Does Treatment with Hydroxyurea and Opioids Affect Age of Death in Sickle Cell Disease Patients?
Authors: Flahiff Charlene M. , Jonassaint Jude C , Jonassaint Charles R. , Adam Soheir S. , Telen Marilyn J. , De Castro Laura M. 
Published: April 2020

Abstract
Hydroxyurea (HU) is used to treat sickle cell disease and has been shown to decrease painful episodes (Charache, 1995) and possibly vaso-occlusive episodes associated morbidity and mortality (Steinberg, 2003). Opioids are often prescribed in adult patients for daily management of their chronic pain. The aim of the current study was to determine the age at death and the effect of treatment with HU and/or opioids prior to death in patients who died from sickle cell disease (SCD) related complications and to compare these parameters to those in our current patients population.
Methods: Age, daily treatment with opioids, and HU treatment were determined for 185 patients currently followed at the Duke Comprehensive Sickle Cell Center (DCSCC) and for 50 patients who died between 2002 and 2008 due to SCD complications and who were regularly followed at the DCSCC for their care. The two cohorts, living and deceased patients were divided based on their treatment modality into the following 4 groups: opioid only, HU only, both drugs, and neither drug. Non-parametric chi-square test was performed to determine whether the treatment modality distribution was different in the deceased group compared to the living group. Analysis of variance was done to determine the relationship between treatment group and age at death.
Results and Discussion: The distribution of treatment modalities in the deceased group was significantly different than that of the living group. The opioids only group had the largest number of patients in the deceased cohort (44%), and this percentage was almost twice that of the living group (25%). (Fig. 1) Moreover, 72 % of the deceased patients were treated with opioids vs. only 53 % of the living patients, perhaps because the sicker patients are often treated with daily opioids. However, the age of death in the opioids only group was 44 ± 15.5 years. (Fig. 2) In the living group, treatment with both drugs or with no drugs were equivalent (28%), while in the deceased group, more patients were treated with both drugs (28%) compared to no drug treatment (18%). The HU only group had the lowest number of deaths (10%), and the percentage of patients in this group was nearly half that the one of the living group (19%). This group also was the oldest at death (58 ±16 years). Age at death was also significantly higher in this group than in each of the other 3 groups (p&lt;0.05). The low use of HU in the deceased cohort, along with the higher age of death, support the reported effectiveness of this drug in reducing morbidity associated with SCD. The age of the living patients receiving treatment with both drugs was the same as that of the deceased. Similarly the age of the non treated living patients was comparable with that of the deceased group. Interestingly, the interaction of the 2 therapeutic interventions (HU and opiates) had a significant effect on the age at death (p=0.003). We conclude that opioid treatment, either alone or in conjunction with HU, appears to have a significant effect on the age at death and warrants further investigation.