBook was made possible through the Janice Beitel Edwin Poon generous contribution of time and effort of our RN, MScN, CNCC(c) BSc, RRT/RRCP, MBA esteemed colleagues.

Funding for this ebook was provided by the Kim Bowman Louise Pope-Rhoden Trillium Gift of Life Network, working in RN, BScN, Med RN cooperation with the Royal College of Physicians and Surgeons of Canada. Pierre Cardinal Karim Soliman The Trillium Gift of Life Network would also MD, FRCPC, MScEpi MD, FRCPC like to acknowledge the leadership of Canadian Blood Services (Canadian Council for Donation and Transplantation) as well as members of the Sonny Dhanani Sam Shemie MD FRCPC MD, FRCPC national forums that contributed to the development of the leading practice guidelines on which this material is based. Ronish Gupta Sabira Valiani MD, FRCPC MD, FRCPC Peer review of this eBook was provided by: Claudio Martin MD, FRCPC, Giuseppe Pagliarello MD, FRCSC, Mike Hartwick Alissa Visram Michael Sharpe MD, FRCPC, MD, MEd, FRCPC MD Jeffery Singh MD, FRCPC

Andrew Healey Lindsay Wilson MD, RDCS, RDMS, FRCPC MHA(c), BA Content

Design Note 3 Unlike a traditional printed publication, this Contributors eBook was designed to be experienced in a non- 5 linear manner with the thought that clinicians can Neurological Declaration of Death use the material as reference or at the bedside. Donor Management 38 Within the material you will see several conceptual maps that represent expert consensus on how to approach a particular treatment goal. These maps, allow you to jump around the book content quickly. The book also includes a set of icons that provide access to layers of information that we hope you will find useful. Tap this shape to jump to an overview map for the current chapter Tap this shape to jump to an overview map for a different chapter Tap this symbol to jump to a sub-map within the chapter

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Organ Donation in Ontario: A Guide for Critical Care Residents Neurological Declaration of Death

Authors: Sonny Dhanani MD FRCPC, Michael Hartwick MD MEd FRCPC, Sabira Valiani MD FRCPC, Alissa Visram MD, Pierre Cardinal MD MScEpi FRCPC, Janice Beitel RN MScN CNCC(c), Ian M Ball MD MSc FRCPC, Karim Soliman MD FRCPC, Eli Malus MD FRCPC, Lindsay Wilson MHA(c) BA, Sam D. Shemie MD FRCPC, Andrew Healey MD FRCPC Collaborators: Louise Pope-Rhoden RN, Kim Bowman RN BScN MEd, Edwin Poon B.Sc. RRT

Introduction Brain death is defined as the irreversible loss of consciousness com- criteria and to establish donor eligibility. This chapter reviews the bined with the irreversible loss of all brainstem functions, including the concept of brain death, pathophysiology, and diagnostic criteria for capacity to breathe. For patients who die as a result of severe brain declaration including minimum clinical criteria and ancillary testing. injury, standard end-of-life care should include offering the option In addition, it presents a clinical approach to the declaration of neuro- of organ and tissue donation. All patients who are suspected of being logical death which is supported by evidence for each task performed during brain dead should have an assessment to document death by neurologic the process (refer to the interactive map under Clinical Approach).

Organ Donation in Ontario: A Guide for Critical Care Residents 5 Key Concepts

Brain Death Concept death was formally adopted in the UK in 19953 of death is the process and procedure to deter- In Canada, brain death is defined as the In the United States, the Uniform Deter- mine death in the context of a ventilated patient irreversible loss of the capacity for conscious- mination of Death Act states than “an indi- with irreversible brain failure. It should never ness combined with the irreversible loss of all vidual who has sustained irreversible cessation be confused with other forms of severe brain brainstem functions, including the capacity to of all functions of the entire brain, includ- injury, such as unconsciousness, reversible coma, breathe.The concept of brain death served to ing the brainstem, is dead.” It is important to persistent vegetative state, cortical death or 5,6 address 2 major issues that arose as a result of understand that the clinical bedside evaluation anencephaly . advances in health care in the 1960’s:1 practi- assesses the complete loss of brainstem function, cal issues that arose with the advent of inten- but it does not distinguish between brainstem Pathophysiology sive care units with artificial airways and death, as may be seen in isolated brainstem Regardless of the primary etiology of brain mechanical ventilators regarding the treatment infarction, or whole brain death that involves injury, tissue edema or mass effect leads to the 4 of apneic patients and ethical concerns assoc- the cerebrum and the brainstem . final common pathway characterized by iated with organ donation arising from the then- increasing intracranial pressure, which progres- new discipline of transplant surgery 2. The clini- Brain death is a term and a concept that sively impairs cerebral blood flow. As pressure cal appearance of brain death was first described remains a source of misunderstanding for many rises inside the rigid intracranial vault, it may in seminal work by the French in 1959 and practitioners, casual observers, and the public. do so heterogeneously throughout the brain termed “coma dépassé” meaning “a state beyond From a physiological perspective, it is better or selectively within compartments. Pressure- coma”. In 1968, the Ad Hoc Committee of the understood as irreversible brain arrest or com- related ischemia ensues leading to further Harvard Medical School defined irreversible plete and irreversible cessation of clinical func- neuronal/glial injury, abnormal vascular auto- coma and brain death and the definition of tions of the brain. Neurological determination regulation, and edema7. This contributes to a irreversible loss of brainstem function in brain continued rise in ICP until intracranial pressure 3 Diagnosis of brain death: Statement issued by the honor- ary secretary of the Conference of Medical Royal Colleges 5 Wijdicks EF, "Brain death worldwide: Accepted fact but and Their Faculties in the United Kingdom on 11 October no global consensus in diagnostic criteria", Neurology, 1976. BMJ. 1976;2:1187-8 2002;58;20-25 4 The President’s Council on Bioethics: Controversies in the 6 Bernat JL.Contemporary controversies in the definition of 1 Mollaret P, Goulon M. Le coma dépassé. Rev Neurol determination of death: a white paper by the President’s death. Prog Brain Res. 2009;177:21-31. (Paris). 1959;101:3-15 Council on Bioethics 2008. http://bioethicsprint.bioethics. 7 Shemie SD, Doig C, Belitsky P. Advancing towards a 2 A definition of irreversible coma: Report of the Ad Hoc gov/reports/death/Controversies%20in%20the%20Deter- modern death: The path from severe brain injury to Committee of the Harvard Medical School to Examine the mination%20of%20Death%20for%20the%20Web%20 neurological determination of death. CMAJ. 2003 Apr Definition of Brain death. JAMA. 1968;205:337-40 (2) 15;168(8):993-5.

Organ Donation in Ontario: A Guide for Critical Care Residents - Neurological Declaration of Death 6 exceeds arterial inflow pressure and irreversible cil for Donation and Transplantation (CCDT) documentation is completed. A second exam is brain arrest/failure occurs. In response to rising 2003 Forum on Severe Brain Injury to Neu- necessary for the purposes of organ donation, intracranial pressure, the brain herniates through rological Determination of Death, and 2007 consistent with existing provincial laws. paths of least resistance, most commonly seen Forum on Brain Blood Flow in the Neuro- as downward descent of the brainstem and cere- logical Determination of Death. Adaptations If conditions capable of mimicking neuro- bellum through the foramen magnum. Cellular have been made based on other newer recom- logical death cannot be corrected or if any part disruption and herniation triggers an inflamma- mendations9,10,11. of the neurological exam cannot be reliably tory cascade that affects cardiorespiratory func- interpreted or fully performed, then the tion and hormonal regulation. This cascade The physician must work in accordance with appropriate use of ancillary testing, where affects pituitary and hypothalamic function, provincial standards (Map2 ) to iden- specifically indicated, is required. Even with the and the brainstem resulting in catecholamine, tify irreversible proximate cause for death addition of ancillary testing, all feasible comp- thyroid, and vasopressin abnormalities. The and account for conditions capable of mim- onents of the clinical neurological exam should be duration of time from injury to brain death may icking neurologic death (Map 3 ). Once completed by two physicians. Once ancillary vary, depending on mechanism and severity of potential confounding conditions are identified testing confirms the findings of the clini- initial injury and the response to neuro- and corrected, the physician with appropriate cal exam, then the pronouncement of neuro- protective therapies8. skills and knowledge must perform a clinical logic death is complete. Contacting the TGLN neurologic exam confirming neurologic death Donation Support Physician may be appro- Clinical Approach (Map 1 ) (Map 4 ). Once the exam is completed priate to discuss best practices for management Neurologic Determination of Death is a and is consistent with neurologic death, the of neurological determination of death and detailed clinical examination that documents pronouncement of death with specific organ donation. the complete and irreversible loss of conscious- 9 Shemie SD, Doig C, Dickens B, Byrne P et al. Severe brain ness and absence of brainstem function includ- injury to neurological determination of death: Canadian ing the capacity to breathe. In accordance with Council for Donation and Transplantation Forum recommendations. CMAJ. 2006 Mar 14;174(6):S1-13. the Trillium Gift of Life Network Act, Tril- 10 Shemie SD, Lee D, Sharpe M, Tampieri D, Young B; Ca- lium Gift of Life Network (TGLN) endorses nadian Critical Care Society. Brain blood flow in the neurological determination of death: Canadian expert report. recommendations from the Canadian Coun- Can J Neurol Sci. 2008 May;35(2):140-5. 11 Wijdicks EF, Varelas PN, Gronseth GS, Greer DM; Amer- 8 Dhanani S and Shemie SD. “Brain Death”. Pediatric Crit- ican Academy of Neurology.Evidence-based guideline up- ical Care Medicine: Basic Science and Clinical Evidence, date: determining brain death in adults: report of the Qual- 2nd Edition. Eds Derek S. Wheeler, Hector R. Wong, ity Standards Subcommittee of the American Academy of Thomas P. Shanley, Springer, 2014 Neurology. Neurology. 2010 Jun 8;74(23):1911-8.

Organ Donation in Ontario: A Guide for Critical Care Residents - Neurological Declaration of Death 7 Conclusion The neurologic determination of death is currently the standard of practice as one of the prereq- uisites to organ donation in ventilated patients with irreversible cessation of all clinical functions of the brain. It is being used to initiate withdrawal of mechanical support discussions and is a prerequisite to organ donation. Its concept has been internationally accepted as a medical and legal definition of death in many countries with advanced health care systems. Brain death is defined as the irreversible loss of the capacity for consciousness combined with the irreversible loss of all brainstem functions, including the capacity to breathe. NDD remains a fundamentally clinical examination establishing a clear mechanism for catastrophic brain injury in the absence of confounding or reversible factors. Ancillary radiologic testing is only recommended when a full clinical exam cannot be reliably completed or when mimickers of neurological death cannot be rapidly and completely reversed. Stringent legal and clinical criteria exist to ensure transpar- ency, safety and trust in the process.

Organ Donation in Ontario: A Guide for Critical Care Residents - Neurological Declaration of Death 8

Map 1 - Overview Neurological Declaration of Death

t p

a h C o Return t

Conditions capable of Declaring Work process in accordance ensure identify Proximate cause identify and correct mimimicking neurologcal Neurological with Provincial Standards Death death

Findings from neurological examination cannot be completed once conditions or reliably interpreted if it is anticipated that have been All feasible components of still need to OR corrected, complete neurological examination perform Conditions capable of mimicking death cannot be completely and rapidly corrected contact Clinical examination of neurological death

Donation Support Physician if completed and consistent with death, declare

to advise on need for

Death Ancillary tests and confirm

Map 2 - Provincial Standards Neurological Declaration of Death

t p

a h C Declaring Ret n to Neurological ur Death Working in Accordance with No association to Provincial Physicians with the proposed recipient Standards which specify AND Full and current licensure for independent medical practice in the relevant Canadian jurisdiction AND Skill and knowledge in the management of patients with severe brain injury and in NDD in the patient's Minimum of two age group determinations

if performed in

Neonates Infants (30 days to Children (1 year or older), (less than 30 days) less than 1 year) adolescents, and adults

done done either done

At different times with a At different times with Simultaneously or at minimum of 24 hours no specified time different times with no between interval between specified time interval determinations determinations between determinations

Map 3 - Mimickers of Neurological Death Neurological Declaration of Death

e t

p Defined as: Core temperature a 0 h < 34 C in infants, children C Re to Declaring and adults: core temperature turn Neurological 0 Death < 36 C in newborn Identifying Hypothermia correct, then Conditions proceed to Capable of Mimicking Neurological Death consider Electrolyte abnormalities

Neuromuscular blockade

Unresuscitated shock if Consult the deemed Donation Support Physician uncorrectable Peripheral nerve or muscle dysfunction if Inborn errors of metabolism, unsure severe liver and/or renal dysfunction Wait until medication has been Clinically significant drug metabolized/excreted, or give Hypoxic brain damage either intoxications, liver and antidotes secondary to cardiac arrest Clinical renal dysfucntion - hypothermia Examinaition of Neurological Death 24 hours following return of wait for then proceed to spontaneous circulation

Map 4 - Clinical Examination of Neurological Death Neurological Declaration of Death

t p

a h C R to eturn Declaring Neurological Death Clinical Examination of perform confirm Neurological Assessment Deep unresponsive coma Death

perform assess

Adults, adolescents, Apnea test Brainstem reflexes and children (1 year or older)

if performed in recognize Cough and Gag Reflexes Corneal Reflexes Vestibulo Ocular Response Infants Chronic respiratory (30 days to less than 1 year) insufficiency and responsiveness add oculocephalic reflex to only supranormal levels of assessment carbon dioxide OR Patients dependent on Neonates (less than 30 days and minimum Select image to see a hypoxic drive time from birth of 48h, and correct demonstration of gestational age of 36 weeks) oculocephalic relex. add both oculocephalic and suck reflex Requires internet connection. assessment. Minimum core temperature consult 36 degrees C

Donation Support Physician Identifying Proximate Cause Kim Bowman

Description Rationale However these conditions must also be associ- Identification of a proximate cause of death is In order for NDD to be declared, a definitive ated evidence of increased intracranial pressure a prerequisite to NDD. There must be definite cause of death must be identified and condi- or cerebral edema in order to lead to irreversible clinical or neuroimaging evidence of an acute tions mimicking neurological death must be neuronal injury. In the clinical judgement of central nervous system (CNS) event consis- ruled out. The identified proximate cause of the treating physician, the proximate cause of tent with the irreversible loss of neurological death must be consistent with irreversible loss death must be confirmed by a clinical presenta- function1. of neurological function1. tion (e.g. prolonged circulatory arrest) or neuro- Examples of conditions leading to neurological imaging (e.g. cerebral edema on CT head) that death may include (but are not limited to) the fully explain neurological death1. NDD for the following: purposes of donation cannot take place unless a • Acute brain injury - e.g. cerebrovascular proximate cause has been established. Return to overview map accidents, head trauma, intracranial tumors, intracranial hemorrhage or acute hydrocephalus • Hypoxic-ischemic injury - e.g. resuscitated cardiac arrest, near drowning asphyxia, hypovolemic shock • CNS infection - e.g. meningitis, encephali- tis • Miscellaneous - e.g. Metabolic encepha- lopathy from liver disease, diabetic ketoac- idosis, metabolic disorders, acute hyponatremia or vasculitis2.

1 Shemie SD, Doig C, Dickens B, et al. Severe brain injury 2 "Determination of Death". Donation Resource Manual: A to neurological determination of death: Canadian forum Tool To Assist Hospitals With The Process Of Organ And recommendations. CMAJ : Canadian Medical Association Tissue Donation. 6th ed. Toronto: Queen's Printer, 2014. Journal. 2006;174(6):S1-S12. doi:10.1503/cmaj.045142. Print.

Organ Donation in Ontario: A Guide for Critical Care Residents - Neurological Declaration of Death 13 Findings from the Neurological Examination Cannot be Completed or Reliably Interpreted Louise Pope-Rhoden, Janice Beitel

Description tablishes compatibility with death as ancillary high cervical injury2. When findings from the clinical Neurological testing is considered supportive, not • The use of anticholinergic drugs such as 1 Examination cannot be completed or reliably confirmatory of neurological death . atropine that can cause pupillary 2 interpreted dilatation . • Consider consultation with an expert At a minimum, two particular clinical criteria • Fractures to base of skull or petrous tem- opinion, (i.e. TGLN donation support must be met before ancillary tests are performed: poral bone that may obliterate reflex 2 physician or local expert) • An established etiology capable of causing responses on the side of the fracture . • When any component of the clinical neu- neurological death in the absence of • Severe lung disease: Caution must be rological examination cannot be reversible conditions capable of mimick- exercised in considering the validity of the performed, consider performing an ing apnea test if, in the physician’s judgment, ancillary test demonstrating the global ab- neurological death. there is a history suggestive of chronic sence of intracranial blood flow1. • Deep unresponsive coma. respiratory insufficiency and responsiveness to only supranormal levels of carbon Return to Overview Map If a patient is unstable or becomes too dioxide, or if the patient is dependent on unstable to complete any portion of the clinical hypoxic drive. If the physician cannot be Rationale exam (including apnea testing), or the clinical sure of the validity of the apnea test, an a components of the exam cannot be completed, ncillary test should be administered1. Certain injuries or preexisting diseases, espe- ancillary testing may be required to determine Consider seeking an expert opinion cially when very severe, can make the clinical death by neurological criteria. Examples of (e.g.TGLN Donation Support Physician exam unreliable. It is preferable to complete situations where this occurs include: or local expert) before proceeding to the Neurological Exam including the apnea test • High cervical cord injury-- the efferent ancillary testing. and to then seek an expert opinion, (i.e. TGLN pathway for the cough/gag reflex are the donation support physician or local expert) phrenic nerve and the innervation of before proceeding to ancillary testing. A neu- the thoracic and abdominal musculature rological exam must be conducted that es- which cannot be assessed in patients with 1 Shemie SD, Doig C, Dickens B, et al. Severe brain injury to neurological determination of death: Canadian forum 2 Australian and New Zealand Intensive Care Society (AN- recommendations. CMAJ : Canadian Medical Association ZICS) THE ANZICS STATEMENT ON DEATH AND Journal. 2006;174(6):S2,3. doi:10.1503/cmaj.045142. ORGAN DONATION (pgs 20,21) Edition 3.2 2013

Organ Donation in Ontario: A Guide for Critical Care Residents - Neurological Declaration of Death 14 Conditions Capable of Mimicking Death Cannot be Completely or Rapidly Corrected Kim Bowman

Description Rationale May include but are not limited to factors Conditions capable of mimicking neurologi- such as hypothermia, electrolyte abnormali- cal death have been well cited in numerous do- ties, neuromuscular blockage etc. nation related documents 1,2. In order to de- • If such conditions cannot be complete- termine neurological declaration of death for ly or rapidly corrected, a clinical exam the purposes of donation, conditions capa- 3 should still be conducted to the extent ble of mimicking neurological death should possible. be identified and corrected. Ancillary testing • An ancillary test should be considered1. should be considered if in the physician’s judge- • Consult with the donation support physi- ment some of these conditions cannot be fully corrected or if correction of a mimicker of neurological death (e.g. a serum sodium of >160), Return to overview map would unduly prolong the time period before donation as perceived by the donor’s family. cian (DSP) or local expert should be Because ancillary testing is considered support- considered before ordering any ancillary ive, not confirmatory of neurological death, a tests to ensure that all efforts have been neurological exam must be conducted that made to perform neurological declara- establishes (to the extent possible) compatibility 2 tion of death (NDD) using clinical criteria with death . Consider seeking an expert opin- including the apnea test. ion (e.g.TGLN Donation Support Physician or local expert) before proceeding to ancillary testing.

2 "Determination Of Death". Donation Resource Manu- al: A Tool To Assist Hospitals With The Process Of Organ And Tissue Donation. 6th ed. Toronto: Queen's Printer, 1 Shemie SD, Doig C, Dickens B, et al. Severe brain injury 2014. Print. to neurological determination of death: Canadian forum 3 Shemie, Sam D. et al. "International Guideline Develop- recommendations. CMAJ : Canadian Medical Association ment For The Determination Of Death". Intensive Care Journal. 2006;174(6):S1-S12. doi:10.1503/cmaj.045142. Med 40.6 (2014): 788-797. Web.

Organ Donation in Ontario: A Guide for Critical Care Residents - Neurological Declaration of Death 15 Contact Donation Support Physician Eli Malus, Sonny Dhanani

Description be committed to the integrity of this system. firmatory, of neurologic death. Contact Donation Support Physician (DSP) or A consultation to the DSP is always done with local expert: TGLN 1-877-363-8456 acknowledgements of ethical practice standards Contacting the DSP or local expert should be and with the utmost professionalism considered before ordering any ancillary tests Rationale to ensure that all efforts have been made to When findings from neurological examination perform NDD using clinical criteria includ- The Donation Support Physician (DSP) is an cannot performed or reliably interpreted OR ing the apnea test. It is our experience that on intensivist on-call and available by phone 24/7 conditions mimicking neurological death can- occasion, with advice from a DSP or local within Ontario. Their main role is to support not be corrected, it is important to consider expert, it still may be possible to perform NDD and advise the provincial resource centre, the contacting either the DSP or a local expert to using clinical criteria obviating the need for an- organ and tissue donation coordinator, and the discuss concerns or performing ancillary tests. cillary tests. If after consultation with the DSP Even though TGLN documents suggest that or local expert it is deemed that an ancillary Return to overview map ancillary tests may be performed in these situa- test is required, the DSP/local expert can also tions, these tests should only be ordered during help guide the selection of the most appropriate appropriate situations while considering risks ancillary test given the clinical situation and most responsible physician. Discussions might and benefits of the chosen ancillary test The local expertise. include donor identification, declaration of DSP or local expert can help determine their death, organ suitability, and donation logistics. appropriateness given the clinical context. If examination according to the minimum clini- Consultation with a physician expert from cal criteria (to the extent possible) is compati- TGLN prior to declaration of death may appear ble with death, an ancillary test demonstrating to represent a conflict of interest. However, it is the global absence of intracranial blood flow well recognized that appropriate expertise and supports the declaration of death1. Any experience for NDD is greatest at the OPO with ancillary test is considered supportive, not con- the organ and tissue donation coordinator and the donation support physician. This is an im- 1 Shemie SD, Doig C, Dickens B, et al. Severe brain injury portant mechanism to support this process and to neurological determination of death: Canadian forum physicians invested in the donation system will recommendations. CMAJ : Canadian Medical Association Journal. 2006;174(6):S1-S12. doi:10.1503/cmaj.045142.

Organ Donation in Ontario: A Guide for Critical Care Residents - Neurological Declaration of Death 16 Determining Neurological Death in Neonates According to Provincial Standards Louise Pope-Rhoden

Description unresolved2. Should uncertainty or confounding issues arise The brainstem examination is different in • The physicians performing NDD should that cannot be resolved, the time interval may neonates (36 weeks, gestation to 29 days old have special expertise in the patient’s age be extended according to physician judgement, (corrected for gestational age)1: group. The minimum level of physician or an ancillary test demonstrating absence of 2 • Minimum clinical criteria include absence qualifications should be understood as intracranial blood flow may be used . The 48 of oculocephalic reflex and suck reflex. specialists with skill and knowledge in the hour recommendation from injury to first • Minimum temperature must be a core management of newborns/infants/chil- determination reflects a reduced certainty of 1 temperature 36°C1. dren and/or adolescents, respectively with neurological prognostication in the newborn . • Minimum time from birth to first deter- brain injury and the determination of 1 mination is 48 h1. death based on neurological criteria . • Two examinations are required, by two Rationale Return to overview map It is prudent to have an independent examina- Return to sub map tion because of the lack of collective experience and research on brain death in this age group a repeat examination no less than 24 hours different physicians, at a minimum time apart is recommended to ensure independent interval of 24 hours between each exam- confirmation by another qualified physician, ination is required1. regardless of the primary mechanism of the • Ancillary testing, as defined by demonstra- brain injury. Accuracy of gestational age should tion of the absence of intracranial blood be supported by clinical history (e.g., dates and flow, should be performed when any of prenatal ultrasound) and physical examination. the minimum clinical criteria cannot be Inability to confirm a gestational age > 36 weeks established or confounding factors remain should preclude NDD.

1 Shemie SD, Doig C, Dickens B, et al. Severe brain injury to neurological determination of death: Canadian forum 2 CCDT 2003 Severe brain injury to neurological determi- recommendations. CMAJ : Canadian Medical Association nation of death Canadian Forum Report and Recommen- Journal. 2006;174(6):S2,3. doi:10.1503/cmaj.045142. dations

Organ Donation in Ontario: A Guide for Critical Care Residents - Neurological Declaration of Death 17 Determining Neurological Death in Infants According to Provincial Standards Janice Beitel, Pierre Cardinal

Description Rationale For infants (30 days to 1 year, corrected for Given less widespread experience with NDD gestational age)1: for infants, a repeat examination at a different • Two examinations are required that should point in time is recommended to ensure inde- be performed at different times by two pendent confirmation by another qualified different physicians physician, regardless of the primary mechanism • There is no recommended minimum time of the brain injury. It is prudent to have an interval between examinations independent examination because of the lack of • The physicians performing NDD should collective experience and research on brain death have special expertise in the patient’s age in this age group. There is no recommended group. minimal time interval between determinations. Should uncertainty or confounding issues arise Return to overview map that cannot be resolved, the time interval may Return to sub map be extended according to physician judgement, or an ancillary test demonstrating absence of intracranial blood flow may be used2. • The minimum level of physician qualifications should be understood as specialists with skill and knowledge in the management of newborns/infants/children and/or adolescents, respectively.

