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.
Author(s): Beaudoin FL(1), Lin C, Guan W, Merchant RC.
Affiliation(s): Author information:
(1)The Department of Emergency Medicine, Rhode Island Hospital, The Alpert
Medical School of Brown University, Providence, RI.
Publication date & source: 2014, Acad Emerg Med. , 21(11):1193-202
OBJECTIVES: 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.
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