Overview of the current use of levosimendan in France: a prospective observational cohort study.

BACKGROUND: Following the results of randomized controlled trials on levosimendan, French health authorities requested an update of the current use and side-effects of this medication on a national scale. METHOD: The France-LEVO registry was a prospective observational cohort study reflecting the indications, dosing regimens, and side-effects of levosimendan, as well as patient outcomes over a year. RESULTS: The patients included (n = 602) represented 29.6% of the national yearly use of levosimendan in France. They were treated for cardiogenic shock (n = 250, 41.5%), decompensated heart failure (n = 127, 21.1%), cardiac surgery-related low cardiac output prophylaxis and/or treatment (n = 86, 14.3%), and weaning from veno-arterial extracorporeal membrane oxygenation (n = 82, 13.6%). They received 0.18 ± 0.07 µg/kg/min levosimendan over 26 ± 8 h. An initial bolus was administered in 45 patients (7.5%), 103 (17.1%) received repeated infusions, and 461 (76.6%) received inotropes and or vasoactive agents concomitantly. Hypotension was reported in 218 patients (36.2%), atrial fibrillation in 85 (14.1%), and serious adverse events in 17 (2.8%). 136 patients (22.6%) died in hospital, and 26 (4.3%) during the 90-day follow-up. CONCLUSIONS: We observed that levosimendan was used in accordance with recent recommendations by French physicians. Hypotension and atrial fibrillation remained the most frequent side-effects, while serious adverse event potentially attributable to levosimendan were infrequent. The results suggest that this medication was safe and potentially associated with some benefit in the population studied.

Long-Term Consequences of COVID-19: A 1-Year Analysis.

Long-lasting symptoms after SARS-CoV-2 infection have been described many times in the literature and are referred to as Long COVID. In this prospective, longitudinal, monocentric, observational study, we collected the health complaints of 474 patients (252 ambulatory and 222 hospitalized) at Lausanne University Hospital 1 year after COVID-19 diagnosis. Using a self-reported health survey, we explored cardiopulmonary, vascular, neurological, and psychological complaints. Our results show that age, Charlson comorbidity index, and smoking habits were associated with hospital admission. Regarding the vascular system, we found that having had thromboembolism before SARS-CoV-2 infection was significantly associated with a higher risk of recurrence of thromboembolism at 1 year. In the neurologic evaluation, the most frequent symptom was fatigue, which was observed in 87.5% of patients, followed by "feeling slowed down", headache, and smell disturbance in 71.5%, 68.5%, and 60.7% of cases, respectively. Finally, our cohort subjects scored higher overall in the STAI, CESD, Maastricht, and PSQI scores (which measure anxiety, depression, fatigue, and sleep, respectively) than the healthy population. Using cluster analysis, we identified two phenotypes of patients prone to developing Long COVID. At baseline, CCS score, prior chronic disease, stroke, and atrial fibrillation were associated with Long COVID. During COVID infection, mechanical ventilation and five neurological complaints were also associated with Long COVID. In conclusion, this study confirms the wide range of symptoms developed after COVID with the involvement of all the major systems. Early identification of risk factors associated with the development of Long COVID could improve patient follow-up; nevertheless, the low specificity of these factors remains a challenge to building a systematic approach.

Electric toy car to reduce anxiety before a cardiac catherisation: randomised controlled trial.

