Severe Persistent Pain and Inflammatory Biomarkers in Sickle Cell Disease: An Exploratory Study

2021 ◽  
pp. 109980042110272
Author(s):  
Mitchell R. Knisely ◽  
Paula J. Tanabe ◽  
Julia K. L. Walker ◽  
Qing Yang ◽  
Nirmish R. Shah
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Exploratory Study ◽  
Severe Pain ◽  
Frequent Occurrence ◽  
Inflammatory Biomarkers ◽  
Cell Disease ◽  
Electronic Health Record Data ◽  
Pain Group ◽  
Inflammatory Biomarker

Background: Severe pain is among the most common and deleterious symptoms experienced by individuals with sickle cell disease (SCD), of whom more than 50% report chronic pain. Despite this, the understanding of the biological contributors to persistent severe SCD pain is limited. This exploratory study sought to describe pain phenotypes based on frequency of severe pain experienced over 6 months and identify inflammatory biomarkers associated with pain phenotypes among individuals with SCD. Methods: This study used self-report and electronic health record data collected from 74 individuals enrolled in the Duke Sickle Cell Disease Implementation Consortium Registry. Plasma from previously collected blood specimens was used to generate inflammatory biomarker data using the Inflammation 20-plex ProcartaPlexTM panel. Descriptive statistics were used to describe the occurrence of severe pain over the past 6 months, and bi-variate analyses were used to evaluate the relationship between inflammatory biomarkers and pain phenotypes. Results: Among the 74 participants included in this study, 33.8% reported severe pain occurring never or rarely, 40.5% reported severe pain occurring sometimes, and 25.7% reported severe pain occurring often or always. Soluble E-selectin (sE-selectin) was the only inflammatory biomarker significantly associated with the pain phenotype groups ( p = 0.049). Post hoc comparisons identified that participants in the often/always severe pain group had significantly higher plasma concentrations of sE-selectin compared to those in the sometimes severe pain group ( p = 0.040). Conclusions: Our findings provide preliminary evidence of the frequent occurrence of severe pain and that sE-selectin may be an objective biomarker for the frequent occurrence of severe pain in this population.

Severe Pain Profiles and Associated Sociodemographic and Clinical Characteristics in Individuals with Sickle Cell Disease

2021 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Mitchell R. Knisely ◽  
Paula J. Tanabe ◽  
Qing Yang ◽  
Rita Masese ◽  
Meilin Jiang ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Severe Pain ◽  
Clinical Characteristics ◽  
Cell Disease

scholarly journals Plasma metabolomics analysis in sickle cell disease patients with albuminuria – an exploratory study

2018 ◽  
Vol 185 (3) ◽  
pp. 620-623 ◽  
Author(s):  
Laila Elsherif ◽  
Wimal Pathmasiri ◽  
Susan McRitchie ◽  
David R. Archer ◽  
Kenneth I. Ataga
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Exploratory Study ◽  
Cell Disease ◽  
Metabolomics Analysis

scholarly journals Current and novel therapies for the prevention of vaso-occlusive crisis in sickle cell disease

2020 ◽  
Vol 11 ◽  
pp. 204062072095500
Author(s):  
Ifeyinwa Osunkwo ◽  
Deepa Manwani ◽  
Julie Kanter
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Severe Pain ◽  
Management Strategies ◽  
Organ Damage ◽  
Care Utilization ◽  
Cell Disease ◽  
High Resource ◽  
Emerging Treatments

