Ketamine Sedation in the Intensive Care Unit: A Survey, Systematic Review, Network Meta-analysis, and Pilot Study Protocol

Abstract

This thesis consists of two studies presented as two separate manuscripts (one has been published in a peer-reviewed journal and the other is in the process of being submitted to a peer-reviewed journal) and a protocol for a pilot randomized controlled trial. The overarching aim of this thesis was to explore the evidence examining the use of ketamine as a sedative for critically ill mechanically ventilated patients in the Intensive Care Unit (ICU).

We conducted a national survey to understand the beliefs and practices of Canadian ICU physicians regarding the use of ketamine as a continuous intravenous sedative in critically ill patients and to gauge interest in participating in a randomized controlled trial (RCT). We surveyed 400 physician members of the Canadian Critical Care Society and found that most respondents rarely use ketamine as a continuous infusion for sedation or analgesia in the ICU. We found that there were a number of clinical circumstances that would make physicians more likely to use ketamine such as asthma exacerbation and established tolerance to opioids. Conversely, physicians were concerned about the potential side effects of ketamine, particularly psychotropic effects including delirium. Overall, the majority of physicians surveyed agreed that there is a need for a clinical trial to evaluate the effectiveness and safety of ketamine as a sedative infusion in the ICU. The results of this survey informed the second manuscript which is a systematic review examining the use of procedural sedation medications in acutely ill patients.

Prospective data examining ketamine as a continuous sedative in critically ill patients is sparse and insufficient for pooled analysis. Therefore, we focused on an indirect source of evidence, the role of ketamine as a procedural sedation drug. In order to summarize this data, we performed a systematic review and network meta-analysis (NMA) comparing all peri-procedural sedative drugs in acutely ill patients. The NMA provides the ability to include indirect data into the pooled point estimates. We performed a search of multiple databases and found 82 RCTs (8,105 patients) that met eligibility criteria, 78 conducted in the Emergency Department and 4 in the ICU. Compared to alternative medications, we found that ketamine was associated with the fewest respiratory adverse events based on high certainty evidence. Furthermore, we found that combining ketamine with propofol resulted in the highest patient satisfaction (high certainty) and the fewest cardiac adverse events (low certainty).

The final component of this thesis is a pilot RCT protocol examining the feasibility of a larger RCT assessing the efficacy and safety of an adjunctive ketamine continuous infusion in mechanically ventilated ICU patients. We plan to submit this protocol for peer-reviewed funding as a first step to address this clinically important question.