Adverse Effects Associated With Multimodal Analgesic Regimens in Critically Ill, Nonintubated Patients: A Systematic Review and Meta-Analysis.

Objective: To evaluate the safety of utilizing multimodal analgesic regimens in critically ill, nonintubated patients. Data Sources: A systematic review was conducted using Embase, MEDLINE, Cochrane, SciELO, Web of Science, and the Korean Journal Index. Clinical trials of critically ill, nonintubated patients that contained complete safety outcomes date, including the incidence of specific adverse drug effects (ADE) associated with a multimodal analgesic medication or regimen, were included. Study Selection and Data Extraction: The primary outcome was the incidence of adverse drug effects associated with multimodal analgesics in comparison to standard-of-care analgesic strategies in our patient population. The secondary outcome was a subgroup analysis of adverse drug effect by type and by medication. Data Synthesis: 10 trials were included in this systematic review, of which 6 were randomized control trials that were evaluated in the meta-analysis. There was no statistically significant difference with respect to the primary outcome (mean difference = -0.11, P = 0.31, 95% CI = [-0.35, 0.13]). The subgroup analysis, which was conducted on randomized clinical control trials that documented a single adjunctive analgesic rather than a multimodal regimen, was stratified by the type of adverse effect encountered and the medication in question. There were no statistically significant findings regarding the incidence of specific ADE. Nonrandomized data included in this study support these findings. Conclusions: While concerns of the additive deleterious adverse effects commonly encountered in polypharmacy are valid, our findings support the use of multimodal analgesic regimens in the provision of analgesic in critically ill, nonintubated patients.