Acute chest syndrome is a life-threatening pulmonary complication of sickle cell disease (SCD), defined as a new infiltrate on chest imaging plus ≥2 of the following: pleuritic chest pain, hypoxemia, tachypnea, or fever. [1] It is the leading cause of death in SCD and the second most common reason for hospitalization. [2-3] Approximately 50% of patients with SCD will experience ACS in their lifetime, and up to 20% of adult patients progress to respiratory failure requiring mechanical ventilation. [3-4]
1. History
- Onset and context: Determine whether symptoms began acutely or evolved during a vaso-occlusive crisis (VOC) — ACS commonly develops within the first 3–4 days of a pain episode [1]
- Respiratory symptoms: Cough, dyspnea, chest pain (pleuritic), wheezing
- Fever: Present in most children; adults are often afebrile [2]
- Pain location: Chest, back, or abdominal pain — back pain and diffuse/multifocal pain are associated with higher ACS risk [5-6]
- Timing: Night-time onset of VOC pain is an independent risk factor for ACS progression [6]
- Recent triggers: URI symptoms prior to admission, recent surgery (especially abdominal), general anesthesia, dehydration [5][7]
- SCD genotype: HbSS and HbSβ⁰-thalassemia carry the highest risk [4]
- Important negatives: Absence of respiratory symptoms does not exclude ACS — initial CXR may be negative [7]
2. Alarm Features
- SpO₂ <90% despite supplemental oxygen → urgent exchange transfusion [2]
- Rapidly progressive respiratory distress with increasing O₂ requirements [2][8]
- Declining hemoglobin despite simple transfusion [2]
- Progressive or multilobar pulmonary infiltrates [2][9]
- Altered mental status — may signal multiorgan failure syndrome (MSOF) with concurrent neurologic, renal, or hepatic dysfunction [1]
- Bilateral pleural effusions and multilobar atelectasis/consolidation predict severity [9]
- Fever >38.5°C with reduced SpO₂ and leukocytosis are predictors of impending ACS [9]
3. Medications
- Empiric antibiotics (required):
- IV cephalosporinoral macrolideS. pneumoniaeMycoplasmaChlamydiaNIH + 1[2][8]
- Analgesics: Opioids for pain control — titrate to relieve pain without causing sedation/hypoventilation, which promotes atelectasis and worsens ACS [4][8]
- Bronchodilators: Inhaled β-agonists for bronchospasm [4]
- Hydroxyurea: Primary preventive therapy; reduces ACS incidence (RR 0.42 vs standard care) [10-11]
- Transfusion therapy: Simple transfusion (10 mL/kg pRBCs) when Hb drops >1 g/dL below baseline; exchange transfusion for severe/progressive cases [2]
- Contraindicated/caution:
- Dexamethasone — may improve inpatient outcomes but is associated with rebound pain and rehospitalization; no longer routinely recommended [10][12]
- Excessive IV fluids — avoid hyperhydration, which can worsen pulmonary edema; maintain euvolemia [12]
- Meperidine — avoid due to seizure risk in SCD patients
4. Diet
- Hydration: Maintain euvolemia with oral and IV fluids; avoid both dehydration (triggers sickling) and overhydration (worsens pulmonary edema) [12]
- Oral intake: Encourage as tolerated; no specific dietary restrictions during acute episode
- Long-term: Adequate folate supplementation; consider vitamin D assessment, though vitamin D deficiency has not been clearly linked to ACS risk specifically [13]
5. Review of Systems
- Pulmonary: Cough, dyspnea, pleuritic chest pain, wheezing, hemoptysis
- Constitutional: Fever, malaise, fatigue
- MSK: Bone pain (especially back/chest wall) — may represent concurrent VOC or rib infarction
- Neurologic: Headache, confusion, focal deficits (concern for concurrent stroke or MSOF)
- GI: Abdominal pain (may mimic or coexist with splenic sequestration, hepatic sequestration)
- GU: Dark urine (hemolysis), decreased urine output (renal involvement in MSOF)
6. Collateral History and Family History
- Baseline hemoglobin and HbS% — critical for transfusion decision-making [2]
- SCD genotype (HbSS, HbSC, HbSβ⁰, HbSβ⁺) — affects severity and transfusion approach [2]
- Prior ACS episodes — history of ACS is a strong predictor of recurrence [5]
- Asthma/reactive airway disease — significantly increases ACS incidence [5][7]
- Transfusion history: Alloantibody status, prior transfusion reactions
- Hydroxyurea adherence and current disease-modifying therapy
- Vaccination status: Pneumococcal, meningococcal, H. influenzae [1]
