Sedation & Analgesia

1. Sedation & Analgesia Dr SamirSahu, Dr NirajMishra, Dr SamirMishra, Dr D. Bindhani, Dr SanghamitraMishra, Dr Rakesh Roy

2. Pharmacological Principles • Volume of Distribution • Hydrophilic – low – morphine • Lipophilic – high – midazolam • Hepatic dysfunction – flow dependant – morphine • P-450 – midazolam. Fentanyl • Genetic variability – midazolam, Fentanyl

3. Analgesics

4. Opoids - Complications • Hypotension • Respiratory depression • Gastric retention & ileus • Constipation

5. Sedatives

6. Benzodiazepines - complications • Delirium • Post traumatic stress disorder

7. Propofol • Decreases ICP • Not affected by renal & hepatic failure • Hypotension • Immunosuppressant effects • Change Infusion sets every 12 hours • Propofol related infusion syndrome (PRIS) (>83 mcg/kg/min>48 hrs)

8. Unwanted side-effects of sedative agents General Over sedation Delayed awakening/extubation • Clonidine • Hypotension • Rebound HTN • Bradycardia Benzodiazepines Hypotension Respiratory depression Agitation/Confusion Propofol Hypertriglyceridemia CVS depression Hypotension Opioids Abuse potential Respiratory depression Lack of orientation Constipation

9. Dexmedetomidine • Highly selective alpha-2 agonist • Anxiolysis, cooperative sedation without respiratory depression • Onset – 15 min • Peak concentration within 1 hr of infusion • Hepatic metabolism • Not significantly affected by renal failure

10. Overview of Current Sedative and Analgesic Agents

11. Dexdine vs. Other Sedative/AnalgesicsComparison of Clinical Effects

12. Dexdine vs. Other Sedative/AnalgesicsComparison of Adverse Effects

13. What are your practices ?

14. Practices in different ICUs • Short term sedation • Long term sedation • Analgesia • Bolus/infusion

15. Current Sedation Practice • Used in 70% of MV patients • Trend towards lighter sedation guided by sedation assessment tool • Nurse driven sedation protocol • Daily sedation interruption

16. How often the target is achieved? Target of interventions (sedation) 2,3 • Optimum sedation, (neither under- nor over-sedation) • Free from anxiety & pain • Calm & cooperative patient 1. Crit Care. 2000;4(suppl 1):S110, 2. NEJM 2000;342:1471-1477, 3. Crit Care Med.2005;33:1266-1271.

17. SCCM guidelines 2002 • Short term < 24 – propofol or midazolam • Long term >24 – lorazepam • Analgesia – morphine or fentanyl

18. Commonly used Agents

19. Intermittent Dosing • Morphine (56%) • Lorazepam (61%) • Midazolam (56%) • Haloperidol (81%)

20. Continuous Infusion • France >90% • Sweden 99% • Australia >70% • Canada - 26% in few patients, 38% in 25-75% of patients, 26% in most patients • 64% continuous & 10% boluses (Tanios, 2009) • Propofol(87%) & Fentanyl(96%) were more likely to administered as continuous infusion.

21. Do you practice daily interruption of Sedation ?

22. Daily Interruption • Daily interruption of sedative infusion …....... Kress et al, N Eng J Med 2000 • Stop infusion till patient is awake or agitated • Restarted at half the original dose & titrated to clinical targets • Reduced duration of MV • Reduced duration of ICU stay • Better assessment of patients sedation needs • Reduces drug bioaccumulation

23. Safety Screen for Daily interruption • No active seizure • No alcohol withdrawal • No agitation • No paralysis • No myocardial ischaemia • Normal ICP

24. Daily Interruption • Canada 40% • Denmark 31% • Germany 34%

25. Do you have a Sedation & Analgesia Protocol in your ICU ?

26. Sedation Protocols • Australia 54% • Germany 52% • US 64% • UK 80% • Canada 43% Reduces duration of MV, ICU stay, reduces treatment delays, Improves communication, Standardizes therapy, increased dedicated education

27. Do you use any Sedation assessment scale in your ICU ?

28. Assessment Tools • Ramsay(1974) – most commonly used • RASS • SAS

29. Protocols, Assessment Tools & Daily Interruptions

30. Pain Assessment Tools • CPOT – Critical Care Pain Observation Tool

31. Delirium Assessment Tool • CAM-ICU – confusion assessment method for the ICU

32. Local Survey

33. Patient Assessment • Is the patient comfortable ? • Is the patient in pain ? • Is the patient agitated ?

34. ‘Wake up & Breath’ • Girard et al, (Awakening & Breathing Controlled trial) :Lancet, 2008. • 3.1 more ventilator free days • ICU stay & Hospital stay reduced by 4 days

35. Safety screen for SBT • No agitation • SpO2 >88% with FiO2 50% • PEEP < 8 • No myocardial ischaemia • No vasopressors • Inspiratory effort

36. Determinants of Practice • Cost • Duration of action • Familiarity • Level of Experience • Level of Education

37. Strøm et al,Lancet2010;375:475-480. • In the general intensive care unit of Odense University Hospital, Denmark, standard practice is a protocol of no sedation • No sedation or intermittent sedation. • The control group was sedated with 20 mg/mL of propofol for 48 hours and 1 mg/mL of midazolam thereafter, with daily interruption until awake. • Both groups received bolus doses of 2.5 or 5 mg of morphine.

