Biomarker-based risk model to predict persistent multiple organ dysfunctions after congenital heart surgery: a prospective observational cohort study.

BACKGROUND: Multiple organ dysfunction syndrome (MODS) is an important cause of post-operative morbidity and mortality for children undergoing cardiac surgery requiring cardiopulmonary bypass (CPB). Dysregulated inflammation is widely regarded as a key contributor to bypass-related MODS pathobiology, with considerable overlap of pathways associated with septic shock. The pediatric sepsis biomarker risk model (PERSEVERE) is comprised of seven protein biomarkers of inflammation and reliably predicts baseline risk of mortality and organ dysfunction among critically ill children with septic shock. We aimed to determine if PERSEVERE biomarkers and clinical data could be combined to derive a new model to assess the risk of persistent CPB-related MODS in the early post-operative period. METHODS: This study included 306 patients < 18 years old admitted to a pediatric cardiac ICU after surgery requiring cardiopulmonary bypass (CPB) for congenital heart disease. Persistent MODS, defined as dysfunction of two or more organ systems on postoperative day 5, was the primary outcome. PERSEVERE biomarkers were collected 4 and 12 h after CPB. Classification and regression tree methodology were used to derive a model to assess the risk of persistent MODS. RESULTS: The optimal model containing interleukin-8 (IL-8), chemokine ligand 3 (CCL3), and age as predictor variables had an area under the receiver operating characteristic curve (AUROC) of 0.86 (0.81-0.91) for differentiating those with or without persistent MODS and a negative predictive value of 99% (95-100). Ten-fold cross-validation of the model yielded a corrected AUROC of 0.75 (0.68-0.84). CONCLUSIONS: We present a novel risk prediction model to assess the risk for development of multiple organ dysfunction after pediatric cardiac surgery requiring CPB. Pending prospective validation, our model may facilitate identification of a high-risk cohort to direct interventions and studies aimed at improving outcomes via mitigation of post-operative organ dysfunction.

Biomarker-based risk model to predict persistent multiple organ dysfunctions after congenital heart surgery â€" A prospective observational cohort study.

Background: Multiple organ dysfunction syndrome (MODS) is an important cause of post-operative morbidity and mortality for children undergoing cardiac surgery requiring cardiopulmonary bypass (CPB). Dysregulated inflammation is widely regarded as a key contributor to bypass-related MODS pathobiology, with considerable overlap of pathways associated with septic shock. The pediatric sepsis biomarker risk model (PERSEVERE) is comprised of seven protein biomarkers of inflammation, and reliably predicts baseline risk of mortality and organ dysfunction among critically ill children with septic shock. We aimed to determine if PERSEVERE biomarkers and clinical data could be combined to derive a new model to assess the risk of persistent CPB-related MODS in the early post-operative period. Methods: This study included 306 patients <18 years old admitted to a pediatric cardiac ICU after surgery requiring cardiopulmonary bypass (CPB) for congenital heart disease. Persistent MODS, defined as dysfunction of two or more organ systems on postoperative day 5, was the primary outcome. PERSEVERE biomarkers were collected 4 and 12 hours after CPB. Classification and Regression Tree methodology was used to derive a model to assess the risk of persistent MODS. Results: The optimal model containing interleukin-8 (IL-8), chemokine ligand 3 (CCL3), and age as predictor variables, had an area under the receiver operating characteristic curve (AUROC) of 0.86 (0.81-0.91) for differentiating those with or without persistent MODS, and a negative predictive value of 99% (95-100). Ten-fold cross-validation of the model yielded a corrected AUROC of 0.75. Conclusions: We present a novel risk prediction model to assess the risk for development of multiple organ dysfunction after pediatric cardiac surgery requiring CPB. Pending prospective validation, our model may facilitate identification of a high-risk cohort to direct interventions and studies aimed at improving outcomes via mitigation of post-operative organ dysfunction. Clinical Trial Registration Number: This study does not meet criteria for a clinical trial per the WHO International Clinical Trials Registry Platform as no intervention was performed.

