The Use of Procedural Sedation in Children

Total Page:16

File Type:pdf, Size:1020Kb

The Use of Procedural Sedation in Children PAEDIATRIC MEDICINES RESEARCH GROUP DIVISION OF GRADUATE ENTRY MEDICINE AND HEALTH SCHOOL OF MEDICINE UNIVERSITY OF NOTTINGHAM THE USE OF PROCEDURAL SEDATION IN CHILDREN BADRIYAH SHADID ALOTAIBI BPharm, MSc. THESIS SUBMITTED TO THE UNIVERSITY OF NOTTINGHAM FOR THE DEGREE OF DOCTOR OF PHILOSOPHY SEPTEMBER, 2016 DEDICATION DEDICATED WITH LOVE TO MY PARENTS, MY HUSBAND, MY CHILDREN AND ALL MY FAMILY MEMBERS IN SAUDI ARABIA. I ABSTRACT The use of sedation for diagnostic and therapeutic procedures in children is common and leads to considerable debate. Evaluating this subject is complicated by differences in the methods and the outcomes used for sedation assessment in children reported in the literature which are large. This thesis used systematic literature reviews, a prospective study and a national survey to evaluate several aspects of paediatric sedation. A systematic review of the safety and effectiveness of chloral hydrate in three categories of procedural sedation was conducted. For painless procedural sedation, chloral hydrate was more effective for shorter imaging procedures, such as CT scanning. The incidence of adverse events was 1,951 occurring in 14439 patients (13.5%), with hypoxia the most frequent. Moderate hypoxia (SpO2 85%–90%) was seen in 281 cases of 14439 patients (1.9%) of children. For painful procedural sedation, the success rate of chloral hydrate was variable (35%–100%). Hypoxia was the most common adverse event, occurring in 95 of 1810 patients (5.2%). Most (66 cases/1810 patients, 3.6%) were mild however moderate hypoxia occurred in 29 of 1810 patients (1.6%). The incidence of adverse events was higher during painful procedures than during painless procedures: 313AEs/1810 patients (17.3%) versus 1,951AEs/14439 patients (13.5%). The most frequent use of chloral hydrate as a treatment was to reduce agitation during mechanical ventilation, followed by treatment of neonatal diseases and treatment of neurological disorders. The reported success rate was high throughout all treatment procedures (86%–100%). The incidence of hypoxia was found to be the II highest, when it was used for the treatment of agitation 71 cases/438 patients (16.2%). Due to the heterogeneity between the studies it was not possible to perform meaningful statistical analysis. The effectiveness and safety of triclofos (a chloral hydrate derivative) was evaluated for procedural sedation in children, in a systematic review of the literature. The success rate was variable (ranging from 50 to 100%), shorter procedures such as CT scanning were more likely to be successful. Vomiting and hypoxia were the most frequently reported adverse events, 10% (62/613) and 7.8% (48/613) respectively. A systematic literature review of the safety and effectiveness of paraldehyde as a sedative agent for children was performed, as it was named as a second line agent in the sedation policy of the Derbyshire Children's Hospital. The literature is scant; only five studies were located and involved 157 patients. The reported effectiveness of paraldehyde ranged from 75- 93%. Vomiting was the most commonly reported adverse event (2 cases/8 patients, 25%). Due to the small numbers of patients and poor methodology of studies, its clinical use cannot be supported. A further systematic literature review of 29 studies involving 6342 children on the safety and effectiveness of midazolam for imaging procedures was conducted. The procedural success rate was variable (0%–100%, median 82%). Hypoxia was the most commonly reported adverse event (74 cases/2046 patients, 3.6%) with (32 cases/2046 patients) 1.6% of cases being reported as moderate hypoxia. Palatability of the two most commonly used sedative agents, chloral hydrate and midazolam, was evaluated by conducting a literature review and