Acute chest syndrome in children with sickle cell disease: Data from a national AIEOP cohort identify priority areas of intervention in a hub-and-spoke system.

Acute chest syndrome (ACS) is a frequent cause of hospitalization in sickle cell disease (SCD). Despite advances in acute care, many settings still lack knowledge about ACS best practices. After the AIEOP Guidelines were published in 2012, suggesting standardized management in Italy, a retrospective study was performed to assess the diagnostic and therapeutic pathways of ACS in children. From 2013 to 2018, 208 ACS episodes were presented by 122/583 kids in 11 centres. 73 were male, mean age 10.9 years, 85% African, 92% HbSS or Sß°. In our hub-and-spoke system, a good adherence to Guidelines was documented, but discrepancies between reference centres and general hospitals were noted. Improvement is needed for timely transfer to reference centres, use of incentive spirometry, oxygen therapy and pain management.

Sputum interleukin-6 level as a marker of severity during acute chest syndrome in children with sickle cell disease.

Acute chest syndrome (ACS) is a leading cause of morbimortality in sickle cell disease (SCD). In this prospective observational study, we investigated sputum interleukin-6 (IL-6) level as an ACS severity marker during 30 ACS episodes in 26 SCD children. Sputum IL-6 levels measured within the first 72 h of hospitalisation for ACS were significantly higher in patients with oxygen requirement ≥2 L/min, ventilation (invasive and/or non-invasive) length ≥5 days, bilateral and/or extensive opacities on chest X-ray or erythrocytapheresis requirement. Sputum IL-6 could serve as an ACS severity marker to help identify patients requiring targeted anti-inflammatory treatments such as tocilizumab.

Left ventricular global longitudinal strain and acute myocardial injury in patients with sickle cell disease admitted to the intensive care unit for vaso-occlusive crisis.

In patients with sickle cell disease (SCD), SCD-related cardiomyopathy may be partly due to repeated ischaemic events related to sickling during vaso-occlusive crises, but few clinical studies support this hypothesis. We evaluated the incidence of acute myocardial ischaemia during vaso-occlusive crises as assessed by the left ventricular global longitudinal strain (LVGLS) and high-sensitive cardiac troponin T (hs-cTnT). We included adult patients with SCD admitted to the intensive care unit (ICU) for vaso-occlusive crisis. We collected hs-cTnT and measured LVGLS with echocardiography at admission (day 1), day 2, day 3 and ICU discharge. Among 55 patients included, considering only the first hospitalization of patients admitted several times, 3 (5%) had elevated hs-cTnT at ≥1 time point of the ICU stay. It was ≤2 times the upper limit of normal in two of these patients. LVGLS was altered at ≥1 time point of the ICU stay in 13 (24%) patients. Both hs-cTnT and LVGLS were abnormal at ≥1 time point of the hospital stay in 2 (4%) patients. Acute myocardial injury as assessed by troponin elevation and LVGLS impairment was a rare event during vaso-occlusive crises.

SNAP: Supportive non-invasive ventilation for acute chest syndrome prevention for hospitalized children with sickle cell disease: Perspectives of patients, parents, and the healthcare team.

RATIONALE: Acute chest syndrome (ACS) often develops during hospitalizations for sickle cell disease (SCD) vaso-occlusive episodes and may be triggered by a combination of chest wall splinting, opioid use, hypoventilation, and atelectasis. In 2017, Boston Medical Center's general pediatric inpatient unit instituted the novel use of bi-level positive airway pressure (BiPAP) as "supportive non-invasive ventilation for ACS prevention" (SNAP) to prevent ACS and respiratory decompensation. OBJECTIVE: The goals of this qualitative study were to identify perceived benefits, harms, facilitators, and barriers to use of SNAP. METHODS: We conducted semi-structured key informant interviews at three sites with different levels of SNAP implementation (Site 1: extensive implementation; Site 2: limited implementation; Site 3: not yet implemented) regarding experiences with and/or perceptions of SNAP. Interviews and coding were guided by the Promoting Action on Research Implementation in Health Services (PARiHS) framework. RESULTS: Thirty-four participants (physicians, nurses, respiratory therapists, child life specialists, psychologists, youth with SCD, and parents) completed interviews. Major themes included: (i) participants perceive BiPAP as effective at preventing ACS, and for those with medically stable ACS, for preventing respiratory decompensation. (ii) BiPAP use is appropriate on the general pediatric inpatient unit for medically stable patients with SCD. (iii) Improving the patient experience is the most important factor to optimize acceptance of BiPAP by patients and families. CONCLUSION/FUTURE DIRECTIONS: SNAP is perceived as effective and appropriate for hospitalized pediatric patients with SCD. Improving the patient experience is the biggest challenge. These data will inform a future protocol for a multicenter hybrid effectiveness/implementation trial of SNAP.

