Monday, October 27, 2014

Steroids for Acute Chest Syndrome?

Clinical Scenario:

A 41 year-old male with a history of well-controlled sickle cell disease and a remote history of CVA and Acute Chest Syndrome (ACS) presents to the ED with three days of left sided chest, shoulder, and flank pain. The pain was subacute in onset, was not pleuritic, was worse with movement, and was not improved with NSAIDs. He also complained of a dry cough but reported no fevers. He had an oxygen saturation of 88% on room air, but his vital signs were otherwise normal. His physical exam demonstrated clear lungs and pain with palpation of his left shoulder and left anterior chest wall. His EKG showed stable borderline LVH. Labs were notable for a negative troponin and Hgb of 5.8, and a left basilar airspace opacity on lateral chest X-ray. He was given IV fluids, morphine, and IV ceftriaxone & azithromycin to cover for Community-Acquired PNA (CAP) triggering Acute Chest Syndrome.

Clinical Question:

Do steroids have a role in treatment of Acute Chest Syndrome?

Plain CXR showing patchy infiltrates of acute chest syndrome. Image credit from AccessMedicine.

Literature Review:

Several retrospective studies from the late 1990s and early 2000s found conflicting results with regards to the effect of steroids on length-of-stay (LOS) and readmission rates [1]. The first RCT designed to answer this question published results in 1998. This group randomized 43 children with ACS to IV dexamethasone or placebo. The authors found that those receiving steroids were admitted an average of 33 fewer hours and had reduced rate of blood transfusion [2].

retrospective review of over 5,000 hospitalizations for ACS at 32 different hospitals over a four year period was undertaken to try to better answer this question. This group found that pediatric patients admitted with ACS who received corticosteroids had longer LOS (8.0 days vs 5.2 days, p < 0.0001) and higher readmission rates (4.4% vs 1.9%) with an OR of 2.4 (95% CI 1.6-3.5) [1]. This study also found considerable variation in use of steroids among the 32 hospitals reviewed, anywhere from 10-86%. The patients who received steroids seemed to be a sicker cohort, as steroid use was associated with comorbid asthma, use of supplemental oxygen, use of inhaled nitric oxide, ICU admission, need for mechanical ventilation, and higher illness severity score. However, the increased LOS and readmission rate trends remained significant even when the authors attempted to control for these factors with propensity score modeling. Interestingly, in this study only 40% of SCD patients with concomitant asthma who were admitted for ACS were given steroids, though it is unclear from this retrospective review of ICD-9 coding whether or not these patients were having an acute exacerbation of asthma.

There is some concern that the variation in steroid use may be related to concerns of steroids causing other clinical complications in these patients. A retrospective case-control study from 2006, which included patients from St. Louis Children’s Hospital, found an association between sickle cell patients with hemorrhagic strokes and recent corticosteroid use [3]. Other studies have found associations of steroid use with higher rates of avascular necrosis and vaso-occlusive crises (presumably the cause of prolonged LOS and readmit rates seen in some studies) [1,4].

A recent review attempted to summarize the available evidence, but in its conclusions the authors noted: "It is clear that the role of corticosteroid therapy in SCD and its complications is anything but settled" [4]. They admit that wide variation in practice pattern as well as use of different agents, dosages, and routes of administration complicates any attempt at meta-analysis. The authors of both the large retrospective study and the review paper admit that patients with comorbid asthma are likely undertreated due to concerns over adverse effects of steroids [1,4]. Though there is not enough evidence to make any definitive recommendation, the authors suggest following standard guidelines for asthma treatment in patients with comorbid asthma and ACS, with the provision that a low-end dose (max 60 mg/day) be utilized and a slow taper employed to avoid "rebound" vaso-occulsive crisis. 


- There does not appear to be strong evidence supporting the routine use of steroids in SCD patients presenting with ACS.

- If the patient has a concomitant condition for which steroids would usually be indicated, particularly acute asthma exacerbation, then their cautious use is likely warranted.

Further FOAMed reading:

1) "Acute Chest Syndrome" from UMEM Educational Pearls.
2) "Acute Chest Syndrome" on Peds EM Morsels. Excellent summary of diagnosis and management.
3) "Sickle Cell Disease, Answers" on EM Lyceum. Evidence-based review of several clinical issues regarding ED management of SCD patients.
4) "Sickle Cell: 10 Things Every EP Should Know About SCD" from EP Monthly. Addresses several common misconceptions about ED management of SCD.

[1] Sobota A, et al. Corticosteroids for acute chest syndrome in children with sickle cell disease: variation in use and association with length of stay and readmission. Am J Hematol 2010; 85:24.
[2] Bernini JC, et al. Beneficial effect of intravenous dexamethasone in children with mild to moderately severe acute chest syndrome complicating sickle cell disease. Blood 1998; 92:3082.
[3] Strouse JJ, et al. Primary hemorrhagic stroke in children with sickle cell disease is associated with recent transfusion and use of corticosteroids. Pediatrics. 2006 Nov;118(5):1916-24.
[4] Ogunlesi F, et al. Systemic Corticosteroids in Acute Chest Syndrome: Friend or Foe? Paediatr Respir Rev. 2013 Oct 31.

Submitted by Brendan Fitzpatrick, PGY-3
Edited by C. Sam Smith, PGY-3
Faculty review by Doug Char


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