Correlations between global clotting function tests, duration of operation, and postoperative chest tube drainage in pediatric cardiac surgery

Background: Systemic coagulation disorders after cardiac surgery represent serious postoperative complications. There have been few reports, however, identifying preoperative coagulation tests that predict postoperative bleeding. The aim of the present study was to investigate the relationship between postoperative hemorrhage and coagulation parameters determined by global coagulation assays, to define potential predictive markers. Methods: Twenty‐one pediatric patients were enrolled. Blood samples were collected before and 24 h after cardiac surgery. Laboratory investigations included platelet count, hematocrit, classical coagulation tests [prothrombin time, activated partial thromboplastin time, thrombin‐antithrombin complex (TAT)], rotation thromboelastometry (ROTEM), and the thrombin generation test (TGT). The duration of the surgical procedure was recorded. Chest tube drainage was monitored for 24 h after operation as an index of postoperative hemorrhage. Results: Comparisons between preoperative and postoperative results indicated that TAT increased significantly after operation, whereas ROTEM parameters did not show a hypercoagulable pattern. Preoperative endogenous thrombin potential (ETP) measured in the TGT and clot formation time (CFT) in the ROTEM correlated with chest tube drainage. The classical coagulation tests were not informative. Postoperatively, peak height and ETP in TGT, all ROTEM parameters, and duration of surgery were correlated with chest tube drainage. Duration of surgery was correlated with postoperative ROTEM parameters but not with TGT. Postoperative maximum clot firmness and AUC were correlated with platelet count decrease ratio. Conclusions: The preoperative CFT and ETP provide useful indices for predicting postoperative chest tube drainage volume. In addition, the duration of surgery also correlated with chest tube drainage and affected ROTEM parameters.     

Bleeding following deep hypothermia and circulatory arrest in children

Deep hypothermic circulatory arrest (DHCA) is a technique of extracorporeal circulation commonly used in children with complex congenital heart defects undergoing surgical repairs. The use of profound cooling (20 degrees C) and complete cessation of circulation allow adequate exposure and correction of these complex lesions, with enhanced cerebral protection. However, the profound physiologic state of DHCA results in significant derangement of the coagulation system and a high incidence of postoperative bleeding. This review examines the impact of DHCA on bleeding and transfusion requirements in children and the pathophysiology of DHCA-induced platelet dysfunction. It also focuses on possible pharmacologic interventions to decrease bleeding following DHCA in children.     

Platelet-activated clotting time does not measure platelet reactivity during cardiac surgery.

BACKGROUND: Platelet dysfunction is a major contributor to bleeding after cardiopulmonary bypass (CPB), yet it remains difficult to diagnose. A point-of-care monitor, the platelet-activated clotting time (PACT), measures accelerated shortening of the kaolin-activated clotting time by addition of platelet activating factor. The authors sought to evaluate the clinical utility of the PACT by conducting serial measurements of PACT during cardiac surgery and correlating postoperative measurements with blood loss. METHODS: In 50 cardiac surgical patients, blood was sampled at 10 time points to measure PACT. Simultaneously, platelet reactivity was measured by the thrombin receptor agonist peptide-induced expression of P-selectin, using flow cytometry. These tests were temporally analyzed. PACT values, P-selectin expression, and other coagulation tests were analyzed for correlation with postoperative chest tube drainage. RESULTS: PACT and P-selectin expression were maximally reduced after protamine administration. Changes in PACT did not correlate with changes in P-selectin expression at any time interval. Total 8-h chest tube drainage did not correlate with any coagulation test at any time point except with P-selectin expression after protamine administration (r = -0.4; P = 0.03). CONCLUSIONS: The platelet dysfunction associated with CPB may be a result of depressed platelet reactivity, as shown by thrombin receptor activating peptide-induced P-selectin expression. Changes in PACT did not correlate with blood loss or with changes in P-selectin expression suggesting that PACT is not a specific measure of platelet reactivity.     

