Hematologic Derangements among Children with Unoperated Cyanotic Congenital Heart Disease in Ethiopia.

Background: Surgical treatment has transformed the course and outcome of congenital heart defects in high-income countries, but children with congenital heart diseases in sub-Saharan Africa, where access to cardiac surgery is limited, often experience the natural course of untreated lesions and their complications. The objective of this study was to determine the prevalence of hematologic derangements among Ethiopian children with unoperated cyanoticcongenital heart diseases, to identify factors associated with coagulopathy in this population, and to describe how these complications are managed in this setting. Methods: In this single-center cross-sectional study, we prospectively collected clinical and demographic data from children (<18 years) with cyanotic congenital heart diseases. Blood samples were collected to measure hematologic parameters. Polycythemia was defined as hematocrit >50% and thrombocytopenia as <150,000 per microliter. Results: Among 70 children recruited, the overall prevalence of polycythemia and thrombocytopenia was 63% (n=44) and 26% (n=18), respectively. On multivariate logistic regression analysis, hematocrit ≥65% (p-value=.024), and oxygen saturation <85% (p-value=.018) were independently associated with moderate or severe thrombocytopenia. Thirty-one (44%) patients had undergone therapeutic phlebotomy, and 84% (26/31) of these patients received iron supplementation. Conclusion: We report a high prevalence of polycythemia and thrombocytopenia in Ethiopian children with untreated cyanotic congenital heart diseases. There was variable implementation of iron supplementation and therapeutic phlebotomy, highlighting the need to optimize supportive management strategies in this population to mitigate the risk of life-threatening complications.

Serum Iron Status of Children with Cyanotic Congenital Heart Disease in Lagos, Nigeria.

OBJECTIVES: Cyanotic congenital heart disease (CCHD) predisposes patients to iron deficiency due to compensatory secondary erythrocytosis. This study aimed to determine the serum iron status and prevalence of iron deficiency among children with cyanotic congenital heart disease attending the Paediatric Cardiology outpatient clinic of Lagos State University Teaching Hospital, Lagos, Nigeria. METHODS: This cross-sectional case-control study took place between May and October 2015 at the Lagos State University Teaching Hospital. A total of 75 children with cyanotic congenital heart disease and 75 apparently healthy age-, gender- and socioeconomically-matched controls were analysed to determine serum iron status and the prevalence of iron deficiency as defined by the World Health Organization criteria. RESULTS: The mean age of the children was 47.5 ± 2.9 months (range: 6-144 months old). Iron deficiency was significantly more frequent among CCHD patients compared to control subjects (9.3% versus 0%; P = 0.006). While latent iron deficiency was more prevalent among children in the control group compared to those with CCHD, this difference was not statistically significant (13.3% versus 9.3%; P = 0.303). No cases of iron deficiency anaemia were observed in the studied sample. CONCLUSION: Neither the children in the control group nor those with CCHD had iron deficiency anaemia. However, iron deficiency was significantly more prevalent among children with CCHD in Lagos. Periodic serum iron status screening is therefore recommended for this population.

S100B increases in cyanotic versus noncyanotic infants undergoing heart surgery and cardiopulmonary bypass (CPB).

AIMS: S100B has been proposed as a consolidated marker of brain damage in infants with congenital heart disease (CHD) undergoing cardiac surgery and cardiopulmonary bypass (CPB). The present study aimed to investigate whether S100B blood levels in the perioperative period differed in infants complicated or not by cyanotic CHD (CHDc) and correlated with oxygenation status (PaO2). METHODS: We conducted a case-control study of 48 CHD infants without pre-existing neurological disorders undergoing surgical repair and CPB. 24 infants were CHDc and 24 were CHD controls. Blood samples for S100B assessment were collected at six monitoring time-points: before the surgical procedure (T0), after sternotomy but before CPB (T1), at the end of the cross-clamp CPB phase (T2), at the end of CPB (T3), at the end of the surgical procedure (T4), at 24 h postsurgery (T5). RESULTS: In the CHDc group, S100B multiples of median (MoM) were significantly higher (p < .05, for all) from T0 to T5. PaO2 was significantly lower (p < .05, for all) in CHDc infants at T0-T1 and at T4 while no differences (p > .05, for all) were found at T2, T3, T5. Linear regression analysis showed a positive correlation between S100B MoM at T3 and PaO2 (R = 0.84; p < .001). CONCLUSIONS: The present data showing higher hypoxia/hyperoxia-mediated S100B concentrations in CHDc infants suggest that CHDc are more prone to perioperative brain stress/damage and suggest the usefulness of further investigations to detect the "optimal" PaO2 target in order to avoid the side effects associated with reoxygenation during CPB.

