---
id: "haematology-acute-chest-syndrome"
title: "Acute Chest Syndrome"
type: "condition"
specialties: ["Haematology", "Respiratory Medicine", "Emergency Medicine"]
subspecialties: ["Sickle Cell Disease", "Critical Care"]
synonyms: ["ACS", "Sickle Chest Crisis"]
icd10: ["D57.0"]
snomed: ["111293003"]
last_updated: "2025-12-22"
evidence_level: "High"
emergency_status: true
red_flags:
  - "SpO2 < 90% despite oxygen"
  - "Rapidly progressive infiltrates"
  - "Multilobar disease"
  - "Need for exchange transfusion"
audience:
  - clinician
  - student
  - layperson
---

# Acute Chest Syndrome

## 1. Clinical Overview

### Summary
Acute chest syndrome (ACS) is the leading cause of death in sickle cell disease. Defined as new pulmonary infiltrate + respiratory symptoms/fever. Treat with oxygen, transfusion, antibiotics, pain control, and incentive spirometry. Exchange transfusion is life-saving for severe cases.

### Key Facts
- **Definition**: New pulmonary infiltrate + respiratory symptoms in SCD
- **Leading cause of death** in sickle cell disease
- **Incidence**: 10-30% of SCD patients
- **Key treatment**: Exchange transfusion for severe cases

### 1.1. Critical Alerts
- **Acute chest syndrome (ACS)** is the leading cause of death in sickle cell disease
- **Rapid progression** can occur within hours - early recognition is critical
- **New pulmonary infiltrate + any respiratory symptom** in SCD = ACS until proven otherwise
- **Exchange transfusion** is life-saving for severe cases
- **Incentive spirometry** is both preventive and therapeutic

### 1.2. Key Diagnostics
- Chest X-ray (new infiltrate required for diagnosis)
- CBC with reticulocyte count
- Type and crossmatch (phenotypically matched blood)
- ABG/VBG (hypoxemia assessment)
- Blood cultures
- Respiratory pathogen panel if available

### 1.3. Emergency Treatments
- **Oxygen**: Target SpO2 >95%
- **Pain control**: IV opioids (morphine, hydromorphone)
- **Simple transfusion**: Hb <7 g/dL or drop >1g from baseline
- **Exchange transfusion**: Severe ACS, rapidly progressive, SpO2 <90% despite O2
- **Antibiotics**: Ceftriaxone + azithromycin (cover atypicals)
- **Incentive spirometry**: Every 2 hours while awake

---

## 2. Epidemiology

Acute chest syndrome (ACS) is a potentially life-threatening complication of sickle cell disease (SCD) characterized by a new pulmonary infiltrate on imaging involving at least one complete lung segment, accompanied by respiratory symptoms and/or fever.

### 3.1. Diagnostic Criteria

**National Acute Chest Syndrome Study Group Definition**:
- New radiodensity involving at least one complete lung segment AND
- One or more of the following:
  - Fever (>38.5°C)
  - Chest pain
  - Respiratory symptoms (cough, dyspnea, tachypnea, hypoxia)

### Epidemiology
- **Incidence**: 10-30% of SCD patients will have at least one episode
- **Mortality**: 1-3% in adults (higher than children)
- **Peak incidence**: 2-4 years in children; young adults in HbSS
- **Seasonality**: More common in winter (respiratory infections)
- **Recurrence**: Half of patients will have recurrent episodes

### Risk Factors

| Factor | Mechanism |
|--------|-----------|
| HbSS genotype | Most severe form of SCD |
| Higher steady-state Hb | More cells to sickle |
| Lower HbF | Less protective fetal hemoglobin |
| History of ACS | Predicts future episodes |
| Severe VOC | Often precedes ACS |
| General anesthesia/surgery | Hypoxia, dehydration triggers |
| Asthma | Increased severity of ACS |

---

## 3. Pathophysiology

### Mechanisms of ACS

**Multiple Contributing Etiologies**

| Mechanism | Contribution | Features |
|-----------|--------------|----------|
| **Infection** | 30% | Viral, atypical bacteria, bacteria |
| **Fat embolism** | 10-20% | From bone marrow necrosis during VOC |
| **In situ sickling** | Most common in adults | Pulmonary vascular obstruction |
| **Hypoventilation** | Secondary | From chest wall pain (rib infarcts) |
| **Pulmonary infarction** | Common | Vaso-occlusion of pulmonary vessels |

### Pathophysiological Cascade

Trigger (infection, VOC, fat embolism, hypoventilation) ↓ Sickling in pulmonary vasculature ↓ Vaso-occlusion and inflammation ↓ Ventilation-perfusion mismatch ↓ Hypoxemia ↓ More sickling (vicious cycle) ↓ Progressive respiratory failure ↓ Multi-organ failure if untreated

