Comparison of Nebulized Ketamine to Intravenous Subdissociative Dose Ketamine for Treating Acute Painful Conditions in the Emergency Department: A Prospective, Randomized, Double-Blind, Double-Dummy Controlled Trial.
Tommy Nguyen, Mo Mai, Amulya Choudhary, Slavic Gitelman, Jefferson Drapkin, Antonios Likourezos, Sarah Kabariti, Rukhsana Hossain, Karina Kun, Ankit Gohel, Patrizia Niceforo, Michael A. Silver, Sergey Motov
Annals of emergency medicine October 1, 2024 DOI: 10.1016/j.annemergmed.2024.03.024 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized controlled trial Double-blind Peer reviewed |
|---|---|
| Sample size | 150 |
| Population | Adult emergency department patients with acute painful conditions and a numerical rating scale pain score of ≥5 |
| Intervention | Nebulized ketamine |
| Dose | 0.3 mg/kg intravenous, 0.75 mg/kg nebulized |
| Duration | Single dose, outcomes measured up to 120 minutes |
| Topics | Esketamine Ketamine |
| Keywords | Pain management Ketamine therapy Emergency medicine Medical research Drug delivery systems |
| Citations | 11 |
| Key findings | Intravenous and nebulized ketamine produced equivalent reductions in pain scores at 30 minutes, with no clinically important difference between the two routes. |
Abstract
We aimed to assess and compare the analgesic efficacy and adverse effects of intravenous subdissociative-dose ketamine to nebulized ketamine in emergency department (ED) patients with acute painful conditions. We conducted a prospective, randomized, double-blind, double-dummy clinical trial in adult patients (ages 18 and older) with a numerical rating scale pain score of ≥5. We randomized subjects to receive either a single dose of 0.3 mg/kg of intravenous (IV) ketamine or 0.75 mg/kg of nebulized ketamine through a breath-actuated nebulizer. Primary outcome was the difference in pain scores on the numerical rating scale between groups at 30 minutes postmedication administration. The secondary outcomes included the need for rescue analgesia, occurrences of adverse events in each group, and the difference in pain scores at 15, 30, 60, 90, and 120 minutes. We calculated a 95% confidence interval (CI) for a mean difference at 30 minutes, with a minimum clinically important difference set at 1.3 points. We enrolled 150 subjects (75 per group). Mean pain scores through numerical rating scale were 8.2 for both groups at baseline, which decreased to 3.6 and 3.8 at 30 minutes, yielding a mean difference of 0.23 (95% CI -1.32 to 0.857). We observed no clinically concerning changes in vital signs. No serious adverse events occurred in any of the groups throughout the study period. We found no difference between the administration of IV and nebulized ketamine for the short-term treatment of moderate to severe acute pain in the ED, with both treatments providing a clinically meaningful reduction in pain scores at 30 minutes.
Comparable studies
Other randomized controlled trials on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Subanesthetic Effects of the Noncompetitive NMDA Antagonist, Ketamine, in Humans Healthy human subjects recruited from the community | 1994 | Randomized controlled trial | n = 19 |
| Antidepressant Efficacy of Ketamine in Treatment-Resistant Major Depression: A Two-Site Randomized Controlled Trial Patients with treatment-resistant major depression experiencing a major depressive episode | 2013 | Randomized controlled trial | n = 73 |
| Remifentanil-induced Postoperative Hyperalgesia and Its Prevention with Small-dose Ketamine Patients undergoing major abdominal surgery | 2005 | Randomized controlled trial | n = 75 |
| Efficacy of Intravenous Ketamine for Treatment of Chronic Posttraumatic Stress Disorder Patients with chronic PTSD related to a range of trauma exposures | 2014 | Randomized controlled trial | n = 41 |
| Ketamine-Induced Deficits in Auditory and Visual Context-Dependent Processing in Healthy Volunteers Healthy volunteers | 2000 | Single-blind placebo-controlled study | n = 20 |
Citations in the library
Cited by 2
- Esketamine/Ketamine: Dual‐Action Mechanisms and Clinical Prospects beyond Anesthesia in Psychiatry, Immunology, and Oncology Advanced Science December 14, 2025
- A Promising Route for Established Indications: A Systematic Review of Nebulized Ketamine in Pain. Current Pain and Headache Reports April 30, 2025