Heparin reversal in off-pump coronary artery bypass surgery: complete,partial, or no reversal?

Several clinical studies have reported that avoiding cardiopulmonary bypass reduces postoperative bleeding. The purpose of this study is to verify that protamine during off-pump coronary artery bypass surgery produces significant reduction of postoperative bleeding.Sixty consecutive patients undergoing off-pump coronary artery bypass surgery were prospectively randomized in three groups: Group A received 1 mg of protamine every 100 IU of heparin, Group B 0.5 mg of protamine every 100 IU of heparin, and Group C none. The three groups were analyzed for differences in preoperative cardiac function, pre-, intra-, and postoperative coagulation profile, intraoperative variables, and postoperative bleeding.In the three study groups, no statistically significant difference was found in preoperative cardiac function, pre- and intraoperative coagulation profile, and prothrombin time, activated partial thromboplastin time, platelet count in the first postoperative day. In Group A, total postoperative bleeding, use of packed red blood cells, and mild pericardial effusion prevalence at discharge were significantly lower only when compared to Group C, but they were not significantly different when compared to Group B.In off-pump coronary artery bypass surgery, heparin should be reverted with protamine, otherwise the postoperative bleeding risk might increase. Partial heparin reversal might not increase postoperative bleeding risk, but it may reduce dose-dependent protamine adverse effects.     

Blood coagulation and autologous blood transfusion in cardiac surgery

Study Objective: To review the basic pathophysiology of altered coagulation associated with cardiopulmonary bypass and autologous blood transfusion in cardiac surgery.

Design: Review of rational use of heparin, mechanisms and treatment of coagulation disorders, and autologous blood transfusion.

Setting: Cardiac surgery in community and academic hospitals.

Patients: Adult cardiac surgical patients.

Main Results: Heparin is most commonly used for anticoagulation during cardiopulmonary bypass. Although activated clotting time is widely used to assess heparin-induced anticoagulation, the minimum time to prevent clotting during cardiopulmonary bypass remains unclear. Activated clotting time is affected by many factors other than heparin, such as antithrombin III, blood temperature, platelet count, and age. The rational use of activated clotting time still must be defined.

The frequency of abnormal bleeding after cardiopulmonary bypass is significant. Although inadequate surgical hemostasis is the most frequent cause of bleeding, altered coagulation often is present. A decreased number of functional platelets is one of the important causes of bleeding diathesis. Platelet dysfunction is induced by perioperative medication such as aspirin. Cardiopulmonary bypass decreases functional platelets by degranulation, fragmentation, and loss of fibrinogen receptors. Medications such as prostacyclin and iloprost may be useful to protect these platelets. Desmopressin increases factor VIII:C and von Willebrand's factor, leading to a decrease in bleeding time. Desmopressin may be useful to decrease blood loss in repeat cardiac operations, complex cardiac surgery, and abnormal postoperative bleeding.

Patients undergoing coronary artery bypass grafting immediately after streptokinase infusion also are at risk for abnormal bleeding. Transfusion of fresh frozen plasma and cryoprecipitate may be necessary.

Autologous blood transfusion is cost-effective and the safest way to avoid or decrease homologous blood transfusion. Predonation, intraoperative salvage, and postoperative salvage are encouraged. Erthroprotein may be useful in increasing the amount of predonation red cells.

Conclusions: Coagulation disorders in cardiac surgery are caused by many factors, such as heparin, platelet dysfunction, and fibronolysis. Rational use of blood component therapy and medications such as heparin, protamine, and desmorpessin are mandatory. Autologous blood transfusions is very useful in decreasing or obviating the use of homologous blood transfusion.     