BACKGROUND: Anxiety before an invasive intervention is associated in children with persistent psychological disorders. We studied the effect of the transfer to the catheterisation room by an electric toy car on the anxiety of children and their parents before a cardiac catheterisation. METHODS: Forty-eight children with a median age of 5.6 years [4.2-7.0] were randomised to either riding on an electric car to go to the catheterisation laboratory or being transported lying supine on a gurney. Anxiety assessments were performed by a physician blinded to group allocation on the day before the procedure (T0) and at anaesthesia induction (T1). The modified Yale Preoperative Anxiety Scale Short Form (mYPAS-SF) and visual analogue scale for anxiety (VAS-A) were used in the children and the VAS-A in the parents. RESULTS: The mYPAS-SF, VAS-A-child, and the VAS-A-parent scores were significantly higher at T1 than at T0 (p < 0.001, p < 0.001, and p = 0.005, respectively). The primary outcome (the median mYPAS-SF score at T1) was not significantly different in the two groups when males and females were combined. At T1, the VAS-A-child score, however, was significantly lower in the intervention than the control group (22 versus 55, p < 0.001). In the boys, the median mYPAS-SF score at T1 was significantly lower in the intervention group (25.0 versus 51.0, p = 0.024). No difference was observed in girls. The VAS-A parent score was lower at T1 in the intervention group (60 versus 87, p = 0.05). CONCLUSION: Riding to the catheterisation laboratory on an electric toy car decreased anxiety in boys and decreased parental anxiety.

A case series of transcatheter Potts Shunt creation in a pediatric population affected with refractory pulmonary artery hypertension: focus on the role of ECMO.

PURPOSE: Patients with suprasystemic idiopathic pulmonary hypertension (S-PAH) have a poor prognosis. Therapeutic options are limited. Reverse Potts shunt creation modifies physiology transforming patients with PAH into Eisenmenger physiology with a better outcome. Percutaneous transcatheter stent secured aortopulmonary connection (transcatheter Potts Shunt, TPS) is a feasible very high-risk procedural option in such patients. We report our experience with patients undergoing TPS at our institution requiring extracorporeal membrane oxygenation (ECMO) support. METHODS: A prospective observational study of patients with drug-refractory PAH, worsening NYHA class, and right ventricular failure undergoing TPS. Two patients required rescue ECMO for cardiac arrest during the procedure. Subsequently, "standby ECMO" was available in all the following cases and elective support was provided in patients with extremely poor conditions. RESULTS: Ten pediatric patients, underwent TPS at our institution. Two patients were rescued by ECMO after cardiac arrest during the shunt creation. This occurred as a result of the acute loading of the left ventricle (LV) after retrograde aortic arch filling through the Potts shunt. Following this, another two patients underwent elective ECMO after the uneventful induction of anesthesia. They all died postoperatively despite a successful TPS procedure. The causes of death were not related to the use of ECMO, but the complication of severe PAH. Six patients with successful TPS did not require ECMO and survived. CONCLUSIONS: TPS is a pioneering procedure offering the opportunity to treat high-risk idiopathic drug-refractory PAH patients. Acute LV failure is a complication of TPS in patients with S-PAH. Elective ECMO, an option to avoid circulatory arrest and acute profound hypoxia secondary to exclusive right-to left shunt systemic perfusion by Potts shunt and LV dysfunction with resulting pulmonary edema, may be used at the early stage of the learning curve, but it does not influence the prognosis of these patients which remains poor.

Chronic Kidney Disease in Adolescents after Surgery for Congenital Heart Disease.

BACKGROUND: The onset of chronic kidney disease (CKD) is an important prognostic factor in young adults with congenital heart disease (CHD). Although it is likely that CKD is manifest early in CHD patients, the prevalence among adolescents is still unknown. The National Kidney Foundation's Kidney Disease Improving Global Outcomes guidelines 2012 recommend new equations for the estimated glomerular filtration rate (eGFR) and highlight the importance of albuminuria for CKD screening. The objective of the present study was to estimate the prevalence of CKD in CHD adolescents. METHODS: This observational cross-sectional study included 115 patients aged 10-18 years attending the cardiologic outpatient clinic at our institution as a follow-up after cardiac surgery in infancy related to various CHDs. CKD assessment used the CKD criteria 2012, including eGFR equations based on serum creatinine and cystatin C, and measurement of albuminuria. RESULTS: No patient had an eGFR <60 mL min-1 1.73 m-2. However, 28.7% of all patients (95% CI 20.7-37.9) had eGFRbetween 60 and 89 mL min-1 1.73 m-2 when estimated by the bedside Schwartz creatinine-based equation,and 17.4% (95% CI 11.2-24.1) had eGFRbetween 60 and 89 mL min-1 1.73 m-2 when estimated by the Zappitelli equation, combining creatinine and cystatin C. Of all patients, 20.0% (95% CI 12.1-26.7) had orthostatic proteinuria, and none had persistent albuminuria. CONCLUSIONS: There was no evidence of CKD in the present population aged 10-18 years. The significance of an eGFR between 60 and 90 mL min-1 1.73 m-2 is not concordant for this age range and requires further investigations.

