Transfusion-Associated Circulatory Overload

Transfusion associated circulatory overload is acute cardiogenic pulmonary edema from volume load during or within 12 hours of a transfusion. The circulation cannot handle the infused volume or rate, so hydrostatic pulmonary edema results. Incidence is about 1% of transfused patients and up to 5 to 10% in critically ill patients, and it is a leading cause of transfusion-related death along with transfusion-related lung injury. It is underrecognized.

Risk factors

• Age over 70 years and infancy
• Heart failure, valvular disease, renal failure and severe anemia (chronic anemia has an expanded plasma volume)
• Positive fluid balance and concurrent IV fluids
• Rapid transfusion (over 2 to 4 mL/kg/h), large volumes, and plasma products
• Low albumin and pulmonary disease, and perioperative and obstetric settings

Pathophysiology: acute volume expansion raises left atrial pressure, so fluid crosses into alveoli, and large volumes of plasma carry colloid that may also raise oncotic pressure with later shifts. Recovery is usually fast with treatment, but mortality is about 5 to 15% in severe cases. Complications: respiratory failure, arrhythmia, myocardial ischemia and death.

• Acute dyspnea, orthopnea, cough, tachypnea and hypoxemia during or up to 12 hours after the transfusion
• Tachycardia and hypertension (a distinguishing feature, compared with hypotension in lung injury)
• Raised jugular venous pressure, a third heart sound, bibasal crackles, peripheral edema and headache
• Fever is uncommon, and a small number have it
• Red flags: saturation under 90%, hypertension over 180/110 mmHg, arrhythmia, chest pain and elderly or cardiac patients

1. Clinical diagnosis: at least three of: acute respiratory distress, tachycardia, hypertension, acute or worsening pulmonary edema on imaging, and evidence of positive fluid balance, with onset within 12 hours.
2. Chest radiograph: bilateral infiltrates, vascular redistribution, enlarged cardiac silhouette and effusions.
3. Natriuretic peptide: a rise over 1.5 times the pre-transfusion value supports the diagnosis (BNP over 1200 pg/mL favors overload), with a falling level after diuresis.
4. Echocardiography: raised filling pressures, left atrial enlargement, and dysfunction.
5. Other tests: ECG, troponin, creatinine, blood gases, and review of fluid balance and rate of transfusion.
6. Response to diuretics supports overload (distinguishing from lung injury).

Differentials: transfusion-related acute lung injury, anaphylaxis, bacterial contamination, hemolytic reaction, acute coronary syndrome and cardiogenic pulmonary edema from other causes.

1. Stop the transfusion and keep IV access. Sit the patient upright with legs dependent.
2. Oxygen to saturation over 94%, and non-invasive ventilation (continuous positive airway pressure 5 to 10 cmH2O) or intubation for respiratory failure.
3. Diuretic: furosemide 40 mg IV (20 to 80 mg, 1 mg/kg in children, maximum 40 mg) given over 2 to 5 minutes, repeated after 30 to 60 minutes if urine output is under 100 mL in the first hour. Use higher doses in renal impairment. Monitor potassium and creatinine.
4. Vasodilator for hypertension: glyceryl trinitrate 0.4 mg sublingually every 5 minutes up to 3 doses, or 10 to 200 micrograms/min IV infusion.
5. Phlebotomy or renal replacement therapy (ultrafiltration) in refractory overload and in renal failure.
6. Avoid morphine for dyspnea unless the patient is distressed with severe symptoms (use 2.5 mg IV).
7. Resuming transfusion: only after stabilization and when the transfusion is still needed. Give each unit slowly, over 3 to 4 hours (up to a maximum of 4 hours per unit), with furosemide 20 to 40 mg IV before or during.
8. Prevention for at-risk patients:
   • Confirm the need for transfusion (restrictive thresholds: hemoglobin under 70 g/L, or under 80 g/L with cardiac disease).
   • Transfuse one unit at a time and reassess before the next.
   • Rate of 1 mL/kg/h in adults at risk (children 1 to 2 mL/kg/h, with a maximum of 5 mL/kg/h), and aliquots of red cells in small volumes (5 mL/kg) for infants.
   • Review and stop concurrent IV fluids, and monitor fluid balance, vital signs and oxygen saturation.
   • Use concentrated products (albumin, prothrombin complex concentrate, fibrinogen concentrate) in place of large volumes of plasma where possible.
9. Report the reaction to the blood service for hemovigilance.

Follow-up: review heart and renal function, and adjust chronic diuretics for patients on regular transfusion (such as those with thalassemia or myelodysplasia). Counsel the patient and the transfusion team on slower rates for future transfusions.