scholarly journals Tiered Oral Therapy Protocol for Sickle Cell Vaso-Occlusive Crisis

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3446-3446
Author(s):  
Margaret Guy ◽  
Lauren Magee ◽  
Jessica Keiser ◽  
Nicole Carter ◽  
DaleMarie Vaughan ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Length Of Stay ◽  
Sickle Cell ◽  
Readmission Rate ◽  
Oral Therapy ◽  
Historical Control ◽  
Hospital Charges ◽  
Cell Disease ◽  
Readmission Rates ◽  
Therapy Protocol

Background: Adults with sickle cell disease (SCD) often present with extremely painful acute vaso-occlusive crises (VOC). VOC guidelines quote studies supporting early initiation of opioids, but are lacking in a standardized approach to achieve adequate analgesia and subsequent de-escalation. Various SCD studies comparing continuous basal versus demand bolus patient-controlled analgesia (PCA) show conflicting outcomes. Thus the objective of our pilot was to develop a standardized approach to pain management utilizing PCA and a Tiered Oral Therapy Protocol (TOTP) in an effort to affect healthcare utilization by decreasing length of stay without increasing readmission rates. Methods: We studied admissions of 31 SCD (any genotype) patients (8 males, 23 females) ≥ 18 years old, all African-American, admitted for VOC, and treated by hospitalist providers using TOTP on one medical unit at Virginia Commonwealth University Health System from July 2018 to June 2019. Inpatient admissions for one calendar year prior to the initial TOTP admission served as the patient's historical control. TOTP is guided by the patient's individualized treatment plan and starts with continuation of their home basal dosing, demand dose only PCA, and immediate-release oral opioids for additional breakthrough pain. TOTP goals are aggressive up-titration of opioids until adequate analgesia. After a period of stability the next phase encourages timely, aggressive down-titration of opioids to speed discharge. We primarily compared length of stay (LOS), hospital charges, and 30-day readmission rates for TOTP vs historical controls. Secondarily, we compared adverse safety events: opioid-related rapid responses, naloxone administration, or falls. Results: Utilization of TOTP resulted in reductions in LOS (21%, 4.7 days controls vs. 3.7 days TOTP, p<0.014), and hospital charges ($1,627,497.73 controls vs. $944,528.96 TOTP, p=0.1403), and an insignificant increase in the 30-day readmission rate (35.6% controls vs. 42.7% TOTP, p=0.5027). Hospital charge data is difficult to interpret as a full year of post TOTP encounters are not available for all patients. There were no TOTP vs. historical control differences in opioid-related safety events. Conclusion: Standardization of therapy using the TOTP improved length of stay and reduced charges for patients with sickle cell disease admitted for acute VOC without increasing adverse safety events or significantly impacting the 30 day readmission rate. We have enlarged this pilot to include other VCU medical units, to test whether we can reproduce our initial one-unit success. Further, we recommend TOTP implementation and testing in other hospitals to exclude secondary trends, since TOTP was but one among several interventions in a VCU Adult SCD Medical Home. Figure Disclosures Smith: Novartis: Consultancy, Honoraria.

scholarly journals Improved Utilization Amongst Adult Sickle Cell Disease Patients: A Multi-Disciplinary Medical Home Approach

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 22-23
Author(s):  
Daniel Sop ◽  
Shirley Johnson ◽  
Benjamin Jaworowski ◽  
Wally R Smith
Keyword(s):  
Sickle Cell Disease ◽  
Length Of Stay ◽  
Sickle Cell ◽  
Medical Home ◽  
Research Funding ◽  
Readmission Rate ◽  
Cost Savings ◽  
Multidisciplinary Teams ◽  
Cell Disease ◽  
Number Of Patients

