Introduction: Pain is the most common complication of sickle cell disease (SCD) and a frequent cause of acute care utilization. It can be acute due to vaso-occlusive crisis or chronic with over 50% of adults experiencing chronic pain.1 Having chronic pain was associated with both high daily opioid use (≥ 90 MME) and worse quality of life (3,4). High daily opioid use in SCD was also associated with higher acute care utilization5 and ~50% of SCD adults presenting to a large urban acute-care centre were on chronic daily opioids.2 Opioids have been the mainstay of treatment for both acute and chronic pain in SCD however there is emerging evidence of the poor efficacy and high toxicity/morbidity associated with continuous daily use of opioids in any patient. These adverse effects include tolerance, dependency, opioid induced hyperalgesia, worsening of mood disorders, constipation and opioid withdrawal. The current opioid crisis demands that we identify alternatives to reduce daily high-dose opioids for treating SCD chronic pain that may also reduce acute care utilization and quality of life. Buprenorphine is a partial Mu receptor agonist and Kappa receptor antagonist. This product is approved to treat chronic pain. Naloxone is a Mu receptor antagonist. Buprenorphine/naloxone (B/N) combination products have been used to treat opioid use disorders and is increasingly used off-label to treat chronic pain in patients with opioid dependence. There is currently no published data on the use of buprenorphine alone or B/N in the management of chronic pain in adults with SCD. METHODS: We hypothesized that use of B/N in adults with SCD reduce both acute care utilization and daily opioid use while improving overall clinical outcomes. Using a retrospective chart audit we evaluated patients transitioned to B/N between January 1st, 2016 and April 30th, 2018 who had at least six months of follow up post transition. Patients were expected to follow up in clinic at least weekly for the first 4 visits, biweekly for 4 visits, and then monthly with a SCD provider and psychotherapist. We evaluated Morphine Equivalent Daily Dose (MEDD), acute care (ED) visits, inpatient (IP) admissions, length of stay (LOS), comorbid psychiatric diagnosis, hemoglobin S% (HbS) and F% (HbF) as markers of adherence to disease modifying therapy use and serum ferritin. MEDD was calculated by averaging monthly opioid use and included both outpatient prescriptions from the state's-controlled substance database and inpatient opioid doses administered from the electronic medical record, respectively. ED/IP visits (normalized on an annual basis), average LOS, and lab values were compared over two time-periods: from the date of entry into our SCD program to the date of initiation of B/N (switch date), and from the switch date to the last follow-up date. MEDD was compared for the 6 months pre- and post- initiation of B/N. Outcomes were analysed using generalized linear mixed models with the pre- and post-switch date as the fixed factor in the model. A random effect for subject was included to account the repeated observations. Results: Twenty-four patients were evalauted: 67% Female; median age 36 years (range 18 - 65). Genotype distribution: HbSS 15 (63%); HbSC 5 (21%); SB+Thal 4 (17%); 92% had a comorbid psychiatric condition (major depression, bipolar disorder, generalized anxiety disorder). Our results (summarized in Table 1) demonstrate significant reductions in acute care utilization (ED/IP visits, average IP LOS) and MEDD after initiation of B/N (p<0.001). No significant differences were noted in Ferritin level and HbF% between pre- and post-initiation of B/N. There was a trend towards reduced HbS% as a marker of adherence to monthly erythrocytapheresis however sample size was small. Conclusion: These results demonstrate that Buprenorphine/naloxone is effective in reducing acute care utilization among adults with SCD and drastically lowering the amount of daily opioids used to manage chronic pain. The impact of B/N on acute care utilization and daily opioid use was independent of adherence to disease modifying therapy (hydroxycarbamide and chronic erythrocytapheresis). Disclosures Osunkwo: Micella Biopharma: Other: DSMB Member ; Terumo: Speakers Bureau; Pfizer: Consultancy; Novartis: Consultancy, Speakers Bureau. Symanowski:Boston Biomedical: Membership on an entity's Board of Directors or advisory committees; Eli Lilly: Membership on an entity's Board of Directors or advisory committees; Immatics: Membership on an entity's Board of Directors or advisory committees; Carsgen Therapeutics: Membership on an entity's Board of Directors or advisory committees.