Organ Donation in Ontario: A Guide for Critical Care Residents - Neurological Declaration of Death 18 Hypothermia as a Mimicker of Neurological Death Louise Pope-Rhoden, Janice Beitel

Description Rationale history (e.g. dates and prenatal ultrasound) and • Core temperature should be obtained When body temperature is below normal, hypo- physical examination. Inability to confirm a through central blood, rectal or esopha- thermia should be considered as a confounding gestational age >36 weeks should preclude 1 geal–gastric measurement1. factor which might prevent the observation of NDD . The higher recommended temperature • The core body temperature required neurologic responses and/or mimic neurologi- threshold in neonates reflects uncertainty about to apply the minimum clinical criteria cal death. Confounding conditions that may hypothermic effects on neurological function in should be 34°C in infants, children, and invalidate testing for cessation of brain function the newborn and the fact that normothermia is 1 adults2. include naturally occurring and/or therapeutic an easily attainable standard . • The brainstem examination is different hypothermia3. There is little evidence to inform in neonates, for newborns aged 36 weeks the threshold temperature below which NDD gestation to 29 days old (corrected for becomes unreliable. Given the lack of evidence, a consensus decision was made to Return to overview map adopt 36°C and 34°C as rational, safe and Return to sub map attainable standards in neonates and in any patients older than 1 month, respectively. Ideally, temperature should be as close to gestational age) minimal core body normal as possible as these threshold tempera- temperature should be 36°C1. tures are the minimal temperature at which the test is considered valid. Raising a patient’s temperature to 34°C (or to 36°C in neonates) is also easy to achieve1.

1 Shemie SD, Doig C, Dickens B, et al. Severe brain injury In neonates, it is also important to ensure the to neurological determination of death: Canadian forum accuracy of gestational age based on clinical recommendations. CMAJ : Canadian Medical Association Journal. 2006;174(6):S2-4. doi:10.1503/cmaj.045142. 2 Trillium Gift of Life Network (TGLN), Guidelines for the 3 S. D. Shemie, L. Hornby, A. Baker, et al. Internation- neurological determination of death (NDD) for the pur- al guideline development for the determination of brain poses of organ donation in ontario: adult and paediatric death Intensive Care Med (2014) 40:791 DOI 10.1007/ patients 1 year and older s00134-014-3242-7

Organ Donation in Ontario: A Guide for Critical Care Residents - Neurological Declaration of Death 19 Electrolyte Abnormalities as Mimickers of Neurological Death Lindsay Wilson, Louise Pope-Rhoden, Sonny Dhanani

Description Rationale Before completing the neurological exam- Certain metabolic abnormalities, including ination or apnea test: severe hypophosphatemia, hypocalcemia, • Recognize and correct any severe electro- hypomagnesemia, hypernatremia, hyponatre- lyte abnormality including:1,2 mia, and hypoglycemia may impact the ability ◼◼Hypophosphatemia (< 0.4mmol/L)1 to declare death based on neurological criteria. ◼◼Hypocalcemia (<1.0 mmol/L ionized) The effect of electrolyte abnormalities result- ◼◼Hypomagnesemia (<0.8 mmol/L) ing in a condition capable of mimicking neu- ◼◼Hypernatremia (>160 mmol/L)1 rologic death is theoretical in that there are no ◼◼Hyponatremia (<125 mmol/L)1 specific reports of cases of misdiagnosis resulting from electrolyte abnormalities alone and no reported guidance on actual thresholds for Return to overview map appropriate electrolyte targets. However, correc- Return to sub map tion of electrolyte levels are based on established clinical standards and accepted physiological normals levels1. All metabolic abnormalities • Recognize and correct hypoglycemia should be corrected before completing NDD (<4 mmol/L) if it is believed that they might interfere with the interpretation of the clinical examination or apnea test results2.

1 "Determination Of Death". Donation Resource Manual: A Tool To Assist Hospitals With The Process Of Organ And Tissue Donation. 6th ed. Toronto: Queen's Printer, 2014. Print. 2 Shemie SD, Doig C, Dickens B, et al. Severe brain injury to neurological determination of death: Canadian forum recommendations. CMAJ : Canadian Medical Association Journal. 2006;174(6):S2,3. doi:10.1503/cmaj.045142.

Organ Donation in Ontario: A Guide for Critical Care Residents - Neurological Declaration of Death 20 Neuromuscular Blockade as a Mimicker of Neurological Death Kim Bowman, Janice Beitel

Description Rationale Stop any neuromuscular blockade agent before Neuromuscular blocking agents inhibit the performing the clinical examination or apnea action of acetylcholine by blocking neuromus- test for NDD1. cular transmission and thus causing paralysis of all skeletal muscles. Common agents include vecuronium, pancuronium, cisatracurium and rocuronium. Depolarizing agents such as suc- cinylcholine are short acting and often not a consideration in the ICU patient but should also be recognized. Neuromuscular blockade will affect all striated muscles including the Return to overview map diaphragm and therefore will mimic unresponsiveness and lead to absence of breathing during Return to sub map apnea tests1,2. Cranial nerve functions are also affected with the exception of the pupillary light reflex which is preserved in normal patients on neuromuscular blocking agents. Thus, any neuromuscular blockade agent should be stopped before performing the clinical examination or apnea test for NDD2. If any concerns about persisting pharmacologic neuromuscular blockade, train of four testing to confirm reversal of paralysis should be conducted. 1 Shemie SD, Doig C, Dickens B, et al. Severe brain injury to neurological determination of death: Canadian forum recommendations. CMAJ : Canadian Medical Association Journal. 2006;174(6):S1-S12. doi:10.1503/cmaj.045142. 2. International guideline development for the determination of death Intensive Care Med (2014) 40:788–797 DOI 10.1007/s00134-014-3242-7

Organ Donation in Ontario: A Guide for Critical Care Residents - Neurological Declaration of Death 21 Unresuscitated Shock as a Mimicker of Neurological Death Kim Bowman, Janice Beitel

Description Rationale Recognize and treat unresuscitated shock: Shock is associated with inadequate oxygenated • Persistent hypotension despite fluid circulation to the brain2. In the presence of resuscitation and vasopressors unresuscitated shock (i.e. persistent hypoten- AND/OR sion despite fluid resuscitation and vasopres- • Persistent hypoperfusion despite fluid sors or persistent hypoperfusion despite fluid resuscitation or inotropes1. resuscitation or inotropes), the motor response, • In the presence of shock refractory to cranial nerve examination and apnea test may resuscitative measures, contact the dona- be falsely positive mimicking neurological tion support physician (DSP) or local death. It is important to assess for both hypo- expert before proceeding with NDD or tension and hypoperfusion and to correct the ordering ancillary tests. shock state prior to proceeding with a diagnosis of brain death for the purposes of donation. In Return to overview map the presence of shock refractory to all resuscitative measures, a consultation with the DSP Return to sub map or local expert should be considered before ordering ancillary tests2.

1 "Determination Of Death". Donation Resource Manual: A Tool To Assist Hospitals With The Process Of Organ And 2 International guideline development for the determination Tissue Donation. 6th ed. Toronto: Queen's Printer, 2014. of death Intensive Care Med (2014) 40:788–797 DOI Print. 10.1007/s00134-014-3242-7

Organ Donation in Ontario: A Guide for Critical Care Residents - Neurological Declaration of Death 22 Peripheral Nerve or Muscle Dysfunction as a Mimicker of Neurological Death Karim Soliman

Description Rationale Consider peripheral nerve or muscle dys- Certain peripheral nerve and muscle diseases, function as mimickers of neurological death especially when very severe, can make it diffi- especially in the presence of diseases that may cult to interpret the result of the neurological lead to severe neuromuscular dysfunction such exam especially the apnea test. In the presence as: of severe neuromuscular diseases, the motor • Myasthenia gravis response, cranial nerve examination and apnea • Guillain-Barre Syndrome test may be falsely positive mimicking neuro- • Botulism logical death. In such cases, it is preferable to complete the clinical neurological examination, including the apnea test, and to then seek a second opinion or consultation with neurology. Return to overview map Ancillary testing may be warranted to confirm Return to sub map absence of brain blood flow. An expert opinion (e.g. TGLN donation support physician or a local expert) before proceeding to ancillary testing should also be considered1.

Organ Donation in Ontario: A Guide for Critical Care Residents - Neurological Declaration of Death 23 Inborn Errors of Metabolism as Mimickers of Neurological Death Kim Bowman, Janice Beitel

Description Rationale be made to correct any metabolic abnormality Always perform a detailed review of the past Inborn errors of metabolism (IEM) may that might play interfere with the neu- medical history to exclude inborn errors of result in unresponsiveness and preclude the rological declaration of death. If the metabolic metabolism (IEM). diagnosis of neurological determination of abnormalities cannot be corrected, it is prefer- death. IEM typically present in the neonatal pe- able to complete the neurological examination, riod or infancy but can occur at any time, even including the apnea test, and then consider in adulthood1. Potential symptoms include: hy- consultation with an expert (e.g.TGLN poglycemia, metabolic acidosis, and electrolyte Donation Support Physician or a local expert) imbalances. Diagnoses include fructose intol- before proceeding to ancillary testing. erance, galactosemia, phenylketonuria (PKU)2. As a minimum consideration, a thorough Return to overview map review of the patient’s medical history should be conducted to exclude IEM. Return to sub map Severe metabolic disorders may appear as part of the primary presentation. Symptoms and signs can complicate management for the physician and thus may impact the ability to declare death based on neurological criteria3. Attempts should

1 Emedicine.medscape.com,. "Inborn Errors Of Metabo- lism: Background, Pathophysiology, Epidemiology". N.p., 2016. Web. 2 Mar. 2016. 2 Updated by: Chad Haldeman-Englert, and the A.D.A.M. Editorial team. "Inborn Errors Of Metabolism: Medlin- eplus Medical Encyclopedia". Nlm.nih.gov. N.p., 2016. Web. 3 Mar. 2016. 3 Shemie SD, Doig C, Dickens B, et al. Severe brain injury to neurological determination of death: Canadian forum recommendations. CMAJ : Canadian Medical Association Journal. 2006;174(6):S1-S12. doi:10.1503/cmaj.045142.

Organ Donation in Ontario: A Guide for Critical Care Residents - Neurological Declaration of Death 24 Clinically Significant Drug Intoxications as Mimickers of Neurological Death Ian Ball, Pierre Cardinal

Description or considering ancillary test is warranted. A could never confound the clinical NDD giv- Many drugs can affect neurological function consultation with a DSP or local expert should en their short half-lives. Opioids and sedative and may even mimic neurological death. Given be considered. hypnotics are the agents most likely to con- the disastrous consequences of a false positive found the NDD examination, particularly when NDD, it is essential to always consider drugs Rationale administered at high doses, for long durations, as potential confounders especially in the ab- A negative urine “drug screen” is completely or in patients with compromised hepatic and/ sence of a clear proximate cause of death. This inadequate for ruling out the presence of con- or renal function. Clinicians should be proac- can be very challenging given that a complete founding agents because most hospital urine tive at stopping these agents as early as possi- drug history is often missing and that current 'drug screens' only test for five or six classes of ble when they are not required clinically (i.e. screening tests are notoriously inaccurate. In drugs. Even when the drug belongs to one of for ICP control), in anticipation of an NDD these classes, a negative result does not neces- assessment. When agents are required therap- eutically, clinicians are well advised to use short Return to overview map sarily exclude an intoxication given the poor performance of these tests (low sensitivity and acting agents that are less reliant on hepatic Return to sub map specificity)1,2,3. Positive test results do not metabolism, such as propofol. In addition, necessarily confound the interpretation of the antidotes (particularly naloxone and flumaze- clinical examination for NDD. For example, nil) are not recommended as they may addition, patients considered for NDD may patients who overdose on sympathomimetic precipitate acute withdrawal, leading to have hepatic and renal dysfunction or be hypo- agents (e.g. cocaine) may sustain intracranial catecholamine surges that may be injurious to thermic which may influence the metabolism hemorrhages and irreversible neurological in- vulnerable organs. and action of various drugs in unpredictable jury as a result of the overdose, yet these agents Clinicians should consider consultation with ways. It is important to distinguish drugs that 1 Hammett-Stabler CA, Pesce AJ, Cannon DJ: Urine may have played a role in the primary presen- drug screening in the medical setting. Clin Chim Acta local poison centers when drug intoxica- tation of coma (i.e. overdose) versus drugs that 2002;315:125-135. tion may be affecting the NDD assessment. 2 Hepler BR, Sutheimer CA, SUnshine I: The role of the Consider seeking an expert opinion (e.g.TGLN are used in routine ICU care. For lingering toxicology laboratory in emergency medicine.II. Study effects of therapeutic narcotics or sedatives that of an integrated approach. J Toxicol Clin Toxicol 1984- Donation Support Physician or local expert). 85;22:503-528. may impair appropriate neurologic examina- 3 Kellerman AL, Fihn SD, Logerfro JP, et al: Impact of tion, delaying the testing for neurologic death drug screening in suspected overdose. Ann Emerg Med 1987;16:1206-1216.

Organ Donation in Ontario: A Guide for Critical Care Residents - Neurological Declaration of Death 25 Hypoxic Brain Damage Secondary to Cardiac Arrest as a Mimicker of Neurological Death Karim Soliman

Description Rationale mimickers of neurological death3,4. Testing Consider hypoxic-ischemic brain damage Hypoxic-ischemic injury post cardiac arrest can should be delayed until the patient has been secondary to cardiac arrest as mimicker of mimic neurological death especially in the first rewarmed. neurological death. In particular the first 24 24 hours post arrest. Canadian guidelines hours post arrest where the clinical exam may be require a minimum of 24 hours between confounded. cardiac arrest and clinical declarations1. Sever- al other national neurological death declaration guidelines carry an observation period between anoxic-ischemic brain injury and neurological declarations2. Current recommendation in Ontario is to delay declaration testing until Return to overview map 24 hours after the time of the hypoxic-ischemic event. Clinical context is important and Return to sub map consultation with the DSP or local expert should be considered.

When hypothermia is used post arrest, the prolonged effect of sedatives due to altered drug metabolism may warrant further consideration to ensure that they too are not potential

1 Shemie SD, Doig C, Dickens B, et al. Severe brain injury to neurological determination of death: Canadian forum recommendations. CMAJ : Canadian Medical Association Journal. 2006;174(6):S1-S12. doi:10.1503/cmaj.045142. 3 Wijdicks EF, Determining Brain Death. Continuum: Life- 2 Wijdicks EF. Brain death worldwide: Accepted fact but long Learning in Neurology 2015;21:1419 no global consensus in diagnostic criteria. Neurology 4 Greer DM, Busl KM. Pitfalls in the Diagnosis of Brain 2002;58;20-25 Death. Neurocritical Care 2009; 11:276–287

Organ Donation in Ontario: A Guide for Critical Care Residents - Neurological Declaration of Death 26 Apnea Testing During Clinical Examination of Neurological Death Lindsay Wilson, Edwin Poon

Description 1-4 L/minute (alternatively set ventilator condensation 2 An apnea test is typically the last of the clinical to achieve this effect) . • Ventilator circuit is not resting on tests performed for purposes of declaring NDD ◼◼For patients with high FiO2 or PEEP patient’s body and involves the following steps1: requirements, the following may be • Ventilator Trigger Sensitivity setting • Attempt to achieve normal baseline arte- prepared for use to maintain optimal within reasonable range rial gases: pH 7.35-7.45, PaCO₂ 35-45 oxygenation: • Ventilator Apnea Alarm is off or at mmHg, PaO₂ > 100 mmHg2. • Connect a BVM system with a com- most lenient allowable setting • Preoxygenate with 100% O2 for 10 min- plete seal (reusable bags are suggested • Ventilator Apnea Backup Ventilation utes2. for their air tight qualities) to the in- setting is off or at most lenient allow- • Apply one of either open-circuit technique line O2 flow meter. able setting or closed-circuit technique as described • Attach appropriate PEEP valve and • FiO2 = 1 swivel ETT adapter for patient sup- • Change ventilator mode to CPAP / Return to overview map port. PEEP-only • Inflate the BVM system with inline O • Set CPAP level to PEEP level of Return to sub map 2 to the minimal setting required for ad- ventilation settings prior to apnea test equate inflation of the BVM system; • For monitoring during the apnea test: below: suggest using O2 flow greater than or a) If using O2 tubing: 3 Open-circuit technique (“Flow” apnea equal to 10 l/minute . • Draw patient’s gown to umbilicus level testing): Closed-circuit technique (“CPAP” ap- to facilitate the observation of the ◼◼Disconnect ETT from ventilator and in- nea testing): thorax and abdomen and confirm the sert catheter into ETT to deliver O₂ at ◼◼The patient remains on mechanical lack of respiratory effort ventilation for the duration of the apnea b) If using BVM with PEEP: 1 Shemie SD, Ross H, Pagliarello J, Baker AJ, Greig PD, Brand T, et al. Organ donor management in Canada: rec- test • Observe as above ommendations of the forum on Medical Management to ◼◼Ensure the following conditions on the • Provide one breath after bag-valve- Optimize Donor Organ Potential. CMAJ : Canadian Med- ical Association Journal 2006;174(6):S13-32. ventilator: mask set-up has been attached 2 "Determination Of Death". Donation Resource Manu- • Ventilator circuit is free of water or • At completion of spontaneous exhala- al: A Tool To Assist Hospitals With The Process Of Organ tion and bag-valve-mask refill, the And Tissue Donation. 6th ed. Toronto: Queen's Printer, 3 Trillium Gift of Life Network (TGLN), Neurological De- 3 2014. Print. termination of Death Policy and Procedure. 2014. apnea test begins .

Organ Donation in Ontario: A Guide for Critical Care Residents - Neurological Declaration of Death 27 c) If using closed-circuit technique: Notes: death determinations (including apnea • Observe for apnea as described in • If the patient becomes unstable at any testing) are required, though there is no section (a) time, it is recommended to draw recommended minimum time interval • Also observe ventilator waveform and arterial blood gases before putting the between determinations. Physician rate patient back on the ventilator, as they qualifications should be understood as • Verify apnea for a period of 5-15 minutes. may have met the requirements outlined specialists with skill and knowledge in the 4 A physician must be present to observe above . management of infants5. the chest and abdomen continuously to • If the test fails to meet the criteria listed ensure the absence of respiratory effort above or an apnea test cannot be com- Rationale while the patient is not being ventilated. pleted due to patient instability, a repeat The minimum clinical criteria as a Canadian Ensure cardiovascular status and oxygen exam, ancillary testing, or both may be medical standard for neurological death include saturations remain stable2. required. Discussion with TGLN is rec- absent respiratory effort based on an apnea • Draw arterial blood gases after 5, 10, and ommended4. test. Apnea testing involves driving up pCO₂ • For patients over one year, a single apnea Return to overview map levels to a maximum point to elicit respiratory test may be performed if both physicians response (while supporting oxygenation). are present at the time of the test5. Return to sub map Cooler body temperature may impact clinical • For neonates (36 weeks gestation to <30 testing for neurological death, and can prolong days), two neurological death determina- the time required for apnea tests due to decreased 15 minutes, then reconnect ventilator4. tions (including apnea testing) are production of CO2. Caution must be exercised required, with a minimum interval of 24 in considering the validity of the apnea test Absence of capacity to breathe is confirmed if all hours between examinations. Physician in cases of chronic respiratory insufficiency or three of the following thresholds (documented qualifications should be understood as dependence on hypoxic respiratory drive4. If by arterial gas measurement) have been met: specialists with skill and knowledge in the the physician cannot be sure of the validity of • PaCO2 ≥ 60 mmHg, and management of newborns5. the apnea test, an ancillary test should be • PaCO2 ≥ 20 mmHg rise above baseline, • For infants (30 days to 1 year, correct- administered. Consider consultation with an • and pH ≤ 7.282 ed for gestational age), two neurological expert opinion (e.g.TGLN Donation Support Physician or local expert) before proceeding to 4 Trillium Gift of Life Network (TGLN), Guidelines for the 5 Shemie SD, Doig C, Dickens B, et al. Severe brain injury neurological determination of death (NDD) for the pur- to neurological determination of death: Canadian forum ancillary testing. poses of organ donation in ontario: adult and paediatric recommendations. CMAJ : Canadian Medical Association patients 1 year and older. Journal. 2006;174(6):S2,3. doi:10.1503/cmaj.045142.

Organ Donation in Ontario: A Guide for Critical Care Residents - Neurological Declaration of Death 28 Recognition of Chronic Respiratory Insufficiency and Response to Supranormal Levels of Carbon Dioxide During Apnea Testing Karim Soliman Description Rationale be considered with caution3. In these cases, Recognize chronic respiratory insufficiency and The main objective of apnea testing is to test consultation with expert opinion should be response to only supranormal levels of carbon respiratory drive via a carbon dioxide challenge. considered (e.g. TGLN donation support phy- dioxide as special consideration when undergo- In patients with chronic carbon dioxide reten- sician or a local expert) to discuss the use of ing apnea testing in setting of neurological test. tion due to COPD or other diseases, central ancillary testing based on this clinical context. and peripheral chemoreceptors have been reset to the new baseline carbon dioxide levels and the kidneys compensate for the chronic respiratory acidosis1,2. Special consideration should be given to these patients so that their pre-apnea exam arterial blood gas is normalized to their baseline. This will prevent the apnea testing Return to overview map from being unnecessarily prolonged and hence Return to sub map is safer for the patient.

The guidelines also suggest that in patients with chronic respiratory insufficiency who only respond to supranormal levels of carbon dioxide, the validity of the apnea exam must

1 Acid-Base Response to Chronic Hypercapnia in Man. Newton C. Brackett, Jr., M.D., Charles F. Wingo, M.D., Orhan Muren, M.D., and Jose T. Solano, M.D. N Engl J Med 1969; 280:124-130 3 Shemie SD, Doig C, Dickens B, et al. Severe brain injury 2 Lumb, BL. Nunn’s Applied Respiratory Physiology. 7th to neurological determination of death: Canadian forum edition. Churchill Livingston, c2016. Chapter 5: Control recommendations. CMAJ : Canadian Medical Association of Breathing. Journal. 2006;174(6):S1-S12. doi:10.1503/cmaj.045142.

Organ Donation in Ontario: A Guide for Critical Care Residents - Neurological Declaration of Death 29 Recognition of Patients Dependant on Hypoxic Drive During Apnea Testing Karim Soliman, Pierre Cardinal

Description Rationale integrate the response from sensors3,4. Most Recognize patients with central hypoventilation The Canadian guideline recommends the iden- patients not only have an impaired response as a contraindication to interpreting the apnea tification of patients who are dependent on to hypercarbia but also to hypoxemia. Such test for neurological death declarations1. their hypoxic drive to breathe1. Such patients patients would not be adequately challenged usually suffer from either congenital or with rising carbon dioxide levels thus any acquired central hypoventilation. Recently, concerns with the performance or interpreta- congenital central hypoventilation syndrome tion of apnea testing warrants ancillary testing. has been to be linked to mutations of the In these cases, it is important that consultation PHOX2B gene2. Acquired hypoventilation with expert opinion should be considered (e.g. is associated with traumatic, ischemic, and TGLN donation support physician or a local inflammatory processes affecting the brain- expert) to discuss the use of ancillary testing. 3 Return to overview map stem . Congenital disorders such as myelo- meningocele associated with Arnold Chiari Return to sub map Type II malformation may also lead to central hypoventilation. The pathogenesis of hypoventilation in these patients is usually multi- factorial denoting conditions resulting from underlying neurologic disorders affecting the sensors ( i.e. peripheral and central chemoreceptors, and mechanoreceptors) and/or the central controller that receive input and

3 Muzumdar H, Arens R. Central Alveolar Hypoventilation 1 Shemie SD, Doig C, Dickens B, et al. Severe brain injury 2 Amiel J, Laudier B, Attie-Bitach T, et al. Polyalanine ex- Syndromes. Sleep Medicine Clinics. 2008;3:601-615. to neurological determination of death: Canadian forum pansion and frameshift mutations of the paired like ho- 4 Ramanantsoa N, Gallego J. Congenital central hypoventi- recommendations. CMAJ : Canadian Medical Association meobox gene PHOX2B in congenital central hypoventila- lation syndrome. Respiratory Physiology & Neurobiology. Journal. 2006;174(6):S1-S12. doi:10.1503/cmaj.045142. tion syndrome. Nat Genet 2003;33(4): 459–61. 2013;189:272-279.

