Acute Kidney Injury After Neonatal Aortic Arch Surgery: Deep Hypothermic Circulatory Arrest Versus Moderate Hypothermia With Distal Aortic Perfusion.

BACKGROUND: Acute kidney injury (AKI) is a common complication observed after neonatal aortic arch repair. We studied its incidence after procedures carried out using deep hypothermic circulatory arrest (DHCA) versus moderate hypothermia with distal aortic perfusion (MHDP), usually through the common femoral artery. In both groups, continuous regional cerebral perfusion (RCP) was used during the time required for aortic arch repair. METHODS: A total of 125 neonates underwent aortic arch repair. Between 2007 and 2012, DHCA with RCP was used in 51 neonates. From 2013 to 2019, MHDP with RCP was performed on 74 newborns. Operative complexity was similar in both periods. Acute kidney injury was defined as a significant elevation of serum creatinine and was classified according to the neonatal modified n-KDIGO (neonatal Kidney Disease: Improving Global Outcomes) stages 1 to 3 (Kidney Disease Improving: Global Outcomes). RESULTS: Acute kidney injury was observed in a total of 68 patients (68/125: 54.4%). In the majority (44/68: 64.7%), n-KDIGO stage 1 occurred. Stage 2 (n = 14) and stage 3 (n = 10) were observed more frequently after DHCA versus MHDP: 29.4% (15/51) versus 12.2% (9/74), P = .02. At cardiopulmonary bypass end, lactate levels were significantly higher (P = .001) after DHCA: 3.4 (2.9-4.3) mmol/L compared to 2.7 (2.3-3.7) mmol/L after MHDP. Early mortality was 12% (15/125) in the entire cohort. It was 17.6% (9/51) after DHCA versus 8.1% (6/74) after MHDP, however not statistically significant (P = .16). CONCLUSION: Mild (stage 1) AKI occurred frequently after neonatal aortic arch repair. The use of MHDP was associated with a significantly lower incidence of moderate (stage 2) and severe (stage 3) AKI forms.

Bilateral Pulmonary Artery Banding before Norwood Procedure: Survival of High-Risk Patients.

BACKGROUND: This study reports midterm results of high-risk patients with hypoplastic left ventricle treated with initial bilateral pulmonary artery banding (PAB) before secondary Norwood procedure (NP). METHODS: Retrospective study of 17 patients admitted between July 2012 and February 2017 who underwent this treatment strategy because diagnosis or clinical status was associated with high risk for NP. Survival was compared with that of patients who underwent primary NP. RESULTS: Mean Aristotle comprehensive complexity score for NP would have been 19.7 ± 2.6. Risk factors included obstructed pulmonary venous return (n = 9), body weight < 2.5 kg (n = 7), total anomalous pulmonary venous connection (n = 3), and necrotizing enterocolitis (n = 1). Ten patients had a score ≥ 19.5. Early survival after PAB was 82.4% (14/17). NP was performed in 14 patients after improvement of clinical condition at a median age of 56 days and a weight ≥2,500 g. There was no 30-day mortality, but one interstage death. One patient died later after Glenn operation. One-year survival after primary PAB followed by NP was 70.6 ± 11.1%. During the same period, 35 patients with overall lower risk factors underwent primary NP; early postoperative survival and 1-year survival were 88.6 ± 5.4% and 68.6 ± 7.8%, respectively. There was no significant difference in survival between the two groups (p = 0.83) despite higher risk in the secondary Norwood group (p <0.0001). CONCLUSIONS: PAB before NP in high-risk patients constituted salvage management. Primary PAB provided enough time for stabilization and control of most risk factors. It allowed midterm survival equivalent to the survival after primary NP in lower risk neonates.

A Prospective Clinical Trial Measuring the Effects of Cardiopulmonary Bypass Under Mild Hypothermia on the Inflammatory Response and Regulation of Cold-Shock Protein RNA-Binding Motif 3.

