Inpatient Use of Extended-Release (ER) Opioids for Vaso-Occlusive Crisis Associated with Increased Length of Stay for ER Opioid-Naïve Patients

Background: The intermittent acute pain syndrome associated with sickle cell disease (SCD) is a poorly understood phenomenon with complex pathophysiology. Given the broad spectrum of analgesic interventions, including immediate-release (IR) and extended-release (ER) opioids, healthcare providers are challenged with the task of safely and effectively escalating inpatient opioid regimens, especially in the setting of limited guidelines outlining the combination of different opioid formulations. Despite SCD being the most common genetic disorder in the United States, more research is required to improve physician expertise with appropriate and timely pain management of vaso-occlusive crisis.

Methods: This study was a retrospective chart review (n=200) of patients with known SCD requiring hospitalization for acute pain secondary to vaso-occlusive crisis without an alternative etiology of pain symptoms. The review included a patient population aged 18-67 years old with 43.5% males and 56.5% females hospitalized from 2/1/2022 to 5/6/2022. The primary outcome measure was hospital length of stay (LOS) for adequate pain control compared against varying factors of inpatient opioid-prescribing practices, including initiation or continuation (if prescribed within 6 months prior to admission encounter per PDMP review) of an ER opioid formulation, degree of morphine milligram equivalents (MME) escalation from outpatient regimen, utilization of a sickle cell analgesic order set, and initiation of patient-controlled analgesia pump (PCA). A secondary outcome measure investigated was the quantitative comparison of highest daily prescribed MME in relation to the aforementioned inpatient variables. Data analysis was completed using Wilcoxon Rank Summary analysis, with a significant p-value set to < 0.05.

Results: Among the primary outcome analysis, the only significant factor affecting LOS was the introduction of an ER opioid. The results show that within the patient cohort naïve to an outpatient ER opioid (n=105), ER opioid-incorporated inpatient analgesic regimens resulted in a significantly increased mean LOS compared to IR opioid monotherapy regimens, with an average of 8.8 inpatient days as compared to 5.3 days, respectively (p-value < 0.001). For the patients prescribed an outpatient ER opioid at baseline (n=95), the continuation of an inpatient ER opioid did not result in a significant change in mean LOS, calculated as 6.7 days vs. 6.0 days in the continued and non-continued groups, respectively (p-value = 0.716). Among the secondary outcome measures, utilization of a sickle cell order set and PCA did not significantly affect degree of MME escalation.

Conclusions: Limited evidence-based recommendations for the treatment of acute pain episodes in SCD has resulted in widely varying opioid regimens prescribed by inpatient providers and has created clinical challenges regarding the optimization of pain management. This study investigated inpatient opioid regimens utilized in treatment of vaso-occlusive crisis and found that the initiation of ER opioids resulted in increased length of stay for ER opioid-naïve patients as compared to treatment with IR opioids alone. These results question the benefit of inpatient ER opioids in relation to the risk of opioid dependence and MME escalation.