Reducing Exposure to Opioid and Benzodiazepine Medications for Pediatric Cardiac Intensive Care Patients: A Quality Improvement Project.

OBJECTIVES: To evaluate the effect of implementation of a comfort algorithm on infusion rates of opioids and benzodiazepines in postneonatal postoperative pediatric cardiac surgery patients. DESIGN: A quality improvement project, using statistical process control methodology. SETTING: Twenty-five-bed tertiary care pediatric cardiac ICU in an urban academic Children's hospital. PATIENTS: Postoperative pediatric cardiac surgery patients. INTERVENTIONS: Implementation of a guided comfort medication algorithm which consisted of key components; a low dose opioid continuous infusion, judicious use of frequent as needed opioids, initiation of dexmedetomidine infusion postoperatively, and minimal use of benzodiazepines. MEASUREMENTS AND MAIN RESULTS: Among the baseline group admitted over the 18 month period prior to comfort algorithm implementation, 58 of 116 intubated patients (50%) received a continuous opioid infusion, compared with 30 of 41 (73%) for the implementation group over the 9-month period following implementation. Following algorithm implementation, opioid infusion rates were decreased and benzodiazepine infusions were nearly eliminated. Dexmedetomidine use and infusion rates did not change. Although mean duration of sedative drug infusions did not change with implementation, the frequency of high outliers was diminished. Duration of mechanical ventilation, length of ICU stay (outcome measures), and the frequency of unplanned extubation (balancing measure) were not affected by implementation. CONCLUSIONS: Implementation of a pediatric comfort algorithm reduced opioid and benzodiazepine dosing, without compromising safety for postoperative pediatric cardiac surgical patients.

Efficacy and safety of recombinant tissue plasminogen activator for venous thrombosis after paediatric heart surgery.

OBJECTIVE: Reports in the literature of treatment with recombinant tissue plasminogen activator following cardiac surgery are limited. We reviewed our experience to provide a case series of the therapeutic use of tissue plasminogen activator for the treatment of venous thrombosis in children after cardiac surgery. The data describe the morbidity, mortality, and clinical outcomes of tissue plasminogen activator administration for treatment of venous thrombosis in children following cardiac surgery. DESIGN: The study was designed as a retrospective case series. SETTING: The study was carried out in a 25-bed cardiac intensive care unit in an academic, free-standing paediatric hospital. Patients All children who received tissue plasminogen activator for venous thrombosis within 60 days of cardiac surgery, a total of 13 patients, were included. Interventions Data was collected, collated, and analysed as a part of the interventions of this study. Measurements and main results Patients treated with tissue plasminogen activator were principally young infants (median 0.2, IQR 0.07-0.58 years) who had recently (22, IQR 12.5-27.3 days) undergone cardiac surgery. Hospital mortality was high in this patient group (38%), but there was no mortality attributable to tissue plasminogen activator administration, occurring within <72 hours. There was one major haemorrhagic complication that may be attributable to tissue plasminogen activator. Complete or partial resolution of venous thrombosis was confirmed using imaging in 10 of 13 patients (77%), and tissue plasminogen activator administration was associated with resolution of chylous drainage, with no drainage through chest tubes, at 10 days after tissue plasminogen activator treatment in seven of nine patients who had upper-compartment venous thrombosis-associated chylothorax. CONCLUSIONS: On the basis of our experience with administration of tissue plasminogen activator in children after cardiac surgery, tissue plasminogen activator is both safe and effective for resolution of venous thrombosis in this high-risk population.

Impaired cerebral autoregulation in preoperative newborn infants with congenital heart disease.

