article179

AID-ICU

"Haloperidol for Delirium in Intensive Care Unit Patients".

The New England Journal of Medicine. Year Published. Volume(Issue):pages.
PubMed•Full text•PDF

1 Clinical Question
2 Bottom Line
3 Major Points
4 Guidelines
5 Design
6 Population
6.1 Inclusion Criteria
6.2 Exclusion Criteria
6.3 Baseline Characteristics
7 Interventions
8 Outcomes
8.1 Primary Outcomes
8.2 Secondary Outcomes
9 Criticisms
10 Funding
11 Further Reading

Clinical Question

Does the use of haloperidol lead to a greater number of days alive and out of the hospital at 90 days compared to placebo in ICU patients with delirium?

Bottom Line

The use of haloperidol in ICU patients with delirium did not result in a significantly greater number of days alive and out of the hospital at 90 days compared to placebo.

Major Points

Guidelines

Currently, the use of haloperidol is not supported by clinical practice guidelines as evidence of its effect on delirium in ICU patients is limited.

Design

- Multicenter, blinded, parallel-group, randomized, placebo-controlled trial.
- N=1,000 patients with acute ICU admission and delirium.
- Haloperidol vs. placebo.
- Enrollment: June 14, 2018 - April 9, 2022.
- Mean follow-up: 90 days after randomization.
- Analysis: Intention-to-treat.
- Primary outcome: Number of days alive and out of the hospital at 90 days after randomization.

Population

Inclusion Criteria: Adult patients 18 years or older admitted to ICU for an acute condition with delirium diagnosed by CAM-ICU or ICDSC.
Exclusion Criteria: Patients ineligible based on CAM-ICU or ICDSC criteria.
Baseline Characteristics: Balanced between the two groups; included both hypoactive and hyperactive delirium patients.

Interventions

Patients received either intravenous haloperidol (2.5 mg 3 times daily plus as-needed doses up to 20 mg) or placebo. Treatment was administered in the ICU for as long as delirium continued and as needed for recurrences.

Outcomes

Primary Outcomes: The mean number of days alive and out of the hospital at 90 days was 35.8 in the haloperidol group and 32.9 in the placebo group (P=0.22). Mortality at 90 days was 36.3% in the haloperidol group and 43.3% in the placebo group.
Secondary Outcomes: Number of days alive without delirium or coma in the ICU, number of days alive without mechanical ventilation, the number of patients with serious adverse reactions, number of patients receiving rescue medication, and days with rescue medication per patient.

Criticisms

Low number of international sites and potential selection bias in screening may limit generalizability. The composite nature of the primary outcome and lack of detailed data on coexisting conditions and sedative use are limitations for interpretation of the trial results.

Funding

The trial was supported by grants from Innovation Fund Denmark, the Regional Medicines Fund, Zealand Region Research Fund, Intensive Care Symposium Hindsgavl, and the Foghts Foundation.