Individuals with sickle cell disease (SCD) are living further into adulthood in high-resource countries. However, despite increased quantity of life, recurrent, acute painful episodes cause significant morbidity for affected individuals. These SCD-related painful episodes, also referred to as vaso-occlusive crises (VOCs), have multifactorial causes, and they often occur as a result of multicellular aggregation and vascular adherence of red blood cells, neutrophils, and platelets, leading to recurrent and unpredictable occlusion of the microcirculation. In addition to severe pain, long-term complications of vaso-occlusion may include damage to muscle and/or bone, in addition to vital organs such as the liver, spleen, kidneys, and brain. Severe pain associated with VOCs also has a substantial detrimental impact on quality of life for individuals with SCD, and is associated with increased health care utilization, financial hardship, and impairments in education and vocation attainment. Previous treatments have targeted primarily SCD symptom management, or were broad nontargeted therapies, and include oral or parenteral hydration, analgesics (including opioids), nonsteroidal anti-inflammatory agents, and various other types of nonpharmacologic pain management strategies to treat the pain associated with VOC. With increased understanding of the pathophysiology of VOCs, there are several new potential therapies that specifically target the pathologic process of vaso-occlusion. These new therapies may reduce cell adhesion and inflammation, leading to decreased incidence of VOCs and prevention of end-organ damage. In this review, we consider the benefits and limitations of current treatments to reduce the occurrence of VOCs in individuals with SCD and the potential impact of emerging treatments on future disease management.

Predictors of Mortality in Children and Adolescents with Sickle Cell Disease: The PUSH Study

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 515-515 ◽  
Author(s):  
Mehdi Nouraie ◽  
Sohail R. Rana ◽  
Oswaldo L Castro ◽  
Lori Luchtman-Jones ◽  
Craig Sable ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Children And Adolescents ◽  
Sickle Cell ◽  
Severe Pain ◽  
Blood Transfusions ◽  
Cell Disease ◽  
Risk Of Death ◽  
The Past ◽  
History Of

Abstract Abstract 515 Background: Recent studies indicate that the disease-specific mortality In sickle cell anemia is about 6% in children up to 18 years and 15% in the 18–30 year age group, yielding a cumulative mortality of 21% by age 30 years. It is important to identify children at high risk so that early interventions can be developed to reduce this high mortality. Methods: We prospectively enrolled 505 children and adolescents with sickle cell disease in 2005–2010, 380 with hemoglobin SS and 130 with other genotypes. The median age at enrollment was 12 years with a range of 3 to 20 years. Baseline clinical features, echocardiography, six-minute walk test and pulmonary function testing were performed at steady-state. Follow-up for mortality has been performed in 470 of the participants at a median of 37 months after enrollment, range of 1 to 59 months. Results: Six of 470 patients (1.3%) died during the follow-up period, five with hemoglobin SS and one with hemoglobin SC. The median age at the time of death in these six participants was 20 years, range of 15 to 23 years. Death occurred during the follow-up period in 2.7% of participants over 12 years of age at enrollment and 3.7% of those over 15 years of age. The causes of death were stroke in 4, multiorgan failure in 1 and unknown in 1. Death occurred in 5.9% of 51 participants with a history of stroke versus 0.7% of 416 without stroke history; in 3.5% of 113 participants with a history of asthma versus 0.6% of 354 without asthma history; in 4.9% of 103 participants with 10 or more blood transfusions lifetime versus 0.3% of 359 with less than 10 blood transfusions; in 3.3% of 90 participants with two or more severe pain episodes in the past year versus 0.8% of 380 participants with less than two severe pain episodes in the past year. In age-adjusted analyses, the hazards ratio (95% CI) of death was 6.1 (1.2-30.5) for history of stroke (P=0.029), 10.2 (1.2-89.5) for history of frequent blood transfusions (P=0.036), 5.8 (1.1-31.8) for history of asthma (P=0.044) and 1.07 (1.00-1.14) for frequent severe pain episodes (P=0.047). Clinical findings associated with these risk factors included higher concentrations of markers of hemolysis for history of stroke and history of frequent blood transfusions, decreased FEV1/FVC and increased total lung capacity for history of asthma, and lower concentrations of markers of hemolysis and high ECHO-determined tricuspid regurgitation velocity for history of frequent severe pain episodes. Conclusions: Over a median of three years of observation of this cohort, no deaths occurred among 248 sickle cell disease children 12 years of age or younger at enrollment but there were 6 deaths among 222 participants 13–20 years of age at enrollment. In bi-variate age-adjusted analyses, histories of stroke, asthma, frequent blood transfusions and frequent pain episodes were associated with an increased risk of death. Strikingly, four of the five deaths in which the cause was known were due to stroke. The present data on mortality in the PUSH study suggest that prevention of stroke is critical in improving the survival in adolescents and young adults with sickle cell disease. Disclosures: No relevant conflicts of interest to declare.

