Abstract
Introduction Sickle Cell Disease (SCD) is an autosomal recessive blood disorder caused by defective hemoglobin that leads to the “sickling” of red blood cells (RBCs). This abnormal shape leads to SCD also being characterized by acute and chronic pain, where acute pain occurs during vaso-occlusive crises (VOC) when sickled RBCs cause the occlusion of blood flow in small vessels, instigating widespread inflammation and tissue damage. Over time, patients with SCD can also develop chronic pain, though the full pathophysiology has yet to be fully understood. However, a major contributor to the development of chronic pain in patients with SCD is thought to be the consequences of the long-term effects of VOC, including avascular necrosis, bone infarctions, hyperalgesia after a VOC, and central sensitization. As with many conditions characterized by pain, chronic pain control can be difficult to achieve in patients with SCD. While recommended pain management is multifactorial, combining non-pharmacological methods, non-opioid medications, and opioids, the acute use of opioids is considered a standard of care in managing severe VOC. Outpatient opioid prescriptions are also commonly used by clinicians for these patients with the goal of decreasing the number of required hospital visits, and to treat patients with chronic pain, though analyses have not shown effectiveness in their use for long-term pain relief. Indeed, a higher outpatient dose of opioids has been associated with a greater number of visits (Prince, 2022). Given opioids are not indicated for other types of chronic pain, it raises the question of whether outpatient opioid prescriptions do actually prevent hospital visits for patients with SCD, or may even lead to increasing medical needs.
Methods To further investigate the relationship between outpatient opioid prescriptions and pain control, a retrospective chart review of patients (n = 237) who had at least one visit to the Grady sickle cell acute care clinic in January, March, or April of 2024 was conducted. For the year prior to their visit, the daily average amount of prescribed outpatient morphine milligram equivalents (MME), number of visits to an emergency department (ED) and inpatient admissions, and total days in hospital were calculated. Prescription information was collected from the Georgia Prescription Drug Monitoring Program. We hypothesized that a total higher dose of outpatient opioids prescribed would be positively correlated with all three of the previously mentioned parameters.
Results/Discussion The calculated one-tailed Pearson coefficient indicated a significant positive correlation between average daily outpatient MME and number of ED visits (r = 4.052, P < .0001), number of hospital admissions (r = .3565, P < .0001), and total number of days in hospital (r = .3854, P < .0001). Overall, these findings provide evidence that the continued prescription of outpatient opioids for patients with SCD may not prevent, and may even increase the risk of, hospital visits. The mechanism for these findings has yet to be fully determined, as well as the directionality: While it may be that higher outpatient opioid doses contribute to an increased requirement of healthcare, it could equally be true that patients with increased healthcare needs require more opioid pain medication. Nevertheless, there are multiple mechanisms by which opioid medications could increase the risk for patients with SCD needing care: Opioid hyperalgesia is a serious concern, and may be a significant contributing reason as to why some patients may have higher numbers of emergency room visits and admissions despite a higher dose of opioids. Opioid tolerance is also a concern, where patients with SCD on chronic opioids may have more difficulty obtaining proper pain control. Multiple studies have already shown opioids have poor efficacy for chronic pain, indicating that better chronic pain management strategies than outpatient opioids are likely needed. Further studies will be needed to better determine the balance between pain control in SCD and prevention of overprescribing of opioids.
