Protamine-Induced Hypotension and Pulmonary Arterial Hypertension

Protamine is a routinely used safe antidote for heparin reversal in cardiovascular surgeries. Protamine was first introduced to prolong the action of insulin preparations. As protamine interacts with platelets and fibrinogen and has an anticoagulant effect of its own, minimal amount is given to neutralize heparin present in plasma. Although infrequent, protamine is associated with serious adverse drug reactions (ADRs), especially in patients with previous history of protamine hypersensitivity. Here, we report a case of protamine-induced pulmonary arterial hypertension and peripheral vascular collapse in a 60-year-old diabetic male patient who had undergone on-pump coronary artery bypass grafting in a tertiary care center. This was a definite, nonpreventable, severe ADR as per causality, preventability, and severity assessment scale. This patient had no previous history of protamine hypersensitivity and was not on any insulin preparations. Despite precise timely treatment and other resuscitative measures, the patient expired subsequent to these ADRs. This case report throws light on the grave requirement in urgent evolvement of pharmacogenetic and pharmacokinetic tools to detect patients who are at risk of precipitating these ADRs and thus to take precautions to prevent them

Reversión de la anticoagulación en pacientes con dosis altas de heparina: protamina en dosis standard versus dosis reducidas / Reversal anticoagulation in patients with high doses heparin: protamine in standard doses versus small doses

Evaluar y comparar, en pacientes sometidos a circulación extracorpórea (CEC), la reversión de la anticoagulación con dos dosis distintas de protamina: una dada en forma proporcional a la heparina usada versus una dosis calculada según peso del paciente, independiente de la heparina administrada. Material y Método: Se incorporaron los pacientes que para la CEC requirieron una dosis de heparina superior a 300 U•kg-1. Los criterios de exclusión fueron: alteraciones de las pruebas de coagulación preoperatorias y paro circulatorio hipotérmico. La técnica anestésica, el uso de fármacos y el uso de hemoderivados fue de decisión del anestesista. Para la reversión con protamina los pacientes fueron aleatorizados en dos grupos: Grupo A o dosis estándar: Reversión con 0,8 mg protamina por cada 100 U de heparina usada. Grupo B o dosis reducida: Reversión con 2,4 mg protamina•kg-1, independiente de la dosis de heparina usada. La protamina fue preparada por una persona ajena al pabellón y el equipo tratante era ciego al grupo del paciente. El seguimiento de los pacientes las primeras 24 h en UTI fue realizado por una persona ciega al grupo del paciente. Resultados: Hubo solamente una diferencia demográfica: más mujeres en el grupo B (p = 0,029). En el preoperatorio no hubo diferencias en hematocrito, recuento de plaquetas, tratamiento anticoagulante oral (TACO) y heparina preoperatoria, tipo de cirugía y uso de aspirina. En el intraoperatoriono hubo diferencias en el tiempo de coagulación activada (TCA) basal, hematocritos en CEC, TCA en CEC y duración de CEC. La dosis de heparina por kg de peso fue mayor en el grupo B (p = 0,0433). La relación protamina/heparina total fue 0,81 para el Grupo A y 0,44 para el Grupo B, las que fueron diferentes (por el diseño del estudio)...

Objective: To evaluate and compare reversal of anticoagulation with different dose regimens of protamine in patients undergoing to CPB (cardiopulmonary bypass), one given according to the heparin dose administered and another calculated according to patient’s weight. Patients y Methods: Patients subjected to CPB and receiving a heparin dose greater than 300 IU/kg were enrolled. Exclusion criterias were: preoperative coagulopathy and hypothermic circulatory arrest. The anesthetic technic, drugs given and blood products transfusion were decided by the attending anesthesiologist. Patients were randomized to: Group A or standard dose: Reversal with 0.8 mg of protamine for each 100 IU of heparin given. Group B or reduced dose: Reversal with 2.4 mg of protamine per kilogram of patient’s weight, independent of heparin dose used. The protamine was prepared for a person blinded to group allocation, same as the team taking care of the patient. The patient’s follow up in the ICU during the first 24 hours was also done by someone blinded to group allocation. Results: There was only one demographic difference at baseline: more women in Group B (p = 0.029). There were no differences among the preoperative: hematocrit, platelets count, oral anticoagulant treatment, heparin administration, aspirin consumption and surgical plan. In the intraoperative course there were no differences in the baseline ACT, hematocrit during CBP, ACT in CBP and CBP duration. The average heparin dose (adjusted per kilogram) was greater in Group B (p = 0.0433).The protamine/heparin ratios were different among groups (Group A 0.81; Group B 0.44), as expected in this study design. The activated coagulation time (ACT)...