Learning Objectives

„ Rationale and Logics ICU Sedation „ Sedation/Analgesia Algorithm Towards Humanitarian Treatment „ Sedative/Analgesic Agents Tzong-Luen Wang „ Evaluation and Monitoring MD, PhD, JM, FESC, FACC, FCAPSC Chief, ED, Shin-Kong Wu Ho-Su Memorial Hospital Prof., Medical School, Fu-Jen Catholic University 990201

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• Sedation comes from the Latin word sedare. • Sedare = to calm down or to alleviate fear Rationale and Logics

„ Principles of Ethics „ Harm Free „ Beneficiary Hypnosis Analgesia „ Effective

„ Humanity

„ Comfortable „ Self Determination ± Muscle „ Confidentiality Relaxation

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Rationale and Logics Rationale and Logics

„ Causes of and risk factors for „ Causes of and risk factors for „ Fear, anxiety, agitation, ICU psychosis agitation and delirium agitation and delirium „ Age >70 „ BUN/creatinine ratio > 18 „ Unpleasant recall and memory „ Transfer from a nursing home „ Renal failure, creatinine > 2.0 „ History of depression „ Liver disease „ History of dementia, stroke, or „ Congestive heart failure epilepsy, Alcohol abuse within past „ Self-extubation and medical device month „ Cardiogenic or septic shock „ Tobacco use removal „ Drug overdose or ilicit drugs „ Myocardial infarction „ HIV infection „ Infection „ Medications „ Physical injury „ CNS pathology „ Hypo- or hypernatremia „ Urinary retention or fecal impaction „ Hypo- or hyperglycemia „ Tube feeding „ Desynchronize with mechanical „ Hypo- or hyperthyroidism „ Rectal of bladder catheters „ Hypothermia or fever „ Physical restraints „ Hypoxia ventilation „ Central line catheters „ Acidosis or alkalosis „ Malnutrition of vitamin deficiencies „ Pain „ Procedural complications „ Additional cost: e.g. DRG „ Fear and anxiety „ Visual of hearing impairment „ Sleep disruption

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1 Rationale and Logics Rationale and Logics

„ Pain in ICU „ Pain in ICU „ Inadequate Sedation „ Postoperative would and „ Endotracheal tubes, incisional discomfort suctioning „ All ICU patients suffer from severe sleep „ Trauma, including soft „ Repositioning deprivation. tissue injury, burns, bone „ Physical therapy fractures, and so on „ Drug infusion „ REM sleep is only 6% (vs. Normal 25 %). „ Acute myocardial ischemia, „ Monitoring devices infarction and myocarditis „ Disturbed circadian rhythm „ ……… „ Visceral organ pain and „ Stress J neuroendocrine response acute abdomen „ Subarachnoid hemorrhage (K ACTH, GH, Aldosterone, Adrenaline, .....) „ Pneumonia and pleurodynia „ Release of cytokines J inflammatory „ Peripheral neuropathies response.

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Rationale and Logics Rationale and Logics

„ Significance of Pain Management „ Improve patient comfort. „ Reduce physical stress. „ Normalize metabolic and endocrine responses. „ Reduces postoperative complications. „ Facilitate interventions. „ Allow effective ventilation. „ Encourage sleep. „ Prevent post-ICU psychosis. „ Prevent development of chronic pain.

Critical Care 2008;12(suppl 3):S6 9 10

Rationale and Logics Rationale and Logics

„ Individual Consideration „ Correct underlying conditions. „ Consider underlying metabolic and endocrine capacities „ Consider adverse effects of sedatives and anagelsics

ATICE: Critical Care 2008;12(suppl 3):S6 11 12

2 Rationale and Logics Rationale and Logics

ATICE: Critical Care 2008;12(suppl 3):S6 Critical Care 2008;12(suppl 3):S6 13 14

Rationale Rationale and Logics and Logics

Phamacotherapy Semin Resp Crit Care Med 2000;20(6):662-672. 2001;22(2):211-225.

