Sedation in the Surgery Patient

1. Sedation in the Surgery Patient Colby Miller Pharm.D., BCPS Critical Care Specialist Sinai Hosptial

2. Case 1 JS is a73 year old female admitted to SICU after tumor debulking surgery for stage IV ovarian cancer (omentectomy, TAH/BSO, SBR) EBL 700 ml, PRBCs 2 units, 2.7 L IVF Patient extubated in the PACU but reintubated for respiratory distress and transferred to the SICU. She is unable to be extubated and on day 4 is diagnosed with a pseudomonal VAP. She is started on piperacillin/tazobactam and tobramycin. PMH: Right mastectomy for breast cancer HLD HTN OA Depression Chronic back pain Home medications: exemestane 25mg qd diltiazem 240mg qd rosuvastatin 2.5mg qd paroxetine 30mg qd risedronate 35mg qweek oxycodone CR 40mg bid Start off with a patient caseStart off with a patient case

3. Patient�s report pain/discomfort with common ICU procedures such as ETT suctioning and dressing changesPatient�s report pain/discomfort with common ICU procedures such as ETT suctioning and dressing changes

4. Complications of UnderSedation ?

5. Complications of UnderSedation Patient recall (PTSD) Device removal Ineffectual mechanical ventilation Initiation of neuromuscular blocker therapy Myocardial or cerebral ischemia Decreased family satisfaction with care Increased catacholamine release, metabolic stress, cardiovascular stress, impaired wound healing and immune fxnIncreased catacholamine release, metabolic stress, cardiovascular stress, impaired wound healing and immune fxn

6. Complications of OverSedation ?

7. COMPLICATIONS OF OVER SEDATION Prolonged mechanical ventilation Need for additional diagnostic testing Increased length of ICU and hospital stay Increased risk of complications Ventilator-associated pneumonia Thromboembolic events Drug withdrawal

8. Incidence of Inadequate Sedation Quantify Quantify

9. Goals of sedation and analgesia Relieve pain and anxiety Improve compliance with care Optimize safety Avoid or reduce delirium Don�t want to under sedate or over sedate. So what are the goals?Don�t want to under sedate or over sedate. So what are the goals?

10. How do we assess sedation?

11. Desirable features of sedation scales Easy to administer, recall and interpret Clear definitions of each level Discretion between each level of scale Proven validity Inter-rater reliability (including in different settings)

12. Many levels of sedation and no levels of agitationMany levels of sedation and no levels of agitation

17. Key Points Use validated tools Monitor patients frequently Target: Tolerance of ICU environment Pain and anxiety control Patient/ventilator synchrony Avoid under-sedation Avoid excess or prolonged sedation

19. CASE 2 TC is a 21 year old male s/p multiple GSW to abdomen. Patient is taken to OR for ex-lap. He undergoes SBR, repair of liver laceration, exploration of retroperitoneal hematoma and washout of abdomen. He is transferred to the SICU after the OR with an open abdomen. He is returning to the OR in 3 days for washout/reexploration. His pain is being treated appropriately with fentanyl RASS Score assessed on admission to SICU is +3 and nonpharmacological interventions have been implemented. The RASS score is now +2. Goal RASS? Which sedative medication should be ordered? What are our options? What are our options?

20. Non-pharmacological measures Minimize: Blood draws X-rays Blood pressure measurements Blood glucose measurements Dimming lights at night (sleep-wake cycle) Massage, therapeutic touch and music therapy

21. Selection of Sedatives Benzodiazepines Diazepam Lorazepam Midazolam Propofol Dexmedetomidine Haloperidol, other neuroleptics What are our options?What are our options?

22. Medication Selection Pharmacokinetic / dynamic properties of medications Patient-specific characteristics SCCM Guidelines (last updated in 2002) Clinical trials since 2002 What data is available to us to guide medication selection?What data is available to us to guide medication selection?

23. PROPERTIES OF MEDICATIONS Onset and offset of effect Duration Drug metabolism Presence of active metabolites Effectiveness of medication Adverse effects Costs related to drug acquisition Costs related to duration of therapy For example a medication might cost more money but if it can get a patient off the ventilator faster it may save money in the long runFor example a medication might cost more money but if it can get a patient off the ventilator faster it may save money in the long run

25. Dexmedetomidine Alpha2-adrenoceptor agonist Produces sedation and analgesia but no respiratory depression Side effects should be anticipated: blood pressure reduction heart rate reduction Bradycardia and sinus arrest have been reported Caution should be exercised when administering Precedex to patients with advanced heart block and/or severe ventricular dysfunction A few more words on precedexA few more words on precedex

26. Hyperosmolarity, elevated anion and osmol gaps, metabolic and lactic acidosis, acute renal failure, contact dermatitis, seizures, mental status changes, cardiac arrhythmias, and asystole. Osmolar gap can be used as a surrogate marker for serum propylene glycol concentration. (2 x serum sodium [mEq/L]) + (glucose [mg/dl]/18) + (BUN [mg/dl]/2.8). In critically ill patients, receiving lorazepam for sedation, an osmol gap above 10 was associated with concentrations previously reported to cause toxicity. Propylene glycol as a solventPropylene glycol as a solvent