a prospective study at the Derbyshire Children's Hospital. Only 9 studies were identified during the literature review. Of these, 8 studies evaluated the palatability of midazolam, while only 2 evaluated the palatability of chloral hydrate. Midazolam was reported as more III acceptable to patients than chloral hydrate. The prospective study supported this, and showed that patient acceptance of midazolam was good, while it was poor for chloral hydrate. The success rate of procedures was lower with midazolam, then chloral hydrate. A further literature review evaluated the use of sedation in Middle Eastern countries. Limited numbers of reports were found. Of the 37 studies, the majority (43%) were conducted in Turkey, within single centres and only examined a single procedure. Very limited evidence on the use of sedation guidelines was reported. Further exploration of the current sedation practice in the Kingdom of Saudi Arabia was done using a national survey. The questionnaires were completed by 81 health care professionals. Only 61% documented the use of sedation guidelines, although 91% reported monitoring of patients during procedural sedation. The most commonly reported agents for both painless and painful procedures were chloral hydrate and midazolam. This research aimed to add to the evidence base for paediatric sedation. The results suggest a need for future research to cover further areas, including the safety and effectiveness of other drugs, worldwide practice and patient monitoring. IV PUBLICATIONS, PRESENTATIONS AND AWARDS RELATED TO THIS THESIS Publications and presentations related to this thesis Paper: 1. Alotaibi B, Choonara I, Sammons H. Safety of Chloral Hydrate for Dental Procedural Sedation in Children: A Systematic Review of the Literature (Paper submitted to International Journal of Paediatric Dentistry). Conference abstracts: 1. Alotaibi B, Choonara I, Sammons H. Safety and Clinical Effectiveness of Chloral Hydrate for Painless Procedural Sedation in Children. Arch Dis Child 2014, 99:1, a169. 2. Alotaibi B, Choonara I, Sammons H. Midazolam for Imaging Procedural Sedation in Children: A Systematic Review. Arch Dis Child 2015, 100:e1. 3. Alotaibi B, Choonara I, Sammons H. Safety and clinical effectiveness of triclofos for procedural sedation in children: a systematic review. Arch Dis Child 2015, 100:e1. Oral presentation: 1. Safety and Clinical Effectiveness of Chloral Hydrate for Painless Procedural Sedation in Children, Oral presentation at National Child Health Workshop, September 18th, 2013, Derby, United Kingdom and at 7th Saudi Students Conference-UK, February 1st 2014, Edinburgh, United Kingdom. V 2. Safety and Clinical Effectiveness of Chloral Hydrate for Painful Procedural Sedation in Children, Oral presentation at National Child Health Workshop, 16 September 2014, Derby, United Kingdom. Poster presentation: 1. Safety and Clinical Effectiveness of Chloral Hydrate for Painless Procedural Sedation in Children, RCPCH Annual Conference, April 8th to 10th, 2014. Birmingham, UK. 2. Midazolam for Imaging Procedural Sedation in Children: A Systematic Review, at NPPG 20th Annual Conference and Exhibition, 7-9 November 2014, Nottingham, UK and at the 15th ESDPPP Congress, Belgrade, Serbia. 3. Safety and Clinical Effectiveness of Triclofos for Procedural Sedation in Children: A Systematic Review, NPPG 20th Annual Conference and Exhibition, 7-9 November 2014, Nottingham, UK. 4. Safety and Clinical Effectiveness of Paraldehyde for Procedural Sedation in Children, the 8th Saudi Students Conference-UK, February 1st 2015, London, UK. Rewards/Awards: 1. Best scientific presentation, 7th Saudi Students Conference, Edinburgh, 01 February 2014. For Safety and Clinical Effectiveness of Chloral Hydrate for Painless Procedural Sedation in Children VI ACKNOWLEDGEMENTS Praise be to Allah and may His peace and Blessings be upon all the prophets. Thanks, first and