鱼精蛋白个体化使用减少心脏直视手术后患者出血的研究

目的比较个体化与按体重给予鱼精蛋白对体外循环(CPB)手术后患者出血和输血量的影响,以减少CPB后出血并发症的发生。方法40例拟在CPB下行择期心脏手术的成年患者随机分为两组,实验组:根据肝素-鱼精蛋白滴定法结果给予鱼精蛋白;对照组:术前给予肝素,按1∶1的比例给予鱼精蛋白。记录术后1 h、2 h和24 h的胸腔引流量和输血量。结果实验组鱼精蛋白用量明显大于对照组(P0.05),而胸腔引流量(出血量)于术后1 h(180±83 ml vs.285±156 ml,P=0.012)、2 h(74±31 ml vs.114±44 ml,P=0.002)、24 h(465±167 ml vs.645±207 ml,P=0.004)和红细胞悬液输入量(0.15±0.27 Uvs.0.80±0.96 U,P=0.018)均少于对照组。结论与目前临床上使用的根据CPB前肝素用量给予鱼精蛋白的方法比较,滴定法指导的个体化给予鱼精蛋白能减少CPB后患者的胸腔引流量(出血量)和红细胞输入量。     

Clinical role of blood heparin level monitoring during open heart surgery.

Protamine has been used for neutralizing heparin and its dosage is decided by the initial fixed dose of heparin. Adequate protamine neutralization is very important to reduce complications. To attenuate excess reactions, in particular, whole blood heparin concentration during and after cardiopulmonary bypass was measured using Hepcon, and the efficacy of optimal protamine dose in open heart surgery was evaluated. Twenty patients were randomly divided into two comparable groups, P and C. In the C group, heparin was neutralized with an initial fixed dose of protamine, 1.67 mg protamine per milligram total heparin (n = 8). In the P group, protamine dose was determined for residual heparin concentration (n = 12). In the P group, blood heparin concentrations at 60 minutes after the establishment of cardiopulmonary bypass, just after cardiopulmonary bypass and first protamine administration were 2.35 +/- 0.14, 2.31 +/- 0.17 and 0.13 +/- 0.08 U/ml, respectively. Concentrations reached zero with the second protamine administration. The requirement of transfusion (659 +/- 224 vs. 1559 +/- 323 ml, p = 0.0314), pulmonary vascular resistance index just after the protamine administration (190 +/- 22 vs. 286 +/- 18 dyne.s.cm-5.m2, p = 0.0137) and the IL-8 levels (just after protamine: 26.9 +/- 5.1 vs. 43.5 +/- 5.9 pg/ml, p = 0.0499, 12 hours after cardiopulmonary bypass: 37.1 +/- 12.1 vs. 86.8 +/- 20.0, p = 0.0435) in the P group were significantly lower than those in the C group. These data suggested that heparin level monitoring in whole blood may be useful to determine the optimal dose of protamine resulting in the decrease of a requirement of blood components in open heart surgery and attenuating in transient pulmonary hypertension and excess protamine-induced inflammatory reactions.     

Comparison of two protocols for heparin neutralization by protamine after cardiopulmonary bypass

Twenty patients undergoing cardiac operations were randomly assigned to two protocols for heparin neutralization by protamine after cardiopulmonary bypass. In all patients protamine chloride was given at a ratio of 1 unit of protamine to 1 unit of injected heparin. In Group I (10 patients) all protamine was infused within 10 minutes after termination of cardiopulmonary bypass. Group II (10 patients) received 75% of the calculated protamine dose within 10 minutes after termination of bypass and the remainder after transfusion of all blood in the heart-lung machine. Plasma heparin levels were significantly lower in Group II 5 minutes after transfusion of all blood in the heart-lung machine and were 0.13 units/ml (standard deviation 0.04) in Group I and 0.06 units/ml (standard deviation 0.05) in Group II (p less than 0.001) 60 minutes after bypass. Activated partial thromboplastin time mirrored the changes in plasma heparin, whereas activated clotting time (Hemochron) was too insensitive to detect these low plasma heparin levels. We conclude that the two-dose protocol resulted in more complete heparin neutralization than the one-dose protocol.     

