Conscious Sedation

1. Conscious Sedation Morbidity, Mortality, and a Review of the Literature Nathaniel S. Winstead, MD, MS

2. Overview Why sedate? Guidelines for sedation bolus vs intermittent combination therapy - midazolam and meperidine Adverse outcomes Endoscopy without sedation Alternatives to sedation

3. Case #1 57 year old man presents with rectal bleeding PMH PVD, CAD, ESRD on dialysis PSH: CABG Meds: Norvasc, Metoprolol, Epogen, Clonidine, ASA Labs: Hct 21 (baseline 29)

4. Case #1 (con�t) 2u of PRBC�s during dialysis Directly to endoscopy after dialysis BP 154/72, HR 82, O2 Sats 98% Versed 3mg IVP, Demerol 50mg IVP as a single bolus 20 minutes into the procedure, seizure-like activity noted, O2 saturation 96%, no hypotension initially, but quickly develops PEA Code called- Narcan/Flumazenil, Epi/Atropine Patient expires

5. Case #2 96 year old male s/p CVA undergoing PEG for enteral nutrition Versed 2mg IVP, Demerol 50mg IVP as a single bolus BP at baseline 147/71, P 63, O2 Sat 95%, 8 minutes later BP 49/35 mm Hg, HR 65, apneic Receives Flumazenil and Narcan BP and spontaneous respirations restored

6. Case #3 56 year old female intubated x 10days for profound hypothyroidism and diaphragmatic dysfunction Extubated x 5d prior to EGD Baseline: BP 123/71, HR 96, O2 Sats 100% Midazolam 3mg IVP, Meperidine 50mg IVP as single bolus 10 minutes later: BP 85/46, HR 99, O2 Sats 99% Receives � amp Narcan (? b/p recovery?) 2.5 hrs post EGD, re-intubated for hypercapnia

7. Overview

8. Why give sedation? Outcomes One study (Canada) demonstrated that sedation was a predictor of procedural success (OR 3.8, 95% CI 2.5-5.7) However, in those over 75 a trend was observed predicting effectiveness of placebo over active medication (OR 0.75, 95% CI 0.25-2.3) Total cost of procedure and recovery time higher for active medication group 10% cross over from placebo arm to active medication arm

9. Why give sedation? Outcomes Non-western patients (Finnish) undergoing colonoscopy either received midazolam (average dose 2.9 mg), placebo, or nothing No difference between the groups in measures of technical success (cecal intubation rate, procedure time) One study of American patients had 95% success rates of unsedated colonoscopies (age group? indications?) Similar results in 2 other studies, but all had similar limitations � one endoscopist, no randomization

10. Why give sedation? Satisfaction Studies of sedated patients predict that more educated patients and those who underwent longer procedures were more likely to be dissatisfied (?) Usually measured as willingness to repeat the procedure and patient tolerance (pain, anxiety, etc.)

11. Why give sedation? Satisfaction A study of Japanese patients showed significantly decreased pain and anxiety and significantly increased patient cooperation in patients receiving midazolam prior to colonoscopy (where is the data?)

12. What guidelines are available? Why do we use midazolam and meperidine? How should we sedate?

13. Definition of Levels of Sedation

14. ASA Practice Guidelines for Sedation and Analgesia Synopsis: Patients should be expressly consented for sedation. Preparation, monitoring, recording, support staff, training, etc. Do not do deep sedation in office procedures � unless you�re equipped. Do not use induction agents (propofol, methohexital, or ketamine) � unless you�re equipped.

15. ASA Physical Status Classification System � Predict risk P1 � A normal, healthy patient P2 � A patient with mild systemic disease P3 � A patient with severe systemic disease P4 � A patient with severe systemic disease that is a constant threat to life P5 � A moribund patient who is not expected to survive without the operation P6 � A declared brain-dead patient whose organs are being removed for donor purposes

16. Why do we use midazolam and meperidine? In the beginning (?) endoscopists used various agents especially barbiturates which were usually given in small doses intramuscularly (historical � you need to be more specific) Advanced therapeutic endoscopy became widely applied at about the same time that benzodiazepines came to market.