### Fat Embolism Syndrome

- Bone marrow necrosis during VOC releases fat emboli
- Fat emboli travel to pulmonary circulation
- Fatty acids cause direct lung injury
- Phospholipase A activation → inflammation
- Often follows severe VOC by 1-3 days
- More common cause in adults than children

### Infectious Etiology

**Common Pathogens in ACS**

| Type | Organisms |
|------|-----------|
| Viral | RSV, influenza, parainfluenza, rhinovirus |
| Atypical bacteria | *Chlamydia pneumoniae*, *Mycoplasma pneumoniae* |
| Bacteria | *S. pneumoniae*, *H. influenzae* |

---

## 4. Clinical Presentation

### Symptoms

| Symptom | Frequency | Notes |
|---------|-----------|-------|
| Chest pain | 75-90% | May be pleuritic or vaso-occlusive |
| Fever | 60-80% | Suggests infection |
| Cough | 50-60% | Productive or non-productive |
| Dyspnea | 50-60% | Key warning sign |
| Tachypnea | 30-50% | May precede hypoxemia |
| Arm/leg pain | Common | Often concurrent VOC |

### Physical Examination

**Vital Signs**
- Fever (may be absent in severe cases)
- Tachycardia
- Tachypnea
- Hypoxemia (SpO2 often <95%)

**Pulmonary Examination**
| Finding | Significance |
|---------|--------------|
| Decreased breath sounds | Consolidation, effusion |
| Crackles/rales | Infiltrate |
| Wheeze | Asthma component, bronchospasm |
| Dullness to percussion | Effusion, consolidation |

**General SCD Examination**
- Pallor (anemia)
- Jaundice (hemolysis)
- Tenderness over bones (VOC sites)

### Clinical Course

**Typical Progression**
- Often develops 1-3 days into hospitalization for VOC
- May present de novo without prior VOC
- Can progress rapidly over hours
- Bilateral infiltrates associated with worse outcomes

**Severity Classification**

| Severity | Features |
|----------|----------|
| Mild | Fever and cough, single lobe infiltrate, SpO2 >5% |
| Moderate | Multilobar infiltrates, SpO2 90-94% on room air |
| Severe | Bilateral infiltrates, SpO2 <90%, progression on O2, mechanical ventilation |

---

## 5. Clinical Examination

(Integrated into Clinical Presentation above)

### Red Flags (Life-Threatening)

### Critical Warning Signs

| Red Flag | Concern | Action |
|----------|---------|--------|
| SpO2 <90% despite O2 | Severe respiratory failure | ICU, exchange transfusion |
| Rapidly progressing infiltrates | Impending respiratory failure | Exchange transfusion |
| Multilobar disease | Severe ACS | ICU admission |
| Altered mental status | Hypoxemia or stroke | Urgent assessment |
| Need for high-flow O2 or NIV | Severe disease | ICU, exchange transfusion |
| Chest pain + rib infarcts | Fat embolism risk | Close monitoring |
| Hb <5 g/dL | Profound anemia | Emergent transfusion |

### Progression to Respiratory Failure

**Warning Signs**:
- Increasing oxygen requirements
- Work of breathing increasing
- New bilateral infiltrates
- Rising lactate
- Declining mental status

---

## 6. Investigations

### Differential Diagnosis

| Condition | Key Features |
|-----------|--------------|
| Pneumonia (non-SCD) | Similar presentation; ACS is essentially pneumonia + sickling |
| Pulmonary embolism | Consider if D-dimer elevated, history of VTE |
| COVID-19 | Travel/exposure history, PCR positive |
| Acute pulmonary edema | Underlying cardiac disease, BNP elevated |
| Asthma exacerbation | Wheeze, prior asthma, clear CXR |
| Rib infarction alone | Normal CXR, focal bone pain |
| Splenic sequestration | Left-sided pain, dropping Hb, splenomegaly |

### ACS Mimics in SCD

| Condition | Distinguishing Features |
|-----------|------------------------|
| VOC with chest pain | No infiltrate on CXR |
| Fat embolism syndrome | Follows severe VOC, more thrombocytopenic |
| PE | CT-PA shows clot; may co-exist with ACS |
| Sickle hepatopathy | Liver tenderness, elevated LFTs |

---

## Diagnostic Approach

### Initial Assessment

**Priority Actions**
1. ABCs - assess oxygenation and work of breathing
2. Continuous SpO2 monitoring
3. Chest X-ray STAT
4. IV access and labs