Clinical role of blood heparin level monitoring during open heart surgery

Protamine has been used for neutralizing heparin and its dosage is decided by the initial fixed dose of heparin. Adequate protamine neutralization is very important to reduce complications. To attenuate excess reactions, in particular, whole blood heparin concentration during and after cardiopulmonary bypass was measured using Hepcon®, and the efficacy of optimal protamine dose in open heart surgery was evaluated. Twenty patients were randomly divided into two comparable groups, P and C. In the C group, heparin was neutralized with an initial fixed dose of protamine, 1.67 mg protamine per milligram total heparin (n = 8). In the P group, protamine dose was determined for residual heparin concentration (n = 12). In the P group, blood heparin concentrations at 60 minutes after the establishment of cardiopulmonary bypass, just after cardiopulmonary bypass and first protamine administration were 2.35 ± 0.14, 2.31 ± 0.17 and 0.13 ± 0.08 U/ml, respectively. Concentrations reached zero with the second protamine administration. The requirement of transfusion (659 ± 224 vs. 1559 ± 323 ml, p = 0.0314), pulmonary vascular resistance index just after the protamine administration (190 ± 22 vs. 286 ± 18 dyne·s·cm^?5·m², p = 0.0137) and the IL-8 levels (just after protamine: 26.9 ± 5.1 vs. 43.5 ± 5.9 pg/ml, p = 0.0499, 12 hours after cardiopulmonary bypass: 37.1 ± 12.1 vs. 86.8 ± 20.0, p = 0.0435) in the P group were significantly lower than those in the C group. These data suggested that heparin level monitoring in whole blood may be useful to determine the optimal dose of protamine resulting in the decrease of a requirement of blood components in open heart surgery and attenuating in transient pulmonary hypertension and excess protamine-induced inflammatory reactions.     

Heparin monitoring during cardiopulmonary bypass in congenital heart surgery

The Hepcon/HMS system automatically provides the activated clotting time and a whole blood heparin concentration. It also provides the adequate protamine dose by titration of protamine to heparin. 45 patients undergoing congenital heart surgery with cardiopulmonary bypass (CPB) were studied by the Hepcon/HMS device. We measured the heparin dose response before heparin administration, and the ration between the dose of protamine (ml) which was necessary for heparin neutralization at the termination of CPB and the dose of total heparin (ml) in each patient. The value of heparin dose response ranged 120-390 (mean 228) IU/kg. The ratio between protamine dose and heparin dose varied 0.11-0.99 (mean 0.55). There was a statistically significant correlation between the duration of CPB and this ratio (r = -0.51, n = 45, p = 0.0005). From the standpoint of variances in the value of heparin dose response, conventional way of the heparin administration according to the patient's body weight alone may cause inadequacy of anticoagulation during CPB. A dose of protamine determined by Hepcon device that is smaller than a conventional dose of protamine prevents inadvertent overdose and, therefore, can reduce the adverse effects excessive protamine has.     

Use of heparin-coated cardiopulmonary bypass circuit with low-dose heparin reduces postoperative bleeding.

Postoperative bleeding was examined in patients undergoing cardiopulmonary bypass with a heparin-coated circuit and low-dose heparin. Out of 150 patients who underwent cardiopulmonary bypass for longer than 90 minutes, 74 received a standard dose (300 IU/kg) of heparin with an uncoated circuit (group C) and 76 received a low-dose (150 IU/kg) of heparin with a heparin-coated circuit (group H). The coagulation and fibrinolytic systems were investigated in 24 patients. Re-opening of the chest due to bleeding was performed in 5 patients in group C (7%), but none of the patients in group H (p=0. 03). The median of blood loss in the first 12 hours after surgery was 292 ml in group C, and 216 ml in group H (p=0.006). There were no significant differences in the peak thrombin-antithrombin complex concentration between the two groups. The plasmin-alpha 2 plasmin inhibitor complex concentrations after protamine administration were 1.9 ng/ml (median) in group C and 1.1 ng/ml in group H (p=0.002). The use of heparin-coated cardiopulmonary bypass circuits with low-dose heparin suppressed the activation of fibrinolysis. This may explain the reduction in postoperative bleeding.     

