SEDATION IN THE ICU-SHIFTS & STRATEGIES

1. SEDATION IN THE ICU-SHIFTS & STRATEGIES DR. RAKESH K. CHAWLA MD,FCCP(USA) SR. CONSULTANT RESPIRATORY MEDICINE, CRITICAL CARE AND SLEEP DISORDERS JAIPUR GOLDEN HOSPITAL,SAROJ HOSPITAL & RAJIV GANDHI CANCER INSTITUTE MOBILE-09810072860

2. NISO FINANCIAL GRANT FOR THIS LECTURE.PURE ACADEMIC

3. Sedation in the ICU The ICU is a hostile environment and while pain is often the root cause of distress experienced by the patient in the unit , anxiety, dyspnoea, delirium and sleep deprivation may be additive or synergistic.

4. Everyone who works in Intensive Care Unit(I.C.U) has already faced an anxious and agitated patient requiring sedation for different goals such as management of difficult airway, improvement of mechanical ventilation or just as adjuvant therapy to commonly procedures done in Intensive Care Medicine.

5. Majority of critically ill patients experience significant distress, anxiety, and agitation during their intensive care unit stays. Numerous factors, including sleep deprivation, unfamiliar environment, delirium, adverse medication effect, pain, and extreme anxiety can contribute to ICU patient distress.

6. Intensivists often employ various sedative agents to relieve ICU associated distress and prevent secondary complications of such distress. There are a variety of pharmacologic agents used for this purpose, including benzodiazepines, propofol, antipsychotic agents, and alpha agonists.

7. Important patho-physiologic mechanisms affected by ICU – associated distress include significant increases in catecholamines, cortisol, growth hormone, vasopressin, prolactin, glucagon, fatty acids, and protein catabolism. Clinically significant sequelae of this physiologic dysregulation include fluid and electrolyte imbalances, altered wound healing , and disturbances of the sleep wake cycles.

8. ICU sedation is aimed at keeping the patient comfortable but easily arousable. Deep sedation with or without muscle relaxants is rarely indicated and is associated with a higher incidence of delirium and death. Analgo – sedation is administered to relieve pain, anxiety and discomfort and to facilitate treatment and nursing. .

9. Providing analgesia first, and adding sedation as required (“analgo - sedation”).

10. 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) What We Know About ICU Agitation/Discomfort

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

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

14. Antibiotics Acyclovir Amphotericin B Cephalosporins Ciprofloxacin Imipenem – cilastatin (Primaxin , Merck) Ketoconazole Metronidazole Penicillin Rifampin Trimethoprim – Sulfamethoxazole Anticonvulsants Phenobarbital Phenytoin Cardiac Drugs Captopril Clonidine Digoxin Dopamine Labetalol Lidocaine Nifedipine Nitroprusside Propranolol Quinidine Sulfate Corticosteroids Dexamethasone Methylprednisolone Opiold Analgesics Codeine Meperidine Morphine Sulfate Miscellaneous Drugs Anticholinergics Benzodiazepines Hydroxyzine Ketamine Metoclopramide Nonsteroidal anti – inflammatory drugs Theophylline Medications Associated With Agitation in ICU Patients

15. 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 Recall in the ICU

16. 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 • Treatment or Diagnostic procedures Goals of Sedation in ICU

17. 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 Characteristics of an ideal sedation agents for the ICU

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

19. Causes for Agitation Sedatives Sedation

20. Incidence of Inadequate Sedation Kaplan L, et al. Crit Care 2000;4(suppl 1):S110.

21. Sedation: Background • Significant issues with some current agents • Opiate/benzodiazepine – tolerance, efficacy • Chloral hydrate - predictability • Pentobarbital – agitation, duration • Propofol – limited access in some jurisdictions • Ketamine – emergence reactions, tolerance 2-adrenoreceptor agonists • Prototype agent is clonidine • Recent applications in clinical practice- Sedation, Behavior disorders , Drug withdrawal , Hypertension

22. Complications of Under/Over Sedation Under sedation Patient recall (PTSD) Device removal Ineffectual mechanical ventilation Initiation of neuromuscular blocker therapy Myocardial or cerebral ischemia Decreased family satisfaction with care Over sedation • Prolonged mechanical ventilation • Need for additional diagnostic testing • Increased length of ICU and hospital stay • Increased risk of complications • Ventilator-associated pneumonia • Thrombo-embolic events • Drug withdrawal

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

24. AGITATED PATIENT

25. 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 Oversedation

26. DEEPLY SEDATED

27. 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 Daily Goal is Arousable, Comfortable Sedation

28. 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.) Protocols and Assessment Tools

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

30. How do we assess sedation?

31. Sedation Scales : Very useful , very underused.

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

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

34. 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 Sedation Scoring Scales

35. Sedation should be targeted to a Ramsay score of 2 to 3.

39. The Riker Sedation-Agitation Scale

40. MASS (Motor Assessment Scale ) The MASS is scored from 0 (patient unresponsive) to 6 (dangerously agitated, uncooperative patient).

41. The Motor Activity Assessment Scale

42. VICS (Vancouver Interaction and Calmness Scale) The VICS consists of two separate scores, the interaction score and the calmness score. Each score is composed of five categories , with each category graded on a scale .

43. SAS (Sedation – Agitation Scale) The SAS is scored from 1 (unarousable ) to 7 (dangerous agitation).

45. AVRIPAS This scale consists of four components : (a) agitation; (b) alertness; (c) heart rate; (d) respiration. Agitation, alertness , and respiration are measured on a 5 point scoring system. Heart rate is measured on a 4 point scale . The overall sedation score for this system is a sum of each component , with scores ranging from 1 (sedated) to 19 (need for more sedation).

46. Bloomsbury Also known as the University College London Hospitals sedation protocol, this scale spans from -3 (unarousable) to +3 (agitated and restless). There is also categorization for natural sleep. The bloomsbury scale appears to have a high association with the Ramsay Sedation Scale.

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

48. 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 Sedation Options: Benzodiazepines (Midazolam and Lorazepam)

49. Benzodiazepines

50. 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 Sedation Options: Propofol