Complications of Massive Transfusion

Rapid transfusion of large volumes of stored blood overwhelms normal physiology. The main metabolic complications are hypocalcaemia from citrate, hypothermia, hyperkalaemia, acidosis and dilutional coagulopathy. Together with hypothermia and acidosis, coagulopathy forms a lethal cycle that makes bleeding harder to stop. Prevention and early correction matter more than treating established abnormalities.

Citrate. Stored blood components contain citrate as anticoagulant, which binds calcium. A healthy liver clears citrate rapidly, but it accumulates with rapid infusion (more than about 1 unit every 5 minutes), liver failure, hypothermia and shock.

Potassium. Stored red cells leak potassium, and levels rise with the age of the unit, irradiation and the rate of infusion.

Risk context. Hypocalcaemia reduces myocardial contractility and clotting and is a strong predictor of death in massive transfusion.

Special groups. Neonates and small children (small blood volume, rapid potassium rise), patients with liver failure or renal failure, hypothermic patients, and those with pre-existing cardiac disease.

Hypocalcaemia and citrate toxicity.

• Signs: hypotension, narrow pulse pressure, poor response to vasopressors, prolonged QT, arrhythmia, tetany, seizures and ongoing oozing.

• Measure ionised calcium (not total calcium, which is unreliable in transfusion). Treat when ionised calcium is under about 1.1 mmol/L, and urgently when under 0.9 mmol/L.

Hyperkalaemia.

• Signs: peaked T waves, widened QRS, loss of P waves, bradycardia and arrest.

• Treat when potassium is over 5.5 mmol/L with ECG changes, or over 6.5 mmol/L.

Hypothermia.

• Core temperature under 36 degrees Celsius is abnormal, and under 34 degrees Celsius significantly impairs coagulation, platelet function and drug clearance.

Acidosis.

• pH under 7.2 with raised lactate and base deficit, from shock, with citrate adding to alkalosis later.

Dilutional and consumptive coagulopathy. Fibrinogen is the first factor to fall, followed by platelets and clotting factors. Hyperfibrinolysis can add to bleeding.

Other effects. Hypomagnesaemia, hyperglycaemia, late metabolic alkalosis (citrate converts to bicarbonate), transfusion related acute lung injury, transfusion associated circulatory overload and acute haemolysis from uncrossmatched blood.

Red flags. Arrhythmia, refractory hypotension, bleeding that does not respond to products, core temperature under 34 degrees Celsius.

Hypocalcaemia.

• Give calcium chloride 1 g (10 mL of 10%) intravenously over 5 to 10 minutes through a large or central vein, or calcium gluconate 3 g (30 mL of 10%) through a peripheral line. Repeat to keep ionised calcium at or over 1.1 mmol/L.

• Give calcium early in massive transfusion, for example after the first 4 units, and give through a separate line from blood.

• Give magnesium sulphate 2 g intravenously if magnesium is low or arrhythmia occurs.

Hyperkalaemia.

• Calcium chloride 1 g intravenously for ECG changes.

• Insulin 10 units of soluble insulin with 25 g of glucose (50 mL of 50% dextrose), and salbutamol 10 to 20 mg nebulised.

• Use fresher red cells or washed red cells in neonates and when possible in rapid transfusion in small children.

• Renal replacement therapy if refractory.

Hypothermia.

• Warm all products and fluids through a validated warmer, use forced air warming, warm the room, remove wet clothing and cover the patient.

• Avoid cold fluids, and monitor core temperature.

Acidosis.

• Restore perfusion, control bleeding and give balanced resuscitation. Sodium bicarbonate is not a routine treatment and is considered only with severe acidosis (pH under 7.1) and haemodynamic compromise.

Coagulopathy. Replace fibrinogen early, platelets and plasma as results direct, give tranexamic acid, and correct calcium and temperature.

Special groups.

• Neonates and small children: prefer fresh or washed red cells, warm all products, and monitor calcium and potassium closely.

• Liver failure: more calcium may be needed and clearance of citrate is slow.

• Renal failure: potassium accumulates, so monitor closely.

Monitoring. Ionised calcium, potassium, magnesium, blood gas and lactate every 30 to 60 minutes, continuous ECG, core temperature and urine output.

Complications. Cardiac arrest from hyperkalaemia or hypocalcaemia, refractory shock, coagulopathy, lung injury, multi organ failure and death.

Referral and escalation. Intensive care early, nephrology for refractory hyperkalaemia, and haematology for coagulopathy.

Disposition. After control, correct residual abnormalities, continue warming and monitor for rebound hyperkalaemia and metabolic alkalosis over the next 24 hours.