Impact of the perioperative inotropic support in grown-up congenital heart patients undergoing cardiac surgery: a propensity score adjusted analysis.

BACKGROUND: Grown-up congenital heart (GUCH) patients represent a growing population with a high morbidity risk when undergoing reparative surgery. A main preoperative feature is right ventricular failure, which represents a risk factor for postoperative low cardiac output syndrome. Levosimendan has a potentially beneficial effect. This retrospective study included consecutive GUCH patients with surgeries in a tertiary cardiothoracic centre between 01-01-2013 and 01-10-2017, to test the hypothesis that the postoperative use of levosimendan might be associated with shorter time of mechanical ventilation, when compared with the use of milrinone. To adjust for bias related to the probability of treatment assignment, it uses the inverse propensity score weighting methodology. RESULTS: Overall 363 patients had GUCH surgeries during the study period, their mean age was 31.39 ± 15.31 years, 87 patients were eligible for analysis in the Levosimendan group and 117 in the Milrinone group. The propensity score used pre- and intraoperative variables and resulted in a good balance between covariates. The Levosimendan group included patients with higher preoperative risk scores, a higher prevalence of left and right ventricular failure, who required more often the addition of epinephrine, renal replacement therapy, prolonged mechanical ventilation and intensive care stay. However, after propensity score weighting, patients in the Levosimendan group had shorter durations of mechanical ventilation (average treatment effect - 37.59 h IQR [- 138.85 to - 19.13], p = 0.01) and intensive care stay (average treatment effect - 3.11 days IQR [- 10.03 to - 1.48], p = 0.009). The number of days of additional epinephrine support was shorter and the vasoactive inotropic scores lower. CONCLUSION: We report a beneficial effect in terms of duration of mechanical ventilation and intensive care stay, and on inotropic requirements of the use of levosimendan following GUCH surgeries. The use of levosimendan in this setting requires validation at a larger scale.

Cell-Cycle Arrest Biomarkers: Usefulness for Cardiac Surgery-Related Acute Kidney Injury in Neonates and Infants.

OBJECTIVES: Cell cycle arrest urine biomarkers have recently been shown to be early indicators of acute kidney injury in various clinical settings in critically ill adults and children. The product of tissue inhibitor metalloproteinase -1 and insulin-like growth factor binding protein-7 concentrations/1,000 (TIMP-1) × (IGFBP-7) provides stratification of acute kidney injury-risk in adults with critical illness. The present study explores the predictive accuracy of (TIMP-1) × (IGFBP-7) measured early after cardiopulmonary bypass for cardiac surgery-related acute kidney injury in neonates and infants, a population in whom such data are not yet available. DESIGN: Prospective, observational. SETTING: A tertiary referral pediatric cardiac ICU. PATIENTS: Fifty-seven neonates and 110 infants undergoing surgery with cardiopulmonary bypass. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: (TIMP-1) × (IGFBP-7) was measured on the NephroCheck (Astute Medical, San Diego, CA) platform preoperatively, less than 1 hour of cardiopulmonary bypass and 1-3 hours of cardiopulmonary bypass. The incidence of postoperative acute kidney injury, dialysis, and/or death were compared among quintiles of postoperative (TIMP-1) × (IGFBP-7). Multivariable regression was used to assess the added predictive value for renal events of (TIMP-1) × (IGFBP-7) over clinical models. Basal (TIMP-1) × (IGFBP-7) increased with age at surgery (regression coefficient = 0.004 ± 0.001; p = 0.005). (TIMP-1) × (IGFBP-7) increased after cardiopulmonary bypass. Neonates had lower postoperative (TIMP-1) × (IGFBP-7) compared with older infants, despite undergoing longer surgeries and experiencing a higher incidence of postoperative renal events. (TIMP-1) × (IGFBP-7) was not associated with acute kidney injury, dialysis, and/or death and was not a predictor of the aforementioned events when added to a clinical acute kidney injury model including age, duration of cardiopulmonary bypass, and mechanical ventilation prior to surgery. CONCLUSIONS: These findings question the usefulness of (TIMP-1) × (IGFBP-7) for the prediction of cardiac surgery-related acute kidney injury in neonates and infants when measured within 3 hours of cardiopulmonary bypass.

