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Precipitation of protamine by cefazolin.

In our institution, cefazolin sodium (Panpharma, BN 106231) is the prophylactic antibiotic of choice in cardiac surgery. A dose of cefazolin 1gm IV is given during induction of anesthesia and an additional dose after coming off bypass. Recently, during an open heart surgery, we administered cefazolin (second dose) immediately after the reversal of heparinization with protamine sulphate (Medeva Pharma, BN 507030). Immediate precipitation in the IV line was noted. The infusion was stopped in time before the precipitate reached the patient. We subsequently mixed cefazolin in the dilution recommended by the manufacturer and protamine in-vitro and confirmed the observation of dense precipitation visually. Protamine is strongly basic (1); we postulate that alteration of pH (cefazolin pH is 4.5 to 6) (2) or physical incompatibility may have caused the precipitation of protamine by cefazolin. Precipitation of protamine may also cause inadequate reversal of heparinization and increase the risk of surgical bleeding. We wish therefore, to alert our colleagues to this interaction and recommend that protamine and cefazolin be infused separately with care.