1. Assessing and Managing Sedation in the Intensive Care and the Perioperative Settings

2. SEDATION Curriculum Learning Objectives Manage adult patients who need sedation and analgesia while receiving ventilator support according to current standards and guidelines Use validated scales for sedation, pain, agitation, and delirium in the management of these critically ill patients Assess recent clinical findings in sedation and analgesia management and incorporate them into the management of patients in the acute care, procedural, and surgical sedation settings

3. Procedural Sedation Major Applications Surgical –Neurosurgery –Bariatric surgery –Oral –Plastic/reconstructive –Biopsy –CV surgery Endoscopic –Bronchoscopy –Fiberoptic intubation –Colonoscopy

4. Growth of Ambulatory Surgery Centers (ASC) ASCs increased outpatient operations from < 10% in 1979 to 50% in 1990 1 From 1993 to 2001 2 –ASCs in metropolitan areas increased by 150% –Hospital outpatient surgeries increased 28% –Inpatient surgeries decreased by 4.5% 70% of surgical interventions in the United States are outpatient procedures 1 1.Pregler JL, et al. Anesthesiol Clin North America. 2003;21(2):207-228. 2.Bian J, et al. Inquiry. 2009-2010;46(4):433-447.

5. Common Agents for Conscious Sedation Mustoe TA, et al. Plast Reconstr Surg. 2010;126(4):165e-176e.

6. Factors Jeopardizing Safety Risk of major blood loss Extended duration of surgery (> 6 h) Critically ill patients (evaluate and document prior to procedure) Need for specialized expertise or equipment (cardio- pulmonary bypass, thoracic or intracranial surgery) Supply and support functions or resources are limited Inadequate postprocedural care Physical plant is inappropriate or fails to meet regulatory standards Eichhorn V, et al. Curr Opin Anaesthesiol. 2010;23(4):494-499.

7. Standardized Monitoring Hemodynamic –ECG –Blood pressure Respiration –Oxygenation (SpO 2 by pulse oximetry, supplemental oxygen) –Ventilation (end tidal CO 2, EtCO 2 ) Temperature (risk of hypothermia) Higher risk at remote locations –Inadequate oxygenation/ventilation –Oversedation –Inadequate monitoring Eichhorn V, et al. Curr Opin Anaesthesiol. 2010;23(4):494-499.

8. Endoscopic Procedures

9. Sedation for Endoscopy Desirable qualities –Permits complete diagnostic exam –Safe –Diminishes memory of the procedure –Permits rapid discharge after procedure Risk factors –Depth of sedation –ASA status –Medical conditions –Pregnancy –Difficult airway mgt –Extreme age –Rapid discharge time Runza M. Minerva Anestesiol. 2009;75:673-674.

10. Drugs for Fiberoptic Intubation Agent Class ExampleAdvantagesConsiderations GABA agonist Benzodiazepine Midazolam Quick onset Injection not painful Short duration Not analgesic Airway reflexes persist GABA agonist Benzodiazepine Propofol Quick onsetRespiratory depression Unconsciousness Decreased bp, cardiac output Increased HR OpioidFentanyl Remifentanil Analgesic Cough suppressive Respiratory depression  2 Agonist DexmedetomidinePt easily arousable Anxiolytic Analgesic No respir. depression Transient hypertension Hypotension Bradycardia Summary courtesy of Pratik Pandharipande, MD.

11. Propofol vs Combined Sedation in Flexible Bronchoscopy Randomized non-inferiority trial 200 diverse patients received propofol or midazolam/hydrocodone 1 o endpoints –Mean lowest SaO 2 –Readiness for discharge at 1h Result –No difference in mean lowest SaO 2 –Propofol group had  Higher readiness for discharge score (P = 0.035)  Less tachycardia  Higher cough scores Conclusion: Propofol is a viable alternative to midazolam/hydrocodone for FB Stolz D, et al. Eur Respir J. 2009;34:1024-1030.

12. Dexmedetomidine vs Midazolam for Upper Endoscopy 50 adults undergoing upper endoscopy Dexmedetomidine Bolus 1 µg/kg Infusion 0.2 µg/kg/hr ( n = 25) Midazolam 0.07 mg/kg Total dose 5 mg (n = 25) Demiraran Y, et al. Can J Gastroenterol. 2007;21(1):25-29.