Venoarterial Extracorporeal Membrane Oxygenation Therapy in Patients with Sickle Cell Disease: Case Series and Review for Intensive Care Physicians.

Sickle cell disease (SCD) is associated with substantial morbidity and early mortality in afflicted adults. Cardiopulmonary complications that occur at increased frequency in SCD such as pulmonary embolism, pulmonary arterial hypertension, and acute chest syndrome can acutely worsen right ventricular function and lead to cardiogenic shock. Mechanical circulatory support including venoarterial extracorporeal membrane oxygenation (VA ECMO) is being increasingly utilized to treat hemodynamic collapse in various patient populations. However, a paucity of literature exists to guide the use of mechanical circulatory support in adults with SCD where disease-related sequela and unique hematologic aspects of this disorder may complicate extracorporeal therapy and must be understood. Here, we review the literature and describe three cases of adult patients with SCD who developed cardiogenic shock from acute decompensated right heart failure and were treated clinically with VA ECMO. Using an in vitro ECMO system, we investigate a potential increased risk of systemic fat emboli in patients with SCD who may be experiencing vaso-occlusive events with bone marrow involvement given the high-volume shunting of blood from venous to arterial systems with VA ECMO. The purpose of this study is to describe available extracorporeal life support experiences, review potential complications, and discuss the special considerations needed to further our understanding of the utility of VA ECMO in those with SCD.

Lipid and hemolysis parameters predicting acute chest syndrome in adulthood with sickle cell disease.

Sickle cell disease (SCD) is a lifelong blood disorder affecting approximately 100,000 people in the United States and is one of the most common monogenic diseases. A serious complication of SCD is acute chest syndrome (ACS). ACS is a condition with a high rate of morbidity and mortality. The aim of the study was to assess hemolysis and lipid parameters in a cohort of confirmed SCD patients to predict ACS development in the following year.Standard lipid were performed (triglycerides, total cholesterol, high-density cholesterol, low-density cholesterol) panel to calculate of non-HDL-C, large buoyant LDL cholesterol (lbLDL-C) and small dense LDL cholesterol (sdLDL-C) with Sampson equation. Hemolysis and hematologic parameters were also evaluated.Among 91 patients included between September 2018 and June 2021, thirty-seven patients had history of ACS and 6 patients developed ACS during following year. In unadjusted logistic regression, total bilirubin was associated with ACS occurrence (RR: 1.2 [1.05-1.51] p = 0.013). Concerning lipid profile, non-HDL-C (RR: 0.87 [0.0.67-0.99] p = 0.04) and sdLDL-C (RR: 0.78 [0.49-0.96] p = 0.03) were associated with ACS occurrence decrease. C-reactive protein was associated with ACS occurrence (RR: 1.27 [1.065-1.85] p = 0.011).Based on these findings, this study demonstrated that several biomarker easily available can be used at steady state to predict ACS in the following year. The validation of these results are required to ensure the reproducibility of the findings.

Enhancing diagnostic precision for acute chest syndrome in sickle cell disease: insights from dual-energy CT lung perfusion mapping.

