A European consensus statement on the use of four-factor prothrombin complex concentrate for cardiac and non-cardiac surgical patients.

Modern four-factor prothrombin complex concentrate was designed originally for rapid targeted replacement of the coagulation factors II, VII, IX and X. Dosing strategies for the approved indication of vitamin K antagonist-related bleeding vary greatly. They include INR and bodyweight-related protocols as well as fixed dose regimens. Particularly in the massively bleeding trauma and cardiac surgery patient, four-factor prothrombin complex concentrate is used increasingly for haemostatic resuscitation. Members of the Transfusion and Haemostasis Subcommittee of the European Association of Cardiothoracic Anaesthesiology performed a systematic literature review on four-factor prothrombin complex concentrate. The available evidence has been summarised for dosing, efficacy, drug safety and monitoring strategies in different scenarios. Whereas there is evidence for the efficacy of four-factor prothrombin concentrate for a variety of bleeding scenarios, convincing safety data are clearly missing. In the massively bleeding patient with coagulopathy, our group recommends the administration of an initial bolus of 25 IU.kg-1 . This applies for: the acute reversal of vitamin K antagonist therapy; haemostatic resuscitation, particularly in trauma; and the reversal of direct oral anticoagulants when no specific antidote is available. In patients with a high risk for thromboembolic complications, e.g. cardiac surgery, the administration of an initial half-dose bolus (12.5 IU.kg-1 ) should be considered. A second bolus may be indicated if coagulopathy and microvascular bleeding persists and other reasons for bleeding are largely ruled out. Tissue-factor-activated, factor VII-dependent and heparin insensitive point-of-care tests may be used for peri-operative monitoring and guiding of prothrombin complex concentrate therapy.

The role of fibrinogen and fibrinogen concentrate in cardiac surgery: an international consensus statement from the Haemostasis and Transfusion Scientific Subcommittee of the European Association of Cardiothoracic Anaesthesiology.

To date, data regarding the efficacy and safety of administering fibrinogen concentrate in cardiac surgery are limited. Studies are limited by their low sample size and large heterogeneity with regard to the patient population, by the timing of fibrinogen concentrate administration, and by the definition of transfusion trigger and target levels. Assessment of fibrinogen activity using viscoelastic point-of-care testing shortly before or after weaning from cardiopulmonary bypass in patients and procedures with a high risk of bleeding appears to be a rational strategy. In contrast, the use of Clauss fibrinogen test for determination of plasma fibrinogen level can no longer be recommended without restrictions due to its long turnaround time, high inter-assay variability and interference with high heparin levels and fibrin degradation products. Administration of fibrinogen concentrate for maintaining physiological fibrinogen activity in the case of microvascular post-cardiopulmonary bypass bleeding appears to be indicated. The available evidence does not suggest aiming for supranormal levels, however. Use of cryoprecipitate as an alternative to fibrinogen concentrate might be considered to increase plasma fibrinogen levels. Although conclusive evidence is lacking, fibrinogen concentrate does not seem to increase adverse outcomes (i.e., thromboembolic events). Large prospective multi-centre studies are needed to better define the optimal perioperative monitoring tool, transfusion trigger and target levels for fibrinogen replacement in cardiac surgery.

Differences in regional cerebral oximetry during cardiac surgery for patients with or without postoperative cerebral ischaemic lesions evaluated by magnetic resonance imaging.

BACKGROUND: Near infrared spectroscopy (NIRS) is widely used to monitor regional cerebral tissue oxygenation (rScO2). We compared rScO2 values during cardiac surgery in patients with or without new cerebral ischaemic lesions on diffusion weighted magnetic resonance imaging (DWI). We hypothesised patients with new cerebral lesions would have impaired tissue oxygenation reflected in their rScO2 values. METHODS: NIRS and DWI data were collected in 152 elective cardiac surgery patients. Absolute rScO2 values, duration of desaturation below thresholds (baseline, 10%, and 20%), and accumulated cerebral desaturation load were compared between patients with or without new cerebral lesions on DWI. Primary outcome was time below 10% from rScO2 baseline. RESULTS: The time below 10% from rScO2 baseline was significantly longer for patients with new cerebral lesions than for patients without [median (inter-quartile range): 11.0 (0.4; 37.5) min vs 1.8 inter-quartile range: (0.05; 20.9) min, P=0.02]. Furthermore, they had a higher accumulated desaturation load below baseline (P=0.02) and 10% below baseline (P=0.02). Finally, their absolute minimum rScO2 value was significantly lower (P=0.01). However, the frequency of patients with desaturation below 10% and 20% was comparable between patients with and without new cerebral lesions. Receiver-operating characteristic curve analysis did not identify a clear-cut critical threshold among the investigated rScO2 variables. CONCLUSIONS: Use of NIRS identified significant group differences in rScO2 values between patients with or without new ischaemic lesions. However, a critical threshold could not be identified because of a high variation in NIRS values across both groups. CLINICAL TRIAL REGISTRATION: NCT 02185885.

