In this episode, I’ll discuss expectations for the onset of action of IM medications used for acute agitation.
When caring for an acutely agitated patient, the delay between IM medication administration and the onset of action can seem exceedingly long. Staff and patient safety continue to be at risk until agitation resolves, and minutes seem to pass like hours.
Knowing the time until the onset of action to expect is essential in order to manage clinician expectations and resources. Giving additional doses of sedatives before the first has had adequate time to work can result in a stacking effect of the medications and potentially result in over-sedation or even cardio-respiratory compromise.
The risk:benefit between additional doses of medication and waiting for medication onset exists on a continuum that needs to take into account the risk of the patient violently injuring themselves or staff against the risk of oversedation.
Common IM medications given for acute agitation are:
Midazolam
Olanzapine
Ziprasidone
Haloperidol
Combination therapy with haloperidol+lorazepam
Two studies are particularly useful in identifying the time until onset of action that can be expected with these medications. The first is a multi-arm study published in Annals of Emergency Medicine that looked at monotherapy with IM midazolam, olanzapine, ziprasidone, and 5 or 10 mg of haloperidol. The second is a review article in BMJ that summarizes the available evidence on combination therapy, most commonly haloperidol+lorazepam.
For monotherapy, the median time until onset of sedation (and the minutes until 80% chance of sedation) are as follows:
Midazolam 5 mg IM = 12 (30) minutes
Olanzapine 10 mg IM = 14 (30) minutes
Ziprasidone 20 mg IM = 17 (60) minutes
Haloperidol 5 mg IM = 20 (60) minutes
Haloperidol 10 mg IM = 19 (45) minutes
While the number of minutes to onset is not as well-defined for combination therapy of lorazepam and haloperidol, the BMJ review indicates that combination therapy is usually accompanied by a faster onset of action.
Knowing these times to onset of action can help pharmacists evaluate unique patient scenarios and weigh the risks of additional medication doses with continued non-medication strategies such as verbal de-escalation or physical restraint.
Here is a case example to illustrate this:
A 65 year-old woman with a significant cardiac history presented to the ED via law enforcement with acute agitation, suicidal ideation, and ethanol intoxication. She was not cooperating with examination and was physically aggressive to staff, on top of her recently expressed interest in self-harm. Verbal attempts to de-escalate and gain cooperation were not successful. She was given IM doses of 5 mg haloperidol, 2 mg lorazpeam, and 50 mg diphenhydramine but 30 minutes later still required the presence of a security officer and intermittent verbal de-escalation and physical restraint to maintain safety. The provider considered an additional dose of haloperidol but after consulting the pharmacist about the time to onset of action for the medications given, elected to continue verbal de-escalation and physical restraint for a bit longer. 5 minutes later, the patient became sedated and cooperative. In this case, additional medications that might have had an interaction with the patient’s cardiac history or ethanol intoxication were avoided by the provider’s awareness of the time to onset of action for IM sedatives.
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