Successful use of a reduced dose of protamine after cardiopulmonary bypass.

The dose of protamine necessary to reverse heparin was examined in 60 patients. Half the patients (controls) received a reversal dose of protamine equal to the entire amount of heparin given them, while half received a reversal dose based on a heparin half-life of 2 hours. Postoperative chest drainage for the first 12 hours and for 48 hours was markedly reduced in patients given the reduced dose of protamine. Platelet counts were higher and postoperative clotting studies varied less from control in patients receiving the smaller dose of protamine. The authors suggest reevaluation of the dose of protamine necessary to reverse the anticoagulant effects of heparin in patients for cardiopulmonary bypass, since larger doses protamine may contribute to the conditions which increase postoperative bleeding.     

Risk factors reducing blood transfusion requirements in pediatric open heart surgery after introduction of vacuum assisted circuits

OBJECTIVES: Open heart surgery without homologous blood transfusion remains difficult in children. The introduction of vacuum-assisted cardiopulmonary bypass circuits to reduce priming volume for pediatric patients has improved the percentage of transfusion-free operations. We retrospectively analyzed blood transfusion risk factors to further reduce blood transfusion requirements after vacuum-assisted circuit introduction. METHODS: From March 1995 to June 1996, 49 patients weighing between 5 and 20 kg underwent cardiac surgery with cardiopulmonary bypass at our institution, excluding hospital deaths. We retrospectively analyzed risk factors influencing blood use in 37 patients with no blood priming in cardiopulmonary bypass after introducing a vacuum-assisted system. Factors selected for univariate analysis were age, body weight, cyanosis, preoperative Hb, operation time, cardiopulmonary bypass time, aortic cross-clamping time, and intraoperative and postoperative bleeding volume. Correlation between total bleeding volume/body weight and cardiopulmonary bypass time was studied by regression analysis. RESULTS: As risk factors, univariate analysis identified cyanotic disease, longer operation time (> 210 minutes), longer cardiopulmonary bypass time (> 90 minutes), longer aortic cross-clamping time (> 45 minutes), greater intraoperative bleeding volume/body weight (> 4 ml/kg), and greater postoperative bleeding volume/body weight (> 15 ml/kg). Regression analysis showed a significant positive correlation between total bleeding volume/body weight and cardiopulmonary bypass time. CONCLUSIONS: Cyanotic disease and long bypass time are risk factors in reducing blood transfusion requirements in pediatric open heart surgery after introduction of vacuum-assisted circuits. Further efforts are needed, however, to reduce blood transfusion requirements, particularly in these children.     

Anticoagulant monitoring and neutralization during open heart surgery--a rapid method for measuring heparin and calculating safe reduced protamine doses

Confident monitoring of heparin during cardiopulmonary bypass and subsequent neutralization by protamine has been hampered by the absence of an accurate, reproducible, rapid, simple, and specific assay for heparin. By using two new instruments in tandem, one of which produced 0.5 ml of plasma in 1 min and one which specifically measures heparin in 3-4 min, heparin levels are available in approximately 5 min. By performing heparin assays at a variety of intervals, it was demonstrated that 76% of patients receiving common doses of heparin during cardiopulmonary bypass may have plasma levels that are potentially too low. Minimum neutralizing doses of protamine may be calculated using the formula: (estimated blood volume + pump prime volume) X (plasma heparin level/100) X 1.1 + 50. These doses were nearly two-thirds of previous doses and were unassociated with increased bleeding, clotting, or clinically significant heparin rebound.     