The feasibility of tricuspid annular plane systolic excursion performed by transesophageal echocardiography throughout heart surgery and its interchangeability with transthoracic echocardiography.

Tricuspid annular plane systolic excursion (TAPSE) is a robust measure of RV function, but the performance of transesophageal echocardiography (TEE) measured TAPSE during surgery is not well established. We aim to evaluate feasibility of various TEE views before, during and after surgery. Furthermore, we compare performance of individual TEE measurements depending on view and method (AMM- and M-mode as well as 2D) as well as TAPSE measured using TEE with transthoracic echocardiography (TTE) TAPSE. The study was conducted from January 2015 through September 2016. In 47 patients with normal left ventricular ejection fraction, TEE was prospectively performed during coronary artery bypass grafting surgery. TAPSE and tricuspid annulus tissue Doppler imaging (TDI) were recorded in five different views at pre-specified time points during surgery. Data were analyzed for availability (obtainable/readable images) and reliability (intra-/inter-observer bias and precision). Finally, TEE TAPSE was compared to TTE TAPSE immediately before and after surgery. TAPSE and TDI with TEE was achievable in > 90% of patients in the transgastric view during surgery. The AM- and M-mode had the best reliability and the best correlation with TAPSE measured with TTE. The deep transgastric view was achievable in less than 50% after sternotomy, and TAPSE measured from 2D had a poorer performance compared to the AM- and M-mode. TDI demonstrated a high reliability throughout surgery. RV function can be evaluated by TAPSE and TDI using TEE during surgery. TEE values from the transgastric view demonstrated high performance throughout surgery and a good agreement with TTE TAPSE measurements.

Systematic review of the association of venous oxygenation and outcome in adult hospitalized patients.

BACKGROUND: Adequate tissue oxygenation is necessary to maintain organ function. Low venous oxygen saturation may reflect impaired tissue oxygenation, and may be used as a predictive tool and a therapeutic target to improve the care of critically ill patients. We therefore conducted a systematic review of the existing literature reflecting these aspects. METHODS: We searched electronic databases in January 2016 for relevant studies on venous oxygen saturation for treatment guidance and patient outcome. We sub-grouped results based on patient groups and setting. RESULTS: The search resulted in 5590 papers of which 42 studies were deemed relevant. The majority of the studies in cardiac and abdominal surgery patients showed associations between low venous oxygen saturation and increased mortality and morbidity, in particular increased length of intensive care. However, the cut-off level for low venous oxygen saturation varied between < 55 and 70% and all studies had high risk of bias. In patients with septic shock, recent randomized trials showed no benefit of early resuscitation guided by venous oxygen saturation. CONCLUSION: Low venous oxygen saturation may be associated with increased mortality, morbidity and length of intensive care in patients following cardiac or abdominal surgery. However, the wide range of cut-off levels and low quality of evidence hampers the clinical application. In patients with septic shock, the present evidence does not support goal-directed therapy using venous oxygen saturation during early resuscitation.

