Paul M. Kirshbom

Extracorporeal membrane oxygenation for infant postcardiotomy support: significance of shunt management.

BACKGROUND After repair of complex congenital heart defects in infants and children, postcardiotomy cardiac failure requiring temporary circulatory support can occur. This is usually accomplished with the use of extracorporeal membrane oxygenation (ECMO). ECMO management of patients with single-ventricle physiology and aorto-pulmonary shunts can be particularly challenging. We retrospectively reviewed our experience with postcardiotomy support with particular attention to those children with single-ventricle palliation. METHODS Thirty-five consecutive children (age 1 to 820 days, median 19 days) out of 1,020 patients (3.4%) required mechanical support (ECMO) after repair of congenital cardiac lesions from February 1994 to April 1999. Twenty-five patients underwent two ventricle repairs and 10 patients had single-ventricle palliation. Various parameters analyzed included strategies of shunt management, presence of presupport cardiac arrest, and timing of support initiation. RESULTS Overall hospital survival for these 35 patients was 61%. There were four additional late deaths. Hospital survival was the same for those patients in whom support was initiated for failure to wean from cardiopulmonary bypass in the operating room versus those patients in whom support was initiated after successful separation from cardiopulmonary bypass (6 of 10 vs 15 of 25 or 60% survival). In those patients with shunt-dependent pulmonary circulation, survival was significantly improved in those patients in which the aorto-pulmonary shunt was left open (4 of 5 with open shunt vs 0 of 4 with occluded shunt (p = 0.048). CONCLUSIONS The ability to readily implement postcardiotomy support is vital to the management of children with complex congenital cardiac disease. Overall survival can be quite satisfactory if support is employed in a rational and expedient manner. In patients with single-ventricle physiology and aorto-pulmonary shunts, leaving the shunt open during the period of support can result in markedly improved outcomes.

Gastrointestinal Carcinoids: Characterization by Site of Origin and Hormone Production

ObjectiveTo describe a large series of patients with carcinoid tumors in terms of presenting symptoms, hormonal data, stage at diagnosis, pathologic features, and survival. Summary Background DataPublished series have described significant prognostic features of carcinoid tumors as site of origin, age, sex, stage at diagnosis, presence of high hormone levels, and increased T stage. Of these, stage at diagnosis and T stage seem to emerge most often as independent predictors of survival in multivariate analyses. Of carcinoid tumors, those arising from a midgut location have higher levels of serotonin and serotonin breakdown products, as well as more frequent metastatic disease at presentation, than those arising from either foregut or hindgut locations. MethodsA prospective database of carcinoid patients seen at Duke University Medical Center was kept from 1970 to the present. Retrospective medical record review was performed on this database to record presenting symptoms, hormonal data, pathologic features, and survival. Statistical methods included analysis of variance, Kaplan-Meier analysis, and Mantel-Cox proportional hazard survival analysis, with P < .05 considered significant for all tests. ResultsCarcinoids arising in different locations had different presentations: rectal carcinoids presented significantly more often with gastrointestinal bleeding, and midgut carcinoids presented significantly more often with flushing, diarrhea, and the carcinoid syndrome. Patients with midgut tumors had significantly higher levels of serotonin and serotonin breakdown products, corresponding to higher metastatic tumor burdens. Although age, stage, region of origin, and urinary level of 5-hydroxyindoleacetic acid predicted survival by univariate analysis, only the latter three were independent predictors of survival by multivariate analysis. Of the patients with metastatic disease at diagnosis, those with midgut tumors had better survival than those with foregut or hindgut tumors. ConclusionsAlthough region of origin is certainly an important factor in determination of prognosis, stage of disease at presentation is more predictive of survival. Pancreatic and midgut carcinoids are metastatic at diagnosis more often than those arising in other locations, leading to a worse overall prognosis. Among patients with distant metastases, patients with midgut primary tumors have improved survival despite increased hormone production compared with patients with tumors arising in other primary sites.