Optimization of thromboelastography-guided platelet transfusion in cardiovascular surgery

Objectives  

Platelet dysfunction is a major cause of bleeding complications in patients undergoing cardiovascular surgery under cardiopulmonary bypass (CPB). Thromboelastography (TEG) can be used to assess post-CPB coagulopathy, but its utility in guiding platelet transfusion (PT) after CPB is unclear. This study assessed the utility of a TEG-guided PT protocol in patients undergoing cardiovascular surgery under CPB.     

Gerinnungsmanagement bei Eingriffen mit extrakorporaler Zirkulation

After cardiac surgery with extracorporeal circulation, approximately 20% of patients show significant bleeding tendencies and 5% require re-intervention. In 50% of patients undergoing re-operation, no surgical cause can be determined, suggesting coagulopathy after cardiopulmonary bypass (CPB). For perioperative management of transfusion of blood products and coagulation factor concentrates, a clinical algorithm for the perioperative hemostatic therapy in patients undergoing cardiac surgery with CPB has been developed. The currently available evidence and the point of care methods routinely accessible in our institution (blood gas analysis, ACT, point of care Quick value, aPTT and platelet count) were used. The intervention with plasma products, coagulation factor concentrates and hemostatic drugs after extracorporeal circulation are described. Extensive bleeding history as well as the efficacy and side effects of antifibrinolytic treatment are discussed.     

Coagulation Profile of Neonates Undergoing Arterial Switch Surgery With Crystalloid Priming of the Cardiopulmonary Bypass Circuit

ObjectivesThe aim was to evaluate changes in the coagulation profile of cyanotic neonates, to analyze the effects of cardiopulmonary bypass (CPB) with crystalloid priming on their coagulation status, and to determine factors predicting a requirement for hemostasis-derived transfusion.DesignRetrospective cohort.SettingSingle-center, tertiary academic hospital.ParticipantsIn total, 100 consecutive neonates who underwent arterial switch surgery between December 2014 and June 2020.InterventionsRotational thromboelastometry (ROTEM) and coagulation parameters before surgery and before termination of CPB were evaluated. Transfusion of platelets, fresh frozen plasma, and fibrinogen, defined as hemostasis-derived transfusion (HD transfusion), were determined. Patients with and without HD transfusion were compared to identify predictors.Measurements and Main ResultsAfter CPB, fibrinogen was reduced by 24.5% (interquartile range [IQR] 8.9-32.1) to 201 mg/dL (IQR 172-249), resulting in a reduction of FIBTEM A10 by 20% (1.8-33.3) to 8 mm (6-11). The platelet count decreased by a median of 47.2% (25.6-61.3) to 162 × 10³/µL (119-215). However, the median fibrinogen concentration and platelet count remained within normal range. Neonates with abnormal ROTEM results were more likely to receive HD transfusions. The HD transfusions were more likely with lower preoperative FIBTEM maximum clot firmness values (p = 0.031), lower hemoglobin concentrations at termination of CPB (p = 0.02), and longer CPB duration (p = 0.017). Perioperative hemostasis without any HD transfusion was achieved in 64 neonates.ConclusionsGuidance from ROTEM analyses facilitates hemostasis management after neonatal CPB. Circuit miniaturization with transfusion-free CPB is associated with acceptable changes in ROTEM in most patients, and allows sufficient hemostasis without any HD transfusions in most patients.     

The systemic inflammatory response after cardiac surgery with cardiopulmonary bypass in children

Paediatric cardiac surgery often requires cardiopulmonary bypass (CPB) during the surgical intervention. CPB is known to elicit a systemic inflammatory response with activation of the complement and coagulation systems, stimulation of cytokine production, cellular entrapment in organs, neutrophil activation with degranulation, platelet activation, and endothelial dysfunction. These changes are associated with a risk of postoperative organ dysfunction and increased morbidity and mortality in the postoperative period. Clinical studies have concentrated on measurement of inflammatory markers and mediators in peripheral blood, where the systemic inflammatory response in the paediatric cardiac patient seems to be different from the adult case. Looking at the organ level, experimental studies have the advantage of providing information contributing to a better understanding of the pathological events that may lead to the deteriorated organ function. This review focuses on the systemic inflammatory response after cardiac surgery with CPB in children and experimental CPB models.     

