Patients In Sickle Cell Crisis Research Articles

Double Trouble: COVID-19 Infection Exacerbates Sickle Cell Crisis Outcomes in Hospitalized Patients—Insights from National Inpatient Sample 2020

Background: This study investigated the impact of COVID-19 on patients with sickle cell crisis (SCC) using National Inpatient Sample (NIS) data for the year 2020. Methods: A retrospective cohort analysis was conducted utilizing International Classification of Diseases (ICD-10) codes to identify adults who were admitted with a principal diagnosis of sickle cell crisis. The primary outcomes examined were inpatient mortality, while the secondary outcomes assessed included morbidity, hospital length of stay, and resource utilization. Analyses were conducted with STATA. Multivariate logistic and linear regression analyses were used to adjust for confounding variables. Results: Of 66,415 adult patients with a primary SCC diagnosis, 875 were identified with a secondary diagnosis of COVID-19 infection. Unadjusted mortality rate was higher for SCC patients with COVID-19 (2.28%) compared to those without (0.33%), with an adjusted odds ratio (aOR) of 8.49 (p = 0.001). They also showed increased odds of developing acute respiratory failure (aOR = 2.37, p = 0.003) and acute kidney injury requiring dialysis (aOR = 8.66, p = 0.034). Additionally, these patients had longer hospital stays by an adjusted mean of 3.30 days (p < 0.001) and incurred higher hospitalization charges by an adjusted mean of USD 35,578 (p = 0.005). Conclusions: The SCC patients with COVID-19 presented higher mortality rates, increased morbidity indicators, longer hospital stays, and substantial economic burdens.

Prevalence of Cannabis Use Disorder and Its Association with Major Adverse Cardiac Events in Patients with Sickle Cell Crisis: Insights from the National Inpatient Sample

Background: Cannabis use has grown in popularity, with the possible therapeutic advantages being widely debated, one of which is in Sickle Cell Crisis (SCC). With increasing surveys reporting overlapping use of recreational and medicinal cannabis and high addiction potential, the aim of this nationwide study is to investigate the relationship between cannabis use disorder (CUD) in SCC patients. Methods: Using ICD-10 codes, the National Inpatient Sample-2020 was utilized to identify adult (>18 years) hospitalized patients due to SCD with and without crisis and further divided into patients with SCC with CUD (SCC+CUD+) and patients with SCC without CUD (SCC+CUD-). The prevalence of CUD in SCC and Major Adverse Cardiac Events [MACE, Acute Myocardial Infarction (AMI); Atrial Fibrillation (AFib) and cardiac arrest] were the primary outcomes; other associated comorbidities, Length of Stay (LOS), and hospitalization costs were secondary outcomes. After examining the baseline features on descriptive analysis, to compare the variables, Pearson's chi-squared test and Mann- Whitney U test were used to compare categorical and continuous data, respectively. Multivariable analyses were performed, controlling covariates, to assess the odds of MACE in the CUD+ vs. CUD- cohort. Results: Out of a total of 77,610 SCC adult hospitalizations, 4,535 (5.8%, p<0.001) had CUD. The median age of hospitalization for the CUD+ cohort was lower (28 years) than for the CUD- cohort (31 years). They were often of black ethnicity (95.8% vs. 95.3%, p=0.03), Medicaid enrollees (55.3% vs. 46.3%, p<0.001), and were hospitalized as non-electively (98.6% vs. 97.5%, p<0.001) to urban teaching hospitals (87% vs. 85.5%, p<0.001) in the Southern (47.7% vs. 53.7%, p<0.001) region. Chronic Pulmonary diseases (29.3% vs. 24.1%, p<0.001), prior venous thromboembolism (21.1% vs. 25.3%, p<0.001), hypertension (17.3% vs. 23.3%, p<0.001) and depression (16.3% vs 13.5%, p<0.001) were the majorly associated comorbidities in both (SCC+CUD+) and (SCC+CUD-) cohorts. On analysis of MACE in SCD patients with crisis; AMI (0.6% vs 0.7%, p=0.28), AFib (0.3% for both, p<0.001), cardiac arrest (0.3% for both, p = 0.89) were comparable in both SCC cohorts with and without CUD, suggesting no significant difference in MACE between these patient groups except for AFib. However, after adjusting for confounders, on multivariable analysis, none of the MACE (AMI: OR=0.85, CI= 0.35-2.05, p=0.71; AFib: OR=0.81, CI= 0.39-1.69, p= 0.57; cardiac arrest: OR = 1.23, CI= 0.39-3.86, p= 0.71) were found to be significant, p>0.05 for all. In (SCC+CUD+) and (SCC+CUD-) patients, there was no difference observed in LOS (4 days in both) and hospitalization costs (USD 29,216 vs. USD 31,604). Conclusion: Our study evaluated the prevalence and association between CUD and its cardiovascular effects during SCC, bringing light on an essential and understudied association in SCC patients while adjusting for other major concomitant mixed substance abuses like tobacco and alcohol. The observed disparities in MACE require further exploration via prospective research to better understand the possible recreational and therapeutic implications of cannabis use in patients with SCC.

