Acute chest syndrome

01OverviewDefinition, clinical context and the essential points that orientate the chapter.

The syndrome is defined clinically and radiographically, not by one cause. Sickled cells obstruct pulmonary microvasculature, infection increases inflammation, marrow necrosis releases fat and embolic material, and painful splinting causes dependent atelectasis. Each lowers oxygen, which drives further sickling and creates a dangerous feedback loop. Adults often develop multilobar severe disease and may have fewer overt infective features than children. A person's steady-state saturation and haemoglobin provide context, but new decline is actionable even if an absolute value looks only mildly abnormal.

Assessment begins at the bedside. Repeat respiratory rate, work of breathing, saturation, temperature and mental state; examine for consolidation, wheeze, pleural signs and fluid overload. Obtain full count, reticulocytes, renal and liver tests, haemolysis markers, group-and-save and cultures. Chest radiography is initial imaging, while CT pulmonary angiography addresses a credible embolic question rather than routinely defining ACS. Blood gas is useful in deterioration, but sampling must not delay oxygen or escalation.

Care combines respiratory support, reversal of triggers and haematological rescue. Use adequate analgesia without suppressing cough or ventilation and employ regular incentive spirometry during painful admissions. Give antibiotics because infection cannot be reliably separated at presentation. Fluids replace deficit cautiously. Transfusion decisions consider oxygen requirement, haemoglobin change, extent of infiltrate, trajectory and baseline viscosity. Deterioration should prompt exchange discussion before invasive ventilation becomes unavoidable; if ventilation is needed, lung-protective critical care and specialist transfusion continue together.

Key points

Acute chest syndrome is a new pulmonary infiltrate involving at least one lung segment with fever and/or respiratory symptoms in a person with sickle-cell disease.
Causes overlap: infection, pulmonary vaso-occlusion, bone-marrow fat embolism, atelectasis, hypoventilation and fluid overload may contribute within one episode.
It can be present on arrival or develop one to three days into a vaso-occlusive pain admission, especially with rib pain, sedation or reduced inspiration.
Cough, chest pain, fever, tachypnoea, wheeze, hypoxia or falling saturation from personal baseline should trigger chest imaging and repeated assessment.
A normal early radiograph does not exclude evolving disease; repeat imaging is appropriate when physiology worsens and may lag behind examination.
Give supplemental oxygen for hypoxaemia, use incentive spirometry or coached deep breathing, treat bronchospasm when present and avoid fluid overload.
Empirical antibiotics should cover typical and atypical respiratory pathogens according to local antimicrobial guidance after appropriate cultures when feasible.
Simple transfusion improves oxygen carriage in selected moderate disease, but avoid excessive haemoglobin and viscosity, especially when baseline haemoglobin is high.
Automated or manual red-cell exchange is considered for severe, rapidly progressive or poorly responsive disease and requires urgent specialist and transfusion coordination.
Venous thromboembolism, bacterial pneumonia, pulmonary oedema, opioid hypoventilation and asthma may mimic or coexist and need parallel evaluation.

02AetiologyUnderlying causes, associations and risk factors, with why each one matters.

Pulmonary infection

Viral, typical bacterial and atypical organisms can trigger endothelial inflammation and sickling; microbiological confirmation is often absent, so initial therapy cannot depend on a positive culture.

Marrow fat embolism

Bone-marrow infarction releases fat and cellular material into pulmonary vessels, often causing abrupt hypoxia, thrombocytopenia, neurological features and extensive bilateral change.

Atelectatic hypoventilation

Rib or spinal pain, opioid sedation and immobility reduce deep inspiration, producing dependent collapse that worsens regional hypoxia and promotes further sickling.

Pulmonary vaso-occlusion

Adhesive sickled cells and inflammation obstruct pulmonary microcirculation directly, causing ventilation-perfusion mismatch, tissue injury and progressive infiltrates.

03PathophysiologyThe causal sequence from the underlying abnormality to symptoms and harm.

1
Hypoxic amplification
Reduced alveolar or vascular oxygenation increases haemoglobin S polymerisation, which intensifies obstruction and creates a self-reinforcing decline in pulmonary gas exchange.
2
Inflammatory permeability
Activated neutrophils, platelets and endothelium increase microvascular injury and capillary leak, adding oedema and impaired diffusion to the obstructive process.
3
Viscosity constraint
Raising haemoglobin too high with simple transfusion can increase viscosity because circulating cells still include haemoglobin S-containing erythrocytes, limiting safe correction.

04Clinical features and red flagsSymptoms, examination findings, patterns of presentation and time-critical warnings.

Evolving admission syndrome

Fever, cough, chest pain or falling saturation appears after admission for bone pain, sometimes before a clear radiographic infiltrate.

Radiographic criterion

A new segmental infiltrate supports the syndrome when paired with fever or respiratory features and is not merely chronic scarring.

Severe trajectoryRed flag

Rapid oxygen escalation, multilobar change, falling platelets, acidosis or altered consciousness predicts dangerous progression and prompts exchange discussion.