foremost, to Allah for granting me the chance and the ability to complete this thesis. This research would not have been accomplished successfully without the support and help of the following people to whom I am extremely grateful and obliged. First, Gratefulness, admiration and appreciation all go to my supervisors: Dr. Helen Sammons and Prof. Imti Choonara. I can confidently say that without their help and support, I would have never made it this far. Not only have they been a source of inspiration, but also a tremendous academic resource as I have learnt so much from their vast experience and knowledge. They have always been there to respond to any queries I had or any issues I experienced with any aspect of my research. I must say that I owe them so much. Second, I would like to thank my parents who have provided all sorts of encouragement for me to complete my studies successfully. Their care and trust instilled so much drive and determination in me to tackle life challenges head on. I would also like to give my gratitude to my husband, children and my friend Mrs/Thavalamar for their valuable and extensive support throughout this arduous but worthwhile academic journey in the UK. No words can describe my appreciation for other family members and friends who have been a source of inspiration and guidance. I would also like to thank all researchers, men and women, in all disciplines and wish them all success in their respective professions. VII A tremendous salute should be finally given to the Medical Services Department in the Saudi Armed Forces for believing in me and for assuming the financial costs of this postgraduate course. Without excluding anyone, I thank all those involved in this research endeavour for their comments and feedback, all of which contributed to moulding this dissertation into what it presently
Recommended publications
  • Analgesia and Sedation in Hospitalized Children
    Analgesia and Sedation in Hospitalized Children By Elizabeth J. Beckman, Pharm.D., BCPS, BCCCP, BCPPS Reviewed by Julie Pingel, Pharm.D., BCPPS; and Brent A. Hall, Pharm.D., BCPPS LEARNING OBJECTIVES 1. Evaluate analgesics and sedative agents on the basis of drug mechanism of action, pharmacokinetic principles, adverse drug reactions, and administration considerations. 2. Design an evidence-based analgesic and/or sedative treatment and monitoring plan for the hospitalized child who is postoperative, acutely ill, or in need of prolonged sedation. 3. Design an analgesic and sedation treatment and monitoring plan to minimize hyperalgesia and delirium and optimize neurodevelopmental outcomes in children. INTRODUCTION ABBREVIATIONS IN THIS CHAPTER Pain, anxiety, fear, distress, and agitation are often experienced by GABA γ-Aminobutyric acid children undergoing medical treatment. Contributory factors may ICP Intracranial pressure include separation from parents, unfamiliar surroundings, sleep dis- PAD Pain, agitation, and delirium turbance, and invasive procedures. Children receive analgesia and PCA Patient-controlled analgesia sedatives to promote comfort, create a safe environment for patient PICU Pediatric ICU and caregiver, and increase patient tolerance to medical interven- PRIS Propofol-related infusion tions such as intravenous access placement or synchrony with syndrome mechanical ventilation. However, using these agents is not without Table of other common abbreviations. risk. Many of the agents used for analgesia and sedation are con- sidered high alert by the Institute for Safe Medication Practices because of their potential to cause significant patient harm, given their adverse effects and the development of tolerance, dependence, and withdrawal symptoms. Added layers of complexity include the ontogeny of the pediatric patient, ongoing disease processes, and presence of organ failure, which may alter the pharmacokinetics and pharmacodynamics of these medications.