Background Worldwide, Sickle Cell Disease (SCD) is the most common monogenetic disorder. SCD is costly to the American health care system: $460,151 per patient for the 100,000 affected US patients. Biological and behavioral health comorbidities with limited hospital resources contributed to a cost increase in SCD readmissions at the Virginia Commonwealth University Health System (VCUHS) from 2012-2016, after a long history of decline. With increasing census, in FY16 the 30-day SCD readmission rate was 33.7%, up from 22.5% in FY14. The average SCD length of stay was 6.7 days, compared with an expected length of 4.2 days. The number of ED visits for SCD patients in FY17 was projected to be double that of FY14. The percent of ED returns in 3 days was projected to be triple that of FY14. Method The VCU Adult SCD Medical Home (ASCMH) was funded and launched to address this issue, based on the success of a pilot that showed cost savings of $333,000 for 5 patients in 12 months. The SCD ASCMH officially began January 1,2018 with a two-year pilot funding period. The ASCMH was structured and designed using quality improvement (QI) principles and consisted of multidisciplinary teams to coordinate inpatient care, emergency care, and ambulatory care respectively. Evaluation compared utilization during CY 2017 (pre-intervention) versus CY 2019 (2 years post intervention). For all patients we compared the average 30-day readmission rate, the average length of stay (ALOS), the average 3-Day ED return rate, the number of ED discharges, the numbers of inpatient days, inpatient discharges, and outpatient visits, the number of patients who used the ED, and total VCU charges. Results Among 541 (2017) and 592 (2019) SCD adults, including 40.6% males and 59.4% females, comparing pre-intervention to intervention, average utilization and VCU charges were either numerically or statistically significantly reduced. Mean 30-day readmission rates were reduced (31.60% vs 20.40%) ALOS was reduced (5.6 days vs 4.3 days), inpatient days were reduced (5313 days vs 3340 days), and total charges were significantly reduced ($15,664,895 vs $13,939,842). Conclusion At VCU, a multi-disciplinary ASCMH that featured intensive case management (CM) reduced annual utilization and cost savings for adult SCD patients. CM program elements that were most effective should be studied in the future and next steps should include a randomized controlled trial that can demonstrate evidence of their efficacy in strengthening and improving utilization Table Disclosures Smith: Emmaeus Pharmaceuticals, Inc.: Consultancy; GlycoMimetics, Inc.: Consultancy; Novartis, Inc.: Consultancy, Other: Investigator, Research Funding; Shire, Inc.: Other: Investigator, Research Funding; Imara: Research Funding; Novo Nordisk: Consultancy; Ironwood: Consultancy; Pfizer: Consultancy; Incyte: Other: Investigator; Health Resources and Services Administration: Other: Investigator, Research Funding; NHLBI: Research Funding; Patient-Centered Outcomes Research Institute: Other: Investigator, Research Funding; Global Blood Therapeutics, Inc.: Consultancy, Research Funding; Shire: Research Funding.

scholarly journals Hospitalization Events among Children and Adolescents with Sickle Cell Disease in Basra, Iraq

Anemia ◽  
2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Zeina A. Salman ◽  
Meaad K. Hassan
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Readmission Rate ◽  
Length Of Hospital Stay ◽  
Acute Chest Syndrome ◽  
Cell Disease ◽  
Opioid Use ◽  
Asthma Symptoms ◽  
The Mean ◽  
High Readmission Rate

Objectives. Despite improvements in the management of sickle cell disease (SCD), many patients still experience disease-related complications requiring hospitalizations. The objectives of this study were to identify causes of hospitalization among these patients and factors associated with the length of hospital stay (LOS) and readmission.Methods. Data from 160 patients (<14 years old) with SCD who were admitted to the Basra Maternity and Children’s Hospital from the first of January 2012 through July 2012 were analyzed.Results. The main causes of hospitalization were acute painful crises (73.84%), infections (9.28%), acute chest syndrome (8.02%), and acute splenic sequestration crisis (6.32%). The mean LOS was4.34±2.85days. The LOS for patients on hydroxyurea (3.41±2.64days) was shorter than that for patients who were not (4.59±2.86days),P<0.05. The readmission rate (23.1%) was significantly higher among patients with frequent hospitalizations in the previous year (OR 9.352, 95% CI 2.011–43.49), asthma symptoms (OR 4.225, 95% CI 1.125–15.862), and opioid use (OR 6.588, 95% CI 1.104–30.336). Patients on hydroxyurea were less likely to be readmitted (OR 0.082, 95% CI 0.10–0.663).Conclusions. There is a relatively high readmission rate among patients with SCD in Basra. The use of hydroxyurea significantly decreases the LOS and readmission rate.