- Penicillin prophylaxis compliance (pediatric patients)
7. Risk Factors
- HbSS or HbSβ⁰-thalassemia genotype (highest risk) [4]
- Asthma or reactive airway disease [5][7]
- Prior ACS episodes [5]
- Active VOC — ~15.7% of VOC admissions progress to ACS [5]
- Recent surgery (especially abdominal) or general anesthesia [2][7]
- Higher baseline WBC count and leukocytosis [5][9]
- Asplenia (functional or surgical) [9]
- Low baseline hemoglobin [9]
- Elevated CRP and diffuse pain at ED presentation [6]
- Upper respiratory tract infection preceding admission [5]
- Younger age (peak incidence 2–4 years in children) [2]
- Inadequate incentive spirometry during VOC hospitalization [8]
8. Differential Diagnosis
- Pneumonia — ACS is clinically indistinguishable from pneumonia; treat empirically for both [1-2]
- Pulmonary embolism/thromboembolism — consider CT angiography if clinical suspicion is high [1]
- Asthma exacerbation — common comorbidity; radiographic features (peribronchial thickening, atelectasis) may differ from ACS consolidation [14]
- Pulmonary fat embolism — from bone marrow infarction during VOC; a major non-infectious cause [2][15]
- Splenic sequestration crisis — can present with abdominal pain and acute anemia
- Myocardial ischemia/infarction — obtain ECG and troponin in adults [16]
- Pulmonary hypertension with acute decompensation
- Rib/sternal infarction — chest wall pain without pulmonary infiltrate
- COVID-19 or other viral pneumonitis — test as clinically indicated [7]
9. Past Medical History
- Number and severity of prior ACS episodes — recurrence is common
- Frequency of VOC and hospitalizations
- Prior stroke or silent cerebral infarcts
- Chronic lung disease or baseline pulmonary function
- Transfusion history — alloimmunization status, delayed hemolytic transfusion reactions
- Splenectomy or functional asplenia
- Avascular necrosis, nephropathy, retinopathy — markers of disease severity
- Surgical history — especially recent procedures
10. Physical Exam
- Vitals: Fever, tachypnea, tachycardia, SpO₂ <95% (critical threshold) [2]
- Pulmonary: Rales, rhonchi, wheezing, decreased breath sounds, dullness to percussion (effusion), increased work of breathing, retractions [2][4]
- Cardiac: Murmur (flow murmur common in chronic anemia), gallop (volume overload)
- Abdomen: Splenomegaly (sequestration), hepatomegaly, tenderness
- Extremities: Signs of concurrent VOC (swelling, tenderness)
- Neurologic: Mental status changes, focal deficits (MSOF, concurrent stroke)
- Skin: Jaundice/icterus (hemolysis), pallor (acute anemia)
11. Lab Studies
- CBC with differential and reticulocyte count — hemoglobin often drops sharply below baseline; leukocytosis is common [2][16]
- Type and screen/crossmatch — anticipate transfusion need; check for alloantibodies
- Hemoglobin electrophoresis (HbS%) — guides exchange transfusion decisions (target HbS <30%) [8]
- Basic metabolic panel, LFTs, LDH, total bilirubin — assess for hemolysis and organ involvement [5]
- Blood cultures and sputum cultures [16]
- CRP — elevated CRP at presentation is an early risk factor for ACS [6]
- ABG — if significant hypoxemia or respiratory distress
- Troponin — recommended in adults to evaluate for myocardial injury [16]
- Procalcitonin — may help guide antibiotic therapy per recent guidelines [17]
12. Imaging
- Chest radiograph (AP and lateral) — first-line and diagnostic hallmark; look for new segmental/lobar opacity consistent with consolidation (not atelectasis) [2-3]
- Children: upper/middle lobe involvement more common [2]
- Adults: multilobar disease more common [2]
- CXR may be initially negative — repeat if clinical suspicion persists [7]
- Lung ultrasound — emerging modality with demonstrated promise for early detection; may identify consolidation and pleural effusion before CXR changes [4][17]
- CT chest — consider when diagnosis is uncertain, to evaluate for PE, or when CXR findings are equivocal [4][17]
- Echocardiography — consider in severe cases to assess for pulmonary hypertension and right heart strain [17]
13. Special Tests
- Incentive spirometry — both diagnostic (declining volumes) and therapeutic; 87% relative risk reduction of ACS when used during VOC hospitalization [8]
- Continuous pulse oximetry — essential for monitoring [2]
- Nasopharyngeal swab — viral panel (influenza, RSV, COVID-19)