17. Why do we use midazolam and meperidine? Complications: IV access � pain, localized reactions, phlebitis, septic phlebitis Topical analgesia � diminished gag, true allergy, systemic absorbtion causing arrhythmias, seizures, altered mental status Drug administration � oversedation, hypotension, arrhythmias, respiratory depression

18. Why do we use midazolam and meperidine? TOO MANY WORDS Initially the preferred benzodiazepine for endoscopy was IV diazepam. Diazepam is poorly water soluble and IV diazepam causes significant chemical phlebitis. Midazolam has a superior amnestic effect compared to diazepam and shorter recovery times Initially midazolam was dosed identically to diazepam, but in 1987 an FDA warning was issued advising lower doses. �Fatally easy to give� Colonoscopy and EGD can be painful procedures, so using a narcotic in combination is reasonable. Meperidine is inexpensive, particularly compared to fentanyl. Using a combination of a sedative and a narcotic reduces the dose requirement of each, but pharmacodynamic studies of �synergy� are lacking and literature is equivocal with regards to a combination being more effective than a single agent. ASA/ASGE guidelines: �The propensity for combinations of sedative and analgesic combinations to cause respiratory depression and airway obstruction emphasizes the need to appropriately reduce the dose of each component as well as the need to continually monitor respiratory function.�

19. Why do we use midazolam and meperidine? Diazepam - poorly water soluble, causes phlebitis Midazolam - superior amnestic effect, shorter recovery time Midazolam - 1987 FDA advised lower doses. �Fatally easy to give� Colonoscopy and EGD may be painful, narcotic added to benzo Meperidine is inexpensive compared to fentanyl Combination of a sedative and a narcotic ? dose requirement of each pharmacodynamic studies of �synergy� are lacking literature is equivocal combination more effective than a single agent? ASA/ASGE guidelines: �The propensity for combinations of sedative and analgesic combinations to cause respiratory depression and airway obstruction emphasizes the need to appropriately reduce the dose of each component as well as the need to continually monitor respiratory function.�

20. How should we sedate? ASGE and ASA recommend titration Initial doses of midazolam of 0.5 to 2.0 mg followed by doses of 0.5 to 1 mg with at least two minutes between doses. �improves patient comfort and decreases cost� Expert opinion Two large RCTs demonstrate that in outpatients a single bolus is safe and effective (show the data?) One recent study of sedation by a titration approach showed 67.5% of patients were deeply sedated (how was this determined)

21. How should we sedate? A study performed in the USA randomized 101 patients to either receive a single bolus of midazolam/meperidine or titration with midazolam/meperidine until they had ptosis or slurred speech or hypoxemia or hypotension precluded further sedation. Age 18-65, no active use of narcotics or benzodiazepines, no pulmonary disease requiring home oxygen, no NYHA class III or IV, no ESLD, no ESRD

22. How should we sedate?

23. How should we sedate?

24. How should we sedate? An Italian study randomized 253 patients undergoing colonoscopy to either 5mg midazolam bolus + placebo or 5mg midazolam bolus + 50mg meperidine bolus. Pts aged 18-75, no chronic benzodiazepine use, ASA class P1 or P2 only, no major psychiatric disease, no previous colon resection, had to be willing to undergo unsedated endoscopy (?), first time procedures only. No difference in outcomes between the groups in rates of technical success, procedure time, or endoscopist rating of difficulty.

25. How should we sedate?

26. How do we prevent adverse events? Follow the guidelines � limit sedation to moderate, have properly trained staff, resuscitation equipment. Even unsedated procedures carry significant risk of cardiopulmonary AEs. Unsedated EGDs performed in cirrhotic pts and non-cirrhotic controls � no significant differences.

27. Which patients can undergo unsedated endoscopy? Older patients Men Patients who are not anxious Absence of abdominal pain history

28. What alternatives are available? Combined audio/visual distraction decreased requirements for sedative medication (physician-administered) and patient�s perceived pain in one study. Another study by the same group showed music alone decreased the amount of patient-administered sedation.