We present a case of a 68-year-old male with type 2 diabetes, who was on insulin lispro protamine and underwent elective CABG. Shortly after protamine administration to reverse heparin during extracorporeal circulation (ECC), the patient experienced anaphylactic shock, manifesting as tachycardia, hypotension, facial flushing, periorbital edema, and elevated serum tryptase levels. Despite prompt treatment with volume resuscitation, epinephrine, and corticosteroids, the patient’s condition remained unstable, necessitating a second period of ECC for additional bypass grafting.

The case contributes to the clinical literature by providing an illustrative example of how protamine hypersensitivity can complicate postoperative recovery, emphasizing the importance of vigilance and comprehensive management strategies in preventing and addressing such reactions.