- Secretory phospholipase A₂ (sPLA₂) — elevated levels precede ACS and may serve as a biomarker, though not widely used clinically [15]
- Oil-red O staining of bronchoalveolar lavage — diagnostic of pulmonary fat embolism (rarely performed acutely) [15]
14. ECG
- Indications: Obtain in all adults with SCD presenting with chest pain [16]
- Findings to assess:
- Sinus tachycardia (most common)
- Right heart strain pattern (RV hypertrophy, right axis deviation) — suggests pulmonary hypertension
- ST-segment changes — evaluate for concurrent myocardial ischemia
- Arrhythmias — may occur with severe hypoxemia or electrolyte derangements
- Troponin should accompany ECG in adults [16]
15. Assessment
ACS is a clinical-radiographic diagnosis: new pulmonary infiltrate + ≥2 of: pleuritic chest pain, hypoxemia, tachypnea, or fever in a patient with SCD. [1] The etiology is multifactorial — infection (most common in children), fat embolism, in situ sickling, and thromboembolism — and in many cases no specific cause is identified. [2] ACS can present de novo or evolve insidiously during a VOC admission. Severity ranges from mild, self-limited disease to fulminant respiratory failure and MSOF. Adults tend to present more severely with multilobar disease, while children more often have fever and single-lobe involvement. [2] Approximately 13% require mechanical ventilation and 3% die. [15]
16. Treatment Plan
Initial stabilization:
- Supplemental O₂ to maintain SpO₂ >95% (NHLBI) or >92% (some protocols) [2][8]
- IV fluids — isotonic, euvolemic maintenance; avoid overhydration [12]
- Incentive spirometry — 10 maximal inspirations every 2 hours while awake [2][8]
Antibiotics:
- IV cephalosporinoral macrolideNIH + 1[2][8]
Analgesia:
- Multimodal approach: IV opioids (morphine or hydromorphone) titrated to pain relief without oversedation, plus NSAIDs (ketorolac) if no contraindication [4]
- Intranasal fentanyl for rapid onset in ED [18]
Bronchodilators:
- American Journal of Emergency Medicine[4]
Transfusion:
- Simple transfusion (10 mL/kg pRBCs): when Hb drops >1 g/dL below baseline and patient is symptomatic; goal Hb ~10 g/dL [2][8]
- Exchange transfusion (erythrocytapheresis): Indicated for rapidly progressive ACS — SpO₂ <90% despite O₂, worsening respiratory distress, progressive infiltrates, or Hb decline despite simple transfusion; goal HbS <30% [2][8]
- Requires hematology, critical care, and/or apheresis consultation [2]
- Transfer to tertiary center if erythrocytapheresis is unavailable [8]
Prevention (long-term):
- Hydroxyurea — reduces ACS incidence by ~58% (RR 0.42) [10]
- Chronic transfusion therapy for recurrent moderate-to-severe ACS [12]
- Pneumococcal and influenza vaccination [1]
17. Disposition
- All patients with ACS require hospitalization (NHLBI consensus recommendation) [2]
- ICU admission criteria:
- SpO₂ <90% despite supplemental O₂
- Need for exchange transfusion
- Rapidly progressive respiratory failure
- Multilobar disease with worsening trajectory
- Signs of MSOF (neurologic, renal, hepatic decline) [1-2]
- Need for BiPAP or mechanical ventilation
- Nearly one-third of pediatric ACS cases require ICU or high-dependency care [5]
- Hematology consultation — for all ACS cases; urgent for transfusion decisions, especially in HbSC or HbSβ⁺-thalassemia [2]
- Transfer to a tertiary SCD center if exchange transfusion capability is unavailable [8]
18. Follow Up / Return Precautions
- Outpatient hematology follow-up within 1–2 weeks of discharge
- Pulmonary function testing after recovery — ACS causes long-term decline in lung function [19]
- Hydroxyurea initiation or optimization if not already on therapy, especially after a first or recurrent ACS episode [10-11]
- Return precautions — instruct patients/families to seek immediate care for:
- Fever ≥38.5°C (101.3°F)
- New or worsening chest pain, cough, or shortness of breath
- Increasing fatigue, pallor, or jaundice
- Altered mental status
- Expected course: Most patients improve within several days with aggressive treatment; however, recurrence is common and each episode may cause cumulative lung damage [2]
- Vaccination review at follow-up: ensure pneumococcal, meningococcal, influenza, and COVID-19 vaccines are up to date [1]
- Incentive spirometry education for home use during future VOC episodes [8]
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