婴儿深低温体外循环术后肺表面活性物质的变化

目的 比较婴儿先天性心脏病在深低温停循环(DHCA)或深低温低流量(DHLF)下行心内直视手术后肺表面活性物质(PS)活性水平的变化. 方法 根据采用的体外循环(CPB)方法不同,将20例室间隔缺损伴肺动脉高压的婴儿分为DHCA组和DHLF组,每组10例.测定CPB前,CPB结束5分钟和2小时时PS活性水平的饱和卵磷脂/总磷脂(SatPC/TPL)和饱和卵磷脂/总蛋白(SatPC/TP)值和肺静态顺应性. 结果 DHLF组术后住ICU时间明显长于DHCA组(P<0.05), DHLF组术后SatPC/TPL、SatPC/TP和肺静态顺应性下降的幅度均明显大于DHCA组(P<0.01). 结论 DHLF较DHCA更能引起PS活性水平的降低,从而引起更严重的肺损伤.     

体外循环对血小板功能影响的研究

选择心脏瓣膜替换术病人１０例，用流式细胞术（ＦＣＭ）方法在围术期定量检测血小板质膜蛋白Ｉｂ、ＩＩｂ／ＩＩａ复合物、血小板α颗粒膜蛋白、溶酶体完整膜蛋白－ＣＤ６３及血小板计数等项血小板膜糖蛋白指标进行统计学处理。结果表明体外循环中血小板计数、膜糖蛋白Ｉｂ均明显下降；α－颗粒膜蛋白１４０、溶酶体完整膜蛋白及膜糖蛋白Ｉｂ／ＩＩａ均显著增高。证实体外循环（ＣＰＢ）对血小板膜糖蛋白的影响，更深入了解ＣＰＢ导致血小板功能获得性损害的分子机制。     

Platelet-activated Clotting Time Does Not Measure Platelet Reactivity during Cardiac Surgery

Background: Platelet dysfunction is a major contributor to bleeding after [1] cardiopulmonary bypass (CPB), yet it remains difficult to diagnose. A point-of-care monitor, the platelet-activated clotting time (PACT), measures accelerated shortening of the kaolin-activated clotting time by addition of platelet activating factor. The authors sought to evaluate the clinical utility of the PACT by conducting serial measurements of PACT during cardiac surgery and correlating postoperative measurements with blood loss.

Methods: In 50 cardiac surgical patients, blood was sampled at 10 time points to measure PACT. Simultaneously, platelet reactivity was measured by the thrombin receptor agonist peptide-induced expression of P-selectin, using flow cytometry. These tests were temporally analyzed. PACT values, P-selectin expression, and other coagulation tests were analyzed for correlation with postoperative chest tube drainage.

Results: PACT and P-selectin expression were maximally reduced after protamine administration. Changes in PACT did not correlate with changes in P-selectin expression at any time interval. Total 8-h chest tube drainage did not correlate with any coagulation test at any time point except with P-selectin expression after protamine administration (r = -0.4; P = 0.03).     

Effect of polymer coating (poly 2-methoxyethylacrylate) of the oxygenator on hemostatic markers during cardiopulmonary bypass in children