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Rationale and Logics

Crit Care Med 2002;30(1):119-141. Swiss Med Wkly 2004;134:333-346. 17 18

3 Non-pharmacological interventions Sedative/Analgesic Agents

„ Good nursing. „ Easy to titrate „ Psychological: „ Rapid onset of action - Explanation. - Reassurance. „ Short-acting „ No adverse effects „ Physical: „ No active or toxic metabolites - Touching & message. - Environment „ No drug interaction - Prevent constipation „ Lack of accumulation with prolonged use - Physiotherapy. „ Cost effective - Tracheostomy.

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Sedative/Analgesic Agents Sedative/Analgesic Agents

„ IV Anaesthetics: - Propofol - Thiopentone. - Ketamine - Etomidate.

„ Benzodiazepines: -Midazolam. - Lorazepam

Critical Care 2008;12(suppl 3):S4 21 22 European Society of Intensive Care Medicine http://www.esicm.org

Sedative/Analgesic Agents Propofol (1)

„ Propofol „ Properties: 1. Rapid onset, short acting, less cumulative „ Benzodiazepine 2. less analgesia 1. Diazepam 3. Anti-convulsant effect 4. Lipid-soluable 2. Midazolam 5. Reduced IICP : 3. Lorazepam Decrease cerebral metabolic oxygen requirement 18-36%

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4 Propofol (2) Propofol (3) „ Dosing and Administration „ Propofol Infusion Syndrome Š Rare, but often fatal 1. Loading dose: 0.5mg/kg Š Originally described in kids 2. Maintain dose: 5-50 mcg/kg/min Š Adults: neurological or inflammatory dz, severe infection, receiving catecholamine and/or steroids 3. Less affected by renal or liver failure Š Propofol impairs free fatty acid utilization and „ Disadvantages mitochondrial activity Š Imbalance in energy demand and supply 1. Hypotension Š Clinical 2. Potent respiratory depressant: apnea with bolus Š Heart failure 3. Lipid (soybean emulsion): Hypertriglyceridemia; Š Rhabdomyolysis Pancreatitis; Pain on injection; Bacteremia Š Renal Failure 4. Expensive Š Metabolic acidosis

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Midazolam Midazolam „ Properties „ Dosing of Midazolam 1. Rapid onset, short-acting 1. Loading dose:0.1-0.5mg/kg 2. water-soluable benzodiazepine 2. Maintain dose:0.01-0.2mg/kg/hour 3. Hypnosis, amnesia and anxiolysis 3. Metabolized via cytochrome P450 system of liver „ Drug Interaction of Midazolam 4. Elimination half-life from 1-4 hours to 4-12 hours in 1. Inhibit midazolam metabolism: liver function impairment Erythromycin, clarithromycin Itraconazole, „ Disadvantage of Midazolam fluconazole, ketoconazole, cimetidine, diltiazem, propofol 1. Hypotension 2. Respiratory depression 2. Promote midazolam metabolism: Phenytoin, carbamazepine rifampicin 3. Quick offset results in paradoxical agitation 4. Drug interaction

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Lorazepam Lorazepam

„ Properties „ Dosing of Lorazepam 1. Loading dose:1-2 mg bolus 1. Lower lipid-solubility than midazolam 2. Maintain dose:0.5-10 mg/hour 2. hypnosis, amnesia and anxiolysis 3. 10 mcg/kg/min propofol=1 mg/hr lorazepam 3. Less hypotension „ Disadvantage of Lorazepam 4. Lower cost 1. Longer time to peak effect 2. Long half-life 3. Diarrhea, ATN, Lactic acidosis

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5 Diazepam Comparison

„ Highly lipid-soluble benzodiazepine 常用例示 „ Prolong time to recovery of consciousness „ Less use in ICU

1. Pain and thrombophlebitis 2. Long half-life (20-40 hours) 3. Excessive sedation

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Swiss Med Wkly 2004;134:333-346. 33 34 Swiss Med Wkly 2004;134:333-346.