    [Show full text]
  • Safe Injection Practices for Administration of Propofol
    Safe Injection Practices for Administration of Propofol CECIL A. KING, MS, RN; MARY OGG, MSN, RN, CNOR ABSTRACT Sepsis and postoperative infection can occur as a result of unsafe practices in the administration of propofol and other injectable medications. Investigations of infec- tion outbreaks have revealed the causes to be related to bacterial growth in or contamination of propofol and unsafe medication practices, including reuse of syringes on multiple patients, use of single-use medication vials for multiple pa- tients, and failure to practice aseptic technique and adhere to infection control practices. Surveys conducted by AORN and other researchers have provided addi- tional information on perioperative practices related to injectable medications. In 2009, the US Food and Drug Administration and the Centers for Disease Control and Prevention convened a group of clinicians to gain a better understanding of the issues related to infection outbreaks and injectable medications. The meeting participants proposed collecting data to persuade clinicians to adopt new practices, developing guiding principles for propofol use, and describing propofol-specific, site-specific, and practitioner-specific injection techniques. AORN provides resources to help perioperative nurses reduce the incidence of postoperative infection related to med- ication administration. AORN J 95 (March 2012) 365-372. © AORN, Inc, 2012. doi: 10.1016/j.aorn.2011.06.009 Key words: sterile injectable medications, propofol, sepsis, safe injection prac- tices, safe medication
    [Show full text]
  • Statement on Safe Use of Propofol 2019
    Statement on Safe Use of Propofol Committee of Origin: Ambulatory Surgical Care (Approved by the ASA House of Delegates on October 27, 2004, and amended on October 23, 2019) Because sedation is a continuum, it is not always possible to predict how an individual patient will respond. Due to the potential for rapid, profound changes in sedative/anesthetic depth and the lack of antagonist medications, agents such as propofol require special attention. Even if moderate sedation is intended, patients receiving propofol should receive care consistent with that required for deep sedation. The Society believes that the involvement of an anesthesiologist in the care of every patient undergoing anesthesia is optimal. However, when this is not possible, non-anesthesia personnel who administer propofol should be qualified to rescue* patients whose level of sedation becomes deeper than initially intended and who enter, if briefly, a state of general anesthesia.** • The physician responsible for the use of sedation/anesthesia should have the education and training to manage the potential medical complications of sedation/anesthesia. The physician should be proficient in airway management, have advanced life support skills appropriate for the patient population, and understand the pharmacology of the drugs used. The physician should be physically present throughout the sedation and remain immediately available until the patient is medically discharged from the post procedure recovery area. • The practitioner administering propofol for sedation/anesthesia should, at a minimum, have the education and training to identify and manage the airway and cardiovascular changes which occur in a patient who enters a state of general anesthesia, as well as the ability to assist in the management of complications.
    [Show full text]
  • Prediction of Premature Termination Codon Suppressing Compounds for Treatment of Duchenne Muscular Dystrophy Using Machine Learning
    Prediction of Premature Termination Codon Suppressing Compounds for Treatment of Duchenne Muscular Dystrophy using Machine Learning Kate Wang et al. Supplemental Table S1. Drugs selected by Pharmacophore-based, ML-based and DL- based search in the FDA-approved drugs database Pharmacophore WEKA TF 1-Palmitoyl-2-oleoyl-sn-glycero-3- 5-O-phosphono-alpha-D- (phospho-rac-(1-glycerol)) ribofuranosyl diphosphate Acarbose Amikacin Acetylcarnitine Acetarsol Arbutamine Acetylcholine Adenosine Aldehydo-N-Acetyl-D- Benserazide Acyclovir Glucosamine Bisoprolol Adefovir dipivoxil Alendronic acid Brivudine Alfentanil Alginic acid Cefamandole Alitretinoin alpha-Arbutin Cefdinir Azithromycin Amikacin Cefixime Balsalazide Amiloride Cefonicid Bethanechol Arbutin Ceforanide Bicalutamide Ascorbic acid calcium salt Cefotetan Calcium glubionate Auranofin Ceftibuten Cangrelor Azacitidine Ceftolozane Capecitabine Benserazide Cerivastatin Carbamoylcholine Besifloxacin Chlortetracycline Carisoprodol beta-L-fructofuranose Cilastatin Chlorobutanol Bictegravir Citicoline Cidofovir Bismuth subgallate Cladribine Clodronic acid Bleomycin Clarithromycin Colistimethate Bortezomib Clindamycin Cyclandelate Bromotheophylline Clofarabine Dexpanthenol Calcium threonate Cromoglicic acid Edoxudine Capecitabine Demeclocycline Elbasvir Capreomycin Diaminopropanol tetraacetic acid Erdosteine Carbidopa Diazolidinylurea Ethchlorvynol Carbocisteine Dibekacin Ethinamate Carboplatin Dinoprostone Famotidine Cefotetan Dipyridamole Fidaxomicin Chlormerodrin Doripenem Flavin adenine dinucleotide