PURPOSE: Acute chest syndrome (ACS) is secondary to occlusion of the pulmonary vasculature and a potentially life-threatening complication of sickle cell disease (SCD). Dual-energy CT (DECT) iodine perfusion map reconstructions can provide a method to visualize and quantify the extent of pulmonary microthrombi. METHODS: A total of 102 patients with sickle cell disease who underwent DECT CTPA with perfusion were retrospectively identified. The presence or absence of airspace opacities, segmental perfusion defects, and acute or chronic pulmonary emboli was noted. The number of segmental perfusion defects between patients with and without acute chest syndrome was compared. Sub-analyses were performed to investigate robustness. RESULTS: Of the 102 patients, 68 were clinically determined to not have ACS and 34 were determined to have ACS by clinical criteria. Of the patients with ACS, 82.4% were found to have perfusion defects with a median of 2 perfusion defects per patient. The presence of any or new perfusion defects was significantly associated with the diagnosis of ACS (P = 0.005 and < 0.001, respectively). Excluding patients with pulmonary embolism, 79% of patients with ACS had old or new perfusion defects, and the specificity for new perfusion defects was 87%, higher than consolidation/ground glass opacities (80%). CONCLUSION: DECT iodine map has the capability to depict microthrombi as perfusion defects. The presence of segmental perfusion defects on dual-energy CT maps was found to be associated with ACS with potential for improved specificity and reclassification.

Beyond pulmonary embolism: Alternative diagnosis and incidental findings on CT pulmonary angiography in sickle cell disease.

BACKGROUND: Sickle cell disease (SCD) is a genetic hematological disorder associated with severe complications, such as vaso-occlusive crises, acute chest syndrome (ACS), and an increased risk of thromboembolic events, including pulmonary embolism (PE). The diagnosis of PE in SCD patients presents challenges due to the overlapping symptoms with other pulmonary conditions. Our previous study revealed that nearly 96% of computed tomography pulmonary angiography (CTPA) scans in SCD patients were negative for PE, highlighting a gap in understanding the significance of CTPA findings when PE is absent. METHODS: In this retrospective follow-up study conducted at the Salmaniya Medical Complex in Bahrain, we examined SCD patients with HbSS genotypes who underwent CTPA from January 1, 2018, to December 31, 2021, for suspected PE, but the results were negative. The aim of this study was to identify alternative diagnoses and incidental findings from CTPA scans. Experienced radiologists reviewed the CTPA images and reports to assess potential alternative diagnoses and incidental findings, incorporating an additional analysis of chest X-rays to evaluate the diagnostic value of CTPA. Incidental findings were classified based on their location and clinical significance. RESULTS: Among the 230 evaluated SCD patients (average age 39.7 years; 53% male) who were CTPA negative for PE, 142 (61.7%) had identifiable alternative diagnoses, primarily pneumonia (49.1%). Notably, 88.0% of these alternative diagnoses had been previously suggested by chest radiographs. Furthermore, incidental findings were noted in 164 (71.3%) patients, with 11.0% deemed clinically significant, necessitating immediate action, and 87.8% considered potentially significant, requiring further assessment. Notable incidental findings included thoracic abnormalities such as cardiomegaly (12.2%) and an enlarged pulmonary artery (11.3%), as well as upper abdominal pathologies such as hepatomegaly (19.6%), splenomegaly (20.9%), and gallstones (10.4%). CONCLUSION: This study underscores the limited additional diagnostic yield of CTPA for identifying alternative diagnoses to PE in SCD patients, with the majority of diagnoses, such as pneumonia, already suggested by chest radiographs. The frequent incidental findings, most of which necessitate further evaluation, highlight the need for a cautious and tailored approach to using CTPA in the SCD population.

Morbidity and Mortality Associated with COVID-19 and Acute Chest Syndrome in Sickle Cell Disease Patients.

SUMMARYCOVID-19 infection has emerged as a comorbidity that can significantly increase morbidity and mortality in sickle cell patients with ACS (acute thoracic/chest syndrome). The aim of our study was to assess COVID-19-related morbidity and mortality in sickle cell patients with ACS. This was a retrospective, descriptive study of patient records followed over a 36-month period from January 2020 to December 2022. The study was conducted at the national blood transfusion center in Dakar. The sex ratio (M/F) was 0.82. The median age was 26 (17-39) years. The most represented age group was between 21 and 30 years. Factors associated with death were: at baseline, SS genotype, presence of comorbidities (asthma, chronic obstructive pulmonary disease, viral hepatitis B, ischemic heart disease), osteonecrosis of the femoral head, and use of NSAIDs (non-steroidal anti-inflammatory drugs) at diagnosis of COVID-19; at the diagnosis of ACS associated with COVID-19, respiratory distress, hypoxia (Sa02 < 92%), creatininemia >18.5 mg/l, CRP >192 mg/l, lymphopenia; the therapeutic modalities associated with death were: transfusion of RBCs (packed red blood cells) and curative anticoagulation. This study shows that patients with comorbidities and/or chronic complications of sickle cell disease can develop severe forms of ACS associated with COVID 19, leading to death. Other factors linked to death, notably diagnostic and therapeutic, were also identified in the course of this study.

