Andrew J. Parry

Serum S100 protein: A potential marker for cerebral events during cardiopulmonary bypass

BACKGROUND There is no simple method to determine the incidence or severity of brain injury after a cardiac operation. A serum marker equivalent to cardiac enzymes is required. S100 protein leaks from the cerebrospinal fluid to blood after cerebral injury. We sought to determine the pattern of release after extracorporeal circulation (ECC). METHODS Thirty-four patients without neurologic problems underwent coronary bypass using ECC. Four had carotid stenoses. Nine others underwent coronary bypass without ECC. Serum S100 levels were measured before, during, and after the operation. RESULTS S100 was not detected before sternotomy. Postoperative levels of S100 were related to duration of perfusion (r = 0.89, p < 0.001). Patients who did not have ECC had undetectable or fractionally raised levels except in 1 who suffered a stroke. No patient in whom ECC was used suffered an event, but those with carotid stenosis had greater S100 levels. CONCLUSIONS S100 protein leaks into blood during ECC and may reflect both cerebral injury and increased permeability of the blood brain barrier. S100 is a promising marker for cerebral injury in cardiac surgery if elevated levels can be linked with clinical outcome.

Early and Intermediate Outcomes After Repair of Pulmonary Atresia With Ventricular Septal Defect and Major Aortopulmonary Collateral Arteries Experience With 85 Patients

BACKGROUND Pulmonary atresia with ventricular septal defect (VSD) and major aortopulmonary collaterals (MAPCAs) is a complex lesion with marked heterogeneity of pulmonary blood supply. Traditional management has involved staged unifocalization of pulmonary blood supply. Our approach has been to perform early 1-stage complete unifocalization in almost all patients. METHODS AND RESULTS Since 1992, 85 patients with pulmonary atresia, VSD, and MAPCAs have undergone unifocalization (median age, 7 months). Complete 1-stage unifocalization and intracardiac repair were performed through a midline approach in 56 patients, whereas 23 underwent unifocalization in a single stage with the VSD left open, and 6 underwent staged unifocalization through sequential thoracotomies. There were 9 early deaths. During follow-up (1 to 69 months), there were 7 late deaths. Actuarial survival was 80% at 3 years. Among early survivors, actuarial survival with complete repair was 88% at 2 years. Reintervention on the neo-pulmonary arteries was performed in 24 patients. CONCLUSIONS Early 1-stage complete unifocalization can be performed in >90% of patients with pulmonary atresia and MAPCAs, even those with absent true pulmonary arteries, and yields good functional results. Complete repair during the same operation is achieved in two thirds of patients. There remains room for improvement; actuarial survival 3 years after surgery is 80%, and there is a significant rate of reintervention. These results must be appreciated within the context of the natural history of this lesion: 65% of patients survive to 1 year of age and slightly >50% survive to 2 years even with surgical intervention.

Results of 102 cases of complete repair of congenital heart defects in patients weighing 700 to 2500 grams

BACKGROUND Published data suggest that low birth weight is a risk factor for poor outcome in corrective surgery for many cardiac defects. Congenital heart defects in low birth weight infants are typically managed with supportive therapy or palliative operations, with definitive repair delayed. The morbidity associated with such approaches is high. METHODS Since 1990 complete repair of congenital heart defects (other than patent ductus arteriosus) has been performed in 102 infants no larger than 2500 g (median 2100 g, range 700-2500 g), including 16 no larger than 1500 g. Defects included ventricular septal defect (n = 22), tetralogy of Fallot complexes (n = 20), transposition complexes (n = 13), aortic coarctation (n = 12), interrupted arch (n = 10), truncus arteriosus (n = 8), atrioventricular septal defect (n = 6), total anomalous pulmonary venous return (n = 5), and other (n = 6). RESULTS Preoperative morbidity was more common among patients referred late for surgical correction. There were 10 early deaths (10%) attributable to cardiac failure (n = 4), arrhythmia (n = 1), multiorgan failure (n = 1), sepsis (n = 1), idiopathic coronary artery intimal necrosis (n = 1), foot gangrene (n = 1), and pulmonary hemorrhage (n = 1). No patient had postbypass intracerebral hemorrhage. At follow-up (median 36 months) there were 8 late deaths, and 8 patients underwent 10 reinterventions. There was no evidence of neurologic sequelae attributable to the operation. CONCLUSIONS In general, delaying repair of congenital heart defects in low birth weight infants does not confer a benefit and is associated with higher preoperative morbidity. Complete repair of both simple and complex lesions can be achieved in such cases with good results. Growth after repair approximates the normal curve for low birth weight infants without heart disease. It is recommended that such infants, especially when they have symptoms, undergo early surgical repair rather than prolonged medical management or other forms of palliation.