Lower limit of adequate oxygen delivery for the maintenance of aerobic metabolism during cardiopulmonary bypass in neonates.

BACKGROUND: The objective of cardiopulmonary bypass (CPB) is to maintain an adequate balance between oxygen delivery (Do2) and consumption. The critical Do2 is that at which consumption becomes supply dependent. This study aimed to identify the critical Do2 in neonates, who have higher metabolic rates than adults. METHODS: In a retrospective cohort of neonates, Do2 was calculated from CPB parameters recorded during aortic cross-clamping. High lactate concentration measured after aortic unclamping (lactOFF) was used to identify anaerobic metabolism. Data were analysed using mixed linear and proportional odds regression models. The relationship between Do2 and temperature was analysed in a subgroup of patients with lactOFF <2.5 mM, thought to have had balanced oxygen delivery and consumption. The estimated regression coefficient was further used to adjust hypothetical Do2 thresholds, and Do2 excursions below the threshold were quantified as magnitude-durations. The lowest threshold that provided magnitude-durations and linked with an increase in lactOFF was used as the lowest suitable (critical) Do2 at 37°C. RESULTS: Overall, 22 896 time points were analysed in 180 neonates. In 40 patients with lactOFF <2.5 mM, Do2 varied by 22.87 (0.70) ml min-1 m-2 °C-1. When varying the Do2 threshold between 340 and 380 ml min-1 m-2, excursions below the threshold were linked with incremental lactOFF. A 100 ml m-2 excursion below the 340 ml min-1 m-2Do2 threshold increased the risk of a 1 mM increment in lactOFF by 22% (odds ratio: 1.22; 95% confidence interval: 1.02-1.45). CONCLUSIONS: It was found that 340 ml min-1 m-2 is likely to represent the lowest suitable Do2 required in neonates to maintain aerobic metabolism during normothermic CPB.

Single-Shot Cold Histidine-Tryptophan-Ketoglutarate Cardioplegia for Long Aortic Cross-Clamping Durations in Neonates.

