Mediastinal Bleeding After Cardiopulmonary Bypass in Pediatric Patients

Background. The purpose of our review was to develop simple clinical recommendations to reduce the need for allogeneic blood transfusions in children undergoing cardiac operations.

Methods. The literature on hemostasis as it relates to children, cardiac disease in children, and pediatric heart surgery was reviewed. We also reexamined the efficacy of several strategies in this patient population: on-site monitoring of coagulation, transfusion of fresh whole blood, and administration of desmopressin, ε-aminocaproic acid, or aprotinin.

Results. Children with heart disease may present with preoperative thrombocytopenia, reduced platelet aggregation, and a decreased level of von Willebrand factor. Infants less than 6 months of age show a significant dilution of coagulation factors and decreased platelet counts during cardiopulmonary bypass. Fresh whole blood reduces blood loss in children younger than 2 years undergoing complex operations. Desmopressin does not reduce bleeding, whereas on-site monitoring, synthetic antifibrinolytics, and aprotinin require further evaluation in pediatric cardiac surgical patients.

Conclusions. The use of fresh whole blood to reduce blood loss in children younger than 2 years undergoing complex heart operations is recommended. Therapy for excessive bleeding after cardiopulmonary bypass will vary according to the patient's age, platelet count, and activated partial thromboplastin and prothrombin times.     

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.     

Blood management issues: getting clots together when you want them

Coagulation is a complex process that allows whole blood to form clots at tissue and vessel sites where damage has occurred. Activation of the hemostasis system causes platelets and fibrin-containing clot to stop the bleeding. Perfusionists must find ways to preserve the coagulation system if we are to avoid bleeding in the cardiopulmonary bypass patient. It is still unclear what techniques are best to continue maintaining hemostasis and avoiding transfusion in patients requiring cardiopulmonary bypass (CPB). There are numerous factors that come into play with the use of CPB including deactivating the coagulation system with anticoagulants, hemodilution of the circulating blood volume, inflammatory response, and a possible pro-coagulant response from protamine with heparin reversal once the surgical procedure has been completed and CPB terminated. All these factors make achieving hemostasis post CPB extremely difficult. This review attempts to assess what is currently being discussed in the literature, which may improve hemostasis with cardiopulmonary bypass. There is still no one technique that will improve hemostasis post CPB. Perhaps the answer may lie in a combination of reported techniques that may in some way lead to the preserving of coagulation factors during CPB.     

On-site coagulation monitoring does not affect hemostatic outcome after cardiac surgery

BACKGROUND: Rapid coagulation tests are now available for monitoring of bleeding patients after cardiac surgery. As inappropriate blood use in these patients may be due to lack of timely coagulation data, we studied the effect of an algorithm with on-line coagulation monitoring on transfusions in these patients. METHODS: Prospectively, patients bleeding (>1.5 ml kg(-1) 15 min(-1)) after cardiac surgery were randomly assigned to two groups: in group A (n=28), hemostatic treatment during the immediate recovery period (1 h after surgery) was based on an algorithm with on-site hemostasis monitoring, whereas during the same period group B patients (n=30) were managed solely according to the clinician's judgement; laboratory tests other than activated clotting time after heparin neutralization were prohibited. RESULTS: Cumulative chest tube drainage up to 16 h and total transfusion requirements did not differ between the groups. Using a platelet transfusion trigger of 100x10(9)/l, significantly more patients received platelets during the immediate recovery period in the algorithm group than in the control group (14 vs. 3 patients, P=0.001). Desmopressin acetate was administered more often in group A than in group B (8 vs. 2 patients, P=0.04). CONCLUSIONS: Algorithm-based therapy increased utilization of hemostatic interventions during the immediate recovery period without any obvious benefit to the hemostatic outcome. Re-evaluation of the platelet transfusion trigger seems warranted.     

