The complex association of daily opioid dose with visits for pain in sickle cell disease: tolerance or treatment refractory pain?

INTRODUCTION
Opioids are used for acute and chronic pain in patients with sickle cell disease. How outpatient opioid regimens relate to acute care visits is of interest given risks of high opioid doses and high hospital utilization. A prior study by our group suggested outpatient opioid treatment for chronic pain could contribute to a vicious cycle of treatment-refractory acute pain, greater acute care utilization, and escalating opioid doses. This larger naturalistic observational study was undertaken to determine if the results were reliable across multiple acute care settings.


METHODS
One year of clinical data on patients (n = 291) followed in the Sickle Cell Center for Adults (August 2018 to July 2019) were extracted, including visits to the emergency department, infusion center, and inpatient admissions. Outpatient opioid dosage was used to predict acute care treatment in generalized linear models controlling for patient, disease, and treatment characteristics.


RESULTS
Outpatient opioid dosage predicted dosage during visits, but not visit length or pain relief. Higher outpatient opioid dosage was associated with greater number of visits. However, in post hoc analyses this relationship was nonlinear; with clear positive association only for those prescribed the lowest 50% of dosages.


DISCUSSION
Higher outpatient opioid dosage predicted higher dosages during acute care visits to achieve the same pain score improvement, more consistent with opioid tolerance than treatment-refractory pain. The relationship of outpatient opioid dosage with number of acute care visits was more complex, suggesting opioid consumption at lower levels is driven by intermittent acute pain, and at higher levels by chronic pain.