Clinical bottom line
Subdissociative-dose ketamine is an effective alternative to opioids for acute pain management in the emergency department (ED), offering comparable analgesia with a distinct side effect profile. Ketamine may reduce opioid requirements and associated risks, particularly in patients with contraindications to opioids or at risk of opioid-related adverse events. However, variability in dosing protocols and patient populations, as well as limited long-term safety data, necessitate cautious integration into practice. Ketamine represents a valuable adjunct or alternative in multimodal acute pain strategies (Olejnik et al., 2025; Duhaime et al., 2020; Beaudrie-Nunn et al., 2023).
What the evidence shows
Duhaime et al. (2020) conducted a randomized controlled trial comparing subdissociative ketamine to opioids for acute pain in the ED, demonstrating non-inferior pain reduction at 30 and 60 minutes post-administration. Ketamine was associated with fewer respiratory depressions but more transient psychomimetic effects.
Olejnik et al. (2025) performed a systematic review and network meta-analysis in pediatric populations, confirming ketamine’s efficacy in acute pain management with a favorable safety profile relative to opioids.
Beaudrie-Nunn et al. (2023) reported on ketamine’s analgesic efficacy in various acute pain etiologies, noting rapid onset and opioid-sparing effects, though mild side effects such as dizziness and nausea were more common.
Downing et al. (2026) reviewed intranasal ketamine versus intravenous opioids, finding intranasal ketamine a practical, effective option with ease of administration and acceptable tolerability.
Sin et al. (2015) earlier established the safety and utility of subdissociative ketamine doses in the ED, supporting its role in multimodal pain management.
Caveats and uncertainty
Heterogeneity in ketamine dosing regimens and administration routes complicates direct comparisons and standardization.
Psychomimetic side effects, though generally transient, may limit use in some patients.
Long-term outcomes and repeated dosing safety data are limited.
Most studies focus on short-term pain relief; functional outcomes and patient satisfaction require further evaluation.
Ketamine’s efficacy relative to opioids in specific pain types (e.g., fractures, abdominal pain) needs more targeted research.
How this may change practice
Emergency clinicians may increasingly adopt subdissociative ketamine as a first-line or adjunct analgesic, especially for patients at risk of opioid-related adverse effects.
Intranasal ketamine offers a noninvasive alternative suitable for rapid administration when IV access is challenging.
Protocols incorporating ketamine can reduce opioid consumption and potentially mitigate opioid-related complications.
Education on ketamine’s side effect profile and monitoring requirements will be essential for safe implementation.
Multimodal analgesia strategies integrating ketamine may improve acute pain management outcomes in the ED.