OBJECTIVE: More than 30% of European pediatric cardiac surgery centers use single-dose cold histidine-tryptophan-ketoglutarate cardioplegia (Custodiol; Dr Franz Köhler Chemie GmbH, Bensheim, Germany). In neonates with transposition of the great arteries, arterial switch surgery (ASO) implies aortic division, and it is unknown whether repeated ostial cannulation causes intimal insult and affects long-term results, and therefore, single-dose Custodiol is appealing. The present study investigated the association among myocardial no-flow duration, postoperative troponins, and postoperative outcomes in neonates undergoing ASO with Custodiol cardioplegia. DESIGN: Retrospective analysis of the association among myocardial no-flow duration, postoperative troponin release (concentration magnitude × measurement duration within 48 h), and outcomes using stratification according to coronary anatomy and attending surgeon. SETTING: Single-institutional, tertiary pediatric cardiac surgery unit of a university hospital. PARTICIPANTS: The study comprised 101 neonates undergoing ASO. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The mean age of patients was 6.1 ± 5.4 days, the cardiopulmonary bypass duration was 108.7 ± 54.1 minutes, the temperature during cross-clamping was 31.1°C ± 1.7°C, the duration of mechanical ventilation was 4 (3-6) days, the length of intensive care unit stay was 7 (5-8) days, delayed sternal closure occurred in 32 (31.7%) patients, and no patients died. The myocardial no-flow duration averaged 62.3 ± 14.6 minutes and was linked with both troponin release (p = 0.04) and low cardiac output syndrome, as assessed by the requirement for delayed sternal closure (p = 0.03), regardless of cardiopulmonary bypass duration and temperature. Eighty-two percent of the patients with myocardial no-flow duration >74 minutes necessitated delayed sternal closure. CONCLUSIONS: Single-dose Custodiol may be inadequate for prolonged cross-clamping durations without myocardial perfusion in neonates.

Somatic and cerebral near infrared spectroscopy for the monitoring of perfusion during neonatal cardiopulmonary bypass.

OBJECTIVES: The somatic-cerebral regional oxygen saturation (rSO2) gradient has the potential to reveal a low cardiac output state at an early stage, when systemic vascular resistance increases in order to maintain cerebral perfusion, and results in a drop in somatic rSO2. We hypothesized that during neonatal cardiopulmonary bypass (CPB), the somatic-cerebral rSO2 gradient can also signal poor perfusion, as assessed by an increase in lactate concentration. METHODS: In a retrospective review of neonatal bypass records, we investigated the association between the somatic-cerebral rSO2 gradient and serial lactate measurements. The somatic-cerebral rSO2 gradient, i.e. the area between the somatic and cerebral rSO2, was calculated for each CPB time interval between 2 lactate measurements, using the trapezoidal method. The association between the somatic-cerebral rSO2 gradient and lactate variation was explored using a mixed model for repeated measurements adjusted for the CPB temperature across intervals. RESULTS: A total of 94 CPB intervals were analysed in 24 neonates, median age 6 days, median weight 3.1 kg. The median lactate variation per interval was +0.2 mmol l-1 (range -1.5 to +2.7), the median somatic-cerebral gradient was 0 (range -1229% min to +2049% min) and the median CPB temperature was 29.5°C (IQR 28.1-33.4). There was an independent association between the lactate increase and the somatic-cerebral rSO2 gradient (regression coefficient = -0.0006 ± 0.0002, P = 0.009). CONCLUSIONS: A decrease in the somatic-cerebral rSO2 gradient was associated with an increase in lactate concentration, suggesting that the somatic-cerebral rSO2 gradient is a useful monitoring tool for the adequacy of perfusion during neonatal CPB.

Recent achievements and future developments in neonatal cardiopulmonary bypass.

A primary goal of improving neonatal cardiopulmonary bypass has been making the circuit smaller and reduce the blood contacting surfaces. As bypass circuit size has decreased, bloodless surgery has become possible even in neonates. Since transfusion guidelines are difficult to construct based on existing literature, these technical advances should be taken advantage of in conjunction with an individualized transfusion scheme, based on monitoring of oxygen availability to the tissues. For the majority of neonatal heart operations, several centers have shifted toward normothermic bypass even for complex neonatal surgeries, in order to avoid the adverse effects of hypothermia. Deep hypothermic circulatory arrest is no longer a necessity but an option, and selective antegrade cerebral perfusion has become common practice; however, technical uncertainties with regard to this technique have to be addressed, based on reliable neurologic monitoring. Maintenance of patient-specific heparin concentrations during bypass is another key goal, since neonates have lower baseline antithrombin concentrations and, therefore, a higher risk for inadequate thrombin inhibition and postoperative bleeding. Due to the immaturity of their hemostatic system, the standard coagulation tests alone are inappropriate to guide hemostatic therapy in neonates. The use of indirect heparin concentration assays and global viscoelastic assays in the operating room is likely to represent the optimal strategy, and requires validation in neonates. Monitoring of global and regional indexes of oxygen availability and consumption on bypass have become possible; however, their use in neonates still has outstanding technical issues which should be addressed and hence needs further validation. Due to the immaturity of the neonatal myocardium, single-shot cold cardioplegia solutions are thought to confer the best myocardial protection; their superiority when compared to more conventional modalities, however, remains to be demonstrated.

