Perioperative Benzodiazepine Use and Incidence of Intraoperative
Awareness: A Systematic Review and Meta-analysis
Haris Saud BHSc1, Henry He BSc1, Eugene Wang BSc1, Emilie
Belley-Côté MD PhD FRCPC2,3, Jessica Spence MD PhD FRCPC3,4
1 Michael G. DeGroote School of Medicine, McMaster University. 2
Department of Medicine (Cardiology), McMaster University. 3
Population Health Research Institute (PHRI), Hamilton, Canada. 4
Departments of Anesthesia and Critical Care, McMaster
University.
Introduction§ Benzodiazepines are used
perioperatively because of minimal effects on hemodynamic
parameters and anxiolytic, sedative, and amnestic properties.
§ Benzodiazepines are also believed to prevent intraoperative
awareness and are recommended by the American Society of
Anesthesiologists for patients at high risk of awareness.
§ The risk of having awareness was significantly decreased with
benzodiazepine administration.
§ However, the risk of not having awareness (which included an
additional five trials) was not statistically different between
benzodiazepine and non-benzodiazepine groups.
Objectives§ We performed a systematic review
and meta-analysis to evaluate the effect of perioperative
benzodiazepine administration on the incidence of intraoperative
awareness
Methods§ We conducted a systematic review in the context of a
larger protocol,
which includes additional outcomes beyond intraoperative
awareness (e.g., delirium incidence and duration, postoperative
cognitive decline, in-hospital mortality, patient satisfaction,
ICU/hospital length of stay, and postoperative nausea and
vomiting.
§ Major databases (Cochrane CENTRAL, MEDLINE, EMBASE, PsychINFO,
CINAHL, and Web of science) were searched from inception to
February 2019 for randomized controlled trials (RCTs) evaluating
the administration of benzodiazepines as compared to any other
medication/control in patients undergoing cardiac and noncardiac
surgery.
§ Two reviewers used a predefined eligibility criteria to
independently perform duplicate and abstract screening, full-text
review, data extraction, and risk of bias assessment using the
Cochrane Collaboration risk of bias (ROB) tool.
§ We pooled trial results using a random effects model. Because
of low event rates, we undertook a sensitivity analysis assessing
the probability of not having awareness when benzodiazepines were
administered.
§ We evaluated the quality of evidence using the Grading of
Recommendations, Assessment, Development and Evaluation (GRADE)
approach.
Results§ After duplicate removal, 26161 studies were screened,
688 studies
underwent full-text review, and eleven trials were included.§
These eleven RCTs included 1611 patients (655 in benzodiazepine
arms and 956 in non-benzodiazepine arms) that reported on
intraoperative awareness.
§ Using the Cochrane ROB tool, we judged the risk of bias to be
high in four studies and unclear for the remaining seven (see
Figure 1).
§ The overall incidence of awareness across all studies was
3.0%.
Conclusions§ Intraoperative awareness is rare and, although it
remains unclear
whether benzodiazepines prevent awareness, it is unlikely they
have a large effect on this outcome.
§ The quality of evidence for this inquiry is currently very
low. § Further trials, with larger sample sizes, are recommended
to
investigate the extent of the effect of benzodiazepines on
intraoperative awareness.
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Haris Saud, BHScMichael G. DeGroote School of Medicine, McMaster
University, Hamilton, CanadaEmail: [email protected]
§ The risk of awareness was significantly decreased when
benzodiazepines were administered (RR = 0.37, 95% CI = [0.21,
0.64], P = 0.0004, I2 = 0%), although this analysis excluded five
trials with no events (see Figure 2, top).
§ When we considered the risk of not having awareness, all
eleven trials were included and there was no significant difference
between benzodiazepine and non-benzodiazepine groups (RR = 1.05,
95% CI = [0.97, 1.14], P = 0.22, I2 = 94%, very low quality of
evidence) (see Figure 2, bottom).
§ We were unable to explain observed heterogeneity using
pre-specified subgroup analyses.
Figure 1. Risk of Bias Analysis
Figure 2. Forest plot comparisons of benzodiazepine and
non-benzodiazepine groups and risk of having awareness (top) and
risk of not having awareness (bottom)