Identification of Risk Factors for Sickle Cell Crisis Readmissions: A Community Center Experience

Introduction: Sickle cell disease (SCD) exerts a significant morbidity and mortality burden worldwide, with 300,000 infants being diagnosed with SCD annually. The term sickle cell crisis (SCC) encompasses several acute conditions under its umbrella, namely vaso-occlusive crisis, aplastic crisis, splenic sequestration crisis, dactylitis, and acute chest syndrome. SCC has been established to be a known cause of readmissions across the year with studies showing 17% of the population returning two to three times annually. This has resulted in a high mean length of stay for this diagnosis (5.3 days) in comparison to an index hospitalization (4.9 days), with a mean cost of $8485 per admission. Readmissions owing to SCC have relayed a significant burden of 95,445 hospitalization days and a total charge of $609 million in the US. Despite the high morbidity and financial burden it imposes, limited studies have been performed studying the risk factors for readmissions in these patients. Despite the establishment of a framework of recommendations and guidelines, there appears to be a high incidence of readmissions and discrepancies in adherence to evidence based recommendations. We performed a retrospective study to evaluate the risk factors for patients hospitalized in three community hospitals between October 2021 and August 2022. Methods: The admissions database of a community health system across three hospitals was scanned for admissions with SCC between the time period October 2021 and August 2022. ICD9 and ICD-10 codes of SCC were used. 50 patients found with the admitting diagnosis code of SCC and 103 encounters were included. After excluding patients who left against medical advice before initiation of treatment, those with the wrong diagnosis and incomplete documentation, a cohort of 47 patients with 100 encounters was attained. Patient charts were reviewed and demographic variables such as age, gender and race were studied. Readmissions and the length of stay were assessed for risk factors with the help of a chi square test. Risk factors assessed included use of pain medications (opioids with non-steroid anti-inflammatory medications versus monotherapy), use of IV Fluid Boluses, placement of Hematology consult, having an established primary care physician and the use of hydroxyurea as a home medication. Results: 87% of the patient population was African American with equal gender distribution (Males 51%; Females 49%). 59% of the patient population lay in the age group of 18-35. 49% of the patient population was noted to have readmissions within the time frame studied with 29% of the patient population having a length of stay of more than 3 days. 100% of the patients without an established primary care physician (PCP) were noted to have readmissions in comparison to 3.6% of the patients with an established PCP (p< 0.01). Length of stay was less than 3 days for 91.3% of the patients treated with the combination of opioids and NSAID's for pain in comparison to 64.9% of the patients that were not treated with this combination (p= 0.014). It was noted however, that 37% of the population was on hydroxyurea outpatient and 44% of the cases had involved hematology for the inpatient management of these patients. IV Fluid boluses and their association with length of stays in our patient population was unequivocal. 52.7% of the patients on hydroxyurea had readmissions within 30 days as opposed to 28.6% of the patients not on the drug. This was likely explained by non-compliance to the medication. No deaths were reported in this patient cohort. Conclusion: Several risk factors for readmissions in SCC patients exist in the community setting. Our findings reported that lack of close outpatient follow up is associated with higher readmission rates. In addition, we also observed that the type of medical pain management (combination vs monotherapy) played a role in length of stay with combination therapy being linked to shorter hospitalization stay. Integrated education for various medicine specialties regarding management guidelines should be instituted. In addition, maximum utilization of social work and case management for ensuring close follow ups for this patient population may further mitigate readmissions of SCC patients in the community setting.

