The Effect of Ketamine on Hypoventilation During Deep Sedation with Midazolam and Propofol: a Randomised, Double-blind, Placebo-controlled Trial

Background: Hypoventilation is a major cause of morbidity and mortality in patients having procedures under sedation. Few clinical strategies have been evaluated to reduce intraoperative hypoventilation during surgical procedures under deep sedation.

Objective: The primary objective of this investigation was to examine the effect of ketamine on hypoventilation in patients receiving deep sedation for surgery with midazolam and propofol.

Design: The study was a randomised, placebo-controlled, double-blind clinical trial.

Setting: Intraoperative.

Patients: Healthy women undergoing breast surgery.

Intervention: Randomised to receive ketamine (0.5 mg kg bolus, followed by an infusion of 1.5 μg kg min) or isotonic saline.

Main Outcome Measure: Duration of hypercapnia measured continuously with a transcutaneous carbon dioxide (TCO2) monitor.

Results: Fifty-four participants were recruited. Patient and surgical characteristics were similar between the study groups. The median percentage of the sedation time with TCO2 more than 6.7 kPa in participants in the ketamine group, 1.2% (95% confidence interval, CI, 0 to 83), was less than that in the isotonic saline group (65%, 95% CI, 0 to 88; P = 0.01). Severe hypoventilation (TCO2 >8.0 kPa) was also less in the ketamine group, median 0% (95% CI, 0 to 11.7) compared with 28% (95% CI, 0 to 79.3; P = 0.0002) for the isotonic saline group. The ketamine group required less airway manoeuvres (chin lift) to keep the SaO2 greater than 95% median (95% CI) [0 (0 to 3) compared with 3 (0 to 16) in the isotonic saline group] (P = 0.004).

Conclusion: Ketamine decreased the duration and severity of hypercapnia in patients undergoing deep sedation with propofol. The addition of ketamine may reduce hypoventilation and adverse effects in patients having procedures under sedation.

Trial Registration: clinicaltrials.gov identifier: NCT01535976.