Therapeutic hypothermia during cardiac surgery has been widely used for neuroprotection and to attenuate the systemic inflammatory response due to cardiopulmonary bypass (CPB). Experimental data suggest that cold-shock protein RNA-binding motif 3 (RBM3), which is induced in response to hypothermia, plays a key role in hypothermia-induced organ protection. To date, investigation on RBM3 has been performed exclusively in vitro or in animal models, and the detection and regulation of RBM3 in human blood has not been investigated until now. The aim of this study was to investigate the level of RBM3 protein and cytokine expression profile involved in the inflammatory response in patients with congenital heart disease undergoing cardiac surgery involving CPB and therapeutic hypothermia. A single-center prospective trial with 23 patients undergoing cardiac surgery with CPB was performed. RBM3 protein was quantified in blood serum samples collected from patients and healthy individuals employing a new developed enzyme-linked immunosorbent assay. Cytokine levels were analyzed from dry blood spot samples using a Quanterix Simoa Immunoassay. For the first time, RBM3 protein was detected in blood samples of patients with congenital heart disease undergoing cardiac surgery. Hereby, RBM3 protein concentrations were significantly elevated in patients after cardiac surgery with CPB and mild hypothermia as compared with pre-surgery levels. Moreover, a complex immune reaction with significant induction of pro-inflammatory cytokines (interleukin [IL]-1 beta, IL-6, IL-8, IL-16, IL-18, monocyte chemotactic protein 1, CC-chemokine ligand [CCL]3, CCL4, intercellular adhesion molecule-1) in response to CPB was detected. Significantly elevated vascular endothelial growth factor and matrix metallopeptidase 3 concentrations reflecting ischemia/reperfusion-induced injury were observed 24 hours after weaning from CPB. The use of CPB is still associated with a complex inflammatory response. RBM3 protein is measurable in blood samples of patients with significantly higher concentrations after cardiac surgery with CPB and mild-to-moderate hypothermia. RBM3 is a new candidate as a biomarker for therapeutic hypothermia and a possible new therapeutic target for organ protection.

Hypothermia During Cardiopulmonary Bypass Increases Need for Inotropic Support but Does Not Impact Inflammation in Children Undergoing Surgical Ventricular Septal Defect Closure.

Minimizing the systemic inflammatory response caused by cardiopulmonary bypass is a major concern. It has been suggested that the perfusion temperature affects the inflammatory response. The aim of this prospective study was to compare the effects of moderate hypothermia (32°C) and normothermia (36°C) during cardiopulmonary bypass on markers of the inflammatory response and clinical outcomes (time on ventilator) after surgical closure of ventricular septal defects. During surgical closure of ventricular septal defects under cardiopulmonary bypass, 20 children (median age 4.9 months, range 2.3-38 months; median weight 7.2 kg, range 5.2-11.7 kg) were randomized to a perfusion temperature of either 32°C (Group 1, n = 10) or 36°C (Group 2, n = 10). The clinical data and blood samples were collected before cardiopulmonary bypass, directly after aortic cross-clamp release, and 4 and 24 h after weaning from cardiopulmonary bypass. Time on ventilation as primary outcome did not differ between the two groups. Other clinical outcome parameters like fluid balance or length of stay in the intensive care were also similar in the two groups. Compared with Group 2, Group 1 needed significantly higher and longer inotropic support (P < 0.001). In Group 1, two infants had junctional ectopic tachycardia, and another had a pulmonary hypertensive crisis. Perfusion temperature did not influence cytokine release, organ injury, or coagulation. Cardiopulmonary bypass temperature does not influence time on ventilation or inflammatory marker release. However, in the present study, with a small patient cohort, patients operated under hypothermic bypass needed higher and longer inotropic support. The use of hypothermic cardiopulmonary bypass in infants and children should be approached with care.

Suturing of penetrating wounds to the heart in the nineteenth century: the beginnings of heart surgery.

The beginnings of cardiac surgery go back to the 19th century. This article describes the history of the first attempts to operate on the heart. In 1882, Dr Block from Danzig, and in 1895, Simplicio Del Vecchio, published reports of animal experiments showing that the suturing of heart wounds is possible. After unsuccessful attempts by Axel Cappelen in Norway and Guido Farina in Italy, it was Ludwig Rehn of Germany who first sutured a laceration of the right ventricle of a human heart. Shortly afterward, Antonio Parrozzani successfully sutured a stab wound of the left ventricle. Following cardiac surgery back to its very beginnings, it is striking that the first attempts in the 19th century to repair the injured heart were regarded with great skepticism, and that heart suturing only slowly became an established method of treatment. Once the concept of cardiac surgery had become accepted, however, many kinds of operations were developed, paving the way for an explosion in the number of cardiac operations, as we well know, in the century that followed.