P‐TS‐1 | A Case of a Possible Transfusion‐Associated Fatality: The Continued Challenges of Managing and Treating Patients in Sickle Cell Crisis

P‐TS‐1 | A Case of a Possible Transfusion‐Associated Fatality: The Continued Challenges of Managing and Treating Patients in Sickle Cell Crisis

Role of social disparity in 30-day readmissions and healthcare utilization in patients with history of sickle cell crisis in United States: Cross-sectional analysis from US national database.

e18666 Background: Factors like age, mental status, spirituality, financial security, and clinic attendance affect hospital admissions/readmissions in sickle cell disease patients. To further understand the predisposing factors associated with increased readmissions in sickle cell disease patients, this study examined the relationship between readmission rates and socioeconomic status of Sickle cell patients in the US. Methods: All adult hospitalized patients in the Nationwide Readmission Database (NRD) for the year 2019 were captured. The sample population included all patients with primary diagnosis of Sickle cell crisis, identified using ICD-10 codes (International Classification of Diseases, tenth edition). We used the Wilcoxon rank sum test to compare continuous variables and chi square test for categorical variables. Predictors of readmission were analyzed using multivariate logistic regression models. We used StataCorp LLC MP4 17 version to perform statistical analysis. Results: The sample size included 48,715 patients admitted with sickle cell crisis, of which 55.12% were females and 44.88% were males. The mean age of presentation was 32.84 years. The rate of all cause 30-day readmission in patients admitted with Sickle cell crisis was 27.19%. The total hospital charges for these readmitted patients during the year 2019 was 507 million dollars and total length of stay was 69,418 days (about 190 years). The most common causes of readmissions were Sickle cell crisis including Acute chest syndrome and splenic sequestration crisis, followed by sepsis due to MRSA and femoral fractures. After adjusting for confounders on multivariate analysis, compared to patients belonging to income category 1 ( < $46,000), patients in category 2 ($46,000-$58,999) had 11% lower risk (p-value 0.018) and category 3 had 16% lower risk (p-value 0.008) of 30-day readmission. However, there was no increased risk of death based on socioeconomic status (OR 1.03, p-value 0.875). Conclusions: Our study concludes that socioeconomically deprived Sickle cell crisis patients are at higher risk of readmissions. Factors like poor living situation, lack of means for transportation, potential lower level of education leading to decreased medication compliance and clinic follow ups could be attributed to these findings. Interventions targeting this population can help reduce healthcare burden and patient morbidity significantly. [Table: see text]

Timing matters: An analysis of the relationship between red cell transfusion timing and hospitalization outcomes in sickle cell crisis patients using the National Inpatient Sample database.

