Patients undergoing elective cardiac surgery with cardiopulmonary bypass. Heparin and protamine dosing for anticoagulation during cardiopulmonary bypass cpb and its reversal after cpb, respectively, is usually given. Adjusted calculation model regarding heparin and protamine in. Cytokine removal might therefore improve outcomes of patients undergoing cardiac surgery. Although serum heparin is neutralized by a proper dose of protamine after 7. Patients treated with antifibrinolytic agents aprotinin, r proic or tranexamic acid were excluded. Patients should be carefully monitored using either the activated partial thromboplastin time or the activated clotting time, carried out 515 minutes after. The use of a dose response curve to individualize heparin and protamine dosage.
Cardiopulmonary bypass cpb is a technique in which a machine temporarily takes over the function of the heart and lungs during surgery, maintaining the circulation of blood and the oxygen content of the patients body. Jia et al established a pk model to predict heparin concentrations during cardiac surgery, suggesting a lower protamine dosing regimen after termination of cpb. The improved biocompatibility of the cardiopulmonary bypass circuits made possible by the use of surfaceimmobilized heparin may allow for a reduction in the amount of heparin administered systemically. The etiologic role of protamine in the pathogenesis of this condition is uncertain, and multiple factors have been present in most cases.
Management of coagulation during cardiopulmonary bypass. Cardiac surgery with cpb cannot occur if the heart is still beating. Anticoagulant and sideeffects of protamine in cardiac surgery. Heparin doseresponse and individual calculation of protamine dose for each patient is also possible with the heparin management test. A prospective study of the risk of an immediate adverse reaction to protamine sulfate during cardiopulmonary bypass surgery. Subjects and methods sixty patients scheduled for first time elective coronary artery bypass grafting. Group 3 patients received the highest heparin doses p less than 0. Assessment of coagulation the patients coagulation system was assessed at two time points.
Evaluation of a new formula for calculating heparin dose. Hyperheparinemia or bleeding has been reported in experimental animals and in some patients 30 min utes to 18 hours after cardiac surgery under cardio pulmonary bypass in spite of complete neutralization. In the reversal of uf heparin following cardiopulmonary bypass, either a standard dose of protamine may be given, as above, or the dose may be titrated according to the activated clotting time. Management of postop cardiac surgery patients critical. This response can, in severe cases, lead to systemic hypotension and organ dysfunction. Heparin dosing and monitoring for cardiopulmonary bypass. We studied the inhibitory effect of a reduced protamine dose, the duration of impaired platelet function and. The effects of etomidate and propofol induction on. Intravenous protamine administration is associated with a risk of severe systemic reactions. Cardiorespiratory effects of protamine after cardiopulmonary. Dec 01, 2019 highprotein, noncardiogenic pulmonary edema associated with the use of protamine has been reported in patients on cardiopulmonary bypass who are undergoing cardiovascular surgery.
Heparinase i, a specific heparindegrading enzyme with a therapeutic halflife ranging from 5. In this study, the administration of pf4 to patients was both safe and effective in the doses used. Cardiopulmonary bypass with heparincoated circuits and. Bical4 1 research director, laboratory of experimental physiology, institute of myology, paris, france. The purpose of this study was to determine risk factors for adverse events following protamine administration after cardiopulmonary bypass. Administration of protamine sulfate for heparin neutralization after cardiopulmonary bypass may be associated with adverse reactions such as transient hypotension to cardiovascular. Original article a comparison of low vs conventionaldose heparin for minimal cardiopulmonary bypass in coronary artery bypass grafting surgery y. After cpb termination, heparin was neutralized with protamine sulfate at adose 1. Anaphylaxis to protamine during cardiovascular surgery. Protamine reduced the platelet aggregation by 50% in heparinised patients undergoing cardiac surgery with cpb. Protamine sulfate injection, usp for intravenous use warning protamine sulfate can cause severe hypotension, cardiovascular collapse, noncardiogenic pulmonary edema, catastrophic pulmonary vasoconstriction, and pulmonary hypertension. Cardio plegia can be a cold solution that ishigh in. Protamine dose and heparin concentration during cardiopulmonary bypass correlated best with postoperative mediastinal drainage.