Heparin dosing and monitoring for cardiopulmonary bypass. A comparison of techniques with measurement of subclinical plasma coagulation

Subclinical plasma coagulation during cardiopulmonary bypass has been associated with marked platelet and clotting factor consumption in monkeys. To better define subclinical coagulation in man, we measured plasma fibrinopeptide A concentrations before, during, and after cardiopulmonary bypass. Patients were assigned to one of three groups of heparin management: group 1 (n = 10)--initial heparin dose 300 IU/kg, with supplemental heparin if the activated coagulation time fell below 400 seconds; group 2 (n = 6)--initial heparin dose 250 IU/kg, with supplemental heparin if activated coagulation time was less than 400 seconds; and group 3 (n = 5)--initial heparin dose 350 to 400 IU/kg, with supplemental heparin if whole blood heparin concentration was less than or equal to 4.1 IU/ml. Activated coagulation time and heparin concentration were measured every 30 minutes during cardiopulmonary bypass, and fibrinopeptide A was measured at hypothermia, normothermia, and whenever activated coagulation time was less than 400 seconds. Quantitative and qualitative blood clotting competence was assessed after cardiopulmonary bypass, including mediastinal drainage for the first 24 hours. Fibrinopeptide A values were markedly elevated during cardiopulmonary bypass but were well below the levels present before and after cardiopulmonary bypass. Fibrinopeptide A correlated inversely with heparin concentration during cardiopulmonary bypass (r = -0.46, p = 0.03), but higher fibrinopeptide A levels during cardiopulmonary bypass did not correlate with post-cardiopulmonary bypass coagulopathy. Group 3 patients received the highest heparin doses (p less than 0.05) and had the greatest postoperative blood loss (p less than 0.05). Protamine dose and heparin concentration during cardiopulmonary bypass correlated best with postoperative mediastinal drainage. Our findings support the following conclusions: (1) compensated subclinical plasma coagulation activity occurs during cardiopulmonary bypass despite activated coagulation time greater than 400 seconds or heparin concentration greater than or equal to 4.1 IU/ml; (2) post-cardiopulmonary bypass mediastinal drainage correlates strongly with increased heparin concentration during cardiopulmonary bypass (p less than 0.05) and protamine dose (p less than 0.05); and (3) during cardiopulmonary bypass at both normothermia and hypothermia, activated coagulation times greater than 350 seconds result in acceptable fibrinopeptide A levels and post-cardiopulmonary bypass blood clotting.     

Modified Ultrafiltration Attenuates Dilutional Coagulopathy in Pediatric Open Heart Operations

Background. Extreme hemodilution caused by relatively large prime volumes required for cardiopulmonary bypass in infants causes a dilutional coagulopathy, characterized by low concentrations of fibrinogen and other circulating coagulation factors. Modified ultrafiltration results in hemoconcentration and is associated with decreases in postoperative bleeding and transfusion requirements in children. This study was undertaken to quantify the effect of modified ultrafiltration on concentrations of fibrinogen, plasma proteins, and platelets in infants and small children.

Methods. Twenty patients less than 15 kg were studied. Cardiopulmonary bypass circuits were primed with crystalloid solutions. Red blood cells were added during cardiopulmonary bypass for hematocrits less than 15%. Colloid solutions were not administered. Concentrations of fibrinogen, plasma proteins, and platelets, and hematocrit were measured before cardiopulmonary bypass, before modified ultrafiltration, and after modified ultrafiltration.

Results. Modified ultrafiltration was associated with significant (p < 0.001) increases in hematocrit (19% ± 6% to 31% ± 9%), fibrinogen (65 ± 29 to 101 ± 45 mg/dL), and total plasma proteins (2.7 ± 0.3 to 4.9 ± 0.7 g/dL), but no change (p = 0.129) in platelet count.

Conclusions. We conclude that modified ultrafiltration significantly attenuates the dilutional coagulopathy associated with cardiopulmonary bypass in infants.     