Modified ultrafiltration improves cerebral metabolic recovery after circulatory arrest

Modified ultrafiltration uses hemofiltration of the patient and bypass circuit after separation from cardiopulmonary bypass to reverse hemodilution and edema. This study investigated the effect of modified ultrafiltration on cerebral metabolic recovery after deep hypothermic circulatory arrest. Twenty-six 1-week-old piglets (2 to 3 kg) were supported by cardiopulmonary bypass (37 degrees C) at 100 ml.kg-1.min-1 and cooled to 18 degrees C. Animals underwent 90 minutes of circulatory arrest followed by rewarming to 37 degrees C. After being weaned from cardiopulmonary bypass, animals were divided into three groups: controls (n = 10); modified ultrafiltration for 20 minutes (n = 9); transfusion of hemoconcentrated blood for 20 minutes (n = 7). Global cerebral blood flow was measured by xenon 133 clearance methods: stage I--before cardiopulmonary bypass; stage II--5 minutes after cardiopulmonary bypass; and stage III--25 minutes after cardiopulmonary bypass. Cerebral metabolic rate of oxygen consumption, cerebral oxygen delivery, and hematocrit value were calculated for each time point. At point III, the hematocrit value (percent) was elevated above baseline in the ultrafiltration and transfusion groups (44 +/- 1.8, 42 +/- 1.8 versus 28 +/- 1.7, 30 +/- 0.7, respectively, p < 0.05). Cerebral oxygen delivery (ml.100 gm-1.min-1) increased significantly above baseline at point III after ultrafiltration (4.98 +/- 0.32 versus 3.85 +/- 0.16, p < 0.05) or transfusion (4.59 +/- 0.17 versus 3.89 +/- 0.06, p < 0.05) and decreased below baseline in the control group (2.77 +/- 0.19 versus 3.81 +/- 0.16, p < 0.05). Ninety minutes of deep hypothermic circulatory arrest resulted in impaired cerebral metabolic oxygen consumption (ml.100 gm-1.min-1) at point III in the control group (1.95 +/- 0.15 versus 2.47 +/- 0.07, p < 0.05) and transfusion group (1.72 +/- 0.10 versus 2.39 +/- 0.15, p < 0.05). After modified ultrafiltration, however, cerebral metabolic oxygen consumption at point III had increased significantly from baseline (3.12 +/- 0.24 versus 2.48 +/- 0.13, p < 0.05), indicating that the decrease in cerebral metabolism immediately after deep hypothermic circulatory arrest is reversible and may not represent permanent cerebral injury. Use of modified ultrafiltration after cardiopulmonary bypass may reduce brain injury associated with deep hypothermic circulatory arrest.

Intermediate-term mortality and cardiac transplantation in infants with single-ventricle lesions: Risk factors and their interaction with shunt type

OBJECTIVE The study objective was to identify factors associated with death and cardiac transplantation in infants undergoing the Norwood procedure and to determine differences in associations that might favor the modified Blalock-Taussig shunt or a right ventricle-to-pulmonary artery shunt. METHODS We used competing risks methodology to analyze death without transplantation, cardiac transplantation, and survival without transplantation. Parametric time-to-event modeling and bootstrapping were used to identify independent predictors. RESULTS Data from 549 subjects (follow-up, 2.7 ± 0.9 years) were analyzed. Mortality risk was characterized by early and constant phases; transplant was characterized by only a constant phase. Early phase factors associated with death included lower socioeconomic status (P = .01), obstructed pulmonary venous return (P < .001), smaller ascending aorta (P = .02), and anatomic subtype. Constant phase factors associated with death included genetic syndrome (P < .001) and lower gestational age (P < .001). The right ventricle-to-pulmonary artery shunt demonstrated better survival in the 51% of subjects who were full term with aortic atresia (P < .001). The modified Blalock-Taussig shunt was better among the 4% of subjects who were preterm with a patent aortic valve (P = .003). Lower pre-Norwood right ventricular fractional area change, pre-Norwood surgery, and anatomy other than hypoplastic left heart syndrome were independently associated with transplantation (all P < .03), but shunt type was not (P = .43). CONCLUSIONS Independent risk factors for intermediate-term mortality include lower socioeconomic status, anatomy, genetic syndrome, and lower gestational age. Term infants with aortic atresia benefited from a right ventricle-to-pulmonary artery shunt, and preterm infants with a patent aortic valve benefited from a modified Blalock-Taussig shunt. Right ventricular function and anatomy, but not shunt type, were associated with transplantation.

Nesiritide in infants and children with congestive heart failure.