OBJECTIVE: Heparin and other oxygenator coatings have been used in attempts to reduce hemostatic activation during cardiopulmonary bypass (CPB). This study evaluated whether an oxygenator coated with poly 2-methoxyethylacrylate (PMEA) (X-coating; Terumo Corporation, Tokyo, Japan) would cause less activation of coagulation and fibrinolytic systems during CPB in children than a noncoated oxygenator. DESIGN: Observational study. SETTING: University-affiliated children's hospital. PATIENTS: Twenty-six patients, 3 months to 5 years old, who underwent congenital heart surgery for repair of a ventricular septal defect, atrial septal defect, or both. INTERVENTIONS: Patients were divided into 2 age-matched groups based on the type of oxygenator used: a noncoated oxygenator (group NC) versus a PMEA-coated oxygenator (group C). MEASUREMENTS AND MAIN RESULTS: Blood samples for coagulation and fibrinolytic markers were compared before, during, and after CPB. Despite increases in thrombin generation markers (F1.2 and TAT) at certain times during CPB in group C compared to group NC, a comparison over all times during CPB were not statistically different between groups. Overall D-dimer concentrations during CPB were elevated in group C compared to group NC (p = 0.02). Active tPA and active PAI-1 were not different between groups during or after CPB. Group C had higher platelet counts (181,000 +/- 29,000) during CPB than group NC (155,000 +/- 57,000, p = 0.04) but not postoperatively. Twelve hours postoperatively, chest tube outputs were 8.8 +/- 3 mL/kg in group C and 19.1 +/- 12 mL/kg in group NC (p = 0.003). The corresponding outputs 24 hours after surgery were 12.4 +/- 3 mL/kg and 24 +/- 11 mL/kg, respectively (p = 0.005). CONCLUSIONS: Except for a somewhat higher platelet count during CPB, there was no indication that PMEA coating resulted in less activation of coagulation and fibrinolytic systems. The lower postoperative chest tube output observed after CPB with PMEA-coated oxygenators needs to be studied further.     

Thromboelastometric (ROTEM) findings in patients suffering from isolated severe traumatic brain injury

Severe traumatic brain injury (sTBI) is often accompanied by coagulopathy and an increased risk of bleeding. To identify and successfully treat bleeding disorders associated with sTBI, rapid assessment of coagulation status is crucial. This retrospective study was designed to assess the potential role of whole-blood thromboelastometry (ROTEM(?), Tem International, Munich, Germany) in patients with isolated sTBI (abbreviated injury scale [AIS](head) ≥3 and AIS(extracranial) <3). Blood samples were obtained immediately following admission to the emergency room of the Trauma Centre Salzburg in Austria. ROTEM analysis (EXTEM, INTEM, and FIBTEM tests) and standard laboratory coagulation tests (prothrombin time index [PTI, percentage of normal prothrombin time], activated partial thromboplastin time [aPTT], fibrinogen concentration, and platelet count) were compared between survivors and non-survivors. Out of 88 patients with sTBI enrolled in the study, 66 survived and 22 died. PTI, fibrinogen, and platelet count were significantly higher in survivors (p<0.005). Accordingly, aPTT was shorter in this group (p<0.0001). ROTEM analysis revealed shorter clotting times in extrinsically activated thromboelastometric test (EXTEM) and intrinsically activated thromboelastometric test (INTEM) (p<0.001), shorter clot formation times in EXTEM and INTEM (p<0.0001), and higher maximum clot firmness in EXTEM, INTEM, and FIBTEM (p<0.01) in survivors compared with non-survivors. Logistic regression analysis revealed extrinsically activated thromboelastometric test with cytochalasin D (FIBTEM) MCF and aPTT to have the best predictive value for mortality. According to the degree of coagulopathy, non-survivors received more RBC (p=0.016), fibrinogen concentrate (p=0.01), and prothrombin complex concentrate (p<0.001) within 24?h of arrival in the emergency room. ROTEM testing appeared to offer an early signal of severe life-threatening sTBI. Further studies are warranted to confirm these results and to investigate the role of ROTEM in guiding coagulation therapy.     

Platelet-rich plasma sequestration, with therapeutic platelet yields, reduces allogeneic transfusion in complex cardiac surgery