OBJECTIVES: To characterize cerebral autoregulation (CA) in preoperative newborn infants with congenital heart disease (CHD). METHODS: This was a prospective, pilot study of term newborns with CHD who required intensive care. Continuous mean arterial blood pressure (MAP), cerebral tissue oxygen saturation (SCTO2) via near-infrared spectroscopy, and arterial oxygen saturation (SaO2) were collected. Significant low-frequency coherence between MAP and SCTO2 was used to define impaired CA in 20-minute epochs. Cerebral fractional tissue oxygen extraction (FTOE) = (SaO2 - SCTO2)/SaO2 was calculated. Spearman's and rank bi-serial correlations and logistic linear models accounting for multiple measures were used to identify associations with impaired CA and coherence. RESULTS: Twenty-four term neonates were evaluated for 23.4 ± 1.8 hours starting the first day of life. Periods of SaO2 variability >5% were excluded, leaving 63 ± 10 epochs per subject, 1515 total for analysis. All subjects demonstrated periods of abnormal CA, mean 15.3% ± 12.8% of time studied. Significant associations with impaired CA per epoch included greater FTOE (P = .02) and lack of sedation (P = .02), and associations with coherence included greater FTOE (P = .03), lack of sedation (P = .03), lower MAP (P = .006), and lower hemoglobin (P = .02). CONCLUSIONS: Term newborns with CHD display time-varying CA abnormalities. Associations seen between abnormal CA and greater FTOE, lack of sedation, and lower hemoglobin suggest that impaired oxygen delivery and increased cerebral metabolic demand may overwhelm autoregulatory capacity in these infants. Further studies are needed to determine the significance of impaired CA in this population.

An International Survey of Corticosteroid Use for the Management of Low Cardiac Output Syndrome.

OBJECTIVE: Limited evidence exists on use of corticosteroids in low cardiac output syndrome following cardiac surgery. We sought to determine physicians' practices and beliefs with regard to corticosteroids therapy for low cardiac output syndrome. DESIGN: Multinational internet-based survey. SETTING: Pediatric Cardiac Intensive Care Society member database. SUBJECTS: Pediatric cardiac intensive care physicians. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We received 188 responses from 85 centers throughout the world including 57 U.S. congenital heart centers, eight Canadian centers, and 20 international centers. The majority of respondents (51%) reported performing at least 200 bypass cases per year and had separate dedicated cardiac ICUs (57%). Most physicians (89%) rarely or never prescribe corticosteroids for mild low cardiac output syndrome (single vasoactive agent and mildly decreased perfusion), whereas 94% of those surveyed sometimes or always administer corticosteroids to patients with severe low cardiac output syndrome (two or more vasoactive agents and persistent hypotension). Hydrocortisone was the most commonly used corticosteroids (88%), but there was no consensus on dosage used. There was a variable approach to cortisol level measurement and cortisol stimulation testing to inform therapy with corticosteroids. A majority of respondents (75%) stated that they would be willing to randomize patients with severe low cardiac output syndrome into a trial of corticosteroids efficacy. CONCLUSIONS: Our survey demonstrates considerable practice variability with regard to the type of patients in whom corticosteroids are administered, adrenal axis testing is performed, and dosage of hydrocortisone used. The majority of physicians, however, stated their willingness to randomize patients with severe low cardiac output syndrome in a corticosteroids trial. This survey identified multiple areas for future research on use of corticosteroids for low cardiac output syndrome.

Peritoneal Dialysis vs Furosemide for Prevention of Fluid Overload in Infants After Cardiac Surgery: A Randomized Clinical Trial.

