Purpose The purpose of this study was to compare the analgesic efficacy and safety of subdissociative-dose ketamine (SDK) for the treatment of acute pain in geriatric patients.
Background Geriatric patients presenting with acute pain pose a challenge to providers because of age-related changes in absorption, metabolism, clearance, and polypharmacy. Previous research suggests geriatric patients’ acute pain is under treated in the emergency department. This has led many providers to consider administration of non-opioid analgesics for acute pain in geriatric patients.
Ketamine is an NMDA receptor antagonist that decreases pain via blockade of central sensitization, hyperalgesia, and wind-up in the spinal cord. Administration of subdissociative-dose ketamine, 0.1-0.3 mg/Kg, has demonstrated effective acute pain relief in non-geriatric patients with acute traumatic and nontraumatic pain either as a bolus or as a short infusion. An infusion over 15 minutes has been shown to decrease psychoperceptual side effects, nausea and vomiting, and dizziness. However, there have been no prospective trials evaluating the efficacy of subdissociative-dose ketamine administered as an infusion in geriatric patients presenting to the emergency department with acute pain complaints.
Methodology This was a prospective, double-blind, randomized controlled trial of patients aged 65 years or older experiencing moderate-to-severe acute abdominal, flank, cancer, or musculoskeletal pain >5 on 0-10 numeric rating scale. Investigators, nurses, and statisticians were blinded to group assignment. Patients were randomized to either ketamine 0.3 mg/Kg or 0.1 mg/Kg morphine diluted in 100 mL administered over 15 minutes. Fentanyl 0.5 µg/mL was administered for breakthrough pain. The primary outcome was a difference in pain scores at 30 minutes after infusion of the study medications. Secondary outcomes included the need for rescue analgesics at 30 or 60 minutes; pain scores at 15, 60, 90, and 120 minutes; and adverse effects. Adverse effects of study medications were evaluated with the Side Effect Rating Scale for Dissociative Anesthetics (SERSDA) and the Richmond Agitation Sedation Scale (RASS). Statistical analysis and sample size calculations were appropriate.
Result There were 60 patients enrolled in the study, with 59 completing the study (ketamine group N = 29 vs. morphine group N = 30). No significant differences were found in baseline patient characteristics. Mean age was 77 years, 23% were male, and mean baseline pain scores were approximately 9 on a scale of 0-10. Abdominal pain was the most common source of pain in both the ketamine and morphine groups (47% vs. 33%, P = NS), followed by fracture (17% vs. 23%, P = NS). Cancer pain rates were higher in the ketamine group (16.7% vs. 2.2%, P = NS).
There was no significant difference in pain scores at 30 minutes between the ketamine and morphine groups (Figure 1). However, the rate of full resolution of pain was significantly higher in the ketamine group at 15 minutes (52% vs. 17%, P < 0.05). Likewise, the ketamine group had a higher percent of patients whose pain scores were reduced to 3 at 15 minutes after administration compared to the morphine group (73% vs. 53%, P < 0.05). No significant differences were found in the need for rescue analgesia at any time point, or in any other outcomes at 30, 60, 90, or 120 minutes.
The rate of adverse effects was higher in the ketamine group at 15 minutes (87% vs. 47%, P < 0.05) and 30 minutes (73% vs. 37%, P < 0.05) compared to the morphine group. The rate of dizziness was significantly higher at 15 min.(63% vs. 30%, P < 0.05) and 30 min. (53% vs. 23%, P < 0.05) in the ketamine group. Rates of adverse effects in the ketamine group peaked at 15 minutes (Figure 2). No differences in adverse effects between the ketamine and morphine groups were found at 60 min. or later. No differences were found in the rate of fatigue or nausea between the groups at any time point (Table 1). No serious adverse effects occurred in either group.
Conclusion Subdissociative-dose ketamine administered – 0.3 mg/Kg over 15 minutes – resulted in similar analgesic efficacy but with much faster onset compared to morphine 0.1 mg/Kg for treatment of acute pain in the emergency department geriatric population. However, psychoperceptual side effects were more common in patients who received ketamine, though for a relatively short period of time.
Subdissociative-dose ketamine is becoming a popular alternative to opioids for the treatment of acute pain in the Emergency Department. At my small overseas critical-access hospital my emergency department colleagues have found subdissociative-dose ketamine to be efficacious with minimal side effects in the treatment of acute pain. This has allowed them to reduce the frequency of opioid administration. This is especially important given the opioid epidemic. With proper training and a written protocol we were able to expand this practice to our multiservice ward so our nurses could administer a subdissociative-dose ketamine infusion over 15 minutes for acute pain. This has decreased the number of times the anesthesia provider gets called in to manage acute pain. I would encourage anesthesia providers at other institutions to consider developing a subdissociative-dose ketamine protocol. You may find similar benefits.