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  • 1.3 Roy N Skousen, DO Hillcrest Medical Center, Staff Anesthesiologist Director Neuro-Surgical and Obstetrical Anesthesia Services Associate Professor Clinical Anesthesia Oklahoma State University College of Osteopathic Medicine Tulsa, Oklahoma

2. 4 Disclosure The Academy for Continued Healthcare Learning (ACHL) requires that the faculty participating in a CME/CE activity disclose any relevant affiliation or other financial relationship (1) with the manufacturers of any commercial product(s) and/or provider(s) of commercial services discussed in an educational presentation, and (2) with any commercial supporters of the activity. Conflict resolution must occur prior to the CME/CE activity. The ACHL also requires participating faculty to disclose when unapproved/unlabeled uses of a product are discussed in a CME/CE activity. The faculty member has provided the following disclosure information. Dr Roy N Skousen, has disclosed the following commercial/financial relationships: Member of Speakers Bureau for Baxter Pharmaceuticals. The faculty discloses that they will discuss the unapproved/off label use of sedatives and analgesics. The Academy for Continued Healthcare Learning staff members and others involved with the planning, development, and review of the content for this activity have no relevant affiliations or financial relationships to disclose. 3. 5 The content for this activity was developed independently of the commercial supporter. All materials are included with permission. The opinions expressed are those of the faculty and are not to be construed as those of the publisher or grantor. This educational activity was planned and produced in accordance with the ACCME Essential Areas and Elements, Policies, and Standards for Commercial Support as well as the ACPE Criteria for Quality and Interpretive Guidelines. Recommendations involving clinical medicine in a continuing medical education (CME/CE) activity must be based on evidence that is accepted within the profession of medicine as adequate justification for their indications and contraindications in the care of patients. All scientific research referred to, reported, or used in CME/CE in support or justification of a patient care recommendation must conform to the generally accepted standards of experimental design, data collection, and analysis. Participants are advised that one or more presentations in this CME/CE activity may contain references to unapproved or unlabeled uses of drugs or devices. Participants should note that the use of these agents outside current approved labeling is considered investigational and are advised to consult current prescribing information for these products. Disclaimer 4. 6 Learning Objectives Upon completion of this activity, participants will Evaluate methods for the systematic assessment of patient sedation and analgesia in acute care settings to optimize use of appropriate sedatives and analgesics Compare safety and efficacy of various sedatives and analgesics to aid in the selection of appropriate agents for procedural, nonsurgical sedation Analyze current research data to re-evaluate use of sedatives and analgesics in specific patient populations Assess the safety and efficacy of dexmedetomidine as either the primary sedative or as an anesthetic adjuvant during surgery 5. Overview of Current Sedative and Analgesic Agents 6. 8 Characteristics of an Ideal Sedative Rapid onset of action allows rapid recovery after discontinuation1 Effective at providing adequate sedation with predictable dose response1,2 Easy to administer1,3 Lack of drug accumulation1 Few adverse effects1-3 Minimal adverse interactions with other drugs1-3 Cost-effective3 Predictable dose response2 Promotes natural sleep4 1 Ostermann ME, et al. JAMA. 2000;283:1451-1459. 2 Jacobi et al. Crit Care Med. 2002;30:119-141. 3 Dasta JF, et al. Pharmacother. 2006;26:798-805. 4 Nelson LE, et al. Anesthesiol. 2003;98:428-436. 7. 9 Overview of Current Sedative and Analgesic Agents Drug Class Examples Year FDA Approved Opioids Morphine Prior to 1938 Fentanyl 1968 Butyrophenones Haloperidol 1967 Benzodiazepines Diazepam 1963 Lorazepam 1963 Midazolam 1985 Sedatives/hypnotics Propofol 1989 2 agonists Clonidine 1986 Dexmedetomidine 1999 8. Ranges Reported in Healthy Patients* and ICU Patients Comparison of Pharmacokinetics 3 Bhana N, et al. Drugs. 2000;59:263. 4 Prescribing information for respective drugs. 5 Mallikaarjun S, et al. J Clin Pharmacol. 2004;44:179-187. 0.32-0.64 mL/kg/hr2Dexmedetomidine3 1.9-4.36-23Clonidine2 17-316.3-32Propofol1 1.2-4.110-15Lorazepam1 4.3-6.63.4-11Midazolam1 0.4-0.921-120Diazepam1 8.6-15.06.9-36.0Fentanyl1 8.6-23.02.0-5.5Morphine1 10-1328-38Haloperidol1 Hepatic/renal insufficiency Hepatic impairment Hepatic/renal insufficiency Hepatic/renal insufficiency Hepatic insufficiency Hepatic insufficiency Hepatic insufficiency Renal insufficiency Systemic Clearance (mL/kg/min) Elimination Half-life (hr)Agent Potential for Accumulation4 *Healthy patients: no renal or hepatic disease 3.45-4.5 L/h75Aripiprazole4,5 7.57Olanzapine4 -- 7.57Ziprasidone4 Hepatic insufficiency Hepatic insufficiency 1 Wagner BKJ, et al. Clin Pharmacokinet. 