Swift, safe, and science-based control of pain is one of the most important tasks we do in the ED, one we are called upon to treat regularly. The rise of subdissociative ketamine in particular has led the charge in analgesic innovation in the emergency department, and the recent release of the KetaBAN trial is yet another ketamine-driven step forward in growing our therapeutic armamentarium.
KetaBAN is the latest production from the research group at Maimonides, a team at the forefront of analgesic innovation in emergency medicine. (Ann Emerg Med. 2021 Jul 3; doi: 10.1016/j.annemergmed.2021.04.031.) The authors randomized a convenience sample of patients from the emergency department who were deemed appropriate for the study by the treating physician. They had a range of painful conditions, the most common being traumatic and atraumatic musculoskeletal pain.
Patients received 0.75 mg/kg, 1.0 mg/kg, or 1.5 mg/kg of ketamine poured into a breath-actuated nebulizer. “The utilization of the breath-actuated nebulizer for [this] study allowed patients to be in control of their pain management by self-administering analgesic in a breath-triggered fashion,” the authors wrote. “This self-control, in addition to noninvasiveness, rapidity, and titratability, could [lead] to improved pain management.”
The primary outcome assessed was difference in pain scores at 30 minutes. Unsurprisingly, ketamine did a good job in all patients, dropping pain scores by about four points on a standard 11-point scale no matter which dose was employed. The minimal clinically significant difference in pain scores that the authors sought—1.3 points between groups—was not found; no significant difference in analgesic efficacy was identified across the three groups. No profound differences in adverse events were seen across the three groups, with about a quarter of patients in each group reporting mild dizziness.
Interesting subtleties emerge when diving into the study a bit deeper. Each group was administered a weight-based dose, but the amount of ketamine actually ingested through the nebulizer bore only slight resemblance to their allocated group. The 0.75 mg/kg and 1.0 mg/kg group consumed 43.3 mg and 48.5 mg of drug, respectively, with an escalation to 78.5 mg in the 1.5 mg/kg cohort.
Given ketamine's bioavailability via inhalation amounting to less than half compared with the intravenous route, it's notable that the amount of active drug each patient received resembles common IV analgesic doses. Most patients also reported sustained pain relief hours after ketamine administration, far beyond its effective therapeutic window, suggesting that ketamine's supraspinal blockade of the NMDA receptors has durable antinociceptive influence, which is a finding consistent with the drug's growing use in refractory chronic pain syndromes.
KetaBAN may have immediate clinical applications for many physicians around the country. A breath-actuated nebulizer is needed, of course (don't aerosolize ketamine all throughout the department with a jet nebulizer), but sufficient clinical experience and comfort exist with ketamine to employ the technique without too much preparation or perseveration.
For those without contained nebulizer systems, however, KetaBAN will more likely be used to continue to inform the pharmacological flexibility and clinical cross-cutting of ketamine, such as the employment of a mucosal atomization device and the application of ketamine intranasally for pain control.
Intranasal ketamine is not uncommonly employed for pain control or procedural sedation in children. Its use is also growing in the prehospital community, where forward-leaning emergency medical services agencies have introduced the technique for a broad array of painful conditions with good outcomes. (Ann Emerg Med. 2019;74:241; https://bit.ly/3hM37uG.)
Curiously, intranasal ketamine is not regularly used in adults with painful conditions in the emergency department despite a handful of trials that continue to present the same findings we see across the spectrum of ketamine studies: The drug provides effective analgesia for a host of painful conditions with a small but sizable proportion of patients experiencing mild dizziness or nausea. (World J Emerg Med. 2016;7:19; World J Urol. 2021;39:1263.)
I use a reasonable amount of intranasal ketamine in my practice, particularly for patients with painful conditions where I want to avoid opioids or when a multimodal analgesic approach might be most successful. Consider, for example, a patient presenting with severe low back pain, limiting ambulation. These patients can often present a significant pain control challenge, but ketamine combined with other targeted and evidence-based agents can lead to improved outcomes. (EMN. 2019;41:14; http://bit.ly/2Tob2ix.)
I write so often about the seemingly never-ending array of medications and maneuvers we have at our disposal to treat painful conditions, yet it often seems we are presented with situations that force us to develop even more techniques and tricks. The KetaBAN trial contributes to the growing reassurance that ketamine is an eminently adaptable and consistently safe medication for pain control in the emergency department.
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Dr. Pescatoreis the chief physician for the Delaware Division of Public Health and an emergency physician at Einstein Healthcare Network in Philadelphia. He is also the host with Ali Raja, MD, of the podcast EMN Live, which focuses on hot topics in emergency medicine:http://bit.ly/EMNLive. Follow him on Twitter@Rick_Pescatore, and read his past columns athttp://bit.ly/EMN-Pescatore.