A Novel Brain Injury Biomarker Correlates with Cyanosis in Infants with Congenital Heart Disease.

Cyanotic heart lesions are a complex subset of congenital heart disease (CHD) in which patients are desaturated until surgical repair or palliation. We hypothesized that a direct relationship would exist between degree of desaturation and presence of systemic inflammation and brain injury in unrepaired patients less than 1 year of age. The pre-operative desaturation with augmented systemic inflammation would predict a more complex post-operative course. Fifty patients with CHD were enrolled in this study and classified as cyanotic (O2 ≤ 90%) or acyanotic (O2 > 90%) based on SpO2. Serum inflammatory mediators measured included interleukins (IL)-6, IL-8, IL-12p70, IL-10, IL-1ß, tumor necrosis factor (TNF)-α, interferon (INF)-γ; macrophage inhibitory factor (MIF) and a novel brain biomarker, phosphorylated neurofilament heavy subunit (pNF-H). Twenty-two cyanotic and 28 acyanotic subjects were enrolled with SpO2 of 78 ± 18% and 98 ± 2% (p < 0.001), respectively, and mean age of 72 days (range 2-303) and 102 days (range 1-274), respectively. Cyanotic vs acyanotic subjects had elevated serum IL-6 (6.6 ± 7.6 vs 2.9 ± 2.9 pg/ml, p = 0.019) and pNF-H (222 ± 637 vs 57 ± 121 pg/ml, p = 0.046), and both biomarkers correlated with degree of desaturation (Spearman rank-order correlation ρ = - 0.30, p = 0.037 and ρ = - 0.29 p = 0.049, respectively). Post-operative inotrope scores at 24 h and duration of mechanical ventilation correlated inversely with pre-operative oxygen saturation (ρ = - 0.380, p = 0.014 and ρ = - 0.362, p = 0.020, respectively). The degree of pre-operative desaturation correlated with a more complicated post-operative course supporting the need for advanced peri-operative therapy in this population.

Comparison of trace element levels after cardiopulmonary bypass between cyanotic and acyanotic patients.

Trace elements are essential micronutrients for the human body. In this study, we evaluated the alterations in copper, chromium, manganese, selenium, magnesium, zinc, iron, arsenic, boron, and silicon levels in children with cyanotic and acyanotic CHD who underwent cardiac surgery with cardiopulmonary bypass. Participants were divided into the following three groups: patients acyanotic CHDs (n=34), patients with cyanotic CHDs (n=30), and healthy controls (n=30). Blood samples were collected before the surgery and 1 hour after the sternum was closed. Serum trace elements were determined by Inductively Coupled Plasma Optical Emission Spectrometer-ICAP 6000. The baseline serum arsenic, manganese, and zinc levels of both patient groups were lower compared with controls, but there was no significant difference between baseline serum trace element levels of cyanotic and acyanotic patients. In both the patient groups, there was a significant decrease in postoperative serum arsenic, boron, copper, and zinc levels, and a significant increase in postoperative serum iron and magnesium levels. Silicon levels increased in cyanotic patients. Alterations in trace element levels were in the same direction in cyanotic and acyanotic patients. Copper, zinc, and manganase replacement may be needed after on-pump cardiac surgery.

Paediatric breath-holding spells are associated with autonomic dysfunction and iron deficiency may play a role.