Objectives: Nesiritide (synthetic B-type natriuretic peptide) has been shown to be effective in the management of acute decompensated heart failure in adults. The role of nesiritide in pediatric heart failure has not been examined. In the present study, we reviewed our initial experience with nesiritide in children with primary heart failure or low cardiac output after heart surgery. Methods: Nesiritide was administered in an open-label fashion to patients with heart failure who were already receiving inotropic and diuretic therapy. Between July 2003 and August 2004, 30 patients aged 5 days to 16.7 yrs (median age, 4.6 months) received nesiritide therapy. Diagnoses included single-ventricle congenital defect (n = 5), two-ventricle congenital defect (n = 13), heart transplant (n = 5), and dilated cardiomyopathy (n = 7). Sixteen patients were started on nesiritide within 2 wks of corrective or palliative heart surgery. The majority of subjects (n = 24) received an initial bolus dose. Continuous infusion dosage ranged between 0.005 and 0.02 &mgr;g·kg−1·min−1. Nesiritide was discontinued for possible side effects in two patients (arrhythmia and hypotension). Duration of therapy ranged from 1 to 24 days (median, 4 days). Results: Administration of nesiritide was associated with improvement in fluid balance from positive 0.8 ± 1.9 mL·kg−1·hr−1 at baseline to negative 0.3 ± 1.8 mL·kg−1·hr−1 after 24 hrs of therapy (p = .02). There was a nonsignificant trend toward a reduction in right atrial pressure (9.2 ± 3.9 vs. 11.2 ± 4.1, p = .08). Conclusions: Nesiritide is well tolerated in children with heart failure and is associated with improved diuresis. Further prospective studies will be needed to compare nesiritide with other vasoactive agents and examine the cost-efficacy of this therapy.

Results with the freestyle porcine aortic root for right ventricular outflow tract reconstruction in children

BACKGROUND The ideal choice for valved reconstruction of the right ventricular outflow tract (RVOT) in children is undetermined. This study explores the Freestyle porcine aortic root for these patients. METHODS From January 1998 to December 2002, 56 patients ages 1.6 to 29.9 years old (mean 11.8 years old) underwent RVOT reconstruction using a Freestyle porcine aortic root. The patients averaged 1.9 prior operations (range 0 to 5) for tetralogy of Fallot +/- pulmonary atresia (28 patients), critical pulmonary stenosis (10 patients), Ross procedure (5 patients), pulmonary atresia/intact ventricular septum (4 patients), complete atrioventricular septal defect +/- tetralogy of Fallot (4 patients), and others (5 patients). At time of RVOT reconstruction, 42 patients (75%) had additional procedures including the following: tricuspid or mitral repair (24 patients), pulmonary arterioplasty +/- Glenn (12 patients), ventricular septal defect closure (5 patients), aortic valve replacement (3 patients), placement of a cardioverter/defibrillator or pacemaker (3 patients), and others (8 patients). RESULTS One patient developed mediastinitis; another was treated for Candida endocarditis (his excised homograft unexpectedly grew Candida). All patients are well on follow-up from 2 to 60 months (mean 30 +/- 20 months) with no deaths. The patient with endocarditis underwent conduit replacement for recurrent pulmonary stenosis 3.5 years postoperatively. Echocardiography revealed mild or no pulmonary insufficiency in 93%. The calculated mean peak systolic RVOT gradient by echocardiography was 19.7 +/- 15.4 mm Hg. CONCLUSIONS These data demonstrate excellent results with the Freestyle bioprosthesis for RVOT reconstruction in children. This valve may serve as a readily available alternative to homograft valves in RVOT reconstruction, particularly since early insufficiency seems to be less problematic. Questions of long-term durability and significance of echocardiographic stenosis remain unanswered.

Heart Transplantation in Children With a Fontan Procedure

BACKGROUND Previous studies have reported that children with a prior Fontan procedure have decreased survival after heart transplantation. We examined 190 primary pediatric heart transplants. METHODS Since 1988, 27 (14.2%) of 190 children less than 18 years old undergoing primary heart transplantation had a Fontan procedure 3.7 ± 4.3 years before transplantation. Compared with 163 (85.8%) non-Fontan primary transplants, the Fontan patients were similar in age (8.2 ± 5.0 vs 6.5 ± 6.0 years), presensitization, and pretransplant clinical status. More Fontan patients had prior operations (100% vs 50%; p < 0.0001) and needed pulmonary artery reconstruction (100% vs 23.5%; p < 0.0001). Twelve (44%) had protein-losing enteropathy. RESULTS Donor ischemic times (211 ± 72 vs 170 ± 61 minutes; p = 0.0018) and cardiopulmonary bypass times (197 ± 91 vs 121 ± 53 minutes; p < 0.0001) were greater in the Fontan group as were durations of ventilator support (4.9 ± 6.6 vs 2.6 ± 3.9 days; p = 0.018) and hospital stay (20.2 ± 17.5 vs 14.3 ± 12.4 days; p = 0.0435). The Fontan group had one 30-day mortality. One-year actuarial survival (81.5% vs 84.6%, Fontan vs non-Fontan) and five-year actuarial survival (65.5% vs 66.2%, Fontan vs non-Fontan) were similar, as was rejection incidence at one year (2.0 ± 2.0 vs 1.7 ± 1.9 episodes per patient; p = 0.3972). Five Fontan patients (18.5%) required retransplantation 4.9 ± 3.6 years posttransplant compared with 18 non-Fontan patients (11.0%) retransplanted 5.2 ± 3.4 years posttransplant (p = 0.3346). CONCLUSIONS Contrary to prior reports, we did not identify any early or midterm disadvantage for children undergoing heart transplantation after a previous Fontan procedure despite more complex transplant operations. We contend that carefully selected children with a failing Fontan circulation can do as well as other children with heart transplantation.