Evaluation of Intravenous Diphenhydramine Use in Patients with Sickle Cell Vaso-Occlusive Crisis

2020 ◽  
pp. 001857872095417
Author(s):  
Katherine Rector ◽  
Shelby Merchant ◽  
Rachel Crawford ◽  
Justin R. Arnall ◽  
James Symanowski ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Length Of Stay ◽  
Sickle Cell ◽  
Cell Disease ◽  
Median Length ◽  
Significant Difference ◽  
Oral Group ◽  
Icd 10 ◽  
Secondary Endpoints ◽  
Group 2

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.

Variation in hospitalizations and hospital length of stay in children with vaso-occlusive crises in sickle cell disease

2005 ◽  
Vol 44 (2) ◽  
pp. 182-186 ◽  
Author(s):  
Julie A. Panepinto ◽  
David C. Brousseau ◽  
Cheryl A. Hillery ◽  
J. Paul Scott
Keyword(s):  
Sickle Cell Disease ◽  
Length Of Stay ◽  
Sickle Cell ◽  
Hospital Length ◽  
Hospital Length Of Stay ◽  
Cell Disease

The Incidence of Neonatal Abstinence Syndrome in Babies Born to Women with Sickle Cell Disease: A Single Center Study

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3225-3225
Author(s):  
Cynthia L Anderson ◽  
Karin J Blakemore ◽  
Sophie Lanzkron
Keyword(s):  
Sickle Cell Disease ◽  
Length Of Stay ◽  
Sickle Cell ◽  
Maternal Age ◽  
Neonatal Abstinence Syndrome ◽  
Abstinence Syndrome ◽  
Cell Disease ◽  
Live Births ◽  
Hospital Stays ◽  
The Mean

Abstract Abstract 3225 BACKGROUND: Little is known about the neonatal outcomes of infants born to mothers with SCD. Women with SCD are often treated for pain with opioid medication either intermittently or chronically throughout pregnancy. The incidence of withdrawal or neonatal abstinence syndrome has not been well described making counseling of these women about the risks and benefits of opioid therapy during pregnancy difficult. The objective of this study was to determine the incidence of neonatal abstinence syndrome (NAS) in babies born to women with sickle cell disease. METHODS: All pregnancies in women with sickle cell disease were identified within the Johns Hopkins Hospital between January 1, 2001 and January 1, 2011. Retrospective data collection was performed using the electronic medical record. Demographic and outcome information recorded included maternal age, gestational age at time of delivery, outcome of pregnancy, maternal genotype, neonatal intensive care unit (NICU) admissions, neonatal abstinence syndrome diagnosis and neonatal length of stay. Student t-tests and chi square analysis were used to compare outcomes as appropriate. RESULTS: 69 unique patients were identified. From these 69 women, 94 pregnancies were identified. Of these 94 pregnancies, 83 live births were noted. The other 11 pregnancies included 3 spontaneous abortions, 3 ectopic pregnancies, 4 terminations and 1 fetal death in utero. The mean maternal age at time of delivery was 25.5 +/− 5.1 years. The mean gestational age was 36 weeks 2 days (median 36 weeks 6 days with a range of 31 weeks 4 days to 39 weeks 3 days). Of the 83 live births noted in this retrospective cohort, 22 (27%) of these infants were admitted to the NICU and17 (20%) were diagnosed with neonatal abstinence syndrome. Of the 17 infants born with NAS, 12 infants (70%) were born to mothers with SS disease, 3 infants (18%) to mothers with Sβthalassemia and 2 infants (12%) to mothers with SC disease. 53% of babies born with NAS were delivered by C-section which was not statistically significantly different than babies born without NAS (42% p=0.60) The mean birth weight of the babies with NAS was 2521 grams compared to babies without NAS which was 2853 grams (p=0.07). 59% of babies with NAS required NICU care compared to 16% of babies without NAS (p<0.001). The mean length of stay for babies with NAS was significantly longer than those babies without NAS (14.7 days vs. 5.8 days, p=0.003). Of the babies without NAS, 44% had extended hospital stays due to baby-associated complications and the mean LOS was 10.6 days; 10% had extended hospital stays due to complications of the mother with a mean LOS of 6.5 days; and the mean LOS for the 45% of those without mother or baby complications was 2.5 days. CONCLUSIONS: Current recommendations include the use of opioids as needed for vaso-occlusive pain in pregnancies complicated by sickle cell disease. While effective, our study demonstrates that a significant percentage of infants exposed to opioids in utero develop neonatal abstinence syndrome. Future studies are indicated to delineate a dose-response relationship if one exists as well as alternative therapies to address this newly recognized important neonatal co-morbidity. Disclosures: Lanzkron: Hemaquest: Membership on an entity's Board of Directors or advisory committees; NHLBI: Research Funding.

