1. Sedation during mechanical ventilation : A trial of benzodiazepine and opiate in combination Crit Care Med 2006 Vol. 34, No. 5 R2 이윤정 Paul S. Richman, MD; Daniel Baram, MD ; Marie Varela, PharmD; Peter S. Glass, MBChB

2. Sedation is often used in the early phase of critical illness, when symptoms are most acute and care is most interventional. In 1995, the Society of Critical Care Medicine (SCCM) : evidence-based medicine recommendations regarding the ‘ preferred’ agents. – Midazolam and propofol : short-term sedation – Lorazepam : long-term sedation – Haloperidol : treating delirium –Morphine and Fentanyl : analgesic agents in critically ill patients. Sedative and analgesic drugs are distinct agents, although complementary and sometimes synergy ( British Journal of Anaesthesia, 2001, Vol. 87, No. 2 186-192 ) Introduction

3. AIM : a randomized trial of the efficacy of continuous sedation with midazolam and fentanyl compared with midazolam alone in ventilated ICU patients at our institution. Ramsay Sedation Scale 1 Patient is anxious and agitated or restless, or both 2 Patient is cooperative, oriented and tranquil 3 Patient responds to commands only 4 Patient exhibits brisk response to light glabellar tap or loud auditory stimulus 5 Patient exhibits a sluggish response to light glabellar tap or loud auditory stimulus 6 Patient exhibits no response

4. ICU from September 2002 to January 2004 : continuous sedation was indicated and mechanical ventilation was likely to continue 48 hrs. Study Procedures : Baseline data collected over 4 hrs included ventilator settings, arterial blood gases, intravenous fluids, and level of sedation, assessed by a modified Ramsay Sedation Score (RSS) “Awakening,” defined as RSS at least one level below (less sedated than) the target RSS. Methods

5. Completion of the Study Protocol : Data collection continued for up to 72 hrs while the patient remained on mechanical ventilation. The primary outcome : variable was the number of hours per day with RSS deviating from its target value Methods

6. Results

7. Table 1. Clinical characteristics of subjects

8. Figure 1. The number of hours per day that patients’ Ramsay sedation score (RSS) deviated from the target value (left bars) was lower in the co-sedation group (p.002, Wilcoxon rank sum test) ; the mean number of dose adjustments per day (right bars) tended to be lower in the co-sedation group (nonsignificant trend).

9. Figure 2. (p =.04) (p =.21) (p =.79)

10. Table 2. Incidence of adverse events

11. First study todirectly assess the impact of co-sedation, compared with a control group not receiving opiates, over a prolonged (3-day) period. First to evaluate in a controlled fashion how this synergism translates to a clinical benefit. Small study size, this difference was statistically significant Discussion

12. Small patient population. 13 of 30 (43%) of our study participants were daily users of alcohol or sedatives RSS is a commonly used tool for assessing adequacy of sedation.  suffers from difficulty in interpretation. Limitation

13. Co-sedation using midazolam and fentanyl in combination is more effective than midazolam alone, without increased toxicity, in mechanically ventilated ICU patients Conclusion