AIM: This study assessed cardiac performance and iron in subjects aged 12-36 months with breath-holding spells (BHSs). METHODS: We consecutively recruited 40 subjects (55% male) experiencing BHSs from the general paediatric outpatients department at the Children's Hospital, Ain Shams University, Egypt, from 2015 to 2016. The 20 matched comparisons were mainly healthy siblings. The workup included iron levels and electrocardiograms. RESULTS: The age at the onset of BHSs was 5-24 months with a median monthly frequency of 13. Almost two-thirds of the patients had cyanotic spells, and one-third had pallid spells, lasting 25-90 seconds. Lower serum iron levels and higher QT dispersion and T-wave dispersion were recorded in patients than the comparison group, and 4.8% had dysrhythmia and bradycardia. We observed higher durations of bradycardia during attacks and higher occurrences of dysrhythmia during cyanotic spells, which were more frequent in patients with prolonged or frequent BHSs. CONCLUSION: Our study of patients aged 12-13 months supported the theory of autonomic dysfunction in BHSs. The ECG findings, especially in patients with prolonged or frequent spells, need to be studied further to evaluate the risk of life-threatening events. Iron deficiency may play a role in autonomic dysfunction in patients with BHSs.

Early or late fresh frozen plasma administration in newborns and small infants undergoing cardiac surgery: the APPEAR randomized trial.

BACKGROUND: In newborns and small infants undergoing cardiac surgery with cardiopulmonary bypass (CPB) and blood priming, it is unclear whether there is reduced blood loss if fresh frozen plasma (FFP) is added to the CPB priming volume. This single-centre, randomized trial tested the hypothesis that the administration of FFP after CPB (late FFP group) is superior to FFP priming (early FFP group) in terms of postoperative bleeding and overall red blood cell (RBC) transfusion. METHODS: Seventy-three infants weighing <10 kg were randomly allocated to receive FFP to supplement RBCs in the CPB priming solution ( n =36) or immediately after CPB ( n =37). The primary endpoint was a difference in postoperative blood loss; secondary endpoints included the amount of RBCs and FFP transfused through the first 48 postoperative hours. RESULTS: All patients were included in the analysis. Patients in the late FFP arm had greater postoperative mean blood loss than patients in the early FFP arm [33.1 ( sd 20.6) vs 24.1 (12.9) ml kg -1 ; P =0.028], but no differences in transfusions were found. The subgroup of cyanotic heart disease patients had comparable results, but with greater use of RBCs in the late FFP group. CONCLUSIONS: In infants undergoing cardiac surgery, FFP in the priming solution appears slightly superior to late administration in terms of postoperative bleeding. CLINICAL TRIAL REGISTRATION: www.ClinicalTrials.gov , NCT02738190.

Topical and low-dose intravenous tranexamic acid in cyanotic cardiac surgery.

Background Coagulopathy is a major problem in surgery for cyanotic congenital heart disease. Tranexamic acid has been used both topically and systemically and plays a vital role in pediatric cardiac surgery by reducing blood loss and blood product requirement. We aimed to determine the anti-fibrinolytic effectiveness of low-dose systemic or topical tranexamic acid or a combination of both. Methods Seventy-five patients were divided in 3 groups of 25. Group A patients were given tranexamic acid 20 mg kg-1 intravenously after sternotomy and 20 mg kg-1 after heparin reversal. Group B patients were given tranexamic acid 50 mg kg-1 in 20 mL of saline intrapericardially before sternal closure, with the drain clamped for 20 min. Group C patients were given tranexamic acid 20 mg kg-1 intravenously after sternotomy and 50 mg kg-1 intrapericardially before sternal closure. A number of clinical variables were recorded in the first 3 postoperative days. Ventilator time, intensive care unit stay, and outcome were also recorded. Results Chest tube drainage and blood product requirements were lowest in group C. Blood urea and serum creatinine levels were higher in groups A and C ( p < 0.05). Intensive care unit stay and ventilator time were similar in all 3 groups. No patient died and none had a seizure or other neurological event or thromboembolic complication postoperatively. Conclusion The combination of low-dose intravenous and topical tranexamic acid reduces postoperative blood loss and blood product requirement without incurring neurological, renal or thromboembolic complications. We recommend the routine use of topical and low-dose systemic tranexamic acid in cyanotic pediatric cardiac surgery.

The Association Between Cyanosis and Thromboelastometry (ROTEM) in Children With Congenital Heart Defects: A Retrospective Cohort Study.