Vaso-occlusive pain crisis is a debilitating complication of sickle cell disease (SCD) and it is the most common cause of hospitalization among these individuals. We studied the inpatient outcomes among patients admitted with sickle cell crisis based on the timing of red blood cell transfusion. In this retrospective study, we used the United States National Inpatient Sample (NIS) data for the year 2019, to identify adult patients hospitalized with the principal diagnosis of sickle cell crisis who received simple red blood cell transfusion during their hospitalization. Patients were divided into two groups. Those who received simple red cell transfusion within 24hours of admission were classified as early transfusion. After adjusting for confounders, the mean adjusted length of stay for patients with early transfusion was significantly lower than those who received a late blood transfusion by 3.51days (p-value < 0.001) along with a decrease in mean adjusted hospitalization charges and cost, by 25,487 and 4,505 United States Dollar (USD) respectively. The early red cell transfusion was also associated with a decrease in inpatient mortality, demonstrated by an adjusted odds ratio (aOR) of 0.19 (p-value 0.036), and a reduction in in-hospital sepsis, with an aOR of 0.28 (p-value < 0.001), however, no statistically significant difference was found between the two groups regarding acute respiratory failure requiring intubation, vasopressors requirement, acute kidney injury requiring dialysis and intensive care unit (ICU) admission. We recommend timely triage and reassessment to identify sickle cell crisis patients requiring blood transfusion. This intervention can notably affect the inpatient length of stay, resource utilization, and hospitalization outcomes.

Manual Partial Exchange Transfusion a Cost Effective Life Saving Intervention in Sickle Cell Crisis: Single Centre Retrospective Data Analysis

Introduction: Sickle cell disease (SCD) poses a considerable health burden in lower middle income country (LMIC) like India. One ICMR survey reported about 20% of children with SCD died by the age of two years and 30% of children with SCD amongst the tribal community in India died before they reached adulthood. Data on mortality rate in the adult population with SCD is sparse. Our centre data shows that despite the availability of Hydroxyurea and supportive care, almost one-third of hospitalized Sickle Cell Crisis patients develop life threatening complications. Manual Partial Exchange Transfusion is a cost-effective intervention to decrease mortality in Sickle Cell Crisis. But perhaps, it is an underutilized therapy. In India, the cost incurred for each session of exchange transfusion, if done by the RBC apheresis machine, is $420. Whereas Manual Exchange Transfusion costs only $70(including the cost of the central venous catheter) for the first session followed by $15 for each subsequent session. Aim: A single centre retrospective data analysis to evaluate the outcome of Sickle Cell Crisis patients undergoing Manual Partial Exchange Transfusion during hospitalization. Material and Method: A total of 553 SCD patients on regular follow up at the Haemato Oncology Care Centre (HOCC) from July 2012 to July 2020 were evaluated.169 patients were hospitalized for treatment of Sickle Cell Crisis at the Bhailal Amin General Hospital and Sterling Hospital Vadodara. The data was retrieved after the IRB/Apex committee approvals for retrospective analysis. The indication for exchange transfusion was Acute Chest Syndrome 19(35%), Hepatic cell crisis 11(20%), Vaso Occlusive Crisis not responding to the conservative line of therapy in 48 hours of treatment 11(20%), Cerebrovascular Accident (CVA) 5 (9%), Avascular Necrosis of Femur with excruciating pain 3 (6%), Complicated Dengue with Multi-organ failure 3 (6 %), Priapism 1 (2%) and Splenic Sequestration 1 (2%). Central venous access was secured with a central venous catheter or dialysis catheter. Simple packed cell volume was transfused to 11(20%) patients and 5(9%) patients received platelet transfusion. The cut-off values for HB and Platelet count were 8 gm% and 50000/cumm, respectively at the time of the Manual Partial Exchange Transfusion procedure. Blood volume withdrawn was 5 to 10 ml /kg, followed by an equal volume of packed cell volume transfusion at every session. The procedure was repeated every 12 hr or 24 hr depending on the clinical condition of the patient. HbS value was reassessed post 4 sessions with repeat testing done after 2 to 4 sessions if the observed HbS value was more than 30% or more than 10% (for CVA) after 4 sessions. The endpoint was clinical recovery with HbS less than 30% or no clinical recovery despite the achievement of HbS less than 10%. In CVA the endpoint was HBS less than 10%. Results: Manual Partial Exchange Transfusion was carried out in 54/169 (32 %) hospitalized patients. The median age was 25yrs (range 5 yrs to 69 yrs), with male predominance [Males 42(77%) and females 12(23%)].Pre procedure HbF value was &amp;lt;10% in 13(24%), 10 to 20% in 23 (43%) and &amp;gt;20% in 18(33%). A total of 50 out of 54 (93%) patients recovered completely. 28 (52%) patients were hemodynamically stable with normal SPO2 on room air at the time of Manual Partial Exchange Transfusion with an average of 7 days of hospitalization. All of these patients recovered completely with less than 5 sessions of Manual Partial Exchange Transfusion. 26(49%) patients were critically ill and had an average of 12 days of hospitalization. They were on Ventilator and Inotrope support at the time of Manual Partial Exchange Transfusion. 14/26(54%) critically ill patients recovered completely with an average of 6 sessions of Manual Partial Exchange Transfusion. 12/26(46%) critically ill patients succumbed even though post exchange HBS value decreased to less than 10%. The overall mortality rate of SCD patients in this analysis was 12/553 (2.1%), significantly lower than what was historically reported as 30% in the ICMR survey. Underlying Dengue viral infection associated with Multi-organ dysfunction and Fulminant hepatic failure were risk factors for mortality observed in our study. Conclusion: Manual Partial Exchange Transfusion is highly effective in reducing mortality in Sickle Cell Crisis. It is feasible and cost-effective in small centres lacking apheresis machine facility. Disclosures No relevant conflicts of interest to declare.

