Ketamine: Comparison of IV Push vs. IV Drip

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.

Inclusion Criteria:

- Emergency Medicine patients

- Adult patients (18-65 years of age)

- Moderate to severe pain (Numeric Pain Rating Score =5).

- Patients must be awake, alert and oriented to time, place and person.

- Patients must be able to demonstrate understanding of the informed consent, and also
able to verbalize how much pain they are having on the 10 point Numeric Rating Pain
Scale, and the nature of the side effects they may be experiencing from the IV
analgesia

Exclusion Criteria:

- Patients with cognitive deficits that are not able to demonstrate understanding as
described above.

- Patient's reported weight of less than 45kg or more than 115kg.

- Patients with altered mental status, alcohol intoxication, eye trauma.

- Patients with hemodynamic instability (Systolic Blood pressure <90), and malignant
hypertension.

- allergy to ketamine

- Pregnancy or breast feeding.