hot take on the AID-ICU trial of haloperidol for management of delirium in ICU ? this is the largest MC-RCT to date on haloperidol for treatment of delirium (in comparison, MINDS enrolled 192 patients in the haloperidol group).

Haloperidol for the Treatment of Delirium in ICU Patients | NEJM

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Original Article from The New England Journal of Medicine — Haloperidol for the Treatment of Delirium in ICU Patients

https://www.nejm.org/doi/full/10.1056/...

55% of patients had hyperactive delirium. this is much better than MINDS (which contained ~90% hypoactive), but probably still not ideal. (at this point, does anyone actually think that haloperidol helps with hypoactive delirium ??)

other than dilution of the patient population by patients with hypoactive delirium (who are unlikely to benefit & might conceivably be harmed by over-sedation), the methodology seems pretty solid.

patients in the haloperidol group recieved 2.5 mg haloperidol IV q8 plus PRN doses up to a max cumulative dose of 20 mg/day. the median dose of haloperidol was ~8 mg/day for the overall patient population (hyperactive patients probably tended to get more, I would imagine).

the primary endpoint was days alive and outside the hospital. there wasn't a statistically significant benefit, although there was a trend towards benefit - especially among patients with hyperactive delirium.

days alive & out of hospital is a tough endpoint to impact, because there are *so* many reasons patients stay in the hospital (logistics, etc). if we look at delirium-free days, there was a larger signal of possible benefit - but still not a statistically significant difference.

but there was a statistically significant *mortality* benefit in favor of the haloperidol group! hard to interpret exactly what this means (it's probably not replicable). but it's a strong signal that haloperidol is, at a minimum, *safe.*

extrapyramidal side effects seem to be very rare. a few patients were withdrawn due to QT prolongation, but there's no real signal for increased arrhythmia in the haloperidol group:

so, to recap: - largest RCT investigating IV haloperidol for ICU delirium - only 55% with hyperactive delirium (may have diluted benefit) - overall some trends towards benefit, but nonsignificant - patients in the haloperidol group had lower mortality & few adverse events

even before publication of this study, I don't think that anyone really believed that medication is the cure for delirium (haloperidol, or any other drug for that matter) so I don't think that anyone would be using haloperidol for hypoactive delirium - at least I hope not ?

however, for a patient with hyperactive delirium that is interfering with management (e.g., risk of removing lines/tubes), haloperidol seems reasonable to facilitate safe patient care. this study may support that IV haloperidol is a *safe* approach in this scenario.