Table 4

A priori hypotheses to explain clinical heterogeneity

SubgroupHypothesis deliriumHypothesis postoperative cognitive impairment
Comparisons to dexmedetomidineComparison with dexmedetomidine will show more delirium with benzodiazepines.Comparison with dexmedetomidine will show more postoperative cognitive impairment with benzodiazepines.
Comparisons to propofolComparison with propofol will show more delirium with benzodiazepines.Comparison with propofol will show more postoperative cognitive impairment with benzodiazepines.
Comparisons to opioidsComparison with opioids will show more delirium with opioids.Comparison with opioids will show more postoperative cognitive impairment with benzodiazepines.
Higher dose (5 mg midazolam equivalent) or infusion vs lower dose (<5 mg midazolam equivalent) or bolus dosingHigher dose or infusion administration will be associated with an increased risk of delirium.Higher dose or infusion administration will be associated with an increased risk of postoperative cognitive impairment.
High risk of bias vs low risk of biasHigh risk of bias studies will be associated with larger risk of delirium.High risk of bias studies will show more cognitive impairment.
Elderly (>75 years) vs younger patientsDelirium will be more common when benzodiazepines are administered to elderly patients.Postoperative cognitive impairment will be more common when benzodiazepines are administered to elderly patients.
Preoperative and intraoperative benzodiazepine administration vs postoperative benzodiazepine administrationDelirium will be more common when benzodiazepines are administered after surgery and opposed to when benzodiazepines are administered preoperatively or intraoperatively.Postoperative cognitive impairment will be more common when benzodiazepines are administered after surgery and opposed to when benzodiazepines are administered preoperatively or intraoperatively.