### Antipsychotic Medications for Delirium in the Intensive Care Unit (MIND-USA Study)
Links to original sources: Wiki Journal Post Full Journal Article
#### "Antipsychotic Medications for Delirium in the Intensive Care Unit" The New England Journal of Medicine. Pubmed • Full text • PDF
Does the use of haloperidol or ziprasidone reduce the duration of delirium in ICU patients with acute respiratory failure or shock?
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.
Delirium is common in critically ill patients and is associated with increased mortality, longer ICU stay and hospitalization, increased costs, and higher risk of long-term cognitive impairment. Antipsychotic medications like haloperidol and ziprasidone have been commonly used to manage delirium in the ICU despite limited evidence from smaller trials. The current MIND-USA study found no significant difference in delirium duration with haloperidol, ziprasidone, or placebo.
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.
- 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
- 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
- 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.
- 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
- 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
Supported by grants from the National Institutes of Health and the Department of Veterans Affairs Geriatric Research Education and Clinical Center.
The full article can be found on the New England Journal of Medicine website, ClinicalTrials.gov number NCT01211522.