TY - JOUR

T1 - Pharmacological and non-pharmacological interventions to prevent delirium in critically ill patients

T2 - a systematic review and network meta-analysis

AU - Burry, Lisa D.

AU - Cheng, Wei

AU - Williamson, David R.

AU - Adhikari, Neill K.

AU - Egerod, Ingrid

AU - Kanji, Salmaan

AU - Martin, Claudio M.

AU - Hutton, Brian

AU - Rose, Louise

N1 - Funding Information: This study was funded by the Canadian Institutes of Health Research (CIHR) (Grant No. CIHRFRN144048). The funding body did not have input into the design, conduct or reporting of this systematic review.

PY - 2021

Y1 - 2021

N2 - 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 alpha2 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.

AB - 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 alpha2 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.

KW - Critical care

KW - Delirium

KW - Non-pharmacological interventions

KW - Pharmacological

KW - Prevention

U2 - 10.1007/s00134-021-06490-3

DO - 10.1007/s00134-021-06490-3

M3 - Review

C2 - 34379152

AN - SCOPUS:85112345522

VL - 47

SP - 943

EP - 960

JO - European Journal of Intensive Care Medicine

JF - European Journal of Intensive Care Medicine

SN - 0935-1701

IS - 9

ER -