Patients were observed post operatively for any adverse effects. Cardiorespiratory effects of protamine after cardiopulmonary bypass in man. Management of coagulopathy associated with cardiopulmonary bypass. At the present time all bypass cases get the standard monitors plus an aline. Two hundred fiftyfour patients requiring cardio pulmonary bypass were enrolled in this prospective study over a 7month period. Risk factors include high dose or overdose, rapid administration see warnings and dosage and. Method to calculate the protamine dose necessary for reversal of. Convincing evidence from invitro and invivo studies suggest that an overdose of protamine has anticoagulant effects which might lead to bleeding complications. A prospective study of the risk of an immediate adverse reaction to protamine sulfate during cardio pulmonary bypass surgery. In 56 patients, protamine was dosed in a fixed ratio cd, while 62. Listing a study does not mean it has been evaluated by the u. A pharmacokinetic model for protamine dosing after cardiopulmonary bypass article pdf available in journal of cardiothoracic and vascular anesthesia 305 april 2016 with 64 reads. There was a transient fall in arterial pressure and a more prolonged increase in pulmonary artery pressure. Case report dramatic postcardiotomy outcome, due to.
Appropriate gas exchange shall be maintained during. The cardiorespiratory changes following the injection of protamine sulphate 6 mgkg were studied in 15 patients who had undergone cardiopulmonary bypass. Feb 27, 2016 protamine once bypass is terminated, and after removal of venous cannula,protamine is given to reverse heparin, usually during a 510 min period. Patients were allocated randomly to receive either propofol or etomidate. P usp for intravenous use warning protamine sulfate can cause severe hypotension, cardiovascular collapse, noncardiogenic pulmonary edema, catastrophic pulmonary vasoconstriction, and pulmonary hypertension.
Guidelines for using bivalirudin during cardiopulmonary. Department protocol is to add an additional 100 iukg of heparin to the calculated heparin dose concentration to ensure a heparin bolus dose that will result in an act greater than 480 seconds. The primary aim of this study was to investigate whether heprocalcbased dosage of heparin can reduce protamine usage compared with traditional dosage. Thus, we developed an original formula, which takes into account baseline act. A primer was published by the cardiac surgery team at the university of washington, using the ibook electronic format. Adjusted calculation model regarding heparin and protamine. Cardiac anesthesiology made ridiculously simple ucsf dept of. P jan 07, 2008 optimal heparin dosing regimens for cardiopulmonary bypass heparin dosing the safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Efficacy and safety of heparinase i versus protamine in. In order to use the cpb, the heart must be stopped.
The adverse effects of the cardiopulmonary bypass machine. History the first operation performed using cardiopulmonary bypass and open cardiotomy was on april 5, 1951 by dr. Management of coagulation during cardiopulmonary bypass bja. Protamine is used after cardiopulmonary bypass cpb to reverse the anticoagulant effects of heparin and restore coagulation. Dose ratio 1 mg protamine per 10 iu of heparin, based on precpb heparin dose. Protamine once bypass is terminated, and after removal of venous cannula,protamine is given to reverse heparin, usually during a 510 min period. This study was performed to elucidate the effects of cardiopulmonary bypass using heparincoated circuits and reduced heparinization on hemostatic variables and clinical outcome. Guidelines for using bivalirudin during cardiopulmonary bypass surgery during cardiopulmonary bypass procedures, systemic anticoagulation to prevent thrombosis in the patient as well as the circuit is utilized.
Additional doses of heparin during cardiopulmonary bypass should be determined by using an act andor heparin protamine assay. A pharmacokinetic model for protamine dosing after. The secondary aim was to investigate whether heprocalcbased dosage of protamine will affect the amount of. Protamine is commonly administered in a fixed protaminetoheparin ratio based on the intraoperative weightadjusted dose of heparin, irrespective of the heparin concentration remaining in the circulation at the end of cpb. Back ground factors such as age, sex, bw, baseline act, heparin dose, act, liver and renal function, and preoperative heparin therapy were recorded to analyze the relationship between heparin dose and act values. If adequately dosed, protamine neutralises heparin and reduces the risk of postoperative bleeding. In the reversal of uf heparin following cardiopulmonary bypass, either a standard dose of protamine may be given, as above, or the dose may be titrated according to the activated. Evaluation of a new formula for calculating heparin dose for cardiopulmonary bypass patients. Validation of viscoelastic coagulation tests during cardiopulmonary bypass. Patient information for prosulf 10mgml solution for injection including dosage instructions and possible side effects. It is available as a free download from the apple ibook store. The technique allows the surgical team to oxygenate and circulate the patients blood, thus allowing the surgeon to operate on the heart. Cardiopulmonary bypass is commonly used in operations involving the heart.
Type 3 catastrophic pulmonary vasoconstriction manifested by elevated pulmonary arterial pressure, systemic hypotension from peripheral. The journal of thoracic and cardiovascular surgery, 69, 685689. Although the formula assumes activated clotting time act to be within normal range, baseline act varies in each patient. Anticoagulant and sideeffects of protamine in cardiac. Heparin and antithrombin iii levels during cardiopulmonary.