Platelet dysfunction is the most common cause of nonsurgical bleeding after cardiopulmonary bypass (CPB). We hypothesized that reinfusion of a therapeutic quantity of platelets sequestered before CPB would decrease the need for allogeneic platelet transfusion, as well as decrease bleeding and total allogeneic transfusion, in cardiac surgery patients at moderately high risk for bleeding. Fifty-five patients undergoing either reoperative coronary artery bypass (CABG) or combined CABG and valve replacement were randomized to control or platelet-rich plasma sequestration (pheresis) groups. All patients received intraoperative epsilon-aminocaproic acid infusions. There was no significant difference between groups with respect to preoperative characteristics, duration of CPB, or target postoperative hematocrit. Mean platelet yields were 6.2 +/- 2.1 units (3.1 x 10(11) platelets). Mean pheresis time was 44 min. Allogeneic platelets (range = 6-12 units) were transfused to 28% of control patients, compared with 0% of pheresis patients (P < 0.01). Allogeneic packed red blood cells were transfused to 45% of control patients (1.2 units per patient) versus 31% of pheresis patients (0. 7 unit per patient) (P = 0.35). Total allogeneic units transfused were significantly reduced in the pheresis group (P < 0.02). Mediastinal chest tube drainage was not significantly decreased in the pheresis group. In this prospective, randomized study, therapeutic platelet yields were obtained before CPB. In contrast with recent studies with low platelet yields, these data support the conclusion that platelet-rich plasma sequestration is effective in reducing allogeneic platelet transfusions and total allogeneic units transfused in cardiac surgery patients at moderately high risk for post-CPB coagulopathy and bleeding. IMPLICATIONS: Transfusion of allogeneic blood products, including platelets, is common during complex cardiac surgical procedures. In the present prospective, randomized study, a significant reduction in allogeneic platelet transfusion and total allogeneic units transfused was observed after the reinfusion of a therapeutic quantity of autologous platelets sequestered before cardiopulmonary bypass.     

The predictive value of modified computerized thromboelastography and platelet function analysis for postoperative blood loss in routine cardiac surgery

Hemorrhage after cardiopulmonary bypass (CPB) remains a clinical problem. Point-of-care tests to identify hemostatic disturbances at the bedside are desirable. In the present study, we evaluated the predictive value of two point-of-care tests on postoperative bleeding after routine cardiac surgery. Prospectively, 255 consecutive patients were studied to compare the ability of modified thromboelastography (ROTEG) as well as a platelet function analyzer (PFA-100) to predict postoperative blood loss. Measurements were performed at three time points: preoperatively, during CPB, and after protamine administration with three modified thromboelastography and PFA tests. The best predictors of increased bleeding tendency were the tests performed after CPB. The angle alpha is the best predictor (area under the receiver operating characteristic curve 0.69) and, in combination with the adenosine diphosphate-PFA test, the predictive accuracy is enhanced (area under the receiver operating characteristic curve 0.73). The negative predictive value for the angle alpha is 82%, although the positive predictive value is small (41%). Thromboelastography is a better predictor than PFA. In routine cardiac surgery, impaired hemostasis as identified by point-of-care tests does not inevitably lead to hemorrhage postoperatively. However, patients with normal test results are unlikely to bleed for hemostatic reasons. Bleeding in these patients is probably caused surgically. The high negative predictive value supports early identification and targeted treatment of surgical bleeding by distinguishing it from a significant coagulopathy. IMPLICATIONS: Thrombelastography and platelet function analysis in routine cardiac surgery demonstrate high negative predictive values for postoperative bleeding, which supports early identification and targeted treatment of surgical bleeding by distinguishing it from a significant coagulopathy. The positive predictive values are small. The best predictors are thrombelastography values obtained after cardiopulmonary bypass.     

体外循环对室间隔缺损婴儿手术后肺功能的影响

目的评估体外循环(CPB)对是否合并肺动脉高压先天性室间隔缺损(V SD)婴儿手术后肺功能的影响。方法行V SD修补术婴儿20例,根据是否合并肺动脉高压分为肺动脉高压组和无肺动脉高压组,每组各10例。分别于CPB前、CPB后3 h、6 h、9 h、12 h、15 h、18 h、21 h和24h测定肺功能,并记录手术后机械通气时间和重症监护时间。结果CPB前无肺动脉高压组婴儿肺功能各项指标显著优于肺动脉高压组(P<0.01),但CPB后各时间段除呼吸指数(R I)外其它指标均较术前显著降低(P<0.05),尤以CPB后9 h、12 h和15h较明显(P<0.01)。肺动脉高压组CPB后3h肺功能指标较CPB前改善,但在CPB后9h、12h和15h仍明显较CPB前差(P<0.05);CPB后21h、24h两组婴儿肺功能指标开始接近CPB前。结论CPB对V SD婴儿术后肺功能均有不同程度的损害,但对合并肺动脉高压的婴儿,手术带来的益处超过了CPB对肺的损害;积极改善术后心功能,可避免术后肺功能低谷的出现;若术后心功能稳定、无反应性肺动脉高压和肺动脉高压危象的发生,术前合并肺动脉高压的婴儿同样也能早期撤离呼吸机。     