Organ Donation in Ontario: A Guide for Critical Care Residents - Neurological Declaration of Death 30 Confirming Deep Unresponsive Coma During Clinical Examination of Neurological Death Lindsay Wilson

Description examined closely to be distinguished from lating cranial nerves (e.g. pressure on eyebrow). • Assess level of consciousness (Glasgow intact spinal reflexive movements. If there Spinal reflexive movements may include: exten- Coma Scale = 3)1. is difficulty distinguishing between spinal sion-pronation movements of the upper limbs • By definition, “deep unresponsive coma reflexive movements and centrally or non-specific flexion of the lower limbs; includes the absence of any centrally mediated motor responses, consider undulating toe reflex (plantar flexion of great mediated motor responses to pain or cen- consulttion with TGLN or a local expert toe, followed by brief plantar flexion sequen- trally mediated spontaneous movements. to determine whether an ancillary test tially of second to fifth toes); Lazarus sign Any CNS-mediated motor response to should be performed. (bilateral arm flexion, shoulder adduction, pain in any distribution, seizures, decor- hand raising to above the chest, and may in- ticate and decerebrate responses are not Rationale clude flexion of trunk, hips and knees); deep The minimum clinical criteria as a Canadian tendon reflexes; plantar responses, either flexor or extensor; respiratory-like movements (shoul- Return to overview map medical standard for neurological death includes deep unresponsive coma with absence der elevation and adduction, back arching or Return to sub map of bilateral motor responses, excluding spinal intercostal expansion) without significant tidal 2 reflexive movements. Spinal reflexive move- volume; and head turning.” If there are any ments can be either spontaneous or elicited questions about spinal reflexes, it is preferable consistent with NDD. Spinal reflexive by stimulation, including painful stimuli ap- to complete the neurological examination, movements confined to spinal distribution plied to limbs or sternum, tactile stimulation including the apnea test, and consider con- may persist.” 1 applied to palmar or plantar areas, neck flex- sultation with an expert opinion (e.g.TGLN • Test CNS-mediated motor response to ion, limb elevation or hypoxia (as may occur Donation Support Physician) before proceed- pain on all extremities and above the during ventilation disconnection). Spinal ing to ancillary testing. clavicles. Any centrally mediated response reflexes are not to be confused with a patho- to painful stimulation excludes neurological flexion or extension response. Spinal logical death. Movements should be reflexive movements are only observed in a spinal (i.e. not cranial nerve) distribution. They may 1 Shemie SD, Doig C, Dickens B, et al. Severe brain injury to neurological determination of death: Canadian forum be triggered by stimulating spinal nerves (e.g. 2 Australian and New Zealand Intensive Care Society. The recommendations. CMAJ : Canadian Medical Association sternal or nail bed pressure) but not by stimu- ANZICS Statement on Death and Organ Donation (Edi- Journal. 2006;174(6):S1-S12. doi:10.1503/cmaj.045142. tion 3.2). Melbourne: ANZICS, 2013.

Organ Donation in Ontario: A Guide for Critical Care Residents - Neurological Declaration of Death 31 Assessing Brainstem Reflexes in Adults, Adolescents and Children when Examining Neurological Death Lindsay Wilson

Description1,2 logical death. tympanic membrane is perforated. Assess corneal reflex: Assess gag reflex: Consider contacting the TGLN donation sup- • Stimulate the cornea above and below the • Insert a yankauer or tongue depressor to port physician or a local expert if the neuro- pupil with a tissue and observe both stimulate the back of the pharynx. logical exam cannot be completed or there is eyelids for any response. • Any effort to gag excludes neurological doubt regarding the interpretation of some 1 • Any response, such as blinking or tearing death . neurological findings. excludes neurological determination of death. Assess pupillary response: Rationale • In a darkened room, shine a light into The minimum clinical criteria as a Canadian each eye and observe change in pupil size. medical standard for neurological death in- • Absent reflex involves fixed and dilated Return to overview map clude absent brainstem reflexes as defined by pupils that are unreactive to light. Pupils absent gag and cough reflexes and the bilateral Return to sub map smaller than 3 mm in diameter in adults absence of corneal responses, pupillary respons- or any direct or consensual reaction es to light, with pupils at mid-size or greater, exclude neurological death1. and vestibulo-ocular responses. Although the Assess cough reflex: mechanism that moderates the vestibular ocu- Assess caloric/vestibulo-ocular response: • Insert a suction catheter into the endotra- lar response is independent of the presence of • Position head at 30° from horizontal cheal tube and stimulate the trachea. an intact tympanic membrane, many guide- • Using an otoscope, confirm that the exter- • Any effort to cough excludes neuro- lines including the Trillium Gift of Life Guide- nal auditory canals are not obstructed lines currently recommends to halt the cold cal- • Irrigate the auditory canal with at least 50 1 Step-by step overview of the clinical practice guidelines for oric testing and perform ancillary testing if the declaring neurological death in adults and children. Video ml of ice water, and observe both eyes. tympanic membrane is perforated2. In other available at http://www.organsandtissues.ca/s/english-ex- • Any eye movement excludes neurological pert/leading-practices-public-awareness-and-education-2 jurisdictions practice differs. For example, the Canadian Council for Donation and Transplantation death. Australian guidelines state that the presence of (CCDT); 2007. • Five minutes should be observed before 2 "Determination Of Death". Donation Resource Manual: a ruptured tympanic membrane does not inval- A Tool To Assist Hospitals With The Process Of Organ the other auditory canal is irrigated. And Tissue Donation. 6th ed. Toronto: Queen's Printer, • Halt the cold caloric testing if the 2014. Print.

Organ Donation in Ontario: A Guide for Critical Care Residents - Neurological Declaration of Death 32 idate the test2,3. In such cases that the brainstem assessment cannot be completed (i.e. a glass eye), ancillary testing may be recommended4. Con- sider seeking an expert opinion (e.g.TGLN Donation Support Physician or local expert) before proceeding to ancillary testing5.

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3 Australian and New Zealand Intensive Care Society. The ANZICS Statement on Death and Organ Donation (Edi- tion 3.2). Melbourne: ANZICS, 2013. 4 Trillium Gift of Life Network (TGLN), Guidelines for the neurological determination of death (NDD) for the purposes of organ donation in ontario: adult and paediatric patients 1 year and older 5 Shemie SD, Doig C, Dickens B, et al. Severe brain injury to neurological determination of death: Canadian forum recommendations. CMAJ : Canadian Medical Association Journal. 2006;174(6):S1-S12. doi:10.1503/cmaj.045142.

Organ Donation in Ontario: A Guide for Critical Care Residents - Neurological Declaration of Death 33 Assessing Brainstem Reflexes in Infants When Examining Neurological Death Louise Pope-Rhoden, Janice Beitel, Sonny Dhanani

Description1,2 Assess gag reflex: • Using an otoscope, confirm that the exter- Assess corneal reflex: • Insert a yankauer or tongue depressor to nal auditory canals are not obstructed • Stimulate the cornea with a tissue and stimulate the back of the pharynx. • Irrigate the auditory canal with at least 50 observe both eyelids for any response. • Any effort to gag excludes neurological ml of ice water, and observe both eyes. • Any response, such as blinking, excludes death. • Any eye movement excludes neurological neurological determination of death. death Assess pupillary response: • Five minutes should be observed before Assess cough reflex: • In a darkened room, shine a light into the other auditory canal is irrigated. • Insert a suction catheter into the endotra- each eye and observe change in pupil size. • Halt the cold caloric testing if the cheal tube and stimulate the trachea. • Absent reflex involves fixed and dilated tympanic membrane is perforated. • Any effort to cough excludes neurological pupils that are unreactive to light. Pupils death. smaller than 3 mm in diameter or any Consider contacting the TGLN donation direct or consensual reaction exclude support physician or a local expert if the neu- neurological death. rological exam cannot be completed or there Return to overview map is doubt regarding the interpretation of some Return to sub map Assess oculocephalic reflex: neurological findings. • Should only be performed if there is no suspicion of cervical spinal cord injury Rationale • Turn head both left and right looking at In infants (aged 30 days to 1 year (corrected for the position of the eyes gestational age), clinical examination of neuro- • With brain death, the eyes remain logical death is the same as in adults, except 1 Step-by step overview of the clinical practice guidelines for declaring neurological death in adults and children. Video mid-positioned as the head is turned that oculocephalic reflex should also be absent. available at http://www.organsandtissues.ca/s/english-ex- • Any eye movement excludes neurological This test may be more reliable than the vestibu- pert/leading-practices-public-awareness-and-education-2 death Canadian Council for Donation and Transplantation lo ocular reflex in infants due to the unique (CCDT); 2007. anatomy of the external auditory canal2. Al- 2 Shemie SD, Doig C, Dickens B, et al. Severe brain injury Assess caloric/vestibulo-ocular response: to neurological determination of death: Canadian forum though the mechanism that moderates the ves- recommendations. CMAJ : Canadian Medical Association • Position head at 30° horizontally tibular ocular response is independent of the Journal. 2006;174(6):S2-4. doi:10.1503/cmaj.045142.

Organ Donation in Ontario: A Guide for Critical Care Residents - Neurological Declaration of Death 34 presence of an intact tympanic membrane, many guidelines including the Trillium Gift of Life Guidelines currently recommends to halt the cold caloric testing and perform ancillary testing if the tympanic membrane is perforated3. In other jurisdictions practice differs. For example, the Australian guidelines state that the presence of a ruptured tympanic membrane does not invalidate the test3,4.

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3 "Determination Of Death". Donation Resource Manual: A Tool To Assist Hospitals With The Process Of Organ And Tissue Donation. 6th ed. Toronto: Queen's Printer, 2014. Print. 4 Australian and New Zealand Intensive Care Society. The AN- ZICS Statement on Death and Organ Donation (Edition 3.2). Melbourne: ANZICS, 2013.

Organ Donation in Ontario: A Guide for Critical Care Residents - Neurological Declaration of Death 35 Assessing Brainstem Reflexes in Neonates when Examining Neurological Death Louise Pope-Rhoden, Janice Beitel, Sonny Dhanani

Description1 • In a darkened room, shine a light into • Using an otoscope, confirm that the Assess corneal reflex: each eye and observe change in pupil size. external auditory canals are not obstructed • Stimulate the cornea with a tissue and ob- • Absent reflex involves fixed and dilated • Irrigate the auditory canal with at least 50 serve both eyelids for any response. pupils that are unreactive to light. Pupils ml of ice water, and observe both eyes. • Any response, such as blinking, excludes smaller than 3 mm in diameter or any • Any eye movement excludes neurological neurological determination of death. direct or consensual reaction exclude death neurological death • Five minutes should be observed before Assess cough reflex: the other auditory canal is irrigated. • Insert a suction catheter into the endotra- Assess suck reflex: • Halt the cold caloric testing if the tym- cheal tube and stimulate the trachea. • Place and lightly press the pad of the small panic membrane is perforated. • Any effort to cough excludes neurological finger against the roof of the mouth to death. determine if a response (movement of the Consider contacting the TGLN donation tongue, mouth or pharynx) is elicited support physician or a local expert if the Return to overview map • Any sucking action excludes the diagnosis neurological exam cannot be completed or there of neurological death is doubt regarding the interpretation of some Return to sub map neurological findings. Assess oculocephalic reflex: Assess gag reflex: • Should only be performed if there is no Rationale • Insert a yankauer or tongue depressor to suspicion of cervical spinal cord injury In neonates 36 weeks gestation to 29 days stimulate the back of the pharynx. • Turn head both left and right looking at old (corrected for gestational age), the clinical • Any effort to gag excludes neurological the position of the eyes examination of Neurological Death is the same death. • With brain death, the eyes remain as in adults, except that both oculocephalic Assess pupillary response: mid-positioned as the head is turned reflex and suck reflex should also be absent, and • Any eye movement excludes neurological the minimum temperature must be a core tem- 1 Step-by step overview of the clinical practice guidelines for death perature of 36°C. The accuracy of gestational declaring neurological death in adults and children. Video available at http://www.organsandtissues.ca/s/english-ex- age should be supported by clinical history (e.g. pert/leading-practices-public-awareness-and-education-2 Assess caloric/vestibulo-ocular response: dates and prenatal ultrasound) and physical Canadian Council for Donation and Transplantation • Position head at 30° horizontally (CCDT); 2007. examination. Inability to confirm a gestational

Organ Donation in Ontario: A Guide for Critical Care Residents - Neurological Declaration of Death 36 age >36 weeks should preclude NDD2.

Although the mechanism that moderates the vestibular ocular response is independent of the presence of an intact tympanic membrane, many guidelines including the Trillium Gift of Life Guidelines currently recommends to halt the cold caloric testing and perform ancillary testing if the tympanic membrane is per- forated3. In other jurisdictions practice differs. For example, the Australian guidelines state that the presence of a ruptured tympanic membrane does not invalidate the test3,4.

Return to overview map

Return to sub map

A call to the TGLN donation support physician or local expert is warranted to discuss individual cases.

2 Shemie SD, Doig C, Dickens B, et al. Severe brain injury to neurological determination of death: Canadian forum recommendations. CMAJ : Canadian Medical Association Journal. 2006;174(6):S2-4. doi:10.1503/cmaj.045142. 3 "Determination Of Death". Donation Resource Manu- al: A Tool To Assist Hospitals With The Process Of Organ And Tissue Donation. 6th ed. Toronto: Queen's Printer, 2014. Print. 4 Australian and New Zealand Intensive Care Society. The ANZICS Statement on Death and Organ Donation (Edi- tion 3.2). Melbourne: ANZICS, 2013.

Organ Donation in Ontario: A Guide for Critical Care Residents - Neurological Declaration of Death 37 Donor Management Authors: Ian M Ball MD MSc FRCPC, Andrew Healey MD FRCPC, Karim Soliman MD FRCPC, Alissa Visram MD, Sabira Valiani MD FRCPC, Michael Hartwick MD MEd FRCPC, Eli Malus MD FRCPC, Ronish Gupta MD FRCP, Pierre Cardinal MD MScEpi FRCPC, Janice Beitel RN MScN CNCC(c), Sam D. Shemie MD FRCPC, Sonny Dhanani MD FRCPC Collaborators: Louise Pope-Rhoden RN, Kim Bowman RN BScN MEd, Lindsay Wilson MHA(c) BA

Introduction For the purposes of this chapter, donor management begins at the time tance, as it ensures consented donors are actually able to donate and affects of the declaration of neurological death and ends at the time of organ both the number and quality of organs available for transplantation. The retrieval. This chapter will not address the management of Donation After brain dead donor may experience autonomic dysfunction that results in Cardiac Death donors. Medical management is critical to actualizing the precipitous changes in vital signs, potentially compromising transplant- individual or family’s intent to donate and maximizing the benefit of that able organs, with consequences on graft function, graft survival, and intent. Attentive patient care during this period is of paramount impor- overall transplantability.

38 Donor Management

Until recently, the donor management litera- detrimental effects on families of consented 4 organs)3. The delay between declaration of ture was underdeveloped, and physicians were donors. A review of 1,554 organ donors revealed neurologic death and organ retrieval can be compelled to rely on physiology, and extrapo- that the average time from neurolog- advantageous. With appropriate management lations from related research. Fortunately, there ic declaration of death to organ procurement of fluids and vasoactive agents, it is not un- is an increasing body of literature available to was 34 hours, and that in 15% of cases, pro- common for cardiac function to improve guide physicians through donor management curement took place greater than 48 hours af- over the first 24-36 hours, particularly after a decisions, and this trend is expected to increase ter declaration1. During this time period, the cardiac arrest. in the coming years. potential donor must be aggressively managed in order to minimize end-organ dysfunction, Canadian guidelines have been created to In the past, organ donors were sometimes increase the number of organs available for standardize the multisystem management4. relegated to a less important status than other surgical recovery, and optimize the post-trans- These have been used to create Trillium Gift of critically ill patients. We encourage clinicians plant graft function. This is important as it has Life Network and hospital specific order sets to view donors not just as patients deserving been shown that almost one-quarter of potential for the management of the potential organ of the highest quality end of life care, but also donors were unable to donate due to pre-pro- donor after neurological determination of death. for their ability to save and enhance the lives of curement instability2. In addition, meeting or- A close collaborative relationship and excellent recipients. This requires attention and vigilance gan donor management goals (normal cardiac, communication between the ICU team and the to principles of multi-organ support and pulmonary, renal and endocrine parameters) organ and tissue donation coordinators is para- resuscitation. increases rates of organ procurement (≥ mount for optimal organ donor management.

Key Concepts The process of organ transplantation is often lengthy, and the physiologic changes prior to 1 Inaba K, Branco BC, Lam L, et al. Organ donation and time to procurement: Late is not too late. J Trauma - Inj 3 Kotloff RM, Blosser S, Fulda GJ, et al. Manage- and after neurologic death can lead to irrevers- Infect Crit Care. 2010;68(6):1362-1366. doi:10.1097/ ment of the Potential Organ Donor in the ICU. ible end-organ dysfunction preventing organ TA.0b013e3181db30d3\r00005373-201006000-00014 [pii]. Crit Care Med. 2015;43(6):1291-1325. doi:10.1097/ 2 Malinoski DJ, Patel MS, Daly MC, Oley-Graybill C, Salim CCM.0000000000000958. donation. Missed opportunities to donate have A. The impact of meeting donor management goals on 4 Shemie SD, Ross H, Pagliarello J, et al. Organ donor man- obvious ramifications on the number of the number of organs transplanted per donor. Crit Care agement in Canada: Recommendations of the forum on transplants, but more importantly, may have Med. 2012;40(10):2773-2780. doi:10.1097/CCM.0b013e- Medical Management to Optimize Donor Organ Potential. 31825b252a. CMAJ. 2006;174:S13-S30. doi:10.1503/cmaj.045131.

Organ Donation in Ontario: A Guide for Critical Care Residents - Donor Management 39 Donor Management

Normalization of hemodynamics with appro- benefit of that intent. After brain death, the Clinical Approach (Map 1 ) priate fluid, vasopressors, and inotropes may be time needed to obtain consent, assess suit- The multisystem management of the potential necessary based on the clinical situation (Map ability, and organize transplant recovery teams donor starts with the neurologic determination 9 ,10 ). Aggressive treatment of may be prolonged. During this phase, risks for of death, consent for donation, and the in- arrhythmias is warranted. Neurogenic hemodynamic instability and compromise stitution of standardized order sets outlining pulmonary edema may occur requiring of end organ function are high necessitating the necessary monitoring and investigations increased support. More aggressive standard aggressive, and standardized donor man- required. In essence, the intensive care is strategies should be instituted if ARDS is pres- agement strategies to improve the opportunity optimized as per any other patient, and should ent. A balanced approach is needed for fluid to donate and increase the number and quality not be considered as different or unique. The resuscitation to optimize renal perfusion but of transplants. optimization of oxygenation and hemody- minimize pulmonary edema. Infections, both namic parameters are considered. In addition, isolated and systemic, do not preclude the unique physiology including autonomic in- donation and should be treated. One of the most stability and hormonal dysregulation should be common physiologic complications of neuro- attended to. logic death includes abnormalities in hormonal regulation. Diabetes insipidus is common and Standard monitoring and investigation should be identified early to prevent hypo- (Map 2 ) to ensure appropriate oxy- volemia and hypernatremia. Triple hormonal gen delivery to end organs should continue. therapy with methylprednisolone, thyroxine, Organ specific investigations (Map 3 ) may and insulin has shown to improve potential for also be needed to ensure suitability for donation and improve organ utilization (Maps eventual transplantation. This may include 4-8 ). additional and repeated laboratory samples as well as specific testing for function such as bron- Summary/Conclusion choscopy, echocardiography, and ultrasound. Successful medical management of the organ Routine prophylaxis measures such as for DVT, donor is critical to actualizing the individual or ulcers, VAP should be continued. family’s intent to donate and maximizing the

Organ Donation in Ontario: A Guide for Critical Care Residents - Donor Management 40

Map 1 - Overview Donor Management

t p

a h C o Return t Standard investigations and monitoring DVT prophylaxis

Organ specific initiate investigations Stress ulcer

Donor Management with Support Prophylaxis Decubitus ulcer From TGLN of perform

VAP

Central line associated Management blood stream infection

of Hemodynamics/ Endocrine system Circulation

Infection Respiratory system GI system Renal system

Map 2 - Standard Investigations and Monitoring Donor Management

t p

a h C o Return t

Donor Standard Management with Support Invetigations and From TGLN Monitoring Investigations to meet targets initiate (when(when applicable) applicable) including

including

Standard Monitoring monitoring Investigation Interval Target to meet targets to meet targets including... CBC q4h Hg > 70g/L

INR and PT q6h including Biochemistry Serum Na <150, normal Electrolytes q4h K,P04, Ca, Mg BUN, Cr q6h Monitor Interval Target Blood Glucose q4h BG <= 10 MAP > 70 AST, ALT, GGT, Bilirubin (total, SBP >100 direct), LDH, total protien, albu- q4h ECG Monitoring, Pulse oximetry hourly HR 60-120 min, amylase, lipase O2 sats >95% Microbiology Urine output via catheter and q1h 0.5-3 ml/kg/h Blood, urine, and ETT culture daily urometer Organ matching and suitability pH 7.35 - 7.45 TGLN will Microbiologic testing, HLA sub- ABG q4h PaCO2 35-45 mmHg arrange PaO2 > 80mmHg type, Blood type

Map 3 - Organ Specific Investigations Donor Management

t p

a h C o Return t Baseline ECG, 2D Hemodynamically if consider Serial echo echo, TnI or TnT unstable Bronchoscopy with bronchial washing sent for perform if perform initial culture, gram stain

One of: Heart Donor Lung Donor 1) male > 55, female > 60 Donor Management 2) Two risk factors AND with Support From TGLN perform daily male >40, female >45 if possible if possible 3) >Three risk factors 4) History of cocaine use 5) Upon transplant Organ Specific CXR program request Investigations

request if possible if possible Weight > 100kg or BMI > 30 or Coronary Kidney Donor Liver Donor if HCVAb positive angiogram or request by the transplant program if perform perform Urinalysis Requested by transplant program Transplant program consult Ultrasound Ultrasound or perform other investigations

Map 4 - Management of Endocrine Deficiency Donor Management

t p

a h C Elevated urine R o eturn t output Vasopressin in all patients if add Intermittent DDAVP

Donor Management with Support Elevated From TGLN serum [Na] administer targeting Management of Endocrine Deficiency administer Diabetes insipidus Urine output 0.5-3 mL/kg/h, anticipate Serum sodium Free water 130-150 mmol/L (IV or enterally) LV dysfunction secondary to thyroid hormone deficiency

Lung administer donation Thyroid hormone replacement administer in all patients

High dose steroids

Map 5 - Managing Infection Donor Management

t p

a h C o Return t

Antibiotics initiate Donor Management with Support From TGLN Proven or presumed if infection Management of Infection be aware Transplant program may delay donation to continue Measures to reduce provide time for treatment hospital-acquired infection to take effect

Map 6 - Management of the Gastrointestinal System Donor Management

t p

a h C o Return t

Enternal nutrition only

continue

Donor Management Glycemic control with Insulin infusion target BG <=10 with Support From TGLN

Management of the GI System Possible liver Hyponatremia/ consider avoid donation Hypernatremia

if small bowel donation considered, consult Donation Support Physician

Map 7 - Management of the Renal System Donor Management

t p

a h C o Return t

Pre-defined BP and perfusion targets ensure

Donor Management with Support From TGLN Nephrotoxic agent avoid Management of the Renal System

Administering isotonic fluid administer Fluid bolus prior to consider solution prior to contrast administration contrast administration

consider

Mild hypothermia (temp 34-35C)

Map 8 - Management of the Respiratory System Donor Management

t p

a h C Lung protective R to eturn ventilatory strategy Steroids in all patients (non ARDS patients) PF ratio, PIP, • PEEP of 8-10 cm H2O monitor Pplat, PaCO2 administer • Apnea tests performed Donor Management by using continuous with Support institute or continue From TGLN positive airway verify Tidal volume Management of pressure appropriate for ideal the Resiratory Patient does not meet • Closed circuit for body weight System ARDS criteria airway suction consider if • Recruitment maneuvers after disconnect from the ventilator • Tidal volumes of Patient meets 6-8 mL/kg of Tidal volume ARDS criteria predicted body weight appropriate for ideal body weight verify institute or continue Lung protective ventilation strategy monitor PF ratio, PIP, (ARDS patients) Pplat, PaCO2

if refractory hypoxemia Rescue measures to optimize oxygenation

consider Recruitment manouevers

Map 9 - Management of Hemodynamic Abnormalities Donor Management

t p

a h C o Return t

Shock

Donor Management with Support From TGLN

Management of Systematic data Current hypotheses and recognize and Hypertension perform to challenge Hemodynamic manage collection management plan Abnormalities

Arrhythmia Map 10 - Management of Hemodynamic Abnormalities - Shock Donor Management

Donor Management First choice with Support Catecholamine induced Thyroid Predefined BP and From TGLN verify consider Norepinephrine then titrate to anticipate myocardial dysfunction replacement perfusion targets Management of Dobutamine Hemodynamic Abnormalities Management monitor of Adverse effects Hemodynamic (e.g. arrhythmia) Vasopressin Abnormalities; instituted Shock Other vasopressors Distributive verify consider (first choice titrate to anticipate type shock norepinephrine)

Steroid monitor administration consider Adverse effects (Ischemic events) Hypovolemia verify secondary to DI titrate to or other causes Vasopressin Fluid resuscitation instituted institute monitor Adverse effects if high urine (pulmonary edema) output or [Na] high Administer Fluid resuscitation DDAVP in addition to vasopression select

monitor titrate to Type of crystalloid (based on serum Na)

Adverse effects (pulmonary edema) Performing Prophylaxis for Organ Donors Louise Pope-Rhoden

Description Rationale Start or continue measures to prevent: As intensivists become increasingly involved in • Deep vein thrombosis donor management, it is imperative that the • Stress ulcers same rigor that is applied to the care of living • Decubitus ulcers patients be employed in the care of organ • Ventilator-associated pneumonia Donors1. Through provision of meticulous and • Central line-associated aggressive care, and in collaboration with the bloodstream infection TGLN and transplant teams, the intensivist has the opportunity to both preserve the option of organ donation for patients and their families and provide the gift of life to others. Return to Overview map

1 Kotloff RM, Blosser S, Fulda GJ, et al. Manage- ment of the Potential Organ Donor in the ICU. Crit Care Med. 2015;43(6):1291-1325. doi:10.1097/ CCM.0000000000000958.