Early results of the extracardiac conduit Fontan operation

BACKGROUND Among the modifications of the Fontan operation, the extracardiac approach may offer the greatest potential for optimizing early postoperative ventricular and pulmonary vascular function, insofar as it can be performed with short periods of normothermic partial cardiopulmonary bypass and without cardioplegic arrest in most cases. In this study, we reviewed our experience with the extracardiac conduit Fontan operation, with a focus on early postoperative outcomes. METHODS AND RESULTS Between July 1992 and April 1997, 51 patients (median age 4.9 years) underwent an extracardiac conduit Fontan operation. Median cardiopulmonary bypass time was 92 minutes and has decreased significantly over the course of our experience. Intracardiac procedures were performed in only 5 patients (10%), and the aorta was crossclamped in only 11 (22%). Intraoperative fenestration was performed in 24 patients (47%). There were no early deaths. Fontan failure occurred in 1 patient who was a poor candidate for the Fontan procedure. Transient supraventricular tachyarrhythmias occurred in 5 patients (10%). Median duration of chest tube drainage was 8 days. Factors significantly associated with prolonged resource use (mechanical ventilation, inotropic support, intensive care unit stay, and hospital stay) included longer bypass time and higher Fontan pressure. At a median follow-up of 1.9 years, there was 1 death from bleeding at reoperation. CONCLUSIONS The extracardiac conduit Fontan procedure can be performed with minimal mortality and morbidity. Improved results may be related to advantages of the extracardiac approach and improved preservation of ventricular and pulmonary vascular function.

Altered regulation of the ET-1 cascade in lambs with increased pulmonary blood flow and pulmonary hypertension.

Plasma concentrations of endothelin-1 (ET-1) are increased in children with congenital heart disease associated with increased pulmonary blood flow. However, the role of ET-1 in the pathophysiology of pulmonary hypertension remains unclear. Preproendothelin-1 gene expression is increased in adults with advanced pulmonary hypertension. To characterize potential early molecular alterations in the ET-1 cascade induced by increased pulmonary blood flow and pulmonary hypertension, fetal lambs underwent in utero placement of an aortopulmonary vascular graft (shunt). RNase protection assays and Western blot analysis were performed on lung tissue prepared from 4-wk-old shunt lambs and age-matched controls. Endothelin-converting enzyme-1 [the enzyme responsible for the production of active ET-1 from big ET-1, mRNA (411%, p < 0.05)] and protein (170%, p < 0.05) were increased in lung tissue prepared from shunt lambs, compared with age-matched controls. Endothelin type A receptor (the receptor that mediates vasoconstriction), mRNA (246%, p < 0.05), and protein (176%, p < 0.05) also were increased in lung tissue prepared from shunt lambs compared with age-matched controls. Conversely, endothelin type B receptor (the receptor that mediates vasodilation), mRNA (46%, p < 0.05), and protein (65%, p < 0.05) were decreased in shunt lambs. Both the mRNA and protein levels for preproendothelin-1 were unchanged. Thus we conclude that increased pulmonary blood flow and pulmonary hypertension induce early alterations in the ET-1 cascade that result in increased ET-1 production, increased ET-1-mediated vasoconstriction, and decreased vasodilation. These early alterations in gene expression may contribute to the development of pulmonary hypertension and its associated enhanced pulmonary vascular reactivity.

Resection of subaortic stenosis; can a more aggressive approach be justified?