Impact of Heparin- or Nonheparin-Coated Circuits on Platelet Function in Pediatric Cardiac Surgery.

BACKGROUND: Extracorporeal circuit coating has been shown to improve coagulation derangements during pediatric cardiopulmonary bypass (CPB). This study compared platelet function and hemostasis activation in pediatric cardiac surgery conducted with nonheparin coating (Balance; Medtronic, Minneapolis, MN) versus heparin-based coating (Carmeda; Medtronic) circuits. METHODS: A prospective, randomized, double-center trial was conducted in children older than 1 month undergoing congenital heart disease treatment. Blood samples were collected at baseline (T0), 15 minutes after the start of CPB (T1), and 15 minutes (T2) and 1 hour after the conclusion of CPB (T3). The primary end point of the study was to detect potential differences in ß-thromboglobulin levels between the two groups at T2. Other coagulation and platelet function indicators were analyzed as secondary end points. RESULTS: The concentration of ß-thromboglobulin increased significantly at T2 in both groups. However, there was no significant difference between the groups across all time points. There was no difference in the secondary end points between the groups. CONCLUSIONS: The two circuits showed similar biological effects on platelet function and coagulation. This observation may be useful in optimizing the conduct of CPB and in rationalizing its cost for the treatment of congenital heart disease.

Lactate clearance in infants undergoing surgery for congenital heart disease.

Measurement of lactate concentrations during cardiac surgery with cardiopulmonary bypass (CPB) is a reliable monitoring tool for the assessment of the adequacy of perfusion, and a predictor of poor outcome. However, increased lactate production, which is multifactorial (anaerobic metabolism, hyperglycemia), increased lactate load by packed red blood cell (PRBC) transfusions, and decreased lactate clearance may all result in hyperlactatemia. The aim of this study was to estimate the clearance of lactate in infants undergoing surgery with CPB, using the lactate load from the PRBCs transfusions received during CPB. Retrospective cohort of infants <1 year of age with repeated lactate measurements during CPB, and a known lactate concentration in the PRBCs used during CPB were evaluated. All patients received PRBCs in the prime and during CPB to maintain hematocrit >35% and venous saturation >70%. Lactate kinetics were estimated across several time intervals between two lactate measurements, using a single compartment model. The lactate load was calculated as the product: PRBC-lactate concentration * volume. The rate of endogenous lactate production was assumed to be unchanged (maintenance of high oxygen deliveries and normoglycemia throughout CPB). Overall, 87 calculations were performed in 27 patients, then averaged per patient. The mean lactate half-life was 12.36 min [10.67-14.06], the mean clearance was 0.09 L/min [0.06-0.11], the indexed lactate clearance was 0.36 L/min/m2 [0.28-0.44]. Lactate clearance increased significantly with age. The half-life of lactate in infants is comparable with that reported in adults with CPB, and lactate clearance is higher. Knowing the high lactate content of PRBCs, lactate clearance rather than absolute concentration is potentially a better indicator of the adequacy of perfusion during CPB in infants.

Low perfusion pressure is associated with renal tubular injury in infants undergoing cardiac surgery with cardiopulmonary bypass: A secondary analysis of an observational study.