Importance: Fluid overload after congenital heart surgery is frequent and a major cause of morbidity and mortality among infants. Many programs have adopted the use of peritoneal dialysis (PD) for fluid management; however, its benefits compared with those of traditional diuretic administration are unknown. Objective: To determine whether infants randomized to PD vs furosemide for the treatment of oliguria have a higher incidence of negative fluid balance on postoperative day 1, as well as avoidance of 10% fluid overload; shorter duration of mechanical ventilation, intensive care unit stay, and inotrope use; and fewer electrolyte abnormalities. Design, Setting, and Participants: This single-center, unblinded, randomized clinical trial compared methods of fluid removal after cardiac surgery from October 1, 2011, through March 13, 2015, in a large tertiary pediatric hospital in Ohio. The parents or guardians of all eligible infants (aged <6 months) undergoing cardiac surgery with catheter placement for PD were approached for inclusion. No patients were withdrawn for adverse effects. Recruitment was powered for the primary outcome, and analysis was based on intention to treat. Patients randomized to PD were hypothesized to have superior outcomes. Interventions: Infants received intravenous furosemide (1 mg/kg every 6 hours) or a standardized PD regimen. Main Outcomes and Measures: The primary end point was incidence of negative fluid balance on postoperative day 1. Secondary end points included incidence of fluid overload, duration of mechanical ventilation and intensive care unit stay, electrolyte abnormalities and repletion doses, duration of inotropic administration, and mortality. Results: Seventy-three patients (47 boys [64%] and 26 girls [35%]; median age, 8 [interquartile range (IQR), 6-14] days) received treatment and completed the trial. No difference was found between the PD and furosemide groups in the incidence of negative fluid balance on the first postoperative day. The furosemide group was 3 times more likely to have 10% fluid overload (odds ratio [OR], 3.0; 95% CI, 1.3-6.9), was more likely to have prolonged ventilator use (OR, 3.1; 95% CI, 1.2-8.2), and had a longer duration of inotrope use (median, 5.5 [IQR, 4-8] vs 4.0 [IQR, 3-6] days) and higher electrolyte abnormality scores (median, 6 [IQR, 4-7] vs 3 [IQR, 2-5]) compared with the PD group. No statistically significant differences in mortality (3 patients [9.4%] in the furosemide group vs 1 patient [3.1%] in the PD group) or length of cardiac intensive care unit (median, 7 [IQR, 6-12] vs 9 [IQR, 5-15] days) or hospital (15 [IQR, 10-28] vs 14 [IQR, 9-22] days) stay were observed. No serious complications were observed. Dialysis was discontinued early in 9 of 41 patients in the PD group for pleural-peritoneal communication. Conclusions and Relevance: Use of PD is safe and allows for superior fluid management with improved clinical outcomes compared with diuretic administration. Use of PD should be strongly considered among infants at high risk for postoperative acute kidney injury and fluid overload. Trial Registration: clinicaltrials.gov Identifer: NCT01709227.

Arginine-vasopressin therapy in hypotensive neonates and infants after cardiac surgery: response is unrelated to baseline ventricular function.

We hypothesised that infants with ventricular dysfunction after cardiac surgery have impaired haemodynamic response to arginine-vasopressin therapy. We retrospectively reviewed the medical records of neonates and infants treated with arginine-vasopressin within 48 hours of corrective or palliative cardiac surgery who underwent echocardiographic assessment of ventricular function before initiation of therapy. Patients were classified as "responders" if their systolic blood pressure increased by ⩾10% without increase in catecholamine score or if it was maintained with decreased catecholamine score. Response was assessed 1 hour after maximum upward titration of arginine-vasopressin. A total of 36 children (15 neonates) were reviewed (17 male). The median (interquartile) age was 10.4 weeks (1.1-26.9), and the median weight was 4.3 kg (3.2-5.8). Diagnoses included single ventricle (eight), arch abnormalities (five), atrioventricular septal defect (four), double-outlet right ventricle (three), tetralogy of Fallot (three), and others (13). In all, 12 patients (33%) had ventricular dysfunction. Only 15 (42%) responded favourably according to our definition 1 hour after the "target" arginine-vasopressin dose was achieved. Ventricular dysfunction was not associated with poor response. The overall mortality was 25%, but mortality in patients with ventricular dysfunction was 42%. Favourable response was associated with shorter ICU stay (9.5 days versus 19.5 days, p=0.01). We conclude that arginine-vasopressin fails to increase blood pressure in ~50% of hypotensive children after cardiac surgery. The response rate does not increase with duration of therapy. Ventricular function does not predict haemodynamic response. The mortality in this group is very high. Prospective comparison of vasopressin with other vasoactive agents and/or inotropes is warranted.

Single-Stage Repair of an Unusual Association: Congenital Gerbode Defect, Hypoplastic Aortic Arch, and Partially Anomalous Pulmonary Venous Return in an Infant.

