麻豆传媒

Intensive care unit (ICU) patients who received haloperidol (Haldol) for delirium fared no better on the trial's primary outcome at 3 months than those who received placebo.

At 90 days, the mean number of days alive and out of the hospital was 35.8 (95% CI 32.9-38.6) in the haloperidol group and 32.9 (95% CI 29.9-35.8) in the placebo group, with an adjusted mean difference of 2.9 days (95% CI -1.2 to 7.0, P=0.22), reported Nina Andersen-Ranberg, MD, of Zealand University Hospital in Køge, Denmark, and co-authors in the .

Delirium affects 30 to 50% of ICU patients and is associated with increased morbidity and mortality. Clinical practice do not support using haloperidol for delirium because evidence of its effect is limited, Andersen-Ranberg and co-authors observed.

AID-ICU adds to the findings of the MIND-USA study, they noted. In the , ICU patients with delirium were randomly assigned to receive haloperidol, placebo, or ziprasidone (Geodon). The trial showed no significant difference in the number of days alive without delirium or coma or in mortality at 90 days between the haloperidol group and placebo group.

"For 50 years, antipsychotics have been used in the hospital for delirium," said MIND-USA researcher Wes Ely, MD, MPH, of Vanderbilt University in Nashville, Tennessee.

"In MIND-USA, we showed that antipsychotics, including intravenous haloperidol, did not help with delirium," Ely told 麻豆传媒. "That paper got the guidelines changed so they no longer recommend haloperidol."

But there still are clinicians who treat ICU delirium with haloperidol, Ely noted. "There's a danger if they don't get the message that haloperidol isn't of help," he said. "If they keep reaching for this drug whenever a patient has delirium, they turn their brain off about what actually is the right thing to do for that patient."

"MIND-USA told the doctor to quit thinking you are doing the patient a favor by reaching for haloperidol," Ely continued. "Instead, you have to think about how can I actually help the person? Which is get them out of the bed, get the family members there, take care of their underlying disease, and stop the drugs that are causing the delirium, like sedatives and analgesics that are not helping them," he said.

"Nonpharmacological interventions are the treatments of choice for delirium," he emphasized. "That's what the guidelines are helping people focus their attention on."

In AID-ICU, Andersen-Ranberg and co-authors randomly assigned adults with delirium who had been admitted to the ICU for an acute condition to receive intravenous haloperidol (2.5 mg three times daily, plus 2.5 mg as needed up to a total daily dose of 20 mg) or placebo. Other antipsychotic drugs during the ICU stay were not allowed.

Haloperidol or placebo was given as long as delirium continued. The primary outcome was the number of days alive and out of the hospital 90 days after randomization.

A total of 987 patients were included in the final analyses: 501 in the haloperidol group and 486 in the placebo group. The haloperidol group received a median daily dose of 8.3 mg for a median of 3.6 days.

Ninety-day mortality was 36.3% in the haloperidol group and 43.3% in the placebo group (adjusted absolute difference, -6.9 percentage points, 95% CI -13.0 to -0.6). "Although our results suggest that mortality may have been lower with haloperidol than with placebo, no conclusions may be drawn," Andersen-Ranberg and co-authors stated.

"Potential reasons for the suggestion of a between-group difference in mortality that was observed in our trial, as opposed to the findings of the MIND-USA trial, may include a larger sample size, broader inclusion criteria, older patient age, less use of open-label antipsychotic agents, and more patients with hyperactive delirium in our trial than in the MIND-USA trial," they wrote.

Serious adverse reactions occurred in 2.2% of the haloperidol group and 1.9% of the placebo group. The number of patients receiving rescue medication was similar in the two groups. Physical restraint was used in 1.9% of people in the haloperidol group and 2.1% in the placebo group.

The study had little information about co-existing conditions beyond risk factors for delirium. It also lacked details about other sedatives, pain medications, or interventions that patients received that may have influenced some outcomes, including mortality. "That's a real limitation," Ely noted. "We don't know the answer because the study did not record those drugs."

In addition, the composite nature of the primary outcome "may challenge the interpretation of the results, since the point estimate for mortality was lower and the point estimate for length of hospital stay was higher in the haloperidol group than in the placebo group," the researchers acknowledged.

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