Ketamine: Comparison of IV Push vs. IV Drip
Condition: Pain
Study type: Interventional

Summary: 
      Our previous published research comparing the efficacy of intravenous ketamine to morphine
      has shown ketamine to provide equivalent relief of moderate to severe acute pain in emergency
      medicine patients. Secondary analysis of the previous published research has also revealed
      ketamine to have statistically more side effects. The investigators believe that increasing
      the time of administration of the ketamine, from a push injection to a drip infusion, will
      minimize the side effects experienced by recipients of ketamine.
    

Detailed description: 
      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. At low
      (sub-dissociative, analgesics) doses of 0.1-0.4 mg/kg either as an adjunct to opioid
      analgesics or as a single agent, ketamine provides good analgesia while preserving airway
      patency, ventilation, and cardiovascular stability. In addition, the low-dose of ketamine
      increases the analgesic potency of opioids thus decreasing their requirements. Several recent
      studies of low-dose ketamine administered together with morphine provided acceptable pain
      relief to 55-60% of patients with minor side effects of dizziness, nausea and feeling of
      unreality. More recently the investigators conducted a research comparing Low-Dose Ketamine
      to Morphine for Moderate to Severe Pain in the Emergency Department with respect its
      analgesic efficacy and safety. Results demonstrated similar pain relief at 30 min between 2
      groups. However, 70% of patients in ketamine group had minor side effects at 5 min and 35% of
      patients at 30 min, as compared to 51% at 5 min. and 31% at 15 min. in the morphine group.
      The most common side effects reported by ketamine patients were dizziness, nausea, feeling of
      unreality, and mood changes.

      Based on the above mentioned data from our previous published research study, we hypothesized
      that low-dose ketamine given as a short infusion over 15 min will provide similar analgesic
      efficacy as an intravenous push-dose but with much less side effects. There are several
      research papers that support our hypothesis.

      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 and
      patients in the K group received 0.2 mg/kg of intravenous ketamine over 10 minutes, and the
      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)).

      A double-blind trial of 40 adult patients with acute musculoskeletal trauma compared a
      low-dose ketamine by subcutaneous infusion (0.1 mg/kg/h) with intermittent 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 ketamine group required supplementary analgesia.

      A prospective case series of 20 unselected adult ED patients with acute pain that evaluated
      analgesic feasibility of low-dose ketamine infusion was conducted in an urban public hospital
      over a course of 5 months. Patients received 15mg of intravenous push dose ketamine that was
      followed by continuous ketamine infusion at 20mg per hour for one hour. Optional morphine (4
      mg) was offered at 20, 40 and 60 minutes. Pain intensity was assessed at regular intervals
      for 2 hours using a 10-point verbal numerical rating scale (NRS), along with vital signs and
      levels of sedation. Results showed that fifteen patients reported clinically significant pain
      relief at 60 minutes and 13 at 120 minutes; and eighteen patients reported mild or modest
      side effects including dizziness, fatigue and headache.
    

Intervention name(s): Ketamine
Intervention type(s): Procedure
Intervention description(s): IV Push or or IV Drip
Intervention MeSH terms: Ketamine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Analgesia; ketamine