We present the case of a two-month-old male with congenital Gerbode defect, hypoplastic aortic arch, and left-sided partially anomalous pulmonary venous return. The patient underwent single-stage surgical repair, which consisted of aortic arch advancement with resection of the coarctation segment, pulmonary vein repair, and primary closure of the Gerbode defect. The anomalous pulmonary vein posed a particular challenge due to its size and distance from the left atrium, which we approached with a posterior atrial wall trapdoor baffle technique, without mobilizing the affected vein. Postoperatively and at one year follow-up, there was no evidence of residual lesions and there was unobstructed flow pattern across the aortic arch and the affected pulmonary vein.

Cardiac intensive care for the neonate and child after cardiac surgery.

PURPOSE OF REVIEW: The focus of postoperative care in the pediatric patient with congenital heart disease has become a reduction in length of stay and morbidity. This review will discuss strategies to achieve this goal and recent studies to support current practices. RECENT FINDINGS: Most agree that prolongation of the length of stay following a cardiac surgery contributes to morbidity. Postoperative feeding difficulty, hyperglycemia, acute kidney injury, fluid overload, and prolonged intubation contribute significantly to length of stay. SUMMARY: Postoperative care of the neonate and child following a cardiac surgery remains challenging with limited data to drive our practices. Patients remain at risk for significant morbidity, and future studies should focus on recognizing predictors of morbidity, prevention, and treatment.

Ectopic expression of Fas Ligand on cardiomyocytes renders cardiac allografts resistant to CD4(+) T-cell mediated rejection.

Fas Ligand limits inflammatory injury and permits allograft survival by inducing apoptosis of Fas-bearing lymphocytes. Previous studies have shown that the CD4(+) T-cell is both sufficient and required for murine cardiac allograft rejection. Here, utilizing a transgenic mouse that over-expresses Fas Ligand specifically on cardiomyocytes as heart donors, we sought to determine if Fas Ligand on graft parenchymal cells could resist CD4(+) T-cell mediated rejection. When transplanted into fully immunocompetent BALB/c recipients Fas Ligand transgenic hearts were acutely rejected. However, when transplanted into CD4(+) T-cell reconstituted BALB/c-rag(-/-) recipients, Fas Ligand hearts demonstrated long-term survival. These results indicate that Fas Ligand over-expression on cardiomyocytes can indeed resist CD4(+) T-cell mediated cardiac rejection and suggests contact dependence between Fas Ligand expressing graft parenchymal cells and the effector CD4(+) T-cells.

Improved outcomes with peritoneal dialysis catheter placement after cardiopulmonary bypass in infants.

BACKGROUND: Acute kidney injury (AKI) is common in infants after cardiopulmonary bypass and is associated with poor outcomes. Peritoneal dialysis improves outcomes in adults with AKI after bypass, but pediatric data are limited. This retrospective case-matched study was conducted to determine if the practice of peritoneal dialysis catheter (PDC) placement during congenital heart surgery is associated with improved clinical outcomes in infants at high risk for AKI. METHODS: Forty-two infants undergoing congenital heart surgery with planned PDC placement (PDC+) were age-matched to infants undergoing similar surgery without PDC placement (PDC-). Demographic, baseline and outcome data were compared. Our primary outcome was negative fluid balance on postoperative days 1 to 3. Secondary outcomes included time to negative fluid balance, time to extubation, frequency of electrolyte corrective medications, inotrope scores, and other clinical outcomes. RESULTS: Baseline data did not differ between groups. The PDC+ group had a higher percentage of negative fluid balance on postoperative days 1 and 2 (57% vs 33%, P = .04; 85% vs 61%, P = .01). The PDC+ group had shorter time to negative fluid balance (16 vs 32 hours, P < .0001), earlier extubation (80 vs 104 hours, P = .02), improved inotrope scores (P = .04), and fewer electrolyte imbalances requiring correction (P = .03). PDC-related complications were rare. CONCLUSIONS: PDC use is safe and associated with earlier negative fluid balance and improved clinical outcomes in infants at high risk for AKI. Routine PDC use should be considered for infants undergoing cardiopulmonary bypass. Further prospective studies are essential to prove causative effects of PDC placement in this population.

Peritoneal dialysis does not adversely affect kidney function recovery after congenital heart surgery.