13. Upper Endoscopy Results Dexmedetomidine was similar to midazolam –Gagging –Patient satisfaction –Patient discomfort –Anxiety scores –Recovery time Dex was superior to midazolam –Endoscopist satisfaction –Retching –Total number of patients having any type of side effects Variable Midazolam (n = 25) Dex (n = 25) P-value Time to full recovery, min 37.6±1142±12.50.30 Patients fully recovered, n (%) 15 min 12 (48)10 (40)0.56 30 min 20 (80)18 (72)0.74 45 min 25 (100) 0.99 Demiraran Y, et al. Can J Gastroenterol. 2007;21(1):25-29. Recovery

14. Dexmedetomidine Increases Comfort in AFOI Double-blinded randomized trial Midazolam +/- dexmedetomidine Awake fiberoptic intubation (AFOI) Patient comfort rated by 2 observers Bergese SD, et al. J Clin Anesth. 2010;22(1):35-40. Total Comfort Score (max = 35) Pre- oxygenation Introduction of scope Introduction of ET tube n = 24 n = 31

15. Use of Sedation for Colonoscopy Cohen LB. Gastrointest Endosc Clin N Am. 2010;20(4):615-627. Colonoscopies With Sedation (%)

16. Sedative Use for Colonoscopy: USA Cohen LB, et al. Am J Gastroenterol. 2006;101(5):967-974. BZD + Opioid and/or Propofol

17. Endoscopist Choices for Their Own Colonoscopy 41% 14% 8% Cohen LB, et al. Am J Gastroenterol. 2006;101(5):967-974. * More than one answer was permitted Propofol No Sedation BZD Alone Opiod Alone

18. Outpatient Colonoscopy: Study Design 90 colonoscopy patients Dex 1 µg/kg over 15 mins, then 0.2 µg/kg/hr (n = 19) Meperidine 1 mg/kg with midazolam 0.05 mg/kg (n = 21) Fentanyl 0.1-0.2 mg on demand (n = 24) Jalowiecki P, et al. Anesthesiology. 2005;103(2):269-273.

19. Study halted after 64 subjects because of AE in the Dex group Hb saturation and respiration rate variations not observed Outpatient Colonoscopy: Results Jalowiecki P, et al. Anesthesiology. 2005;103(2):269-273. Dex (n = 19) Meperidine (n = 21) Fentanyl (n = 24) Average MAP reduction26%14%3% Maximum BP reduction 50% (4 cases) 35%30% Mean HR reduction17%9%7% Lowest HR40 bpm (2 cases)50 bpm Vertigo & nausea (n)500 Time to discharge readiness (min)853932 Jaw thrust maneuver06 (29%)0

20. Jalowiecki P, et al. Anesthesiology. 2005;103(2):269-273. Outpatient Colonoscopy: Hemodynamics * P < 0.05 after Bonferroni correction

21. Elective Colonoscopy: Can the Patient Control Sedation? Patient-controlled sedation (PCS) with propofol-remifentanil (PR) –Rapid sedation –Rapid recovery –More airway rescue needed with PR than with MDZ-fentanyl Prospective, randomized, open-label trial –n = 25 Patient-controlled sedation (PCS) –n = 25 Anesthesiologist-administered sedation (AAS) Procedure –Outpatient colonoscopy –All patients received propofol-remifentanil –100% oxygen via an anesthesia mask –Continuous spirometry and bispectral index (BIS) monitoring Primary endpoint: oversedation –Respiratory rate –BIS Mandel JE, et al. Gastrointest Endosc. 2010;72(1):112-117.

22. Outpatient Colonoscopy: Respiratory Depression Mandel JE, et al. Gastrointest Endosc. 2010;72(1):112-117. Respiratory Rate (breaths/min) Relative Frequency AAS group used more mean total drug Safety interventions –Criterion: 30s of SaO 2 < 90% –PCS: 0/25 –AAS: 5/25 Median BIS values –PCS: 88.1 –AAS: 71.7 P < 0.001

23. Bariatric Surgery

24. Propofol or BZD/Narcotics for Pre-Surgical Endoscopy? Endoscopy prior to bariatric surgery Anesthesiologist-monitored sedation (AMS) –IV propofol (n = 51) Surgeon-monitored sedation (SMS) –IV narcotics and benzodiazepines Study design –Observational study –Data from patient survey –Doses/regimens not reported Results –Generally no difference between methods –Trend toward amnesia in AMS group Patient YES responses (%) P < 0.02 Madan AK, et al. Obes Surg. 2008;18(5):545-548.