Organ Donation in Ontario: A Guide for Critical Care Residents - Donor Management 51 Standard Monitoring to Meet Targets Janice Beitel

Description • Optional pulmonary artery catheter in Standard monitoring of potential donors situ or central venous line (central venous 1,2,3 includes1,2: oximetry) • Vital signs q1h • Core temperature q4h Rationale • Continuous electrocardiogram (EKG) Close monitoring of hemodynamic and monitoring ventilatory function is required to optimize • Continuous pulse oximetry resuscitation and maintain optimal organ • Arterial blood pressure q1h function at the time of surgical recovery 1, 2,3,4. • Continuous central venous pressure Monitoring for possible sources of infections is (CVP) monitoring also recommended.

Return to Overview map Return to Standard Investigations and Monitoring map

• Urine output q1h • Infectious disease assessment (via q24h blood, urine & sputum cultures)1

1 "Donor Screening and Testing". Donation Resource 3 Menza R. Evaluation and Assessment of Organ Donors. Manual: A Tool To Assist Hospitals With The Process Of In: Dianne LaPointe R, Linda O, Teresa S, ed. by. A Organ And Tissue Donation. 6th ed. Toronto: Queen's Clinician's Guide to Donation and Transplantation. 1st ed. Printer, 2014. Print. Lenexa: NATCO, The Organization for Transplant 2 Shemie SD, Ross H, Pagliarello J, Baker AJ, Greig PD, Professionals; 2016. Brand T, et al. Organ donor management in Canada: 4 Kotloff RM, Blosser S, Fulda GJ, et al. Manage- recommendations of the forum on Medical Management ment of the Potential Organ Donor in the ICU. to Optimize Donor Organ Potential. CMAJ : Canadian Crit Care Med. 2015;43(6):1291-1325. doi:10.1097/ Medical Association Journal 2006;174(6):S13-32. CCM.0000000000000958.

Organ Donation in Ontario: A Guide for Critical Care Residents - Donor Management 52 Standard Investigations to Meet Targets Janice Beitel

Description either pulmonary artery catheter in situ or Rationale Standard investigations for all potential donors central venous line, respectively Standard investigations provide baseline in- include1,2: • Liver profile – Bilirubin (total and direct), formation on organ function and physiologi- • ABO - Blood Group (Cross and Type) AST, ALT, ALP, LDH, Total Protein, cal homeostasis3. Potential organ donors may • Arterial Blood Gases (ABGs)on positive Albumin, Amylase, Lipase, GGT q4h be hemodynamically unstable with electrolyte end expiratory pressure (PEEP) 8-10 cm • PT/INR, PTT q6h disturbances related to the underlying cause of • Electrolytes, Creatinine, Urea, Glucose, 2, 3 H2O q2-4h. Contact the transplant team death, disease process or treatments . Standard for patients on higher PEEP who may Ca, PO4, Mg, Lactate q4h investigations are well accepted in practice and become hypoxemic with lower PEEP • CK, CK-MB q4-8h serial testing provides trending information on levels. • Troponin (I or T) q8h organ function for the early identification and • CBC q4h • Urinalysis q24h correction of electrolyte imbalances and/or the • C & S – sputum, urine and blood implementation of other interventions to meet Return to Overview map (include gram stain) q24h targets2. • 12 lead EKG Return to Standard Investigations and • CXR q4h Monitoring map

Note: • Serum Lactate q 2-4h Please see organ specific investigations for • Mixed venous blood gases or central lung and heart serological tests for infectious venous oxygen saturation q6h through diseases are requested by TGLN and sent to be processed in central laboratories in Ontario

1 "Donor Screening and Testing". Donation Resource Man- ual: A Tool To Assist Hospitals With The Process Of Or- gan And Tissue Donation. 6th ed. Toronto: Queen's Print- er, 2014. Print. 2 Shemie SD, Ross H, Pagliarello J, Baker AJ, Greig PD, 3 Menza R. Evaluation and Assessment of Organ Donors. Brand T, et al. Organ donor management in Canada: rec- In: Dianne LaPointe R, Linda O, Teresa S, ed. by. A Cli- ommendations of the forum on Medical Management to nician's Guide to Donation and Transplantation. 1st ed. Optimize Donor Organ Potential. CMAJ : Canadian Medi- Lenexa: NATCO, The Organization for Transplant Pro- cal Association Journal 2006;174(6):S13-32. fessionals; 2016.

Organ Donation in Ontario: A Guide for Critical Care Residents - Donor Management 53 Investigations for Heart Donors Andrew Healey

Description biochemistry, and echocardiography sig- The EKG and Troponin are useful to assess for • EKG nificantly increases the number of hearts conduction abnormalities and ongoing isch- 6 • Troponin I or T q12h suitable for transplantation as the often emia . In Canada, Health Canada requires • Baseline echocardiography severe myocardial dysfunction resolve with these investigations of all donors where possi- • If hemodynamically unstable,or reduced time and hormonal replacement therapy ble. When initially abnormal, serial ECGs and 1,2,3,4,5 ejection fraction on baseline echo, (T4) . The heart is rarely ruled out Troponins assist transplanters assess suitability perform serial echocardiogram for transplantation based on the initial as commonly the abnormalities are transient. 5 • In patients with risk factors, request echocardiogram . Therefore, medical coronary angiography support and re-evaluation by serial echo- The hemodynamic assessment of all donors cardiogram should be performed prior to begins with a surface echocardiogram7. This decisions about transplantability. begins the assessment of the suitability of the Return to Overview map 3. Knowledge of the data supporting heart for transplant but also critically informs improvement will assist intensivists in the hemodynamic management of patients Return to Organ Specific discussing the need for serial evaluation who are not heart donors. The time following Investigations map with colleagues and the healthcare team. herniation is associated with an initial excess of 1 Casartelli M, Bombardini T, Simion D, Gaspari MG, Pro- sympathetic outflow, followed by loss of sym- caccio F. Wait, treat and see: echocardiographic monitoring pathetic tone and systemic vascular resistance. Rationale of brain-dead potential donors with stunned heart. Car- diovasc Ultrasound. 2012;10:25. These result in often dramatic changes in the In evaluating the heart donor, three critical key 2 Zaroff JG, Babcock WD, Shiboski SC. The impact of left ECG, Troponin and the echocardiogram. Both concepts should be considered: ventricular dysfunction on cardiac donor transplant rates. J left ventricular dysfunction and vasodilation Heart Lung Transplant. 2003;22(3):334-7. 1. With the advent of expertly managed ven- 3 Mascia L, Mastromauro I, Viberti S, Vincenzi M, Zanello often lead to hypotension. In the most hemody- tricular assist devices, the quality of the M. Management to optimize organ procurement in brain namically unstable potential donors, echocar- donor heart must be sufficient that trans- dead donors. Minerva Anestesiol. 2009;75(3):125-33. 4 Borbely XI, Krishnamoorthy V, Modi S, et al. Temporal 6 Shemie SD, Ross H, Pagliarello J, et al. Organ donor man- plantation of the donor heart results in Changes in Left Ventricular Systolic Function and Use of agement in Canada: recommendations of the forum on mortality reduction compared to ongoing Echocardiography in Adult Heart Donors. Neurocrit Care. Medical Management to Optimize Donor Organ Potential. 2015;23(1):66-71. CMAJ. 2006;174(6):S13-32. circulatory support. 5 Sopko N, Shea KJ, Ludrosky K, et al. Survival is not com- 7 Venkateswaran RV, Townend JN, Wilson IC, Mascaro JG, 2. (Serial examinations of the heart by EKG, promised in donor hearts with echocardiographic abnor- Bonser RS, Steeds RP. Echocardiography in the potential malities. J Surg Res. 2007;143(1):141-4. heart donor. Transplantation. 2010;89(7):894-901.

Organ Donation in Ontario: A Guide for Critical Care Residents - Donor Management 54 diography can provide information on causes intensivists to remember that coronary artery with both the contrast load and the transfer of of instability (e.g. stress cardiomyopathy) and disease in an allograft progresses rapidly and is donors. guide a goal-directed resuscitation and choice one of the main causes of graft loss after of initial vasopressors 7. While early echocar- transplantation. The CCDT guidelines6 sug- The use of the pulmonary artery catheter is of- diography may assist the physician with gest if one of the following are present, coronary ten found within algorithms for donor manage- management of the hemodynamics, an abnor- angiography should be performed: ment6. Experience over time with CVP moni- mal echocardiogram should not be seen as an toring, targeted therapy to address deficits in exclusion to potential heart donation 5. There 1. male > 55 or female > 60 organ perfusion and serial echocardiography is a significant body of literature that cites the 2. two cardiac risk factors* AND male > 40 has diminished the need for PA catheters. In marked effects of time and hormonal treatment, or female >45 special circumstances in the donor or recipient, resulting in the resolution of both regional and 3. > three risk factors a pulmonary artery catheter might be request- 4. history of cocaine use ed to evaluate a specific parameter of donor Return to Overview map 5. transplant program request heart function. This is almost exclusively per- Return to Organ Specific formed at the request of the accepting transplant Investigations map *Risk Factors include: smoking, hypertension, program and after all other testing suggests diabetes, hyperlipidemia, body mass index > suitability of the organ. global left ventricular dysfunction to complete 32, family history of the disease, prior histo- recovery 1,2,3,4,5 In special circumstances, trans- ry of coronary artery disease, ischemia on esophageal echocardiography may be required electrocardiogram, anterolateral regional wall at the request of the transplant teams or in the motion abnormalities on echocardiogram, event transthoracic echocardiography does not 2-dimensional echocardiographic assessment produce adequate imaging windows. of ejection fraction of ≤ 40%.

Coronary angiography is an essential and often The authors recommend contact with the organ final step in the assessment of the donor heart donor organization with all other data prior to suitability. In perfect circumstances, angiogra- proceeding to coronary angiography to ensure phy is not required but this is rare. It behoves potential suitability as there is risk associated

Organ Donation in Ontario: A Guide for Critical Care Residents - Donor Management 55 Investigations for Lung Donors Janice Beitel, Pierre Cardinal, Andrew Healey, Kim Bowman

Description ABG’s (challenge gases) are routinely drawn

For any potential donors when lungs are being after 20 min on a FiO2 of 1 to assess the PaO2:- considered for transplantation, perform: FiO2 ratio. Chest radiography is used to assess • Arterial Blood Gases q 4h on 100% O atelectasis, infiltrates, or infection in combina- 2 3 (challenge gases) tion with other clinical findings . Although not • Chest radiography q41,2 supported by strong evidence, investigations • Bronchoscopy 1,2 a second bronchoscopy (CXR/ABGs) are requested every four hours is performed in recovery surgery1 to monitor lung function. The role of bedside • Bronchoalveolar lavage (BAL) 2 ultrasound to evaluate lung volume status and • BAL gram stain, culture and sensitivity cardiac function is evolving, but is not considered standard at this time. Bronchoscopy is required to investigate any CXR findings, Return to Overview map identify aspiration, infection and to clear air- Return to Organ Specific way secretions as needed 3. Bronchoscopy is also Investigations map performed to exclude any endobronchial lesions and to define anatomy. A bronchial lavage for Rationale gram stain and sensitivity may help confirm infection and refine treatment that will often Ongoing assessment for oxygenation oc- need to continue in the immunocompromised curs throughout management and organ recipient 2,3. A second bronchoscopy is almost specific investigation of the potential donor. universally repeated in the OR by the transplant 1,3 1 "Donor Screening and Testing". Donation Resource Man- team prior to lung recovery . ual: A Tool To Assist Hospitals With The Process Of Or- gan And Tissue Donation. 6th ed. Toronto: Queen's Print- er, 2014. Print. 2 Shemie SD, Ross H, Pagliarello J, Baker AJ, Greig PD, 3 Menza R. Evaluation and Assessment of Organ Donors. Brand T, et al. Organ donor management in Canada: rec- In: Dianne LaPointe R, Linda O, Teresa S, ed. by. A Cli- ommendations of the forum on Medical Management to nician's Guide to Donation and Transplantation. 1st ed. Optimize Donor Organ Potential. CMAJ : Canadian Medi- Lenexa: NATCO, The Organization for Transplant Pro- cal Association Journal 2006;174(6):S13-32. fessionals; 2016.

Organ Donation in Ontario: A Guide for Critical Care Residents - Donor Management 56 Investigations for Liver Donors Janice Beitel, Pierre Cardinal, Andrew Healey, Kim Bowman

Description transplant team, especially if the donor Donor serum sodium greater than 155 has been For any potential donors when liver is weighs over 100 kg or has a body mass weakly associated with primary liver dysfunc- being considered for potential transplantation, index greater than 30. tion in transplant recipients but reversible if 4 biochemical tests should include: 1,2,3 • Uncommonly, intraoperative liver biopsy hypernatremia is corrected . • Bilirubin (total and direct), AST, ALT, ALP, LDH, Total Protein, Albumin, Amy- Note: While the use of ultrasound to assess for fat- lase, Lipase, GGT q 4 h Serologic testing is requested by TGLN and ty liver remains controversial, the test may • INR, PTT q6 sent to be processed in in central laboratories be requested by the transplant program when • Serum sodium levels should be in Ontario donor characteristics are associated with an maintained within normal ranges of increased risk of graft failure in the recipient. 135 - 145 mmol/L Rationale Ultrasounds are also requested to assist with Assessment of liver enzymes through biochem- assessment especially when the donor is located 3 Return to Overview map ical testing provides information to assess for in a geographically remote area . The transplant team will very rarely perform liver biopsies Return to Organ Specific acute ischemia related to events either pre- Investigations map ceding or surrounding neurological death 2,3,4. intraoperatively at the time of procurement in Repeated testing provides the opportunity to donors who weigh over 100 kg or have a body 3 • Liver ultrasound may be requested by see a trend in liver enzymes as an indication mass index greater than 30 . that the insult is over and the liver is show- 1 "Donor Screening and Testing". Donation Resource Man- ual: A Tool To Assist Hospitals With The Process Of Or- ing signs of recovery. Since the bile ducts gan And Tissue Donation. 6th ed. Toronto: Queen's Print- have only one blood supply (hepatic artery), er, 2014. Print. they are most susceptible to ischemic injury 2 Shemie SD, Ross H, Pagliarello J, Baker AJ, Greig PD, Brand T, et al. Organ donor management in Canada: rec- placing the potential recipient at risk for bile ommendations of the forum on Medical Management to duct complications. Optimize Donor Organ Potential. CMAJ : Canadian Medi- cal Association Journal 2006;174(6):S13-32. 3 Menza R. Evaluation and Assessment of Organ Donors. In: Dianne LaPointe R, Linda O, Teresa S, ed. by. A 4 Kotloff RM, Blosser S, Fulda GJ, et al. Manage- Clinician's Guide to Donation and Transplantation. 1st ed. ment of the Potential Organ Donor in the ICU. Lenexa: NATCO, The Organization for Transplant Crit Care Med. 2015;43(6):1291-1325. doi:10.1097/ Professionals; 2016. CCM.0000000000000958.

Organ Donation in Ontario: A Guide for Critical Care Residents - Donor Management 57 Investigations for Kidney Donors Alissa Visram, Sabira Valiani, Pierre Cardinal

Description Rationale younger than 65 with a creatinine of 133µmol/L In addition to the standard investigations A urinalysis is a useful screening tool to assess or greater, an abnormal urinalysis, or a history 2 needed for all NDD donors, investigations for for microscopic hematuria and proteinuria, of hypertension or diabetes . If a kidney biopsy renal donors should include: both of which can be markers of glomerular is warranted, it is usually performed intraoper- • Urinalysis daily pathology and may affect the decision to trans- atively at the time of procurement, and not in 2 • Serum creatinine and urea every 6 hours plant the kidney1. Persistent microscopic hema- the intensive care unit . A kidney biopsy in a • Uncommonly, intraoperative kidney turia should prompt a workup to exclude uro- potential extended criteria donor can identify biopsy (if age >65, or age <65 with a logic causes such as urinary tract infections or conditions such as glomerulosclerosis, vascular history of hypertension, diabetes, nephrolithiasis. If the microscopic hematu- abnormalities, or interstitial fibrosis that may abnormal urinalysis, or serum creatinine ria persists, consultation with the transplant affect the decision of the team to transplant the 3 >133µmol/L) - this decision is made in physician is warranted in order to determine if a kidney . Expanded criteria donors are those kidney biopsy is required. Urinalysis and urine who are at increased risk of graft failure, and Return to Overview map culture are Health Canada requirements of all include donors older than 60 years, or those 50- 59 years with at least two comorbidities (cere- Return to Organ Specific organ donors. brovascular cause of death, renal insufficiency, Investigations map 4 Routine evaluation of the donor’s creatinine and or hypertension) . concert with the transplant team and the urea is used to monitor for objective signs of procedure usually carried out intraopera- end organ dysfunction and acute kidney injury. The Society of Critical Care Medicine tively at the time of procurement. Serial measurements can document 2 Shemie SD, Ross H, Pagliarello J, et al. Organ donor man- • Consider radiographic imaging of kidneys improvement (or deterioration) with time and agement in Canada: Recommendations of the forum on Medical Management to Optimize Donor Organ Potential. if requested by the transplant teams. treatment. CMAJ. 2006;174:S13-S30. doi:10.1503/cmaj.045131. Indications for radiographic imaging 3 Kotloff RM, Blosser S, Fulda GJ, et al. Manage- include donors with a family history of The Canadian guidelines recommend kidney ment of the Potential Organ Donor in the ICU. Crit Care Med. 2015;43(6):1291-1325. doi:10.1097/ polycystic kidney disease, renal stones or biopsies for patients older than 65, or those CCM.0000000000000958. other urologic abnormalities. 4 Port F, Bragg-Gresham J, Metzger R, Dykstra D, Gilles- 1 Andrews P, Burnapp L, Manas D, Bradley J, Dudley C. pie B, Young E, Delmonico F, Wynn J, Merion R, Wolfe Summary of the British Transplantation Society/Renal As- R, Held P. Donor characteristics associated with reduced sociation UK Guidelines for Living Donor Kidney Trans- graft survival: an approach to expanding the pool of kid- plantation. Transplantation. 2012;93:666-673. ney donors. Transplantation. 2002;74:1281-1286.

Organ Donation in Ontario: A Guide for Critical Care Residents - Donor Management 58 suggests that radiographic imaging of the kidneys may be warranted in donors who have a family history of polycystic kidney disease, or a history of renal stones or urologic abnormal- ities3. Renal imaging in Canada is currently performed only on the request of the transplant teams.

Return to Overview map Return to Organ Specific Investigations map

Organ Donation in Ontario: A Guide for Critical Care Residents - Donor Management 59 Anticipating Diabetes Insipidus in the Organ Donor Michael Hartwick, Sonny Dhanani

Description of water from the kidneys. After brain death, a lack of AVP leads to unregulated renal losses of • Anticipate that diabetes insipidus (DI) is free water resulting in a state of diabetes insip- common in patients who are dead by idus1. Diabetes insipidus is confirmed if urine neurological criteria. output remains excessive (> 4mL/kg/h) as well • Insert a foley catheter and monitor fluid as dilute (< 200 mOsm/kg•H O) and associ- inputs and outputs. 2 ated with hypernatremia (> 145mmol/L) and • Recognize dilute urine an increased serum osmolality (> 300mOsm/ (< 200 mOsm/kg•H O), 2 kg•H O)2. In the context of brain death, polyuria (> 4mL/kg/h), 2 diabetes insipidus should be presumed even if as well as hypernatremia (> 145mmol/L) all criteria are not met, especially in the context as signs of diabetes insipidus in the of clinical hypovolemia. potential NDD donor.

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Return to Endocrine Deficiency map

Rationale Arginine vasopressin (AVP) is a peptide that is formed in the hypothalamus and then stored in as well as secreted from the posterior pituitary. Its anti-diuretic effect on the V2 receptors 1 Loh JA, Verbalis JG. Disorders of water and salt metab- within the renal collecting system promotes olism associated with pituitary disease. Endocrinol Metab the reabsorption of free water. AVP regulates Clin North Am 2008; 37:213–234 2 Trillium Gift of Life Network. Donation Resource Manu- extracellular fluid volume by the reabsorption al: A tool to assist hospitals with the process of organ and tissue Donation. Queen's Printer for Ontario: 2010.

Organ Donation in Ontario: A Guide for Critical Care Residents - Donor Management 60 Anticipating LV Dysfunction Secondary to Thyroid Hormone Deficiency Sonny Dhanani stores, a shift from aerobic to anaerobic metab- Description olism, and a reduction in cardiac function. In addition, thyroid replacement has been shown To anticipate the transient left ventricular car- to exert a positive effect on myocardial gene ex- diac dysfunction after brain death that may be pression2. In animal models, the transition to responsive to empiric thyroid hormone replace- anaerobic metabolism is reversed with T3 re- ment. placement and is accompanied by a return of myocardial function3,4. Rationale Thyroid hormone plays a part in cardiovascular The evidence supports starting thyroxine in regulation by improving both contractility and the presence of LV dysfunction. However, in chronotropy, as well as by decreasing systemic light of minimal harm, the recommendation is vascular resistance. The damage to the hypotha- to start thyroid replacement even without confirmed LV dysfunction as part of empiric triple Return to Overview map hormonal therapy regimens (vasopressin, and corticosteroids)5. Return to Endocrine Deficiency map lamic-pituitary axis that ensues with herniation 2 James SR, Ranasinghe AM, Venkateswaran R, McCabe triggers hormonal dysregulation and may lead CJ, Franklyn JA, Bonser RS.The effects of acute triiodothyronine therapy on myocardial gene expression in brain 1 to clinical hypothyroidism . However, in some stem dead cardiac donors. J Clin Endocrinol Metab. 2010 patients, the clinical picture is more consistent Mar;95(3):1338-43. 159. 3 Novitzky D, Cooper DK, Rosendale JD, et al: Hormonal with sick euthyroid syndrome rather than true therapy of the brain-dead organ donor: Experimental and hypothyroidism. Animal models demonstrate clinical studies.Transplantation 2006; 82:1396–1401 significant decline in triiodothyronine (T3) 4 Cooper DK, Novitzky D, Wicomb WN: The pathophysi- ological effects of brain death on potential donor organs, and free thyroxine (T4) levels after brain death. with particular reference to the heart. Ann R Coll Surg This results in a depletion of myocardial energy Engl 1989; 71:261–266 5. Kutsogiannis DJ, Pagliarello G, Doig C, Ross H, She- 1 1. Chen EP, Bittner HB, Kendall SW, et al: Hormonal mie SD. Medical management to optimize donor organ and hemodynamic changes in a validated animal model of potential: review of the literature. Can J Anaesth. 2006 brain death. Crit Care Med 1996; 24:1352–1359 Aug;53(8):820-30.