BACKGROUND: Children with congenital heart defects (CHD) have quantitative and qualitative differences in coagulation compared with healthy children. Secondary to polycythemia and increased deformability of red blood cells, cyanosis may be an important confounding factor for altered whole-blood coagulation in this population with potential implications for interpreting intraoperative thromboelastometry (TEM) for children with CHD undergoing major surgery. The primary aim of the study was to evaluate the association between cyanosis in children with CHD and measures of whole-blood coagulation determined using TEM (ROTEM [Tem International, GmbH, Munich, Germany]). METHODS: In this retrospective cohort study, children who underwent congenital cardiac surgery in a 12-month period between April 2014 and 2015 were investigated. Children who were receiving antiplatelet or anticoagulant medications in the preoperative period were excluded. Eligible children were categorized by the presence of cyanosis, defined as an oxyhemoglobin concentration ≤85%. Multivariable linear regression analyses were used to determine the relationship between cyanosis and TEM outcomes (primary outcome, fibrinogen/fibrin polymerization [FibTEM] maximal clot firmness [MCF]) adjusting for potential confounding factors. RESULTS: Three hundred forty-five TEM profiles from 320 children were included in the cohort for analysis. Twenty-two percent (76/345) of children had cyanotic CHD. Clot firmness measured using the FibTEM assay was decreased in cyanotic children compared with noncyanotic children, median difference (95% confidence interval) interim [2 (0-3) mm; P = .01], and maximal [2 (1-3) mm; P = .01] clot firmness. The association between cyanosis and fibrinogen/fibrin polymerization clot firmness was not significant (A10, P = .7; MCF, P = .7) after adjusting for confounding factors (hematocrit, platelet count, and sex). There was a significant association between cyanosis and intrinsically activated clot firmness (A10, P = .03; MCF, P = .02), but not other TEM outcomes, after adjusting for confounding factors. CONCLUSIONS: Cyanotic children had decreased clot firmness in the fibrinogen/fibrin polymerization component of the clot compared with noncyanotic children, but the association between cyanosis and clot firmness was accounted for by differences in hematocrit, platelet count, and sex between groups. These findings will help guide the identification and treatment of coagulopathy in this vulnerable population.

Elevated serum levels of ghrelin and TNF-α in patients with cyanotic and acyanotic congenital heart disease.

BACKGROUND: The levels of ghrelin and tumor necrosis factor alpha (TNF-α) are considered biological markers of congenital heart diseases (CHD). The present meta-analysis was conducted to investigate the clinical significance of serum levels of ghrelin and TNF-α in children with (CHD). METHODS: Chinese and English scientific literature databases were searched to retrieve published studies relevant to ghrelin, TNF-α and CHD. Manual search was additionally employed to identify other relevant studies from cross-references. The retrieved studies were screened on the basis of our stringent inclusion and exclusion criteria to select high quality case-control studies for meta-analysis. RESULTS: We initially retrieved 108 published studies (20 in Chinese and 88 in English) from database searches. Finally, 6 case-control studies (5 in English and 1 in Chinese) were enrolled in our meta-analysis, and contained a total of 160 cyanotic congenital heart disease (CCHD) patients and 215 acyanotic congenital heart disease (ACHD) patients, along with 162 healthy controls. The results of meta-analysis showed that serum levels of ghrelin and TNF-α in CCHD or ACHD children were significantly higher than those in healthy controls. CONCLUSIONS: Our meta-analysis results showed that serum levels of ghrelin and TNF-α are elevated in children with CHD, and could be used as effective biologic markers in early diagnosis of CHD.

Serum albumin perturbations in cyanotics after cardiac surgery: Patterns and predictions.