Repair of anomalous origin of the left coronary artery from the pulmonary artery in infants and children.

OBJECTIVE: Although mortality after direct aortic reimplantation for anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) has significantly decreased, many questions remain unanswered. METHODS: Between 1986 and June 2010, we operated on 27 consecutive pediatric patients with anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA). All patients underwent reestablishment of a dual coronary system with direct aortic reimplantation of the left coronary artery into the aorta. Postoperative extracorporeal mechanical circulatory support was necessary in 7 cases. In all 7 patients, hemodynamic stability was achieved after 4 to 10 days of support. Mitral valve repair was performed in 9 patients with severe mitral valve incompetence and resulted in stable mitral valve function during follow-up as long as 19 years. RESULTS: There were no early or late deaths. During follow-up (3 months-17.5 years), both early and late improvement of myocardial function was observed in all patients. Reduced left ventricular regional function late after successful surgical correction of ALCAPA was related to the presence of left ventricular myocardial scar tissue, as detected by magnetic resonance imaging. CONCLUSIONS: Despite the absence of early and late mortality, the long-term prognosis for patients after reimplantation of ALCAPA into the aorta is not clear. Scars and perfusion deficits of the left ventricle may not be detected by standard echocardiographic evaluation of global left ventricular function and therefore may be underestimated. We therefore recommend lifelong surveillance of these patients, including magnetic resonance imaging.

Predictors for the use of left ventricular assist devices in infants with anomalous left coronary artery from the pulmonary artery.

BACKGROUND: Left ventricular (LV) mechanical circulatory support (MCS) may be necessary after repair of anomalous left coronary artery from the pulmonary artery. We evaluated LV function parameters for their ability to predict postoperative need for MCS. METHODS: Fourteen infants (median age, 3.6; range, 2.3 to 12 months) underwent direct aortic reimplantation of the left coronary artery. We compared preoperative LV end-diastolic diameter, end-diastolic pressure, ejection fraction, and fraction of shortening of 8 patients with successful weaning from cardiopulmonary bypass (group 1) and 6 patients with unsuccessful weaning from cardiopulmonary bypass and temporary MCS support (group 2). RESULTS: No perioperative or late deaths occurred. All patients at follow-up were free of reoperation (median follow-up, 10.4 years [range, 1.4 to 17 years]). Median preoperative LV end-diastolic diameter (47 [range, 41 to 60 mm] vs 32 mm [range, 21 to 36 mm]) and LV end-diastolic pressure (20 [range, 18 to 25 mm Hg] vs 12 mm Hg [range, 7 to 20 mm Hg]) were significantly higher in group 2 than in group 1 (p = 0.002 and p = 0.048). LV ejection fraction (0.28 [range, 0.19 to 0.37] vs 0.43 [range, 0.23 to 0.76]) and LV fraction of shortening (9% [range, 7% to 15%] vs 22% [range 13% to 30%]) were significantly lower in group 2 than in group 1 (p = 0.035 and p = 0.002). MCS support duration ranged from 4 to 12 days. There were no significant differences in LV function parameters at discharge or during follow-up between the groups. CONCLUSIONS: A preoperative LV end-diastolic diameter above 40 mm is the strongest predictor for postoperative temporary MCS after anomalous left coronary artery from the pulmonary artery repair in infancy. However, even with temporary MCS, direct aortic reimplantation for anomalous left coronary artery from the pulmonary artery can be performed with no mortality and excellent LV recovery.

The first closure of the persistent ductus arteriosus.

Congenital heart disease began to be a treatable condition when, in 1938, Robert Edward Gross first successfully ligated a persistent ductus arteriosus. This overview traces the historical development from Munro's first idea of how to close a patent ductus, presented in 1907, to the clinical ligation or division of the ductus. Surgical treatment of the infected ductus began with an unsuccessful attempt by Strieder, but it was not until Tubbs' and Touroff's successful operations that it was actually accomplished.

Biomarker responses during mid-term mechanical cardiac support in children.