BACKGROUND: Earlier work on adults undergoing surgery with cardiopulmonary bypass suggests that there is a close relationship between the lower limit of the cerebral and renal autoregulation pressures. Although cerebral autoregulation during bypass in infants has been extensively investigated, the impact of bypass on kidney function is not well known. It is, nevertheless, acknowledged that the main pathophysiological process involved in cardiac surgery-related kidney damage is tubular injury, and that urine neutrophil gelatinase-associated lipocaline (uNGAL) is a reliable biomarker of injury. OBJECTIVE: To identify the most predictive bypass variable for the measurement of renal injury, its threshold value and the most predictive time below that threshold. DESIGN: Observational study linking electronically recorded bypass perfusion pressure and oxygen delivery rate with intra-operative uNGAL excretion. Variations in bypass variables were accounted for by their excursions below several thresholds. SETTING: French tertiary referral paediatric cardiac centre. PATIENTS: A total of 72 infants in whom uNGAL was measured within 1 h of bypass. INTERVENTIONS: None. MAIN OUTCOME MEASURE: Renal injury, identified by a high creatinine normalised uNGAL concentration (>21.2 µg mmol). RESULTS: At the end of bypass, 43.75% of infants had high uNGAL. A more than 40% pressure drop below the normal age-standardised mean arterial pressure was associated with high uNGAL. Receiver operating curve [interquartile range] areas were 0.626 [0.501 to 0.752] for a more than 40% drop, and 0.679 [0.555 to 0.804] for a more than 50% drop. A more than 40% pressure drop for 19.5 min provided a 0.65 negative predictive value for high uNGAL, and a more than 50% pressure drop for 5.4 min provided a 0.67 negative predictive value. The link between uNGAL and oxygen delivery rate was negligible. CONCLUSION: Maintaining the perfusion pressure above 60% of the normal age-standardised mean arterial pressure may provide an effective renal protective strategy. TRIAL REGISTRATION: Registered on October 11, 2010, ClinicalTrials.gov Identifier: NCT01219998.

Postoperative B-type natriuretic peptide monitoring for the assessment of the magnitude of shunting through Blalock-Taussig anastomoses.

BACKGROUND: The Modified Blalock-Taussig shunt (MBTS) is the most common palliative operation performed in patients with complex cardiac defects. Postoperative morbidity and mortality rates are high, mainly due to shunt thrombosis and over-shunting. Over-shunting may be difficult to identify postoperatively based on conventional criteria. Since plasma B-type natriuretic peptide (BNP) concentrations correlate with the magnitude of shunting in various left-to-right shunt cardiac defects, we investigated its ability to identify postoperative MBTS over-shunting. METHODS AND RESULTS: This retrospective, observational study included 42 consecutive patients (median age 9.50days, IQR: 6.00-58.25) undergoing MBTS for obstruction of the pulmonary blood flow at a tertiary referral pediatric cardiac center. The BNP threshold concentrations which accurately predicted outcome and MBTS over-shunting were derived using the ROC methodology. 443 BNP concentrations were analysed. The presence of atrio-ventricular valve regurgitation was the most important component of overall variance (72.75%). In 34 patients without regurgitation, BNP concentrations were predictive of a duration of mechanical ventilation >8days and of intensive care stay >11days, with ROC areas of 0.655 [0.597-0.719], 0.650 [0.589-0.711], a negative predictive value for the >1035pgmL-1 threshold of 0.93 and 0.96 respectively. SaO2 was less accurate for the prediction of both outcomes. In patients in whom the pulmonary flow was entirely MBTS-supplied, a BNP concentrations >1052pgmL-1 was predictive of a pulmonary-to-systemic ratio>2. CONCLUSION: In MBTS patients without atrio-ventricular valve regurgitation, maintaining BNP below 1000pgmL-1 may represent a therapeutic target to avoid over-shunting.

Postoperative Bleeding After Change in Heparin Supplier: A Cardiothoracic Center Experience.