Organ Donation in Ontario: A Guide for Critical Care Residents - Donor Management 61 Administering Intermittent DDAVP when Managing Donors Sonny Dhanani, Ronish Gupta, Pierre Cardinal, Andrew Healey

1 Description splanchnic blood flow . recent retrospective analysis of 458 neurologically deceased adult kidney donors suggest- To administer vasopressin and or intermittent Diabetes insipidus without hypotension may ed that those treated with desmopressin actu- DDAVP in most potential donors after brain also be managed with desmopressin (1-desami- ally had improved pre-recovery renal function death. no-8-d-arginine vasopressin, or DDAVP). Des- (creatinine 97 ± 44 vs 124 ± 106 µmol/L; p < mopressin is an AVP analogue whose mechanism 0.001)4. Rationale of action is highly specific for the V2 vasopres- In either case, AVP infusions or desmopressin Although the mechanism has not been estab- sin receptors in the renal collecting system. This boluses should be titrated to target serum sodi- lished, diabetes insipidus has the potential property allows desmopressin to inhibit diuresis um levels 130 – 155 mmol/L and urine output to impair organ function beyond that sim- with virtually no vasopressor side effect. Multi- 0.5 – 3 mL/kg/h. If needed, AVP and desmo- ply resulting from diuresis, hypovolemia, and ple routes of administration are available, but pressin may also be used simultaneously for pa- hemodynamic instability. Potential organ do- the intravenous route is preferred in the tients who continue to have a high urine output organ donor2. Although concerns for potential despite treatment with AVP alone. Intermittent Return to Overview map thrombogenic complications have been raised intravenous DDAVP 4 micrograms every 6 Return to Endocrine Deficiency map with desmopressin use, it does not seem to hours is a common regimen. Intravenous AVP impair graft survival. One trial of 97 adult or- can be titrated between 0.5 units/h and maxi- gan donors randomized to receive desmopressin mum of 2.4 units/h. Intravenous maintenance nors with diabetes insipidus may be managed or nothing for diabetes insipidus demonstrat- fluids to maintain blood pressure and perfusion with an intravenous AVP infusion or inter- ed no impairment in pre-procurement renal and the administration of free water (either mittent desmopressin. An AVP infusion is function or post-transplant need for dialysis through the enteral route (free water flushes) or the preferred agent for patients with concom- in those who received desmopressin3. A more intravenously (D5W)) should be considered to 5 itant hypotension. Given that it provides the 1 Chen JM, Cullinane S, Spanier TB, Artrip JH, John R, Ed- aggressively correct hypernatremia . dual benefits of anti-diuresis as well as hemo- wards NM, Oz MC, Landry DW. Vasopressin deficiency 4 Dunser MW, Mayr AJ, Ulmer H, Knotzer H, Sumann dynamic support, it is administered in most and pressor hypersensitivity in hemodynamically unstable G, Pajk W, Friesenecker B, Hasibeder WR. Arginine va- organ donors. Circulation 1999; 100 (suppl II):II-246. sopressin in advanced vasodilatory shock: a prospec- NDD patients who are not hypertensive. In 2 Pennefather SH, Bullock RE, Mantle D, Dark JH. Use of tive, randomized,controlled study. Circulation. 2003 May hypertensive patients, AVP is best avoided giv- low dose arginine vasopressin to support brain-dead organ 13;107(18):2313-9. donors. Transplantation 1995; 59(1):58-62. 5 Kutsogiannis DJ, Pagliarello G, Doig C, Ross H, She- en concerns around possible interference with 3 Nakagawa K, Tang JF. Physiologic response of human mie SD. Medical management to optimize donor organ end-organ perfusion based on animal models of brain death and the use of vasopressin for successful or- potential: review of the literature. Can J Anaesth. 2006 gan transplantation. J Clin Anesth. 2011 Mar;23(2):145-8. Aug;53(8):820-30.

Organ Donation in Ontario: A Guide for Critical Care Residents - Donor Management 62 Administering Free Water in the Organ Donor Sonny Dhanani, Pierre Cardinal, Andrew Healey lead to the accumulation of compensatory strategies, it is recommended to target normal Description idiogenic osmoles in donor organs. Once trans- serum sodium levels by selecting appropriate planted, significant intracellular fluid shifts may maintenance intravenous fluids, the ear- If euvolemic with serum Na between 135-145 develop as these organs are exposed to the ly recognition of diabetes insipidus and mmol/L: recipient normal serum; the different osmo- hypovolemia, and the aggressive correction of • Initial maintenance intravenous fluids lalities resulting in a water influx into the hypernatremia. should be administered to achieve euvole- transplanted organs. mia with 0.9%NS or Ringer’s Lactate If euvolemic with serum Na>145mmol/L: Traditionally, hypernatremia was considered to • Administer a IV bolus of 250 mL of D5W be independently associated with hepatic and or free water enterally renal dysfunction or graft loss after transplan- • and immediately assess for diabetes tation. However, more recent evidence suggests insipidus that this effect may be less significant than once Return to Overview map believed and that detrimental effects of hypernatremia are reversible if serum sodium levels Return to Endocrine Deficiency map are corrected 1,2,3.

Given that avoiding or treating hypernatremia is • Change maintenance fluids to D5W. easily achieved using inexpensive management If clinically hypovolemic and hypernatremic: • Administer Ringer’s Lactate bolus of 1 Bloom MB, Raza S, Bhakta A, et al. Impact of Deceased Organ Donor Demographics and Critical Care End Points 500 mL IV on Liver Transplantation and Graft Survival Rates. J • Once fluid resuscitated administer free Am Coll Surg. 2015;220(1):38-47. doi:10.1016/j.jamcoll- water (intravenously or enterally) surg.2014.09.020. 2 Kazemeyni SM, Esfahani F. Influence of hypernatremia and polyuria of brain-dead donors before organ pro- Rationale curement on kidney allograft function. Urol J. 2008 Sum- mer;5(3):173-7. Hypernatremia (serum sodium > 155 mmol/L) 3 Mangus RS, Fridell JA, Vianna RM, Milgrom ML, secondary to excessive sodium administration Chestovich P, Vandenboom C,Tector AJ. Severe hypernatremia in deceased liver donors does not impact during resuscitation or diabetes insipidus may early transplant outcome. Transplantation. 2010 Aug 27;90(4):438-43.

Organ Donation in Ontario: A Guide for Critical Care Residents - Donor Management 63 Donation Delays Due to Infection Treatment Alissa Visram, Sabira Valiani, Pierre Cardinal, Andrew Healey

Description Rationale promptly treated with pathogen-directed anti- • Invasive bacterial infection may not be a It is important to appreciate that bacterial in- biotic therapy. Empiric antibiotic therapy may contraindication to organ donation. fections are not necessarily contraindications to be considered in those NDD donors at risk of • In the presence of proven or suspected organ donation1,2. Donors in the intensive care bronchopneumonia. Similarly, NDD donors bacterial infection, organ procurement unit are at increased risk of bacterial infections with bacterial meningitis may also be suitable may be delayed to ensure that donors are from sources such as indwelling catheters/ organ donors assuming that they receive antibi- treated with appropriate targeted antibiot- indwelling monitoring devices3, bronchopneu- otic therapy directed at the presumed pathogen. ics and to reduce the risk of transmission monia or other sites as observed in all critically Of note, a similar antibiotic regimen is often to the recipient. ill patients. On occasion, the event leading to continued for a 5-10 day duration in recipients • Consult with transplant team and infec- NDD may be infectious in origin (e.g. bacterial whose organs are retrieved from donors with 2 tious diseases specialists to determine the meningitis). However, bacteremic donors who proven or suspected infections . The risks asso- appropriate duration of therapy. receive pathogen-directed antibiotic therapy ciated with organ procurement from fungemic for 24 to 48 hours prior to organ procurement donors has not been clearly established but this Return to Overview map transmit few, if any, infections to the recipi- too does not represent a contraindication to ents4. Therefore, bacteremic donors should be transplantation. Expert consultation is advised Return to Management of Infection map in the event of fungemia. 1 Shemie SD, Ross H, Pagliarello J, et al. Organ donor management in Canada: Recommendations of the forum on Medical Management to Optimize Donor Organ Potential. Consultation with infectious disease specialists CMAJ. 2006;174:S13-S30. doi:10.1503/cmaj.045131. may be beneficial in order to provide recom- 2 Kotloff RM, Blosser S, Fulda GJ, et al. Manage- ment of the Potential Organ Donor in the ICU. mendations regarding the choice of antibiotic. Crit Care Med. 2015;43(6):1291-1325. doi:10.1097/ In addition, the transplant team should be CCM.0000000000000958. 3 Cerutti E, Stratta C, Romagnoli R, Serra R, Lepore M, Fop informed of any proven or suspected infections F, Mascia L, Lupo F, Franchello A, Panio A, Salizzoni M. (whether bacterial, fungal, or viral) as this will Bacterial- and fungal-positive cultures in organ donors: 1 Clinical impact in liver transplantation. Liver Transpl. influence the decision to transplant or its timing . 2006;12:1253-1259. 4 Cohen J, Michowiz R, Ashkenazi T, Pitlik S, Singer P. Successful Organ Transplantation from Donors with Acinetobacter Baumannii Septic Shock. Transplantation. 2006;81:853-855.

Organ Donation in Ontario: A Guide for Critical Care Residents - Donor Management 64 Enternal Nutrition in the Organ Donor Kim Bowman

Description Rationale • Medical management of the donor is The influence of donor nutrition on graft sur- similar to the management of critically vival has been previously studied in several small ill patients animal studies but not formally in humans2. • Routine enteral feedings should be Tube feedings may be beneficial for small bow- initiated and continued in donors1 el donors due to a perceived protective effect on • If initiated, parenteral nutrition should mucosal structure3. It is recommended that be continued1 nutrition in donors be continued. Feedings should be discontinued on call to the operating Return to Overview map room prior to organ recovery. Earlier dis- Return to Management of continuation may be requested if lung retrieval Gastrointestinal System map is being considered1.

2 Kutsogiannis, D.J., Shemie, S.D., Doig, C. Donor Organ Management: Literature Review (short version). Edmon- ton: The Canadian Council for Donation and Transplanta- tion, 2004. 1 Shemie SD, Ross H, Pagliarello J, et al. Organ donor man- 3 Kotloff RM, Blosser S, Fulda GJ, et al. Manage- agement in Canada: Recommendations of the forum on ment of the Potential Organ Donor in the ICU. Medical Management to Optimize Donor Organ Potential. Crit Care Med. 2015;43(6):1291-1325. doi:10.1097/ CMAJ. 2006;174:S13-S30. doi:10.1503/cmaj.045131. CCM.0000000000000958.

Organ Donation in Ontario: A Guide for Critical Care Residents - Donor Management 65 Glycemic Control in the Organ Donor Kim Bowman, Sonny Dhanani, Andrew Healey

Description Rationale • Loss of glycemic control part of hormonal The goals of donor management are similar to changes accompanying brain death1 those used to treat other patients in the ICU. • Hyperglycemia is not uncommon in brain Hemodynamic stability, normovolemia and dead donors normothermia should be preserved. Endocrine • Glucose level should be assessed q4h2 and disorders (including changes in glycemic normal parameters maintained control) are commonly observed in brain dead 1 • Standard management includes maintain- donors . ing glucose level of 6-10 mmol/L3 Several factors may impact glucose levels, including underlying diabetes mellitus, pancreatic Return to Overview map insufficiency, and hypotonic dextrose solutions used for the treatment of free water replacement Return to Management of in patients with hypernatremia. Traditionally, Gastrointestinal System map protocols have recommended to initiate and titrate insulin infusion to maintain serum glucose level at 6-10 mmol/L3. Without specific evidence in NDD patients, more recent guidelines recommend that glucose should be maintained within normal parameters, as per current practice in the ICU3. 1 Kutsogiannis, D.J., Shemie, Sam D., Doig, Christopher. Donor Organ Management: Literature Review (short version). Edmonton: The Canadian Council for Donation and Transplantation, 2004.

2 "Donor Screening and Testing". Donation Resource Man- 3 Kotloff RM, Blosser S, Fulda GJ, et al. Manage- ual: A Tool to Assist Hospitals with The Process Of Or- ment of the Potential Organ Donor in the ICU. gan And Tissue Donation. 6th ed. Toronto: Queen's Print- Crit Care Med. 2015;43(6):1291-1325. doi:10.1097/ er, 2014. Print. CCM.0000000000000958.

Organ Donation in Ontario: A Guide for Critical Care Residents - Donor Management 66 Avoid Hyponatremia or Hypernatremia Janice Beitel, Andrew Healey

Description • Standard investigation to manage targets and/or mimic neurological death1,2, specifically Serum sodium levels should be maintained (frequent electrolyte monitoring) hypernatremia (> 160 mmol/L) is of concern. within normal ranges of 135 - 145 mmol/L to • Assessment of underlying causes (free Further, donor serum sodium greater than 155 enable pronouncement of neurological death1, water diuresis, diabetes insipidus, osmotic has been weakly associated with primary liver promote optimal donor organ function2, and diuresis (e.g. glucosuria)) dysfunction in transplant recipients but re- 2,3 improve liver outcomes for transplant recipi- • Treating diabetes insipidus with v versible if hypernatremia is corrected . Giv- ents 2,3,4. asopressin infusions or desmopressin en the potential impact of serum sodium • Administering vasopressin infusions in abnormalities on pronouncement of death by Interventions associated with donor care to patients who are at high risk of death by neurological criteria and possibly liver graft avoid hyper/hyponatremia include1,3,4: neurological criteria and hypotensive outcomes, it is necessary to proactively manage • Appropriate fluid resuscitation and levels and address imbalances. sodium based IV fluids (Ringer Lactate, Return to Overview map Normal Saline) for hyponatremia Return to Management of • Use of hypotonic IV fluids (e.g. D5W) Gastrointestinal System map and enteral free water replacement for hypernatremia 1 Shemie SD, Doig C, Dickens B, et al. Severe brain injury to neurological determination of death: Canadian forum recommendations. CMAJ : Canadian Medical Association Rationale Journal. 2006;174(6):S2,3. doi:10.1503/cmaj.045142. 2 Shemie SD, Ross H, Pagliarello J, et al. Organ donor man- The most common electrolyte disturbances in agement in Canada: Recommendations of the forum on patients who have been pronounced dead by Medical Management to Optimize Donor Organ Potential. CMAJ. 2006;174:S13-S30. doi:10.1503/cmaj.045131. neurological criteria or who are at risk for 3 Kotloff RM, Blosser S, Fulda GJ, et al. Manage- progressing to death are sodium disturbances, ment of the Potential Organ Donor in the ICU. usually hypernatremia. Crit Care Med. 2015;43(6):1291-1325. doi:10.1097/ CCM.0000000000000958. 4 Totsuka E, Dodson F, Urakami A, Moras N, Ishii T, Lee Severe electrolyte abnormalities are considered MC, et al. Influence of high donor serum sodium levels on early postoperative graft function in human liver transplan- a confounding factor which might rarely pre- tation: Effect of correction of donor hypernatremia. Liver vent the observation of neurological responses Transplantation and Surgery 1999;5:421-8

Organ Donation in Ontario: A Guide for Critical Care Residents - Donor Management 67 Consulting the Donation Support Physician when Small Bowel Donation is Considered Louise Pope-Rhoden, Andrew Healey

Description Rationale team. In some circumstances, intravenous anti- Small bowel transplant is the rarest form of or- The selection of small bowel donors varies biotics will also be requested. Some centers may gan transplantation. If small bowel donation is somewhat from donor selection for other ask for a CT with intravenous and oral contrast being considered, consultation with TGLN is organ allografts. The organs procured for in- to define the intra-abdominal anatomy. If the recommended. Should it be determined there testine transplantation include the small bowel latter request is made, consider the potential is potential for small bowel donation: alone or with the some or all of the stomach, for acute kidney injury and discuss with the duodenum, liver, large bowel, and kidneys. donation physician if you are concerned. • Hemodynamics should be optimized While awaiting the organ recovery surgery, it (blood pressure, pressor requirements, and is important that the donor is well oxygenated lactate clearance) to ensure normal and well perfused with normal electrolyte lev- perfusion of the bowel1 els. High dose vasopressors should be avoided or minimized because they can cause splanch- Return to Overview map nic vasoconstriction which leads to intestinal Return to Management of ischemia. Excessive intravenous fluids and/or Gastrointestinal System map a low sodium should be avoided because they can cause bowel edema. Enteral feeds should • Administration of oral and/or intravenous be stopped for at least six hours prior to organ antibiotics to reduce infection and retrieval. bacterial translocation following transplant may be requested1 The unique consequences of intestinal ischemic • Bowel preparation to remove stool from injury could result in bacterial translocation or the colon may be requested intestinal perforation, so donors with excessive vasopressor requirements or prolonged arrest are generally avoided. Intestinal decontamina- tion with enteral antibiotic mixtures is aimed at 1 Kotloff RM, Blosser S, Fulda GJ, et al. Manage- ment of the Potential Organ Donor in the ICU. decreasing the bacterial content of the intestinal Crit Care Med. 2015;43(6):1291-1325. doi:10.1097/ allograft and may be requested by the transplant CCM.0000000000000958.

Organ Donation in Ontario: A Guide for Critical Care Residents - Donor Management 68 BP and Perfusion Targets when Managing the Renal System for NDD Donors Alissa Visram, Sabira Valiani, Pierre Cardinal, Andrew Healey

Description Rationale namic response to a fluid challenge3. Given that • Target a default MAP of ≥ 70 mmHg It is essential to closely monitor both blood assessment of volume status is difficult, we in adult donors1, which can be adjusted pressure and perfusion in NDD patients to suggest focusing on blood pressure and perfu- based on the patient’s baseline blood ensure the early identification of patients in need sion monitoring. In the presence of shock (poor pressure of further resuscitation. Achieving the targeted pressure and/or perfusion), bedside echocardi- 4 • Monitor perfusion and cardiac output pressures and perfusion parameters increases the ography or other tests to assess fluid respon- using the following targets: likelihood of successful multi-organ donation. siveness (e.g. respiratory variation of systolic • Clinical surrogates - no mottling, Frequent reassessments are necessary to ensure pressure, pulse pressure, stroke index, passive capillary refill less than 4 seconds, that therapeutic interventions meet their goals straight leg raising) may help identify patients and warm extremities and do not result in unintended adverse effects. who require fluid administration.

Return to Overview map Both the 2006 Canadian1 and the 2015 SCCM2 In patients with normal pressure and perfusion, fluid should not be administered to ‘protect’ the Return to Management of the guidelines recommend that fluid replacement kidneys. In the absence of hypotension or Renal System map should be administered to maintain euvolemia as defined by central venous pressure (CVP) and hypoperfusion excessive fluid administration • Laboratory surrogates - a normal or pulmonary artery occlusion pressure (PAOP) may also impair renal function as it may lead 5 decreasing lactate, and a central venous measurements. However, using CVP to assess to renal venous congestion . While there are no oxygen saturation ≥ 60% volume is no longer supported by recent work. 3 Marik P, Baram M, Vahid B. Does Central Venous Pres- • Noninvasive means - normal stroke A systematic review has demonstrated that the sure Predict Fluid Responsiveness?*: A Systematic Review of the Literature and the Tale of Seven Mares. Chest. olume by echocardiography, or CVP is not a reliable measure of blood volume 2008;134:172-178. non-invasive cardiac output monitors and cannot be used to predict the hemody- 4 Kumar A, Anel R, Bunnell E, Habet K, Zanotti S, Mar- • Monitor fluid balance as fluid deficit and shall S, Neumann A, Ali A, Cheang M, Kavinsky C, Par- rillo J. Pulmonary artery occlusion pressure and central fluid overload may both adversely affect venous pressure fail to predict ventricular filling volume, the function of kidneys cardiac performance, or the response to volume infusion in normal subjects. Critical Care Medicine. 2004;32:691- 1 Shemie S. Organ donor management in Canada: recom- 2 Kotloff RM, Blosser S, Fulda GJ, et al. Manage- 699. mendations of the forum on Medical Management to Op- ment of the Potential Organ Donor in the ICU. 5 Prowle J, Echeverri J, Ligabo E, Ronco C, Bellomo R. timize Donor Organ Potential. Canadian Medical Associa- Crit Care Med. 2015;43(6):1291-1325. doi:10.1097/ Fluid balance and acute kidney injury. Nat Rev Nephrol. tion Journal. 2006;174:S13-S30. CCM.0000000000000958. 2009;6:107-115.

Organ Donation in Ontario: A Guide for Critical Care Residents - Donor Management 69 randomized control trials comparing a liberal fluid strategy to a restricted one, two retrospective studies in NDD donors suggest that a liberal fluid strategy does not improve renal function6,7 and possibly decreases heart, lung, and kidney procurement for transplantation6.

Return to Overview map Return to Management of the Renal System map

6 Abdelnour T, Rieke S: Relationship of hormonal resuscitation therapy and central venous pressure on increasing organs for transplant. J Heart Lung Transplant 2009; 28:480–485. 7 Miñambres E, Rodrigo E, Ballesteros MA, et al: Impact of restrictive fluid balance focused to increase lung procurement on renal function after kidney transplantation. Nephrol Dial Transplant 2010; 25:2352–2356.

Organ Donation in Ontario: A Guide for Critical Care Residents - Donor Management 70 Avoiding Nephrotoxic Agents when Managing the Renal System Alissa Visram, Sabira Valiani, Pierre Cardinal

Description Rationale Avoid the use of nephrotoxic agents when Much like the care of standard ICU patients, caring for NDD donors, in order to prevent it is recommended that nephrotoxic agents renal injury. (ie: contrast agents, nephrotoxic antibiotics) be avoided if possible when caring for NDD donors, in order to prevent renal injury1.

If aminoglycoside antibiotics are required, once daily dosing is preferred to maximize con- centration dependent bactericidal activity and limit aminoglycoside induced acute kidney Return to Overview map injury. Additionally, monitoring of aminoglycoside levels is recommended when adminis- Return to Management of the tration is required beyond single doses2. When Renal System map vancomycin is used, careful monitoring of levels is important to avoid nephrotoxicity. Appro- priate fluid replacement should be considered in order to optimize renal clearance.

1 Shemie SD, Ross H, Pagliarello J, et al. Organ donor management in Canada: Recommendations of the forum on Medical Management to Optimize Donor Organ Potential. CMAJ. 2006;174:S13-S30. doi:10.1503/cmaj.045131. 2 Khwaja A. KDIGO Clinical Practice Guidelines for Acute Kidney Injury. Nephron Clinical Practice. 2012;120:179- 184.

Organ Donation in Ontario: A Guide for Critical Care Residents - Donor Management 71 Consider Mild Hypothermia when Managing the Renal System Alissa Visram, Pierre Cardinal

Description injury thereby improving allograft function hypothermia group as compared to the normo- Consider targeting a body temperature between post-transplantation. thermia group which suggests that hypother- 34-35°C in NDD renal donors in order to mia does not significantly alter the transplant reduce the rate of delayed renal graft function A study published by Malinoski et al. in 2015 potential of other organs (specifically heart, showed that, in NDD renal donors, targeting lung, liver, or pancreas donation)2. In addition, Rationale a body temperature of 34-35°C (hypothermia) the rate of adverse events was similar in the compared to 36.5-37.5°C (normothermia) experimental and control groups. The results of Currently there are no national or provincial significantly reduced the rate of delayed graft this study cannot be applied to coagulopathic guidelines that recommend altering tem- function (the need for kidney recipients to NDD donors (INR >2.5, PTT > 3 times perature targets based on the organ to be trans- undergo dialysis within 7 days of transplant). normal, platelets <50,000/mcl) or hemodynam- planted. The Trillium Gift of Life Network The beneficial effects of hypothermia on ically unstable donors (>1 vasopressor or one Return to Overview map reducing the rate of delayed graft function was agent at high dose, dopamine >10mcg/kg/min, more pronounced when kidneys were trans- norepinephrine >10mcg/min, or phenyleph- Return to Management of the planted from expanded criteria donors (i.e. old- rine >60mcg/min) as they were excluded from Renal System map er than 60 years, or those 50-59 years with at the study. Though this study did not address least two comorbidities - cerebrovascular cause the effects of donor hypothermia on long term guidelines recommend NDD donor tempera- of death, renal insufficiency, or hypertension) renal outcomes, the findings present a com- ture should be maintained between 35.5 and when compared to standard donors2,3. There pelling argument that hypothermia should be 37°C in order to avoid deleterious effects of was also no significant difference in the num- considered in hemodynamically stable renal hypothermia, such as myocardial suppression, ber of organs transplanted from donors in the NDD donors. hypoxemia, and acidosis1 (see 'Standard In- 2 Niemann CU, Feiner J, Swain S, Bunting S, Friedman M, vestigations and Monitoring'). However, hypo- Crutchfield M, Broglio K, Hirose R, Roberts JP, Malinoski thermia also has potential beneficial effects as it D. Therapeutic hypothermia in deceased organ donors and kidney-graft function. New England Journal of Medicine. may reduce ischemia-reperfusion 2015 Jul 30;373(5):405-14. 3 Port F, Bragg-Gresham J, Metzger R, Dykstra D, Gilles- pie B, Young E, Delmonico F, Wynn J, Merion R, Wolfe 1 Trillium Gift of Life Network. Donation Resource Manu- R, Held P. Donor characteristics associated with reduced al: A tool to assist hospitals with the process of organ and graft survival: an approach to expanding the pool of kid- tissue Donation. Queen's Printer for Ontario: 2010. ney donors. Transplantation. 2002;74:1281-1286.

