Acute chest syndrome

Acute chest syndrome (ACS) is a potentially fatal complication of sickle cell anemia caused by vaso-occlusion of the pulmonary vasculature. Symptoms may include chest pain, shortness of breath, and fever. Diagnosis is based on clinical symptoms and chest imaging findings of new pulmonary infiltrate. Management consists of antibiotics, supportive care with IV fluids and oxygen, and possibly a blood transfusion.

See also sickle cell anemia.

• Vaso-occlusion of the pulmonary vasculature
• Triggers include infection, asthma, surgery/general anesthesia
• Common cause of death in patients with sickle cell anemia ^[1]

• Chest pain
• Fever
• Respiratory distress, cough, shortness of breath, wheezing
• Signs of vaso-occlusive crisis (e.g., pain in arms or legs)
• Rib or sternal pain
• See also “Complications” below.

ACS is a clinical diagnosis supported by characteristic clinical features and the presence of new pulmonary infiltrate on imaging. ^[1]

Laboratory studies

• Routine
  • CBC: anemia, leukocytosis, thrombocytopenia ^[5]
  • Reticulocyte count: low
  • Type and screen and crossmatch
  • BMP and LFTs: signs of multiorgan failure may be present
    • Elevated creatinine
    • Elevated AST and ALT
  • Sputum and blood cultures ^[6]
  • Arterial blood gas: Gold standard for determining partial pressure of oxygen and carbon dioxide ^[7]
• Additional
  • Consider PCR for viral panel and serologies for respiratory pathogens (e.g., Mycoplasma, Legionella): See pneumonia diagnostics.
  • Consider troponin to assess for myocardial injury.

Imaging

• Chest x-ray
  • Indication: all patients suspected of having ACS
  • Supportive findings:
    • New pulmonary infiltrate
    • Segmental, lobar, or multilobular consolidation with or without the presence of pleural effusion
    • If CXR is normal, it should be repeated in 24–48 hours if there is ongoing clinical suspicion for ACS. ^[6]
• CT pulmonary angiography: if there is a concern for pulmonary embolism (PE) ^[8]

Other

• ECG: Assess for acute myocardial injury (see diagnosis of myocardial infarction).
• Bronchoscopy with bronchoalveolar lavage: performed in refractory cases and/or in atypical presentations for assessment of viral or bacterial causes

Management consists of supportive care, antibiotics, evaluation for blood transfusion, and hospital admission with close monitoring and hematology consult. Critically ill or rapidly progressing patients should also receive respiratory and hemodynamic support, evaluation for urgent exchange transfusion, and be admitted to the ICU. ^[1][4][9]

Supportive care

• Respiratory support
  • Supplemental oxygen: target SpO₂ > 95%
  • Identify patients at risk of progression to respiratory failure. ^[1]
    • PaO₂ ≤ 60 mm Hg
    • Opioid-induced respiratory depression
    • Features of impending severe ACS (see “Monitoring”)
  • Initiate NIPPV or invasive mechanical ventilation as needed (see mechanical ventilation and management of ARDS). ^[1]
• Additional supportive care
  • Pain management: opioids administered as scheduled doses or continuous infusion via patient-controlled analgesia
  • IV fluids: Avoid overhydration, which can lead to pulmonary edema. ^[7]
    • For patients with hypovolemia: cautious use of normal saline bolus ^[10]
    • The choice of fluids depends on hydration status.
      • Isotonic fluids are recommended for urgent volume correction.
      • Hypotonic fluids are recommended otherwise, i.e., 5% dextrose in either water, 0.45% normal saline, or 0.22% normal saline.
    • Recommended rate: no greater than 1.5 times the maintenance fluid requirement
  • Bronchodilators (e.g., albuterol ): especially in patients with a history of asthma or evidence of acute bronchospasm
  • Incentive spirometry to prevent atelectasis
  • VTE prophylaxis
  • Treatment of associated complications: See “Complications.”

Avoid overhydration in patients with acute chest syndrome because of the risk of pulmonary edema.