Relief of Acute Chest Syndrome of Sickle Cell Anaemia by Nitric Oxide Inhalation - A Report of 2 Cases

Depletion of nitric oxide (NO) in the microcirculation plays a central role in the pathogenesis of sickle cell disease (SCD) and acute chest syndrome (ACS). Various other mechanisms which are responsible for the sickle-cell vasoocclusive crisis are polymerization of sickle haemoglobin, platelet activation, endothelial damage and leucocyte adhesion. During the sickle cell crisis, the high rate of red blood cell (RBC) destruction leads to release of erythrocyte arginase (into the plasma), which thereby destroys arginine. Arginine, the substrate for NO synthase, once depleted, results in lower levels of NO in vessels, leading to vasoconstriction, pulmonary hypertension and ventilation perfusion mismatch. Increasing the availability of NO therefore has a central role in SCD, especially in cases of ACS. With the prevention of vasoconstriction by NO inhalation therapy in ACS, pain relief can be provided to the patients in sickle cell crisis. We present a report of 2 cases of sickle cell disease with ACS (Acute Chest Syndrome) in whom inhalation of NO through non-invasive ventilation (NIV) brought about pain relief and recovery from ACS.

Erythrocyte membrane ATPase activity in Sickle cell crisis

Background: Sickle cell disease is a genetic disease caused by a point mutation in the beta globin gene on chromosome 11 leading to the substitution of valine in place of glutamic acid in beta subunit of globin molecule. The vaso-occlusive crisis, or sickle cell crisis, is a common painful complication of sickle cell disease in adolescents and adults. Many studies have suggested the alteration in intracellular concentration of various ions associated with sickle cell disease.Aims and Objectives: This study aims to evaluate the activity of red blood cell membrane ATPase activity of sickle cell crisis patients in comparison to sickle cell patients in steady state.Material and Methods: Twenty patients of sickle cell crisis were included in the study. Twenty sickle cell patients in steady state were also registered who served as controls. The RBC Membrane ATPase activity were estimated and expressed as μmol of Pi/μg of protein/hour.Results: The activity of membrane ATPase were found to be significantly high in patients of sickle cell crisis in comparison to steady state ones.Conclusion: Membrane ATPases play a crucial role in the pathophysiology of sickle cell crisis. This study can be a based upon for future studies to understand the pathophysiology of sickle cell crisis and development of diagnostic and treatment modalities for the same.Asian Journal of Medical Sciences Vol.8(5) 2017 27-30

Clinical and Geographic Characterization of 30-Day Readmissions in Pediatric Sickle Cell Crisis Patients.