Paediatric ECMO at low-volume paediatric cardiac centres in the Nordic countries.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is a life-saving resource-intensive technology for patients with respiratory and/or circulatory failure. We aimed to evaluate outcome data from three Nordic paediatric centres comparing with data from the International Registry of the Extracorporeal Life Support Organization (ELSO) and selected high-volume single-centre studies. METHODS: One-hundred nineteen patients < 19 years from 2002 to 2012 were enrolled. Data on demographics and outcome were collected using a standardised registration form. Outcome data were compared with the ELSO registry and high-volume single-centre studies. RESULTS: Demographics, indications and diagnosis were similar to the ELSO register. Survival after ECMO was similar to outcome data from the ELSO register, apart from paediatric cardiac ECMO, where a significantly better survival to discharge was seen in the Nordic centres (68% vs. 49%; P = 0.03). Comparison with high-volume centres in the period after 2005 demonstrated a significantly better survival after cardiac ECMO in a single high-volume centre study, whereas four studies had significantly lower survival after cardiac ECMO. No significant difference was seen in children receiving respiratory ECMO in the Nordic centres and high-volume centres. CONCLUSIONS: Survival after ECMO in three low-volume Nordic centres demonstrated comparable outcome data with ELSO data and data from high-volume centres. We believe regular quality assurance surveys, as the present study, should be performed in order to maintain excellent therapy within the individual ECMO centres.

Metabolic effects of three different inotropic strategies in the newborn piglet myocardium.

INTRODUCTION: Neonates undergoing congenital heart surgery frequently need post-operative inotropic support. Knowledge about the effect of inotropes on myocardial metabolism in the newborn heart is limited, and the choice of inotropic therapy is based mainly on evidence from studies in adults. The aim of this study was to compare the effect of three inotropic strategies on the myocardial metabolism in a neonatal pig model. METHODS: Newborn piglets were randomised to intravenous infusions with: adrenaline and milrinone; dopamine and milrinone; dobutamine in haemodynamically equivalent doses; or isotonic saline, through 3 h. Microdialysis catheters were inserted in the myocardium of the left and right ventricle, and concentrations of lactate, pyruvate, glycerol, and glucose were measured in the microdialysate. In myocardial biopsies, tissue lactate and intracellular glycogen concentrations were determined, and arterial blood samples were analysed for lactate and glucose. RESULTS: No statistically significant differences were observed in haemodynamics between the three interventions. Metabolic variables demonstrated a consistent increase in lactate concentration in blood, myocardial dialysate, and biopsies in milrinone-adrenaline-treated animals. The lactate concentration remained stable in all other groups in all samples. The myocardial lactate/pyruvate ratio did not increase and was not significantly different between groups. CONCLUSION: Milrinone and adrenaline induced significantly higher lactate levels in neonatal piglets. The increase was not caused by myocardial ischaemia, but rather due to a beta-stimulation-induced glycolysis.

Urgent reversal of vitamin K antagonist therapy.

In the developed world, an increasing number of patients receive therapy with vitamin K antagonists (VKA). This group of patients poses an additional challenge in the perioperative management of emergency surgery and trauma. The present review offers a detailed description of some treatment options for reversal of VKA therapy. Optimal treatment of the anticoagulated patient requires a well-balanced intervention securing a reduced risk of haemorrhagic surgical complications as well as optimal anticoagulation post-operatively without exposing the patient to an increased risk of thromboembolic complications. The following factors must be considered in VKA-treated patients scheduled for emergency surgery: (1) the indication for VKA therapy, including the risk of thromboembolic events when the International normalized ratio (INR) is reduced, (2) type of surgery, including the risk of haemorrhagic complications and (3) the pharmacodynamic/-kinetic profile of the therapy used to revert the VKA therapy. Therapeutic options for acute reversal of VKA therapy include: vitamin K, fresh frozen plasma (FFP), prothrombin complex concentrate (PCC) and perhaps activated recombinant factor VII. PCC is a relatively new drug in some European countries and clinical experience is limited compared with the use of FFP. Reversal of VKA anticoagulation with PCC is faster and more efficient compared with FFP, but there are currently no randomized studies demonstrating an improved clinical outcome.

Junctional ectopic tachycardia after surgery for congenital heart disease in children.