Acute chest syndrome in adult patients with sickle cell disease: The relationship with the time to onset after hospital admission.

Data on acute chest syndrome (ACS) in adult sickle cell disease patients are scarce. In this study, we describe 105 consecutive ACS episodes in 81 adult patients during a 32-month period and compare the characteristics as a function of the time to onset after hospital admission for a vaso-occlusive crisis (VOC), that is early-onset episodes (time to onset ≤24 h, 42%) versus secondary episodes (>24 h, 58%; median [interquartile range] time to onset: 2 [2-3] days). The median age was 27 [22-34] years, 89% of the patients had an S/S or S/ß0 -thalassaemia genotype; 81% of the patients had a history of ACS (median: 3 [2-5] per patient), only 61% were taking a disease-modifying treatment at the time of the ACS. Fever and chest pain were noted in respectively 54% and 73% of the episodes. Crackles (64%) and bronchial breathing (32%) were the main abnormal auscultatory findings. A positive microbiological test was found for 20% of episodes. Fifty percent of the episodes required a blood transfusion; ICU transfer and mortality rates were respectively 29% and 1%. Secondary and early-onset forms of ACS did not differ significantly. Disease-modifying treatments should be revaluated after each ACS episode because the recurrence rate is high.

Screening for asthma in preschool children with sickle cell disease.

BACKGROUND: Asthma in preschool children is poorly defined, proving to be a challenge for early detection. The Breathmobile Case Identification Survey (BCIS) has been shown to be a feasible screening tool in older SCD children and could be effective in younger children. We attempted to validate the BCIS as an asthma screening tool in preschool children with SCD. METHODS: This is a prospective, single-center study of 50 children aged 2-5 years with SCD. BCIS was administered to all patients and a pulmonologist blinded to the results evaluated patients for asthma. Demographic, clinical, and laboratory data were obtained to assess risk factors for asthma and acute chest syndrome in this population. RESULTS: Asthma prevalence (n = 3/50; 6%) was lower than atopic dermatitis (20%) and allergic rhinitis (32%). Sensitivity (100%), specificity (85%), positive predictive value (30%), and negative predictive value (100%) of the BCIS were high. Clinical demographics, atopic dermatitis, allergic rhinitis, asthma, viral respiratory infection, hematology parameters, sickle hemoglobin subtype, tobacco smoke exposure, and hydroxyurea were not different between patients with or without history of ACS, although eosinophil was significantly lower in the ACS group (p = 0.0093). All those with asthma had ACS, known viral respiratory infection resulting in hospitalization (3 RSV and 1 influenza), and HbSS (homozygous Hemoglobin SS) subtype. CONCLUSION: The BCIS is an effective asthma screening tool in preschool children with SCD. Asthma prevalence in young children with SCD is low. Previously known ACS risk factors were not seen, possibly from the beneficial effects of early life initiation of hydroxyurea.

Arginine Therapy and Cardiopulmonary Hemodynamics in Hospitalized Children with Sickle Cell Anemia: A Prospective, Double-blinded, Randomized Placebo-controlled Clinical Trial.