PURPOSE: Acute kidney injury (AKI) after cardiopulmonary bypass surgery to correct congenital heart disease is common. We prevent fluid overload and further cardiac compromise in oliguric infants with continuous peritoneal dialysis (CPD). The effect of CPD on kidney recovery is unknown, thus indications to discontinue CPD are unclear. We aimed to determine if CPD affects kidney recovery, measured by urine output and novel urinary AKI biomarker concentrations. METHODS: Twenty infants <90 days old with congenital heart disease who underwent bypass surgery and were post-operatively treated with CPD were randomized at the time of clinical readiness for CPD discontinuation to 1) discontinue CPD (control) or 2) continue 24 h more CPD (experimental). Urine output (ml/kg per h), total output (ml/kg per h) and urinary neutrophil gelatinase-associated lipocalin, interleukin-18, liver-type fatty acid binding protein, and kidney injury molecule-1 were assessed post-surgery until CPD catheter removal. RESULTS: 24 hours preceding randomization, there were no differences in mean urine output or total output; 24 hours post-randomization, the control group had higher mean urine output (4.2 ± 2.6 ml/kg per h vs. 2.8 ± 2.0 ml/kg per h, p = 0.02) but lower total output (6.3 ± 2.1 ml/kg per h vs. 4.7 ± 2.7 ml/kg per h, p = 0.01). Median biomarker concentrations did not differ significantly between groups at any time point. CONCLUSIONS: Our results suggest renal replacement therapy does not change the time course of kidney function recovery.

Interstage attrition between bidirectional Glenn and Fontan palliation in children with hypoplastic left heart syndrome.

OBJECTIVE: With improving operative mortality for staged palliation of hypoplastic left heart syndrome, interstage death accounts for an increasing proportion of hypoplastic left heart syndrome mortality. We investigated risk factors for death or cardiac transplantation during the interstage period between bidirectional Glenn and Fontan procedures in children with hypoplastic left heart syndrome. METHODS: Patients with hypoplastic left heart syndrome who underwent bidirectional Glenn between August 1995 and June 2007 were screened. Standard risk patients, defined by having been discharged after both Norwood and bidirectional Glenn, were included for analysis. Patient demographic, echocardiographic, cardiac catheterization, and operative data were reviewed. Interstage attrition was defined as death or cardiac transplantation more than 30 days after bidirectional Glenn and before the Fontan procedure. Statistical analysis was carried out using the Student t test, Pearson chi-square correlation, and Cox proportional hazard modeling for multivariable analysis. RESULTS: Ninety-two patients with hypoplastic left heart syndrome were alive at 30 days after bidirectional Glenn. Of these patients, 8 died and 3 underwent cardiac transplantation at a median of 391 days (range, 59-1175 days) after bidirectional Glenn, yielding an interstage attrition rate of 12%. Removing the 7 patients who are still awaiting Fontan (but all of whom are at least 3.5 years after bidirectional Glenn) adjusts the attrition rate to 13%. Interstage attrition did not correlate with hemodynamic data obtained at cardiac catheterization, aortic arch obstruction, or right ventricular dysfunction. Multivariable analysis demonstrated that the presence of moderate or severe tricuspid valve regurgitation (hazard ratio, 6.02; 95% confidence interval, 1.56-23.24; P < .01) and weight z score (hazard ratio, 0.38; 95% confidence interval, 0.16-0.88; P = .02) were independent preoperative risk factors for interstage attrition. CONCLUSIONS: Interstage attrition between bidirectional Glenn and Fontan procedures occurred in 12% of our study population. Moderate or greater tricuspid valve regurgitation and low weight z score at the time of bidirectional Glenn are important risk factors for interstage attrition between the bidirectional Glenn and Fontan procedures in children with hypoplastic left heart syndrome.

Enteral potassium supplementation in a pediatric cardiac intensive care unit: evaluation of a practice change.