Organ Donation in Ontario: A Guide for Critical Care Residents - Donor Management 72 Consider Saline to Prevent Contrast Induced Nephropathy Alissa Visram, Sabira Valiani, Pierre Cardinal, Sonny Dhanani, Andrew Healey

Description Rationale presence of diabetes insipidus may confound the urine output assessment. The fluid regimen For prophylaxis against contrast induced ne- In NDD donors with acute kidney injury or suggested above may need to be increased if phropathy in patients with an abnormal creat- an abnormal creatinine who are scheduled to volume contraction is suspected. inine or acute kidney injury, consider admin- receive intravenous contrast, the donor should istering isotonic crystalloid solutions to ensure be adequately hydrated with intravenous The use of N-acetyl-cysteine (NAC) has also normovolemia. isotonic crystalloid solutions1,2,3. Fluids should been previously recommended to prevent con- be started three hours prior to contrast admin- trast induced nephropathy (CIN)1,3. The istration where possible, and should be contin- mechanism by which NAC prevents renal inju- ued three to six hours after contrast exposure. ry has not been clearly established, however its Fluids should be titrated to achieve a urine out- vasodilatory and antioxidant effects are thought put of >150 mL/hour for the first six hours to play a role in renal protection4. Return to Overview map after contrast exposure4, acknowledging that the Return to Management of the 1 Shemie SD, Ross H, Pagliarello J, Baker AJ, Greig PD, In a recent systematic review of various strat- Brand T, et al. Organ donor management in Canada: rec- Renal System map 5 ommendations of the forum on Medical Management egies , none was shown to be clearly effective to Optimize Donor Organ Potential. CMAJ : Canadian for contrast induced nephropathy prevention. Medical Association journal = journal de l'Association medicale canadienne. 2006;174(6):S13-32. doi: 10.1503/ Crystalloid therapy should be instituted first, cmaj.045131. PubMed PMID: 16534070; PubMed Central with NAC administration left to the discretion PMCID: PMCPMC1402396. of the care team. 2 Kotloff RM, Blosser S, Fulda GJ, Malinoski D, Ahya VN, Angel L, et al. Management of the Potential Organ Do- nor in the ICU: Society of Critical Care Medicine/Amer- ican College of Chest Physicians/Association of Organ Procurement Organizations Consensus Statement. Crit- ical care medicine. 2015;43(6):1291-325. doi: 10.1097/ CCM.0000000000000958. PubMed PMID: 25978154. 3 Khwaja A. KDIGO Clinical Practice Guidelines for Acute Kidney Injury. Nephron Clinical Practice. 2012;120:179- 5 Subramaniam RM, Suarez-Cuervo C, Wilson RF,Turban 184. S, Zhang A, Sherrod C, Aboagye J, Eng J, Choi MJ, Hutf- 4 Trillium Gift of Life Network. Donation Resource Manu- less S, Bass EB, Effectiveness of Prevention Strategies for al: A tool to assist hospitals with the process of organ and Contrast-Induced Nephropathy: A Systematic Review and tissue Donation. Queen's Printer for Ontario: 2010. Meta-analysis Ann Intern Med. 2016;164:406-416

Organ Donation in Ontario: A Guide for Critical Care Residents - Donor Management 73 Administering Steroids when Managing the Respiratory System Sabira Valiani, Alissa Visram, Pierre Cardinal

Description Rationale • High-dose methylprednisolone should be High-dose methylprednisolone is recommend- administered to all NDD donors1. ed in all patients for respiratory optimization • The recommended dose of and protection following the neurologic decla- methylprednisolone is 15mg/kg IV daily ration of death (NDD)1. The administration (to a maximum of 1000mg IV daily)2. of high-dose methylprednisolone is believed to mitigate the effects of the inflammatory cascade on organ donor function3. The recommendation for high dose steroid administration is based on a systematic review of nonrandomized studies demonstrating that steroid administration may Return to Overview map improve donor lung PaO2/FiO2 ratios and lung 4 Return to Management of the retrieval rates . Although the evidence is limit- Respiratory System map ed, methylprednisolone administration is recommended for steroid replacement therapy in all NDD patients unless their lungs are not considered suitable for donation. In these patients, stress dose steroids may be still be required to manage shock (see ‘Steroid Administration in Patients with Distributive Shock’).

3 Kotloff RM, Blosser S, Fulda GJ, et al. Manage- ment of the Potential Organ Donor in the ICU. 1 Shemie SD, Ross H, Pagliarello J, et al. Organ donor man- Crit Care Med. 2015;43(6):1291-1325. doi:10.1097/ agement in Canada: Recommendations of the forum on CCM.0000000000000958. Medical Management to Optimize Donor Organ Potential. 4 Dupuis, S., Amiel, J., Desgroseilliers, M., Williamson, D., CMAJ. 2006;174:S13-S30. doi:10.1503/cmaj.045131. Thiboutot, Z., & Serri, K. et al. (2014). Corticosteroids in 2 Trillium Gift of Life Network. Donation Resource Manu- the management of brain-dead potential organ donors: a al: A tool to assist hospitals with the process of organ and systematic review. British Journal Of Anaesthesia, 113(3), tissue Donation. Queen's Printer for Ontario: 2010. 346-359. http://dx.doi.org/10.1093/bja/aeu154

Organ Donation in Ontario: A Guide for Critical Care Residents - Donor Management 74 Lung Protective Ventilation Strategy in NDD Donors - Non ARDS Sabira Valiani, Ian Ball, Alissa Visram, Pierre Cardinal

Description repositioning as required do not meet ARDS criteria (see “Patient meets • Institute a lung protective ventilation • Utilize a judicious fluid management ARDS criteria” for details). This protocol was strategy for NDD donors not meeting strategy tested in a randomized controlled trial of 118 ARDS criteria with the following initial NDD donors, and may increase the number of 1 settings1: Rationale lungs available for transplant . Potential donors • Tidal volume 6-8mL/kg of ideal body In NDD donors not meeting ARDS criteria, with a history of smoking, asthma, COPD, weight for both adult and pediatric lung protective ventilation strategies aim to purulent secretions, aspiration, or infiltrates on donors minimize ventilator induced lung injury which chest x-ray were excluded from the study. NDD • PEEP of 8-10 cm H20 is postulated to be mediated, in part, by donors in the lung protective ventilation (inter- damage caused by overdistention of alveo- vention) arm were ventilated with tidal volumes Return to Overview map li (volutrauma), and ventilation at low lung of 6-8mL/kg of ideal body weight and a PEEP 2 of 8-10 cm H O. Additionally, the intervention Return to Management of the volumes (atelectrauma) . Such strategies gener- 2 Respiratory System map ally consist of some combination of low tidal arm included closed circuit suctioning, recruit- volume ventilation, the use of higher PEEP, ment after any disconnect from the ventilator, • Avoid derecruitment in NDD patients recruitment manoeuvres, and a limitation of and apnea testing performed with continuous by1: plateau airway pressures2,3. positive airway pressure. This was compared to • Performing closed-circuit suctioning a conventional ventilation strategy, consisting • Providing recruitment maneuvers after The Ranieri protocol, which includes low tidal of tidal volumes of 10-12mL/kg of ideal body any disconnection from the ventilator volume ventilation, is the lung protective ven- weight and PEEP of 3-5 cm H2O. The con- • Performing the apnea test using tilation strategy of choice in NDD donors who trol group had open circuit suctioning, no recruitment maneuvers, and apnea testing per- continuous positive airway pressure 2 Slutsky AS, Ranieri VM. Ventilator-induced lung inju- • Institute chest physiotherapy, therapeutic ry. NEJM. 2013;369(22):2126-36. doi: 10.1056/NEJM- formed with high flow oxygen alone. The study bronchoscopy, routine suctioning and ra1208707. demonstrated that a lung protective strategy in 3 Kotloff RM, Blosser S, Fulda GJ, Malinoski D, Ahya VN, potential NDD donors increased the number Angel L, et al. Management of the Potential Organ Do- 1 Mascia L, Pasero D, Slutsky AS, et al. Effect of a lung pro- nor in the ICU: Society of Critical Care Medicine/Amer- of lungs eligible for transplant (from 54% in tective strategy for organ donors on eligibility and avail- ican College of Chest Physicians/Association of Organ the conventional strategy to 95% in the pro- ability of lungs for transplantation: a randomized con- Procurement Organizations Consensus Statement. Crit- trolled trial. JAMA. 2010;304(23):2620-7. doi: 10.1001/ ical care medicine. 2015;43(6):1291-325. doi: 10.1097/ tective strategy, p<0.01) and harvested lungs jama.2010.1796. CCM.0000000000000958.

Organ Donation in Ontario: A Guide for Critical Care Residents - Donor Management 75 (from 27% in the conventional strategy to 54% in the protective strategy, p=0.04). Six-month survival rates did not differ between recipients who received lungs from donors ventilated with the conventional strategy compared with the protective strategy (69% vs 75%, respectively).

The SCCM and Canadian guidelines also recommend further adjuncts to the above lung protective ventilation strategy3,4 These adjuncts include chest physiotherapy, therapeutic bronchoscopy, routine suctioning and repositioning. Finally, judicious fluid management is

Return to Overview map Return to Management of the Respiratory System map recommended to prevent volume overload which may lead to pulmonary edema, while ensuring adequate volume resuscitation3,4.

4 Shemie SD, Ross H, Pagliarello J, et al. Organ donor management in Canada: Recommendations of the forum on Medical Management to Optimize Donor Organ Potential. CMAJ. 2006;174:S13-S30. doi:10.1503/cmaj.045131.

Organ Donation in Ontario: A Guide for Critical Care Residents - Donor Management 76 Monitoring Oxygenation when Managing the Respiratory System - ARDS Sabira Valiani, Alissa Visram, Pierre Cardinal

Description ly explained by cardiac failure or fluid overload1. specifically meeting ARDS criteria, the 2006 • In NDD patients who meet ARDS Pathophysiologically, ARDS is characterized by Canadian guidelines suggest an oxygen satura- 4 criteria, monitor ventilatory management increased shunt and dead space fraction, as well tion >95% in all NDD donors . However, con- 2 and adjust initial settings to meet the as poor lung compliance . In NDD patients sideration should be made to adhering to the following targets: with ARDS, implementation of a lung protec- ARDSnet goal PaO2 is 55-80 mmHg or oxygen • PaO2 55-80 mmHg or oxygen tive ventilation strategy based on the ARDSnet saturation 88-95%, with PEEP titration based saturation 88-95% protocol is recommended (see 'Lung Protective on FiO2. Discussion with TGLN and the dona- 3 • Peak inspiratory pressure (PIP) < 35 Ventilation Strategy for ARDS') . Initial tidal tion support physician to best optimize respira- cm H2O volumes should be set at 6mL/kg of ideal body tory management for these cases may be war- weight. Plateau pressure (Pplat) should then be ranted. In cases of refractory hypoxemia, rescue • Plateau pressure (Pplat) < 30 cm H20 • pH 7.30-7.45, with permissive measured, and tidal volumes can be decreased measures can be used (see 'Instituting Rescue hypercapnea to a minimum of 4mL/kg until Pplat is < 30 Measures for Refractory Hypoxemia'). cm H2O. Return to Overview map Due to the increased dead space in ARDS, The oxygenation target for NDD patients with hypercapnia is common, and the pH goal has Return to Management of the Respiratory System map ARDS is not well defined. Given the lack of ran- been liberalized to 7.30-7.45. In the ARDSnet domized controlled trials in the NDD donors protocol, patients who were difficult to venti- late due to increased dead space were managed 1 Force ADT, Ranieri VM, Rubenfeld GD, Thompson BT, with bicarbonate infusions, or had their Pplat Rationale Ferguson ND, Caldwell E, et al. Acute respiratory distress 3 syndrome: the Berlin Definition. JAMA : the journal of goals liberalized if their pH was less than 7.15 . ARDS is defined clinically by an acute onset the American Medical Association. 2012;307(23):2526-33. Local protocols should be followed in these (less than 7 days) of bilateral infiltrates on chest doi: 10.1001/jama.2012.5669. extreme cases. x-ray or computed tomography (CT) scan, with 2 Ware LB, Matthay MA. The Acute Respirato- ry Distress Syndrome. New England Journal of a PaO2/FiO2 ratio of < 300, which cannot be ful- Medicine. 2000;342(18):1334-49. doi:10.1056/ NEJM200005043421806. 3 ARDS Network. Ventilation with Lower Tidal Volumes as Compared with Traditional Tidal Volumes for Acute 4 Shemie SD, Ross H, Pagliarello J, et al. Organ donor man- Lung Injury and the Acute Respiratory Distress Syndrome. agement in Canada: Recommendations of the forum on New England Journal of Medicine. 2000;342(18):1301-8. Medical Management to Optimize Donor Organ Potential. doi:10.1056/NEJM200005043421801. CMAJ. 2006;174:S13-S30. doi:10.1503/cmaj.045131.

Organ Donation in Ontario: A Guide for Critical Care Residents - Donor Management 77 Considering if Patients Meet ARDS Criteria Sabira Valiani, Ian Ball, Alissa Visram, Pierre Cardinal

Description Rationale with rapid onset infiltrates, which responds well Recognize ARDS in NDD donors, as defined Potential donors that have been declared dead to high levels of PEEP and is generally reversible by an acute onset (less than 7 days) of bilat- by neurological criteria remain at risk for the over hours. eral infiltrates on chest x-ray or computed Acute Respiratory Distress Syndrome (ARDS), tomography (CT) scan, with a PaO2/FiO2 ratio as any other patient who has sustained a similar of < 300, which cannot be fully explained by physiologic insult. The incidence of ARDS in cardiac failure or fluid overload1. severe traumatic brain injury is approximately 20-30%2,3. ARDS is defined by the Berlin Criteria as an acute (<7 days) impairment in oxygenation that is not fully explained by cardiac failure or volume overload, with bilateral Return to Overview map infiltrates on chest x-ray or CT. The impairment in oxygenation is quantified by the ratio Return to Management of the of PaO to FiO (PF ratio), measured at a PEEP Respiratory System map 2 2 of > 5 cm H2O. ARDS is subdivided into mild (PF ratio < 300), moderate (PF ratio < 200), and severe (PF ratio < 100)1. One should distinguish ARDS from neurogenic pulmonary edema that may accompany brain herniation. Neurogenic pulmonary edema often presents

2 Hendrickson CM, Howard BM, Kornblith LZ, Conroy AS, Nelson MF, Zhuo H, et al. The acute respiratory distress syndrome following isolated severe traumatic brain injury. The journal of trauma and acute care surgery. 2016. Epub 2016/02/18. doi: 10.1097/ta.0000000000000982. 3 Aisiku IP, Yamal JM, Doshi P, Rubin ML, Benoit JS, Han- 1 Force ADT, Ranieri VM, Rubenfeld GD, Thompson nay J, et al. The incidence of ARDS and associated mor- BT, Ferguson ND, Caldwell E, et al. Acute respirato- tality in severe TBI using the Berlin definition. The journal ry distress syndrome: the Berlin Definition. JAMA. of trauma and acute care surgery. 2016;80(2):308-12. doi: 2012;307(23):2526-33. doi: 10.1001/jama.2012.5669. 10.1097/TA.0000000000000903.

Organ Donation in Ontario: A Guide for Critical Care Residents - Donor Management 78 Monitoring PF Ratios, Peak and Plateau Pressures, and PaCO2 – Non ARDS Sabira Valiani, Alissa Visram, Pierre Cardinal

Description Rationale In patients who do not meet ARDS criteria, In patients who do not meet ARDS criteria, monitor ventilatory management, and adjust ventilation strategies must be monitored to initial settings to ensure that the following are ensure that adequate ventilation and oxygen- targets are met1,2: ation are being provided, while limiting the

• PaCO2 of 35-45 mmHg and pH 7.35- effects of ventilator induced lung injury. As 7.45 the patient’s clinical status changes, ventilator

• PaO2 > 90 mmHg or oxygen saturation > settings should be adjusted to address chang- 95% ing lung compliance, resistance, dead space, • Peak inspiratory pressure (PIP) < 35 cm shunt, and acid-base status. The 2006 Canadian

H2O guidelines suggest a target pH of 7.35-7.45 and 2 • Plateau pressure (Pplat) < 30 cm H2O PaCO2 of 35-45 mmHg . The recommended lung protective ventilation strategy is based on

Return to Overview map the Ranieri protocol , which uses a target PaO2 Return to Management of the of >90 mmHg (see 'Lung Protective Ventilation 1 Respiratory System map Strategy') . Finally, recommended peak inspi-

ratory pressure (PIP) <35 cm H2O and plateau

pressure < 30 cm H2O were targets used in the ARDSnet protocol3.

1 Mascia L, Pasero D, Slutsky A, et al., Effect of a Lung Protective Strategy for Organ Donors on Eligibility and Availability of Lungs for Transplantation. JAMA. 2010;304:2620. 3 ARDS Network. Ventilation with Lower Tidal Volumes as 2 Shemie SD, Ross H, Pagliarello J, et al. Organ donor man- Compared with Traditional Tidal Volumes for Acute Lung agement in Canada: Recommendations of the forum on Injury and the Acute Respiratory Distress Syndrome. New Medical Management to Optimize Donor Organ Potential. England Journal of Medicine. 2000;342(18):1301-8. Doi: CMAJ. 2006;174:S13-S30. doi:10.1503/cmaj.045131. 0.1056/NEJM200005043421801.

Organ Donation in Ontario: A Guide for Critical Care Residents - Donor Management 79 Lung Protective Ventilation Strategy in NDD Donors - ARDS Sabira Valiani, Ian Ball, Alissa Visram, Pierre Cardinal

Description Rationale also included in local practice protocols. If the NDD donor meets ARDS criteria, NDD donors meeting ARDS criteria should be initiate lung protective ventilation strategies ventilated according to local practice protocols according to the ARDSnet protocol and local that implement low tidal volume ventilation practice protocols, including: based on the ARDSnet protocol1. Low tidal • Low tidal volume ventilation of 4-6mL/kg volume ventilation has been shown to reduce of ideal body weight absolute mortality and increase ventilator free • Goal plateau pressures (Pplat) < 30 cm days in living patients with ARDS1. In NDD

H2O patients, this ventilation strategy is suggested

• PEEP titration based on FiO2 in order to optimize oxygenation and prevent further pulmonary deterioration, thereby pre- Return to Overview map serving the transplant potential of other organs. Return to Management of the In the ARDSnet protocol, patients in the Respiratory System map low tidal volume strategy were ventilated with target tidal volumes of 4-6mL/kg of ideal body weight, and maximal plateau

pressures of 30 cm H2O, compared to conventional ventilation with tidal volumes of 12mL/kg of ideal body weight and maximal

plateau pressures of 50 cm H2O. PEEP was

titrated based on FiO2 requirements, and this or similar titration protocols are generally

1 ARDS Network. Ventilation with Lower Tidal Volumes as Compared with Traditional Tidal Volumes for Acute Lung Injury and the Acute Respiratory Distress Syndrome. New England Journal of Medicine. 2000;342(18):1301-8. doi:10.1056/NEJM200005043421801.

Organ Donation in Ontario: A Guide for Critical Care Residents - Donor Management 80 Instituting Rescue Measures to Optimize Oxygenation in NDD Donors with ARDS and Refractory Hypoxemia Ian Ball, Sonny Dhanani

Description management, not specifically for NDD, support Routine recruitment maneuvers have also not In the donor patient with refractory hypox- the use of neuromuscular blockade to improve shown survival benefit in patients with refrac- emia, several evidence based strategies from the compliance, reduce respiratory work, and lessen tory hypoxemia; however, a systematic review 1 5 non-organ donation literature should be imple- metabolic demand . Individual agents are not published in 2008 and a subsequent Cochrane 6 mented: recommended over others, and local preference Review in 2009 demonstrated that the use of • Neuromuscular blockade1 should be instituted. Prone positioning has also recruitment maneuvers results in transient 2 2 • Prone positioning shown success in ARDS , but also has not been increases in oxygenation by PaO2 and P:F mea- • Recruitment maneuvers with increase in specifically studied in the NDD patient. Local surements. This may be requested by lung peak airway pressure to 30 cm H O for ARDS protocols for prone positioning should recovery teams. The target pressure and time 2 2 30-60 seconds be instituted . for recruitment maneuvers varies by centre; however, the Canadian recommendations are

Return to Overview map There is no high level evidence for nitric oxide, for an increase in pressure to 30 cm H2O for epoprostenol, or oscillation in potential lung 30-60 seconds7,8. Return to Management of the donors, and recent evidence has failed to show Respiratory System map a survival benefit in the general literature3,4. Rationale However, both nitric oxide and epoprostenol may transiently improve systemic oxygenation, Potential donors that have been declared dead by thereby improving oxygen delivery prior to 5 Fan E, Wilcox M, Brower R, Stewart T, Mehta S, Lap- neurologic criteria remain at risk for the Acute insky S, Meade M, Ferguson N. Recruitment Maneu- organ donation. They should be considered vers for Acute Lung Injury. Am J Respir Crit Care Med. Respiratory Distress Syndrome (ARDS), in the second line therapies for cases refractory to more 2008;178:1156-1163. same way that any other non-NDD patient 6 Hodgson C, Keating JL, Holland AE, Davies AR, Smir- evidence based treatments. neos L, Bradley SJ, Tuxen D. Recruitment manoeuvres for who had sustained the same physiologic insult adults with acute lung injury receiving mechanical ventila- would be. Current evidence for ARDS tion. Cochrane Database Syst Rev. 2009 Jan 1;2(2). 3 Adhikari NK et al. Inhaled nitric oxide does not reduce 7 Shemie SD, Ross H, Pagliarello J, et al. Organ donor man- 1 Neuromuscular Blockers in Early Acute Respiratory Dis- mortality in patients with acute respiratory distress syn- agement in Canada: Recommendations of the forum on tress Syndrome Papazian L, Forel J-M, Gacouin A, et al. drome regardless of severity: systematic review and me- Medical Management to Optimize Donor Organ Potential. N Engl J Med 2010; 363:1107-1116 ta-analysis. Crit Care Med. 2014 Feb;42(2):404-12. CMAJ. 2006;174:S13-S30. doi:10.1503/cmaj.045131., 2 Prone Positioning in Severe Acute Respiratory Distress 4 High-Frequency Oscillation in Early Acute Respiratory 8 Trillium Gift of Life Network. Donation Resource Manu- Syndrome. Guérin, C, Reignier J, Richard J-C, et al. N Engl Distress Syndrome Ferguson ND, Cook DJ, Guyat GH, et al: A tool to assist hospitals with the process of organ and J Med 2013; 368:2159-2168 al. N Engl J Med 2013; 368:795-805 tissue Donation. Queen's Printer for Ontario: 2010.

Organ Donation in Ontario: A Guide for Critical Care Residents - Donor Management 81 Consider Recruitment Manoeuvres Sabira Valiani, Alissa Visram, Pierre Cardinal

Description • Recruitment maneuvers done on an FiO2 6-8mL/kg of ideal body weight) for 10 5 • Perform routine recruitment maneuvers in of 1 should be performed with a sustained respiratory cycles . all NDD patients, regardless of PaO /FiO inflation to a pressure of 30 cm 2H O for 2 2 1,3 ratio1 30-60 seconds . Routine recruitment maneuvers are recom- • In NDD patients with refractory hypox- mended by the 2006 Canadian guidelines as emia, perform recruitment maneuvers as Rationale part of the management of all NDD donors 1 a rescue intervention to improve oxygen- Recruitment maneuvers improve oxygenation and continue to be used despite weak evidence . ation1,2 by re-inflating collapsed alveoli4. These recruit- The recommended frequency of these recruitment maneuvers consist of a sustained inflation ment maneuvers has not been specified. to a target pressure, which may result in unintended deleterious effects of hypotension or Rescue recruitment maneuvers are recom- 4 mended by the SCCM and Canadian guide- Return to Overview map pneumothorax . The target pressure and time for recruitment maneuvers varies by centre; lines to potentially improve lung procurement Return to Management of the however, the Canadian recommendations are in NDD donors whose PaO2 to FiO2 ratio is < Respiratory System map 1,2 for an increase in pressure to 30 cm H2O for 300 . These recruitment maneuvers are part of 30-60 seconds1,3. In the Ranieri protocol, which an aggressive lung donor management protocol implemented a lung protective ventilation that includes chest physiotherapy, therapeutic strategy for potential lung donors, recruitments bronchoscopy, routine suctioning and reposi- 1,2,3 were performed by doubling of target tidal tioning, and maintenance of euvolemia . 1 Shemie SD, Ross H, Pagliarello J, et al. Organ donor man- volumes (target tidal volumes in this study were agement in Canada: Recommendations of the forum on Medical Management to Optimize Donor Organ Poten- tial. CMAJ. 2006;174:S13-S30. doi:10.1503/cmaj.045131. Shemie SD, Ross H, Pagliarello J, et al. Organ donor management in Canada: Recommendations of the forum on 3 Trillium Gift of Life Network. Donation Resource Manu- 5 Mascia L, Pasero D, Slutsky AS, Arguis MJ, Berardi- Medical Management to Optimize Donor Organ Potential. al: A tool to assist hospitals with the process of organ and no M, Grasso S, et al. Effect of a lung protective strat- CMAJ. 2006;174:S13-S30. doi:10.1503/cmaj.045131. tissue Donation. Queen's Printer for Ontario: 2010. egy for organ donors on eligibility and availability of 2 Kotloff RM, Blosser S, Fulda GJ, et al. Manage- 4 Slutsky AS, Ranieri VM. Ventilator-induced lung in- lungs for transplantation: a randomized controlled trial. ment of the Potential Organ Donor in the ICU. jury. The New England journal of medicine. JAMA : the journal of the American Medical Association. Crit Care Med. 2015;43(6):1291-1325. doi:10.1097/ 2013;369(22):2126-36. doi: 10.1056/NEJMra1208707. 2010;304(23):2620-7. Epub 2010/12/16. doi: 10.1001/ CCM.0000000000000958. PubMed PMID: 24283226 jama.2010.1796. PubMed PMID: 21156950.

