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University of Miami Miller School of Medicine MD/MPH Program, AAEM/RSA Modern Resident Blog Copy Editor
Bottom Line Up Front:
In comparison to 0.1mg/kg intravenous morphine, multiple studies demonstrated 0.3-0.5mg/kg ketamine was as effective in short term management of acute pain, without any increased risk of severe adverse effects. In addition to primary analgesia, ketamine may be effective as an analgesic adjunct in situations where opioids are contraindicated or for patients who have pain refractory to conventional pharmacologic approaches.
In the setting of the contemporary opioid epidemic, use of opioids for pain relief in the emergency department (ED) has been scrutinized. Opioid prescription presents increased risk for development of opioid use disorder and presents challenges for attainment of adequate pain control in opioid tolerant patients. Alternatives to opioids are an important topic of discussion in emergency medicine as well as in pain management subspecialties. Many institutions are adopting ketamine for analgesic use based on observational data and/or provider choice, but until recently, the high-quality evidence validating ketamine using randomized controlled trials (RCTs) has been limited. This article details a meta-analysis of RCTs comparing low-dose ketamine (LDK) to morphine for analgesia.
Review of Literature:
In a 2018 meta-analysis, three RCTs including 261 adult patients examined the analgesic effects of intravenous (IV) LDK administered in patients with acute pain, compared against IV morphine. The studies included patients with either acute traumatic or non-traumatic pain as a chief complaint, with acuteness defined as the pain having begun within the previous week. Exclusion criteria for this meta-analysis included studies examining ketamine in pediatric patients, lack of randomization, use of placebo, non-use or non-reporting of visual analog scale (VAS) or numeric rating scale (NRS) pain scores, and studies in which there was procedural sedation or co-administration of any analgesic within twenty minutes of IV LDK/opioid administration. While the inclusion criteria were very conservative, a primary focus of this study was to examine only contemporary, high-quality evidence, limiting the majority of recent research on the topic of LDK for ED analgesia.
Patients receiving the analgesic intervention received LDK or morphine administered as an initial one-time dose, single-agent IV bolus, with comparison of pre-post pain score from baseline to a reported time point closest to ten minutes after administration. While there were other time points at which pain was reassessed, ten minutes was chosen as it was a commonly reported time point for reassessment in all trials. Additional analgesia could be provided twenty minutes following the initial dose and was the same as the first dose. The primary outcome measured was mean difference in pain scores following the administration of ketamine or morphine. Change in pain was assessed using the VAS or NRS tools. Secondary outcomes included occurrence of any adverse events or side effects, and the requirement of additional dosing or alternative analgesics to control pain.
The data pooled amongst these trials showed that ketamine and morphine were statistically similar in attenuating pain. Mean change in pain scores were calculated, and the absolute value of recorded pain change in the morphine arm was subtracted from the absolute value of the change in the ketamine arm. None of the trials demonstrated a clinically or statistically significant difference between ketamine and morphine in reduction of pain as measured by the pain score tool. Pooled change between the ketamine and morphine arms was 0.42 (95% CI = –0.70 to 1.54) where positive values suggest ketamine was superior to morphine in reducing pain.
Regarding secondary outcomes, the quality of the evidence was not strong, as the studies included were chosen for equivalence in primary outcome and did not have reliable parity in timing, frequency, severity, or type of assessment of adverse events. However, on review of each the studies’ individual findings regarding adverse effects of ketamine versus morphine administration, more adverse effects were seen with ketamine. These effects were typically mild and most often included dizziness, disorientation, mood changes, and nausea.
Ketamine is an alternative to opioid use for acute pain with a safe side effect profile. Particularly in the setting of the contemporary opioid epidemic, there is a widespread effort to develop reliable alternatives to opioid medications, with policy statements by the American College of Emergency Physicians recommending the use of ketamine.[2,3] This meta-analysis pools and validates recent high-quality data on ketamine dosage equivalency in treatment of acute pain.
1. Karlow N, Schlaepfer CH, Stoll CRT, et al. A Systematic Review and Meta-analysis of Ketamine as an Alternative to Opioids for Acute Pain in the Emergency Department. Acad Emerg Med. 2018;25(10):1086-1097. Accessed 8/19/2019.
2. ACEP Policy Statement: Optimizing the Treatment of Acute Pain in the Emergency Department. 2017. Available at: https://mocep.org/wp-content/uploads/ACEP-2017- Position-Statement-on-Optimizing-the-Treatment-of-Acute-Painin-the-ED-1.pdf. Accessed 8/19/2019.
3. ACEP Policy Statement: Sub-dissociative Dose Ketamine for Analgesia. 2017. Available at: https://www.acep.org/patientcare/policy-statements/sub-dissociative-dose-ketamine-foranalgesia/#sm.00000g2a2cwspdsavfl2p8inb1750. Accessed 8/19/2019.