1997;33:426-453. 2 Khan ZP, et al. Anaesthesia. 1999;54:146-165. 9. 11 Opioids Clinical Effects Analgesia1 Sedation1 1 Harvey MA. Am J Crit Care. 1996;5:7 2 Wagner BKJ, et al. Clin Pharmacokinet. 1997;33:426- 3 Dean AJ, et al. J Psychiatry Neurosci. 2006;31:38 4 Gerra G, et al. Drug Alcohol Depend. 2004;75:37 Adverse Effects Respiratory depression1,2 Hypotension1,2 Bradycardia1,2 Constipation1 Tolerance1 Withdrawal symptoms1,2 Dysphoria3,4 10. 12 Haloperidol Clinical Effects Hypnotic agent with antipsychotic properties1 For treatment of delirium in critically ill adults1 Does not cause respiratory depression1 1 Harvey MA. Am J Crit Care. 1996;5:7-16. 2 Crippen DW. Crit Care Clin. 1990;6:369-392. Adverse Effects Dysphoria2 Adverse CV effects include QT interval prolongation Extrapyramidal symptoms, neuroleptic malignant syndrome (rare)1 Metabolism altered by drug- drug interactions2 F O N Cl OH Haloperidol 11. Benzodiazepines Lorazepam Clinical Effects Sedation, anxiolysis, and amnesia1 Commonly used for long- term sedation2 4 Neale BW, et al. Ann Pharmacother. 2005;39:1732-1736. 5 Wilson KC, et al. Chest. 2005;128:1674-1681. 6 Mathews A, et al. J Psychopharmacol. 2002;16:345-354. 7 Pandharipande P, et al. Anesthesiol. 2006;104:21-26. Adverse Effects Slower onset of action than midazolam2,3 Retrograde and anterograde amnesia can exceed desirability6 Delirium7 Severe Adverse Effect Metabolic acidosis (propylene glycol toxicity)4,5 1 Lerch C, et al. Br Med Bull. 1999;55:76-95. 2 Shafer A. Crit Care Med. 1998;26:947-956. 3 Wagner BKJ, et al. Clin Pharmacokinet. 1997;33:426-453. 12. 14 Benzodiazepines Midazolam Clinical Effects Sedation, anxiolysis, and amnesia1 Rapid onset of action intravenously1 1 Blanchard AR. Postgrad Med. 2002;111:59-74. 2 Harvey MA. Am J Crit Care. 1996;5:7-16. 3 Shafer A. Crit Care Med. 1998;26:947-956. 4 Midazolam [package insert]. Weston, FL: Apotex Corp; 2000. Adverse Effects May accumulate in liver and/or renal failure1 Anterograde amnesia2 Prolonged recovery after long-term use3 Combination with opioids increases hypotensive effects1 Respiratory depression4 Adverse hemodynamic events in pediatric patients with cardiovascular instability4 13. Propofol Clinical Effects Sedation1 Hypnosis1 Anxiolysis1 Muscle relaxation1 ICP1 Cerebral metabolic rate1 Antiemetic2 Adverse Effects Respiratory depression (exacerbated by opioids)1 Hypotension1 Decreased myocardial contractility3 Preservative issues4 Potential for infection4 Tolerance5 Serum triglycerides4 Severe Adverse Effect Propofol infusion syndrome6 4 Diprivan [package insert]. AstraZeneca Pharmaceuticals; 2 5 Zapantis A, et al. Crit Care Nurs Clin N Am. 2005;17:211 6 Riker RR, et al. Pharmacother. 2005;25(5 Pt 2):8S- vey MA. Am J Crit Care. 1996;5:7-16. el CC, et al. Anaesthesist. 2005;54:201-9. ch C, et al. Br Med Bull. 1999;55:76-95. 14. 16 2 Agonists Clonidine Clinical Effects Antihypertensive1,2 Analgesia1 Anxiolysis1 Sedation1 Shivering1 Potentiate effects of opioids, sedatives, and anesthetics1 Decrease sympathetic activity1 1 Kamibayashi T, et al. Anesthesiol. 2000;93:1345-1349. 2 Catapres [package insert]. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals Inc; 2004. 3 Nishina K, et al. Anesthesiol. 2002;96:323-329. Adverse Effects Bradycardia1 Dry mouth1 Hypotension3 15. 2 Agonists Dexmedetomidine Clinical Effects Antihypertensive1,2 Sedation1,2 Analgesia1,2 Shivering3 Anxiolysis4 Patient rousability4 Potentiate effects of opioids, sedatives, and anesthetics1,2 Decrease sympathetic activity1,5 4 Riker RR, et al. Pharmacother. 2005;25(5 Pt 2):8S-18S. 5 Venn RA, et al. Brit J Anaesthesia. 2001;87:684-690. 6 Shehabi Y, et al. Intensive Care Med. 2004;30:2188-2196. Adverse Effects Bradycardia6 Hypotension6 Dry mouth2 Vasoconstriction with rapid infusion or at high doses2 Nausea2 ibayashi T, et al. Anesthesiol. 2000;93:1345-1349. edex [package insert]. Lake Forest, IL: Hospira Inc; 2004. as AG, et al. Stroke. 2003;34:1218-1223. 16. 18 Physiology of 2 Receptors Reprinted with permission from Kamibayashi T, et al. Anesthesiol. 2000;93:1346. 17. Effects of Current Sedative and Analgesic Agents 18. 20 Benzo- diazepines Propofol Opioids 2 Agonists Haloperidol Sedation X X X X X Alleviate anxiety1,2 X X Analgesic properties1-4 X X Promote arousability during sedation2-4 X Facilitate ventilation during weaning2-4 X No respiratory depression1-4 X X Control delirium1-4 X X Comparison of Clinical Effects 1 Blanchard AR. Postgrad Med. 2002;111:5 2 Kamibayashi T, et al. Anesthesiol. 2000;95:1345-1 3 Maze M, et al. Anesthetic Pharmacology: Physiologic Principals and Clinical Practice. Chur


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