Bleeding and management of coagulopathy

Bleeding after cardiac surgery remains a significant problem, increasing both length of stay and mortality, and is caused by multiple factors including dilutional changes, ongoing fibrinolysis, and platelet dysfunction. The evaluation of coagulopathy is problematic because of the long turnaround time of standard coagulation tests. Algorithms involving point of care testing, including thromboelastography and thromboelastometry, have been published; all have the potential to reduce transfusion requirements. Massive transfusion coagulopathy that occurs in trauma can also be seen in complex aortic surgery and other massive bleeding patients and should prompt consideration of a transfusion protocol involving fixed ratios of fresh frozen plasma, platelets, and red blood cells. Pharmacologic agents such as antifibrinolytics are commonly administered, but a multimodal approach to management is important. Recombinant and purified coagulation products are being studied and provide clinicians specific agents to treat targeted deficiencies. A general multi-modal approach is required and recommendations are made for the management of bleeding and coagulopathy in cardiac surgical patients.     

不同年龄发绀型先心病患儿围体外循环期凝血功能的比较

Objective To investigate the changes in blood coagulation during cardiopulmonary bypass (CPB) in children of different ages undergoing open heart surgery for cyanotic congenital heart disease.Methods Sixty children with cyanotic congenital heart disease undergoing open heart surgery under CPB were divided into 3 age groups: Group A(age≤12 mort, n=25), Group B (12mon＜age≤24 mon, n= 17) and Group C (24 mon＜ age＜4 yr, n=18). Venous blood samples were taken immediately after induction of anesthesia(T1) and at 10 min after protamine administration (T2)for determination of activated coagulation time (SonACT), clot rate and platelet function (PF) using Sonoclot coagulation and platelet function analyzer-type DP2951 (Sieuco Co., USA).Results There was significant difference in SonACT, clot rate and PF at T1 among the 3 groups: the SonACT was significantly shorter in Groups B and C than in Group A, the clot rate was significantly higher in Group B than in Group C, and the PF was significantly lower in Group C than in Group A. At T2 , the SonACT was significantly prolonged in all 3 groups, the clot rate was significantly decreased in Groups A and B, and the PF was significantly decreased in Group A.Conclusion There are significant differences in blood coagulation and PF among the 3 different age groups of children with cyanotic congenital heart disease after induction of anesthesia and CPB has different effects on their blood coagulation and PF.     

Management of major blood loss: An update

Haemorrhage remains a major cause of potentially preventable deaths. Trauma and massive transfusion are associated with coagulopathy secondary to tissue injury, hypoperfusion, dilution and consumption of clotting factors and platelets. Concepts of damage control surgery have evolved, prioritizing the early control of the cause of bleeding by non‐definitive means, while haemostatic control resuscitation seeks early control of coagulopathy. Haemostatic resuscitation provides transfusions with plasma and platelets in addition to red blood cells (RBCs) in an immediate and sustained manner as part of the transfusion protocol for massively bleeding patients. Transfusion of RBCs, plasma and platelets in a similar proportion as in whole blood prevents both hypovolaemia and coagulopathy. Although an early and effective reversal of coagulopathy is documented, the most effective means of preventing coagulopathy of massive transfusion remains debated and randomized controlled studies are lacking. Results from recent before‐and‐after studies in massively bleeding patients indicate that trauma exsanguination protocols involving the early administration of plasma and platelets are associated with improved survival. Furthermore, viscoelastic whole blood assays, such as thrombelastography (TEG)/rotation thromboelastometry (ROTEM), appear advantageous for identifying coagulopathy in patients with severe haemorrhage, as opposed to conventional coagulation assays. In our view, patients with uncontrolled bleeding, regardless of its cause, should be treated with goal‐directed haemostatic control resuscitation involving the early administration of plasma and platelets and based on the results of the TEG/ROTEM analysis. The aim of the goal‐directed therapy should be to maintain a normal haemostatic competence until surgical haemostasis is achieved, as this appears to be associated with reduced mortality.     

