Protamine induced Pulmonary Vasoconstriction

Case: 48 years old male with coronary artery disease has been taken for an elective heart-bypass surgery. In the end, protamine reversal was instituted. After a few minutes of protamine infusion, the PAP (pulmonary artery pressure) suddenly increased to 90/40 mm Hg. The protamine was discontinued. PAP was noted to return to normal. The protamine was restarted but the PAP again rapidly increased to 85/37 mm Hg, and the patient became hypotensive. 

Answer: Protamine-induced acute pulmonary hypertension.

Mechanism of action: Complement activation, leading to thromboxane A2 generation causing acute pulmonary hypertension.

Treatment is the application of inhaled Nitric Oxide and hemodynamic support as required. Interestingly, Protamine can be restarted if needed to complete surgery under the protection of inhaled NO! By using iNO, a full reversal dose of protamine can be successfully administered to a patient. Nitric Oxide can be weaned in the next 24 hours after surgery.

Alternatives to protamine for heparin reversal, such as heparinase or recombinant platelet factor 4 can be applied but are usually unavailable.

#cardiovascular

#pulmonary

#pharmacology

References: 

1. Ralley FE. The use of nitric oxide for managing catastrophic pulmonary vasoconstriction arising from protamine administration. Anesth Analg. 1999 Mar;88(3):505-7. doi: 10.1097/00000539-199903000-00007. PMID: 10071995.

2. Lowenstein E. Lessons from studying an infrequent event: adverse hemodynamic response associated with protamine reversal of heparin anticoagulation. J Cardiothorac Anesth. 1989 Feb;3(1):99-107. doi: 10.1016/0888-6296(89)90019-7. PMID: 2520647.

3. Pannu BS, Sanghavi DK, Guru PK, Reddy DR, Iyer VN. Fatal right ventricular failure and pulmonary hypertension after protamine administration during cardiac transplantation. Indian J Crit Care Med. 2016 Mar;20(3):185-7. doi: 10.4103/0972-5229.178185. PMID: 27076733; PMCID: PMC4810899.