Low-Dose Ketamine Infusion In Adult Patients With Sickle Cell Disease – Impact On Management Of Acute Painful Episodes

Acute painful (vaso-occlusive) episode is the clinical hallmark of sickle cell disease (SCD). Individuals with SCD may experience acute episodes of severe debilitating pain that requires an acute care/emergency room visit and/or hospitalization. While parenteral opioids are the mainstay of treatment, the use of these agents may be complicated by toxicity, tolerance, and opioid-induced hyperalgesia. Additionally, using one medication/mode of treatment may be inadequate to achieve optimal safe pain control. Ketamine as an adjuvant treatment (administered in low sub-anesthetic doses) has been recognized for its utility in the management of a variety of painful conditions, ranging from oncologic to post-operative pain. However, there is limited literature supporting its use in treating acute sickle painful episodes. Here we have undertaken a retrospective analysis of adult patients with SCD who were treated with low-dose ketamine infusion during an acute painful episode in order to determine its effects of lowering opioid requirements.

A retrospective chart and database review was conducted on all patients with SCD who received low-dose ketamine infusion during an acute painful episode in the past three years at a single institution. After a review of inpatient pharmacy records, thirty unique subjects with SCD were identified to have received low-dose ketamine infusion during an acute painful episode in the past three years. For each of these subjects, total and daily (24hr) opioid requirements were determined for the admissions of a vaso-occlusive episode where ketamine infusion was used as an adjuvant for pain control and compared to the prior admission. For the ketamine admission, opioid requirements before, during, and after infusion were also compared. The opioid requirement was converted to intravenous morphine equivalents for standardized comparison. Total opioid and daily (24hr) requirements were determined for each admission.

Full analysis of all thirty subjects (uncomplicated and complicated pain crises, ketamine infusion of any duration) revealed that the opioid requirement was significantly lower after ketamine compared to before ketamine was started (Wilcoxon signed-rank test P=0.029). The total opioid requirement during the entire ketamine admission, however, was not significantly different from the total opioid requirement during the non-ketamine admission (P=0.088).

When a sub-analysis was performed on subjects receiving a ketamine infusion for greater than 24 hours (N=22), the 24hr opioid requirement was significantly lower after ketamine compared to before ketamine was started (P=0.0397). The total opioid requirement during the entire ketamine admission was not significantly different from the total opioid requirement during the non-ketamine admission (P=0.194).

When a sub-analysis was performed on subjects with an uncomplicated vaso-occlusive episode (N=17), 24hr opioid requirement was significantly lower after ketamine compared to before ketamine was started (P=0.036). Additionally, the average daily opioid requirement throughout the entire ketamine admission was significantly lower than the average daily opioid requirement during the non-ketamine admission (P=0.001). The total opioid requirement during the entire ketamine admission was not significantly different from the total opioid requirement during the non-ketamine admission (P=1). For the full and subgroup analyses of opioid requirements during the ketamine admission, there was a significantly greater amount of opioid required before the ketamine was started compared to during and after ketamine infusion.

The use of low-dose infusion of ketamine as an adjuvant for pain control in patients with SCD during vaso-occlusive episode resulted in a significant decrease in opioid requirements. Hence it appears that a low-dose ketamine infusion has utility in the treatment of acute pain crises in adult patients with sickle cell disease.

No relevant conflicts of interest to declare.