Does use of the Hepcon point-of-care coagulation monitor to optimise heparin and protamine dosage for cardiopulmonary bypass decrease bleeding and blood and blood product requirements in adult patients undergoing cardiac surgery?

A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was whether use of the Hepcon point-of-care coagulation monitor (Medtronic, Minneapolis, MN) to optimise and monitor heparin and protamine dosage for cardiopulmonary bypass could decrease bleeding and blood and blood product requirements in adult patients undergoing cardiac surgery. Altogether 680 papers were identified on Medline, and 879 on Embase using the reported search strategy. Two further relevant papers were found by hand-searching of reference lists. Fourteen papers represented the best evidence on the topic. The author, journal, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses were tabulated. We conclude that in patients undergoing cardiac surgery, use of the Hepcon coagulation monitor will increase the dose of heparin but decrease the dose of protamine administered compared to more empirical ACT-based dosing regimes. There is some evidence that this leads to less activation of the coagulation system and may be associated with decreased postoperative bleeding and blood product requirements but more work is required to quantify the magnitude of this effect.     

Aprotinin reduces intraoperative and postoperative blood loss in membrane oxygenator cardiopulmonary bypass.

To determine whether aprotinin can provide a significant improvement of hemostasis in cardiopulmonary bypass using a membrane oxygenator, we tested this drug in a prospective, randomized, double-blind, placebo-controlled clinical trial. The subjects were 80 male patients undergoing cardiopulmonary bypass for coronary artery bypass grafting. Forty patients received aprotinin and 40 patients served as placebo controls. Aprotinin (4 x 10(6) KIU) was given as a continuous infusion, starting before operation and continuing until after cardiopulmonary bypass; additionally, 2 x 10(6) KIU aprotinin was added to the pump prime. Intraoperative and postoperative bleeding, respectively two thirds and one third of the total perioperative blood loss, were both significantly reduced in the aprotinin-treated group (p less than 0.01). The total average perioperative blood loss, corrected to a hemoglobin concentration of 7 mmol/L, was 550 mL in the aprotinin-treated patients versus 900 mL in the control patients. This reduction in blood loss, furthermore, significantly decreased the amount of postoperative blood transfusions (p less than 0.05) and increased the percentage of patients who did not receive postoperative donor blood from 42% to 68%. Aprotinin increased the activated clotting time significantly during cardiopulmonary bypass, which led to a reduction in heparin usage. The improved hemostasis during operation, despite the prolonged activated clotting time, might even abolish the need for heparin conversion with protamine at the end of cardiopulmonary bypass, thus allowing retransfusion through cardiotomy suction to be continued, which saves the blood that is currently lost with vacuum suction.     

Heparinase in the activated clotting time assay: monitoring heparin-independent alterations in coagulation function.

The activated clotting time (ACT) is routinely used to monitor heparin during cardiopulmonary bypass surgery. Activated clotting times may be influenced by a number of factors other than heparin. The presence of heparin in blood samples disguises the occurrence of non-heparin-related changes in coagulation function. During cardiopulmonary bypass, it is difficult to ascertain baseline clotting time fluctuations with ACT alone. Previous attempts to establish accurate baseline data were imprecise and involved extensive sample handling. In this study, we present data obtained using a modified (ACT) assay that incorporates heparinase. The heparinase test cartridge (HTC) instantaneously, specifically, and completely removes heparin in the blood sample at the initiation of the test. In conjunction with standard ACT techniques, the clinician is provided with heparin-independent (baseline) and functional clotting data. The HTC/ACT assay was used in a case study involving 19 patients undergoing cardiopulmonary bypass surgery. The data gathered indicate the usefulness of this assay in monitoring incidents of baseline drift, hemodilution, and hypercoagulation and the efficacy of protamine reversal.     

Can extra protamine eliminate heparin rebound following cardiopulmonary bypass surgery?