Management of bleeding and coagulopathy after heart surgery

Mechanisms of bleeding common to virtually all patients after heart surgery are platelet dysfunction, enhanced fibrinolysis, dilution of all components of the coagulation system, and the presence of heparin and protamine. The use of warfarin is increasing in patients with heart disease requiring surgery. The replenishment of vitamin K-dependent factors beyond a normal prothrombin time is not assessable, and the dilution associated with cardiopulmonary bypass can reach coagulopathic levels. Optimal preoperative preparation is required and intraoperative therapy initiated when indicated. Individualized heparin and protamine dosing, antifibrinolytic drug administration, minimization of blood loss and dilution, and minimal time on cardiopulmonary bypass are basic adjuncts to meticulous surgical hemostasis. When bleeding is observed in the postoperative period, a sequential assessment of the probable cause leads to initial therapy while laboratory test results are obtained. Ongoing assessment for hemodynamic instability caused by accumulated mediastinal blood is needed while managing the bleeding patient. A chest radiograph and transesophageal echocardiogram can be useful in diagnosing cardiac tamponade.     

Efficacy of a simple intraoperative transfusion algorithm for nonerythrocyte component utilization after cardiopulmonary bypass

BACKGROUND: Abnormal bleeding after cardiopulmonary bypass (CPB) is a common complication of cardiac surgery, with important health and economic consequences. Coagulation test-based algorithms may reduce transfusion of non-erythrocyte allogeneic blood in patients with abnormal bleeding. METHODS: The authors performed a randomized prospective trial comparing allogeneic transfusion practices in 92 adult patients with abnormal bleeding after CPB. Patients with abnormal bleeding were randomized to one of two groups: a control group following individual anesthesiologist's transfusion practices and a protocol group using a transfusion algorithm guided by coagulation tests. RESULTS: Among 836 eligible patients having all types of elective cardiac surgery requiring CPB, 92 patients developed abnormal bleeding after CPB (incidence, 11%). The transfusion algorithm group received less allogeneic fresh frozen plasma in the operating room after CPB (median, 0 units; range, 0-7 units) than the control group (median, 3 units; range, 0-10 units) (P = 0.0002). The median number of platelet units transfused in the operating room after CPB was 4 (range, 0-12) in the algorithm group compared with 6 (range, 0-18) in the control group (P = 0.0001). Intensive care unit (ICU) mediastinal blood loss was significantly less in the algorithm group. Multivariate analysis demonstrated that transfusion algorithm use resulted in reduced ICU blood loss. The control group also had a significantly greater incidence of surgical reoperation of the mediastinum for bleeding (11.8% vs. 0%; P = 0.032). CONCLUSIONS: Use of a coagulation test-based transfusion algorithm in cardiac surgery patients with abnormal bleeding after CPB reduced non-erythrocyte allogeneic transfusions in the operating room and ICU blood loss.     

Desmopressin does not reduce bleeding and transfusion requirements in congenital heart operations

Background. Desmopressin (DDAVP) has been evaluated in many randomized clinical trials as a means to reduce blood loss and transfusion of allogeneic blood in cardiac operation requiring cardiopulmonary bypass. Desmopressin reduces blood loss in adult patients with excessive bleeding after cardiac operation. Its usefulness in patients undergoing complex congenital heart repair with cardiopulmonary bypass is unproved.

Methods. Sixty patients younger than 40 years of age scheduled for complex congenital heart operation (44 redo, 16 primary) were enrolled in this prospective, randomized, double-blind trial. Desmopressin 0.3 μg/kg or placebo was administered 10 minutes after protamine administration. Transfusion requirements and postoperative blood loss were recorded. Differences were analyzed using analysis of variance with a p value of 0.05 or less used to denote statistical significance.

Results. There were no differences in demographic or surgical characteristics between the DDAVP or placebo groups. There was no difference in blood loss and transfusion requirements between the DDAVP and placebo groups. During the intraoperative postinfusion time period, the median blood loss for redo patients was 343 versus 357 mL/m² for placebo versus DDAVP, respectively, and for primary patients, the median blood loss was 277 versus 228 mL/m².

