Acute Chest Syndrome

Acute Chest Syndrome

An acute lung injury syndrome occurring frequently in patients with sickle cell disease (SCD) defined as:

  • A new pulmonary infiltrate on CXR consistent with alveolar consolidation but not atelectasis involving at least one complete lung segment

Usually accompanied by one or more new signs/symptoms including:

  • Fever to >38.5
  • Chest Pain
  • Hypoxemia relative to baseline
  • Tachypnea
  • Wheezing
  • Cough
  • Increased work of breathing



  • Second most common cause of hospitalization (12.8/100 patient-years) behind vaso-occlusive crisis (VOC)
  • Associated mortality has decreased in modern era of hydroxyurea therapy and early aggressive transfusion therapy
  • ACS-associated mortality is related to underlying pulmonary hypertension and acute cor pulmonale (13% of ACS cases feature cor pulmonale)
    • Pulmonary hypertension in ACS correlates with more severe levels of hemolysis, thrombocytopenia and hepatic dysfunction
      • Aggressive ICU exchange transfusions in these patients
  • 50% of pts are admitted for another reason (most for VOC), often developing signs of ACS on day 2-4 of hospital stay.  10-20% of hospitalized pts with SCD develop ACS.
    • In children ACS often presents as admitting diagnosis
    • ACS is typically preceded by severe limb and chest pain and fevers
  • Peak incidence in children age 2-4 years
  • 80% of pts with ACS have recurrent episodes
  • Presenting symptoms are age dependent
    • <10 years often with: wheezing, cough, fever
    • Adolescents/adults: pain in arms/legs and dyspnea



  • Causes identified in approx 40-50% of pts
    • Three primary mechanisms
      • 1. Pneumonia/systemic infection: Respiratory infection induces excessive inflammatory lung injury response in susceptible SCD pt as compared to  infection in non-SCD pt
        • Infectious agent found in 54% of ACS admission
          • Children<9 y/o: 35% infectious (11% viral, 9% mycoplasma, 9% Chlamydia, 4% typical bacterial)
          • Adolescents (10-19 y/o): 22% infectious (8% Chlamydia, 4% mycoplasma, 3% viral, 3% typical bacterial)
          • Adults >20 y/o: 26% infectious (9% Chlamydia, 7% typical bacterial, 5% mycoplasma, 1% viral)
      • 2. Fat embolism (identified in 16% of cases), more prevalent in adults
        • Generally involves multiple bones
          • Most often pelvis and femur
          • Results in infarction and edema of marrow compartment, with necrosis of marrow compartment and spillage of contents into bloodstream which are carried to and occlude the pulmonary vasculature
        • Suspect this etiology in pts with abrupt multi-organ failure, rapid onset of ARDS, acute increase in PA pressure,  transaminitis, extrathoracic pain, alterations in mental status, prominent thrombocytopenia or coagulopathy
        • More severe course with systemic complications
      • 3. Direct pulmonary infarction from HbS-containing erythrocytes (prevalence unknown)
        • Not as well characterized as etiologies 1-2


Risk Factors

  • Young age
  • Higher steady-state Hgb level
    • ACS events are preceded by fall in baseline Hgb of 0.78 g/dL on average along with rising LDH levels
    • Higher steady state Hgb levels promote VOC followed by acute hemolysis contributing to acute lung injury
  • Decreased HgbF concentrations
  • asthma in children
  • Active smoking or environmental smoke exposure
  • More severe episodes in HbSS than HbSC



  • CXR: At any sign of respiratory symptoms CXR should be obtained serially every 24-48 hours
  • CBC w/ diff, reticulocyte ct:
    • Low Hgb/drop from baseline may indicate acutely worsening tissue hypoxia
    • Acute drop in platelet count often precedes ACS event
      • Functional asplenia manifests in baseline thrombocytosis>400K
      • Drop to <200K is risk factor for multi-lobar ACS and mechanical ventilation
  • Obtain arterial blood gas if significant respiratory distress present
  • Type and cross-match for transfusion
  • Obtain blood cultures if febrile
  • LFTs and BUN/Cr to assess and monitor hepatic and renal function




  • Neurologic complications (22% of adult cases) most often associated with respiratory failure
    • In children can include reversible posterior leukoencephalopathy syndrome, cerebral infarcts, acute necrotizing encephalitis
  • Respiratory failure, especially in pts with a  h/o cardiac disease
  • Widespread hypoxemia can cause additional sickling and vaso-occlusionà multi-organ failure
  • Death



  • Pre-operative blood transfusion in surgical patients
  • Maintenance asthma and compliance to therapy for asthmatic children
  • Maintenance hydroxyurea therapy
  • Incentive spirometry during acute VOC hospitalizations


Acute Management

  • Fluid management
    • Hypovolemia can increase sickling
      • IV crystalloid followed by liberal PO hydration
  • Pain control
    • Increased pain and high dose morphine are both associated with ACS
      • Balance pain control and associated respiratory depression
  • Respiratory Support
    • O2 supplementation to maintain sats>92%
    • Incentive spirometry to prevent atelectasis
    • Bronchodilators may be helpful in asthmatics and those with RAD
  • Antibiotic treatment
    • Guided by regional resistance patterns and season
      • Coverage for atypical bacteria
      • Seasonal influenza
  • Transfusion
    • Transfusion acutely increases Hgb oxygen saturation
      • Has been demonstrated to prevent ACS during major surgery
      • Average increase in oxygen saturation from 86% to 93%
      • Simple and exchange transfusion result in similar improvements
        • Simple transfusion for pts with Hgb<10 g/dL
          • 2-4 units in first 24 hrs followed by maintenance to keep >10
        • Exchange transfusion for severe/rapidly progressing illness
  • Fever control
    • Acetaminophen
    • Beware of NSAIDs if renal involvement
  • Corticosteroids
    • Side effects of avascular necrosis, VOC, association with hemorrhagic stroke
    • Limited support for use
  • Nitrous oxide
    • No effect on duration of pain crisis, narcotic use, pain scores, development of ACS
    • Limited support for use



  1. Vichinsky E.P. et al. Causes and outcomes of acute chest syndrome in sickle cell disease. NEJM 2000
  2. Gladwin M.T. and Rodgers G.P. Pathogenesis and treatment of acute chest syndrome of sickle cell anaemia. Lancet 2000
  3. Neumayr L. et al. Mycoplasma disease and acute chest syndrome in sickle cell disease. Pediatrics 2003
  4. Crabtree E.A. et al. Improving care for children with sickle cell disease/acute chest syndrome. Pediatrics 2011
  5. McCavit T.L. Sickle Cell Disease. Peds in Review 2012