INTRODUCTION: Hypoalbuminemia is a well-recognized predictor of general surgical risk and frequently occurs in patients with cyanotic congenital heart disease (CCHD). Moreover, cardiopulmonary bypass (CPB)-induced an inflammatory response, and the overall surgical stress can effect albumin concentration greatly. The objective of his study was to track CPB-induced changes in albumin concentration in patients with CCHD and to determine the effect of hypoalbuminemia on postoperative outcomes. MATERIALS AND METHODS: Prospective observational study conducted in 150 patients, Group 1 ≤18 years (n = 75) and Group 2 >18 years (n = 75) of age. Albumin levels were measured preoperatively (T1), after termination of CPB (T2) and 48 h post-CPB (T3). Primary parameters (mortality, duration of postoperative ventilation, duration of inotropes and duration of Intensive Care Unit [ICU] stay) and secondary parameters (urine output, oliguria, arrhythmias, and hemodynamic parameters) were recorded. RESULTS: The albumin levels in Group 1 at T1, T2, and T3 were 3.8 ± 0.48, 3.2 ± 0.45 and 2.6 ± 0.71 mg/dL; and in Group 2 were 3.7 ± 0.50, 3.2 ± 0.49 and 2.7 ± 0.62 mg/dL respectively. All patients showed a significant decrease in albumin concentration 48 h after surgery (P < 0.01). Analysis between the groups, however, showed no statistical difference. Eleven patients expired during the study period, and nonsurvivors showed significantly lower serum albumin concentration 48 h after surgery 2.3 ± 0.62 mg/dL versus 3.7 ± 0.56 mg/dL in the survivors (P < 0.05). Receiver operating characteristic curve showed that a baseline albumin cut-off value of 3.3 g/dL predicts mortality with a positive predictive value 47.6% and a negative predictive value of 99.2% (P < 0.05). A strong correlation was seen between albumin levels at 48 h with duration of CPB (r2 = 0.6321), ICU stay (r2 = 0.7447) and incidence of oliguria (r2 = 0.8803). CONCLUSIONS: The study demonstrated similar fall in albumin concentration in cyanotic patients (both adult and pediatric) in response to CPB. Low preoperative serum albumin concentrations (<3.3 g/dL) can be used to identify and prognosticate subset of cyanotics predisposed to additional surgical risk.

The Coagulative Profile of Cyanotic Children Undergoing Cardiac Surgery: The Role of Whole Blood Preoperative Thromboelastometry on Postoperative Transfusion Requirement.

The objective of this study is to evaluate the preoperative coagulation pattern and its association to postoperative blood products transfusion in children with congenital heart disease (CHD), focusing on cyanotic patients (oxygen saturation, SATO 2 < 85%). From January to August 2014, preoperative standard coagulation tests and rotational thromboelastometry assays were performed on 81 pediatric patients (<16 years old) who underwent surgery for CHD with the aid of cardiopulmonary bypass. Sixty patients (74%) were acyanotic and 21 (26%) cyanotic. Mean age at time of surgery was 7.9 months (interquartile range 2.9-43.6 months). Cyanotic patients had a significantly higher hematocrit (P < 0.001), a reduced prothrombin activity (PT) (P = 0.01) level, and a lower platelet count (P = 0.02) than acyanotic patients. An inverse linear association was found between patient's SATO2 and clot formation time (CFT) (INTEM, P = 0.001, and EXTEM, P < 0.0001). A direct linear association was found between patient's SATO2 and maximum clot firmness (MCF) (INTEM, P = 0.04, and EXTEM, P = 0.05). Preoperative cyanosis was also associated with a lower median MCF in FIBTEM (P = 0.02). Cyanotic patients required more frequent postoperative transfusions of fibrinogen (7/21 patients, 33% vs. 4/60 patients, 6.7%, P = 0.01) and fresh frozen plasma (14/21, 67% vs. 25/60, 42%, P = 0.08). Patients with a lower presurgery PT and platelet count subsequently required more fibrinogen transfusion P = 0.02 and P = 0.003, respectively); the same goes for patients with a longer CFT (INTEM, P = 0.01 and EXTEM, P = 0.03) and a reduced MCF (INTEM, P = 0.02 and FIBTEM, P = 0.01) as well. Cyanotic patients showed significant preoperative coagulation anomalies and required a higher postoperative fibrinogen supplementation. The preoperative MCF FIBTEM has become an important factor in our postoperative thromboelastometry-guided transfusion protocols.

Assessment of coagulation profile by thromboelastometry in adult patients with cyanotic congenital heart disease.

