Sedation, Analgesia, and Neuromuscular Blockade in the Adult ICU

1. Sedation, Analgesia, and Neuromuscular Blockade in the Adult ICU GiudittaAngelini, MD University of Wisconsin Madison, WI Gil Fraser, PharmD, FCCM Maine Medical Center Portland, ME Doug Coursin, MD, FCCM University of Wisconsin Madison, WI

2. What We Know About ICU Agitation/Discomfort • Prevalence • 50% incidence in those with length of stay > 24 hours • Primary causes: unrelieved pain, delirium, anxiety, sleep deprivation, etc. • Immediate sequelae: • Patient-ventilator dyssynchrony • Increased oxygen consumption • Self (and health care provider) injury • Family anxiety • Long-term sequelae: chronic anxiety disorders and post-traumatic stress disorder (PTSD)

3. Recall in the ICU • Some degree of recall occurs in up to 70% of ICU patients. • Anxiety, fear, pain, panic, agony, or nightmares reported in 90% of those who did have recall. • Potentially cruel: • Up to 36% recalled some aspect of paralysis. • Associated with PTSD in ARDS? • 41% risk of recall of two or more traumatic experiences. • Associated with PTSD in cardiac surgery

4. Anxiety Pain Acute confusional status Mechanical ventilation Treatment or diagnostic procedures Psychological response to stress Need for Sedation

5. Goals of Sedation in ICU • Patient comfort and • Control of pain • Anxiolysis and amnesia • Blunting adverse autonomic and hemodynamic responses • Facilitate nursing management • Facilitate mechanical ventilation • Avoid self-extubation • Reduce oxygen consumption

6. Characteristics of an ideal sedation agents for the ICU • Lack of respiratory depression • Analgesia, especially for surgical patients • Rapid onset, titratable, with a short elimination half-time • Sedation with ease of orientation and arousability • Anxiolytic • Hemodynamic stability

7. The Challenges of ICU Sedation • Assessment of sedation • Altered pharmacology • Tolerance • Delayed emergence • Withdrawal • Drug interaction

8. Sedation Causes for Agitation Sedatives

9. Undersedation Sedatives Causes for Agitation Agitation & anxiety Pain and discomfort Catheter displacement Inadequate ventilation Hypertension Tachycardia Arrhythmias Myocardial ischemia Wound disruption Patient injury

10. Oversedation Causes for Agitation Sedatives Prolonged sedation Delayed emergence Respiratory depression Hypotension Bradycardia Increased protein breakdown Muscle atrophy Venous stasis Pressure injury Loss of patient-staff interaction Increased cost

11. Correctable Causes of Agitation • Full bladder • Uncomfortable bed position • Inadequate ventilator flow rates • Mental illness • Uremia • Drug side effects • Disorientation • Sleep deprivation • Noise • Inability to communicate

12. Causes of Agitation Not to be Overlooked • Hypoxia • Hypercarbia • Hypoglycemia • Endotracheal tube malposition • Pneumothorax • Myocardial ischemia • Abdominal pain • Drug and alcohol withdrawal

13. Daily Goal is Arousable, Comfortable Sedation • Sedation needs to be protocolized and titrated to goal: • Lighten sedation to appropriate wakefulness daily. • Effect of this strategy on outcomes: • One- to seven-day reduction in length of sedation and mechanical ventilation needs • 50% reduction in tracheostomies • Three-fold reduction in the need for diagnostic evaluation of CNS

14. Protocols and Assessment Tools • SCCM practice guidelines can be used as a template for institution-specific protocols. • Titration of sedatives and analgesics guided by assessment tools: • Validated sedation assessment tools (Ramsay Sedation Scale [RSS], Sedation-Agitation Scale [SAS], Richmond Sedation-agitation Scale [RSAS], etc.) - No evidence that one is preferred over another • Pain assessment tools - none validated in ICU (numeric rating scale [NRS], visual analogue scale [VAS], etc.)

15. Strategies for Patient Comfort • Set treatment goal • Quantitate sedation and pain • Choose the right medication • Use combined infusion • Reevaluate need • Treat withdrawal

16. Overview of SCCM Algorithm 1 2 3 4 Jacobi J, Fraser GL, Coursin D, et al. Crit Care Med. 2002;30:119-141.

17. Assess Pain Separately Pain

18. Visual Pain Scales 0 1 2 3 4 5 6 7 8 9 10 Worst possible pain No pain

19. Signs of Pain • Hypertension • Tachycardia • Lacrimation • Sweating • Pupillary dilation

20. Principles of Pain Management • Anticipate pain • Recognize pain • Ask the patient • Look for signs • Find the source • Quantify pain • Treat: • Quantify the patient’s perception of pain • Correct the cause where possible • Give appropriate analgesics regularly as required • Remember, most sedative agents do not provide analgesia • Reassess

21. Nonpharmacologic Interventions • Proper position of the patient • Stabilization of fractures • Elimination of irritating stimulation • Proper positioning of the ventilator tubing to avoid traction on endotracheal tube

22. Address Pain

23. Opiates • Benefits • Relieve pain or the sensibility to noxious stimuli • Sedation trending toward a change in sensorium, especially with more lipid soluble forms including morphine and hydromorphone. • Risks • Respiratory depression • NO amnesia • Pruritus • Ileus • Urinary retention • Histamine release causing venodilation predominantly from morphine • Morphine metabolites which accumulate in renal failure can be analgesic and anti-analgesic. • Meperidine should be avoided due to neurotoxic metabolites which accumulate, especially in renal failure, but also produces more sensorium changes and less analgesia than other opioids.