Conclusions. The prophylactic use of DDAVP to reduce excessive bleeding or transfusion requirements in patients undergoing complex congenital heart operations is not warranted.     

Anti-bleeding effect of nafamostat mesilate for the surgery of thoracic ascending aorta

During extracorporeal cardiopulmonary bypass (ECB), the activated coagulation and fibrinogenolysis system causes bleeding and postoperative multiple organ failures. We studied the effect of an anti-bleeding agent, nafamostat mesilate (NM) during the surgery of thoracic ascending aorta to decrease a side effect of bleeding. From March 1980 to January 1998, for thoracic ascending aorta operations in our department (true aneurysm, 16-, psudoaneurysm, 2-, and dissection, 11 cases, in 29 cases, respectively), age from 16 to 79 (mean 62.9 +/- 9.5 year of age), we classified the objects in two groups, NM group (intraoperative infusion with NM of 60 mg/hr and with heparin 300 IU/kg) and C group (only with heparin treated, 500 IU/kg). We investigated the preoperative factors (age and aneurysmal diameter), the intraoperative factors (ACT, hematcrit, platelet, aorta clamping time, operative time, ECB time, bleeding volume, and blood transfusion), and the postoperative factors (bleeding and blood transfusion) after the administration of NM. RESULTS: There was no significance for the protection effect of NM infusion on the preoperative and the postoperative factors. However, intraoperative bleeding and blood transfusion volume in NM group were significantly lesser than those in group C. CONCLUSIONS: It might be useful for NM infusion during the surgery of thoracic ascending aorta due to the decrease of volume of intraoperative bleeding and blood transfusion amount with the remarkable anti-bleeding effect.     

Optimal Management of Bleeding and Transfusion in Patients Undergoing Cardiac Surgery

Patients undergoing cardiac surgery with cardiopulmonary bypass (CPB) are at increased risk for excessive perioperative blood loss requiring transfusion of blood products. Point-of-care evaluation of platelets, coagulation factors, and fibrinogen can enable physicians to rapidly assess bleeding abnormalities, facilitate the optimal administration of pharmacological and transfusion-based therapy, and also identify patients with surgical bleeding. The ability to reduce the unnecessary use of blood products in this setting has important implications for emerging issues in blood inventory and blood costs. The ability to decrease surgical time, along with exploration rates, has important consequences for health care costs in an increasingly managed health care environment.     

Multivariate predictors of blood product use in cardiac surgery

OBJECTIVE: To determine factors associated with an increased risk of post-cardiopulmonary bypass (CPB) blood product usage in adult cardiac surgical patients. DESIGN: Prospective observational study. SETTING: Academic hospital. PARTICIPANTS: Patients undergoing cardiac surgery with CPB were studied over a 7-month period. INTERVENTIONS: The outcomes studied were receipt of more than 2 U of packed red blood cells (PRBCs), receipt of any other blood component products (cryoprecipitate, fresh-frozen plasma [FFP], or platelets), or surgical re-exploration for bleeding. Preoperative and intraoperative risk factors for bleeding were analyzed. MEASUREMENTS AND MAIN RESULTS: Increased age and preoperative creatinine level, low body surface area, preoperative hematocrit, nonelective surgery, lower temperature on bypass, and duration of bypass were associated with an increased risk of transfusion of >2 U of PRBCs. Low body surface area, repeat surgery, nonelective surgery, and CPB time were associated with transfusion of platelets, fresh-frozen plasma, or cryoprecipitate and/or surgical re-exploration. The following factors were associated with neither transfusion of more than 2 U of PRBC nor transfusion of platelets, FFP or cryoprecipitate, or surgical re-exploration: gender, preoperative international normalized ratio, preoperative antiplatelet medications, and preoperative intravenous heparin. CONCLUSION: Therapies aimed at reducing transfusion of blood products should be aimed at those patients with low body surface areas, baseline anemia, and those undergoing long or repeat surgeries.     