Venous Thromboembolism In Pregnant Women With Sickle Cell Disease

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2217-2217
Author(s):  
Craig D. Seaman ◽  
Margaret V. Ragni ◽  
Charity G. Moore ◽  
Jie Li ◽  
Jonathan Yabes
Keyword(s):  
Venous Thromboembolism ◽  
Sickle Cell Disease ◽  
Length Of Stay ◽  
Pregnant Women ◽  
Sickle Cell ◽  
Pregnancy Complications ◽  
Categorical Variables ◽  
Acute Chest Syndrome ◽  
Cell Disease ◽  
Discharge Data

Abstract Background The risk of venous thromboembolism (VTE) is increased in pregnancy and sickle cell disease (SCD), yet the rates of pregnancy-related VTE are not firmly established in SCD, nor are other SCD-related complications, including pneumonia, vasooclusive crisis (VOC), and acute chest syndrome (ACS), which may be clinically indistinguishable from VTE. Moreover, the American College of Chest Physicians has made no recommendations regarding thromboprophylaxis in pregnant women with SCD. Methods Inpatient hospital discharge data for PE for the most recent 5-year period available, 2007-2011, were obtained from the Pennsylvania Health Care Cost Containment Council (PHC4). We compared VTE, pregnancy complications, medical co-morbidities, and mortality among pregnant women with and without SCD. Among pregnant SCD women with and without VTE, we also compared rates of pneumonia, vasooclusive crisis (VOC), and acute chest syndrome (ACS). All patient identifiers were removed. Diagnostic categories and co-morbidities were obtained using ICD-9 codes. Data from categorical variables were analyzed by chi-square or Fisher's exact test; and from continuous variables by two-sample Student t-test. Results The prevalence of VTE was 2.8% among pregnant women with SCD. Among pregnant women with SCD and VTE, the rate of pneumonia, 28.6% vs. 4.4%, p=0.043, was significantly higher than in those without VTE. While somewhat higher, the rates of VOC, 57.1% vs. 24.7%, p=0.073, and ACS, 14.3% vs. 2.4%, p=0.177, were not significantly different between pregnant SCD VTE and non-VTE groups. Comparing VTE and non-VTE pregnant SCD women, the rate of pregnancy complications did not differ, p=0.999; nor did the rates of medical co-morbidity, other than diabetes, 28.6% vs. 3.6%, p=0.031. Among the subset of pregnant SCD with pneumonia, the prevalence of VOC, 80.0% vs. 36.1%, p=0.001; ACS, 35.0% vs. 2.9%, p<0.001; and length of stay, 12.5 vs. 4.6 days, p=0.030, were significantly greater than in those without pneumonia. Among the subset of SCD pregnancies with VOC, the prevalence of preeclampsia, 28.4% vs. 13.5%, p=0.003; pneumonia, 15.7% vs. 2.6%, p=0.001; ACS, 12.8% vs. 0.6%, p<0.001; and length of stay, 7.7 vs. 3.6 days, p<0.001, were significantly more common than in those without VOC. Among the subset of SCD pregnancies with ACS, the rates of intrauterine fetal death, 14.3% vs. 1.6%, p=0.036; postpartum infection, 28.6% vs. 6.6%, p=0.016; pneumonia, 50.0% vs. 5.3%, p<0.001; and VOC, 92.9% vs. 36.5%, p<0.001, were significantly higher than in those without ACS. Overall, the rate of VTE, among SCD women with pneumonia, VOC, and/or ACS, 6.6%, was significantly higher than among those without these conditions, 2.2%, p<0.001. Discussion The prevalence of pregnancy-related VTE in women with SCD, while low, 2.8%, appears to be at least 10-fold greater than the general 0.2% incidence of pregnancy-related VTE in the unaffected population. Further, the higher rates of VTE we observed among pregnant women with SCD-related complications, including pneumonia, VOC, or ACS, and the well-recognized potential clinical overlap with VTE, suggest that VTE may be missed in such women, and that VTE rates in pregnant women with SCD may be higher than herein reported or previously recognized. The presence of pneumonia, VOC, or ACS appears to be associated with VTE and may be a potential marker(s) of its occurrence. Prospective studies, however, are needed to determine the incidence of VTE in pregnant women with SCD with and without complicating pneumonia, VOC, and/or ACS. We conclude that pregnancy-related VTE may be more common than previously recognized in pregnant women with SCD and, if confirmed, such women might be candidates for thromboprophylaxis. Disclosures: No relevant conflicts of interest to declare.