### Imaging

**Chest X-ray**
- Required for diagnosis
- New pulmonary infiltrate (any location)
- Lower lobes most common
- May initially be normal - repeat in 24h if clinical suspicion

**CT Chest**
- Consider if PE suspected
- Better characterization of infiltrates
- Not required for diagnosis

### Laboratory Studies

| Test | Purpose | Findings in ACS |
|------|---------|-----------------|
| CBC | Anemia, infection | Hb often drops from baseline |
| Reticulocyte count | Bone marrow response | May be low (aplastic crisis) or high |
| Type and crossmatch | Transfusion preparation | Phenotypically matched if possible |
| ABG/VBG | Oxygenation, ventilation | Hypoxemia common |
| Blood cultures | Bacteremia | Obtain before antibiotics |
| Respiratory viral panel | Identify infection | Common triggers |
| Procalcitonin | Bacterial infection | May help guide antibiotics |
| LDH, bilirubin | Hemolysis | Often elevated |
| Secretory PLA2 | Research marker, may predict | Not routinely available |

### Hemoglobin Goals

- **Know patient's baseline Hb** - drop is significant
- Transfuse to raise Hb to 9-11 g/dL maximum
- **Avoid over-transfusion** - viscosity increases sickling

---

## 7. Management

### Oxygen Therapy

**Target SpO2 >95%**

Mild: Nasal cannula 1-4 L/min Moderate: Face mask 6-10 L/min Severe: Non-rebreather, HFNC, NIV Refractory: Intubation and mechanical ventilation

### Pain Management

**Critical Component of Treatment**

| Medication | Dose | Notes |
|------------|------|-------|
| Morphine | 0.1-0.15 mg/kg IV q3-4h | Standard opioid |
| Hydromorphone | 0.01-0.02 mg/kg IV q3-4h | Alternative to morphine |
| PCA | Patient-controlled | Consider for ongoing pain |
| Ketorolac | 15-30mg IV q6h | Avoid if renal impairment |
| Acetaminophen | 1g PO/IV q6h | Adjunct |

**Important**: Adequate pain control reduces splinting → improves ventilation → prevents progression

### Incentive Spirometry

**Critical Intervention**

Frequency: Every 2 hours while awake Technique: 10 sustained maximum inspirations per session Purpose: Prevents atelectasis, mobilizes secretions

This simple intervention prevents progression and is therapeutic!

### Transfusion Therapy

**Simple Transfusion**

| Indication | Target |
|------------|--------|
| Hb <7-8 g/dL | Increase to 9-10 g/dL |
| Drop > g/dL from baseline | Increase to near baseline |
| Mild-moderate ACS | May be sufficient |

**Exchange Transfusion**

| Indications | Method |
|-------------|--------|
| Severe/rapidly progressive ACS | Automated or manual |
| SpO2 <90% despite supplemental O2 | Target HbS <30% |
| Multilobar disease | Volume-neutral exchange |
| Impending respiratory failure | One blood volume exchange |
| Neurological symptoms | |

**Exchange Goals**:
- Reduce HbS to <30%
- Maintain Hb 9-10 g/dL
- Do not exceed Hb 10-11 g/dL (hyperviscosity)

### Antibiotics

**Empiric Coverage**

Ceftriaxone 2g IV daily + Azithromycin 500mg IV/PO daily (or doxycycline)

Duration: 7-10 days depending on severity Rationale: Covers typical bacteria and atypical (Chlamydia, Mycoplasma)

**Modify based on culture results**

### Bronchodilators

- Consider for patients with wheezing
- Albuterol nebulized q4-6h PRN
- Especially important if history of asthma

### VTE Prophylaxis

- Patients with SCD are hypercoagulable
- Enoxaparin or UFH (adjust for renal function)
- Mechanical prophylaxis if anticoagulation contraindicated

### Fluid Management

- Maintain euvolemia
- Avoid dehydration (sickling risk)
- Avoid overhydration (pulmonary edema risk)
- 1-1.5x maintenance fluids typically

---

## 8. Complications

### Disposition

### ICU Admission Criteria

- SpO2 <90% on supplemental oxygen
- Need for exchange transfusion
- Multilobar infiltrates
- Rapidly progressive disease
- Need for high-flow oxygen, NIV, or intubation
- Hemodynamic instability
- Altered mental status

### Ward Admission

- All patients with ACS require admission
- Mild single-lobe disease with stable oxygenation
- Close monitoring for progression (first 24-48h critical)

### Monitoring Requirements

- Continuous SpO2
- Serial chest X-rays (worsening infiltrates)
- Serial Hb (dropping suggests need for transfusion)
- Regular clinical assessment for deterioration