Thrombography reveals thrombin generation potential continues to deteriorate following cardiopulmonary bypass surgery despite adequate hemostasis

The intrinsic and extrinsic activation pathways of the hemostatic system converge when prothrombin is converted to thrombin. The ability to generate an adequate thrombin burst is the most central aspect of the coagulation cascade. The thrombin-generating potential in patients following cardiopulmonary bypass (CPB) may be indicative of their hemostatic status. In this report, thrombography, a unique technique for directly measuring the potential of patients' blood samples to generate adequate thrombin bursts, is used to characterize the coagulopathic profile in post-CPB patients. Post-CPB hemostasis is typically achieved with protamine reversal of heparin anticoagulation and occasionally supplemented with blood product component transfusions. In this pilot study, platelet poor plasma samples were derived from 11 primary cardiac surgery patients at five time points: prior to CPB, immediately post-protamine, upon arrival to the intensive care unit (ICU), 3 hours post-ICU admission, and 24 hours after ICU arrival. Thrombography revealed that the Endogenous Thrombin Potential (ETP) was not different between [Baseline] and [PostProtamine] but proceeded to deteriorate in the immediate postoperative period. At the [3HourPostICU] time point, the ETP was significantly lower than the [Baseline] values, 1233 +/- 591 versus 595 +/- 379 nM.min (mean +/- SD; n=9, p < .005), despite continued adequacy of hemostasis. ETPs returned to baseline values the day after surgery. Transfusions received, conventional blood coagulation testing results, and blood loss volumes are also presented. Despite adequate hemostasis, thrombography reveals an underlying coagulopathic process that could put some cardiac surgical patients at risk for postoperative bleeding. Thrombography is a novel technique that could be developed into a useful tool for perfusionists and physicians to identify coagulopathies and optimize blood management following CPB.     

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.     

Intraoperative cell salvage in infants undergoing elective cardiac surgery: a prospective trial

BACKGROUND: For a long time intraoperative cell salvage was considered not to be applicable in paediatric patients due to technical limitations. Recently, new autotransfusion devices with small volume centrifugal bowls and dedicated paediatric systems allow efficient blood salvage in small children. The purpose of this prospective non-randomised study was to determine the impact of intraoperative cell salvage on postoperative allogeneic blood products transfusion in infant patients undergoing cardiac surgery with cardiopulmonary bypass. METHODS: Two consecutive cohorts (122 patients) were studied. The first cohort underwent procedures between January 2004 and July 2005 with only blood salvage from the residual volume. The second cohort consisted of patients operated on from August 2005 to December 2006, with additional use of intraoperative cell salvage. The following variables were analysed: peri- and postoperative blood loss, transfusion of homologous blood products and cell salvage product, haematological and coagulation data, measured before, during and after the operation. RESULTS: Additional intraoperative cell salvage significantly enhanced the amount of cell saving product available for transfusion (183+/-56 ml vs 152+/-57 ml, p=0.003) and significantly more patients in this group received the cell saving product postoperatively. Consequently, allogeneic blood transfusion was significantly reduced in volume as well as in frequency. We did not observe any adverse effects of intraoperative cell salvage. CONCLUSION: Intraoperative cell salvage, employed as an adjuvant technique to the residual volume salvage in infants undergoing first time cardiac surgery with cardiopulmonary bypass, was a safe and effective method to reduce postoperative allogeneic blood transfusion. Considering current cell salvage related expense and the cost reduction achieved by diminished allogeneic transfusion, intraoperative cell salvage in infants demonstrated no economic benefit.     

