T . Takeichi et al .: J Extra Corpor Technol 2024 , 56 , 120 – 124 123
to be an idiosyncratic reaction that may be related to previous exposure to protamine [ 12 , 13 ]. On the other hand , Levy , et al concluded that prior NPH insulin use , a history of fish allergy , or prior vasectomy does not represent a contraindication to protamine administration after CPB [ 4 ]. In our case , the patient had no history of NPH insulin and PZI use . Following protamine administration over 10 min from the peripheral venous route , sys PAP increased to 80 mmHg , prompting initiation of iNO therapy , resulting in a subsequent decrease in sys PAP experienced by the patients . The adverse reactions to protamine administration are classified into three types : Type I , characterized by hypotension due to rapid infusion ; Type II , presenting as an anaphylactic-like reaction ; and Type III , associated with severe pulmonary hypertension caused by significant pulmonary vasoconstriction . Type II reactions are further subclassified into a ) immediate-type anaphylactic reactions , b ) immediate-type anaphylactic-like reactions , and c ) delayed-type anaphylactic-like reactions [ 1 , 3 ]. In our case , because of the increased sys PAP , followed soon after protamine administration , a type III protamine reaction was suspected . Pulmonary hypertension due to severe pulmonary vasoconstriction of type III can rapidly occur following protamine administration [ 1 , 3 ]. As a result of starting with iNO therapy , sys PAP gradually decreased . Fortunately , hemodynamics such as sys ABP was no major change . After admission to the ICU , sys PAP was a normal value . More often , this catastrophic pulmonary hypertension results in right ventricular failure , low cardiac output , and systemic arterial hypotension , and interventions such as inhaled NO or epoprostenol , and even veno-arterial extracorporeal membrane oxygenation ( V-A ECMO ) are required [ 2 , 14 ]. Also , to decrease PAP , Zheng Guan et al showed the effectiveness use of epoprostenol to treat severe pulmonary vasoconstriction [ 15 – 17 ]. Heparin reversal by protamine has been reported to cause leukocytosis , and increased levels of complement factor C5b‐9 , interleukin ( IL ) -6 , and IL – 8 [ 18 ]. Our patient experienced not only pulmonary hypertension but also pulmonary edema , possibly related to increased pulmonary vascular permeability , with a P / R ratio of 218 . In the case of protamine type II reaction of delayed-type anaphylactic-like reactions , after 20 – 60 min of administration , this reaction is also observed along with increased pulmonary vascular permeability [ 19 , 20 ]. However , a major contributor to the pulmonary edema in our patient was the excessive fluid balance ; the total fluid balance was 9096 mL . We hypothesize that the reason this patient did not experience right heart failure and systemic hypotension was that this patient had chronic pulmonary hypertension , and therefore , the right ventricle might have been prepared (“ conditioned ”) to tolerate this increased PAP . This is supported by MacNee W , et al . who reported that RV ’ s stroke volume is decreased with increased afterload compared with the left ventricle [ 21 ]. However , despite the RV ’ s thinner wall ( 2 – 5 mm , about one-sixth of the LV ’ s thickness ), it achieves comparable stroke volume and CO to the LV . In pulmonary arterial hypertension ( PAH ), progressive pulmonary vascular disease increases PVR and RV afterload , causing RV wall stress and right ventricular hypertrophy ( RVH ). These changes maintain RV – PA coupling , allowing the RV to adapt and sustain stroke volume . However , with maximal RVH and rising PVR , the RV dilates to maintain CO , a maladaptive response that further increases wall stress [ 22 , 23 ]. As a result , RV failure could be caused .
Funding The authors received no funding to complete this research .
Conflicts of interest The authors declared no conflicts of interest .
Data availability statement All available data are incorporated into the article .
Author contribution statement
T . T . designed the studies . T . T . performed the research and analyzed the data . T . T . provided expertise in clinical data analysis . T . T . wrote the manuscript , and all authors contributed to the final version .
Ethics approval
The study conformed to the Declaration of Helsinki and was approved by the institution ’ s ethics committee in Kitaharima Medical Center , Ono-City , Hyogo Prefecture , Japan . Medical research is subject to ethical standards that promote and ensure respect for all human subjects and protect their health and rights .
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