Vasoocclusive Painful Episodes and the Risk of Acute Chest Syndrome in Children with Sickle Cell Disease: Does the Selection of Parenteral Opioid Matter?

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 442-442
Author(s):  
Ram V. Kalpatthi ◽  
Matt Hall ◽  
Jignesh Dalal ◽  
Gerald M Woods
Keyword(s):  
Sickle Cell Disease ◽  
Length Of Stay ◽  
Respiratory Depression ◽  
Sickle Cell ◽  
Patient Population ◽  
Lower Risk ◽  
Acute Chest Syndrome ◽  
Cell Disease ◽  
Median Length ◽  
Hospitalization Costs

Abstract Background: Vaso-occlusive painful episodes (VOC) is the most common cause of hospitalization in patients with sickle cell disease (SCD) that often requires opioid analgesics and intravenous fluids. However, due to respiratory depression, the use of opioids during these painful episodes has been associated with the risk of development of acute chest syndrome (ACS), the major cause of early mortality in these patients. Nalbuphine is a unique opioid analgesic that effectively treats pain but lacks significant respiratory depression. Previous small scale studies (Pediatr Blood Cancer 2005 and J Pediatr Hematol Oncol 2011) suggested a lower risk of ACS in patients receiving Nalbuphine during VOC when compared with morphine. We sought to compare outcomes and the risk of ACS in pediatric sickle cell patients hospitalized for VOC in relationship to different opioid treatments. Methods: We used the Pediatric Health Information System (PHIS), an administrative database of children's hospitals in the US. Patients ≤ 21 years of age with SCD from 43 hospitals from 2005-2013 were included in the study. SCD patients who had a primary diagnosis VOC (ICD-9 codes 282.62, 282.64, 282.42 and 282.69) were included. VOC hospitalizations were divided into four different narcotic analgesic groups. In bivariate analyses, we compared patient demographics, treatment details, risk of ACS, length of stay, hospital costs, and readmissions across groups using chi-square tests or Kruskal-Wallis tests as appropriate. Multivariable models accounted for hospital clustering with generalized estimating equations for binary outcomes and generalized linear mixed effects models with random hospital intercepts and an exponential distribution (due to skewness of the data) for continuous outcomes. A p-value <.05 was considered statistically significant. Results: From 2005 to 2013, a total of 11260 unique pediatric SCD patients were identified. These patients had 42688 VOC hospitalizations, and received a single parenteral narcotic analgesic during each hospitalization (Morphine 82.2%, Hydromorphone 13.3%, Fentanyl 2.4% and Nalbuphine 2.1% of VOC hospitalizations). Table 1 describes the outcomes of VOC hospitalizations for all four narcotic groups. In unadjusted analysis, patients who received Nalbuphine only had significantly lower risk of ACS diagnosis (5.6%), ICU admissions (0.9%), shorter median length of stay (2 days) and lower median hospitalization costs ($4345) [Table 1]. Patients who received Morphine had less readmission within 3 and 7 days of discharge after VOC hospitalizations (Table 1). Multivariate analysis after adjusting for age, gender, hospital, season, race, payer source, and complex chronic conditions confirmed that patients who received Nalbuphine had significantly lower risk of ACS diagnosis, ICU admissions, shorter median length of stay, and lower median hospitalization costs compared to patients who received Morphine, Hydromorphone or Fentanyl (Table 2). Conclusions: In our largest pediatric in-patient sickle cell cohort, Nalbuphine was associated with significantly lower risk of development of ACS when compared with other opioids. In addition, patients received Nalbuphine had significantly lower ICU admissions, shorter hospital stay and lower hospitalization costs suggesting better pain control. However, our study shows that Nalbuphine in this patient population is rarely utilized. Prospective studies are needed to confirm this association and to elucidate the mechanisms that underlie these beneficial effects of Nalbuphine in this patient population. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures No relevant conflicts of interest to declare.