25. Fentanyl vs Dexmedetomidine Use in Bariatric Surgery 20 morbidly obese patients Roux-en-Y gastric bypass surgery All received midazolam, desflurane to maintain BIS at 45–50, and intraoperative analgesics –Fentanyl (n = 10) 0.5 µg/kg bolus, 0.5 µg/kg/h –Dexmedetomidine (n = 10) 0.5 µg/kg bolus, 0.4 µg/kg/h Dexmedetomidine associated with –Lower desflurane requirement for BIS maintenance –Decreased surgical BP and HR –Lower postoperative pain and morphine use (up to 2 h) Feld JM, et al. J Clin Anesthesia. 2006;18:24-28.

26. 80 morbidly obese patients Gastric banding or bypass surgery Prospective dose ranging study Medication –Celecoxib 400 mg po –Midazolam 20 µg/kg IV –Propofol 1.25 mg/kgIV –Desflurane 4% inspired –Dexmedetomidine 0, 0.2, 0.4, 0.8 µg/kg/h IV Dexmedetomidine as Desflurane Adjuvant in Bariatric Surgery Tufanogullari B, et al. Anesth Analg. 2008;106:1741-1748.

27. More dex 0.8 patients required rescue phenylephrine for hypotension than control pts (50% vs 20%, P < 0.05) All dex groups –Required less desflurane (19%–22%) –Had lower MAP for 45’ post-op –Required less fentanyl after awakening (36%–42%) –Had less emetic symptoms post-op No clinical difference –Emergence from anesthesia –Post-op self-administered morphine and pain scores –Length of stay in post-anesthesia care unit –Length of stay in hospital Dexmedetomidine as Desflurane Adjuvant in Bariatric Surgery: Results Tufanogullari B, et al. Anesth Analg. 2008;106:1741-1748.

28. Oral Surgery

29. Endodontists N = 31 Sublingual Triazolam/Halcion (45.2%) Oral Triazolam/Halcion( 19.5%) No Premedication Agents Used (19.4%) MD Anesthesiologists N = 19 All Agents Identified Are Used (52.6%) Intramuscular Ketamine (26.3%) Oral Midazolam (10.5%) Dental Anesthesiologists N = 75 All Agents Identified Are Used (32.0%) Intramuscular Ketamine (22.4%) Intramuscular Ketamine & Midazolam (14.7%) General Dentists N = 144 Oral Triazolam/Halcion (45.1%) No Premedication Agents Used (25.7%) Sublingual Triazolam/Halcion (13.9%) Periodontists N = 55 Oral Triazolam/Halcion (38.2%) No Premedication Agents Used (32.7%) Sublingual Triazolam (14.5%) Pediatric Dentists N = 33 Demerol and Hydroxyzine Elixir (36.4%) Oral Midazolam (27.2%) No Premedication Agents Used (21.2%) Oral/Maxillofacial Surgeons N = 356 No Premedication Agents Used (54.2%) Oral Midazolam (9.6%) Oral Triazolam/Halcion (8.1%) Public Health Practitioner N = 2 Oral Triazolam/Halcion (50.0%) No Premedication Agents Used (50.0%) Prosthodontists N = 2 Oral Triazolam/Halcion (100%) Dental Anesthesia Survey: Premedication by Specialty Boynes SG, et al. Anesth Prog. 2010;57(2):52-58.

30. Dental Anesthesia Survey: Sedation/Anesthesia Method by Specialty Boynes SG, et al. Anesth Prog. 2010;57(2):52-58. OMFS N = 356 Percent DENT ANES N = 75 PED DENT N = 33 PERIO N= 55 OMD ANES N N = 19 GEN DENT N = 144 ENO N = 31 Oral Sedation IV Conscious Sedation IV Deep Sedation GETA

31. Plastic/Reconstructive Surgery

32. Cosmetic Procedures In 2007, 11.7 million procedures in US –Liposuction –Breast augmentation –Eyelid surgery –Abdominoplasty –Breast reduction Site –Surgeons’ offices54% –Ambulatory centers29% –Hospitals17% Shapiro FE. Curr Opin Anaesthesiol. 2008;21(6):704-710.