OBJECTIVE: To determine incidence, predictors and outcome [intensive care unit (ICU) mortality and length of stay (LOS)] after postoperative junctional ectopic tachycardia (JET) in an unselected paediatric population. DESIGN: Patients with JET (n=89) were compared with non-JET controls (n=178) in a nested case-control study. SETTING: Tertiary ICU at Skejby Sygehus, Aarhus University Hospital, Denmark. PATIENTS: The patient records of all children (n=874) who underwent corrective cardiac surgery on cardio-pulmonary bypass (CPB) between 1998 and 2005 were reviewed for postoperative JET. METHODS AND RESULTS: The association between JET and its potential predictors was examined with multivariate conditional regression analyses. The overall incidence of JET was 10.2%. CPB duration>90 min [adjusted odds ratio (OR) 2.6; 95% confidence interval (CI) 1.1-6.5], high inotropic requirements (adjusted OR 2.6; CI 1.2-5.9) and high postoperative levels of creatine kinase (CK)-MB (adjusted OR 3.1; CI 1.3-7.1) were associated with an increased risk of JET. ICU mortality was higher for patients with JET (13.5%; CI 7.2-22.4%) than for controls (1.7%; CI 0.3-4.8%), and LOS in ICU was 3 times higher in JET patients (median 2 vs. 7 days, p<0.001). CONCLUSIONS: JET occurred in approximately 10% of children following cardiac surgery and was associated with higher mortality and longer ICU stay. Risk factors included high inotropic requirements after surgery and extensive myocardial injury in terms of high CK-MB values and longer CPB duration.

Plasma cytokines do not reflect expression of pro- and anti-inflammatory cytokine mRNA at organ level after cardiopulmonary bypass in neonatal pigs.

BACKGROUND: Plasma concentrations of inflammatory markers are increased in response to the trauma of cardiac surgery and cardiopulmonary bypass (CPB). It is, however, unknown whether the plasma cytokine levels and cytokine mRNA expression at organ level reflect each other. METHODS: Twenty-six piglets (17-19 days) were allocated to the sham-group (sternotomy only, n = 13) or to the CPB-group (sternotomy, 120 min CPB procedure with 60-min aortic cross-clamp, n = 13). The pigs were observed for 0.5 h or 4 h post-CPB. Plasma levels of IL-1beta, IL-6, IL-8 and IL-10 and mRNA expression of TNF-alpha, IL-1beta, IL-6, IL-8, IL-10 and iNOS in organs were registered with concomitant changes in oxygenation index (OI) and expiratory nitric oxide (NO). RESULTS: In pigs killed 0.5 h post-CPB there was a significant increase in IL-10 mRNA in the lungs and kidneys compared with the sham-group. IL-1beta mRNA was detectable in the kidneys and lungs of the CPB-pigs, while IL-6 mRNA was up regulated only in lungs. In pigs killed 4 h post-CPB a significantly higher IL-6 mRNA was found in heart tissue and a lower IL-10 mRNA was found in lungs of CPB pigs compared with the sham-group. There was a concomitant significant increase in OI and increased plasma IL-8 and IL-10 concentrations in the CPB-pigs compared with the sham-pigs. CONCLUSION: The cytokine mRNA expression pattern was very different for the pigs killed already 0.5 h after the CPB procedure compared with the pigs killed 4 h post-CPB. The plasma cytokine levels poorly reflected mRNA expression of the pro- and anti-inflammatory cytokines.

Platelet activity and in vivo arterial thrombus formation in rats with mild hyperhomocysteinaemia.

Elevated plasma levels of total homocysteine (hcy) have been associated with an increased occurrence of arterial thrombosis. In the present study, we investigated the influence of hyperhomocysteinaemia on platelet aggregation and arterial thrombus formation in vivo. Fifty-one rats were included in the study, of which 29 received hcy in the drinking water for 4 weeks. Blood samples were withdrawn for measurement of platelet count and mean platelet volume. Platelet aggregation response in platelet-rich plasma following adenosine diphosphate or collagen stimulation were examined. In vivo thrombus formation was investigated by transillumination and videotape recording of the rat femoral artery after a thrombogenic injury was established. Off-line videotape analysis using computer-assisted planimetry permitted quantification of the thrombus area, and area versus time curves were obtained. In the intervention group receiving hcy, total hcy in plasma increased two-fold to 14.3 micromol/l, as compared with 7.3 micromol/l in the control group (P < 0.001). The platelet count and mean platelet volume did not differ between the two groups. In vivo thrombus formation expressed as the area under the curve or maximum thrombus area was not found to be altered in the presence of an increased homocysteine level, neither was adenosine diphosphate-induced platelet aggregation. However, collagen-induced platelet aggregation significantly decreased in the hcy group (P = 0.02). Pro-thrombotic effects of isolated mild hyperhomocysteinaemia are not supported by the present study in rats.

