Journal Article

Pharmacological and non-pharmacological interventions to prevent delirium in critically ill patients: a systematic review and network meta-analysis

Adhikari, Neill K., Rose, Louise, Hutton, Brian, Williamson, David R., Cheng, Wei, Martin, Claudio M., Egerod, Ingrid, Kanji, Salmaan, Burry, Lisa D.

2021

Overview

Purpose To compare the effects of prevention interventions on delirium occurrence in critically ill adults. Methods MEDLINE, Embase, PsychINFO, CINAHL, Web of Science, Cochrane Library, Prospero, and WHO international clinical trial registry were searched from inception to April 8, 2021. Randomized controlled trials of pharmacological, sedation, non-pharmacological, and multi-component interventions enrolling adult critically ill patients were included. We performed conventional pairwise meta-analyses, NMA within Bayesian random effects modeling, and determined surface under the cumulative ranking curve values and mean rank. Reviewer pairs independently extracted data, assessed bias using Cochrane Risk of Bias tool and evidence certainty with GRADE. The primary outcome was delirium occurrence; secondary outcomes were durations of delirium and mechanical ventilation, length of stay, mortality, and adverse effects. Results Eighty trials met eligibility criteria: 67.5% pharmacological, 31.3% non-pharmacological and 1.2% mixed pharmacological and non-pharmacological interventions. For delirium occurrence, 11 pharmacological interventions (38 trials, N  = 11,993) connected to the evidence network. Compared to placebo, only dexmedetomidine (21/22 alpha 2 agonist trials were dexmedetomidine) probably reduces delirium occurrence (odds ratio (OR) 0.43, 95% Credible Interval (CrI) 0.21–0.85; moderate certainty). Compared to benzodiazepines, dexmedetomidine (OR 0.21, 95% CrI 0.08–0.51; low certainty), sedation interruption (OR 0.21, 95% CrI 0.06–0.69; very low certainty), opioid plus benzodiazepine (OR 0.27, 95% CrI 0.10–0.76; very low certainty), and protocolized sedation (OR 0.27, 95% CrI 0.09–0.80; very low certainty) may reduce delirium occurrence but the evidence is very uncertain. Dexmedetomidine probably reduces ICU length of stay compared to placebo (Ratio of Means (RoM) 0.78, CrI 0.64–0.95; moderate certainty) and compared to antipsychotics (RoM 0.76, CrI 0.61–0.98; low certainty). Sedative interruption, protocolized sedation and opioids may reduce hospital length of stay compared to placebo, but the evidence is very uncertain. No intervention influenced mechanical ventilation duration, mortality, or arrhythmia. Single and multi-component non-pharmacological interventions did not connect to any evidence networks to allow for ranking and comparisons as planned; pairwise comparisons did not detect differences compared to standard care. Conclusion Compared to placebo and benzodiazepines, we found dexmedetomidine likely reduced the occurrence of delirium in critically ill adults. Compared to benzodiazepines, sedation-minimization strategies may also reduce delirium occurrence, but the evidence is uncertain.

• Publisher: Springer Berlin Heidelberg,Springer,Springer Nature B.V
• Subject: Adult / Adults / Analysis / Anesthesia / Anesthesiology / Antipsychotic drugs / Antipsychotics / Arrhythmia / Bayes Theorem / Bayesian analysis / Benzodiazepines / Bias / Canada / Clinical trials / Critical care / Critical Care Medicine / Critical Illness / Delirium / Delirium - prevention & control / Dexmedetomidine / Emergency Medicine / Humans / Intensive / Length of stay / Mechanical ventilation / Medicine / Medicine & Public Health / Meta-analysis / Mortality / Narcotics / Non-pharmacological intervention / Ontario / Opioids / Pain Medicine / Patients / Pediatrics / Pharmacology / Placebos / Pneumology/Respiratory System / Ramelteon / Randomized Controlled Trials as Topic / Ranking / Rankings / Remifentanil / Respiration, Artificial - adverse effects / Systematic Review / United Kingdom / United States / Ventilation / Ventilators