Inpatient management of sickle cell disease (SCD) vaso-occlusive crisis (VOC) often involves use of high-dose opioids, which may result in opioid-induced pruritus (OIP). This OIP is typically treated with antihistamines like diphenhydramine either orally or intravenously. The oversedation adverse effects of diphenhydramine may be magnified when given in combination with high-dose opioid therapy. Current recommendations made by the National Heart, Lung, and Blood Institute endorse using oral rather than intravenous (IV) antihistamines to avoid the cumulative effect on sedation. Despite this guideline, IV diphenhydramine use is still prevalent in many hospitals that treat persons with SCD. We performed a retrospective, single-center, cohort study comparing rates of oversedation among patients who received IV and oral diphenhydramine for management of opioid-induced pruritus in a large SCD inpatient population. Patients with SCD VOC admitted to an urban hospital between June 1, 2016 to July 30, 2017 were included if they were ≥ 18 years old and received either IV or oral diphenhydramine for OIP. Exclusion criteria: Pregnancy, received <24 hours of diphenhydramine, or <50% of their "as needed" doses of diphenhydramine. Primary endpoint: comparative incidence of oversedation in SCD VOC receiving IV versus oral diphenhydramine. Oversedation was defined as meeting two or more of the following criteria: documentation of oversedation in clinician notes, medication doses held by a nurse due to sedation, a PASERO opioid-sedation score ≤3, or documented hypoxemia with O2 percent saturation ≥ 2 points below baseline. Secondary endpoints included: evaluation of hospital length of stay, amount of diphenhydramine administered per day, indication for IV therapy, and number of days receiving diphenhydramine. Individual admissions were portioned by route of diphenhydramine administration cohorts (IV versus oral). Within each cohort, study endpoints were derived at the patient level. Oversedation was determined at the patient level i.e. experiencing at least one occurrence over the course of their admissions. The number of admissions, length of stay, and days of diphenhydramine treatment were totaled across admissions for each patient. The daily dose of diphenhydramine administration (mg/day) was averaged across the admissions per patient. The proportion of subjects experiencing oversedation was summarized by cohort and compared using Fisher's exact test. Length of stay, number of days on treatment, and average daily dose of diphenhydramine were analyzed with analysis of variance (ANOVA) techniques. Length of stay and number of days on treatment were log-transformed prior to statistical analyses. The number of admissions was analyzed with Poisson regression. Fifty unique patients were included in the analysis representing 121 admissions. Seven patients received both formulations on separate admissions and were included in both groups, 15 received oral diphenhydramine, and 42 received the IV formulation. The percent of patients experiencing oversedation was higher in the IV group, however the difference was not statistically significant (p = 0.312). The average number of admissions was significantly higher in the IV versus oral group (2.45 vs. 1.20; p = 0.005) with average and median length of stay also significantly higher in the IV versus oral group (30.57, 16.0 vs. 10.67, 10.0; p = 0.003). Similarly, the average and median number of days on diphenhydramine treatment in the IV group was significantly higher than in the oral group (28.79, 14.5 vs. 9.73, 7.0; p = 0.001). The average daily dose of diphenhydramine was similar in the two cohorts with no compelling indications documented for use of IV over oral formulation. In summary, while we did not find a statistically significant difference in the rates of oversedation with use of IV versus oral diphenhydramine formulations, patients with SCD VOC who received IV diphenhydramine were more likely to have more frequent admissions, and a longer length of stay. These findings have clear impact on clinical outcomes and cost of care and clinicians may consider oral diphenhydramine preferentially in appropriate patients over IV administration. Larger, prospective studies are needed to evaluate the absolute risk to benefit ratio between the two formulations particularly among person receiving concomitant parenteral opioid therapy. Disclosures Osunkwo: Terumo BCT: Speakers Bureau; Prolog Pharmaceuticals LLC: Consultancy; Novartis Pharmaceuticals LLC: Consultancy, Speakers Bureau. Symanowski:Immatics: Other: Data Safety Monitoring Board; Eli Lily & Co: Other: Data Safety Monitoring Board; Boston Biomedical: Other: Data Safety Monitoring Board ; Five Prime Therapeutics: Other: Data Safety Monitoring Board .

Purpose: To compare the incidence of oversedation between oral and parenteral diphenhydramine therapy for treatment of opioid-induced pruritus in patients with sickle cell disease vaso-occlusive crisis (SCD VOC). Methods: This retrospective, single-center, cohort study included patients greater than or equal to 18 years old with sickle cell disease admitted for vaso-occlusive crisis who received either intravenous or oral diphenhydramine for opioid-induced pruritus. Patients were identified through ICD-9 and ICD-10 codes from June 1, 2016 through July 1, 2017. Rates of oversedation were compared between the 2 formulations. Secondary endpoints included length of stay, amount and duration of diphenhydramine, rate of acute chest and indication for IV therapy. Results: Fifty unique patients were included in the analysis representing 121 admissions. Seven patients received both formulations on separate admissions and were included in both groups. Twenty-nine percent of patients in the IV diphenhydramine group experienced oversedation (12/42) versus 13% in the oral diphenhydramine group (2/15, P = .312). The average number of admissions was significantly higher in the IV versus oral group (2.45 vs 1.20; P = .005) with average and median length of stay also significantly higher in the IV versus oral group (30.57, 16.0 vs 10.67, 10.0; P = .003). Conclusion: While there was no statistically significant difference in the rates of oversedation with use of IV versus oral diphenhydramine formulations, patients with SCD VOC who received IV diphenhydramine had more frequent admissions and a longer length of stay. Clinicians may consider oral diphenhydramine preferentially in appropriate patients over IV administration.

Sickle cell disease (SCD) can pose serious maternal and fetal risk in pregnancy. Transfusion, both during and outside of pregnancy, can improve patient morbidity and mortality but carries risk of alloimmunization, complicating future management. This case describes a 29-year-old gravida 1, para 0 woman with sickle cell anemia and rare red blood cell alloantibody (anti-Rh46) who presented with severe vaso-occlusive crisis at 29 weeks with hemoglobin of 7.6 g/dL. Only one unit of compatible blood existed in the country. Planning for transfusion with least-incompatible blood was made. She ultimately underwent cesarean section at 31 weeks and 2 days for abnormal fetal testing. This case highlights that blood products should be utilized judiciously because their adverse effects, like alloimmunization, can increase patient morbidity and mortality.