OBJECTIVES Discrete subaortic stenosis causes left ventricular outflow tract (LVOT) obstruction and often produces aortic regurgitation (AR) which alone may precipitate surgical intervention. Conventional resection relieves the obstruction, but the recurrence rate is high, and the AR is little changed as the thick fibrous membrane which extends onto the valve leaflets remains. We studied whether an aggressive surgical approach could reduce both the severity of AR and rate of recurrence of obstruction associated with discrete subaortic stenosis, and whether this aggressive approach could be justified. METHODS Between June 1992 and April 1996, 37 patients aged 0.5-35 years (median 7.5) underwent resection of a discrete subaortic membrane. Ten underwent re-operation for recurrent obstruction and eight followed previous ventricular septal defect closure. LVOT gradient was measured using the modified Bernoulli equation and AR was graded on a scale of 0-4 (0 = none, 4 = severe). Postoperative assessment was performed early (<7 days) and at mid-term (27.0 months; range 2-59 months). RESULTS There was significant improvement in AR from mild/moderate to none/trivial (P = 0.019) immediately postoperatively and LVOT gradient from 66.9+/-30.4 to 15.1+/-12.2 mmHg (P < 0.0001). By stepwise logistic regression preoperative gradient correlated significantly with postoperative mild/moderate AR (P = 0.015) and LVOT gradient (P = 0.0036). Preoperative mild/moderate AR also correlated with postoperative mild/moderate AR (P = 0.034). Five patients developed complete heart block, four undergoing reoperation for recurrent obstruction, and one preoperatively had right bundle branch block from previous ventricular septal defect repair. At mid-term follow-up there was no increase in AR or LVOT gradient (14.8+/-12.8 mmHg). Early post-operative AR was the strongest predictor of late mild/moderate AR (P = 0.02). Early post-operative gradient was a weaker predictor (P = 0.04). Pre-operative and early post-operative gradient were significant predictors of late gradient (P = 0.0038; <0.0001, respectively). No patient required reoperation for recurrent obstruction; one underwent late aortic valve replacement for severe AR. CONCLUSIONS An aggressive surgical approach to discrete subaortic stenosis produces excellent relief of obstruction and frees the valve leaflets, significantly reducing associated AR at early and mid-term follow-up with low morbidity for primary operation. Long-term follow-up is required to confirm whether this early benefit is maintained.

Atrioventricular valve function after single patch repair of complete atrioventricular septal defect in infancy: How early should repair be attempted?

BACKGROUND Though repair of complete atrioventricular septal defect in infancy has become routine at most centers, it is not unusual for very young infants to be managed medically because of concerns about the fragility of the atrioventricular valve tissue. METHODS Since July 1992, seventy-two infants have undergone primary repair of complete atrioventricular septal defects at a median age of 3.9 months (40% < 3 months). A single-patch technique was used in all patients. The cleft was closed completely in 61 patients and partially (n = 10) or not at all (n = 1) in select patients at risk for valve stenosis. Left atrioventricular valve annuloplasty was performed in 18 patients. On the basis of transesophageal echocardiographic findings, 10 patients were returned to bypass for revision of the valve repair. RESULTS There was one early death in a patient with single left papillary muscle, no early reoperations, and no new permanent arrhythmias. Only three patients had moderate left atrioventricular valve regurgitation at discharge. During a median follow-up of 24 months, there was one late death and five reoperations for left atrioventricular valve regurgitation (n = 2) and/or systemic outflow obstruction (n = 4). Follow-up left atrioventricular valve regurgitation was moderate in three patients, mild in 14, and none/trace in 54. Age had no relation to postoperative atrioventricular valve regurgitation, death, or reoperation. CONCLUSIONS Despite concerns about fragility of valve tissue in very young patients, excellent results can be achieved with meticulous techniques. From neonates to older infants, age at repair does not influence outcome or valve function.

Management and outcomes of delayed sternal closure after cardiac surgery in neonates and infants.

