Written by Clay Smith
Spoon Feed
Ketamine was effective for treatment of agitation, but 30% of patients given higher doses IM by EMS were intubated once in the ED.
Why does this matter?
Often benzodiazepines or antipsychotics are used for sedating agitated patients. Benzos are associated with high rate of intubation (37% in some studies). Antipsychotics may prolong the QT. These agents may take up to 15 minutes to provide adequate sedation. Ketamine has been used for agitation as well. This is a compilation of the key studies on its use for agitation. Usually, the dose is 1mg/kg IV or 3mg/kg IM.
Down the K-hole
This was a systematic review (SR) of 18 studies, 650 patients, involving use of ketamine for agitation in the prehospital and ED setting. Twelve of the 18 were EMS studies. Most were small sample sizes; all were observational. Mean dose was 315mg IM, 4.9mg/kg (…that’s a lot). Given this, it is not surprising that 30% were intubated, most after having been given ketamine by EMS with intubation in the ED. Onset of action was around 7 minutes. Only 1.8% were intubated when ketamine was given in the ED only. Other adverse effects included: vomiting, 5.2%; hypertension, 12.1%; emergence reactions, 3.5; transient hypoxia, 1.8%; and laryngospasm, 1.3%. Dosing of ketamine IM was high in this SR. This may have led to over-sedation and the high intubation rate seen here. Perhaps if the dose was closer to 3mg/kg IM, fewer patients would have been intubated. Intubation was also much higher when given by EMS rather than in the ED. Was this just nervous emergency physicians who interpreted dissociation as not protecting their airway? It’s hard to know.
Another Spoonful
REBEL EM has a helpful post on chemical sedation of the agitated patient.
Source
Ketamine for Rapid Sedation of Agitated Patients in the Prehospital and Emergency Department Settings: A Systematic Review and Proportional Meta-Analysis. J Emerg Med. 2018 Sep 6. pii: S0736-4679(18)30727-3. doi: 10.1016/j.jemermed.2018.07.017. [Epub ahead of print]
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Reviewed by Thomas Davis
The problem with lower doses (<3 mg/kg IM) as the author suggested is that you have a good chance of ending up in the "partial dissociation" dose range, where patients have significant neuropsychiatric side effects that are disturbing both to the patient and to the provider. The high intubation rate may, as stated here, simply be a matter of comfort level on the part of the ED physician, as the studies on this topic did not generally list the reason for intubation.
The dose of 4.9 mg/kg is consistent with the 2011 ACEP Clinical Policy Guideline on procedural sedation with ketamine. The article stated, "there is no apparent benefit to using 1 mg/kg IV rather than 2 mg/kg IV or to using 3 mg/kg IM rather than 4 to 5 mg/kg IM, except perhaps a slightly faster recovery with the lower dose.77 Clinicians should consider simply using the higher dose because ketamine is less consistently effective with lower doses.18
Of historical note, during the 1970s anesthesiologists typically administered much higher ketamine doses (7 to 15 mg/kg IM) than those advocated now, and a systematic review identified no apparent difference in adverse event profiles between the higher and more standard dosing.4
In the large meta-analysis, subdissociative ketamine (????3 mg/ kg IM) demonstrated fewer airway and respiratory adverse effects relative to full dissociative dosing; however, such low doses are inadequate for most painful procedures and showed a higher incidence of recovery agitation.2,3"
Interesting information. It would indeed be nice to know if those patients after arriving in the ER did actually need to have their airway managed definitively, or perhaps it was as you suggested- misinterpretation of dissociation, or any other number of possibilities. In the EMS world where medical and personnel resources are often limited, having ketamine available as a rapid onset sedative agent has been very beneficial to both the patients and the providers. I think it could be argued that even if the 30% did eventually need intubated, you could chalk it up to good aggressive care. Before we started using ketamine for chemical take-down (in the haldol/benadryl/hope&pray days), we saw more combative/altered patients and EMS and law enforcement personnel injuries from perhaps preventable altercations.
You bring up a great point. Not only can the patient harm the people around them, agitated delirium has a mortality rate of 8-16% https://www.ncbi.nlm.nih.gov/pubmed/28990246. One could argue, better to need intubation than the coroner.