BACKGROUND: Patients with cyanotic congenital heart disease (CCHD) have an increased risk of bleeding and thrombotic complications. Prolonged conventional coagulation screening parameters, such as activated partial thromboplastin time or prothrombin time, are reported in less than 20% of CCHD patients. METHODS: The aim of this study was to determine the haemostatic abnormalities in 32 adult patients with CCHD by rotation thromboelastometry (ROTEM) with assessment of coagulation dynamic properties, as a guide for perioperative prophylaxis or haemostatic therapy. The control group consisted of 35 healthy subjects. RESULTS: Our results suggest that CCHD patients, in comparison to healthy controls, had a tendency to hypocoagulate with delayed activation of haemostasis and clot formation, initiated by both intrinsic and extrinsic activators. The growth of the clot was slower and the clot firmness was decreased, which may additionally contribute to bleeding diathesis. Moreover, the clot lysis readings suggest higher clot stability in the CCHD group. All velocity parameters were markedly lower in the CCHD patients, indicating a decreased rate of clot formation. Although coagulation tests and platelet count were normal, the usefulness of rotation thromboelastometry in monitoring or guiding therapy in CCHD patients is demonstrated. CONCLUSION: In conclusion, our results provide new insights into the data on hypocoagulation with impaired clot lysis in adult CCHD patients as determined by ROTEM. Our findings may assist in determining the optimal management of patients with CCHD undergoing surgery.

Outcome following augmentation of superior cavopulmonary blood flow with an arteriovenous fistula.

BACKGROUND: Axillary or brachial arteriovenous fistulae are occasionally created to improve systemic oxygen saturation in patients with functionally univentricular circulation after superior cavopulmonary anastomosis. Different techniques of fistula construction may account for the conflicting results. We sought to determine the impact of axillary arteriovenous fistula on systemic oxygen saturation and survival before subsequent palliation or heart transplantation. METHODS: Medical records of patients who underwent a side-to-side anastomosis between an adjacent axillary artery and vein for cyanosis after superior cavopulmonary anastomosis between 1991 and 2010 were reviewed. RESULTS: The median age (n = 23) at the time of fistula creation was 54 months (4-278 months). There was no operative mortality. The median duration of fistula patency was 48 months (1-174 months). Oxygen saturation improved from 71% ± 10% preoperatively to 84% ± 4% early (P < .05) and 81% ± 4% long term after the arteriovenous fistula (P < .05). Twelve patients underwent additional surgery (total cavopulmonary anastomosis 6, partial biventricular repair 2, and heart transplantation 4) after an interval of 10 to 141 months. Six patients are alive with a patent fistula without subsequent interventions after an interval of 48 to 174 months. Two patients with spontaneous closure or device closure of the fistula are alive after an interval of 76 to 80 months without subsequent interventions. Three deaths occurred with a patent fistula without subsequent interventions after an interval of 1 to 84 months. CONCLUSIONS: Systemic oxygen saturation improved with creation of an axillary arteriovenous fistula after superior cavopulmonary anastomosis. The fistula extended the duration of this stage of palliation without precluding the option for additional palliation or heart transplantation.

The effect of cyanosis on perioperative platelet function as measured by multiple electrode aggregometry and postoperative blood loss in neonates and infants undergoing cardiac surgery.

OBJECTIVES: Platelet dysfunction is one of the major haematological disturbances of cardiopulmonary bypass (CPB). In addition, cyanosis is known to cause further coagulation disturbances. METHODS: We prospectively studied 110 children under 1 year of age for the effects of cyanosis on baseline platelet aggregation, the time course of function on cardiopulmonary bypass, the effect on chest tube drainage (CTD) and the transfusion requirements. Using multiple electrode aggregometry (MULTIPLATE™) with the activators adenosine diphosphate (ADP) and thrombin-related activation peptide (TRAP), platelet aggregation was assessed and examined for predictive value. RESULTS: Neonates under 30 days of age (n = 51) and infants (n = 59) were separated for analysis. Cyanosis had no significant effect on platelet function during the first 24 h after surgery. Similarly, there was no association to perioperative platelet function, CTD or exposures to blood products. ADP after protamine correlated significantly with the total number of exposures for neonates and infants and CTD at 6 h in the newborn group. Upon intensive care unit admission, ADP values correlated to the total number of exposures to blood products. No other platelet function value was able to clinically predict CTD or subsequent blood transfusion requirements. CONCLUSIONS: In our study population, we observed no clinically significant effect of cyanosis on baseline and the perioperative course of platelet function, CTD and the number of exposures to blood products. Therefore, children under 1 year of age do not require a different approach with regard to platelet transfusions, independent of cyanosis. Clinically, platelet function was not a reliable predictor of CTD or blood transfusion requirements.

B-type natriuretic peptide as prognostic marker in tetralogy of Fallot surgery.