    [Show full text]
  • Aminobutyric Acid Type a and Glycine Receptors Influences Their Sensitivity to Propofol
    PERIOPERATIVE MEDICINE A Single Phenylalanine Residue in the Main Intracellular Loop of ␣1 ␥-Aminobutyric Acid Type A and Glycine Receptors Influences Their Sensitivity to Propofol Gustavo Moraga-Cid, Ph.D.,* Gonzalo E. Yevenes, Ph.D.,* Gu¨ nther Schmalzing, M.D.,† Robert W. Peoples, Ph.D.,‡ Luis G. Aguayo, Ph.D.§ Downloaded from http://pubs.asahq.org/anesthesiology/article-pdf/115/3/464/254366/0000542-201109000-00010.pdf by guest on 02 October 2021 ABSTRACT What We Already Know about This Topic • Propofol positively modulates receptors for the inhibitory Background: The intravenous anesthetic propofol acts as a transmitters ␥-aminobutyric acid type A (GABA) and glycine, positive allosteric modulator of glycine (GlyRs) and ␥-ami- but the molecular mechanisms involved are unclear nobutyric acid type A (GABAARs) receptors. Although the role of transmembrane residues is recognized, little is known about the involvement of other regions in the modulatory What This Article Tells Us That Is New effects of propofol. Therefore, the influence of the large in- • A single homologous residue in the large M3-M4 intracellular tracellular loop in propofol sensitivity of both receptors was ␣ loops of the 1 subunits of GABAA and glycine receptors mod- explored. ulates the action of propofol but not of other general anesthetics ␣ ␣ ␤ Methods: The large intracellular loop of 1 GlyRs and 1 2 GABAARs was screened using alanine replacement. Sensitiv- ity to propofol was studied using patch-clamp recording in 80 Ϯ 23%). Remarkably, propofol-hyposensitive mutant re- HEK293 cells transiently transfected with wild type or mu- ceptors retained their sensitivity to other allosteric modula- tant receptors.
    [Show full text]
  • Differential Actions of Ethanol and Trichloroethanol at Sites in the M3 and M4 Domains of the NMDA Receptor Glun2a (NR2A) Subunit AK Salous Marquette University
    Marquette University e-Publications@Marquette Biomedical Sciences Faculty Research and Biomedical Sciences, Department of Publications 11-1-2009 Differential Actions of Ethanol and Trichloroethanol at Sites in the M3 and M4 Domains of the NMDA Receptor GluN2A (NR2A) Subunit AK Salous Marquette University H Ren Marquette University KA Lamb Marquette University Xiang-Qun Hu Marquette University, [email protected] RH Lipsky George Mason University See next page for additional authors Accepted version. British Journal of Pharmacology, Vol. 158, No. 5 (November 2009): 1395–1404. DOI. © 2009 Wiley. Used with permission. This is the peer reviewed version of the following article: "Differential Actions of Ethanol and Trichloroethanol at Sites in the M3 and M4 Domains of the NMDA Receptor GluN2A (NR2A) Subunit," which has been published in final form here: DOI. This article may be used for non- commercial purposes in accordance With Wiley Terms and Conditions for self-archiving. Authors AK Salous, H Ren, KA Lamb, Xiang-Qun Hu, RH Lipsky, and Robert W. Peoples This article is available at e-Publications@Marquette: https://epublications.marquette.edu/biomedsci_fac/95 NOT THE PUBLISHED VERSION; this is the author’s final, peer-reviewed manuscript. The published version may be accessed by following the link in the citation at the bottom of the page. Differential Actions of Ethanol and Trichloroethanol at Sites in the M3 and M4 Domains of the NMDA Receptor GluN2A (NR2A) Subunit AK Salous Department of Biomedical Sciences, Marquette University Milwaukee, WI H. Ren Department of Biomedical Sciences, Marquette University Milwaukee, WI KA Lamb Department of Biomedical Sciences, Marquette University Milwaukee, WI X-Q Hu Department of Biomedical Sciences, Marquette University Milwaukee, WI RH Lipsky Department of Neuroscience, INOVA Fairfax Hospital Falls Church, VA Krasnow Institute for Advanced Study, George Mason University Fairfax, VA RW Peoples Department of Biomedical Sciences, Marquette University Milwaukee, WI British Journal of Pharmacology, Vol.
