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1 1,2 1,3 1,4,5 analgesic agentsedative agent Anti-psychotic Agent neuromuscular blockade, NMB 2008 Surviving Sepsis Campaign 1 Grade 1B 2 Grade 1B 3 train-of-four measurement TOF Grade 1B analgesic agent sedative agent Anti-psychotic Agent neuromuscular blockade, NMB 2008 Surviving Sepsis Campaign 1 Grade 1B r @ms11.hinet.net

2 2 Grade 1B 3 Train of Four Grade 1B 1 severe sepsis acute lung injury acute respiratory distress syndrome, ARDS 18%~46% ARDS 2-4 catecholamine cortisol glucagon Analgesic Agent visual analogue scale VAS 37

3 Adjective Rating Scale (ARS) No Mild Moderate Severe Very Severe Worst Possible Numerical Rating Scale (NRS) Visual Analog Scale (VAS) No Worst Possible 1 11, Benzodiazepine NSAID non-steroidal anti-inflammatory drug, NSAID Meperidine Demerol, Pethidine Meperidine normeperidine normeperidine myoclonus morphine fentanyl hydromorphone Morphine fentanyl 2 4 morphine-6-glucuronide 38

4 10, 45 Morphine Hydromorphone Fentanyl 2 5mg mg g mg/hr mg/hr g/hr PCA Bolus mg mg g Lockout interval Potency 1x 5 10x x 1x 0.2x 600x 0 50% 14 Morphine euphoria Oddi 15 Morphine morphine morphine Hydromorphone morphine morphine 5-10 morphine hydromorphone 16 Fentanyl morphine morphine fentanyl fentanyl morphine fentanyl 3 morphine hydromorphone intermittent fentanyl continuous infusion Fentanyl hydromorphone acetaminophen 39

5 17 18 p.r.n p.r.n patient-controlled analgesia, PCA PCA epidural epidural 19 Sedative Agent 1 85% anxiety agitation delirium 20 21,22 23,24 Ramsay scale Sedation-Agitation Scale SAS Motor Activity Assessment Scale MAAS Ramsay scale Ramsay scale Ramsay scale benzodiazepine propofol Benzodiazepine diazepam valium GABA midazolam Dormicum lorazepam Ativan propofol Dexmedetomidine diazepam Midazolam midazolam benzodiazepine 26 Midazolam hydroxymidazolam cytochrome P450 midazolam Midazolam Lorazepam midazolam 40

6 Ramsay 10, benzodiazepine 10, 45 Midazolam Lorazepam Diazepam mg/kg mg/kg mg/kg mg/kg/hr mg/kg/hr Potency 3x 6x 1x 1.5x 0.5x 1x 0 50% 10, 45 Propofol Dexmedetomidine mg/kg 1 g/kg in 10min < g/kg/min g/kg/min Sympathetic rebound Propofol infusion syndrome 41

7 Lorazepam lorazepam lorazepam propylene glycol lorazepam propylene glycol 27 propylene glycol midazolam propofol Diazepam lorazepam propylene glycol diazepam 28 Propofol GABA Propofol 29 propofol status epilepticus delirium tremens Propofol mg/kg mg/ kg/hr Propofol propofol propofol 1.1 kcal/ml propofol infusion syndrome 30 propofol > 4 6mg/kg/hr > 80% propofol 29 Dexmedetomidine 2 clonidine Dexmedetomidine sympathetic rebound 3 midazolam propofol Lorazepam propofol lorazepam 42

8 26 benzodiazepine propofol 2 agonist Dexmedetomidine 2008 Surviving Sepsis Campaign Grade 1B 1 Grade 1B 23,31 Anti-psychotic Agent 1 87% 20 ICU psychosis haloperidol benzodiazepine benzodiazepine haloperidol 32 2 Haloperidol dopamine Haloperidol QT Torsades de pointes amiodarone 33 neuroleptic malignant syndrome 34 haloperidol mg Neuromuscular Blockade, NMB 1 ARDS 43

9 compliance Succinylcholine Pacuronium Vecuronium Atracurium Pancuronium aminosteroid Pancuronium vagal blockade 36 Vecuronium aminosteroid Vecuronium vecuronium 50-80% Atracurium benzylquinolinium Hoffman degradation 30 Atracurium 3 prolonged weakness postparalytic syndrome 120 CPK pancuronium vecuronium 10, 45 Pancuronium Vecuronium Atracurium 0.1mg/kg 0.1mg/kg mg/kg 1 2 g/kg/min 1 2 g/kg/min 4 12 g/kg/min

10 atracurium 38 critical illness myopathy polyneuropathy 39 pancuronium Atracurium adductor pollicis muscle train-of-four measurement TOF 40,41 TOF TOF Radius TOF Strange vecuronium vs. atracurium 40, Surviving Sepsis Campaign TOF Grade 1B 1 42 Kress daily interruption protocol 23, Surviving Sepsis Campaign Grade 1B daily interruption Grade 1B TOF Grade 1B