Histamine release during cardiopulmonary bypass in neonates and infants

Purpose

Histamine release has been previously documented in adults and children during cardiopulmonary bypass (CPB). It has not been studied in neonates nor during deep hypothermic circulatory arrest (DHCA). Histamine effects could explain many penoperative complications of congenital cardiac surgery such as dysrhythmias and massive oedema. Therefore, documentation of histamine release in the penoperative period is of clinical importance. The source of histamine can be determined by measurement of tryptase which is released with histamine from mast cells but not basophils.

Methods

Blood samples for histamine and tryptase were taken before and after specific events eg. cross-damp removal, during anaesthesia and CPB in 14 infants and seven neonates undergoing complex congenital heart repairs and were analysed by commercial radiommunoassays. Haemodynamic variables and pre and post-op weights were recorded to look for correlation between pathophysiologcal events and histamine release.

Results

Histamine concentration decreased at the start of bypass (0.69 to 0.38 ng · ml^?1 at five minutes, (P < .005). There were no changes associated with DHCA and a small rise with reventilation (P < 0.02). Histamine concentration was lower in neonates than in infants (P < 0.05) during CPB. Plasma histamine and tryptase concentrations did not correlate, suggesting histamine release was from basophils and not from mast celts. Haemodynamic variables did not correlate with histamine concentrations.

Conclusion

There was no major histamine release during CPB in infants and neonates. There was no relationship between histamine concentrations and dinical variables. Histamine released during CPB appears to come from basophils and may be a function of age.     

Infant cardiopulmonary bypass: a procoagulant state.

BACKGROUND: Procoagulant activity after cardiopulmonary bypass (CPB) in infants may predispose to thrombotic and bleeding complications. The induction of tissue factor and prothrombinase activity on endothelial cell membranes is a primary step in the activation of the extrinsic clotting cascade. The purpose of this study is to characterize the fibrinolytic and endothelial procoagulant state in infants undergoing congenital cardiac repairs with and without CPB. METHODS: Fourteen infants (aged 1 to 12 weeks) underwent repair of congenital cardiac defects. Two patients had closed procedures (controls) and 12 had open cardiac procedures. Serum samples were taken before and after CPB, 1, 4, and 24 hours after CPB. Tissue plasminogen activator, plasminogen activator inhibitor-1, interleukin-1beta, interleukin-6, plasma tissue factor, and factor V levels were measured. Human umbilical vein endothelial cell cultures were incubated with serum taken from the above time points and assayed for induction of tissue factor and prothrombinase activity. RESULTS: Control patients had no change from preoperative values in any of the parameters examined. In experimental patients, tissue plasminogen activator levels peaked at 1 hour after CPB and then decreased to normal by 24 hours. Plasminogen activator inhibitor-1 levels peaked at 4 hours after CPB and returned to baseline by 24 hours. The plasma of all patients had no intrinsic tissue factor activity. Induction of tissue factor activity on umbilical vein endothelial cells peaked immediately and again at 24 hours, whereas prothrombinase activity peaked early and stayed elevated. Serum factor V levels were significantly reduced after CPB, but returned to near baseline levels by 24 hours. CONCLUSIONS: Cardiopulmonary bypass is associated with derangement of the coagulation and fibrinolytic systems in infants. The serum of these patients promotes the induction of endothelial procoagulant activity, suggesting that there may be a hypercoagulable state in the postbypass period.