    [Show full text]
  • Clinical Trial of the Neuroprotectant Clomethiazole in Coronary Artery Bypass Graft Surgery a Randomized Controlled Trial Robert S
    Anesthesiology 2002; 97:585–91 © 2002 American Society of Anesthesiologists, Inc. Lippincott Williams & Wilkins, Inc. Clinical Trial of the Neuroprotectant Clomethiazole in Coronary Artery Bypass Graft Surgery A Randomized Controlled Trial Robert S. Kong, F.R.C.A.,* John Butterworth, M.D.,† Wynne Aveling, F.R.C.A.,‡ David A. Stump, M.D.,† Michael J. G. Harrison, F.R.C.P.,§ John Hammon, M.D.,ʈ Jan Stygall, M.Sc.,# Kashemi D. Rorie, Ph.D.,** Stanton P. Newman, D.Phil.†† Background: The neuroprotective property of clomethiazole THE efficacy of coronary artery bypass surgery in the has been demonstrated in several animal models of global and relief of angina and in some circumstances in enhancing Downloaded from http://pubs.asahq.org/anesthesiology/article-pdf/97/3/585/335909/0000542-200209000-00011.pdf by guest on 29 September 2021 focal brain ischemia. In this study the authors investigated the life expectation is now accepted. It is a tribute to the low effect of clomethiazole on cerebral outcome in patients under- mortality of the procedure that interest is now focused going coronary artery bypass surgery. Methods: Two hundred forty-five patients scheduled for on the neurologic and neuropsychological complica- 1–3 coronary artery bypass surgery were recruited at two centers tions. Adverse neurologic outcomes have been found and prospectively randomized to clomethiazole edisilate to occur in 2–6% of patients and neuropsychological (0.8%), 225 ml (1.8 mg) loading dose followed by a maintenance deficits in 10–30%.4–6 These complications are consid- dose of 100 ml/h (0.8 mg/h) during surgery, or 0.9% NaCl ered to be ischemic in nature, being a consequence of (placebo) in a double-blind trial.
    [Show full text]
  • Halogenated Ether, Alcohol, and Alkane Anesthetics Activate TASK-3 Tandem Pore Potassium Channels Likely Through a Common Mechanism S
    Supplemental material to this article can be found at: http://molpharm.aspetjournals.org/content/suppl/2017/03/21/mol.117.108290.DC1 1521-0111/91/6/620–629$25.00 https://doi.org/10.1124/mol.117.108290 MOLECULAR PHARMACOLOGY Mol Pharmacol 91:620–629, June 2017 Copyright ª 2017 by The American Society for Pharmacology and Experimental Therapeutics Halogenated Ether, Alcohol, and Alkane Anesthetics Activate TASK-3 Tandem Pore Potassium Channels Likely through a Common Mechanism s Anita Luethy, James D. Boghosian, Rithu Srikantha, and Joseph F. Cotten Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital, Boston, Massachusetts (A.L., J.D.B., and J.F.C.); Department of Anesthesia, Kantonsspital Aarau, Aarau, Switzerland (A.L.); Carver College of Medicine, University of Iowa, Iowa City, Iowa (R.S.) Received January 7, 2017; accepted March 20, 2017 Downloaded from ABSTRACT The TWIK-related acid-sensitive potassium channel 3 (TASK-3; hydrate (165% [161–176]) . 2,2-dichloro- . 2-chloro 2,2,2- KCNK9) tandem pore potassium channel function is activated by trifluoroethanol . ethanol. Similarly, carbon tetrabromide (296% halogenated anesthetics through binding at a putative anesthetic- [245–346]), carbon tetrachloride (180% [163–196]), and 1,1,1,3,3,3- binding cavity. To understand the pharmacologic requirements for hexafluoropropanol (200% [194–206]) activate TASK-3, whereas molpharm.aspetjournals.org TASK-3 activation, we studied the concentration–response of the larger carbon tetraiodide and a-chloralose inhibit. Clinical TASK-3 to several anesthetics (isoflurane, desflurane, sevoflurane, agents activate TASK-3 with the following rank order efficacy: halothane, a-chloralose, 2,2,2-trichloroethanol [TCE], and chloral halothane (207% [202–212]) .