Sickle cell disease (SCD) is a blood disorder affecting many US children that is often associated with hospital readmission. Although previous studies have reported on the clinical factors that influence readmission risk, potential geographic factors have not been fully investigated. The goal of this study was to investigate the importance of geographic risk factors and to confirm previously derived clinical risk factors that influence readmissions for SCD pain crises. Retrospective analyses were performed on pediatric inpatients with sickle cell crises at a single center. Readmission rates and risk factors were assessed. Geospatial analysis was conducted on point variables that represented health service access, and multivariable logistic regression models were constructed. The study identified 373 patients experiencing sickle cell crises, with 125 (33.5%) having at least one 30-day readmission. Age (mean difference: 2.2 years; P<0.001), length of stay (median difference: 1 day; P<.001), admission pain score>7 of 10 (odds ratio [OR]: 2.21; P<0.01), discharge pain score>4 of 10 (OR: 2.098; P<.01), living within 5 miles of the center's main hospital (OR: 0.573; P=.04), and >3 hospital utilizations in the previous 12 months (OR: 5.103; P<.001) were identified as potential indicators of 30-day readmission risk. Logistic regression models for 30-day readmissions yielded similar results. Increased age, high admission and discharge pain scores, decreased length of stay, and increased hospital utilizations were found to be associated with an increased risk of readmission for sickle cell crisis. Patient's residence was also found to be a significant risk indicator, supporting the utility of geospatial analysis in assessing readmission risk.

Left ventricular myocardial performance assessed by 2-dimensional speckle tracking echocardiography in patients with sickle cell crisis

BackgroundThe status of left ventricle in sickle cell anemia presenting in sickle crisis and follow up has been minimally studied in past. To determine the left ventricular (LV) myocardial performance in these patients, we performed the study to assess two dimensional strains imaging which allowed a rapid and an accurate analysis of global and regional LV myocardial performance in longitudinal, radial, and circumferential directions. MethodsIn this prospective study, 2-dimensional echocardiography (2DE) images of the LV were obtained in 52 subjects which included 32 patients (23 ± 8yrs, 16 male) with homozygous sickle cell anemia (SCA) in sickle cell crisis and 20 healthy controls (23 ± 5 yrs, 11 male) using apical 4-chamber and parasternal short-axis at the basal, mid, and apical levels. Of these 32 patients, 2DE was performed again in 18 patients in follow up (8 months ± 5 days). Longitudinal, circumferential and radial strains (LS, CS and RS respectively) were quantified and compared in an 18-segment model using a novel speckle tracking system (2D Cardiac Performance Analysis, TomTec Imaging System, Munich, Germany). ResultsThere was no significant difference in LV ejection fraction between both the groups (59.32 ± 12.6 vs. 52.3 ± 7.9; p-value > 0.05). In comparison with normal controls and follow up of sickle cell patients, peak LS was significantly attenuated in the subendocardial and subepicardial regions during sickle cell crisis (p < 0.05). However, a significant reduction in circumferential strain was evident only in subepicardial region (p < 0.001). Also patients in sickle cell crisis showed significantly higher radial strain parameters than controls (p < 0.001). ConclusionPatients with SCA presenting in sickle cell crisis have reduced longitudinal shortening. LV myocardial performance remains unaltered due to relatively preserved circumferential shortening and increased radial thickening.

Clinical evaluation of a new functional test for detection of plasma procoagulant phospholipids

The objective of this study was to validate a simple factor Xa-based clotting test developed to monitor procoagulant phospholipids (PPLs) and platelet-derived microparticles (PMPs). This assay is easily automated, giving it a major advantage over the more laborious and expensive flow cytometry, electron microscopy and ELISA techniques in general usage at present. The intra-assay and inter-assay variation coefficients were less than 5% at both low and high levels of PPLs. The test is not affected by other clotting factors is assured by the use of a phospholipid-free animal plasma, which provides excess factor V, fibrinogen and prothrombin. This test was evaluated in apparently healthy volunteers and in selected patient groups associated with increased levels of PMPs in the circulation (diabetes mellitus, sickle cell disease, thyroid cancer and patients with multiple trauma). The study showed that XaCT has a high discriminating power for PPLs and that the patient groups have significantly highly increased PPLs activities when compared with healthy volunteers. Although of a preliminary nature, the test has shown that it has the sensitivity for discriminating severity of disease, as it could detect patients in sickle cell crisis and differentiate between type 1 and 2 diabetes. In conclusion, the combination of reliability, reproducibility and easy performance makes the XaCT assay a simple test to screen for PPLs in plasma samples.

