Ketamine Results in Drop in Pain Scores for Sickle Cell Patients

While it did not exceed morphine in benefit, ketamine has shown the ability to reduce pain scores for patients with acute sickle vaso-occlusive crisis (VOC).

A team, led by Mohammed S. Alshahrani, MD, Emergency and Critical Care Departments, King Fahad Hospital of the University-Imam Abdulrahman Bin Faisal University, evaluated the efficacy and safety of single-dose ketamine infusions for adults with sickle cell disease who presented with acute sickle vaso-occlusive crisis.

The Study

In the parallel-group, prospective, randomized, double-blinded pragmatic trial, 278 patients were randomized to receive either a single dose of ketamine (n = 138) or morphine (n = 140). The treatments were infused for over 30 minutes at the emergency department (ED) at King Fahd Hospital.

The adult patients were diagnosed with sickle cell disease with confirmed hemoglobin electrophoresis results consistent with any sickle cell genotype.

The patients received either a low dose of 0.3 mg/kg of ketamine in 100 mL normal saline or a standard dose of 0.1 mg/kg of morphine in 100 mL normal saline.

Outcomes

The investigators sought primary outcomes of the mean difference in the numerical pain rating score (NPRS) over 2 hours. The score was recorded every 30 minutes for a maximum of 180 minutes.

The investigators also sought secondary outcomes of the cumulative dose of opioids, emergency department length of stay, hospital admission, change in vital signs, and drug-related side effects.

The mean age of the patient population was 29.4 years and the mean NPRS at randomization was 8.6.The mean NPRS for the ketamine morphine group was 8.6 and 8.7 at randomization, respectively.

Pain Reduction

The mean numerical pain rating score over 2 hours was 5.7 in the ketamine group, compared to 5.6 in the morphine group.

Overall, the ketamine group received significantly lower cumulative doses of morphine during the emergency department stay (mean, 4.5 mg) than the morphine group (mean, 8.5 mg).

Both groups did have similar rates of hospital admission, while 6.3% of the ketamine group had drug-related side effects, compared to just 2.2% of the morphine arm.

“Early use of ketamine in adults with VOC resulted in a meaningful reduction in pain scores over a 2-h period and reduced the cumulative morphine dose in the ED with no significant drug-related side effects in the ketamine treated group,” the authors wrote. “We found that the ketamine-based regimen was not superior to the morphine-based regimen in reducing pain score.”

Background

Vaso-occlusive crisis is the most common sickle cell disease complications, often linked to severe and frequently occurring pain that requires emergency department visits and hospitalizations. Patients that are frequently hospitalized are also at an increased risk of early death.

Costs associated with this patient population have also increased in recent years. A 2009 study found the 100,000 patients with sickle cell disease in the US cost more than $1.1 billion.

Standard therapy for these patients include intravenous hydration and opioid analgesia. However, physicians often face challenges in attempting to balance the analgesic and the adverse effects of opioids.

Ketamine is a non-competitive NMDA receptor antagonist that could modulate opioid-induced hyperalgesia by impairing the sensitization of the spinal neurons to nociceptive stimuli. The treatment acts on glutamate and NMDA receptors to modulate the peripheral pain sensitization process along the pain pathways.

Ketamine also might affect neural plasticity on the NMDA and the spinal pathway by preventing the transmission of the generated stimuli toward the central nervous system.

Previously, there was only 1 randomized clinical trial that enrolled pediatric patients with vaso-occlusive crisis randomly administered ketamine or morphine. In the study, investigators found ketamine was non-inferior to morphine at reducing pain scores. The ketamine arm also had increased adverse events, the majority of which were mild and transient.