Low Dose Ketamine Versus Morphine for Moderate to Severe Pain in the Emergency Department: A Prospective, Randomized, Double-Blind Study

Rationale: Opioids are traditionally accepted as a cornerstone of acute pain management in the Emergency Department (ED). Morphine is one of the most commonly used parenteral opioid analgesics whose initial dose of 0.1 mg/kg has been extensively researched and recommended for control of severe acute pain in the ED. However, intravenous administration of opioids is associated with thefollowing side effects: hypotension, respiratory depression, dizziness, pruritis and nausea. In addition, in patients with pre-existing renal and/or hepatic insufficiency, these effects may be pronounced and require interventions. Thus, the administration of an equipotent analgesic that does not cause hypotension and respiratory depression would enhance patient safety in the ED.

Ketamine is a noncompetitive N-methyl D-aspartate (NMDA) receptor antagonist that blocks the release of excitatory neurotransmitter glutamate and provides anesthesia, amnesia and analgesia by virtue of decreasing central sensitization and "wind-up" phenomenon. Due to its high lipid solubility, ketamine rapidly crosses the blood-brain barrier, provides rapid onset of action (peak concentration at is reached 1 minute after IVP) and rapid recovery to baseline (duration of action 5-15 minutes after IVP) (1). When given at subdissociative doses of 0.1-0.5 mg/kg, either as an adjunct to opioid analgesic or as a solo agent, ketamine provides good analgesia while preserving airway patency, ventilation, and cardiovascular stability (2). In addition, a small dose of ketamine may increase the analgesic potency of opioids thus decreasing their dosing requirements (3). Based on the aforementioned facts, ketamine offers an attractive option for providing safe and convenient pain control for patients in the ED.

A double-blind trial of 40 adult patients with acute musculoskeletal trauma compared low-dose ketamine administered by subcutaneous infusion (0.1 mg/kg/h) with intermittent intravenous morphine (0.1 mg/kg IV every 4 hours ) and demonstrated better pain relief, less sedation and less nausea and vomiting with ketamine infusion than with intermittent morphine. In addition, none of the patients in the ketamine group required supplementary analgesia (4). A prospective, randomized trial compared two analgesic regimens, morphine with ketamine (K group) or morphine with placebo (P group) for severe acute pain in 73 trauma patients with a visual analog scale (VAS) score of at least 60/100. Morphine was administered at 0.1mg/kg; patients in the K group received 0.2 mg/kg of intravenous ketamine over 10 minutes while patients in the P group received isotonic sodium chloride solution. The results showed comparable change in VAS score at 30 minutes (34 mm (K) vs. 39 mm (P)) but reduced morphine consumption in the ketamine group (0.14 mg/kg (K) vs 0.2 mg/kg (P)) (5).

A chart review analysis of 35 ED patients receiving low dose ketamine at doses 0.1mg-0.6mg/kg in addition to intravenous morphine demonstrated a decrease in pain intensity for 54% of the patients by a documented 3 point pain decrease on a 10-point scale. The ketamine doses ranged from 5 mg to 35 mg with median dose of 10 mg and mean dose of 15.7mg. In addition, only one patient had a brief dysphoric reaction that did not require intervention (6).

Hypothesis: Intravenous administration of subdissociative dose ketamine at 0.3 mg/kg is superior to intravenous morphine at 0.1 mg/kg in treating moderate and severe acute pain in patients presenting to the ED.