Fat-embolism pattern

Abrupt hypoxia with neurological change, anaemia, thrombocytopenia and diffuse lung change after severe bone pain suggests marrow embolisation.

Asthma overlap

Wheeze and reversible airflow obstruction may worsen hypoxia and require bronchodilator treatment without explaining the new infiltrate alone.

05InvestigationsWhat to request, why it matters and how to interpret it.

Investigation order

Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.

01
Continuous pulse oximetry and observationsFirst step
Why
Detect change from baseline and respiratory deterioration.
Interpretation and limitations
Trend oxygen requirement, work of breathing and sedation; apparent saturation can be unreliable, so reconcile discordant severe symptoms with blood gas.
02
Chest radiograph
Why
Identify and follow a new pulmonary infiltrate.
Interpretation and limitations
Basal or multilobar opacities support ACS, but radiographic change can lag; repeat after clinical worsening rather than accepting an early normal image.
03
Full count, reticulocytes and haemolysis profile
Why
Measure anaemia, marrow response and severity features.
Interpretation and limitations
A haemoglobin fall supports sequestration or haemolysis; thrombocytopenia can accompany severe disease or fat embolism and affects procedures.
04
Group-and-save, antibody history and haemoglobin fraction
Why
Prepare compatible simple or exchange transfusion.
Interpretation and limitations
Historical antibodies and extended phenotype or genotype guide selection; do not delay urgent transfusion-service contact while awaiting every result.
05
Blood cultures and respiratory microbiology
Why
Identify a treatable infective trigger.
Interpretation and limitations
Collect before antibiotics when this causes no delay; negative cultures do not exclude infection or permit stopping sickle-directed care.
06
Arterial or venous blood gas
Why
Assess oxygenation, ventilation and acidosis during deterioration.
Interpretation and limitations
Rising carbon dioxide, acidosis or severe oxygen deficit signals exhaustion and critical-care need; compare with oxygen delivery at sampling.
07
CT pulmonary angiography
Why
Investigate pulmonary embolism when clinical probability justifies it.
Interpretation and limitations
A negative study does not exclude ACS, and contrast or transport risk is weighed against the embolic question.

06Differential diagnosisRealistic alternatives and the features that help distinguish them.

Bacterial pneumonia

Lobar infection can be indistinguishable and may trigger ACS; microbiology and response inform later refinement, but initial antibiotics and sickle management often proceed together.

Pulmonary embolism

Pleuritic pain, hypoxia and tachycardia overlap; disproportionate symptoms, thrombosis signs and standard clinical probability guide CT pulmonary angiography.

Pulmonary oedema

Fluid overload or cardiac dysfunction produces crackles, congestion and hypoxia and can coexist after overhydration, altering fluid and ventilatory management.

Opioid hypoventilation

Sedation, reduced respiratory rate and hypercapnia after analgesia may precede radiographic change, while hypoventilation itself can precipitate acute chest syndrome.

07ManagementImmediate care, first-line treatment, alternatives and escalation.

01RecognitionAct before the infiltrate expandsFirst stepA sickle-cell patient develops fever, cough, chest pain, tachypnoea or falling saturation.

1Repeat ABCDE assessment, compare oxygenation with baseline, obtain chest radiography and blood tests and contact haematology early.
2Give oxygen for hypoxaemia, start protocol antibiotics, maintain effective ventilation-preserving analgesia and use incentive spirometry or coached deep breaths.
3Review fluid balance, bronchospasm, thrombosis and opioid sedation and repeat imaging if clinical decline outpaces the first radiograph.

02Transfusion decisionImprove oxygen carriage without hyperviscosityHypoxia, haemoglobin fall, extensive infiltrate or worsening physiology persists despite initial care.

1Retrieve the full antibody history and baseline haemoglobin and involve transfusion medicine before selecting ABO-compatible, HbS-negative red cells matched for Rh and K and negative for every current or historical alloantigen.
2Use simple top-up transfusion only after reviewing steady-state and current haemoglobin, genotype, regular-transfusion status, HbS burden and viscosity risk. In a non-regularly transfused patient with sickle-cell anaemia and baseline haemoglobin below 90 g/L, BSH advises that post-transfusion haemoglobin should not exceed 100 g/L or rise more than about 10–20 g/L above baseline, particularly when HbS remains above 30%; do not transfuse a high-baseline patient above baseline without specialist direction.
3Arrange urgent red-cell exchange for severe or rapidly progressive disease, inadequate response to simple transfusion or a baseline haemoglobin that makes top-up unsafe. Under specialist direction, an exchange endpoint commonly combines HbS below 30% with a final haemoglobin around 100–110 g/L; the fall in HbS is what permits this endpoint without the same simple-transfusion hyperviscosity risk.

03Critical deteriorationSupport lungs while removing sickling cellsOxygen requirement, acidosis, exhaustion, neurological status or organ function worsens.