11 杜漢祥等 Taiwan Crit. Care Med.2009;10:36-49 圖 2 奇美醫院之止痛 鎮靜 譫妄臨床指引 46

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13 31. Marx WH, DeMaintenon NL, Mooney KF, et al. Cost reduction and outcome improvement in the intensive care unit. J Trauma 1999;46: ; discussion Kosten TR, O'Connor PG. Management of drug and alcohol withdrawal. N Engl J Med 2003;348: Sharma ND, Rosman HS, Padhi ID, et al. Torsades de Pointes associated with intravenous haloperidol in critically ill patients. Am J Cardiol 1998;81: Sing RF, Branas CC, Marino PL. Neuroleptic malignant syndrome in the intensive care unit. J Am Osteopath Assoc 1993;93: Riker RR, Fraser GL, Cox PM. Continuous infusion of haloperidol controls agitation in critically ill patients. Crit Care Med 1994;22: Murray MJ, Cowen J, DeBlock H, et al. Clinical practice guidelines for sustained neuromuscular blockade in the adult critically ill patient. Crit Care Med 2002;30: Freebairn RC, Derrick J, Gomersall CD, et al. Oxygen delivery, oxygen consumption, and gastric intramucosal ph are not improved by a computer-controlled, closedloop, vecuronium infusion in severe sepsis and septic shock. Crit Care Med 1997;25: Segredo V, Caldwell JE, Matthay MA, et al. Persistent paralysis in critically ill patients after long-term administration of vecuronium. N Engl J Med 1992;327: Bolton CF. Neuromuscular manifestations of critical illness. Muscle Nerve 2005;32: Rudis MI, Sikora CA, Angus E, et al. A prospective, randomized, controlled evaluation of peripheral nerve stimulation versus standard clinical dosing of neuromuscular blocking agents in critically ill patients. Crit Care Med 1997;25: Strange C, Vaughan L, Franklin C, et al. Comparison of train-of-four and best clinical assessment during continuous paralysis. Am J Respir Crit Care Med 1997; 156: Kollef MH, Levy NT, Ahrens TS, et al. The use of continuous i.v. sedation is associated with prolongation of mechanical ventilation. Chest 1998;114: Kress JP, Pohlman AS, O'Connor MF, et al. Daily interruption of sedative infusions in critically ill patients undergoing mechanical ventilation. N Engl J Med 2000; 342: Kress JP, Vinayak AG, Levitt J, et al. Daily sedative interruption in mechanically ventilated patients at risk for coronary artery disease. Crit Care Med 2007;35: Marino PL, Sutin KM. The ICU book 3rd ed. Philadelphia: Lippincott Williams & Wilkins;

14 THE APPLICATION OF ANALGESIA, SEDATION, ANTI-PSY- CHOTIC AGENT AND NEUROMUSCULAR BLOCKADE IN SE- VERE-SEPSIS PATIENTS Doh Han Siang 1,2, Chin-Ming Chen 1,3, Kuo-Chen Cheng 1,4,5 Abstract It is very important to appropriately use analgesia, sedation, anti-psychotic agent and neuromuscular blockade in the care of critically ill patients. According to revised Surviving Sepsis Campaign in 2008, the effective application of sedation, analgesia, and neuromuscular blockade takes an important role in the care of severe-sepsis patients, especially those with ventilator use. Thus, we will introduce the principles and guidelines of analgesia, sedation, anti-psychotic agent and neuromuscular blockade in severesepsis patients, including: (1) use sedation protocols with a sedation goal for critically ill mechanically ventilated patients (Grade 1B); (2) use either intermittent bolus sedation or continuous infusion sedation to predetermined end points (sedation scales), with daily interruption/lightening to produce awakening; re-titrate if necessary (Grade 1B); avoid neuromuscular blockade where possible; monitor depth of block with train of four when using continuous infusions (Grade 1B). We wish to improve the high mortality rate and expenditure in severe-sepsis patients under these guidelines. Key words: Analgesia, Sedation, Anti-psychotic agent, Neuromuscular blockade and severe sepsis Correspondence: Dr. Chin-Ming Chen Department of Intensive Care Medicine, Chi-Mei Medical Center, 901 Chung Hwa Road, Yang Kang City, Tainan, Taiwan, Phone: ext 57360; Fax: ; r @ms11.hinet.net Section of Infection, 2 Section of Respiratory Care, 4 Department of Internal Medicine, Chi Mei Medical Center, Tainan Department of Medicine, 3 Department of Respiratory Therapy, 5 Taipei Medical University, Taipei, Taiwan 49