ASA Physical Status Classification Complications of Oversedation

„ Increased time on mechanical ventilation „ Increased length of stay in ICU and/or hospital „ Additional cost of care „ Increased risk of complications „ Need for additional diagnostic testing

題外話 35 36

6 Others 題外話 Tools to Monitor Sedation

„ APACHE II „ Malinas score „ „ Apgar score „ MEWS Ramsay sedation scale (RSS) „ Barnes Akathisia Scale „ Paediatric Glasgow Coma Scale „ Sedation-Agitation scale (SAS) „ Blantyre Coma Scale „ Pain scale „ Dolorimeter pain index „ PIM2 Children scoring system „ Motor activity assessment scale (MAAS) „ Glasgow Coma Scale „ Psoriasis Area Severity Index „ Goldman index „ Rancho Los Amigos Scale „ Richmond agitation-sedation scale (RASS) „ Hamilton-Norwood scale „ Revised Trauma Score „ Hoehn and Yahr scale „ SAPS II „ Adaptation to intensive care environment „ Holmes and Rahe stress scale „ SAPS III (ATICE) „ International Red Cross Wound „ SOFA score Classification System „ Tanner stage „ Minnesota sedation assessment tool (MSAT) „ Life-Events and Difficulties „ Tygerberg score Schedule „ „ Ludwig scale BIS monitor „ AEP monitor

What do they mean? 37 38

Ramsay Sedation Scale Sedation-Agitation Scale

„ 1: Anxious, agitate, or restless „ 1: Unarousable „ 2: Cooperative, oriented and tranquil „ 2: Very sedated „ 3: Responding to commands „ 3: Sedated „ 4: Brisk response to stimulus „ 4: Calm and cooperative „ 5: Sluggish response to stimulus „ 5: Agitated „ 6: No response to stimulus „ 6: Very agitated „ 7: Dangerous agitation

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Motor Activity Assessment Scale Richmond (MAAS) Agitation- „ 0. Unresponsive: Does not move with noxious stimulus „ 1. Responsive only to noxious stimuli: Opens eyes OR raises eyebrows OR turns head toward stimulus OR moves limbs with noxious stimulus Sedation „ 2. Responsive to touch or name: Opens eyes OR raises eyebrows OR turns head toward stimulus OR moves limbs when touched or name is loudly Scale spoken „ 3. Calm and cooperative: No external stimulus is required to elicit movement AND patient is adjusting sheets or clothes purposefully and follows commands „ 4. Restless and cooperative: No external stimulus is required to elicit movement AND patient is picking at sheets or tubes or uncovering self and follows commands „ 5. Agitated: No external stimulus is required to elicit movement AND attempting to sit up OR moves limbs out of bed AND does not consistently follow commands (e.g. will lie down when asked but soon reverts back to attempts to sit up or move limbs out of bed „ 6. Dangerously agitated, uncooperative: No external stimulus is required to elicit movement AND patient is pulling at tubes or catheters OR thrashing side to side OR striking at staff OR trying to climb out of bed AND does not calm down when asked

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7 BIS Monitor (bispectral index ) Tools to Monitor Pain

„ Based on EEG „ General „ Information between cortical and sub- „ Behavior Pain Scale cortical region „ Critical Care Pain Observational Tool „ BIS measures electrical activity in the „ Face, Legs, Activity, Cry, Consolability brain, it provides a direct correlation Observational Tool (FLACC) Scale with depth of consciousness (hypnosis) Score between 0 and 100

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General Pain Scales General Pain Scales

„ Wong-Baker FACES Pain Rating Scale „ Face Legs Arms Cry Consolability scale „ Visual analog scale (VAS) „ McGill Pain Questionnaire (MPQ) 題外話 „ Descriptor differential scale (DDS) „ Faces Pain Scale - Revised (FPS-R) „ Numerical 11 point box (BS-11) „ Numeric Rating Scale (NRS-11) „ Dolorimeter Pain Index (DPI) „ Brief Pain Inventory (BPI) „ Walid-Robinson Pain Index (WRI) = Intensity upon admission (0–10) × Length (in months). „ DSPI=(ΣX*Y)*100 where X is the highest pain level and Y is the percentage of this pain level in the group. The DSPI is different from the simple numeric 0–10 scale in that it is measured for a group of patients with a specific diagnosis whereas the numeric 0–10 pain scale is administered individually.

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Specialized Pain Scales Behavior Pain Scale

„ Pediatric Pain Questionnaire (PPQ) for measuring pain in children „ Premature Infant Pain Profile (PIPP) for measuring pain in premature infants „ Schmidt Sting Pain Index and Starr sting pain scale both for insect stings „ Colorado Behavioral Numerical Pain Scale (for sedated patients) 題外話

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8 Critical Care Pain Observational Tool FALCC Tool

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FALCC Tool

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