1Move to critical care, use blood gas and repeated bedside assessment to select high-flow, non-invasive or invasive support and treat shock or sepsis.
2Coordinate exchange transfusion in parallel with respiratory support, securing appropriate access without allowing a procedure plan to delay oxygenation.
3After recovery review hydroxycarbamide, asthma, sleep-disordered breathing and recurrent-event prevention and update the emergency care plan.

Key medicines and prescribing safety3 treatments · regimens, roles and cautions

Treats respiratory infection that may cause or coexist with acute chest syndrome before microbiology can reliably distinguish mechanisms.

Empirical antibacterial therapy

Start the acute-chest protocol promptly. One common adult community-onset regimen is ceftriaxone 2 g intravenously every 24 hours plus clarithromycin 500 mg orally or intravenously every 12 hours; adapt for acquisition setting, allergy, renal or hepatic function and local resistance.

Obtain cultures without delaying therapy; check severe beta-lactam allergy, macrolide QT prolongation and interactions, broaden for healthcare-associated or resistant infection when indicated, then narrow by results and trajectory.

Relieves a bronchospastic component and improves ventilation but does not treat vaso-occlusion or consolidation itself.

Salbutamol

Give inhaled salbutamol by spacer or oxygen-driven nebuliser at acute-asthma doses when wheeze or reversible bronchospasm is present, repeating according to response.

Tachycardia, tremor, hypokalaemia and lactate rise can confuse deterioration; do not prescribe routinely when no bronchospasm is present.

Raises oxygen carriage and, with exchange, lowers the proportion of sickling erythrocytes during significant ACS.

Antigen-matched red cells

Simple top-up: calculate volume from baseline and current haemoglobin. In a non-regularly transfused patient with sickle-cell anaemia whose baseline haemoglobin is below 90 g/L, do not exceed 100 g/L or raise haemoglobin more than about 10–20 g/L above baseline, particularly when HbS remains above 30%. Red-cell exchange: for severe or rapidly progressive ACS, specialists commonly target HbS below 30% and final haemoglobin around 100–110 g/L, individualized to physiology and viscosity risk.

Use HbS-negative, Rh- and K-matched units that are negative for every current or historical alloantibody. Confirm the full antibody history before selection. Baseline haemoglobin, HbS fraction, hyperviscosity, volume overload, delayed haemolytic transfusion reaction, hyperhaemolysis and iron burden require haematology and transfusion-medicine oversight.

08ComplicationsImportant consequences, why they occur and why they matter clinically.

Respiratory failure

Expanding infiltrates and ventilation-perfusion mismatch can progress to severe hypoxaemia, hypercapnia, exhaustion and need for non-invasive or invasive ventilatory support.

Neurological injury

Severe hypoxia, fat embolism or concurrent cerebral vaso-occlusion can cause confusion, seizure or focal deficit requiring immediate neurovascular assessment.

Multiorgan failure

Systemic inflammation and sickling may produce acute kidney injury, hepatic dysfunction, thrombocytopenia and shock during severe pulmonary disease.

Recurrence and chronic disease

Repeated acute chest episodes increase future risk and may contribute to chronic lung impairment, prompting review of hydroxycarbamide or transfusion prevention.

09Monitoring and follow-upTreatment response, safety checks and longer-term review.

Track oxygen saturation continuously in significant disease and record oxygen delivery, respiratory rate, work, mental state and pain repeatedly.
Repeat chest examination and imaging when the trajectory changes, recognising that radiographic extent may increase after presentation.
Trend haemoglobin, platelets, reticulocytes, bilirubin, renal and liver function and blood gas in moderate or severe episodes.
Monitor sedation and ventilation during opioids, ensuring analgesia remains adequate for deep breathing and coughing.
After simple or exchange transfusion check clinical response, haemoglobin, haemoglobin S fraction when indicated and delayed haemolysis symptoms.
Review fluids, urine output, weight and crackles to avoid both untreated deficit and iatrogenic pulmonary congestion.

10Special situationsVariants, exceptions and circumstances that change the usual approach.

Imaging can lag

Clinical hypoxia and tachypnoea may precede the infiltrate, so a deteriorating patient needs repeat assessment despite an initially clear film.

Mechanisms coexist

Calling an opacity infection does not remove vaso-occlusion, and calling it sickling does not justify withholding antibiotics.

Analgesia protects lungs

Insufficient pain relief worsens splinting, while excessive sedation suppresses ventilation; careful titration prevents both routes to atelectasis.

Exchange is trajectory based

Severity, oxygen need, progression and baseline haemoglobin matter more than waiting for one universal laboratory threshold.

11Common pitfallsFrequent interpretation and management errors.

01
Trusting one early normal chest radiograph.
02
Using fluids as unrestricted routine therapy.
03
Withholding antibiotics because vaso-occlusion seems likely.
04
Simple-transfusing to an unsafe high haemoglobin.
05
Waiting for intubation before arranging exchange.
06
Ignoring opioid hypoventilation during chest deterioration.