Low-dose ketamine improves pain relief in patients receiving intravenous opioids for acute pain in the emergency department: results of a randomized, double-blind, clinical trial.
OBJECTIVE
Low-dose ketamine has been used perioperatively for pain control and may be a useful adjunct to intravenous (IV) opioids in the control of acute pain in the emergency department (ED). The aim of this study was to determine the effectiveness of low-dose ketamine as an adjunct to morphine versus standard care with morphine alone for the treatment of acute moderate to severe pain among ED patients.


METHODS
A double-blind, randomized, placebo-controlled trial with three study groups was conducted at a large, urban academic ED over a 10-month period. Eligible patients were 18 to 65 years old with acute moderate to severe pain (score of at least 5 out of 10 on the numerical pain rating scale [NRS] and pain duration < 7 days) who were deemed by their treating physician to require IV opioids. The three study groups were: 1) morphine and normal saline placebo (standard care group), 2) morphine and 0.15 mg/kg ketamine (group 1), or 3) morphine and 0.3 mg/kg ketamine (group 2). Participants were assessed at 30, 60, and 120 minutes after study medication administration and received rescue analgesia as needed to target a 50% reduction in pain. The primary outcome measure of pain relief, or pain intensity reduction, was derived using the NRS and calculated as the summed pain-intensity (SPID) difference over 2 hours. The amount and timing of rescue opioid analgesia was evaluated as a secondary outcome. The occurrence of adverse events was also measured.


RESULTS
Sixty patients were enrolled (n = 20 in each group). There were no differences between study groups with respect to age, sex, race/ethnicity, preenrollment analgesia, or baseline NRS. Over the 2-hour poststudy medication administration period, the SPIDs were higher (greater pain relief) for the ketamine study groups than the control group (standard care 4.0, interquartile range [IQR] = 1.8 to 6.5; group 1 7.0, IQR = 4.3 to 10.8; and group 2 7.8, IQR = 4.8 to 12.8; p < 0.02). The SPIDs for the ketamine groups were similar (p < 0.46). When compared to standard care, group 2 sustained the reduction in pain intensity up to 2 hours, whereas group 1 was similar to standard care by 2 hours. Similar numbers of patients received rescue analgesia: standard care group, seven of 20, 35%; group 1, four of 20, 20%; and group 2, four of 20, 20% (p = 0.48). Among those receiving rescue analgesia, those in the standard care group received analgesia sooner than either low-dose ketamine group, on average. More participants in the low-dose ketamine groups reported dysphoria and dizziness.


CONCLUSIONS
Low-dose ketamine is a viable analgesic adjunct to morphine for the treatment of moderate to severe acute pain. Dosing of 0.3 mg/kg is possibly more effective than 0.15 mg/kg, but may be associated with minor adverse events. Future studies should evaluate additional outcomes, optimum dosing, and use in specific populations.
The Department of Emergency Medicine, Rhode Island Hospital, The Alpert Medical School of Brown University, Providence, RI.
Francesca L
FL
Beaudoin
Charlie
C
Lin
Wentao
W
Guan
Roland C
RC
Merchant
D059787:Acute Pain / Q000175:diagnosis / Q000188:drug therapy*; D000328:Adult; D000698:Analgesia / Q000379:methods*; D000700:Analgesics / Q000008:administration & dosage; D000701:Analgesics, Opioid / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004636:Emergency Service, Hospital; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D007649:Ketamine / Q000008:administration & dosage*; D008297:Male; D059408:Pain Management / Q000379:methods*; D010147:Pain Measurement; D010865:Pilot Projects; D012189:Retrospective Studies; D013997:Time Factors; D016896:Treatment Outcome
D000700:Analgesics; D000701:Analgesics, Opioid; D007649:Ketamine