Sickle cell pain management meets technology: Everybody wins

Summary Sickle cell disease is a chronic disease characterized by frequent exacerbations of its symptomatology. Intense pain is a hallmark of a sickle cell crisis, yet unfortunately, inadequate pain management in this population is well documented. Frequent visits to the Emergency Department (ED) by those in crisis expose them to several barriers that inhibit effective care, particularly pain management. Suspicion of drug seeking behaviour based on ethnicity or race, requests for specific drugs and doses, administration of large doses of opioid without relief, and a general lack of knowledge regarding pain management among healthcare professionals are some of these barriers. Using information technology, an effort was undertaken to simultaneously address many of the barriers to pain management for sickle cell crisis patients in the emergency department, and enhance the quality of pain management they receive.

Endothelial Function in Patients with Sickle Cell Anemia During and After Sickle Cell Crises

Prior studies have demonstrated increased adherence of sickle cell erythrocytes to vascular endothelial cells. While decreased production of nitric oxide and increased production of adhesion molecules have been implicated in this pathophysiology, the relative contribution of these mechanisms during acute sickle cell crises as compared to steady state conditions have not been elucidated. We studied 10 consecutive young adult patients presenting with a sickle cell crisis. Endothelial function was evaluated by a non-invasive brachial artery shear stress method. Serum levels of adhesion molecules were obtained during the crisis. Both brachial artery responsiveness and serum levels of adhesion molecules were then repeated at steady state. Ten age and gender matched volunteers served as a control group. Impaired endothelial function and impaired endothelium-independent vasodilatation were observed in all sickle cell patients during both steady state and during crisis. Flow mediated dilation (FMD)% was 3.25+/- 2.76% during crisis, 4.57+/- 4.11 at steady state, compared with the control group FMD of 11.64+/- 7.69% (p< 0.001). Flow independent dilation was 10.35+/- 11.3% during crisis, 10.03+/- 6.52% at steady state, compared with control group FID of 24.17+/- 11.87% (p< 0.001). Levels of cell adhesion molecules and markers of inflammation were increased in sickle cell crisis patients compared with the control group: sCD40 ligand levels during the acute crisis were over twice the level of normal matched volunteers (p=0.02), and similarly significant increases were seen for E-selectin (p=0.008), ICAM-1 (p=0.037) and VCAM-1 levels (p=0.01). The levels of each of these biomarkers was not significantly increased during acute crises as compared to patients' recovery state. Sickle cell anemia patients have severe systemic endothelial dysfunction as demonstrated by both brachial artery assessment and increased serum levels of adhesion molecules. These abnormalities characterize not only the sickle cell crisis but also the steady state pathophysiology of sickle cell anemia.

A Shift From Demerol (Meperidine) to Dilaudid (Hydromorphone) Improves Pain Control and Decreases Admissions for Patients in Sickle Cell Crisis

October 2004 30:5 eperidine was first synthesized in 1939 as an M agent and almost immediately became the most commonly prescribed opiate in the United States. At that time, morphine was available only in hypodermic tablets, which had to be dissolved and then injected. Meperidine, on the other hand, was available in solution, which made measuring relatively accurate and administration easier. Initially, it was thought that meperidine would not cause some of the problems associated with morphine such as respiratory depression, constipation, and urinary retention. Practitioners also believed that meperidine had a low potential for habituation and addiction. Enthusiasm for this drug was such that it was estimated in the late 1980s that as many as 60% of physicians in the United States were prescribing it for acute pain and 22% were prescribing it for chronic pain. Despite the popularity of meperidine, there are problems with its use. The metabolism of meperidine results in a neurotoxic metabolite, normeperidine. Normeperidine has half the analgesic strength of meperidine but 2 to 3 times the potency as a central nervous system excitatory agent. It has the propensity to induce anxiety, hyperref lexia, and mood changes. In large doses normeperidine can accumulate and has even been known to cause seizures. Meperidine also interacts unpredictably with monoamine oxidase inhibitors, phenelzine, tranylcypromine, and isocarboxazid. Some interactions are marked by agitation, tremors, fever, seizure, and even apnea and death. In populations where meperidine may be given over a period of several days, as with patients who have sickle cell disease, the potential for accumulation of