BACKGROUND: B-type natriuretic peptide has been extensively studied in patients with cardiovascular disease, but its impact on the perioperative outcome of patients with cyanotic congenital heart defects is still unclear. We assessed the perioperative changes in B-type natriuretic peptide levels and their correlation with preoperative factors and clinical outcomes in a large homogenous group of patients with tetralogy of Fallot undergoing definitive repair at a tertiary care center. METHODS: A prospective study was undertaken in the cardiac operating room and intensive care unit at a single institution; 250 patients with tetralogy of Fallot undergoing intracardiac repair under cardiopulmonary bypass were studied. B-type natriuretic peptide levels were taken at 3 time points and correlated with clinical variables. RESULTS: Baseline B-type natriuretic peptide levels correlated with the degree of cyanosis in all 4 groups. B-type natriuretic peptide levels at 24 h after admission to the intensive care unit correlated with mortality in the adult subset of patients. B-type natriuretic peptide levels > 290 pg mL(-1) in the intensive care unit predicted an increased probability of adverse clinical outcomes. CONCLUSIONS: We demonstrated a rise in serum B-type natriuretic peptide levels in patients with tetralogy of Fallot undergoing definitive repair on cardiopulmonary bypass. B-type natriuretic peptide levels may be monitored to identify patients with cyanosis at increased risk of an augmented inflammatory response to cardiopulmonary bypass.

Dynamics of factor XIII levels after open heart surgery for congenital heart defects: do cyanotic and acyanotic patients differ?

Cardiopulmonary bypass (CPB) reduces coagulation factor levels through hemodilution and consumption. Differences in CPB-induced alterations of factor XIII (FXIII) levels in children with cyanotic and acyanotic congenital heart defects (CHDs) are not well characterized. FXIII activity (determined by Berichrom assay), prothrombin index, activated partial thromboplastin time, and fibrinogen were measured before open heart surgery with CPB and 5 days postoperatively for children older than 3 years with acyanotic (n = 30) and cyanotic (n = 30) CHDs. The preoperative FXIII levels did not differ significantly among the children of the compared groups. The cyanotic patients showed a significantly longer duration of CPB (111.4 ± 45.8 vs 71.5 ± 33.6 min; p = 0.026) and aortic cross-clamp (68.0 ± 27.1 vs 45.4 ± 31.4 min; p = 0.034). The drop in FXIII levels after termination of CPB was more profound for the children with cyanotic CHDs (87.1 ± 13.4 to 49.1 ± 13.2 vs 81.5 ± 12.6 to 58.6 ± 11.1 %, respectively; p = 0.018). The cyanotc patients also were restored to their baseline FXIII levels later than the children with acyanotic CHDs (at 48 vs 24 h). The post-CPB dynamics of the majority of the other coagulation parameters in the compared groups of patients were similar. The cyanotic patients experienced significantly greater postoperative blood loss than the acyanotic patients (12.6 ± 4.9 vs 5.0 ± 2.1 mL/kg; p < 0.001) and were transfused with larger volumes of red blood cells (10.4 ± 6.5 vs 4.2 ± 2.5 mL/kg; p = 0.007). The decrease in FXIII levels after CPB is more profound and lasts longer in children with cyanotic CHDs than in acyanotic patients. The rational strategy of postoperative FXIII replacement therapy for these categories of patients needs to be determined.

Marked changes in platelet count and function following pediatric congenital heart surgery.

BACKGROUND: Reduced hemostatic capacity is common following congenital heart surgery using cardiopulmonary bypass (CPB). The etiology is multifactorial with dilutional coagulopathy, as well as platelet adhesion and activation in the CPB circuit and oxygenator. The purpose of the present study was to evaluate platelet count and function in children following CPB. METHODS: In a prospective, observational study comprising 40 children, platelet count and function (Multiplate Analyzer(®)) were measured before surgery, immediately after bypass, and on the first postoperative day. Furthermore, conventional coagulation analysis and thromboelastometry (ROTEM(®)) were carried out. RESULTS: A significant decrease in platelet count was observed immediately after coming of bypass (P < 0.001) and persisted to the first postoperative day (P = 0.002). Platelet function was reduced immediately after bypass after induction with ADP (P < 0.001) or TRAP (P = 0.03). The duration of CPB correlated significantly with the decrease in platelet count (r = -0.62, P = 0.0001) and reduction in platelet function (r = -0.42-0.63; P < 0.01). Moderate to deep hypothermia during CPB was associated with a decreased platelet function (P = 0.01-0.12), whereas cyanosis or previous heart surgery caused no further changes in platelet function following CPB. CONCLUSION: Both platelet count and platelet function were significantly reduced after CPB in children undertaken correctional heart surgery. Duration of CPB and hypothermia was associated with significant changes in platelet function.