BACKGROUND: The purpose of this study was to determine the effect of mid-term mechanical circulatory support on the natriuretic hormone system in children and to assess whether such changes are associated with myocardial recovery. METHODS: Serial blood samples were collected from 19 children (median age 10.8 years, range 0.2 to 17.5 years), all supported with a pulsatile ventricular assist device (Berlin Heart EXCOR; median support time 55 days). Levels of NT-proBNP were analyzed before and 7 and 30 days after device implantation. In addition, we determined levels of mid-region proANP (MR-proANP) and BNP in 13 of the 19 children. RESULTS: The actuarial survival rate to discharge home was 84%. Two children could be weaned from the system, 14 reached heart transplantation, and 3 died during mechanical circulatory support. Serial measurements of NT-proBNP, BNP and MR-proANP showed a significant down-regulation of all three natriuretic peptides within the first week of support and a further decrease between Days 7 and 30. The lowest NT-proBNP level while on the device (250 pg/ml) was found in the child later weaned, who reached normal levels (71 pg/ml) within 12 weeks after weaning. CONCLUSIONS: Extremely high levels of natriuretic peptides reflect the severity of myocardial failure before device implantation. During mechanical support, the decline of natriuretic peptides appears to be a helpful additional tool in the pre-selection of potential weaning candidates.

Extracorporeal membrane oxygenation for perioperative cardiac support in children I: experience at the Deutsches Herzzentrum Berlin (1987-2005).

We report our experience in pediatric patients supported by extracorporeal membrane oxygenation (ECMO) for perioperative circulatory failure from January 1987 to June 2005. Pediatric patients (n = 110) who had ECMO support for congenital heart defects, myocarditis, and cardiomyopathy (age range, newborn to 18 years; weight range, 2.3-69 kg) were included and divided into three groups based on timing of ECMO support. EMCO support was used preoperatively in 21 patients (19.1%) (mean age, 4 years +/- 8 months; mean weight, 23.7 +/- 8.9 kg). Duration of ECMO support was 8.3 +/- 7 days. Fifty-six patients (56.56%) (mean age, 5.11 +/- 5 years; mean weight, 15.7 +/- 6.9 kg) had intraoperative ECMO support for myocardial insufficiency, low output syndrome, right ventricular failure, left ventricular failure, malignant arrhythmia, pulmonary hypertension, and repeated resuscitation. Mean duration of ECMO support was 4.98 +/- 1 days. Postoperative ECMO support was used in 29 patients (mean age, 7.5 +/- 1 years; mean weight, 23.4 +/- 6.4 kg). Mean duration of ECMO was 4.6 +/- 1 days. Mean postoperative day of ECMO institution was 40.4 +/- 2 days. Our experience shows that ECMO support can be offered perioperatively to any patient with potentially reversible pulmonary, cardiac, or cardiopulmonary failure, excluding those whose outcome is inevitable.

Successful use of bivalirudin as anticoagulant for ECMO in a patient with acute HIT.

A patient with myocardial failure after repair of an acute type A aortic dissection had acute heparin-induced thrombocytopenia develop during extracorporeal membrane oxygenation. Heparin was discontinued and the anticoagulant was switched to the direct thrombin inhibitor bivalirudin given with a bolus of 0.5 mg/kg followed by a continuous infusion of 0.5 mg/kg/h. Using this protocol, activated clotting time values ranged from 200 to 220 seconds. After prolonged extracorporeal membrane oxygenation support and recovery of left ventricular function, a right ventricular assist device was implanted during extracorporeal membrane oxygenation support with bivalirudin anticoagulation. For this procedure an additional bolus of 0.25 mg/kg bivalirudin was given, and the infusion rate increased to 1 mg/kg/h to achieve activated clotting time values of 300 to 350 seconds. Surgery was successfully performed with moderate intraoperative and postoperative blood loss and transfusion requirements.

The more closed the bypass system the better: a pilot study on the effects of reduction of cardiotomy suction and passive venting on hemostatic activation during on-pump coronary artery bypass grafting.

Cardiac surgery with cardiopulmonary bypass (CPB) leads to a powerful activation of the hemostatic system. We assessed to what extent this activation can be attenuated by comparing three different perfusion regimens for on-pump coronary artery bypass grafting (CABG): 1) use of a closed CPB system with aspiration of blood from the operation field via the cardiotomy suction line and active venting of the heart via a roller pump; 2) use of a closed CPB system avoiding aspiration of blood from the operation field via the cardiotomy suction line, but with active venting of the heart; and 3) use of a closed system, avoidance of aspiration of blood from the operation field via the cardiotomy suction line and with passive venting of the heart into the collapsible venous reservoir. Our data show that avoidance of aspiration of blood via the cardiotomy suction line significantly reduces hemostatic activation during on-pump CABG. However, further attenuation of hemostatic activation can be achieved by further closing the system and minimizing the blood/air interface by passive venting of the heart.