An innovative short-stay health care model for treatment of uncomplicated vaso-occlusive crisis in adult sickle cell disease patients in Canada to reduce emergency department utilization

CJEM ◽  
2017 ◽  
Vol 21 (1) ◽  
pp. 55-62 ◽  
Author(s):  
Andrew Binding ◽  
Richard Ward ◽  
Chai Phua ◽  
Veronique Naessens ◽  
Tara O’Brien ◽  
...  
Keyword(s):  
Emergency Department ◽  
Patient Satisfaction ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Discharge Rate ◽  
Historical Control ◽  
Secondary Outcome ◽  
Emergency Department Utilization ◽  
Short Stay ◽  
Cell Disease

AbstractObjectivesPatients with sickle cell disease (SCD) with vaso-occlusive crises (VOC) often visit the emergency department (ED) for management of painful episodes. The primary objective of this pilot study was to evaluate the acceptability of a short-stay model for treatment of VOC in SCD outside of the ED in Toronto, Canada. Secondary objectives were to assess patient satisfaction of this model, barriers to its use and comparison of clinical outcomes to a historical control.MethodsAdult SCD patients with symptoms of an uncomplicated VOC between October 2014 to July 2016 were managed according to best practice recommendations in a short-stay unit as an alternative to the local emergency room. Primary outcome of time to first analgesia, and secondary outcome of discharge rate were compared to a historical control at a local ED from 2009-2012. Satisfaction and barriers to use of the ambulatory care delivery model were assessed by patient survey.ResultsTwenty-one visits were recorded at the short-stay unit during the study period. Average time to first opiate dose was 23.5 minutes in the short-stay unit compared to 100.3 minutes in the ED (p<0.001). Discharge rate from the short-stay unit was 84.2%. Average patient satisfaction with this model of care was high (>4/5 on Likert scale) except for geographic accessibility (85% response rate, n=18).ConclusionThis study demonstrated high patient satisfaction and acceptability of a short-stay model for treatment of uncomplicated VOC in adult SCD patients in Toronto, the first of its kind in Canada.

scholarly journals Safe Use of Hydroxyurea in Sickle Cell Disease Patients Hospitalized for Painful Vaso-Occlusive Episodes: Results of the Randomized, Open-Label Helps Study

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2303-2303
Author(s):  
Nicola Conran ◽  
Kleber Yotsumoto Fertrin ◽  
Claudia de Alvarenga Maximo ◽  
Thais Oliveira ◽  
Clarisse Lobo ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Length Of Stay ◽  
Adverse Events ◽  
Sickle Cell ◽  
Acute Phase ◽  
Standard Of Care ◽  
Cell Disease ◽  
Open Label ◽  
Pain Scores ◽  
To Receive

