Opioid Overdose in Patients with Sickle Cell Disease, Outcomes Among Hospitalized Patients in the United States: A Nationwide Analysis
Authors: Bode Anna , Mumtaz Aqsa , Borja Montes Oscar , Quazi Mohammed , Sohail Amir , Smith Christopher , Sheikh Abu Baker 
Published: December 2024

Introduction
Sickle cell disease (SCD) is a rare inherited hematologic disorder characterized by a missense mutation in the human beta globin gene, leading to the sickle hemoglobin variant HbS. SCD patients are at frequent risk of catastrophic pain events secondary to vaso-occlusive crises. Opioid medications are commonly used to manage severe pain in SCD patients yet concerns about the risk of opioid use in this population has often led to undertreatment of their pain both before and after the onset of the opioid epidemic. Our study aims to analyze outcomes in patients hospitalized with opioid overdose with and without SCD to address the issue of undertreatment of pain in VOC and the concerns that providers have with prescribing opioids to this population of patients.
Methods
Our descriptive, retrospective study used data from the National Inpatient Sample (NIS) database from 2016-2021 to assess outcomes in patients hospitalized with opioid overdose with and without SCD, focusing on in-hospital mortality as the primary outcome. Additionally, we evaluated secondary outcomes including a range of in-hospital complications like mechanical ventilation and anoxic brain injury, among other outcome measures such as discharge outcomes. In our statistical analysis we used multivariate logistic regression (MLR), to adjust for age, hospital bed capacity, race, gender, hospital location, hospital teaching status, hospital´s regional placement, median household income, anticipated primary player, and Elixhauser comorbidities. We also implemented propensity score matching (PSM) to address variables such as patient age, gender, race, income, insurance status, and Elixhauser.
Results
Our study included a total of 479,175 hospitalized patients with Opioid overdose, out of which 1,660 (0.35%) had a concomitant history of sickle cell disease (SCD). After using PSM, both groups (those with SCD and those without) comprised 1,660 patients each. Regarding our primary outcome, we found a disparity in in-hospital mortality between SCD and non-SCD patients with opioid overdose (2.71% vs. 4.5%, adjusted OR [aOR]: 0.67 [95% CI 0.34-1.31], p = 0.242), which was not statistically significant. After PSM, the aOR was calculated to be 0.66 (95% CI 0.28-1.58), with a p-value of 0.353, again indicating no statistically significant difference in mortality between the two groups.
The incidence of opioid overdose related-complications such as invasive mechanical ventilation (22.83% vs. 10.54%, aOR: 0.39 [95% CI 0.28-0.56], p-value &lt;0.001) and anoxic brain damage (4.79% vs. 1.2%, aOR: 0.22, [95% CI 0.08-0.59], p-value: 0.003) were significantly higher in the group without SCD compared to the group with SCD, whereas in the SCD group venous thromboembolism was higher (4.22% vs. 1.88%, aOR: 2.10, [95% CI 1.22 -3.60], p-value: 0.007). Incidence of other complications was assessed, however, there were no statistically significant differences in the incidence of these complications between the two groups. This remained true with PSM, except there was no significant difference when comparing VTE.
Conclusion
In terms of our primary outcome, our data reveals no significant difference in in-hospital mortality between patients with SCD and patients without SCD admitted for opioid overdoses. That is, SCD patients do not have a higher risk of in-hospital mortality than other patients admitted with opioid overdose. These results remained the same with MLR and PSM enhancing the validity of our findings. Regarding our secondary outcomes, our study provides statistically significant evidence that SCD patients are equally or less likely and not more likely, to experience poor outcomes or complications when compared to non-SCD patients after admission to the hospital for opioid overdose. SCD patients were also found to experience more favorable discharge outcomes including less AMA discharges, more discharges to routine care, higher rates of home health care, and lower rates of transfers to other facilities. Again, the results of our study provide statistically significant evidence that SCD patients are equally or less likely and not more likely to experience poor outcomes related to hospitalization and discharge after opioid overdose when compared with non-SCD patients. Evidence from studies such as this may help to decrease undertreatment of VOC pain crises and to improve care for these patients.