OBJECTIVES: Heparin rebound, the reappearance of anticoagulant activity after adequate neutralization with protamine, is thought to contribute to excessive postoperative bleeding after cardiac surgery. We have previously demonstrated that a significant amount of heparin is bound nonspecifically to plasma proteins and is incompletely neutralized by protamine. The aim of this study was to investigate whether clinically important bleeding attributable to heparin rebound can be eliminated by infusion of small amounts of additional protamine for 6 hours postoperatively and whether this treatment can reduce mediastinal blood loss. METHODS: Three hundred patients undergoing elective cardiac surgery were randomized to receive either a continuous infusion of protamine sulphate (25 mg/h for 6 hours) postoperatively or saline placebo. Serial blood samples were obtained to measure thrombin clotting time and anti-factor Xa activity. Heparin bound nonspecifically to plasma proteins was measured after displacement with a chemically altered heparin with low affinity to antithrombin. Mediastinal blood loss and transfusion requirements were recorded. RESULTS: Heparin rebound was demonstrated in every patient in the placebo group as reflected by increased thrombin clotting time, anti-factor Xa activity, and protein-bound heparin between 1 and 6 hours after surgery. In contrast, heparin rebound was eliminated in the protamine infusion group. The thrombin clotting time was normalized and both heparin concentration and protein-bound heparin were almost undetectable (P <.001). There was a modest 13% reduction in postoperative bleeding but this did not reduce blood transfusions. No adverse events were attributable to the extra protamine. CONCLUSIONS: Postoperative protamine infusion was able to almost totally abolish heparin rebound. In the context of this study, protamine infusion resulted in reduced postoperative bleeding but the magnitude was insufficient to alter transfusion requirements.     

Focus on thrombin: alternative anticoagulants

Unfractionated heparin and protamine have been integral to cardiopulmonary bypass since cardiac surgery was first undertaken. These drugs are inexpensive and well understood but are contraindicated in some individuals, and resistance to heparin can be problematic in others. The interplay between the endothelium, anticoagulants, the coagulation cascade, and the inflammatory response that characterizes cardiac surgery may contribute to some of the complications associated with cardiopulmonary bypass. Various alternative drugs and strategies have been used to manage patients unsuitable for heparin or protamine, but each has its own disadvantages. At present, direct thrombin inhibitors may offer the best available alternative to heparin in cardiac surgery, particularly the short-acting bivalirudin, but this class of anticoagulants is relatively expensive and has no reversal agent. Balanced anticoagulation using combinations of drugs that act at different stages in the coagulation system may improve the management of coagulation in cardiac surgery, but careful investigation of this concept is needed.     

The hemostatic mechanism after open-heart surgery. II. Frequency of abnormal platelet functions during and after extracorporeal circulation.

In a prospective study of 13 patients undergoing open-heart surgery with extracorporeal circulation, marked qualitative platelet function defects were observed in addition to the usually occurring drop of the thrombocyte count. At the end of bypass, the following test results were significantly abnormal: concentration of fibrinogen and of circulating fibrin degradation products, platelet count, platelet adhesiveness to glass beads, and platelet aggregation induced by low and high doses of ADP. One to 2 hours after neutralization of heparin with protamine sulfate all abnormal test results improved, but the template bleeding time was markedly prolonged in 10 patients. There was no correlation between length of bypass and platelet fall and between concentration of circulating fibrin degradation products and extent of platelet dysfunction. An apparent correlation was found between the length of the postoperative bleeding time and the number of units of blood transfued during surgery. The results of this study suggest that dilution of the patient's own platelets by nonviable platelets contained in 3-day-old transfused ACD blood and the production of a refractory state of the patient's circulating platelets to ADP induced aggregation played a significant role in the development of platelet function abnormalities during extracorporeal circulation.     

Response to heparinization in adults and children undergoing cardiac operations.