    [Show full text]
  • Pharmacokinetics of Propofol Administered by Target- Controlled Infusion to Alcoholic Patients Frédérique S
    Anesthesiology 2003; 99:576–85 © 2003 American Society of Anesthesiologists, Inc. Lippincott Williams & Wilkins, Inc. Pharmacokinetics of Propofol Administered by Target- controlled Infusion to Alcoholic Patients Frédérique S. Servin, M.D.,* Bernard Bougeois, M.D.,* Roberto Gomeni, Ph.D.,† France Mentré, M.D., Ph.D.,‡ Robert Farinotti, Ph.D.,§ Jean-Marie Desmonts, M.D.ʈ Background: Chronic alcoholic patients are frequently pre- require larger doses of “anesthetic agents,” even in the sented for anesthesia and surgery. These patients require absence of withdrawal symptoms. Although it is com- higher doses of propofol than control patients for induction of monly recommended that the dose of thiopental should anesthesia, but whether this is because of changes in pharma- cokinetics or pharmacodynamics is not known. This study was be increased in alcoholic patients, no pharmacokinetic designed to investigate the influence of chronic ethanol intake or pharmacodynamic changes could be demonstrated in Downloaded from http://pubs.asahq.org/anesthesiology/article-pdf/99/3/576/337574/0000542-200309000-00012.pdf by guest on 26 September 2021 on propofol pharmacokinetics. chronic alcoholic patients.2 Moreover, unnecessarily Methods: Fifteen chronic alcoholic and 15 control patients, high doses may be deleterious in this population in receiving propofol by target-controlled infusion for otolaryn- whom alcohol-related cardiac disease is frequent.3 In gologic surgery, were studied. Blood propofol concentrations 4 were measured at regular intervals during and after the propo- addition to sporadic case reports, a prospective study fol infusion. Nonlinear mixed-effects population models (NON- has shown that the induction dose of propofol was MEM) examining the influence of alcoholism were constructed.
    [Show full text]
  • A New Pharmacokinetic Model of Propofol for Japanese Patients
    Open Journal of Anesthesiology, 2019, 9, 179-188 https://www.scirp.org/journal/ojanes ISSN Online: 2164-5558 ISSN Print: 2164-5531 A New Pharmacokinetic Model of Propofol for Japanese Patients Masahito Omote, Shunsuke Tachibana, Yasuyuki Tokinaga* , Michiaki Yamakage Department of Anesthesiology, Sapporo Medical University School of Medicine, Sapporo, Japan How to cite this paper: Omote, M., Ta- Abstract chibana, S., Tokinaga, Y. and Yamakage, M. (2019) A New Pharmacokinetic Model Target-controlled infusion (TCI) of propofol is used for general anesthesia. of Propofol for Japanese Patients. Open However, the only pharmacokinetic parameter commercially used for Japa- Journal of Anesthesiology, 9, 179-188. nese patients is weight, and pharmacokinetic models are based on European https://doi.org/10.4236/ojanes.2019.99017 physical attributes. Drug metabolism also differs in races. This study aimed to Received: August 25, 2019 identify optimal continuous doses of propofol for Japanese patients and to Accepted: September 16, 2019 create a simulated pharmacokinetic (PK) model. Thirty Japanese patients Published: September 19, 2019 were enrolled. Patients received a constant infusion of 9 mg/kg/h of propo- Copyright © 2019 by author(s) and fol. Arterial blood samples were collected and the time course of plasma Scientific Research Publishing Inc. propofol concentrations was modeled using the nonlinear mixed effects This work is licensed under the Creative model (NONMEM) three-compartmental PK model. We validated the model Commons Attribution International License (CC BY 4.0). by intravenously injecting 10 patients with a TCI driver system programmed http://creativecommons.org/licenses/by/4.0/ with the NONMEM model. Our model’s performance was evaluated using Open Access the median prediction error (MDPE), median absolute prediction error (MDAPE), and Wobble.