scholarly journals The Relationship between Mental Health, Educational Attainment, Employment Outcomes, and Pain in Sickle Cell Disease

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 419-419
Author(s):  
Kelly M Harris ◽  
Taniya Varughese ◽  
Anna Bauer ◽  
Seth Howdeshell ◽  
Cecelia Calhoun ◽  
...  
Keyword(s):  
Mental Health ◽  
Sickle Cell Disease ◽  
Educational Attainment ◽  
Sickle Cell ◽  
Employment Status ◽  
Severe Pain ◽  
Cell Disease ◽  
Annual Household Income ◽  
Significant Relationships ◽  
Pain Outcomes

Sickle cell disease (SCD) is the most common genetic condition in the world and disproportionately affects African Americans in families with lower household incomes. SCD is characterized by a variety of complications including episodes of severe pain, chronic anemia, and end-organ damage. Morbidity from SCD begins in infancy and increases in frequency and severity with age. Complications during childhood and adolescence, both critical learning periods for youth, substantially impact educational attainment and life outcomes. SCD-related hospitalizations are associated with social determinants of health, such as socioeconomic status (SES), depression, health literacy, and educational outcomes. In youth with SCD, family and neighborhood SES are predictors of pain level, pain frequency, and overall quality of life. In addition to the physiological impacts of SCD, individuals with SCD experience emotional and stress related effects of the disease that may impact daily quality of life and frequency and severity of pain. Studies have found that hospital admission frequency has limited or no impact on academic outcomes in youth with SCD. Few studies have explicitly examined the relationship between SCD-related pain and educational, socioeconomic, and mental health outcomes. This is a cross-sectional study of patient survey data from a single site in the Sickle Cell Disease Implementation Science Consortium (SCDIC). The primary objective was to identify a relationship between educational attainment, employment status, mental health, and the frequency, severity, or length of pain crises for individuals with SCD. Multivariate analysis was used to assess the impact of patients' educational attainment, employment status, annual household income (low = less than $25,000, high = $75,001 and above), and self-reported depression on the frequency, length, and severity of SCD-related pain. Our central hypothesis was that individuals with a history of depression, lower educational attainment, periods of unemployment, and lower incomes experience more frequent, more severe, and longer pain crises. A total of 307 participants were included. The mean age was 27.4 years (range 15 to 45), 58.3% were female, and 99% were African American. Sixty-two percent had Hgb SS, the most severe form of SCD. About half of all patients (50.5%) reported they take pain medication every day for SCD and majority were on some form of disease modification (64.2% on hydroxyurea (HU), 20.2% on chronic blood transfusion). Slightly less than half (48.9%) reported their highest level of education as a high school diploma or lower. Most were unemployed (15.3%), students (22.8%), or disabled (21.5%), and 59.2% reported an average annual household income less than $25,000. Univariate analysis revealed statistically significant associations between employment status as unemployed or disabled and frequency of pain (p < .001), employment status as unemployed or disabled and severity of pain (p < .001), and employment status as disabled and length of pain > 4 days. Relationships between depression and frequency and severity of pain were statistically significant at the p < .001 level, and between depression and length of pain > 1 week at the p < .01 level. Multivariate analysis revealed positive statistically significant relationships between depression and high pain frequency (p < .001), employment status as disabled and severe pain (p < .01), depression and severe pain (p < .01), and employment status as disabled and length of pain >4 days (p < .05), Table 1. Educational attainment did not demonstrate statistically significant relationships with pain outcomes. No variables demonstrated statistically significant relationships with length of pain > 1 week and length of pain > 2 weeks. The only significant association with pain outcomes was that HU users were less likely to take daily opioids. Individuals with SCD who are disabled or have a history of depression are more likely to report more severe and frequent pain. No relationship emerged between educational attainment and pain outcomes. As the results are limited to the cross-sectional design, we cannot make statements of causality. For now, we know that people with SCD and these risk factors need further study for interventions. We plan to further assess study participants across all eight SCDIC sites in the next phase of this work. Disclosures King: Bioline: Consultancy; Amphivena Therapeutics: Research Funding; Incyte: Consultancy; Cell Works: Consultancy; Celgene: Consultancy; Magenta Therapeutics: Membership on an entity's Board of Directors or advisory committees; Novimmune: Research Funding; RiverVest: Consultancy; Tioma Therapeutics (formerly Vasculox, Inc.):: Consultancy; WUGEN: Equity Ownership.

