Ketamine May Be Efficacious in Managing Sickle Cell Disease-Related Pain

Findings from a new study indicated the ketamine may be comparable with other opioids in reducing pain associated with vaso-occlusive crises (VOC) in patients with sickle cell disease.

Although ketamine can be used as adjuvant to opioids to control such crises, there is still little evidence that confirms its safety and efficacy in this patient population.

Thus, investigators from the Department of Emergency Medicine, College of Medicine, Imam Abdulrahman Bin Faisal University, Saudi Arabia, conducted a systematic review of the current literature to determine ketamine’s role—as well as its safety and efficacy—in the management of acute painful VOC in pediatric and adult patients.

The studies included in the analysis also reported on ketamine’s analgesic effects and side effects.

As such, as a primary outcome, the investigators measured improvements in pain scale. The secondary outcome was a reduction in opioid utilization and side effects.

The Systematic Review

The final analysis included 14 studies, which consisted of 604 patients. The age of the participants ranged from 7.5-42 years old.

Furthermore, 2 of the studies included only pediatric patients, 3 included pediatric and young adult patients, and 9 included only adult patients.

Of the 14, 11 studies used a numeric rating scale to assess pain.

All included studies were a mix of a randomized controlled trial (n = 1), a retrospective study (n = 1), single-arm observational studies (n = 3), case series (n = 4), and case reports (n = 5).

The investigators noted that the only randomized controlled trial that was available (Lubega et al., 2018) indicated that ketamine was comparable to morphine for controlling pain and lowering scores.

However, it reported a higher incidence of nonlife-threatening, reversible adverse effects related to the drug.

The trial included 240 participants (mean age, 11.8 years) randomized 1:1 to receive 1 mg/kg of intravenous ketamine or 0.1 mg/kg of intravenous morphine.

The most common side effects associated with the drug were nystagmus and dysphoria.

In the retrospective study (Neri et. al), which evaluated a total of 33 patients, those who received a ketamine had a higher pain score than those who received opioid-based patient-controlled analgesia.

The ketamine group experienced short-term adverse effects, including vivid dreams, delusions, and dizziness.

Conclusions and Perspective

Overall, the team concluded that ketamine offers potential in the treatment of pain-related sickle cell events.

“The findings of the included studies highlight that ketamine has promising efficacy for reducing pain during VOCs, which was comparative with other opioids,” they noted. “However, compared to opioids, a higher rate of adverse events was noted in the ketamine group, although these were mild and transient.”

As such, various trials and case studies confirm that ketamine has an analgesic utility for these patients.

One case series (Palm et al.) indicated that ketamine may actually have an added benefit in chronically ill patients as result of its anti-depressant effects.

However, as noted by the investigators, a great limitation of their review was the lack of quantitative studies, especially randomized trials that used ketamine as a monotherapy rather than an adjuvant therapy.

Furthermore, the heterogenous nature of these studies—which had variable dosings and durations of ketamine infusion—precluded them from making conclusive recommendations in regard to ketamine’s use in the sickle cell population.

“We recommend that the correlation between the efficacy and the dose and duration of administration should be tested to optimize the use of ketamine in these patients,” the investigators concluded.

They also indicated a need to assess the influence of gender, location of pain, and duration of infusion on the efficacy of ketamine for VOCs.

The study, "Ketamine for Sickle Cell Vaso‐Occlusive Crises: A Systematic Review," was published online in Saudi Journal of Medicine & Medical Science