Purpose of Review Sickle cell disease (SCD) is an inherited hemoglobinopathy with potential life-threatening complications that affect millions of people worldwide. Severe and disabling acute pain, referred to as a vaso-occlusive crisis (VOC), is a fundamental symptom of the disease and the primary driver for acute care visits and hospitalizations. Despite the publication of guidelines for VOC management over the past decade, management of VOCs remains unsatisfactory for patients and providers. Recent Findings Acute SCD pain includes pain secondary to VOCs and other forms of acute pain. Distinguishing VOC from non-VOC pain may be challenging for both patients and clinicians. Further, although opioids have been the gold-standard for VOC pain management for decades, the current highest standard of care for all acute pain is a multimodal approach that is less dependent on opioids, and, instead incorporates analgesics and adjuvants from different mechanistic pathways. In this narrative review, we focus on a multimodal pharmacologic approach for acute SCD pain management and explore the evidence for existing non-opioid pharmacological adjuncts. Moreover, we present an explanatory model of pain, which is not only novel in its application to SCD pain but also captures the multidimensional nature of the SCD pain experience and supports the need for such a multimodal approach. This model also highlights opportunities for new investigative and therapeutic targets – both pharmacological and non-pharmacological. Summary Multimodal pain regimens that are less dependent on opioids are urgently needed to improve acute pain outcomes for individuals with SCD. The proposed explanatory model for SCD pain offers novel opportunities to improve acute pain management for SCD patients.
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.
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