Organ Donation in Ontario: A Guide for Critical Care Residents - Donor Management 82 Recognize and Manage Hypertension in an Organ Donor Ian Ball, Sonny Dhanani, Andrew Healey

Description ischemia and left ventricular subendocardial Ideal agents include: 3,4 Appropriate agents to manage acute hyperten- ischemia . Despite the lack of supporting high sion secondary to neurologic herniation include level evidence, medical management of brain 1. Hydralazine Hydralazine, phentolamine, and nitroprusside. death induced hypertension is physiologically 2. Phentolamine justified, to optimize transplanted organ 3. *Nitroprusside Rationale outcomes. All should be administered as intravenous infu- Potential donors that have been declared dead The ideal antihypertensive agent needs to have sions in a monitored setting. It is not unusual by neurologic criteria are at risk of malig- predominantly peripheral effects, with minimal for some patients to require multiple antihyper- nant hypertension secondary to a catecholamine inotropy or chronotropy. It needs to be titratable tensive agents. Clinicians should be prepared release resulting from medullary ischemia1,2. and shorter acting. Hypotension subsequent to to administer vasopressors at a moment’s notice spinal cord ischemia with resultant peripheral in case of hypotension from evolving brainstem Return to Overview map vasodilation, decrease in serum catecholamines, ischemia. Return to Management of the and decreased beta receptor activity5,6 is likely Hemodynamics map to follow the hypertensive emergency and will *Caution with infusions administered be worsened by antihypertensive therapy. for greater than 48 hours due to the accumulation of toxic metabolites This is the brain’s effort to maintain an adequate cerebral perfusion pressure. Human autopsy evidence and baboon models of brain death 3 Novitzky D, Horak A, Cooper DK, Rose AG. Electro- demonstrate an association between brainstem cardiographic and histopatho- logic changes developing during experimental brain death in the baboon. Trans- 1 Wilhelm MJ, Pratschke J, Laskowski IA, Paz DM, Til- plant Proc 1989;21:2567-9. ney NL. Brain death and its impact on the donor heart 4 Kolin A, Norris JW. Myocardial damage from acute cere- — lessons from animal models. J Heart Lung Transplant bral lesions. Stroke 1984;15: 990-3. 2000;19:414-8. 5 Shivalkar B, Van Loon J, Wieland W, et al. Variable effects 2 Baroldi G, Di Pasquale G, Silver MD, Pinelli G, Lusa AM, of explosive or gradual increase of intracranial pressure Fineschi V. Type and extent of myocardial injury related on myocardial structure and function. Circulation 1993; to brain damage and its significance in heart transplan- 87:230-9. tation: a morphometric study. J Heart Lung Transplant 6 Wood KE, Becker BN, McCartney JG, et al., Care of the 1997;16:994-1000. Potential Organ Donor. N Engl J Med 2004;351:2730-9.

Organ Donation in Ontario: A Guide for Critical Care Residents - Donor Management 83 Anticipate Catecholamine Induced Myocardial Injury Sonny Dhanani

Description tential for tachydysrhythmias1,2,3. This often re- on the rate of rise in ICP5,6. This culminates in Anticipate catecholamine induced myocar- ferred the “autonomic” or “sympathetic storm” the commonly seen, and often reversible, stress dial dysfunction after typical sympathetic storm during which time significant cardiac dam- cardiomyopathy following herniation. following brain death. age can occur secondary to changes in oxygen consumption and delivery3,4. The release Interestingly, when studied in patients with sub- Rationale of endogenous catecholamines results in arachnoid hemorrhages, autopsies have shown increased peripheral resistance causing a sud- scattered foci of transmural myocardial inju- Myocardial dysfunction may be related to many den increase in myocardial work and oxygen ry that are not seen in patients dying of non- different mechanisms including contusion, consumption possibly leading to myocardial neurogenic causes7,8. Brain dead patients with anoxic-ischemic injuries, or underlying comor- ischemia or infarction. In animals, the rise of elevations in cardiac troponin I and T have been bidities. However, myocardial injury following epinephrine after brain death and the extent of shown to have diffuse subendocardial myocy- Return to Management of myocardial damage have been shown to depend tolysis and coagulative necrosis. Echocardio- Hemodynamics map graphic systolic myocardial dysfunction is Return to Management of Shock map present in 42% of adult brain death and associated with ventricular dysrhythmias. More of- 1 Novitzky D, Wicomb WN, Cooper DKC, Rose AG, Fraser brain death is often related to catecholamine RC, Barnard CW. Electrocardiographic, hemodynamic and 5 Kono T, Morita H, Kuroiwa T, Onaka H, Takatsuka H, endocrine changes occurring during experimental brain Fujiwara A. Left ventricular wall motion abnormalities release. Neurological insults that cause progres- death in the chacma baboon. Heart Transplantation 1984; in patients with subarachnoid hemorrhage: neurogenic sive and sustained rise in intracranial pressure 4:63-9. stunned myocardium. J Am Coll Cardiol 1994; 24:636-40. 2 Ferrera R, Hadour G, Tamion F, Henry JP, Mulder P, Rich- 6 Temes RE, Tessitore E, Schmidt JM, Naidech AM, Fer- produce ischemia of the brainstem. When ard V, Thuillez C,Ovize M, Derumeaux G. Brain death nandez A, Ostapkovich ND,Frontera JA, Wartenberg KE, extension into the medulla oblongata occurs, provokes very acute alteration in myocardial morphology Di Tullio MR, Badjatia N, Connolly ES, Mayer SA,Parra A. the vagal cardiomotor nucleus becomes isch- detected by echocardiography: preventive effect of be- Left ventricular dysfunction and cerebral infarction from ta-blockers. Transpl Int. 2011 Mar;24(3):300-6. vasospasm after subarachnoid hemorrhage. Neurocrit emic, preventing tonic vagal stimuli resulting 3 Li J, Konstantinov IE, Cai S, Shimizu M, Redington Care. 2010 Dec;13(3):359-65. in unopposed sympathetic stimulation. The re- AN. Systemic and myocardial oxygen transport respons- 7 Macmillan CSA, Grant IS, Andrews PJD. Pulmonary and es to brain death in pigs. Transplant Proc. 2007 Jan- cardiac sequelae of subarachnoid haemorrhage: time for sult is a massive release of catecholamines which Feb;39(1):21-6 active management? Intensive Care Med 2002; 28:1012-23. may last for minutes to hours and clinically 4 Pérez López S, Otero Hernández J, Vázquez Moreno N, 8 Tung P, Kopelnik A, Banki N, Ong K, Ko N, Lawton MT, presents as arterial hypertension with the po- et al: Brain death effects on catecholamine levels and sub- Gress D, Drew B, Foster E, Parmley W, Zaroff J. Predic- sequent cardiac damage assessed in organ donors. J Heart tors of neurocardiogenic injury after subarachnoid hemor- Lung Transplant 2009; 28(8):815-820. rhage. Stroke. 2004 Feb;35(2):548-51. Epub 2004 Jan 22.

Organ Donation in Ontario: A Guide for Critical Care Residents - Donor Management 84 ten, the myocardial injury resulting from the sympathetic storm is transient and potentially reversible and has been defined as the “neurogenically stunned myocardium”. With tem- porary support, this often resolves even to the point where the heart may be suitable for transplantation despite a brief period of severe systolic dysfunction9.

Return to Management of Hemodynamics map Return to Management of Shock map

9 Dujardin KS, McCully RB, Wijdicks EF, Tazelaar HD, Seward JB, McGregor CG, Olson LJ. Myocardial dysfunction associated with brain death: clinical, echocardiographic, and pathologic features. J Heart Lung Transplant 2001; 20:350-7.

Organ Donation in Ontario: A Guide for Critical Care Residents - Donor Management 85 Verifying Thyroid Replacement Sonny Dhanani, Ronish Gupta, Pierre Cardinal, Andrew Healey transplantation. However, studies on thyroid Two forms of thyroid replacement are available. Description replacement in the brain dead donor are of low There are advantages of parenteral T3 over T4 quality with poor study design, limiting (stability for intravenous infusion, rapid Thyroid replacement should be considered in objective analysis1,2. onset as T3 does not require peripheral tissue all NDD patients as part of triple-hormonal conversion), but T3 is extremely expensive replacement therapy. Given the limited evidence, some have sug- in comparison to intravenous T4 and may not • Administer T4/ L-thyroxine 100 micro- gested restricting the use of thyroid replacement be commercially available in many countries5. grams IV bolus, then 50 micrograms IV to patients with documented hypothyroidism, There has not been evidence of benefit of one every 12 hours. identified cardiac dysfunction, or hemody- form over the other. Thus, most sites con- OR namic instability. Because of minimal side tinue to use T4 more commonly6. While there • Administer T4/ L-thyroxine 20 micro- effects, many donor management protocols is some evidence for an oral route7, we con- grams IV bolus followed by 10µg/hr IV advocate for its empiric use in all NDD patients. tinue to advocate for intravenous use until lar- infusion Empiric thyroid hormone administration with ger studies of equivalence have been completed. Return to Management of vasopressin and methylprednisolone (so called Hemodynamics map triple hormone therapy) has been shown to Return to Management of Shock map increase the number of transplanted organs, especially the heart3,4. Rationale 1 Klein I, Ojamaak K. Thyroid hormone and the cardiovas- The benefit of using thyroid hormone replace- cular system. NEJM 2001; 344(7): 501. 5 Zuppa AF, Nadkarni V, Davis L, Adamson PC, Helfaer ment therapy in brain dead donors is based on 2 Sazontseva IE, Kozlov IA, Moisuc YG, Ermolenko AE, MA, Elliott MR, Abrams J,Durbin D. The effect of a thy- Afonin VV, Illnitskiy VV. Hormonal response to brain roid hormone infusion on vasopressor support in critical- conflicting weak evidence, though evidence in death. Transplantation Proceedings 1991; 23(5):2467. ly ill children with cessation of neurologic function. Crit animal models is supportive. Alone, T3 replace- 3 James SR, Ranasinghe AM, Venkateswaran R, McCabe Care Med.2004 Nov;32(11):2318-22. CJ, Franklyn JA, Bonser RS.The effects of acute triiodo- 6 Kutsogiannis DJ, Pagliarello G, Doig C, Ross H, She- ment has been shown to reduce vasopressor thyronine therapy on myocardial gene expression in brain mie SD. Medical management to optimize donor organ use and improve cardiac function on echocard- stem dead cardiac donors. J Clin Endocrinol Metab. 2010 potential: review of the literature. Can J Anaesth. 2006 iography. Studies that also include the co- Mar;95(3):1338-43. Aug;53(8):820-30. 4 Roels L, Pirenne J, Delooz H, Lauwers P, Vandermeersch 7 Sharpe MD, van Rassel B, Haddara W. Oral and intra- administration of steroids, and vasopressin have E. Effect of triiodothyronine replacement therapy on venous thyroxine (T4) achieve comparable serum levels been more impressive. These have shown that maintenance characteristics and organ availability in hemo- for hormonal resuscitation protocol in organ donors: a dynamically unstable donors. Transplantation Proceedings randomized double-blinded study.Can J Anaesth. 2013 routine use may improve the chance of heart 2000; 32:1564-6. Oct;60(10):998-1002.

Organ Donation in Ontario: A Guide for Critical Care Residents - Donor Management 86 Consider First Choice Norepinephrine then Dobutamine Sabira Valiani, Alissa Visram, Pierre Cardinal

Description should be instituted along thyroid hor- dial contractility and heart rate. Its effects are • Institute norepinephrine as the vasopres- mone replacement (see 'Verifying Thyroid limited by the development of tachyarrythmias 3 sor of choice in patients who are suspected Replacement'). and vasodilation resulting in hypotension . to have shock secondary to catecholamine Other vasoactive agents, such as dopamine, mil- induced myocardial dysfunction Rationale rinone or epinephrine could also be considered 4 • The maximal dose recommended is In NDD patients presenting with cardiogenic in these situations . Although dopamine is 20mcg/minute or 0.2mcg/kg/minute1, shock, the initial step is to verify that thyroid traditionally considered first line for the man- 2 hormone therapy has been instituted. Thyroid agement of shock in NDD donors, there is lim- • If the targets are not met, the addition of hormone therapy with intravenous T3 may ited evidence to recommend its use over other dobutamine may be considered reduce cardiac dysfunction in NDD patients3. vasopressor agents, and there are concerns that 5 • Recognize and monitor for tachyar- However, patients may remain in shock despite it may lead to increased arrhythmia . thyroid hormone replacement. In these cas- Return to Management of es, vasopressors and inotropes should be add- In NDD patients who are potential heart Hemodynamics map ed based on physiologic rationale1. Norepin- donors, catecholamines should be used with Return to Management of Shock map ephrine is often the first vasopressor of choice caution. The Canadian guidelines state that because it provides both vasoconstrictor downregulation of ß-receptors and depletion 1 rhythmias and hypotension as the most activity via α1-adrenergic stimulation, and ino- of ATP occurs with the use of catecholamines . common adverse effects of dobutamine tropy via ß1-adrenergic stimulation. This The SCCM guidelines also caution about the administration3 results in an improvement in MAP and a small use of α-agonists, as stimulation of this recep- • Milrinone and epinephrine may also increase in cardiac output and stroke volume3. tor predisposes to increased pulmonary be considered as inotropic support. If the administration of norepinephrine fails to • The above vasopressors and inotropes improve perfusion and surrogate markers for cardiac output, an inotrope, such as dobuta- 4 Kotloff RM, Blosser S, Fulda GJ, et al. Manage- 1 Shemie SD, Ross H, Pagliarello J, et al. Organ donor man- ment of the Potential Organ Donor in the ICU. agement in Canada: Recommendations of the forum on mine can be added. Dobutamine has primarily Crit Care Med. 2015;43(6):1291-1325. doi:10.1097/ Medical Management to Optimize Donor Organ Potential. ß1-adrenergic activity, which increases myocar- CCM.0000000000000958. CMAJ. 2006;174:S13-S30. doi:10.1503/cmaj.045131. 5 De Backer D, Biston P, Devriendt J, Madl C, Chochrad 2 Trillium Gift of Life Network. Donation Resource Manu- 3 Hollenberg SM. Vasoactive drugs in circulatory shock. D, Aldecoa C, et al. Comparison of dopamine and al: A tool to assist hospitals with the process of organ and American journal of respiratory and critical care medicine. norepinephrine in the treatment of shock. NEJM. tissue Donation. Queen's Printer for Ontario: 2010. 2011;183(7):847-55. doi: 10.1164/rccm.201006-0972CI. 2010;362(9):779-89. doi: 10.1056/NEJMoa0907118.

Organ Donation in Ontario: A Guide for Critical Care Residents - Donor Management 87 capillary permeability, and may result in coronary vasoconstriction4.

Due to the potential harms of catecholamine administration to NDD patients who are potential heart donors, optimization with thyroid hormone administration should be performed first. If a shock state is persistent, the minimal doses of vasopressors and inotropes required to meet blood pressure and perfusion targets should be instituted.

Return to Management of Hemodynamics map Return to Management of Shock map

Organ Donation in Ontario: A Guide for Critical Care Residents - Donor Management 88 Anticipate Distributive Shock Sonny Dhanani, Pierre Cardinal, Andrew Healey

Description cholamine depletion ensues leading to de- hence cardiac output4,5. Anticipate distributive shock given its high creased systemic vascular resistance and profound 1 prevalence in NDD patients. vasodilation . Overall, sympathetic arrest due to catecholamine and sympathetic hormone depletion Rationale From a hormonal perspective, the combination and consequent reduced systemic vascular of increased intracranial pressure, ischemia and resistance underly hypotension and distributive The etiology of hypotension in brain dead inflammatory mediated damage in neurologic shock in the potential donor. Other etiologies of patients is characterized by low preload due to death interfere with hypothalamus and pitu- distributive shock (e.g. sepsis) should always be vascular volume depletion, neurogenically- itary functioning. As a result, several hormonal considered but are far less common. Aggressive mediated contractile myocardial dysfunction, axes begin to fail. Secretion of arginine vasopres- management of hypotension during the inter- and a fall in the systemic vascular resistance sin from the posterior pituitary is impaired in val from admission to procurement is essential 2,3 Return to Management of over three-quarters of potential organ donors . to prevent the development of multiple organ Hemodynamics map A reduction in vasopressin (a direct vasocon- failure and possibly cardiac arrest5. Return to Management of Shock map strictor), as well as ACTH (cortisol stimulation) result in decreased vascular tone and hypotension. The decreased vascular tone of the venous resulting from a catecholamine and sympathet- capacitance vessels often lowers the mean sys- ic hormone depletion. temic venous pressure reducing venous return,

During the process of brainstem ischemia and herniation, the regulation of sympathetic and 1 Salim A., Martin M., Brown C., et al: Complications of parasympathetic activity becomes unbalanced. brain death: frequency and impact on organ retrieval. Am Surg 2006; 72(5):377-381. Periods of unopposed sympathetic 2 Huang J, Trinkaus K, Huddleston CB, Mendeloff EN, activity known as “sympathetic storm” occur Spray TL, Canter CE. Risk factors for primary graft failure after pediatric cardiac transplantation: importance of re- 4 Shah VR. Aggressive management of multiorgan donor. within minutes of marked increases in intra- cipient and donor characteristics. J Heart Lung Transplant. Transplant Proc. 2008 May;40(4):1087-90. cranial pressure, and coincide with elevated 2004 Jun;23(6):716-22. 5 Zaroff JG, Rosengard BR, Armstrong WF, et al., Consen- levels of circulating catecholamines. With- 3 Nakagawa K, Tang JF. Physiologic response of human sus conference report Maximizing use of organs recovered brain death and the use of vasopressin for successful or- from the cadaver donor: cardiac recommendations. Circu- in hours of this initial phase, a state of cate- gan transplantation. J Clin Anesth. 2011 Mar;23(2):145-8. lation 2002; 106:836-41.

Organ Donation in Ontario: A Guide for Critical Care Residents - Donor Management 89 Verifing Vasopressin Administration for Distributive Shock Sonny Dhanani, Ronish Gupta, Pierre Cardinal

Description romised heart. Supporting this idea, an analysis Adults Given that the sequence of brainstem ischemia of 12,322 donors demonstrated that AVP use • Administer vasopressin at a rate of 2.4 and herniation typically results in diminished was associated with higher numbers of organs 6 units/hour (0.04 units/min) in all adult sympathetic activity as well as AVP deficiency, retrieved per donor (3.75 vs 3.33; p < 0.001) . patients unless hypertensive optimizing vascular tone becomes a priority. Secretion of AVP from the posterior pituitary is Caution should still be maintained when admin- Rationale impaired in over three-quarters of potential istering AVP as reductions in splanchnic blood organ donors. Low-dose AVP infusions have flow have been demonstrated when compared Brain death and hypotension are often asso- been shown to improve hemodynamic stabil- to dopamine2. Additional benefit may be con- ciated with vasopressin deficiency1. Arginine ity and spare catecholamine use2,3. Prolonged ferred to hemodynamically unstable patients Vasopressin (AVP) is a peptide that is formed in hemodynamic stability can be maintained when AVP is used in combination with other Return to Management of after brain death with low-dose AVP (1–2 hormone therapies. Intravenous AVP/vaso- Hemodynamics map units/hour), permitting a significant decrease pressin infusion can be titrated from minimum Return to Management of Shock map in epinephrine and extended preservation of of 0.5 units/h and maximum of 2.4 units/h to renal function4,5. This finding is considered obtain a systolic blood pressure of 100 mmHg advantageous as it may limit excessive catechol- or mean arterial pressure of 70 mmHg. amine driven demands on an already comp- the hypothalamus and then stored in as well as secreted from the posterior pituitary. Its activity 2 Pennefather SH, Bullock RE, Mantle D, Dark JH. Use of upon the V1 receptors of vascular smooth mus- low dose arginine vasopressin to support brain-dead organ donors. Transplantation 1995; 59(1):58-62. cle leads to vasoconstriction (i.e. its “vasopres- 3 Holmes CL, Patel BM, Russell JA, Walley KR. Physiology sor” effect); and its activity upon the V2 recep- of vasopressin relevant to management of septic shock. tors within the renal collecting system promote Chest 2001; 120:989-1002. 4 Nakagawa K, Tang JF. Physiologic response of human the reabsorption of free water (i.e. its “anti- brain death and the use of vasopressin for successful or- diuretic” effect). gan transplantation. J Clin Anesth. 2011 Mar;23(2):145-8. 5 Dunser MW, Mayr AJ, Ulmer H, Knotzer H, Sumann 1 Chen JM, Cullinane S, Spanier TB, Artrip JH, John R, Ed- G, Pajk W, Friesenecker B, Hasibeder WR. Arginine va- 6 Plurad DS, Bricker S, Neville A, Bongard F, Putnam B. Ar- wards NM, Oz MC, Landry DW. Vasopressin deficiency sopressin in advanced vasodilatory shock: a prospec- ginine vasopressin significantly increases the rate of suc- and pressor hypersensitivity in hemodynamically unstable tive, randomized,controlled study. Circulation. 2003 May cessful organ procurement in potential donors. Am J Surg. organ donors. Circulation 1999; 100 (suppl II):II-246. 13;107(18):2313-9. 2012;204(6):856-861. doi:10.1016/j.amjsurg.2012.05.011.

Organ Donation in Ontario: A Guide for Critical Care Residents - Donor Management 90 Steroid Administration in Patients with Distributive Shock Sonny Dhanani, Ronish Gupta, Pierre Cardinal

Description develop a state of adrenal insufficiency and/or steroid replacement therapy (50 milligram bolus • Verify if donor is already receiving high- suppression that is unique to the brain death of hydrocortisone, followed by 10 milligram dose steroid (e.g. methylprednisolone) as process or similar to critically ill patients in per hour continuous infusion). In this study, 1 an immune modulator in preparation for general . A study of 37 adults with severe trau- the group receiving steroid replacement had re- potential lung donation matic brain injury revealed that compared to duced need for norepinephrine (mean 1.18 ± • In presence of shock for patients who are matched non-neurologically deceased patients, 0.92 vs 1.49 ± 1.29 milligrams per hour; p = not on high-dose steroid, administer intra- the 17 neurologically deceased individuals had 0.03), shorter time on norepinephrine (median venous steroids (e.g. hydrocortisone) for significantly lower circulating cortisol levels 874 vs 1,160 minutes; p < 0.0001) and a greater maintenance of hemodynamic targets (234 ± 171 vs 469 ± 182 nmol/L; p < 0.001) likelihood of being weaned off norepinephrine and significantly reduced peak cortisol response support (33.8% vs 9.5%; p < 0.0001). Steroid to ACTH administration (466 ± 174 vs 659 ± use however, was not associated with higher or- 1 2 Return to Management of 157 nmol/L; p = 0.001) . gan procurement or improved graft function . Hemodynamics map Return to Management of Shock map Steroid replacement for the maintenance Therefore, in patients who are not on high-dose of hemodynamic targets in the management steroids (administered in preparation for lung of distributive shock has been recommended. transplantation) and present with cardiovascu- Rationale This is in addition to the recommendation of lar instability requiring inotrope/pressor, rou- high-dose steroid administration for the anti- tine administration of low dose steroids should The anterior pituitary secretes adrenocorti- inflammatory benefits shown for lung transplan- be considered to address the possibility of adre- cotropic hormone (ACTH) which stimulates tation. Note that patient receiving high-dose nal insufficiency. cortisol release from the adrenal glands. steroids in preparation for lung donation do not Cortisol has numerous functions in healthy need to receive stress-dose steroids. A prospec- individuals, but its most relevant roles in the tive multi-centre cluster study of 208 neurolog- organ donor are maintaining hemodynamic ically deceased adults has studied the effect of stability and modulating the body’s immune system. 1 Callahan DS, Kim D, Bricker S, et al. Trends in 2 Pinsard M, Ragot S, Mertes PM, et al. Interest of l Organ Donor Management: 2002 to 2012. J Am Coll ow-dose hydrocortisone therapy during brain-dead organ Surg. 2014;219(4):752-756. doi:10.1016/j.jamcoll- donor resuscitation : the CORTICOME study. Crit Care. It is unclear whether potential organ donors surg.2014.04.017. 2014;18(R158):1-8.