Objectives: To investigate the efficacy, safety, and patterns of management of open sternotomy and delayed sternal closure in infants who were left with an open sternum after cardiac surgery and to assess these patterns for possible correlation with outcome. Design: Retrospective chart review with statistical analysis. Setting: Pediatric cardiac surgery service at a regional referral center based in an urban university teaching hospital. Patients: All 128 patients <1 yr of age who were left with an open sternum after cardiac surgery with cardiopulmonary bypass during the 4‐yr period from July, 1992 to June, 1996. Interventions: Procedures for managing open sternotomy and delayed sternal closure were analyzed retrospectively. No interventions were undertaken for the study. Measurements and Results: Of the 128 patients, 14 (11%) died before sternal closure; delayed sternal closure was performed in the remaining 114. Of these 114, 13 died in the early postoperative period. During sternal closure, significant increases were noted in pulmonary arterial (from 21.1 ± 7.6 mm Hg to 26.1 ± 6.5 mm Hg; p = .006), left atrial (from 8.4 ± 3.4 mm Hg to 11.5 ± 3.7 mm Hg; p < .001), and right atrial pressures (from 7.3 ± 2.5 mm Hg to 9.8 ± 2.5 mm Hg; p < .001). In addition, mean airway pressure (from 7.4 ± 2.0 mm Hg to 8.6 ± 2.4 mm Hg; p < .001) and peak inspiratory pressure (from 29.3 ± 5.4 mm Hg to 31.3 ± 5.6 mm Hg; p = .004) increased. Sternal wound infection occurred in one patient. Conclusions: Delayed sternal closure is an effective approach to the management of neonates and infants at risk for hemodynamic, respiratory, or hemostatic instability early after cardiac surgery. Significant changes in hemodynamics and respiratory variables occur during sternal closure, often requiring adjustment of inotropic and ventilatory management.

The effects of normoxic versus hyperoxic cardiopulmonary bypass on oxidative stress and inflammatory response in cyanotic pediatric patients undergoing open cardiac surgery: a randomized controlled trial.

OBJECTIVES This study investigates the effects of controlled reoxygenation cardiopulmonary bypass on oxidative stress, inflammatory response, and organ function in children undergoing repair of cyanotic congenital heart defects. METHODS Sixty-seven cyanotic patients (median age 15 months, interquartile range 6-49 months) undergoing corrective cardiac surgery were randomized to receive either controlled normoxic (50-0 mm Hg; n = 35) or hyperoxic (150-180 mm Hg; n = 32) cardiopulmonary bypass. Troponin I and 8-isoprostane, C3a, interleukins 6, 8, and 10, cortisol, protein S100, and alpha-glutamate transferase were measured preoperatively and 10 and 30 minutes after starting bypass, on removal of the aortic crossclamp, and 12 and 24 hours thereafter. RESULTS Overall, troponin I and 8-isoprostane levels were lower in the controlled normoxic group (-29%, 95% CI -48% to -3%, P = .03, and -26%, 95% CI -44% to -2%, P = .03, respectively). Protein S100 release was also lower in the normoxic group 10 minutes after starting bypass (-26%, 95% CI -40% to -9%, P = .005) and 10 minutes after aortic crossclamp removal (-23%, 95% CI -38% to -3%, P = .02, respectively), but similar at other time points in the two groups (P >or= .17). The alpha-glutamate transferase release was significantly lower in the normoxic group 10 minutes after aortic crossclamp removal (-28%, 95% CI -44% to -9%, P = .006, respectively) but was similar at other times (P >or= .11). Release of C3a, interleukins 6, 8, and 10, and cortisol was similar in the two groups throughout (P >or= .15). CONCLUSION Controlled reoxygenation on starting cardiopulmonary bypass is associated with reduced myocardial damage, oxidative stress, and cerebral and hepatic injury compared with hyperoxic bypass and similar whole body inflammatory and stress response in cyanotic children undergoing open cardiac surgery.

Spinal Anesthesia with an Indwelling Catheter Reduces the Stress Response in Pediatric Open Heart Surgery

Background:Extreme stress and inflammatory responses to open heart surgery are associated with increased morbidity and mortality. Based on both animal and adult human data, it was hypothesized that spinal anesthesia would be more effective at attenuating these responses than conventional high dose intravenous opioid techniques in infants and young children undergoing open heart surgery. Methods:A prospective randomized controlled clinical trial was performed in 60 children aged up to 24 months undergoing open heart surgery. Patients were randomly assigned to receive either high-dose intravenous opioid or high-dose intravenous opioid plus spinal anesthesia. Spinal anesthesia was administered via an indwelling intrathecal catheter. Results:Spinal anesthesia significantly reduced the stress responses as measured by plasma norepinephrine and epinephrine concentrations (both P < 0.05). Spinal anesthesia reduced plasma lactate concentrations (P < 0.05), but increased fluid requirements during the first postoperative day (P < 0.05). There were no differences in other cardiovascular parameters. Conclusions:Continuous spinal anesthesia reduces stress responses in infants and young children undergoing cardiac surgery with cardiopulmonary bypass more effectively than high-dose intravenous opioids alone.