Critical
Care volume 29, Article number: 126 (2025) Published: 20
March 2025
Background
Although haloperidol is commonly used to treat or prevent
delirium in intensive care unit (ICU) patients, the evidence remains
inconclusive. This study aimed to comprehensively evaluate the efficacy and
safety of haloperidol for delirium treatment and prevention in ICU patients.
Methods
We searched MEDLINE, the cochrane central register of
controlled trials, EMBASE, ClinicalTrial.gov, and PubMed without language
restrictions from database inception to June 27, 2024. We included double-blind
randomized controlled trials (RCTs) on haloperidol versus placebo for treating
and preventing delirium in adult ICU patients. In addition to frequentist
analyses, Bayesian analysis was used to calculate the posterior probabilities
of any benefit/harm and clinically important benefit/harm (CIB/CIH). The primary
outcomes for delirium treatment were all-cause mortality and serious adverse
events (SAEs). For delirium prevention, the primary outcomes included incident
delirium, all-cause mortality, and SAEs. The secondary outcomes for efficacy
were delirium-or coma-free days, ventilator-free days, length of stay in ICU,
length of stay in hospital, and rescue benzodiazepine use. The secondary
outcomes for safety were QTc prolongation and extrapyramidal syndrome.
Results
We included seven RCTs on delirium treatment (n = 1767)
and five on delirium prevention (n = 2509). The Bayesian analysis
showed that, compared to placebo for delirium treatment, haloperidol had a 68%
probability of achieving CIB (defined as risk difference [RD] < −0.02) in
reducing all-cause mortality, a 2% probability of achieving CIH (RD > 0.02) in causing SAEs, and a 78% probability of
achieving CIB (RD < −0.02) in
reducing the need for rescue benzodiazepine use. The probabilities of
haloperidol causing CIH (RD > 0.02) across all other safety
outcomes were low (all < 50%). In frequentist analysis on
delirium treatment, the pooled estimated RD for haloperidol compared to placebo
was -0.05 (−0.09, −0.00; I2 = 0%)
for rescue benzodiazepine use. In Bayesian analysis on delirium prevention,
haloperidol had a 12% probability of achieving CIB in all-cause mortality, a
34% probability of achieving CIB in delirium incidence, and a 0% probability of
achieving CIB in SAEs. Importantly, haloperidol had a 65% probability of
causing CIH (risk ratio > 1.1) for QTc prolongation, while
the posterior probabilities of achieving CIB across all efficacy outcomes were
low (all < 50%). In frequentist analysis on
delirium prevention, all primary and secondary outcomes were not statistically
significant in frequentist analysis.
Conclusion
Our study supported the use of haloperidol for delirium
treatment in adult ICU patients, but not for delirium prevention.
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