Opioid Use Is NOT Associated with in-Hospital Mortality Among Patients with Sickle CELL Disease in the United States: Findings from the National Inpatient Sample
Authors: Akinboro Oladimeji Akinola , Nwabudike Stanley , Edwards Camille , Cirstea Diana , Addo-Tabiri Nana Oduraa , Voisine Michael , Yameen Hassan , Kassim Adetola A. 
Published: October 2019

Abstract
Background
Vaso-occlusive pain crises account for the majority of hospitalizations in patients with sickle cell disease (SCD), and opioids are the mainstay of chronic pain control in SCD. However, a marked increase in opioid-related overdoses and deaths in the United States (US) - 'the US opioid epidemic' - has been documented since 2000. We sought to: i) examine temporal trends in hospitalization rates and in-hospital mortality rates among adults with SCD since the onset of the US opioid epidemic, and ii) compare in-hospital mortality rates for SCD with the rates of opioid prescription-related deaths in the non-SCD general population since the onset of the US opioid epidemic.
Methods
We obtained data from the National Inpatient Sample from 1998 through 2013. We identified hospitalizations for patients with sickle cell disease using discharge diagnoses (ICD-9-CM) codes 282.41, 282.42, 282.60, 282.61, 282.62, 282.63, 282.64, 282.68, and 282.69. We examined hospitalization and in-hospital mortality rates and trends for the entire sample of SCD patients, as well as by the following age groups: 0-17 years, 18-44 years, 45-64 years, and ≥65 years. We also examined in-hospital mortality hospitalization trends by U.S Census Bureau regions viz: Northeast, Midwest, South, and West. Survey weights were applied in estimating the population-based hospitalization rates. We utilized annual mid-year population figures provided by the US Census Bureau as the reference population for each year. Survey analysis and trend analyses were performed with Stata 14.2®(StataCorp, College Station, TX), and Joinpoint Regression Program 4.2.02® (National Cancer Institute), respectively.
Results
There were 1,755,220 hospitalizations among SCD patients in the US from 1998 to 2013. Hospitalization rates for SCD patients initially declined annually by 9.9% (95% CI: 4.0, 15.5) from 39/100,000 persons in 1998 to 27/100,000 persons in 2002, but no significant temporal trends were noted from 2002 to 2013 (figure 1).
However, among young adults with SCD (18-44 years), there was a significant annual increase in hospitalization rates by 3.8% (95% CI: 2.4%, 5.2) from 43/100,000 persons in 2002 to 71/100,000 persons in 2013. Elderly SCD patients (≥65 years) also had a significant annual increase in hospitalization rates by 6.5% (95% CI: 2.9%, 10.2%) from 2.7/100,000 persons in 1998 to 5.4/100,000 persons in 2013. The only region with a significant increase in SCD hospitalization rate was the South with an annual increase of 3.5% (95% CI: 0.6, 6.4) from 2001 through 2011.There was no significant increase in-hospital SCD mortality, in contrast to the 350% increase in non-SCD opioid prescription-related death rates in the US from 1999 through 2013 (figure 2).
Conclusion
Hospitalization rates are rising among most age-groups of adults with SCD. The reasons for this finding are unclear but the rising rates may reflect the fragmentation of care for SCD in adults as well as age-related increases in pain-related comorbidities and SCD complications as SCD patients live longer. However, there has been no associated increase in-hospital SCD mortality, supporting extant data which suggest that the rate of opioid-related deaths in SCD is low, and the use of opioids for pain control may be considered relatively safe in the SCD population.

Disclosures
No relevant conflicts of interest to declare.