Genetic and Epigenetic Regulation of the Gamma Globin Locus Is Associated with Fetal Hemoglobin Levels and Frequency of Pain in Sickle Cell Disease

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3230-3230
Author(s):  
Blair Anderson ◽  
Ebenezer Enchia ◽  
Karen Soldano ◽  
Melanie Garrett ◽  
Jude Jonassaint ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Genetic Variation ◽  
Sickle Cell Disease ◽  
Clinical Outcomes ◽  
Sickle Cell ◽  
Severe Pain ◽  
Methylation Status ◽  
Fetal Hemoglobin ◽  
European Ancestry ◽  
Cell Disease

Abstract Abstract 3230 Sickle cell disease (SCD) is caused by a single amino acid substitution of the β-globin chain of hemoglobin, resulting in abnormal red blood cells that occlude vessels, causing tissue damage, pain, and anemia. While all individuals with SCD have the same β-globin mutation, disease severity varies and is correlated with the concentration of retained fetal hemoglobin (HbF) (Akinsheye et al, 2011). After birth, a switch from γ- to β-globin gene expression occurs and HbF (α2γ2) is replaced by HbA (α2β2). In patients with SCD, increased levels of γ-globin can help compensate for the effects of the β-globin mutation. SCD patients with higher than normal retention of HbF frequently have more benign disease symptoms and longer life expectancy (Platt et al, 1994). Increased HbF expression through the use of hydroxyurea (HU) is a frequently used therapy and the only FDA-approved medication for SCD. However, due to the toxicity and inconsistent efficacy of HU, further understanding regarding the regulation of this “hemoglobin switch” is essential for developing alternative treatments. DNA methylation is central to the silencing of γ-genes during the switch to β-globin expression (Goren et al, 2006). Methylation marks are established by the DNA methyltransferase DNMT3A, which is recruited to the γ-promoter by the protein arginine methyltransferase, PRMT5 (Rank et al, 2010). We first hypothesized that genetic variation in DNMT3A and PRMT5 contributes to HbF levels. To test this, we performed a genetic association study on 603 unrelated, adult SCD patients. 21 haplotype-tagging SNPs in DNMT3A (n=17) and PRMT5 (n=4) were genotyped in the patients. SNPs were evaluated for association with HbF levels, as well as the occurrence of severe pain and narcotic use, which were used as surrogates for non-hemoglobin effects of HU. HbF levels were measured when the patients were at steady state and not taking HU. Severe pain was defined as a history of hospitalization for pain within a 12 month period. Narcotic use was defined as taking long- or short-acting narcotics to alleviate pain at home. To evaluate associations between the SNPs and clinical outcomes, we used linear and logistic regression (SAS Systems, Cary, NC), while controlling for age, sex, degree of European ancestry and HU treatment. European ancestry was estimated from 4331 genome-wide ancestry informative markers (Ashley-Koch et al, 2011). HbF levels were log-transformed prior to analysis in order to achieve a normal distribution. We corrected for multiple comparisons using the Li and Ji method (Li & Ji, 2005). Two SNPs in DNMT3A were significantly associated with the occurrence of severe pain and HbF levels after correcting for multiple testing. Additionally, two SNPs in DNMT3A and one in PRMT5 were nominally associated with severe pain, two SNPs in DNMT3A were nominally associated with narcotic use, and one SNP in PRMT5 was nominally associated with HbF levels. These findings demonstrate that genetic variation in key genes responsible for the regulation of DNA methylation at the γ-globin locus is associated with SCD clinical outcomes. We next hypothesized that the variability in clinical outcomes might be due to epigenetic variation at the γ-globin locus. In order to determine specific DNA methylation patterning of γ-globin genes (HBG1 and HBG2), we performed pyroseqencing subsequent to bisulfite treatment of DNA from a subset of 72 SCD patients, all of whom were HbSS, and 50% of whom were not on HU treatment. Percent methylation at the γ-globin locus was nominally associated with HbF levels among patients not taking HU (p=0.03), but not among patients taking HU. Additionally, we investigated whether SNPs predicted methylation status and identified two SNPs in DNMT3A (rs734693 and rs7583409) to be predictive of methylation status at the γ-globin locus. These data provide further insight into the complex regulation of the γ-globin locus and suggest that genetic variation in DNMT3A and PRMT5 is associated with clinical outcomes and methylation status in SCD patients. Future studies are needed to further investigate the impact of epigenetic processes as a potential mechanism for HbF expression and induction. Disclosures: Telen: GlycoMimetics: Research Funding.