Organ Donation in Ontario: A Guide for Critical Care Residents - Donor Management 91 Considering Other Vasopressor Use in Donors with Distributive Shock Sonny Dhanani, Pierre Cardinal, Andrew Healey

Description Vasopressin Instituted'). Given the abnormal tion and downregulation of beta-receptors. In • Initiate Norepinephrine (0-1.3 mcg/kg/ pituitary-adrenal axis (see 'Verifying Steroid Ad- potential cardiac donors, the guidelines recom- min) and titrate to effect ministration') of NDD patients, it is important mend limiting the maximal infusion rate (e.g. • Select default MAP target of 65 mmHg. to verify that all patients in distributive shock for dopamine, limiting to a rate no higher than Target MAP may be readjusted based on also be receiving corticosteroids to maintain a 10 µg/kg per minute). The recent American the patient’s baseline BP normal vasopressor response to catecholamine. guidelines note that dopamine has traditional- • Monitor for hypoperfusion using clinical However, many NDD patients remain hypo- ly been the first-line vasoactive agent for man- examination (prolonged capillary refill, tensive despite adequate volume resuscitation agement of cardiovascular collapse following cold extremities, presence of mottling); and the administration of vasopressin and cor- brainstem death, but there remain insufficient rising serum lactate; decrease in central ticosteroids and thus may require the addition data to preferentially recommend this drug over 2 venous oxygen saturation; or invasive or of other vasopressors. other vasopressor agents . The guidelines also note that norepinephrine or phenylephrine are Return to Management of The 2006 Canadian guidelines recommend recommended in the predominantly vasodila- Hemodynamics map the use of norepinephrine, epinephrine and/or tory component of shock (low systemic vascular Return to Management of Shock map phenylephrine for hemodynamic support with resistance). In other causes of shock states with dosing titrated to achieve clinical effect, but with low SVR (e.g. septic patients), norepinephrine 1 noninvasive means to identify any de- no predetermined upper limit . The guidelines as compared to dopamine, was demonstrated crease in cardiac output also distinguish between pure vasopressors (va- to increase mean perfusion pressures without • Monitor for ischemic events (extremities, sopressin, phenylephrine) and vasopressors with adverse effects to renal and splanchnic blood 3 bowel, kidneys, and heart) beta-agonist inotropic action (norepinephrine, flow . In addition, the rate of complications, epinephrine). They recommend cautious use of in particular arrhythmia, was lower in patients Rationale vasopressors with beta-agonist action in potential heart donors, given concerns about myo- 2 Kotloff RM, Blosser S, Fulda GJ, et al. Manage- In NDD patients presenting with distributive cardial adenosine triphosphate (ATP) deple- ment of the Potential Organ Donor in the ICU. shock, vasopressin is often the first vasopressor Crit Care Med. 2015;43(6):1291-1325. doi:10.1097/ CCM.0000000000000958.88. of choice because it not only increases vasomo- 1 Shemie SD, Ross H, Pagliarello J, et al. Organ donor man- 3 De Backer D, Creteur J, Silva E, Vincent JL. Effects of do- tor tone but may also treat or prevent the de- agement in Canada: Recommendations of the forum on pamine,norepinephrine, and epinephrine on the splanchnic velopment of diabetes insipidus (see 'Verifying Medical Management to Optimize Donor Organ Potential. circulation in septic shock:which is best? Crit Care Med. CMAJ. 2006;174:S13-S30. doi:10.1503/cmaj.045131. 2003 Jun;31(6):1659-67.

Organ Donation in Ontario: A Guide for Critical Care Residents - Donor Management 92 treated with norepinephrine compared to those treated with dopamine4.

It is therefore recommended that norepinephrine be administered in NDD patients with distributive shock and persistent hypotension despite adequate fluid resuscitation and administration of vasopressin and corticosteroids.

Return to Management of Hemodynamics map Return to Management of Shock map

4 De Backer, D, Biston P, et al. Comparison of Dopamine and Norepinephrine in the Treatment of ShockN Engl J Med 2010; 362:779-789

Organ Donation in Ontario: A Guide for Critical Care Residents - Donor Management 93 Fluid Resuscitation in Distributive Shock Alissa Visram, Sabira Valiani, Pierre Cardinal, Andrew Healey

Description Rationale response to fluid boluses2. A positive response • Recognize the need for fluid bolus admin- The overall goal of donor management is to to a fluid challenge could consist of an increase istration in distributive and hypovolemic ensure adequate end organ perfusion in order in blood pressure (or a decreased need for shock. to preserve organ function for donation. The vasopressor support), increased urine output, • Administer fluid boluses to improve principles of fluid resuscitation in an NDD a decrease in heart rate, or an improvement hemodynamic stability and reach donor are the same as living patients. in peripheral perfusion (e.g. mottling, cool ex- pre-defined blood pressure and perfusion tremities) or other markers of hypoperfusion targets. Fluid resuscitation is indicated in NDD (serum lactate, pulse pressure variation, etc). • Choose fluid resuscitation based on the donors who have hypovolemic or distributive Fluid should not be administered when there is composition and physiologic properties of type shock. The purpose of fluid resuscitation is a lack of a response to the previous fluid bolus, 2 the fluid, as well as the patient’s electrolyte to increase preload and thereby cardiac output1. or if pulmonary edema develops . and acid-base status. The decision to administer a fluid bolus should be based on a clinical assessment suggestive of Isotonic crystalloids or colloids may be chosen Return to Management of for initial fluid resuscitation in NDD donors3. Hemodynamics map hypovolemia. Hypovolemia can be assessed by using static and dynamic indices, and a full dis- There is limited evidence to guide the choice Return to Management of Shock map cussion of the predictive value and limitations of of crystalloid or colloid fluid for initial resus- 3 these indices is beyond the scope of this chapter. citation in NDD patients . In living patients • Recognize that there is no strong evidence However, common indicators of hypovolemia with shock, the administration of 4% albumin, to suggest the preferential use of colloids include significant stroke volume variation or as compared to normal saline, for fluid resus- versus crystalloids when resuscitating significant pulse pressure variation1. citation did not show any mortality benefit, NDD donors in shock. and there were no differences in rates of or- • Avoid hydroxyethyl starch during resusci- The TGLN guidelines suggest fluid bolus- gan failure or days of renal replacement thera- tative efforts given the risk of renal injury es to be administered in 250-500mL aliquots 2 Trillium Gift of Life Network. Donation Resource Manu- (both AKI and delayed renal graft over 10 minutes, with frequent reassessment of al: A tool to assist hospitals with the process of organ and function) tissue Donation. Queen's Printer for Ontario: 2010. 1 Bendjelid K, Romand JA. Fluid responsiveness in mechan- 3 Kotloff RM, Blosser S, Fulda GJ, et al. Manage- ically ventilated patients: a review of indices used in inten- ment of the Potential Organ Donor in the ICU. sive care. Intensive care medicine. 2003;29(3):352-60. doi: Crit Care Med. 2015;43(6):1291-1325. doi:10.1097/ 10.1007/s00134-002-1615-9. CCM.0000000000000958.

Organ Donation in Ontario: A Guide for Critical Care Residents - Donor Management 94 py4. The lack of benefit for colloid resuscitation diabetes insipidus, first correct the patient’s fy that all patients in distributive shock also be in critically ill patients was also confirmed hypovolemia with an isotonic crystalloid (pref- receiving corticosteroids to maintain a normal in a Cochrane review in 20135. It should be erentially ringer’s lactate given its lower sodium vasopressor response to catecholamine. In pa- noted that colloids are more expensive than content) and then correct the hypernatremia tients suspected to be hypovolemic from diabe- crystalloids6. with D5W intravenously or free water enteral- tes insipidus, administration of vasopressin is ly. If the patient is euvolemic, correct the pa- important to limit further fluid loss, and must Ringer’s lactate and 0.9% saline are the recom- tient’s hypernatremia with D5W or free water, accompany fluid resuscitation. Many NDD mended isotonic crystalloid solutions used in as outlined in the “Endocrine - diabetes insip- patients remain hypotensive despite fluid re- the resuscitation of critically ill patients3. Their idus management” sections (see 'Anticipating suscitation and commonly require the addition use should be guided by the patient’s electrolyte Diabetes Insipidus') of other vasopressors or inotropes. and acid-base status. Excessive use of 0.9% When using colloids for fluid resuscitation, the primary options are starches or blood products Return to Management of (ie: albumin or packed red blood cells). The Hemodynamics map Society of Critical Care Medicine and TGLN Return to Management of Shock map guidelines recommend that hydroxyethyl starch (HES) should NOT be used given its saline can lead to hypernatremia or a hyperchlo- association with delayed graft function and remic metabolic acidosis. In NDD donors with renal failure 3,7. hypernatremia and hypovolemia secondary to Fluid resuscitation alone may be unsuccessful in 4 Finfer S, Bellomo R, Boyce N, French J, Myburgh J, Nor- ton R. A comparison of albumin and saline for fluid re- optimizing blood pressure and perfusion in the suscitation in the intensive care unit. The New England NDD donor. Given the abnormal pituitary- journal of medicine. 2004;350(22):2247-56. doi: 10.1056/ NEJMoa040232. adrenal axis (see 'Verifying Steroid Administra- 5 Perel P, Roberts I, Ker K. Colloids versus crystalloids for tion') of NDD patients, it is important to veri- fluid resuscitation in critically ill patients. The Cochrane database of systematic reviews. 2013;2:Cd000567. Epub 7 Shemie SD, Ross H, Pagliarello J, et al. Organ donor man- 2013/03/02. doi: 10.1002/14651858.CD000567.pub6. agement in Canada: Recommendations of the forum on 6 Vassalos A, Rooney K. Surviving Sepsis Guidelines 2012. Medical Management to Optimize Donor Organ Potential. Critical Care Medicine. 2013;41:e485-e486. CMAJ. 2006;174:S13-S30. doi:10.1503/cmaj.045131.

Organ Donation in Ontario: A Guide for Critical Care Residents - Donor Management 95 Anticipate Hypovolemia Secondary to DI or Other Causes Sonny Dhanani, Pierre Cardinal, Andrew Healey

Description Rationale tremia (> 145mmol/L) and an increased serum • To anticipate hypovolemia in brain dead Hypovolemia is frequently observed in brain osmolality (> 300mOsm/kg•H2O). In the con- patient dead patient. Fluid restriction and the ad- text of brain death, diabetes insipidus should be • To identify that diabetes insipidus (DI) is ministration of diuretics and mannitol to presumed even if all criteria not met, especially 2,3 a common cause of hypovolemia in brain treat increased intracranial pressure, hidden in the context of clinical hypovolemia . dead patient blood loss in trauma patients, are but some of • To recognize other causes of hypovolemia the many causes of hypovolemia in potential NDD donors. However, diabetes insipidus is so frequent that it should be expected in all NDD donors. Arginine vasopressin (AVP) is a peptide that is formed in the hypothalamus Return to Management of and then stored in as well as secreted from the Hemodynamics map posterior pituitary. Its anti-diuretic effect on the Return to Management of Shock map V2 receptors within the renal collecting system promotes the reabsorption of free water. AVP regulates extracellular fluid volume by the reabsorption of water from the kidneys. After brain death, a lack of AVP leads to unregulated renal losses of free water resulting in a state of diabetes insipidus. This almost universally leads to free water deficit and hypovolemia1. Diabetes insipidus is confirmed if urine output remains excessive (> 4mL/kg/h) as well as dilute (< 200 2 Ball SG: Vasopressin and disorders of water balance: The mOsm/kg•H2O) and associated with hyperna- physiology and pathophysiology of vasopressin. Ann Clin Biochem 2007;44:417–431 3 Kutsogiannis DJ, Pagliarello G, Doig C, Ross H, She- 1 Loh JA, Verbalis JG: Disorders of water and salt metab- mie SD. Medical management to optimize donor organ olism associated with pituitary disease. Endocrinol Metab potential: review of the literature. Can J Anaesth. 2006 Clin North Am 2008; 37:213–234 Aug;53(8):820-30.

Organ Donation in Ontario: A Guide for Critical Care Residents - Donor Management 96 Verifying Vasopressin Administration in the Context of DI Sonny Dhanani, Ronish Gupta, Pierre Cardinal

Description Rationale < 100 mmHg or mean arterial pressure < 70 3,4 Titrate vasopressin intravenous infusion (0 to Although the mechanism has not been estab- mmHg . a maximal dose of 2.4 units/hr) targeting lished, diabetes insipidus has the potential to a systolic blood pressure above 100 mmHg, se- impair organ function beyond that simply In situations, where signs of diabetes insipidus rum sodium levels between 130 – 155 mmol/L, resulting from diuresis, hypovolemia, and persist despite vasopressin infusion, intermit- and urine output 0.5 – 3 mL/kg/h hemodynamic instability. Potential organ do- tent desmopressin may be added to vasopressin. nors with diabetes insipidus often present with Desmopressin inhibits diuresis but has virtu- hypotension from excessive fluid losses. This ally no vasopressor side effect, so is not helpful may be managed with fluid replacement but in the context of hypotension. more importantly needs to be managed for ongoing losses. A vasopressin (AVP) infusion is In either case, AVP infusions should be Return to Management of the preferred agent for patients with concom- titrated to target systolic blood pressure above Hemodynamics map itant hypotension. It provides the dual bene- 100 mmHg, serum sodium levels 130 – 155 Return to Management of Shock map fits of anti-diuresis as well as hemodynamic mmol/L and urine output 0.5 – 3 mL/kg/h. support1. However, concerns around possible interference with end-organ perfusion exist based on animal models of splanchnic blood flow. For this reason, in hypertensive patients, high-doses of AVP might be avoided2. Vaso- pressin intravenous infusion should be started at 0-2.4 units/hr for systolic blood pressure 3 Nakagawa K, Tang JF. Physiologic response of human 1 Chen JM, Cullinane S, Spanier TB, Artrip JH, John R, Ed- brain death and the use of vasopressin for successful or- wards NM, Oz MC, Landry DW. Vasopressin deficiency gan transplantation. J Clin Anesth. 2011 Mar;23(2):145-8. and pressor hypersensitivity in hemodynamically unstable 4 Dunser MW, Mayr AJ, Ulmer H, Knotzer H, Sumann organ donors. Circulation 1999; 100 (suppl II):II-246. G, Pajk W, Friesenecker B, Hasibeder WR. Arginine va- 2 Holmes CL, Patel BM, Russell JA, Walley KR. Physiology sopressin in advanced vasodilatory shock: a prospec- of vasopressin relevant to management of septic shock. tive, randomized,controlled study. Circulation. 2003 May Chest 2001; 120:989-1002. 13;107(18):2313-9.

Organ Donation in Ontario: A Guide for Critical Care Residents - Donor Management 97 Administer Infusion of DDAVP in Addition to Vasopressin Sonny Dhanani, Ronish Gupta, Pierre Cardinal, Andrew Healey

Description specific affinity for the V2 vasopressin receptors ± 44 vs 124 ± 106 µmol/L; p < 0.001)3,4. 1 In patients in shock and diabetes insipidus (DI) in the renal collecting system . This property treated with vasopressin but with persistently allows desmopressin to inhibit diuresis but Desmopressin boluses should be titrated to high urine output without any vasopressor effect. Multiple routes target urine output 0.5 – 3 mL/kg/h with close • Start desmopressin (DDAVP) 4 of administration are available, but the monitoring of the serum sodium levels (target micrograms IV every 6 hours and titrate intravenous route is preferred in the organ 130 – 155 mmol/L). Intermittent intravenous to urine output 0.5 - 3 mL/kg/hr with donor. Although concerns for potential throm- DDAVP 4 micrograms every 6 hours is a com- close monitoring of serum sodium levels bogenic complications have been raised with mon regiment. Intravenous maintenance fluids (target 130-150 mmol) desmopressin use, it does not seem to impair to maintain blood pressure and perfusion and graft survival2. One trial of 97 adult organ the administration of free water (either through donors randomized to receive desmopres- the enteral route or intravenously) should be 5 Return to Management of sin or nothing for diabetes insipidus demon- considered to correct hypernatremia . Hemodynamics map strated no impairment in pre-procurement Return to Management of Shock map renal function or post-transplant need for dialysis in those who received desmopressin. A more recent retrospective analysis of 458 neuro- Rationale logically deceased adult kidney donors suggested that those treated with desmopressin actu- An AVP infusion is the preferred agent for ally had improved renal function (creatinine 97 patients with both shock and diabetes insipi- 3 Nakagawa K, Tang JF. Physiologic response of human dus (DI) because vasopressin provides the dual brain death and the use of vasopressin for successful or- benefits of anti-diuresis as well as weak vaso- gan transplantation. J Clin Anesth. 2011 Mar;23(2):145-8. 4 Dunser MW, Mayr AJ, Ulmer H, Knotzer H, Sumann pressor support. However, some patients may G, Pajk W, Friesenecker B, Hasibeder WR. Arginine va- continue to have high water losses resulting 1 Chen JM, Cullinane S, Spanier TB, Artrip JH, John R, Ed- sopressin in advanced vasodilatory shock: a prospec- wards NM, Oz MC, Landry DW. Vasopressin deficiency tive, randomized,controlled study. Circulation. 2003 May in hypernatremia despite a vasopressin infu- and pressor hypersensitivity in hemodynamically unstable 13;107(18):2313-9. Epub 2003 May 5. sion. In such patients, desmopressin (1-desa- organ donors. Circulation 1999; 100 (suppl II):II-246. 5 Kutsogiannis DJ, Pagliarello G, Doig C, Ross H, She- mino-8-d-arginine vasopressin, or DDAVP) is 2 Pennefather SH, Bullock RE, Mantle D, Dark JH. Use of mie SD. Medical management to optimize donor organ low dose arginine vasopressin to support brain-dead organ potential: review of the literature. Can J Anaesth. 2006 often added to vasopressin because of its highly donors. Transplantation 1995; 59(1):58-62. Aug;53(8):820-30.

Organ Donation in Ontario: A Guide for Critical Care Residents - Donor Management 98 Select Type of Crystalloid Based on Serum Na in a DI Context Michael Hartwick, Alissa Visram, Sabira Valiani, Sonny Dhanani, Andrew Healey

Description ◾◾ Administer a IV bolus of 250 mL of are recommended. For patients with hypona- • Recognize the need for fluid bolus admin- D5W or free water enterally. tremia, 0.9%NS solution is preferred, whereas istration in hypovolemic shock. ◾◾ Change maintenance fluids to D5W. RL is preferred in the patients with hyperna- 2 • Administer fluid boluses to improve he- tremia given its lower sodium content . Once modynamic stability and reach pre- Rationale the patient becomes euvolemic, Ringer’s lactate defined blood pressure and perfusion The principles of fluid resuscitation in an NDD should be discontinued and the hypernatremia 2 targets. donor are the same as in living patients. Fluid corrected with either D5W or free water . • If clinically hypovolemic and resuscitation is indicated in NDD donors who hyponatremic (serum Na < 135 mmol/L) have hypovolemic shock. The purpose of fluid Hypernatremia (serum sodium > 155 mmol/L) • Administer 0.9%NS 500 mL IV and resuscitation is to increase preload and thereby secondary to excessive sodium administration repeat until fluid resuscitated. cardiac output1. The decision to administer a during resuscitation or diabetes insipidus may fluid bolus should be based on a clinical assess- lead to the accumulation of compensatory Return to Management of ment suggestive of hypovolemia. Hypovolemia idiogenic osmoles in donor organs. Once trans- Hemodynamics map can be assessed by using static and dynamic planted, significant intracellular fluid shifts may Return to Management of Shock map indices, and a full discussion of the predictive develop as these organs are exposed to the value and limitations of these indices is beyond recipient normal serum; the different • If clinically hypovolemic and serum Na the scope of this chapter. However, common osmolalities resulting in a water influx into the 3,4 between 135-145 mmol/L indicators of hypovolemia include significant transplanted organs . • Administer 0.9%NS or Ringer’s stroke volume variation or significant pulse Lactate bolus of 500 mL IV repeat un- pressure variation1. 2 Trillium Gift of Life Network. Donation Resource Manu- al: A tool to assist hospitals with the process of organ and til fluid resuscitated. tissue Donation. Queen's Printer for Ontario: 2010. • If clinically hypovolemic and The fluid selection is guided by the serum 3 Bloom MB, Raza S, Bhakta A, et al. Impact of Deceased hypernatremic (serum Na>145mmol/L) sodium level. In the presence of a normal serum Organ Donor Demographics and Critical Care End Points on Liver Transplantation and Graft Survival Rates. J • Administer Ringer’s Lactate bolus of sodium, either Ringer’s lactate or 0.9% saline Am Coll Surg. 2015;220(1):38-47. doi:10.1016/j.jamcoll- 500 mL IV surg.2014.09.020. 1 Bendjelid K, Romand JA. Fluid responsiveness in mechan- 4 Kazemeyni SM, Esfahani F. Influence of hypernatremia • Once fluid resuscitated administer free ically ventilated patients: a review of indices used in inten- and polyuria of brain-dead donors before organ pro- water (intravenously or enterally) sive care. Intensive care medicine. 2003;29(3):352-60. doi: curement on kidney allograft function. Urol J. 2008 Sum- 10.1007/s00134-002-1615-9. mer;5(3):173-7.

Organ Donation in Ontario: A Guide for Critical Care Residents - Donor Management 99 Traditionally, hypernatremia was thought to be independently associated with hepatic and renal dysfunction or graft loss after transplanta- tion4. However, more recent evidence suggests that this effect may be less significant than once believed4,5. Given that avoiding or treating hypernatremia is easily achieved using inexpensive management strategies, it is recommended to target normal serum sodium levels by selecting with appropriate maintenance intravenous fluids, and the aggressive correction of hypernatremia.

Return to Management of Hemodynamics map Return to Management of Shock map

5 Mangus RS, Fridell JA, Vianna RM, Milgrom ML, Chestovich P, Vandenboom C,Tector AJ. Severe hypernatremia in deceased liver donors does not impact early transplant outcome. Transplantation. 2010 Aug 27;90(4):438-43.

Organ Donation in Ontario: A Guide for Critical Care Residents - Donor Management 100 Titrate to Pre-Defined Targets Sabira Valiani, Alissa Visram, Sonny Dhanani, Pierre Cardinal

Description expertise: normal stroke volume by (e.g. a reduction in perfusion due to arteriolar • Titrate first line agent to pre-defined echocardiography, or non-invasive constriction) as well as adverse effects. Note that blood pressure and perfusion targets1,2 cardiac output monitors there is little clinical evidence to support the • A default target MAP should be ≥ • If the above targets are not met, the proposed targets for both blood pressure and 70mmHg1, which can be adjusted addition of second line agents should be perfusion. based on the patient’s baseline blood considered pressure • Recognize and monitor for common • Monitor perfusion and cardiac output adverse effect of high dose vasopressor using the following targets: and inotrope administration ◾◾ Clinical surrogates: No mottling, capillary refill less than 4 seconds, Rationale It is essential to closely monitor both blood Return to Management of pressure and perfusion in NDD patients to Hemodynamics map ensure the early identification of patients in need Return to Management of Shock map of further resuscitation. Achieving the targeted pressures and perfusion parameters increases the and warm extremities likelihood of successful multi-organ donation ◾◾ Laboratory surrogates: a normal or and the likelihood of maintaining a donor to decreasing lactate, and a central successful procurement3. The response to ther- venous oxygen saturation ≥ 60% apeutic interventions should also be close- ◾◾ Noninvasive means if skills and ly monitored and should encompass not only the intended effect (e.g. a rising blood pressure 1 Shemie SD, Ross H, Pagliarello J, et al. Organ donor man- with vasopressors) but also unintended effects agement in Canada: Recommendations of the forum on Medical Management to Optimize Donor Organ Poten- tial. CMAJ. 2006;174(6 SUPPL.):S13-S30. doi:10.1503/ 3 Malinoski DJ, Patel MS, Daly MC, Oley-Graybill C, Salim cmaj.045131. A. The impact of meeting donor management goals on 2 Trillium Gift of Life Network. Donation Resource Manu- the number of organs transplanted per donor. Crit Care al: A tool to assist hospitals with the process of organ and Med. 2012;40(10):2773-2780. doi:10.1097/CCM.0b013e- tissue Donation. Queen's Printer for Ontario: 2010. 31825b252a.

Organ Donation in Ontario: A Guide for Critical Care Residents - Donor Management 101