Painful vaso-occlusive episodes (VOE) constitute the most frequent acute complication of sickle cell disease (SCD). However, despite the high economic and personal burden of hospitalization for VOE, there exists no therapeutic approach for VOE other than pain management and hydration. Hydroxyurea (HU) is frequently used continuously to augment levels of fetal hemoglobin (HbF) in patients with SCD, in association with clinical amelioration. However, in addition to its cytostatic effects, HU has immediate anti-inflammatory effects that inhibit vaso-occlusive processes in the microcirculation of mice with SCD, mediated by stimulation of cyclic guanosine monophosphate (cGMP) signaling (Almeida et al., Blood 120(14):2879, 2012). The Hydroxyurea in the Emergency Room to Lessen Pain in Sickle Cell Crisis (HELPS) study (NCT03062501) was a phase II, single-center, randomized, open-label interventional Study (Phase II) designed to evaluate, primarily, the safety of moderate-to-high daily doses of HU in SCD patients in the acute phase of VOE management. Thirty HbSS patients were included in the study within 24h of VOE onset at the Hemorio, Rio de Janeiro, Brazil. Inclusion criteria were: Arrival at the ER within 8h previous to inclusion, confirmed VOE associated with a pain scale score of > 6 within the last 24h, and a pain score of >4 at the time of inclusion. Patients with baseline neutrophil counts < 3.0 (103mm-3) and platelet (PLT) counts < 90 (103mm-3) were excluded from the study due to concerns regarding myelosuppression. Females not in use of contraception, patients hospitalized for VOE within the last 4 weeks and those that had received transfusions in the last 8 weeks were also excluded. Fifteen patients were randomized to the non-intervention arm to receive the center's standard of care, while 15 were randomized to the intervention arm to receive 30-45 mg/kg HU immediately upon study inclusion, and up to two more daily HU doses (if still hospitalized), plus standard of care. During hospitalization, pain scores were recorded every 6 hours, blood counts, and transaminases were determined at 24 h. Adverse events (CTCAE version 4.03), pain medication administered, and length of stay were recorded. Patients were recalled for a post-VOE visit at 7 days after the last HU dose for evaluation for physical exam, late adverse events, blood counts, and transaminases. Twenty-nine patients concluded the study, with 14 patients in the non-intervention arm and 15 in the intervention arm (aged 31.3±10.1 yrs). Four and three patients in each group (respectively) were on continuous HU therapy upon inclusion, and one patient in the non-intervention arm continued taking HU (20 mg/kg/day) throughout the study. Patients in the intervention arm each received up to three daily administrations of HU (mean dose, 31±5 mg/Kg/day; mean number of doses administered, 1.6 per patient). One patient experienced emesis within 2 h of first dose and did not receive a top-up dose. With regard to preliminary safety data, adverse events did not differ significantly between the arms; 4 grade 1-2 events occurred in each of the groups within 24 h of inclusion (all nausea/emesis) and nausea and/or pain were reported in 5 and 3 patients in the non-intervention and intervention arms, respectively, throughout the study. One serious adverse event (death due to sepsis) occurred in the non-intervention arm. Transaminases, red blood cell count, Hb and hematocrit did not differ significantly between the two arms at 24h after inclusion and at the post VOE consultation (number returning; 13 and 12, respectively). No myelosuppression was seen, but the intervention group had a significant decrease in leukocyte count and an increase in PLT count at 7 days post HU, compared to baseline (WBC; 11.9±4.8, 16.4 ±7.0 x 103mm-3: PLT; 570±275, 428±139 x 103mm-3, P<0.05, respectively). Sample numbers were too small to detect any statistically significant decrease in length of stay, pain scores, or opioid usage. However, data indicate that the use of up to three consecutive daily doses of approximately 30 mg/kg HU in the acute phase of the management of SCD patients with VOE is feasible and safe, independently of whether patients already take HU on a continuous basis. Results will aid in the design of larger multicenter trials to evaluate the potential efficacy of the use of oral or intravenous HU during hospitalization for SCD VOE. Financial Support: FAPESP, Brazil. Disclosures Fertrin: Agios Pharmaceuticals, Inc.: Research Funding. OffLabel Disclosure: Use of up to 3 doses of hydroxyurea (30-45 mg/kg/day) in patients with sickle cell disease hospitalized for acute painful vaso-occlusive episodes.

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