'We can't have it both ways'

Bravo Dr. Zanga! (AAP News, January) I, too, am young enough to remember my residency and old enough to see the major changes in the practice of primary care pediatrics. I all too well remember my six months in the NICU where we not only ordered care for our patients, we actually carried out that care. We adjusted the ventilators, drew the blood samples, actually performed many tests in the nursery and transported other samples to the pathology laboratory. In the emergency room we would perform the spinal tap and then do the cell counts. We examined stool samples, plated and read streptococcal cultures, pulled blood smears, and looked at KOH slides. On the wards we learned to read our patient9s X-rays, we took care of diabetics in DKA, patients in sickle cell crisis, and asthmatics. In our outpatient rotations, we used specific testing procedures for a wide variety of problems — from the hearing-impaired child to the sexually active teenager. I was truly excited to finish residency and put into practice this wide variety of skills.

Nitric oxide metabolite levels in acute vaso-occlusive sickle-cell crisis.

1) To measure nitric oxide (NO) metabolite levels in patients presenting to the ED in acute vaso-occlusive sickle-cell crisis (SCC), and 2) to determine whether a relationship exists between NO metabolite levels and pain. A prospective, observational study of patients with documented sickle-cell anemia (SCA), aged > or = 18 years, presenting in typical, acute SCC was conducted in an urban, university teaching hospital. Excluded were those with atypical pain or acute, coexistent disease (as evidenced by fever, tachycardia, tachypnea, or hypotension). Pain scores were measured by a 10-cm visual analog scale (VAS). Blood NO metabolite levels for SCC patients and control subjects (healthy volunteers, n = 9; SCA control subjects not in SCC, n = 10) were determined using an NO-specific chemiluminescence technique that measured plasma nitrite and nitrate, the stable end-products of NO. The acute SCC patients were divided into 3 groups, with the range for the SCC-normal (n = 5) group defined as within 2 SD of the healthy volunteer control patients. The SCC-low patients (n = 21) had NO metabolite levels below this range and the SCC-high (n = 21) patients had levels above this range. The SCA and healthy volunteer control groups had similar NO metabolite levels (25.3 vs 22.6 mumol; p = 0.10). The 3 acute SCC groups had the following mean NO levels: 1) SCC-normal = 21.3 +/- 1.6 mumol; 2) SCC-low = 7.2 +/- 1.1 mumol; and 3) SCC-high = 43.7 +/- 3.5 mumol. The SCC-high NO-level group had significantly lower VAS pain scores when compared with the SCC-low and SCC-normal NO-level groups (6.52 +/- 1.85 cm vs 8.76 +/- 0.83 cm, and 8.62 +/- 1.29 cm, p = 0.02). NO metabolite levels vary in SCC patients. Elevated levels are associated with lower pain scores, while lower levels are associated with higher pain scores, indicating that NO metabolites may potentially represent a marker for compensatory mechanisms in SCC tissue ischemia. Further work is needed to delineate the usefulness of NO metabolites in assessing the severity of SCC.

Sickle cell crisis and sensorineural hearing loss: case report and discussion

Patients in sickle cell crisis may complain of unilateral or bilateral hearing loss which is typically a mild to moderate high-frequency sensorineural hearing loss in the affected ear(s). Auditory acuity can return to precrisis levels. A literature review suggests that the etiology is cochlear ischemia. A review of the literature, case study, and discussion will be presented.