BACKGROUND: Potassium supplementation is a common practice in critically ill children, especially those with heart disease. Intravenous potassium supplementation is the standard route of administration in most intensive care units. Although the enteral route is safer and thus may be a reasonable alternative, data on the efficacy of enteral potassium administration are lacking. METHODS: A change of practice to encourage use of enteral potassium was instituted in the cardiac intensive care unit at Texas Children's Hospital, and a review of this practice change was undertaken. The primary outcome of interest was the comparable efficacy of enteral and intravenous potassium administration. Patient demographic data, including urine output, diuretic use, route of potassium administration, and adverse events were documented and analyzed. RESULTS: Seventy-six patients met inclusion criteria and received 399 bolus doses of potassium (166 intravenous and 233 enteral). No patients became hyperkalemic after either route of administration. The increase in serum potassium was similar in both groups of patients. Side effects of the two routes of administration were not different. CONCLUSIONS: The efficacy of enteral potassium is comparable to intravenous potassium for potassium replacement in pediatric patients after congenital heart surgery.

Endocrinopathies in the cardiac ICU.

The past several years have seen an increased appreciation of the potential role of the endocrine system in the recovery process following surgery for congenital heart disease. Many of the hormonal changes following cardiac surgery are adaptive and necessary, whereas activation of proinflammatory cytokine and chemokine responses and some of the metabolic changes following surgery are likely mediators leading to detrimental outcomes. Additionally, other hormonal perturbations may contribute to adverse outcomes. This review examines the pain and the stress response, thyroid function and hyperglycemia following cardiopulmonary bypass (CPB), and the potential role of corticosteroids in the pediatric cardiac critical care unit.

Brain immaturity is associated with brain injury before and after neonatal cardiac surgery with high-flow bypass and cerebral oxygenation monitoring.

BACKGROUND: New intraparenchymal brain injury on magnetic resonance imaging is observed in 36% to 73% of neonates after cardiac surgery with cardiopulmonary bypass. Brain immaturity in this population is common. We performed brain magnetic resonance imaging before and after neonatal cardiac surgery, using a high-flow cardiopulmonary bypass protocol, hypothesizing that brain injury on magnetic resonance imaging would be associated with brain immaturity. METHODS: Cardiopulmonary bypass protocol included 150 mL . kg(-1) . min(-1) flows, pH stat management, hematocrit > 30%, and high-flow antegrade cerebral perfusion. Regional brain oxygen saturation was monitored, with a treatment protocol for regional brain oxygen saturation < 50%. Brain magnetic resonance imaging, consisting of T1-, T2-, and diffusion-weighted imaging, and magnetic resonance spectroscopy were performed preoperatively, 7 days postoperatively, and at age 3 to 6 months. RESULTS: Twenty-four of 67 patients (36%) had new postoperative white matter injury, infarction, or hemorrhage, and 16% had new white matter injury. Associations with preoperative brain injury included low brain maturity score (P = .002). Postoperative white matter injury was associated with single-ventricle diagnosis (P = .02), preoperative white matter injury (P < .001), and low brain maturity score (P = .05). Low brain maturity score was also associated with more severe postoperative brain injury (P = .01). Forty-five patients had a third scan, with a 27% incidence of new minor lesions, but 58% of previous lesions had partially or completely resolved. CONCLUSIONS: We observed a significant incidence of both pre- and postoperative magnetic resonance imaging abnormality and an association with brain immaturity. Many lesions resolved in the first 6 months after surgery. Timing of delivery and surgery with bypass could affect the risk of brain injury.

Endocrinal complications associated with the treatment of patients with congenital cardiac disease: consensus definitions from the Multi-Societal Database Committee for Pediatric and Congenital Heart Disease.