Pulmonary endothelial dysfunction after cardiopulmonary bypass in neonatal pigs.

BACKGROUND: In neonatal pigs cardiopulmonary bypass (CPB) is associated with endothelial dysfunction in isolated large pulmonary arteries. It is, however, of great importance if this functional change extends to the small pulmonary resistance arteries, which are the key regulators of pulmonary flow and pressure. The aim of this study was to assess changes in pulmonary microvascular function after CPB using a clinically relevant pediatric procedure. METHODS: From three groups of neonatal pigs (CPB-, sham- and control group) pulmonary resistance arteries and systemic resistance arteries (from skeletal muscle) were isolated and mounted as ring preparations in wire myographs. Vessel diameters were less than 500 microm. Concentration-response curves were constructed for norepinephrine (NA), vasopressin (Vp), and the thromboxane A2-analog U46619, while the endothelium-dependent and -independent vasodilator functions were assessed as responses to acetylcholine and nitric oxide (NO). RESULTS: Maximum pulmonary vasodilator response to acetylcholine was attenuated after CPB compared with sham-operated and control animals (P=0.04). NO-induced relaxation, and contractile responses to NA, Vp, and U46619 were not influenced by CPB. In systemic arteries no changes in contractile or relaxant responses were seen after CPB. CONCLUSION: CPB seems to induce pulmonary endothelial dysfunction in pulmonary but not peripheral resistance arteries in neonatal piglets.

Dietary supplementation with methionine and homocysteine promotes early atherosclerosis but not plaque rupture in ApoE-deficient mice.

Hyperhomocysteinemia is an independent risk factor for atherothrombosis. However, causality is unproven, and it remains unknown whether hyperhomocysteinemia promotes atherosclerosis, plaque rupture, and/or thrombosis. We evaluated the short- and long-term effects of hyperhomocysteinemia on plaque size and structure in 99 atherosclerosis-prone apolipoprotein E-deficient mice. Hyperhomocysteinemia was induced by methionine (Met) or homocysteine (HcyH) supplementation: low Met (+11 g Met/kg food), high Met (+33 g Met/kg food), low HcyH (0.9 g HcyH/L drinking water), and high HcyH (1.8 g HcyH/L drinking water). Met and HcyH supplementation significantly raised plasma total homocysteine levels by 4- to 16-fold above those observed in mice fed a control diet (up to 146.1 micromol/L). Compared with controls, aortic root plaque size was significantly larger in supplemented groups after 3 months (56% and 173% larger in high-Met and high-HcyH, respectively) but not after 12 months. Hyperhomocysteinemia was associated with an increase in the amount of collagen in plaques after both 3 and 12 months. Mechanical testing of the tail tendons revealed no weakening of collagen after 12 months of hyperhomocysteinemia. Many plaques in both control and supplemented mice appeared rupture prone morphologically, but all aortic root plaques and all but 1 coronary plaque had an intact surface without rupture or thrombosis. Thus, diet-induced hyperhomocysteinemia promotes early atherosclerosis and plaque fibrosis but does not, even in the long term, weaken collagen or induce plaque rupture.

Intravenous magnesium does not influence the activity of the coagulation cascade.

Experimental arterial thrombus formation is reduced during intravenous magnesium infusion. It is well documented that magnesium reduces platelet reactivity, but the antithrombotic effect could also originate from anticoagulant properties or increased fibrinolysis. We therefore evaluated the effect of intravenous magnesium on prothrombin fragment 1 + 2 (F1 + 2), thrombin-antithrombin III complex (TAT) concentrations, and fibrin degradation products (FbDP) in a randomized, cross-over study in 14 healthy volunteers. Citrated blood samples were collected at 0, 30, and 180 min. An additional in vitro study on magnesium's effect on the activity of different coagulation factors was carried out. A transient increase was seen in F1 + 2 and TAT after 30 min but without any significant difference between the placebo and magnesium period. FbDP did not change significantly between the two treatments. Increasing concentrations of magnesium dose-dependently decreased binding of activated factor X to activated factor VII (FVIIa), but the decrease was slight and probably without any significance for coagulation at the concentrations tested. No effect was observed on the activity of FVIIa or activated factor VIII. In conclusion, no significant differences were observed on markers of coagulation or fibrinolytic activity during intravenous magnesium infusion. These results indicate that the observed antithrombotic effect of magnesium is more likely to arise from the previously observed platelet inhibition.