The activated clotting time is an unreliable index of anticoagulation status during cardiopulmonary bypass procedures. However, modern instrumentation (Hemotec Hepcon HMS) now allows the monitoring of free heparin levels via automated protamine titration. In the present study, the standard procedure of anticoagulation at Killingbeck Hospital, Leeds, was investigated. Twenty-two pediatric patients and 20 adult patients undergoing open heart procedures involving cardiopulmonary bypass were given empirical doses of heparin (3 mg/kg body weight bolus), and activated clotting time was maintained at a level greater than 450 seconds using the Hemochron Timer. Heparin neutralization was performed at the termination of the bypass period using an empirical equivalent (3 mg/kg) of protamine sulfate. Mean free heparin concentration (+/- standard deviation) fell from 2.26 (+/- 0.45) mg/kg to 1.39 (+/- 0.34) mg/kg over the period 10 to 40 minutes on bypass in children. In adults, free heparin level declined from 2.56 (+/- 0.58) mg/kg to 1.81 (+/- 0.58) mg/kg over the same period. The biological half-life for heparin was 60 minutes in adults and 35 minutes in pediatric patients. Empirical protamine dosing resulted in excess protamine administration when compared with Hepcon titrated dose requirements: for children: median (range), 80 (12 to 350) versus 33 (12 to 97) mg, p less than 0.001; and for adults: 350 (200 to 500) versus 130 (61 to 237) mg, p less than 0.001. In conclusion, empirical heparin administration (3 mg/kg) does not result in "steady-state" anticoagulation during cardiopulmonary bypass, and empirical administration of protamine takes no account of interindividual differences in heparin sensitivity and biological half-life, which may be assessed using the Hepcon HMS.     

Relationship between granulocyte elastase and C3a under protamine dosing in on-pump cardiac surgery.

OBJECTIVE: The complement cascade and granulocytes are activated in on-pump cardiac surgery. If activation of complement directly regulates granulocytes, granulocyte elastase (GEL) should increase significantly after protamine administration. We examined the effect of protamine on granulocytes by protamine administration and observation of the effect on GEL and C3a. METHODS: Thirty patients who underwent coronary artery bypass grafting were randomly assigned to two groups. In 15 patients, protamine was administered 5 min after the termination of cardiopulmonary bypass, and was administered 35 min after cardiopulmonary bypass in the other 15 patients. All patients were perfused with heparin-coated circuits and received 300 IU/kg heparin and 3 mg/kg protamine. GEL and C3a concentrations were measured at 7 time points. RESULTS: GEL concentrations increased significantly just before aortic declamping and did not increase significantly after protamine administration. C3a concentrations, however, did not increase during cardiopulmonary bypass and did increase significantly after protamine administration. CONCLUSIONS: This study indicates that GEL does not increase after protamine administration and that complement concentration does not directly affect GEL release.     

Heparin Monitoring and Neutralization during Cardiopulmonary Bypass Using a Rapid Plasma Separator and a Fluorometric Assay

Avoidance of over- or underheparinization during cardiopulmonary bypass (CPB) is crucial in preventing bleeding or clotting. Currently no completely satisfactory method is available for measuring heparin levels—a method that would be rapid, inexpensive, specific, and reproducible. We combined the use of two devices, a rapid plasma separator and a fluorometric heparin assay system, in an attempt to satisfy these requirements in 15 patients having CPB during cardiac surgical procedures. The first instrument separates plasma from whole blood using a pneumatic filtration principle, while the heparin assay system measures the effect of heparin on thrombin conversion of a synthetic fluorogenic substrate. Accurate plasma heparin levels can be generated in less than five minutes, and the assays are inexpensive and easy to perform. Performing heparin assays at critical intervals during CPB allowed desired heparin levels to be maintained and the protamine dose for heparin neutralization to be reduced to a minimum. In addition, studies for heparin rebound revealed negligible rebound up to six hours postoperatively despite the reduced doses of protamine. There were no hemorrhagic or clotting complications in the series.