Rationale: Acute changes in cardiopulmonary hemodynamics that include tricuspid regurgitant jet velocity (TRV) elevation measured by Doppler echocardiography are often encountered during sickle cell vasoocclusive pain and acute chest syndrome (ACS). Arginine and nitric oxide depletion develop in patients with these complications. Arginine administration may therefore improve nitric oxide bioavailability and potentiate pulmonary vasodilatation. Objectives: To evaluate effects of l-arginine supplementation on Doppler indices of cardiopulmonary hemodynamics in children with sickle cell anemia experiencing pain. Methods: This was a prospective, double-blinded, randomized placebo-controlled trial of oral arginine in children with sickle cell anemia age 5-17 years hospitalized with severe pain and/or ACS. Measurements and Main Results: Blood biomarkers and Doppler echocardiographic indices of cardiopulmonary hemodynamics were measured before and after supplementation. The mean change in TRV, pulmonary artery systolic pressure, mean pulmonary artery pressure, and other indices of cardiopulmonary hemodynamics were tested with paired Student's t test and correlated with markers of arginine bioavailability using Pearson correlation. Sixty-six children were randomized into arginine versus placebo groups. An elevated TRV ⩾ 2.5 m/s was seen in 40 (61%) patients. A Day 5 Doppler echocardiogram was performed in 47 patients who remained hospitalized. A greater reduction in median TRV occurred in the arginine group than placebo (22.2%, n = 22 vs. 3.8%, n = 25; p < 0.01). A larger percentage increase in global arginine bioavailability was associated with a lower TRV after 5 days of supplementation (r = -0.533; P = 0.001). Significant differences in multiple indices of cardiopulmonary hemodynamics and mean N-terminal pro B-type brain natriuretic peptide were also noted after arginine therapy. Conclusions: Oral arginine supplementation improves cardiopulmonary hemodynamics during sickle cell disease vasoocclusive pain and ACS.Clinical trial registered with Pan African Clinical Trial Registry https://pactr.samrc.ac.za/Search.aspx (PACTR201611001864290).

Cortactin loss protects against hemin-induced acute lung injury in sickle cell disease.

In patients with sickle cell disease (SCD), acute chest syndrome (ACS) is a common form of acute lung injury and a major cause of morbidity and mortality. The pathophysiology of ACS is complex, and hemin, the prosthetic moiety of hemoglobin, has been implicated in endothelial cell (EC) activation and subsequent acute lung injury (ALI) and ACS in vitro and in animal studies. Here, we examined the role of cortactin (CTTN), a cytoskeletal protein that regulates EC function, in response to hemin-induced ALI and ACS. Cortactin heterozygous (Cttn+/-) mice (n = 8) and their wild-type siblings (n = 8) were irradiated and subsequently received bone marrow cells (BMCs) extruded from the femurs of SCD mice (SS) to generate SS Cttn+/- and SS CttnWT chimeras. Following hemoglobin electrophoretic proof of BMC transplantation, the mice received 35 µmol/kg of hemin. Within 24 h, surviving mice were euthanized, and bronchoalveolar fluid (BAL) and lung samples were analyzed. For in vitro studies, human lung microvascular endothelial cells (HLMVECs) were used to determine hemin-induced changes in gene expression and reactive oxygen species (ROS) generation in cortactin deficiency and control conditions. When compared with wild-type littermates, the mortality for SS Cttn+/- mice trended to be lower after hemin infusion and these mice exhibited less severe lung injury and less necroptotic cell death. In vitro studies confirmed that cortactin deficiency is protective against hemin-induced injury in HMLVECs, by decreasing protein expression of p38/HSP27, improving cell barrier function, and decreasing the production of ROS. Further studies examining the role of CTTN in ACS are warranted and may open a new avenue of potential treatment for this devastating disease.

Evaluation of the relationship between intravascular hemolysis and clinical manifestations in sickle cell disease: decreased hemopexin during vaso-occlusive crises and increased inflammation in acute chest syndrome.

The aims of this study were to determine the possible relationships between the levels of hemin, hemopexin, acid sphingomyelinase, nitrite/nitrate (NOx), and other parameters in patients with SCD and to assess whether they were associated with vaso-occlusive crises (VOCs) or acute chest syndrome (ACS). Patients with SCD (homozygous or sickle beta-thalassemia) who were confirmed to have VOC or ACS were included. Blood samples were obtained at admission, on the third day of hospitalization, and at steady state. Demographic characteristics, pain (visual analog scale), complication history, complete blood count, lactate dehydrogenase, and C-reactive protein levels were recorded. Hemin, hemopexin, acid sphingomyelinase, and NOx were measured via ELISA. A total of 31 patients (22 VOC, 9 ACS) were included. Mean age was 16.4 ± 4.7 years. Admission white blood cell count and C-reactive protein levels were significantly higher in the ACS group. Patients with ACS also demonstrated a significant decreasing trend of LDH and an increasing trend of NOx values from admission to steady state. Notably, hemopexin levels were significantly lower on the third day of hospitalization compared to steady-state levels. Despite limited patient count in the ACS group, these patients appear to have strikingly greater inflammatory activation at admission, and the progression of ACS may be associated with LDH and NOx levels. Lower hemopexin levels during hospitalization versus steady state appear to support a role for the administration of hemopexin therapy during crises.

