In this episode, I’ll discuss the effects of ED length of stay when using either midazolam+haloperidol or lorazepam+haloperidol for acute agitation.
Midazolam has a faster onset and shorter time to awakening than lorazepam. ED treatment of acute agitation often includes haloperidol given in combination with a benzodiazepine, and it is not clear whether the onset and offset advantages of midazolam persist when combined with haloperidol in a real-world setting. In order to investigate this, researchers at Northwestern University’s Feinberg School of Medicine published a before-after study using their own large urban ED’s experience.
In January 2019 their institutional guidelines for acute agitation were changed to favor the combination of midazolam 5 mg plus haloperidol 5 mg for parenteral treatment of acute agitation that does not respond to non-pharmacologic de-escalation measures. This recommendation replaced previous guidelines that called for lorazepam 2 mg plus haloperidol 5 mg when parenteral treatment of acute agitation was needed.
This change was made in hopes of the shorter onset/offset for midazolam translating to a shorter ED length of stay for affected patients. The guideline change was rapidly adopted which provided a naturally occurring before-after scenario that the researchers used to study whether effects on ED length of stay were in fact realized.
In their analysis, the authors used only those ED visits in which the combination of 5mg midazolam + 5mg haloperidol or 2mg lorazepam + 5mg haloperidol was co-administered. Almost 1200 patients were included, 618 who received midazolam/haloperidol and 555 who received lorazepam/haloperidol. ED length of stay and serious adverse events were analyzed. In both unadjusted and adjusted analysis, ED length of stay was about 2 hours lower in the group who received midazolam/haloperidol compared with lorazepam/haloperidol.
When subgroup analysis was applied, all groups analysis had shorter length of stay with midazolam however statistical significance was preserved only in the groups of patients who were discharged home from the ED, did not need a psychiatry evaluation, and given repeated doses of medication.
As far as serious adverse events, 4/618 patients who received midazolam compared with 2/555 patients who received lorazepam required intubation. This difference was not statistically significant, and there were no deaths, cardioversions, or instances of patients requiring CPR. The number of intubations may not even be related to the medication used as these patients had reasons for admission like skull fracture, heroin overdose, aspiration pneumonitis, sepsis, and epilepsy.
While this does represent a real-world look at the benefits of using midazolam as the benzodiazepine used to treat acute agitation, it represents effects at only 1 center, and the possibility of unrecognized confounders cannot be excluded. In addition, no comment is made by the authors on concomitant antihistamine use (which is often given with benzodiazepines and antipsychotics for agitation) so it is unknown if the length of stay benefits would persist if diphenhydramine was added to the treatment protocol.
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