Early Initiation of Sub−Anesthetic Ketamine Infusion in Adults with Vaso-Occlusive Crises Is Associated with Greater Reduction in Sickle Cell Pain Intensity: A Single Center’s Experience

Abstract

Objectives Recurrent, severely painful episodes, known as vaso-occlusive crises (VOCs) are the hallmark of sickle cell disease (SCD) and the primary reason for hospitalization. Opioids have been the gold standard for VOC treatment without significant improvement pain outcomes. To aid analgesia and combat opioid related adverse effects (ORAEs), some SCD clinicians have trialed infusions of sub-anesthetic ketamine along with opioids to treat VOCs. In this retrospective analysis, we compared adult SCD patients who received early versus late adjunctive sub-anesthetic ketamine infusions for VOCs. Methods We identified adult SCD patients (age 18–50 years) who presented to Duke University with a VOC and received sub-anesthetic ketamine infusions from July 2015 to June 2019. We assessed both daily opioid consumption (measured as oral morphine milligram equivalents (MME)) and self-reported 0–10 numeric pain ratings (NPR) at one, two, and three days after infusion initiation, as well as one day after discontinuation. Results A total of 56 patients were identified with a median age of 30 years. Compared to late administration, early infusion of sub-anesthetic ketamine was associated with a 24.5% (p = 0.0003) and 25.9% (p = 0.0006) reduction, respectively, in median NPR at one day and two days after infusion initiation but did not persist at three days following initiation of the infusion. A statistically significant reduction in MME was not observed. Conclusion In a non-randomized study of sickle cell patients with VOCs, early sub-anesthetic ketamine infusion led to greater reduction in subjective pain intensity than late initiation of the infusion. Randomized studies should further explore whether early versus late ketamine infusion improves management of acute SCD pain.

Ketamine use for management of vaso‐occlusive pain in pediatric sickle cell disease

“…27 In a recent study in adults with SCD, initiation of ketamine within 3 days of admission was associated with a significant decrease in patient-reported pain. 28 More data are needed to determine whether ketamine infusion should be started at the time of opioid PCA initiation or whether ketamine initiation should be deferred until after it has been determined that opioids are not adequately capturing a patient's pain. Emergency department studies showing a reduction in opioid use and pain when ketamine is given with morphine for acute pain suggest a benefit to ketamine initiation at the time of PCA initiation, but those patients may have more side effects.…”

“…In most patients with VOE, the episode is preceded by a prodromal phase lasting 1–2 days, followed by peaking of pain on day 3, and a duration until approximately day 6 or 7 before resolving 27 . In a recent study in adults with SCD, initiation of ketamine within 3 days of admission was associated with a significant decrease in patient‐reported pain 28 . More data are needed to determine whether ketamine infusion should be started at the time of opioid PCA initiation or whether ketamine initiation should be deferred until after it has been determined that opioids are not adequately capturing a patient's pain.…”