Risk-score based strategy to minimize antibiotic exposure in children with sickle cell disease and fever.

Severe bacterial infections (SBI) have become less frequent in children with sickle cell disease (SCD) in the last decades. However, because of their potential risk of SBI, they usually receive empirical therapy with broad-spectrum antibiotics when they develop fever and are hospitalized in many cases. We performed a prospective study including 79 SCD patients with fever [median age 4.1 (1.7-7.5) years, 78.5% males; 17 of the episodes were diagnosed with SBI and 4 of them were confirmed] and developed a risk score for the prediction of SBI. The optimal score included CRP > 3 mg/dl, IL-6 > 125 pg/ml and hypoxemia, with an AUC of 0.91 (0.83-0.96) for the prediction of confirmed SBI and 0.86 (0.77-0.93) for possible SBI. We classified the patients in 3 groups: low, intermediate and high risk of SBI. Our risk-score-based management proposal could help to safely minimize antibiotic treatments and hospital admissions in children with SCD at low risk of SBI.

Demand-only patient-controlled analgesia for treatment of acute vaso-occlusive pain in sickle cell disease.

BACKGROUND: Sickle cell disease (SCD) is a chronic illness that is associated with frequent admissions for vaso-occlusive episodes (VOE). Opioids are frequently utilized in pain management, but dosing is often provider dependent. Opioids cause both short-term and long-term side effects, so the minimal effective dose is desired. This study examined demand-only patient-controlled analgesia (PCA) in pediatric patients. METHODS: A new clinical practice guideline (CPG) for a single institution was implemented, which eliminated basal infusion dosing for PCAs on hospital admission. The primary aim of this retrospective study was to evaluate length of stay (LOS) before and after implementation of a CPG of demand-only PCA and, in a selected subpopulation, addition of short-term methadone. Secondary aims included opioid utilization, acute chest syndrome (ACS), and hypoxia. Inclusion criteria included SCD, ≤21 years of age, uncomplicated VOE admission, and ≥ 3 and ≤ 8 hospital admissions for SCD pain control within one calendar year. RESULTS: LOS decreased postintervention (7.2 ± 5.1 vs 4.5 ± 3.8 days, P < 0.001). Mean total opioid utilization in morphine equivalents mg/kg markedly decreased between the cohorts (13.3 ± 33.8 vs 3.6 ± 3.0, P < 0.001). ACS (21.9% vs 2.8%, P = 0.004) and hypoxia (28% vs 6.9%, P< 0.001) decreased significantly as well. CONCLUSION: Bolus PCA dosing of opioids resulted in decreased LOS and reductions in opioid utilization, hypoxia, and ACS.

Hemoglobin Target and Transfusion Modality for Adult Patients With Sickle Cell Disease Acute Chest Syndrome.

BACKGROUND: Despite the importance of transfusion in treating sickle cell disease acute chest syndrome, the target hemoglobin and optimal modality for transfusion remain unknown. OBJECTIVES: To compare hospital length of stay (LOS) in intensive care unit (ICU) patients with acute chest syndrome transfused to hemoglobin ≥ 8 g/dL versus patients transfused to hemoglobin < 8 g/dL; and to compare hospital LOS in acute chest syndrome patients treated with and without exchange transfusion. METHODS: We performed a retrospective cohort study of all acute chest syndrome patients treated in the medical ICU at 2 tertiary care hospitals between January 2011 and August 2016 (n = 82). We compared median hospital LOS in patients transfused to hemoglobin ≥ 8 g/dL by the time of ICU transfer to the medical floor versus patients transfused to hemoglobin < 8 g/dL as well as patients who received exchange transfusion versus no exchange transfusion using Wilcoxon rank-sum tests. We modeled the association between hospital LOS and hemoglobin at ICU transfer to the medical floor using multivariable log-linear regression. RESULTS: Median hospital LOS was about half as long for patients transfused to hemoglobin ≥ 8 g/dL versus hemoglobin < 8 g/dL (8.0 versus 16.5 days, P = 0.008). There was no difference in LOS for patients treated with and without exchange transfusion. On average, a 1 g/dL increase in hemoglobin was associated with a 19.5% decrease (95% CI 10.8-28.2%) in LOS, controlling for possible confounding factors. CONCLUSIONS: Transfusion to a hemoglobin target ≥ 8 g/dL is associated with decreased hospital LOS in patients with acute chest syndrome. There was no difference in LOS between patients who received exchange transfusion and those who did not.

