High inpatient dose of opioid at discharge compared to home dose predicts readmission risk in sickle cell disease
Authors: Jin Han, Santosh L. Saraf, Michel Gowhari, Shivi Jain, Robert E. Molokie, Victor R. Gordeuk
Journal: American Journal of Hematology (2018)

Vaso-occlusive crisis (VOC) is the hallmark complication of sickle cell disease (SCD), contributing to the majority of SCD-related healthcare costs in the United States.1 Risk factors, such as prescribing nonsteroidal anti-inflammatory drugs without opioids, older age, and steroid treatment, are associated with readmissions in pediatric SCD patients,2, 3 but limited data exist in adults.4, 5 Premature discharge based on pain scores, absence of primary care providers and multiple VOC-related admissions in the prior year are associated with increased risk of 30-day readmission (30-DR) in adult SCD patients.4, 5 In this report, we analyzed the inpatient and outpatient opioid utilization in a cohort of 70 adult SCD patients hospitalized for an uncomplicated VOC, and found that a high opioid dose during the last 24-hours of the inpatient stay compared with the home dose after discharge is a modifiable risk factor for readmission. Adult (≥18-years old) SCD patients treated at the University of Illinois at Chicago Hospital from 2012 to 2016 who had at least 1 hospitalization for an uncomplicated VOC that was followed by a 30-DR and at least 1 VOC hospitalization without a 30-DR were identified from the electronic medical records. Patients who were admitted 10 or more times per year during any given year from 2012 to 2016 were excluded. Hospitalizations during which patients were pregnant or treated with ketamine and hospitalizations within 30 days of a prior admission were excluded. One hospitalization with a 30-DR and the closest hospitalization without a 30-DR from each patient were used to form the discovery cohort (140 hospitalizations from 70 unique patients). Patient characteristics, inpatient laboratory values, inpatient daily opioid use and daily opioid use after discharge were recorded. The ratio of opioid dose during the last 24-hour inpatient stay/home opioid dose after discharge was calculated. Among the 70 patients included in the discovery cohort, 22 patients had more than 1 hospitalization with a 30-DR between 2012 and 2016. The additional hospitalizations with a 30-DR were matched with the closest hospitalizations without a 30-DR from the same patient, and were used to form a validation analysis (62 hospitalizations from 22 unique patients). A Wilcoxon signed-rank test was performed for comparison. The study was approved by the Institutional Review Board. Among the 70 SCD patients identified, the median (IQR) age was 32.5 (25-44) years, and 67% of the subjects were females. A total of 76% were HbSS/Sβ0 genotype, and 46% were being treated with hydroxyurea and 83% were opioid tolerant patients, defined as daily outpatient opioid dose >60 mg OME. When the hospitalizations with a 30-DR were compared with those without a 30-DR in 70 SCD patients (Table 1), the ratio of opioid dose during the last 24-hour inpatient stay/home opioid dose was higher (median: 1.9 vs 1.5, P = .024). Other relevant clinical variables, including hospital length of stay (LOS), pain score upon discharge, and hemoglobin concentration or WBC count upon discharge, were not significantly different (Table 1). Mean LOS for SCD patients hospitalized for a VOC at our institution was 4.49-6.62 days from 2012 to 2016,6 and appeared longer than the LOS observed in the current cohort (Table 1). The proportion of hospitalizations during which patients used patient controlled analgesia (without a 30-DR vs with a 30-DR, 67% vs 70%), underwent opioid dose tapering (67% vs 66%), or converted IV opioids to oral ones during hospitalization (26% vs 27%) were comparable between the 2 groups. In the validation analysis involving 22 patients, the ratio of opioid dose during the last 24-hour inpatient stay/home opioid dose in the group with a 30-DR was also higher than the ones without a 30-DR (2.0 vs 1.4, P = .033), whereas other clinical variables were comparable (Table 1). Patients with SCD who are admitted for VOC episodes have higher 30-DR rates than other disease states.4, 5 In this report, we identified a high ratio of opioid dose during the last 24-hour inpatient stay/home opioid dose as a modifiable risk factor for 30-DR. A previous report showed that 5 adult SCD patients were readmitted multiple times following VOC-related hospitalizations for opioid withdrawal.5 If patients are treated with much higher dose of opioids in the hospital than their home dose, especially right before discharge, potential opioid withdrawal may trigger the onset of subsequent VOC episodes and readmissions. In the discovery cohort, 37% of readmissions occurred within 10 days after discharge, which might result from withdrawal symptoms. Treatment with higher doses of opioids during hospitalization may also be an indicator of high severity of the VOC episode, which may be related to a subsequent 30-DR if the patient is discharged prematurely. Readmission after VOC hospitalizations is associated with high mortality in SCD patients5; therefore, it is important to identify and amend modifiable risk factors. Since our finding is based on a paired test, some previously identified risk factors for re-admission such as lack of primary care providers and multiple VOC-related admissions in the prior year were not included in the analysis. The pain scores upon discharge between admissions with and those without 30-DR showed no significant difference (Table 1). Here we report that a high ratio of opioid dose during the last 24-hour inpatient stay/home opioid dose is a modifiable risk factor for readmission in the adult SCD patients. The results suggest that tapering the inpatient opioid dose to <150% of patient's home opioid dose before discharge may reduce the readmission risk. Limitations to our study include the following. It is a single-center study with a small sample size and a retrospective design. The readmission risk may be under-estimated by not including patients with more than 10 hospitalizations per year and admissions to other hospitals. The calculation of home opioid dose assumes that opioids were taken around the clock, which is typically the case right after discharge but may not be accurate in all patients. The findings require substantiation in prospective clinical trials to evaluate the relationship between inpatient opioid dose and readmission risk. Nothing to report.