33. Face Lift Surgery Retrospective study –Single surgeon –Multiple anesthetists Groups –N = 77 Standard of care (mainly propofol, ketamine, fentanyl, and midazolam) –N = 78 SOC plus dexmedetomidine –Not randomized, treated per anesthetist choice –All patients in deep sedation Taghinia AH, et al. Plast Reconstr Surg. 2008;121(1):269-276.

34. Face Lift Surgery: Hemodynamic Results Taghinia AH, et al. Plast Reconstr Surg. 2008;121(1):269-276. SOC+ Dex SOC

35. Laparoscopy

36. Ambulatory Gynecologic Laparoscopy ASA I-II patients N = 60 Prospective Randomized Double blind Remifentanil 1 µg/kg over 10 mins then 0.2 µg/kg/min Dex 1 µg/kg over 10 mins then 0.4 µg/kg/hr Salman N, et al. Saudi Med J. 2009;30(1):77-81.

37. Dexmedetomidine associated with Slower recovery Less nausea and vomiting Lower analgesia requirement Recovery Data Group Remifentanil Group DEX Time to eye opening (mins) 3.5 ±1.14.1 ±1.4 Extubation time (mins) 6.1 ±1.6 *7.3 ±1.3 Orientation to person (mins) 9.1 ±2.3 *10.5 ±1.8 Orientation to place and time (mins) 16.1 ±6.3 *21.2 ±11.7 Discharge time (mins) 200.3 ±29.5224.5 ±49.2 *P < 0.05 Salman N, et al. Saudi Med J. 2009;30(1):77-81. Ambulatory Gynecologic Laparoscopy

38. CV Surgery

39. What Do Neurointerventionalists Prefer for AIS Interventions? *Treated as ordinal 4 = Most frequent 3 = Frequent 2 = Least frequent 1 = Never McDonagh DL, et al. Front Neurol. 2010;1:118.

40. General Anesthesia During AIS Intervention? McDonagh DL, et al. Front Neurol. 2010;1:118.

41. Trial of Dexmedetomidine for CV Procedure: Design Prospective, randomized, double-blinded, placebo-controlled multicenter trial Procedure –AV fistula creation and peripheral vascular stent placement –Local anesthesia or peripheral nerve block Patients randomized 2:2:1 –Dex 1.0 mg/kg load, then infusion of 0.6 mg/kg/h –Dex 0.5 mg/kg load, then infusion of 0.6 mg/kg/h –Normal saline 0.9% infusion Drug titrated to achieve a target OAA/S of ≤ 4 Fentanyl in 25 μg increments IV for pain 1 o EP: % patients not requiring MDZ during infusions Huncke TK, et al. Vasc Endovascular Surg. 2010;44(4):257-261.

42. Trial of Dexmedetomidine for CV Procedure: Results Number (%) of Patients Not Requiring Rescue Midazolam (MDZ) The Perioperative Use of MDZ and Fentanyl Huncke TK, et al. Vasc Endovascular Surg. 2010;44(4):257-261.

43. Sedation/Analgesia for Traumatic Brain Injury Goal: reduce ICP by decreasing pain, agitation Saiki RL. Crit Care Nurs Clin North Am. 2009;21:549-559. AgentAdvantagesConsiderations Propofol Short acting Reduces cerebral metabolism, O 2 consumption Improves ICP after 3d Propofol infusion syndrome Barbiturates Reduce ICP Neuroprotection Interfere with neuro exam Hypotension, reduced CBF OCs not improved with severe TBI

44. 44 Randomized, double-blind, placebo-controlled, multicenter 326 pts undergoing MAC for surgery (orthopedic, ophthalmic, vascular, excision of lesions, others < 10%) All patients sedated –Observer’s Assessment of Alertness/Sedation Scale (OAA/S ) to < 4 Sedation with –Dex ± rescue midazolam, or –Placebo + rescue midazolam Fentanyl PRN for pain MAC with Dexmedetomidine Candiotti KA, et al; MAC Study Group. Anesth Analg. 2010;110(1):47-56. MAC = Monitored anesthesia care

45. * * Midazolam UseFentanyl Use Dexmedetomidine Reduces Fentanyl and Midazolam Use During MAC *P < 0.001 compared with placebo, MAC = monitored anesthesia care ** * * * * Candiotti KA, et al; MAC Study Group. Anesth Analg. 2010;110(1):47-56.