27. Propofol-related infusion syndrome (PRIS) Propofol infusion syndrome: (1) the sudden, or relatively sudden, onset of marked bradycardia resistant to treatment, with progression to asystole Bradycardia required plus one of the following: (2) the presence of lipemia (3) a clinically enlarged liver secondary to fatty infiltration (4) the presence of severe metabolic acidosis (5) the presence of muscle involvement with evidence of rhabdomyolysis or myoglobinuria Another word on propofol.. Incidence = Diagnosis of exclusion Reported in doses > 88 mcg/kg/min, old, young, statinsAnother word on propofol.. Incidence = Diagnosis of exclusion Reported in doses > 88 mcg/kg/min, old, young, statins

28. SCCM GuidelinesSCCM Guidelines

29. Key Points Choose medications best suited to the patient�s characteristics Organ function Drug metabolism Risk of side effects Sedation needs differ among patients Patients needs vary over time Can use the SCCM guidelines when patient has no compelling indications to use one medication over anotherCan use the SCCM guidelines when patient has no compelling indications to use one medication over another

30. CASE 2 TC is a 21 year old male s/p multiple GSW to abdomen. Patient is taken to OR for ex-lap. He undergoes SBR, repair of liver laceration, exploration of retroperitoneal hematoma and washout of abdomen. He is transferred to the SICU after the OR with an open abdomen. He is returning to the OR in 3 days for washout/reexploration. His pain is being treated appropriately with fentanyl RASS Score assessed on admission to SICU is +3 and nonpharmacological interventions have been implemented. The RASS score is now +2. Goal RASS? Which sedative medication should be ordered? What are our options? What other information do you need?What are our options? What other information do you need?

31. Why do we need to minimize sedation? Discussed oversedation and its consequences. Also avoid delirium Why do we need to minimize sedation? Discussed oversedation and its consequences. Also avoid delirium

32. Tip #1 SCCM recommended in 2002 guidelinesSCCM recommended in 2002 guidelines

33. 2 LARGE Prospective, two phase study (before/after) Baseline group (no protocol) vs follow-up group (protocol) Analgesia controlled before sedation in follow-up group2 LARGE Prospective, two phase study (before/after) Baseline group (no protocol) vs follow-up group (protocol) Analgesia controlled before sedation in follow-up group

34. Protocol vs no protocol, Protocol group = intermittent boluses first before CI, daily attempt to decrease doses Regular assessment of consciousness and tolerance to ICU environment Duration of MV Control group =10.3 days Algorithm group = 4.4 days Shorter time to arousal 2 days vs 4 days Protocol vs no protocol, Protocol group = intermittent boluses first before CI, daily attempt to decrease doses Regular assessment of consciousness and tolerance to ICU environment Duration of MV Control group =10.3 days Algorithm group = 4.4 days Shorter time to arousal 2 days vs 4 days

35. Tip #2

36. RCT comparing daily interruption of sedatives (midazolam/propofol and analgesia) until patient able to follow 3 of 4 simple commands or became agitated vs usual care. Sedation restarted at half of previous rate when reinitiated. Outcomes Duration of mechanical ventilation ICU length of stay Length of hospital stay Need for diagnostic tests for unexplained altered mental status Both strategies include protocolsBoth strategies include protocols

39. Reduced drug accumulation and additional opportunities for initiating weaning from ventilator. Strategy linked to reduction in ICU complications from shortened ICU LOS Reduced drug accumulation and additional opportunities for initiating weaning from ventilator. Strategy linked to reduction in ICU complications from shortened ICU LOS

40. Patients randomized to daily interruption of sedation (DIS) have fewer symptoms of PTSD compared to control patients No DIS for patients with paralyzed / HTN crisis / status asthmaticus / h/o alcohol abuse (cannot withdraw meds)No DIS for patients with paralyzed / HTN crisis / status asthmaticus / h/o alcohol abuse (cannot withdraw meds)

41. VAP Bundle Concept of DIS has become so important in the ICU that it was incorporated into the VAP Bundle SCCM guidelines also mentions using this or another strategy to minimize sedationConcept of DIS has become so important in the ICU that it was incorporated into the VAP Bundle SCCM guidelines also mentions using this or another strategy to minimize sedation

42. Tip #3

43. RCT comparing a remifentanil-based sedation regimen titrated to response before the addition of midazolam for further sedation vs. midazolam-based sedation regimen with fentanyl or morphine added for analgesia

44. Tip #4 To potential improve outcomesTo potential improve outcomes

45. First article: RCT 106 MV patient in MICU/SICU 2004-2006. Precedex vs ativan for up to 120 hrs and titrated to RASS. Used CAM-ICU to assess for delirium. Second trial: FDA mandated a trial for drug safety and efficacy for > 24 hrsFirst article: RCT 106 MV patient in MICU/SICU 2004-2006. Precedex vs ativan for up to 120 hrs and titrated to RASS. Used CAM-ICU to assess for delirium. Second trial: FDA mandated a trial for drug safety and efficacy for > 24 hrs

46. Tip #5

47. RCT comparing DIS followed by spontaneous breathing trials (SBT) with sedation per usual care (no DIS) plus a daily SBT Outcomes More ventilator-free days (14.7d vs 11.6d) Shorter ICU length of stay (9.1d vs 12.9d) Shorter hospital length of stay (14.9d vs 19.2d) More self-extubations (16 vs 6) with similar reintubation rates

48. Key Points Use protocols to optimize sedation Use titration strategies to minimize sedation Daily interruption of sedation (with SBT) Intermittent vs. continuous therapy Bolus doses before increasing infusion rates Analgesic-based therapy Consider dexmedetomidine