Tissue injury and the inflammatory response to pediatric cardiac surgery with cardiopulmonary bypass: a descriptive study.

BACKGROUND: There are few detailed descriptions of the inflammatory response to cardiac surgery with cardiopulmonary bypass (CPB) in children beyond 24 h postoperatively. This is especially true for the antiinflammatory cytokines and the extent of tissue injury. The aim of the current study was to describe the inflammatory and injury responses in uncomplicated pediatric cardiac surgery with CPB, where methylprednisolone and modified ultrafiltration (MUF) were used. METHODS: Blood samples were collected up to 48 h postoperatively. Cytokines (tumor necrosis factor-alpha and interleukin-6, -1beta, -10, and -1ra), complement (C3d and C4d) and coagulation system (prothrombin activation fragments 1 and 2 and antithrombin III) activation, neutrophil elastase, and the resulting tissue injury (creatine kinase, lactate dehydrogenase, alanine transaminase, amylase, and gamma-glutamyl transferase) were measured. RESULTS: The proinflammatory cytokine release varied widely, in contrast to a clear-cut antiinflammatory response. Cytokine concentrations did not decrease immediately after MUF, and no rebound increases later in the postoperative period were observed. The coagulation system, but not complement, was activated. There was a late release of C-reactive protein. Tissue injury could be quantified biochemically without evidence of hepatic or pancreatic dysfunction. CONCLUSION: In this group of uncomplicated subjects, the antiinflammatory cytokine and tissue injury responses were well defined, in contrast to a variable proinflammatory cytokine release. This was accompanied by activation of the coagulation system but not of complement. Concentrations of inflammatory mediators did not decrease immediately after MUF, and there was no evidence for rebound release later in the postoperative period.

Oral magnesium supplementation induces favorable antiatherogenic changes in ApoE-deficient mice.

Epidemiological studies indicate that dietary magnesium influences atherogenesis. Magnesium inhibits plaque formation in animals receiving a high cholesterol diet, whereas the effect of magnesium in animals on low-fat diet has not been explored. Magnesium sulfate was given in the drinking water (50 mg/mL) to 7-week-old apolipoprotein E-deficient (apoE(-)(/)(-)) mice (n=30). Control animals (n=30) received tap water. At the age of 19 weeks, the extent of atherosclerosis and the density of macrophages were measured in the aortic root, and blood lipids were analyzed. The median plaque area was significantly smaller in magnesium-treated female apoE(-)(/)(-) mice and reached only 66% of control females (P<0.02). Plaque area was also less extensive in magnesium-treated male mice, although not statistically significant. Macrophage density was similar in both groups. Magnesium significantly reduced cholesterol (P<0.05) and triglyceride (P<0.01) levels, whereas high density lipoprotein cholesterol remained stable. No significant differences in body and heart weight were seen between treatment groups for either sex. In conclusion, in apoE(-)(/)(-) mice receiving a low-fat diet, magnesium supplementation significantly inhibited atherogenesis in females but not males. Plaque composition remained unchanged in terms of macrophage density. This was obtained in association with significantly reduced levels of cholesterol and triglycerides.

Cardiopulmonary bypass elicits a pro- and anti-inflammatory cytokine response and impaired neutrophil chemotaxis in neonatal pigs.

