Chest
Volume 119, Issue 4, April 2001, Pages 1151-1159
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Clinical Investigations in Critical Care
Propofol vs Midazolam for ICU Sedation: A Canadian Multicenter Randomized Trial

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Study objectives

To determine whether sedation with propofol would lead to shorter times to tracheal extubation and ICU length of stay than sedation with midazolam.

Design

Multicenter, randomized, open label.

Setting

Four academic tertiary-care ICUs in Canada.

Patients

Critically ill patients requiring continuous sedation while receiving mechanical ventilation.

Interventions

Random allocation by predicted requirement for mechanical ventilation (short sedation stratum, < 24 h; medium sedation stratum,≥≥ 24 and < 72 h; and long sedation stratum, ≥≥ 72 h) to sedation regimens utilizing propofol or midazolam.

Measurements and results

Using an intention-to-treat analysis, patients randomized to receive propofol in the short sedation stratum (propofol, 21 patients; midazolam, 26 patients) and the long sedation stratum (propofol, 4 patients; midazolam, 10 patients) were extubated earlier (short sedation stratum: propofol, 5.6 h; midazolam, 11.9 h; long sedation stratum: propofol, 8.4 h; midazolam, 46.8 h; p < 0.05). Pooled results showed that patients treated with propofol (n = 46) were extubated earlier than those treated with midazolam (n = 53) (6.7 vs 24.7 h, respectively; p < 0.05) following discontinuation of the sedation but were not discharged from ICU earlier (94.0 vs 63.7 h, respectively; p = 0.26). Propofol-treated patients spent a larger percentage of time at the target Ramsay sedation level than midazolam-treated patients (60.2% vs 44.0%, respectively; p < 0.05). Using a treatment-received analysis, propofol sedation either did not differ from midazolam sedation in time to tracheal extubation or ICU discharge (sedation duration, < 24 h) or was associated with earlier tracheal extubation but longer time to ICU discharge (sedation duration, ≥≥ 24 h, < 72 h, or ≥≥ 72 h).

Conclusions

The use of propofol sedation allowed for more rapid tracheal extubation than when midazolam sedation was employed. This did not result in earlier ICU discharge.

Section snippets

Trial Design

This study was a multicenter, randomized, open-label trial conducted in four ICUs in academic medical centers across Canada. These centers were characterized as follows: center 1, a surgical and trauma ICU; center 2, a mixed population of medical-surgical patients and the regional trauma unit; center 3, a mixed medical-surgical unit that also admitted postoperative cardiac surgical cases; and center 4, a mixed medical-surgical unit that was a referral center for patients with difficult,

Results

The trial flow diagram28 is presented in Figure 1. Initial treatment assignment and stratification were equally distributed among centers (data not shown). The trial was terminated prematurely for fiscal reasons.

There were 11 deaths in the midazolam group (13.9%) and 15 deaths (19.5%) in the propofol group (p = 0.37). Hypotension and ventricular tachycardia leading to death developed in one patient receiving propofol, and propofol administration was thought to have possibly contributed to that

Discussion

In this multicenter randomized trial, the use of propofol compared to midazolam for sedation of patients in the ICU was associated with a reduced time to tracheal extubation in evaluable patients, but there was either no difference or a prolonged time to ICU discharge.

We can only speculate as to why ICU discharge was delayed. It could perhaps be explained by problems in the systematic handling of patients within these institutions. For example, any pharmacokinetic advantage to earlier tracheal

Conclusion

Propofol was a satisfactory agent for ICU sedation in this randomized multicenter trial. It permitted earlier tracheal extubation compared to midazolam but did not permit earlier ICU discharge.

Additional Study Investigators

David Stewart, MSc, Study Monitor, Ottawa Civic Hospital, Ottawa, Ontario, Canada; Hugh Devitt, MD, Safety Review Committee, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada; Craig Guenther, MD, Safety Review Committee, University of Alberta Hospitals, Edmonton, Alberta, Canada; Mauricio Calero, MD, Commercial Products Manager, Zeneca Pharma Inc., Mississauga, Ontario, Canada; and Hector Leon, BSc STAT, Data Entry and Statistical Analysis, St. Paul's Hospital, Vancouver, British

Ramsay Sedation Scale

  • 1.

    Anxious and agitated, or restless, or both22

  • 2.

    Cooperative, oriented, and tranquil

  • 3.

    Responding to commands only

  • 4.

    Brisk response to glabellar tap

  • 5.

    Sluggish response to glabellar tap

  • 6.

    No response to light glabellar tap

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  • Cited by (0)

    Presented in part to the American College of Chest Physicians Annual Meeting, New Orleans, LA, October 26––30, 1997.

    This research was supported by Zeneca Pharma Inc. Canada. Dr. Hall has received consultation fees from Zeneca Pharma Inc. and Hoffman-LaRoche Limited. He has no equity interest in either company. Drs. Sandham, Cardinal, Tweeddale, and Anis, and Mr. Moher and Mrs. Wang have no financial relationship with either company.

    A list of additional study investigators is located in Appendix 1

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