Can midazolam be administered to treat a dysphoric reaction to an analgesic dose of ketamine?

Analgesic dose ketamine should not produce significant dysphoria. At subdissociative levels, ketamine modulates NMDA mediated excitatory transmission without the perceptual disturbance associated with dissociative dosing. When compared with placebo, analgesic ketamine demonstrates a similar side effect profile with no meaningful increase in dysphoric reactions or psychoperceptual symptoms (Motov et al., 2015). When dysphoria is reported, it is usually related to administration technique. Rapid IV push creates a transient spike in cortical concentration that can briefly disrupt sensory integration. Slowing the administration is the primary and most effective mitigation strategy.

In rare cases where symptoms are severe or persistent despite correcting the administration rate, a patch can be initiated to discuss further management with the base hospital physician. Although midazolam may be considered in exceptional circumstances, this is not something that should be routinely required for analgesic dose ketamine.

Reference
Motov, S., Rockoff, B., Cohen, V., Pushkar, I., Likourezos, A., Monzut, A., … Fromm, C. (2015). Intravenous subdissociative dose ketamine versus morphine for analgesia in the emergency department: A randomized controlled trial. Annals of Emergency Medicine, 66(3), 222 to 229.