In addition, pf4 had the advantage of rapid administration, within 2 minutes, in comparison with 10 minutes for protamine. Cardiopulmonary bypass cpb is often associated with degrees of complex inflammatory response mediated by various cytokines. Protamine reduces platelet aggregation after cardiopulmonary bypass cpb. Anticoagulation monitoring during cardiac surgery uw. However, risk factors for these events have not been well delineated, thus hampering development of preventive strategies. Pdf a pharmacokinetic model for protamine dosing after.
Protamine sulfate is contraindicated in patients who have shown previous intolerance to the drug. Gastric aspiration, sepsis, and trauma are wellrecognized causes of noncardiogenic pulmonary edema ncpe. Blood pressure and heart rate came to normal with minimal inotropic support protamine started haemostatis done. Weiler jm, gelhaus m, carter j, meng r, benson p, hottel r, schillig rn, vegh a, clarke w. The serum cortisol values were recorded at 3 time points 1 baseline before induction of anesthesia. Protamine in cardiac surgery and haemostasis full text view. However, as its anticoagulant properties are particularly exerted in the absence of heparin, overdosing of protamine may contribute to bleeding and increased. Heparin is the most common agent used, but in selective circumstances, alternate form of anticoagulation may be considered. After the aorta is crossclamped, cardioplegia is administered to stop the heart. Activated clotting times and cardiopulmonary bypass 1. Sites of cannulation for cpb are usually the aorta and the right atrium. The measured heparin dose response hdr slope of the hms is designed to project a prebypass heparinloading dose resulting in an act of 480 seconds.
A brief history of cardiopulmonary bypass eugene a. Heparin dose and postoperative bleeding in patients. In vivo protamine titration using activated coagulation. This was following four years of experiments with dogs. Anticoagulation is essential during cpb in cardiac surgery. After the end of cpb, heparinization was reversed with 10 mg protamine sulfate for each units of the initial heparin dose. The study demonstrates that a single bolus dose of 1. We hypothesized that heparin and protamine dosing based on individual titration curves would improve haemostasis in comparison to standard dosing. Nursing care of the patient undergoing coronary artery bypass. Pdf evaluation of hemodynamic changes due to protamine. We report here the case of a 6dayold boy having presented severe and recurring hypotensions after protamine infusions during cardiac surgery under cardio pulmonary bypass. A pharmacokinetic model for protamine dosing after cardiopulmonary bypass michael i. Anticoagulation during cardiopulmonary bypass society of.
Protamine sulfate is used routinely to neutralize unfractionated heparin after cardiopulmonary bypass cpb during cardiac surgery. The use of a doseresponse curve to individualize heparin and protamine dosage. Antithrombin iii levels in the children were the most predictive r 0. To check the formula, we performed a retrospective observational cohort study of 177 patients undergoing cardiac surgery with cardiopulmonary bypass cpb.
Risk factors for clinically important adverse events after. Fisher summary circulating concentrations of split products of the third complement factor c3c and c3d were measured in five patients before, during and after cardiopulmonary bypass. We compared standard high dose anticoagulation with a low dose heparin regimen in a retrospective study of patients who underwent coronary bypass surgery using minimal cardio pulmonary bypass. Background bleeding complications are common in cardiac surgery. Perioperative handling of heparin and protamine may influence the haemostasis. Cardiopulmonary bypass cpb, first used successfully in the 1950s for its primary role in cardiac surgery, has now also found a place in the management of severe respiratory failure, particularly in neonates, and in emergency hemodynamic support following massive pulmonary embolism, trauma, environmental. Original article a comparison of low vs conventionaldose. Nahush mokadam, has structured the publication in a very logical format, with chapters describing the circuit components, technical aspects of cardiopulmonary. Venous cannulation is by a right atrialinferior vena cava, twostage cannula and arterial.
Evaluation of a new formula for calculating heparin dose for. The systemic circuit bolded in the diagram includes the venous line, membrane oxygenator with integral hardshell venous reservoir lower center, systemic blood pump, arterial filter, and return to the patient via the arterial cannula. Anesthesia, cardiac surgery, cardio pulmonary bypass corresponding author. Neutralisation of systemic anticoagulation with heparin in cardiac surgery with cardiopulmonary bypass requires protamine administration. In many operations, such as coronary artery bypass grafting cabg, the heart is arrested i. Cardiopulmonary bypass an overview sciencedirect topics.