A complication is an event or occurrence that is associated with a disease or a healthcare intervention, is a departure from the desired course of events, and may cause, or be associated with, suboptimal outcome. A complication does not necessarily represent a breech in the standard of care that constitutes medical negligence or medical malpractice. An operative or procedural complication is any complication, regardless of cause, occurring (1) within 30 days after surgery or intervention in or out of the hospital, or (2) after 30 days during the same hospitalization subsequent to the operation or intervention. Operative and procedural complications include both intraoperative/intraprocedural complications and postoperative/postprocedural complications in this time interval. The MultiSocietal Database Committee for Pediatric and Congenital Heart Disease has set forth a comprehensive list of complications associated with the treatment of patients with congenital cardiac disease, related to cardiac, pulmonary, renal, haematological, infectious, neurological, gastrointestinal, and endocrinal systems, as well as those related to the management of anaesthesia and perfusion, and the transplantation of thoracic organs. The objective of this manuscript is to examine the definitions of operative morbidity as they relate specifically to the endocrine system. These specific definitions and terms will be used to track morbidity associated with surgical and transcatheter interventions and other forms of therapy in a common language across many separate databases. As surgical survival in children with congenital cardiac disease has improved in recent years, focus has necessarily shifted to reducing the morbidity of congenital cardiac malformations and their treatment. A comprehensive list of endocrinal complications is presented. This list is a component of a systems-based compendium of complications that will standardize terminology and thereby allow the study and quantification of morbidity in patients with congenital cardiac malformations. Clinicians caring for patients with congenital cardiac disease will be able to use this list for databases, initiatives to improve quality, reporting of complications, and comparing strategies of treatment.

Plasma angiopoietin-2 levels increase in children following cardiopulmonary bypass.

OBJECTIVE: The aim was to investigate the effects of cardiopulmonary bypass (CPB) on plasma levels of the vascular growth factors, angiopoietin (angpt)-1, angpt-2, and vascular endothelial growth factor (VEGF). DESIGN: The design was a prospective, clinical investigation. SETTING: The setting was a 12-bed pediatric cardiac intensive care unit of a tertiary children's medical center. PATIENTS: The patients were 48 children (median age, 5 months) undergoing surgical correction or palliation of congenital heart disease who were prospectively enrolled following informed consent. INTERVENTIONS: There were no interventions in this study. MEASUREMENTS AND RESULTS: Plasma samples were obtained at baseline and at 0, 6, and 24 h following CPB. Angpt-1, angpt-2, and VEGF levels were measured via commercial ELISA. Angpt-2 levels increased by 6 h (0.95, IQR 0.43-2.08 ng mL(-1) vs. 4.62, IQR 1.16-6.93 ng mL(-1), P < 0.05) and remained significantly elevated at 24 h after CPB (1.85, IQR 0.70-2.76 ng mL(-1); P < 0.05). Angpt-1 levels remained unchanged immediately after CPB, but were significantly decreased at 24 h after CPB (0.64, IQR 0.40-1.62 ng mL(-1) vs. 1.99, IQR 1.23-2.63 ng mL(-1), P < 0.05). Angpt-2 levels correlated significantly with cardiac intensive care unit (CICU) length of stay (LOS) and were an independent predictor for CICU LOS on subsequent multivariate analysis. CONCLUSIONS: Angpt-2 appears to be an important biomarker of adverse outcome following CPB in children.

Perioperative neuroprotective strategies.

Long-term neurodevelopmental impairment is common in newborns and infants undergoing corrective or palliative congenital heart surgery. The etiologies of neurodevelopmental morbidity in these children are multifactorial and include prenatal, preoperative, intraoperative, and postoperative factors. Perioperative neurologic monitoring is thought to be integral to prevention or rescue from adverse neurologic events. Recent advances in perfusion techniques for congenital heart surgery now ensure adequate cerebral O(2) delivery during all phases of cardiopulmonary bypass. Periventricular leukomalacia and other serious neurologic injury can be minimized by an optimized perfusion strategy of continuous high-flow, high hematocrit cardiopulmonary bypass, minimal use of deep hypothermic circulatory arrest, antegrade cerebral perfusion during aortic arch reconstruction, pH-stat blood gas strategy, and cerebral monitoring with NIRS and trans-cranial Doppler. Because there is evidence that brain injury can also occur in the prenatal, preoperative, and postoperative periods, improved strategies to prevent injury in these arenas are much needed. Extensive further clinical investigation is warranted to identify neuroprotective management strategies for the operating room and intensive care unit to preserve neurologic function and optimize long-term neurodevelopmental outcomes in children with congenital heart disease.