High haematocrit in cyanotic congenital heart disease affects how fibrinogen activity is determined by rotational thromboelastometry.

INTRODUCTION: Viscoelastometry enables rapid evaluation of coagulopathy in settings such as cardiac surgery but may be influenced by red cell concentration. METHODS: In order to study the effects of supra-physiological red cell concentrations on viscoelastometry, we compared ROTEM® viscoelastometry and plasma coagulation assay results in high haematocrit (HCT; 0.55-0.76 L/L) blood from patients with cyanotic congenital heart disease (CCHD), and in model high HCT blood (HCT 0.45-0.70 L/L). RESULTS: High HCT blood from CCHD patients (median HCT 0.66 L/L) displayed prolonged clot initiation in the EXTEM® test compared to controls and reduced maximum clot firmness (MCF) in the EXTEM (median 51 mm vs 64 mm in controls) and FIBTEM® (7 mm vs 14 mm) tests. The plasma fibrinogen (Clauss; CF) was similar in CCHD blood to controls (median 2.94 g/L vs 2.49) but the whole blood fibrinogen concentration (WBFC) was reduced (1.27 g/L vs 1.58). The FIBTEM MCF correlated linearly with the CF (r(2)=0.68; p<0.0001) and WBFC (r(2)=0.65; p<0.0001) in control blood but this relationship was maintained only with WBFC in CCHD blood. Model high HCT blood showed abnormal ROTEM test results that were similar to CCHD blood, including reduced FIBTEM MCF (14 mm with HCT 0.32-0.44 vs 6mm with HCT 0.63-0.70). The ROTEM results were HCT dependent but independent of plasma clotting times and fibrinogen concentration. CONCLUSION: Supra-physiologic HCT causes abnormal ROTEM test results consistent with increased dilution of fibrinogen and coagulation factors in whole blood by red cells. High HCT should be considered during interpretation of ROTEM test results in clinical settings.

Correlation of a novel noninvasive tissue oxygen saturation monitor to serum central venous oxygen saturation in pediatric patients with postoperative congenital cyanotic heart disease.

Using a novel noninvasive, visible-light optical diffusion oximeter (T-Stat VLS Tissue Oximeter; Spectros Corporation, Portola Valley, CA) to measure the tissue oxygen saturation (StO2) of the buccal mucosa, the correlation between StOz and central venous oxygen saturation (ScvO2) was examined in children with congenital cyanotic heart disease undergoing a cardiac surgical procedure. Paired StO2 and serum ScvO2 measurements were obtained postoperatively and statistically analyzed for agreement and association. Thirteen children (nine male) participated in the study (age range, 4 days to 18 months). Surgeries included Glenn shunt procedures, Norwood procedures, unifocalization procedures with Blalock-Taussig shunt placement, a Kawashima/ Glenn shunt procedure, a Blalock-Taussig shunt placement, and a modified Norwood procedure. A total of 45 paired StO2-ScvO2 measurements was obtained. Linear regression demonstrated a Pearson's correlation of .58 (95% confidence interval [CI], .35-.75; p < .0001). The regression slope coefficient estimate was .95 (95% CI, .54-1.36) with an interclass correlation coefficient of .48 (95% CI, .22-.68). Below a clinically relevant average ScvO2 value, a receiver operator characteristic analysis yielded an area under the curve of .78. Statistical methods to control for repeatedly measuring the same subjects produced similar results. This study shows a moderate relationship and agreement between StO2 and ScvO2 measurements in pediatric patients with a history of congenital cyanotic heart disease undergoing a cardiac surgical procedure. This real-time monitoring device can act as a valuable adjunct to standard noninvasive monitoring in which serum SyvO2 sampling currently assists in the diagnosis of low cardiac output after pediatric cardiac surgery.