Prebypass filtration of cardiopulmonary bypass circuits: an outdated technique?

Filtration of cardiopulmonary bypass (CPB) priming fluid before connection of the circuit to the patient was first accomplished by arterial line filtration. When dedicated prebypass filters (PBFs) with smaller pore sizes became available, a large number of particles could be found on the filter surface. In recent years, modern manufacturing methods for CPB circuit components were believed to be associated with a reduced number of particles found in components of extracorporeal circuits, making separate filtration of CPB priming solution unnecessary. Microemboli generated during the preparation and priming procedure of the CPB circuit may consist of either solid particles or gaseous emboli and may contribute to patient morbidity. Endotoxins found in infusion solutions and CPB priming solutions may trigger inflammatory responses when administered into the circulatory system. Filtration of crystalloid CPB priming solutions with a PBF consisting of a filter membrane with a pore size of 0.2 microm was found to effectively reduce the number of microemboli. Infusion filters with a filter pore size of 0.2 microm were found to reduce the endotoxin contamination in infusion solutions. Prebypass filtration with filters containing pores of 0.2 pm should be a necessity for contemporary perfusion practice.

Factors influencing the change in cerebral hemodynamics in pediatric patients during and after corrective cardiac surgery of congenital heart diseases by means of full-flow cardiopulmonary bypass.

BACKGROUND: The pathophysiology of hypoxic-ischemic brain injury in relation to extracorporeal circulation is multifactorial and can be interpreted, in part, as possible alteration in cerebral perfusion and inadequate oxygen delivery to the brain cells. The aim of this study was to evaluate influencing factors on the change in cerebral blood flow velocity (CBFV) patterns determined by transcranial Doppler sonography (TCD) in infants who undergo corrective cardiac surgery by means of full-flow cardiopulmonary bypass (CPB). METHODS: Included in the study were 67 neonates, infants, and children with a median age of 4 months (0.1-70 months), median weight of 4.8 kg (2.5-18.8 kg), and with cyanotic and noncyanotic congenital heart disease (CHD), who underwent surgical correction of CHD by means of CPB [flow rate 144 +/- 47 ml/kg body weight (BW)] and the alpha-stat strategy. The patients were divided into three groups with respect to the minimum rectal temperature during perfusion: deep hypothermic CPB (<18 degrees C) n=18, moderate hypothermic CPB (22-35 degrees C) n=29, normothermic CPB (36 degrees C) n=20. Continuous determination of mean flow velocity (Vmean) in the middle cerebral artery (MCA) by TCD provided qualitative on-line information on cerebral perfusion. The pulsatility index (PI) was calculated in accordance with the formula: Maximum flow velocity - end - diastolic flow velocity/ Mean flow velocity and was used as a parameter for the qualitative assessment of cerebrovascular resistance after the end of CPB. RESULTS: The Vmean was significantly increased 15 min after cross-clamping in the normothermic group (p=0.03) and decreased in the moderate hypothermic group (p=0.02) and deep hypothermic group (p=0.009). The postoperative Vmean values correlated significantly with age (r=0.79, p<0.0001), weight (r=0.75, p<0.0001), bypass time (r=-0.51, p=0.0006), and minimum rectal temperature (r=0.60, p=0.0001). Mean arterial pressure and hemoglobin concentration, but not pCO2, seem to significantly influence the change in Vmean after the termination of CPB (r=0.5, p=0.001; r=-0.55, p=0.002, respectively). In comparison with the values at the start of CPB, the Vmean was significantly decreased after the end of CPB in the hypothermic and moderate hypothermic groups and still significantly elevated in the normothermic group. The age-independent PI was increased after termination of bypass in all groups (p<0.05) and still slightly elevated after the end of operation in the hypothermic group (p=0.05). CONCLUSIONS: The changes in CBFV patterns before, during, and after the termination of CPB were dependent on age, weight, perfusion pressure, and degree of hypothermia during CPB.