38. Strøm et al,Lancet2010;375:475-480. • Compared with the 58 remaining patients receiving interrupted sedation, the 55 patients receiving no sedation had significantly more days without ventilation (mean, 13.8 ± 11.0 days vs mean, 9.6 ± 10.0 days; mean difference, 4.2 days; 95% confidence interval [CI], 0.3 - 8.1; P = .0191).

39. Strøm et al,Lancet2010;375:475-480. • Patients in the no-sedation group also had a shorter stay in the intensive care unit (hazard ratio [HR], 1.86; 95% CI, 1.05 - 3.23; P = .0316) and a shorter stay in the hospital for the first 30 days studied (HR, 3.57; 95% CI, 1.52 - 9.09; P = .0039). Accidental extubations, the need for computed tomography or magnetic resonance imaging brain scans, and ventilator-associated pneumonia were similar in both groups. However, the no-sedation group had more frequent agitated delirium than the intermittent sedation group (n = 11 [20%] vs n = 4 [7%]; P = .0400).

40. Strøm et al,Lancet2010;375:475-480. • In an accompanying editorial, Dr. Laurent Brochard, from Centre Hospitalier Albert Chenevier–Henri Mondor, and Université Paris-Est, Créteil, France, notes the study limitations but calls the overall results "impressive and promising." • "Use of this strategy will mean that more attention needs to be paid in the daily care of patients, and caregivers will need increased empathy towards patients," Dr. Brochard writes. "Hopefully, these findings will prove beneficial to patients."

41. Sangeeta Mehta, SLEAP Investigators and the Canadian Critical Care Trials Group. JAMA. Published online October 17, 2012. • for critically ill patients receiving mechanical ventilation....a sedation protocol that targeted light sedation, daily sedation interruption did not reduce the duration of mechanical ventilation, offered no additional benefits for patients, and may have increased both sedation and analgesic use and nurse workload.

42. Sangeeta Mehta, SLEAP Investigators and the Canadian Critical Care Trials Group. JAMA. Published online October 17, 2012. • A sedation strategy adding daily interruption to a control group strategy of protocolized sedation that targeted light sedation, which is likely superior to "usual care" of an earlier era. • Reflecting "actual practice in ICUs with variable workloads and ICU staffing models. • Included surgical and medical patients. • The most commonly administered medications to facilitate sedation were midazolam and fentanyl

43. Sangeeta Mehta, SLEAP Investigators and the Canadian Critical Care Trials Group. JAMA. Published online October 17, 2012. • The 2 groups also had similar outcomes for durations of stay in the ICU or hospital, hospital mortality, rates of unintentional extubation, delirium, or tracheostomy. • The interruption group had higher mean daily doses of benzodiazepines and opioids. • Nurse workload was estimated to be higher in the interruption group vs the control group. • Evidence existed that interruption of sedation was more effective for surgical or trauma patients vs medical patients.

44. Pharmaco-economics • Cost of drugs • Reduced ventilator days • Reduced ICU days

45. CT in ICU sedation- 1 Dexmedetomidine reduces the prevalence of Delirium 80 Dexmedetomidine-treated patients spend less time on ventilator 70 60 5.6 days 50 6 3.7 days % of patient suffering from Delirium 40 Dexmedetomidine 4 Dexmedetomidine Midazolam Midazolam 30 Time to extubation in days 2 20 10 0 0 Enrollment 1 2 3 4 5 6 Treatment Day DexdinevsMidazolam DXMD(0.2-1.4 µg/kg/hour) or Midazolam (0.02-0.1mg/kg/hour) N: 375, adult mechanically ventilated patients; Duration: > 24 hr P= .01 P= .01 • DXMD therapy significantly reduced (vsMidazolam) • Median time to extubation by 1.9 days (3.7 vs 5.6 days, P= .01) • Incidence of delirium by 22.6% (P < .001) • Significantly less tachycardia & HTN requiring treatment JAMA 2009;301(5):489-499

46. A Cost-Minimization Analysis of Dexmedetomidine Compared With Midazolam for Long-term Sedation in the Intensive Care UnitDasta JF, Kane-Gill SL, Pencina M, et al Crit Care Med.2010; • Patients who received dexmedetomidine experienced less delirium, fewer nosocomial infections, less tachycardia and hypertension (but more bradycardia), and a shorter time to extubation than patients treated with midazolam. From these data, it appears that the use of dexmedetomidine may be more cost effective, despite higher drug acquisition costs, than the commonly used benzodiazepine anxiolytic medications.

47. Summary • Chose your drugs according to availability, costs & overall benefits • Develop a protocol (Protocolized target-based sedation & analgesia) • Practice daily interruption of continuous sedation • Use an assessment tool to stay at your goal (Indentify goals using validated tools for pain, agitation & sedation • Nurse driven protocol

48. THANK YOUDexdineDexmedetomidine Hydrochloride Macleods Pharmaceuticals Ltd 21st May 2010; Bhubaneshwar