Antibiotic therapy ^[7]

• Obtain blood cultures (two sets) and sputum cultures before starting antibiotics.
• Start empiric antibiotics (see empiric antibiotic therapy for community-acquired pneumonia).
  • Suggested regimen
    • A third-generation cephalosporin (e.g., ceftriaxone )
    • PLUS a macrolide (e.g., azithromycin )
  • Alternative: fluoroquinolone (e.g., levofloxacin )

Blood transfusion

• Simple blood transfusion ^[4]
  • pRBCs indicated if hemoglobin concentration is > 1.0 g/dL below baseline
  • May not be indicated if the patient’s baseline hemoglobin is ≥ 9 g/dL
  • For HbSC or HbS/β-thalassemia, consult hematology.
• Urgent exchange transfusion ^[4]
  • Indications
    • Oxygen saturation < 90% even with supplemental oxygen
    • Worsening respiratory distress
    • Worsening pulmonary infiltrates
    • Hemoglobin concentration continuing to decline after a simple transfusion
  • Consult an apheresis specialist, if applicable.
  • Consider central venous access. ^[11]

• Acute ^[1][3][7]
  • Neurological: altered mental status, seizure, stroke, intracranial hemorrhage ^[1][3]
  • Pulmonary: PE, pulmonary hemorrhage, cor pulmonale
  • Splenic sequestration causing hypovolemic shock
  • Multisystem organ failure
• Chronic ^[1][3][7]
  • Chronic sickle lung disease
  • Pulmonary fibrosis
  • Premature mortality

We list the most important complications. The selection is not exhaustive.

• Pain management
• IV fluids: avoid overhydration
• Blood cultures (2 sets) and sputum cultures
• Start empiric antibiotics (see empiric antibiotic therapy for community-acquired pneumonia).
• Supplemental oxygen
• Rule out alternative causes (e.g., myocardial infarction, PE).
• Hematology consultation
• Evaluate the need for transfusion and obtain type and screen.
• Bronchodilators in patients with a history of asthma or evidence of acute bronchospasm ^[1]
• Incentive spirometry
• Hospital admission
• Transfer to ICU if the patient is at risk of progression to respiratory failure, intubated, and/or requires an exchange transfusion.

1. Howard J, Hart N, Roberts-Harewood M, et al. Guideline on the management of acute chest syndrome in sickle cell disease. Br J Haematol. 2015; 169 (4): p.492-505. doi: 10.1111/bjh.13348 . | Open in Read by QxMD
2. Ballas SK, Lieff S, Benjamin LJ, et al. Definitions of the phenotypic manifestations of sickle cell disease. Am J Hematol. 2009 : p.NA-NA. doi: 10.1002/ajh.21550 . | Open in Read by QxMD
3. Vichinsky EP, Neumayr LD, Earles AN, et al. Causes and Outcomes of the Acute Chest Syndrome in Sickle Cell Disease. N Engl J Med. 2000; 342 (25): p.1855-1865. doi: 10.1056/nejm200006223422502 . | Open in Read by QxMD
4. Evidence-Based Management of Sickle Cell Disease: Expert Panel Report, 2014. https://www.nhlbi.nih.gov/sites/default/files/media/docs/sickle-cell-disease-report%20020816_0.pdf. Updated: September 1, 2014. Accessed: November 27, 2019.
5. Chaturvedi S, Ghafuri DL, Glassberg J, Kassim AA, Rodeghier M, DeBaun MR. Rapidly progressive acute chest syndrome in individuals with sickle cell anemia: a distinct acute chest syndrome phenotype. Am J Hematol. 2016; 91 (12): p.1185-1190. doi: 10.1002/ajh.24539 . | Open in Read by QxMD
6. Al-Salem A. The Acute Chest Syndrome in Sickle Cell Anemia. Springer ; 2015
7. The management of sickle cell disease. https://www.nhlbi.nih.gov/files/docs/guidelines/sc_mngt.pdf. Updated: January 1, 2002. Accessed: February 26, 2020.
8. Dessap AM, Deux J-F, Abidi N, et al. Pulmonary Artery Thrombosis during Acute Chest Syndrome in Sickle Cell Disease. Am J Respir Crit Care Med. 2011; 184 (9): p.1022-1029. doi: 10.1164/rccm.201105-0783oc . | Open in Read by QxMD
9. Yawn et al. Management of sickle cell disease: summary of the 2014 evidence-based report by expert panel members.. JAMA. 2014; 312 (10): p.1033-48. doi: 10.1001/jama.2014.10517 . | Open in Read by QxMD
10. Okomo U, Meremikwu MM. Fluid replacement therapy for acute episodes of pain in people with sickle cell disease. Cochrane Database of Systematic Reviews. 2017 . doi: 10.1002/14651858.cd005406.pub5 . | Open in Read by QxMD
11. Otrock ZK, Thibodeaux SR, Jackups R. Vascular access for red blood cell exchange. Transfusion. 2018; 58 (S1): p.569-579. doi: 10.1111/trf.14495 . | Open in Read by QxMD