Effects of heparin, haemodilution and aprotinin on kaolin-based activated clotting time: in vitro comparison of two different point of care devices

BACKGROUND: During cardiopulmonary bypass (CPB), measurement of kaolin-based activated clotting time (kACT) is a standard practice in monitoring heparin-induced anticoagulation. Despite the fact that the kACT test from the Sonoclot Analyzer (SkACT) has been commercially available for several years, no published data on the performance of SkACT are available. Thus, the aim of this in vitro study was to compare SkACT with an established kACT from Hemochron (HkACT). METHODS: Blood was withdrawn from 25 patients before elective cardiac surgery. SkACT and HkACT were measured in duplicate after in vitro administration of heparin (0, 1, 2 and 3 U/ml), calcium-free lactated Ringer's solution (25% and 50% haemodilution) and aprotinin (200 kIU/ml). RESULTS: A total of 600 duplicate kACT measurements were obtained from 25 cardiac surgery patients. Overall, mean bias +/- SD between SkACT and HkACT was 7 +/- 70 s (1.3% +/- 14.1%). Administration of heparin, haemodilution and aprotinin induced a comparable effect on both activated clotting time (ACT) tests. Mean bias ranged from -4 +/- 39 s (-1.7% +/- 12.9%) to 4 +/- 78 s (3.2% +/- 15.6%) for heparinzed blood samples after haemodilution or aprotinin application and increased after combined aprotinin administration and haemodilution. After haemodilution and administration of aprotinin, both ACT tests were less reliable for values >480 s in heparinized blood samples. CONCLUSION: Accuracy and performance of SkACT and HkACT were comparable after in vitro administration of heparin, aprotinin and haemodilution. Both ACT tests were considerably affected by aprotinin and haemodilution.     

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.     

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.     

Heparin management protocol for cardiopulmonary bypass influences postoperative heparin rebound but not bleeding.

A group of 63 adult patients undergoing cardiac surgical procedures requiring cardiopulmonary bypass (CPB) were studied to examine the relationship between heparin doses administered and postoperative bleeding. Patients were randomly assigned either to receive heparin 200 U/kg and additional heparin as needed to reach and maintain an activated clotting time (ACT) greater than 400 s for CPB (group A, n = 30), or to receive heparin 400 U/kg and additional heparin as needed to reach and maintain a whole blood heparin concentration greater than 4.0 U/ml for CPB (group H, n = 33). Groups were compared for the amount of postoperative bleeding, heparin rebound, homologous transfusion requirements, and standard laboratory coagulation tests. In the last 33 patients studied, additional tests of platelet aggregation and plasma levels of beta thromboglobulin (BTG), antithrombin III, and several markers of fibrinolysis were measured and compared by group. The mean heparin dose was 28,000 +/- 4,800 U for group A and 57,000 +/- 10,700 U for group H (P less than 0.05 for group A vs. group H). At 8 and 24 h postoperatively, mediastinal drainage did not differ significantly between groups (mean 24-h drainage +/- SD = 901 +/- 414 ml in group A, 1035 +/- 501 ml in group H), nor did the incidence of transfusion with homologous blood products.(ABSTRACT TRUNCATED AT 250 WORDS)     

A comparison of low vs conventional-dose heparin for minimal cardiopulmonary bypass in coronary artery bypass grafting surgery

The biocompatibility of minimal extracorporeal circuits has improved; however, anticoagulation is still required. 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 cardiopulmonary bypass. One hundred patients who received 300 IU.kg(-1) heparin were compared with 68 patients who received heparin according to an individually adjusted activated coagulation time target of 300 s, resulting in a mean (SD) heparin dose of 145 (30) IU.kg(-1) . There were no thromboembolic events in either group; however, patients in the low-dose group had lower 24-hour mean (SD) postoperative blood loss than the conventional group (545 (61) vs 680 (88) ml, p=0.001) and a reduced rate of transfusion of allogeneic blood (15% patients transfused vs 32%, p=0.01). An individually tailored low-dose heparin regimen for minimal cardiopulmonary bypass is safe and may be associated with reduced bleeding and lower transfusion requirements.