24. Pharmacology of Selected Analgesics

25. Opioids

26. Opioids

27. Opiate Analgesic Options: Fentanyl, Morphine, Hydromorphone * Offset prolonged after long-term use ** Active metabolite accumulation causes excessive narcosis

28. Sample Analgesia Protocol Numeric Rating Scale

29. Sedation Scoring Scales • Ramsay Sedation Scale (RSS) • Sedation-agitation Scale (SAS) • Observers Assessment of Alertness/Sedation Scale (OAASS) • Motor Activity Assessment Scale (MAAS) BMJ 1974;2:656-659 Crit Care Med 1999;27:1325-1329 J Clin Psychopharmacol 1990;10:244-251 Crit Care Med 1999;27:1271-1275

30. The Ramsay Scale

31. The Riker Sedation-Agitation Scale

32. The Motor Activity Assessment Scale

33. What Sedation Scales Do • Provide a semiquantitative “score” • Standardize treatment endpoints • Allow review of efficacy of sedation • Facilitate sedation studies • Help to avoid oversedation

34. What Sedation Scales Don’t Do • Assess anxiety • Assess pain • Assess sedation in paralyzed patients • Predict outcome • Agree with each other

35. BIS Monitoring

36. BIS Monitoring

37. BIS Range Guidelines BIS Awake 100 Responds to normal voice Axiolysis 80 Responds to loud commands or mild prodding/shaking Moderate sedation 60 Low probability to explicit recalls Unresponsive to verbal stimuli 40 Burst suppression Deep Sedation 20 Flat line EEG 0

38. Address Sedation Yes

39. Choose the Right Drug • Benzodiazepines • Propofol • -2 agonists

40. Sedation Options: Benzodiazepines (Midazolam and Lorazepam) • Pharmacokinetics/dynamics • Lorazepam: onset 5 - 10 minutes, half-life 10 hours, glucuronidated • Midazolam: onset 1 - 2 minutes, half-life 3 hours, metabolized by cytochrome P450, active metabolite (1-OH) accumulates in renal disease • Benefits • Anxiolytic • Amnestic • Sedating • Risks • Delirium • NO analgesia • Excessive sedation: especially after long-term sustained use • Propylene glycol toxicity (parenteral lorazepam): significance uncertain - Evaluate when a patient has unexplained acidosis - Particularly problematic in alcoholics (due to doses used) and renal failure • Respiratory failure (especially with concurrent opiate use) • Withdrawal

41. Sedation Options: Propofol • Pharmacology: GABA agonist • Pharmacokinetics/dynamics: onset 1 - 2 minutes, terminal half-life 6 hours, duration 10 minutes, hepatic metabolism • Benefits • Rapid onset and offset and easily titrated • Hypnotic and antiemetic • Can be used for intractable seizures and elevated intracranial pressure • Risks • Not reliably amnestic, especially at low doses • NO analgesia! • Hypotension • Hypertriglyceridemia; lipid source (1.1 kcal/ml) • Respiratory depression • Propofol Infusion Syndrome - Cardiac failure, rhabdomyolysis, severe metabolic acidosis, and renal failure - Caution should be exercised at doses > 80 mcg/kg/min for more than 48 hours - Particularly problematic when used simultaneously in patient receiving catecholamines and/or steroids

42. Sample Sedation Protocol Sedation-agitation Scale Riker RR et al. Crit Care Med. 1999;27:1325.

43. Sedation Options: Dexmedetomidine • Alpha-2-adrenergic agonist like clonidine but with much less imidazole activity • Has been shown to decrease the need for other sedation in postoperative ICU patients • Potentially useful while decreasing other sedatives to prevent withdrawal • Benefits • Does not cause respiratory depression • Short-acting • Produces sympatholysis which may be advantageous in certain patients such as postop cardiac surgery • Risks • No amnesia • Small number of patients reported distress upon recollection of ICU period despite good sedation scores due to excessive awareness • Bradycardia and hypotension can be excessive, necessitating drug cessation and other intervention

44. Benzodiazepines

45. Propofol

46. Propofol Dosing • 3-5 g/kg/min antiemetic • 5-20 g/kg/min anxiolytic • 20-50 g/kg/min sedative hypnotic • >100 g/kg/min anesthetic

47. Problems with Current Sedative Agents

48. Use Continuous and Combined Infusion Load Maintenance Plasma Level

49. Repeated Bolus Plasma levels

50. Choose the Right Drug Sedation Analgesia Amnesia Hypnosis Anxiolysis Propofol Benzodiazepines Opioids Patient Comfort -2 agonists