Using Nebulized Ketamine in the ED for Analgesia

Educational Objectives

The goal of this program is to improve emergency department analgesia using nebulized ketamine. After hearing and assimilating this program, the clinician will be better able to:

1. Use the optimal route of ketamine administration in the emergency department.
2. Choose an appropriate dose of nebulized ketamine to achieve analgesia.

Summary

Ketamine: acts as a noncompetitive N-methyl-D-aspartate (NMDA) glutamate complex antagonist providing acute pain relief by potentiating opioid analgesia and reducing central sensitization, wind-up phenomena, and hyperalgesia; improves comfort in the spinal cord and central nervous system

Administration: ketamine for analgesia refers to subdissociative (low dose, 0.1–0.3 mg/kg) ketamine, administered intravenously (IV) or as a short infusion (10–15 min); if weight-based dosing is not fixed, a dose of 15 to 30 mg is similarly effective; in the absence of IV access, intranasal administration is the second most common route, particularly in prehospital settings and pediatric emergencies; subcutaneous administration is rarely used in the emergency department (ED), despite its potential benefits; oral ketamine is used off-label; randomized clinical trials and systematic reviews have demonstrated that subdissociative ketamine, either alone or as an adjunct to opioids or nonopioid medications, is effective for short-term analgesia in ED and prehospital care; intranasal ketamine can be combined with fentanyl or nitrous oxide

Adverse events (AEs): the primary barrier to widespread use is psychoperceptual AEs, eg, feelings of unreality or dizziness; these sensations are not full dissociations but can be unsettling; rapid IV push increases the risk; evidence suggests that a short infusion reduces AEs by 44% without compromising analgesia

Nebulized ketamine: a noninvasive option when IV access is unavailable, and intranasal or oral routes are impractical; inhalation enhances patient safety; evidence suggests that nebulized ketamine reduces postintubation sore throat, and pain by 50% without causing major AEs; Jonkman et al (2017) study on healthy volunteers showed that nebulized ketamine yields 20% to 40% of systemic bioavailability, with onset usually occurring within 20 to 40 min; in a busy ED, nebulizing ketamine in an open setting risks exposing caregivers and bystanders to vapors, causing unintended psychoactive effects; a breath-actuated nebulizer (BAN) is an enclosed system that releases medication only when the patient inhales; this design minimizes environmental exposure, prevents overdose by ceasing delivery if the patient becomes overly sedated, and offers flexibility with mouthpiece or mask options

Prehospital area analgesia: Azizikhani et al (2025)—compared IV morphine (0.1 mg/kg) with nebulized ketamine (0.16 mg/kg) in adults with extremity fractures and found no significant difference in pain reduction at 5 and 15 min after administration; opioids caused more nausea and vomiting; ketamine was associated with higher rates of hallucination and dissociation (psychoperceptual disturbances); Patrick et al (2023)—reported a case series of 7 patients treated with nebulized ketamine (1 mg/kg) via BAN; 6 of 7 achieved significant pain relief; MacArthur et al (2024)—found that nebulized fentanyl and nebulized ketamine provided substantial pain relief (30%-45%), with no overall difference in efficacy; subgroup analysis showed that ketamine was more effective for traumatic injuries

Analgesia in the ED: ketaBAN trial—Dove et al (2021) randomized adults to 3 nebulized ketamine doses (0.75, 1, and 1.5 mg/kg); all doses produced short-term pain relief; 0.75 mg/kg was the preferred dose; Nguyen et al (2024)—comparative study found equal efficacy of nebulized ketamine (0.75 mg/kg) and IV ketamine (0.3 mg/kg) at 30 min; Kampan et al (2024)—found that nebulized ketamine (0.75 mg/kg) was as effective as IV morphine (0.1 mg/kg) in geriatric patients with musculoskeletal injuries, with fewer AEs; pediatric case reports—demonstrated promising results, with pain reductions of ≤47% in children with traumatic and nontraumatic injuries

Practical recommendations: include starting with a dose of 0.75 mg/kg, which offers relief equivalent to higher doses; rounding this to 1 mg/kg may simplify preparation for nurses and pharmacists; BAN devices are single-use per patient but allow for multiple doses (≤3); the inhalation time must be standardized between 5 and 15 min to ensure optimal efficacy and safety

Readings

Disclosures

For this program, members of the faculty and planning committee reported nothing relevant to disclose. Dr. Motov's lecture contains information related to the off-label or investigational use of nebulized ketamine for pain relief in the emergency department.

Acknowledgements

Dr. Motov was recorded at the Updates in Emergency Medicine 2025, held on January 21-24, 2025, in Stowe, VT, and presented by University of Vermont Larner College of Medicine. For information about upcoming CME activities from this presenter, please visit https://www.stoweem.com. Audio Digest thanks Dr. Motov and University of Vermont Larner College of Medicine for their cooperation in the production of this program.

CME/CE INFO

Accreditation:

Lecture ID:

AN681902

Qualifies for:

ABA MOCA, Clinical Pharmacology, Pain Management, Controlled Substances, Trauma

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.