OBJECTIVE: Unfractionated heparin is a mixture of glycosaminoglycans with different pharmacologic and pharmacokinetic properties. The literature suggests that blood loss after cardiac surgery is related to both elevated postoperative heparin concentrations and the potency of different heparin brands. DESIGN: An audit of the observed increase in the incidence of cardiac surgery-related bleeding after change in heparin supplier. Patient characteristics were compared between groups before and after a change in heparin brands. SETTING: Tertiary cardiothoracic center. PARTICIPANTS: All patients undergoing cardiac surgery between August 1, 2011, and April 30, 2012. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Two hundred eighty patients underwent surgery before a change in heparin brands and 216 after a change. Their preoperative and intraoperative characteristics were similar. Postoperative chest tube drainages and blood transfusions were significantly greater after the change in heparin brands (postoperative chest drainage 476.8 ± 393.1 v 344.8 ± 323.2 mL/6 h and 1,062.2 ± 738.8 v 841.8 ± 567.4 mL/24 h, respectively; both p < 0.001) despite the administration of larger amounts of protamine, fresh frozen plasma/platelet transfusions, and cryoprecipitate. Heparin recirculation within 24 hours of bypass was noted in about 70% of the samples tested using either anti-factor X activity or the thromboelastography ratio between nonheparinase R and heparinase-modified R and was not associated with the heparin brand. The likelihood ratio chi-square test for nested models identified an added predictive value of the heparin brand when included as a predictor of bleeding (chest drainage >800 mL/6 h) in a model comprising recirculation, assessed using either an elevated anti-factor X activity or ratio between nonheparinase R and heparinase-modified R. CONCLUSION: It is likely that the observed increase in postoperative bleeding was related to the pharmacologic properties of the new heparin brand rather than a higher incidence of heparin recirculation.

Structural equation modelling exploration of the key pathophysiological processes involved in cardiac surgery-related acute kidney injury in infants.

BACKGROUND: Uncertainties about the pathophysiological processes resulting in cardiac surgery-related acute kidney injury (AKI) in infants concern the relative impact of the most prominent risk factors, the clinical relevance of changes in glomerular filtration rate vs tubular injury, and the usefulness of available diagnostic tools. Structural equation modelling could allow for the assessment of these complex relationships. METHODS: A structural model was specified using data from a prospective observational cohort of 200 patients <1 year of age undergoing cardiopulmonary bypass surgery. It included four latent variables: AKI, modelled as a construct of perioperative creatinine variation, of oliguria and of urine neutrophil gelatinase-associated lipocalin (uNGAL) concentrations; the cardiopulmonary bypass characteristics; the occurrence of a post-operative low cardiac output syndrome and the post-operative outcome. RESULTS: The model showed a good fit, and all path coefficients were statistically significant. The bypass was the most prominent risk factor, with a path coefficient of 0.820 (95 % CI 0.527-0.979), translating to a 67.2 % explanation for the risk of AKI. A strong relationships was found between AKI and early uNGAL excretion, and between AKI and the post-operative outcome, with path coefficients of 0.611 (95 % CI 0.347-0.777) and 0.741 (95 % CI 0.610-0.988), respectively. The path coefficient between AKI and a >50 % increase in serum creatinine was smaller, with a path coefficient of 0.443 (95 % CI 0.273-0.596), and was intermediate for oliguria, defined as urine output <0.5 ml kg(-1) h(-1), with a path coefficient of 0.495 (95 % CI 0.250-0.864). A path coefficient of -0.229 (95 % CI -0.319 to 0.060) suggested that the risk of AKI during the first year of life did not increase with younger age at surgery. CONCLUSIONS: These findings suggest that cardiac surgery-related AKI in infants is a translation of tubular injury, predominately driven by the cardiopulmonary bypass, and linked to early uNGAL excretion and to post-operative outcome. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT01219998 . Registered 11 October 2010.