Antipsychotics don't help in hypoactive ICU delirium: MIND-USA

But what about agitated delirium--the reason antipsychotics are actually prescribed?

Neither typical antipsychotics (haloperidol) or newer antipsychotics (ziprasidone) were effective in treating delirium in critically ill patients, in a major randomized trial.

However, nearly all the patients (~90%) had “hypoactive delirium”—not the agitated (“hyperactive”) delirium antipsychotics are almost always prescribed for in the ICU.

Authors enrolled 1,183 adult patients at medical or surgical ICUs at 16 U.S. medical centers who developed delirium while critically ill (on ventilators, BiPAP, vasopressors, or with an intra-aortic balloon pump). Delirium was identified with the CAM-ICU screen.

The delirious ICU patients were randomized to receive either haloperidol (up to 20 mg IV once daily), ziprasidone (40 mg daily), or placebo, for 14 days.

Patients in all three arms had statistically equivalent days free of delirium or coma (about 8 days). The results were reported in the New England Journal of Medicine.

Secondary endpoints -- length of stay in the ICU and hospital; ventilator-free days; or mortality at 30 and 90 days -- were not statistically different either.

Patients receiving antipsychotics did not have significant increases in excessive sedation compared to placebo. More patients receiving ziprasidone experienced prolonged QT intervals on electrocardiogram.

Results from MIND-USA are even more persuasive in the wake of findings from the REDUCE and Hope-ICU trials, neither of which showed a benefit of haloperidol in prevention of ICU delirium.

Treatment with antipsychotics was not obviously harmful, and their use in the ICU is justified occasionally, according to an editorialist:

There will still be some appropriate use of antipsychotics in the ICU, but it is for difficult to control patients who are being dangerous to themselves or others, and the antipsychotic meds can help with symptom control without suppressing respirations, so that can be very clinically helpful and safe."

Prophylactic dexmedetomidine (Precedex) did reduce the incidence of ICU delirium in a randomized trial. There are currently over 90 studies planned or in process exploring the role of so-called "Dex" for the prevention or treatment of delirium.

Study authors used the negative trial results to encourage the use of the so-called ABCDEF bundle, promoted by a major professional society in critical care. It includes sedation interruptions, spontaneous breathing trials, delirium assessments, lightest-reasonable sedation, early mobility, and involving patients' families, and its implementation is associated with better ICU outcomes.

The MIND-USA trial is a kind of bait-and-switch for the practicing clinician. The trial did not ask or answer the question, “do antipsychotics as used in the ICU to calm dangerously agitated patients improve delirium and other outcomes?”

Only about 120 patients had hyperactive delirium out of the 1,183 subjects. That’s not enough power to draw any conclusions about antipsychotics’ benefits in agitated and delirious patients in the ICU—the patients on whom haloperidol and ziprasidone are typically used.

Source: NEJM