    [Show full text]
  • Potentiating Action of Propofol at GABAA Receptors of Retinal Bipolar Cells
    Visual Neurophysiology Potentiating Action of Propofol at GABAA Receptors of Retinal Bipolar Cells Lan Yue,1,2 An Xie,1 Karol S. Bruzik,3 Bente Frølund,4 Haohua Qian,1,5 and David R. Pepperberg1,2 PURPOSE. Propofol (2,6-diisopropyl phenol), a widely used sys- etinal bipolar cells have GABAA and GABAC receptors, which ␥ temic anesthetic, is known to potentiate GABAA receptor ac- Rare pentameric, ligand-gated ion channels activated by -ami- tivity in a number of CNS neurons and to produce changes in nobutyric acid (GABA). GABAA and GABAC receptors mediate fast electroretinographically recorded responses of the retina. inhibitory signaling in bipolar cells of the retina1–3 (see Ref. 4 for However, little is known about propofol’s effects on specific review). Electrophysiological and immunocytochemical data indi- retinal neurons. The authors investigated the action of propo- cate that GABAA and GABAC receptors on bipolar cells are local- fol on GABA-elicited membrane current responses of retinal ized primarily at the axon terminals, postsynaptic to amacrine 5–7 ␣ ␣ bipolar cells, which have both GABA and GABA receptors. cells. Furthermore, expression of GABAA receptor 1, 3, A C ␤ ␥ ␳ ␳ 2/3, and 2 subunits and GABAC receptor 1 and 2 subunits in METHODS. Single, enzymatically dissociated bipolar cells ob- rod bipolar cells has been reported.8–11 However, the specific tained from rat retina were treated with propofol delivered by subunit compositions of these receptors of bipolar cells are as yet brief application in combination with GABA or other pharma- unknown. cologic agents or as a component of the superfusing medium.
    [Show full text]
  • Uniform Classification Guidelines for Foreign Substances and Recommended Penalties Model Rule
    DRUG TESTING STANDARDS AND PRACTICES PROGRAM. Uniform Classification Guidelines for Foreign Substances And Recommended Penalties Model Rule. January, 2018 (V.13.4) Ó ASSOCIATION OF RACING COMMISSIONERS INTERNATIONAL – 2018. Association of Racing Commissioners International 1510 Newtown Pike, Lexington, Kentucky, United States www.arci.com Page 1 of 61 Preamble to the Uniform Classification Guidelines of Foreign Substances The Preamble to the Uniform Classification Guidelines was approved by the RCI Drug Testing and Quality Assurance Program Committee (now the Drug Testing Standards and Practices Program Committee) on August 26, 1991. Minor revisions to the Preamble were made by the Drug Classification subcommittee (now the Veterinary Pharmacologists Subcommittee) on September 3, 1991. "The Uniform Classification Guidelines printed on the following pages are intended to assist stewards, hearing officers and racing commissioners in evaluating the seriousness of alleged violations of medication and prohibited substance rules in racing jurisdictions. Practicing equine veterinarians, state veterinarians, and equine pharmacologists are available and should be consulted to explain the pharmacological effects of the drugs listed in each class prior to any decisions with respect to penalities to be imposed. The ranking of drugs is based on their pharmacology, their ability to influence the outcome of a race, whether or not they have legitimate therapeutic uses in the racing horse, or other evidence that they may be used improperly. These classes of drugs are intended only as guidelines and should be employed only to assist persons adjudicating facts and opinions in understanding the seriousness of the alleged offenses. The facts of each case are always different and there may be mitigating circumstances which should always be considered.
    [Show full text]