#### "Antipsychotic Medications for Delirium in the Intensive Care Unit"
The New England Journal of Medicine.
Pubmed • Full text • PDF

#### Clinical Question
Does the use of haloperidol or ziprasidone reduce the duration of delirium in ICU patients with acute respiratory failure or shock?

#### Bottom Line
In ICU patients with acute respiratory failure or shock, the use of haloperidol or ziprasidone, as compared to placebo, does not significantly alter the duration of delirium.

#### Major Points


#### Guidelines
Current guidelines do not provide clear recommendations on the use of antipsychotic medications for delirium management in the ICU setting, as results from this study.

#### Design
- Randomized, double-blind, placebo-controlled trial
- N=566 ICU patients with delirium due to acute respiratory failure or shock
- Intervention: Haloperidol (max 20 mg/day), ziprasidone (max 40 mg/day), or placebo
- Primary endpoint: Days alive without delirium or coma during 14-day intervention period
- Secondary endpoints: 30-day and 90-day survival, time to freedom from mechanical ventilation, and time to ICU/hospital discharge
- Safety endpoints: Extrapyramidal symptoms and excessive sedation

#### Population
- Inclusion Criteria: ICU patients ≥18 years old with acute respiratory failure or shock and delirium
- Exclusion Criteria: Severe cognitive impairment, high risk for medication side effects, contraindications to study drugs, various other medical exclusions

#### Interventions
- Patients received IV boluses of haloperidol, ziprasidone, or placebo with doses adjusted based on delirium status and side effects
- Median exposure: 4 days
- Co-intervention adherence to the ABCDE bundle was above 88% for all trial groups.

#### Outcomes
- Primary: The median number of days alive without delirium was similar between groups: 8.5 (Placebo), 7.9 (Haloperidol), 8.7 (Ziprasidone) (P=0.26 for overall effect across trial groups)
- Secondary: No significant differences between groups concerning survival or lengths of stay in the ICU and hospital
- Safety: More corrected QT prolongation in ziprasidone group; two cases of torsades de pointes in haloperidol group; no significant difference in other side effects across groups

#### Criticisms
- Trial may not have been adequately powered to detect an effect size of less than 2 days difference in primary outcome
- The effect of higher doses of haloperidol or other antipsychotic medications was not evaluated
- Majority of patients had hypoactive delirium; thus, limited conclusions can be drawn regarding hyperactive delirium
- Excluded certain patient groups that might benefit from antipsychotic treatment, such as those with alcohol withdrawal

#### Funding
Supported by grants from the National Institutes of Health and the Department of Veterans Affairs Geriatric Research Education and Clinical Center.

#### Further Reading
The full article can be found on the New England Journal of Medicine website, ClinicalTrials.gov number NCT01211522.