### Discharge Criteria

- Afebrile >24 hours
- Stable or improving oxygenation on room air
- Pain controlled with oral medications
- Able to use incentive spirometer independently
- Follow-up arranged with hematology

---

## 11. Patient/Layperson Explanation

### Understanding ACS

- Acute chest syndrome is a serious lung complication of sickle cell disease
- It requires hospital treatment with oxygen, transfusions, and antibiotics
- Early recognition and treatment improves outcomes

### Prevention

**Incentive Spirometry**
- Use regularly during any hospitalization
- Prevents lung complications
- 10 breaths every 1-2 hours

**General SCD Management**
- Stay hydrated
- Avoid extremes of temperature
- Vaccinations current (especially pneumococcal)
- Hydroxyurea adherence if prescribed
- Regular hematology follow-up

### Warning Signs After Discharge

Return immediately if:
- Fever >38°C (100.4°F)
- Chest pain
- Difficulty breathing
- Cough worsening
- New or worsening pain

---

## 9. Prognosis & Outcomes

### Special Populations

### Pediatric Patients

- ACS more commonly triggered by infection
- Often better outcomes than adults
- Same treatment principles apply
- Strong emphasis on vaccination

### Pregnancy

- ACS increases maternal and fetal risk
- Exchange transfusion safe in pregnancy
- Close obstetric monitoring
- Consider chronic transfusion program for high-risk

### Post-Operative Patients

- High risk for ACS after surgery
- Preoperative transfusion for major surgery
- Aggressive incentive spirometry post-op
- Optimize pain control to prevent splinting

### Asthma with SCD

- Higher risk for severe ACS
- More aggressive bronchodilator therapy
- Consider steroids if wheezing prominent
- May need inhaled corticosteroids chronically

---

## Quality Metrics

### Performance Indicators

| Metric | Target |
|--------|--------|
| CXR within 2 hours of presentation | >5% |
| Oxygen initiated if SpO2 <95% | 100% |
| Incentive spirometry prescribed | 100% |
| Antibiotics within 4 hours | >0% |
| Type and screen on admission | 100% |
| Hematology consultation | 100% |

### Documentation Requirements

- Baseline hemoglobin
- Transfusion history (alloantibodies)
- Oxygen requirements and SpO2 trends
- Pain management plan
- Incentive spirometry compliance
- Chest X-ray interpretation
- Response to treatment

---

## 10. Evidence & Guidelines

### Key Clinical Pearls

### Diagnostic Pearls

1. **ACS often develops during VOC admission** - watch closely
2. **Normal CXR doesn't exclude impending ACS** - repeat in 24h
3. **Fat embolism may not show infiltrate initially** - clinical suspicion matters
4. **Fever + chest symptoms in SCD = ACS** until proven otherwise
5. **Always compare Hb to patient's baseline** - a "normal" Hb may be low for them

### Treatment Pearls

1. **Incentive spirometry is therapeutic and preventive** - 10 breaths every 2 hours
2. **Exchange transfusion saves lives** in severe ACS - don't delay
3. **Cover atypical organisms** - Mycoplasma, Chlamydia common triggers
4. **Pain control is essential** - splinting leads to atelectasis → worsening
5. **Avoid over-transfusion** - target Hb 9-10, not higher (viscosity)

### Disposition Pearls

1. **All ACS requires admission** - can deteriorate rapidly
2. **ICU for any concerning features** - low threshold
3. **Watch closely first 24-48 hours** - peak of severity
4. **Ensure follow-up** with hematology
5. **Stress incentive spirometry** use on discharge

---

## 12. References

1. Vichinsky EP, et al. Causes and outcomes of the acute chest syndrome in sickle cell disease. National Acute Chest Syndrome Study Group. N Engl J Med. 2000;342(25):1855-1865.
2. Howard J, et al. British Society of Haematology guidelines for the management of acute chest syndrome in sickle cell disease. Br J Haematol. 2015;169(4):492-505.
3. Yawn BP, et al. Management of sickle cell disease: summary of the 2014 evidence-based report by expert panel members. JAMA. 2014;312(10):1033-1048.
4. DeBaun MR, Strunk RC. The intersection between asthma and acute chest syndrome in children with sickle-cell anaemia. Lancet. 2016;387(10037):2545-2553.
5. Miller ST, et al. Prediction of adverse outcomes in children with sickle cell disease. N Engl J Med. 2000;342(2):83-89.
6. Rees DC, et al. Sickle-cell disease. Lancet. 2010;376(9757):2018-2031.

---

## Version History

| Version | Date | Changes |
|---------|------|---------|
| 1.0 | 2025-01-15 | Initial comprehensive version with 14-section template |