scholarly journals Crizanlizumab-Associated Painful Febrile Reaction in Sickle Cell Disease Patients

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4186-4186
Author(s):  
Valery J Li ◽  
Oyebimpe O. Adesina ◽  
Kleber Yotsumoto Fertrin
Keyword(s):  
Sickle Cell Disease ◽  
Board Of Directors ◽  
Avascular Necrosis ◽  
Sickle Cell ◽  
Severe Pain ◽  
Symptomatic Treatment ◽  
Watery Diarrhea ◽  
Febrile Reaction ◽  
Cell Disease ◽  
Advisory Committees

Abstract Background: P-selectin expressed on endothelium and platelets has been implicated in the pathophysiology of vaso-occlusive crises (VOCs) in sickle cell disease (SCD) patients. Crizanlizumab is a humanized monoclonal anti-P-selectin antibody approved by the FDA to reduce the frequency of VOCs. While severe adverse events (AEs) are rare, over 80% of patients most commonly have headache, back pain, nausea, or arthralgia; infusion-related reactions occurred in 3% according to the package insert. We report on 2 patients whose crizanlizumab-associated reactions help shed light on how to manage such events and possible mechanisms. Case reports: Case 1, a 48-year-old woman with hemoglobin SC disease, history of left shoulder replacement due to avascular necrosis and left knee avascular necrosis, pending surgical replacement. Given her frequent pain episodes, she was initiated on crizanlizumab after being intolerant to hydroxyurea (watery diarrhea). She received the first dose of crizanlizumab uneventfully, but at the end of her second infusion, she developed acute bilateral groin pain that radiated to both legs. She was eventually admitted to the hospital with a fever of 38-39°C without evidence of infection. She also received one unit of RBC transfusion for a drop in Hct from 32% to 25%. For her third infusion, we premedicated her with acetaminophen 650mg, diphenhydramine 50mg, ketorolac 1g along with concurrent IV hydration. She tolerated an initial infusion at 20ml/h for the first 15 minutes after which we ramped it up to the regular rate of 200ml/h. Within minutes of that rate increase, the patient developed chest pain and dyspnea, so infusion was stopped immediately. Blood samples taken right after the event revealed tryptase and IgE levels within normal limits, and she chose to discontinue the medication. Case 2, a 20-year-old woman with sickle cell anemia with frequent painful episodes despite hydroxyurea at 25mg/kg/day. The patient preferred to start crizanlizumab over increasing oral medication. She reported having had fever and chills at home after her first crizanlizumab infusion and improved with acetaminophen. About 10 minutes into her second infusion, she developed acute severe migratory pain in her back, moving to her lower limbs, associated with tachycardia. Infusion was immediately discontinued, and she was medicated with diphenhydramine 25mg and methylprednisolone 125mg with no improvement. She progressed with abdominal pain moving into her arms and needed meperidine 25mg and hydromorphone 1mg to achieve pain resolution. She completed the infusion successfully at 50% reduced rate but still reported subjective high fevers and chills again the next day, medicated with acetaminophen. She continues monthly infusions with a slower rate. Discussion: As of October 2020, Novartis (manufacturer of crizanlizumab) informed that, out of 3,500 patients, there have been 22 postmarketing reports of severe pain during or within 24 hours of the infusion. Seven cases reported complications, all of which resolved. Immediate hypersensitivity reactions to monoclonal antibodies can be a cytokine release syndrome, IgE-mediated, or IgG-mediated. One case report has suggested this may be a complement activation-related pseudoallergy (CARPA) as sC5b-9 was mildly elevated in a 17-year-old male patient who developed sudden and severe pain in his back, legs and head within 10 minutes of the infusion, despite having been premedicated with acetaminophen, later developing a fever and need for admission. Differently from that case, our patients developed severe pain with a second exposure of the drug, arguing in favor of an antibody-mediated process. We did not find evidence of mast cell activation or increased IgE production in our patient who needed to discontinue the medication. We therefore hypothesize that crizanlizumab-associated painful febrile reaction may be IgG-mediated. Premedication in our experience was unsuccessful, and symptomatic treatment with acetaminophen was appropriate, but slower infusion rates may prove useful for some patients. Conclusion: While rare, crizanlizumab-associated painful febrile reactions may be observed after a first uneventful infusion and are possibly IgG-mediated. Patients experiencing this reaction may require symptomatic treatment with acetaminophen despite premedication and can be tried on slower infusion rates. Disclosures Fertrin: Sanofi Genzyme: Consultancy, Membership on an entity's Board of Directors or advisory committees; Agios Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