Suboptimal vancomycin levels in critically ill children with sickle cell disease and acute chest syndrome.

OBJECTIVES: This is a pilot retrospective study to assess the effect of glomerular hyper-filtration (GHF) related to sickle cell disease (SCD) on vancomycin clearance and ultimately on therapeutic drug levels in children admitted to the pediatric intensive care unit (PICU) with acute chest syndrome (ACS). METHOD: The patients' steady-state vancomycin trough levels (VTL) and the area under the curve (AUC) were compared with those of age- and gender-matched control group; matching was made at a 1:3 ratio. RESULTS: Twelve SCD patients with ACS and treated with vancomycin were compared with 36 non-SCD patients (control group). Compared with the control patients, the ACS patients had significantly lower initial serum VTL (median = 6.00 mcg/mL vs. 9.75 mcg/mL) (p = 0.007), and their average VTL were still lower (median = 6.65 mcg/mL vs. 10.00 mcg/mL) post vancomycin dose adjustment (p = 0.039). The time to achieve the therapeutic vancomycin level was significantly longer for the ACS patients (median = 4.75 days) than for the control group (median = 1 day) (p = 0.009). The AUC was also significantly lower in the ACS patients (median = 293 mg*h/L) than in the control group (median = 405.5 mg*h/L) (p = 0.007). The AUC was negatively associated with creatinine clearance (Beta Coefficient = -0.366, p-value=<0.001) even when adjusted for receiving loading dose, standard dose per weight, and severity of critical illness. CONCLUSION: These findings support the attributed role of the GHF associated with SCD leading to lower vancomycin level in ACS cases. Therefore, the standard dosing approach for vancomycin in ACS patients may be ineffective. We thus advocate for individualized dosing with careful monitoring of drug levels to account for GHF.

High risk and low prevalence diseases: Acute chest syndrome in sickle cell disease.

INTRODUCTION: Acute chest syndrome (ACS) in sickle cell disease (SCD) is a serious condition that carries with it a high rate of morbidity and mortality. OBJECTIVE: This review highlights the pearls and pitfalls of ACS in SCD, including diagnosis and management in the emergency department (ED) based on current evidence. DISCUSSION: ACS is defined by respiratory symptoms and/or fever and a new radiodensity on chest imaging in a patient with SCD. There are a variety of inciting causes, including infectious and non-infectious etiologies. Although ACS is more common in those with homozygous SCD, clinicians should consider ACS in all SCD patients, as ACS is a leading cause of death in SCD. Patients typically present with or develop respiratory symptoms including fever, cough, chest pain, and shortness of breath, which can progress to respiratory failure requiring mechanical ventilation in 20% of adult patients. However, the initial presentation can vary. While the first line imaging modality is classically chest radiograph, lung ultrasound has demonstrated promise. Further imaging to include computed tomography may be necessary. Management focuses on analgesia, oxygen supplementation, incentive spirometry, bronchodilators, rehydration, antibiotics, consideration for transfusion, and specialist consultation. Empiric antibiotics that cover atypical pathogens are necessary along with measures to increase oxygen-carrying capacity in those with hypoxemia such as simple transfusion or exchange transfusion. CONCLUSIONS: An understanding of ACS can assist emergency clinicians in diagnosing and managing this potentially deadly disease.

A case of autopsy discovery of acute chest syndrome triggered by pulmonary embolism in a sickle cell patient.

This is a case report about a 7-year-old male child with sickle cell anemia (S/ß+) who died unexpectedly during hospitalization, justifying the performance of a forensic autopsy completed by histological examination of organ fragments and toxicological analyses of biological fluids. The diagnosis retained was pulmonary thromboembolism as the cause of death occurring in the context of an acute chest syndrome (ACS). The mechanism of occurrence of this pulmonary embolism was vascular stasis caused by sickle cell disease. The search for etiologies of ACS complicating sickle cell disease should not exclude pulmonary embolism with red cell dense fibrin clot..