BACKGROUND: Cardiopulmonary bypass (CPB) induces a systemic inflammatory response and organ dysfunction, especially in children. Plasma concentration of inflammatory markers are increased in response to the trauma of cardiac surgery and CPB. The aim of the present study was to investigate whether the CPB procedure in itself elicits increased levels of inflammatory markers in neonatal pigs. METHODS: The inflammatory response was measured in piglets undergoing sternotomy alone (sham group, n=13) or sternotomy and CPB (n=14). Inflammatory mediators were measured at baseline and at fixed time-points during and after CPB. IL-8, IL-10 and TNF-alpha levels and C-reactive protein (CRP) concentrations were measured in plasma samples. Polymorphonuclear neutrophils (PMN) chemotaxis was measured ex vivo, and CD-18 expression using an immunofluorescence technique. RESULTS: Immediately after the CPB procedure increased IL-8 levels were found in the CPB group, but not in sham operated animals (P=0.005). Simultaneously, a marked IL-10 response was measured in the CPB group. Concurrently, PMN chemotaxis decreased in CPB animals but not in the sham group (P=0.04). CD-18 expression and CRP levels were not significantly different between groups and TNF-alpha showed no changes in either group. The chemotactic response did not correlate with plasma IL-8 or IL-10, nor with CD-18 expression. CONCLUSION: The CPB procedure elicited a systemic inflammatory response in terms of significantly elevated plasma levels of IL-8 and IL-10. Furthermore, a temporary and simultaneous decrease in PMN chemotaxis was observed immediately after CPB.

Increased platelet reactivity and significant changes in coagulation markers after cavopulmonary connection.

OBJECTIVE: To evaluate platelet reactivity and coagulation markers after surgical palliation of univentricular hearts. DESIGN AND PATIENTS: Cross sectional survey of 24 patients, median age 11 (range 4-22) years, at 2 (range 0.5-6) years after a total cavopulmonary connection (TCPC; n = 14) or a bidirectional Glenn anastomosis (Glenn; n = 10). MAIN OUTCOME MEASURES: Platelet reactivity and/or coagulation markers were measured in 20 patients (four excluded because of anticoagulant treatment) and compared with 33 healthy controls, median age 12 (range 6-16) years. RESULTS: None of the patients had clinically apparent thromboembolic events. However, increased platelet reactivity was observed ex vivo both after collagen induced platelet aggregation (median 73% (interquartile range 61-84%) in patients, and 61% (47-69%) in controls; p < 0.01), and after ADP induced platelet aggregation (69% (53-77%) in patients, and 56% (40-66%) in controls; p < 0.05). Concentrations of protein S antigen, antithrombin III, and protein C activity were reduced after both TCPC and Glenn. A concomitant decrease was seen in coagulation factor II, VII, X, and factor VII clot activity. CONCLUSIONS: Several abnormalities in the coagulation system were observed after bidirectional Glenn anastomosis, similar to alterations previously described in Fontan operated and TCPC patients. Antithrombotic treatment in these patients is still an unresolved issue, but aspirin is often recommended. This study shows that such a strategy is rational and the results suggest that antiplatelet treatment may be advantageous, either alone or in combination with oral anticoagulant treatment.

Improvement in growth, and levels of insulin-like growth factor-I in the serum, after cavopulmonary connections.

INTRODUCTION: The total cavopulmonary connection, and the bidirectional Glenn anastomosis, are widely used for palliation of patients with complex functionally univentricular hearts. Little attention has been paid to the potential for postoperative growth in children after these operations, which are now performed at increasingly younger age. MATERIAL AND RESULTS: Physical growth, and levels of insulin-like growth factor I in the serum, were measured in 20 patients, aged 11.5 +/- 5.6 years, 2 (0.5-6) years after a total cavopulmonary connection in 12, or a Glenn anastomosis in 8. All patients were in functional class I or II of the categorisation of the New York Heart Association, with excellent haemodynamic and angiographic findings. None of the patients had clinical signs of protein losing enteropathy. Controls included 33 healthy children, aged 11.5 +/- 2.7 years. Preoperatively, the mean Z-scores for weight and height were negative, -1.1 +/- 0.8 and -0.5 +/- 1.5. At follow-up, both parameters had improved significantly by 1.1 +/- 0.9 and 0.8 +/- 1.2 percentiles, and Z-scores were comparable between the two groups (p=0.81 for weight and p=0.88 for height). No correlations were found between haemodynamics and the improvement in growth noted during follow-up. Increases equal to, or greater than 2 standard deviations for weight and height were seen only in children undergoing surgery before the age of 5 years. A significant correlation between age at operation and improvement in growth, however, could not be found. Levels of growth factor measured in the serum were not statistically different from levels in healthy children for either group of patients (p=0.07 for girls and p=0.37 for boys). CONCLUSION: Physical growth improved significantly following the surgical procedures. The concentrations of the growth factor measured in the serum were not different from levels in healthy children, suggesting normal nutritional status in both palliative situations.