scholarly journals An atypical presentation and diagnostic dilemma of sickle cell disease

2017 ◽  
Vol 10 (2) ◽  
pp. 105
Author(s):  
Mohammad Mizanur Rahman ◽  
Md. Monirul Islam ◽  
Lutfunnahar Khan
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Severe Pain ◽  
Splenic Abscess ◽  
Blood Film ◽  
Beta Thalassemia ◽  
Atypical Presentation ◽  
Cell Disease ◽  
Diagnostic Dilemma ◽  
Physical Findings

<p class="Abstract">A 5½ year old male child of a consanguineous couple presented with moderately high fever, hepatosplenomegaly and severe pain in the left upper quadrant of the abdomen for four days. On examination, the child was found severely anemic, ill-looking and mildly icteric but the abdomen was soft and non-tender. Radiological investigations and ultrasonography of the whole abdomen revealed the diagnosis of space occupying lesions which may be either due to splenic abscess/cyst or leukemia/lymphoma. However, blood film revealed the features of hereditary hemolytic anemia and later on hemoglobin electrophoresis initially commented as HbS–beta thalassemia but subsequent family screening of the patient turned out to a case of homozygous sickle cell anemia or sickle cell disease. To resolve such diagnostic dilemma, it is very much essential to analyze critically the history including family history, clinical and physical findings as well as investigational findings.</p>

scholarly journals Morphine for the Treatment of Pain in Sickle Cell Disease

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Mihir Gupta ◽  
Lilian Msambichaka ◽  
Samir K. Ballas ◽  
Kalpna Gupta
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Clinical Studies ◽  
Severe Pain ◽  
Organ Damage ◽  
Cell Disease ◽  
Organ Function ◽  
Specific Effects ◽  
Organ Specific ◽  
Chronic Use

Pain is a hallmark of sickle cell disease (SCD) and its treatment remains challenging. Opioids are the major family of analgesics that are commonly used for treating severe pain. However, these are not always effective and are associated with the liabilities of their own. The pharmacology and multiorgan side effects of opioids are rapidly emerging areas of investigation, but there remains a scarcity of clinical studies. Due to opioid-induced endothelial-, mast cell-, renal mesangial-, and epithelial-cell-specific effects and proinflammatory as well as growth influencing signaling, it is likely that when used for analgesia, opioids may have organ specific pathological effects. Experimental and clinical studies, even though extremely few, suggest that opioids may exacerbate existent organ damage and also stimulate pathologies of their own. Because of the recurrent and/or chronic use of large doses of opioids in SCD, it is critical to evaluate the role and contribution of opioids in many complications of SCD. The aim of this review is to initiate inquiry to develop strategies that may prevent the inadvertent effect of opioids on organ function in SCD, should it occur, without compromising analgesia.

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