Reperfusion Syndrome

Reperfusion syndrome is the systemic inflammatory, metabolic and haemodynamic response when blood flow is restored to a tissue that has been ischaemic. It is seen after release of an aortic cross-clamp, revascularisation of an ischaemic limb or organ, reperfusion of a transplanted liver or kidney, thrombolysis, thrombectomy and return of spontaneous circulation after cardiac arrest.

Epidemiology. Post-reperfusion syndrome after liver graft reperfusion affects about 25 to 30% of recipients. Its frequency depends on the duration and extent of ischaemia.

Definition in transplantation. A fall in mean arterial pressure of over 30% from baseline for at least 1 minute within the first 5 minutes of reperfusion.

Pathophysiology. During ischaemia, adenosine triphosphate falls, anaerobic metabolism raises lactate, and sodium and calcium accumulate. On reperfusion, a burst of reactive oxygen species, calcium overload and mitochondrial permeability pore opening cause cell injury. Cold, acidic and hyperkalaemic effluent enters the circulation, causing vasodilation, myocardial depression, bradycardia and arrhythmia. Inflammatory mediators activate neutrophils and endothelium, and may cause distant organ injury (lung, kidney, gut) and coagulopathy.

Presentation is abrupt hypotension, bradycardia or asystole, arrhythmia, raised pulmonary artery pressure, hyperkalaemia, acidosis, hypothermia, coagulopathy and, later, multiorgan dysfunction. Limb reperfusion produces swelling, pain and compartment syndrome.

Red flags.

• Hypotension with bradycardia or asystole immediately after unclamping.
• Potassium over 6.0 mmol/L or severe acidosis (pH under 7.2).
• Rapid onset of pulmonary hypertension or right heart failure.

Diagnosis is clinical, with continuous arterial pressure, ECG and frequent arterial gas (potassium, lactate, pH, ionised calcium, glucose). In major vascular or transplant surgery, use echocardiography and viscoelastic testing as available.

Differential diagnosis. Haemorrhage, anaphylaxis, air or thrombotic embolism, myocardial infarction and sepsis.

Prevention. Warm the patient and fluids. Pre-load with volume. Wash out preservation solution from grafts where applicable. Correct potassium, acidosis and calcium before reperfusion. Reperfuse slowly in a staged fashion if possible. Warn the surgical team before unclamping.

Treatment of haemodynamic collapse.

• Calcium chloride 10% 5 to 10 mL IV (or calcium gluconate 10% 10 to 20 mL), repeated for hypocalcaemia.
• Vasopressor: phenylephrine 50 to 200 microgram IV, noradrenaline 0.05 to 0.5 microgram/kg/min, or vasopressin 0.01 to 0.04 units/min. Adrenaline 10 to 50 microgram IV boluses for bradycardia or low output.
• Atropine 0.5 to 1 mg IV for bradycardia.
• Sodium bicarbonate 50 mmol IV only for pH under 7.1 or severe hyperkalaemia.
• Hyperkalaemia: calcium, insulin 10 units IV with glucose 25 g, and salbutamol 10 to 20 mg nebulised. Dialysis for refractory cases.

Right heart failure and pulmonary hypertension. Inhaled nitric oxide 20 ppm, inhaled epoprostenol, milrinone 0.25 to 0.75 microgram/kg/min, avoiding hypoxia and acidosis.

Limb or organ reperfusion. Early fasciotomy and fluid for rhabdomyolysis.

Coagulopathy. Replace fibrinogen, platelets and plasma directed by viscoelastic tests, and give tranexamic acid 1 g IV when hyperfibrinolysis is shown.

Monitoring. Arterial pressure, central venous pressure, potassium, lactate, ionised calcium, temperature, coagulation, urine output and creatine kinase.

Referral and escalation. Intensive care and the responsible surgical or transplant team.

Special groups. In renal impairment, anticipate higher potassium. In cardiac disease, avoid large volume loads.