Postoperative Cerebral Oxygenation in Hypoplastic Left Heart Syndrome After the Norwood Procedure

BACKGROUND Cerebral near-infrared spectroscopy (NIRS) is being used with increasing frequency in the care of pediatric patients after surgery for congenital heart disease. Near-infrared spectroscopy provides a means of evaluating regional cerebral oxygen saturation (cSaO(2)) noninvasively, with correlations to cardiac output and central venous saturation. Prior studies have demonstrated that systemic venous saturation can predict outcome after the Norwood procedure. With this in mind, we sought to determine whether regional cSaO(2) by NIRS technology could predict risk of adverse outcome after the Norwood procedure. METHODS We reviewed the first 48 hours of postoperative hemodynamic data on 50 patients with hypoplastic left heart syndrome at our institution who underwent the Norwood procedure. Cerebral oxygen saturation data within 48 hours of surgery were analyzed for association with subsequent adverse outcome, which was defined as intensive care unit length of stay greater than 30 days, need for extracorporeal membrane oxygenation, or hospital death after 48 hours. RESULTS There were 18 adverse events among the 50 subjects. The mean cSaO(2) for the entire cohort at 1 hour, 4 hours, and 48 hours after surgery was 51% +/- 7.5%, 50% +/- 9.4%, and 59% +/- 8.1%, respectively. Mean cSaO(2) for the first 48 postoperative hours of less than 56% was a risk factor for subsequent adverse outcome (odds ratio 11.9, 95% confidence interval: 2.5 to 55.8). Mean cerebral NIRs of less than 56% over the first 48 hours after surgery yielded a sensitivity of 75.0% and a specificity of 79.4% to predict those at risk for subsequent adverse events. CONCLUSIONS Low regional cerebral oxygen saturation by NIRS in the first 48 hours after the Norwood procedure has a strong association with subsequent adverse outcome. Monitoring of cerebral saturation can serve as a valuable monitoring tool and can identify patients at risk for poor outcome.

The bidirectional Glenn operation: a risk factor analysis for morbidity and mortality.

OBJECTIVE Patients with single ventricle heart defects often undergo a palliative bidirectional Glenn operation. For this operation, we analyzed potential risk factors for morbidity and mortality. We also evaluated the effects of a persistent left superior vena cava by comparing the outcomes of unilateral and bilateral operations. METHODS We reviewed the clinical records of 270 consecutive patients who underwent a bidirectional Glenn operation between 2001 and 2007. A total of 226 patients underwent unilateral operations and 44 patients underwent bilateral operations. Patient characteristics included weight and age, single ventricle morphology, vena caval anatomy, and previous surgery. Operative details included cardiopulmonary bypass technique and duration, pulmonary artery management, hemi-Fontan construction, concomitant procedures, and hemodynamics. Outcome data included duration of chest tube drainage, lengths of intensive care unit and hospital stay, morbidity, and mortality (<30 days). RESULTS The median length of chest tube drainage was 2.4 days (range 1-20 days). Risk factors for prolonged drainage were elevated central venous pressure (P = .015) and transpulmonary gradient (P = .011). The median lengths of stay in the intensive care unit and hospital were 50 hours (range 20-1628 hours) and 5 days (range 2-83 days), respectively. Risk factors for both included prolonged cardiopulmonary bypass time, elevated central venous pressure and transpulmonary gradient, and right ventricular morphology. Overall, 72 of 270 patients (27%) had 116 postoperative complications. Risk factors included prolonged cardiopulmonary bypass time (P = .002) and elevated central venous pressure (P = .029). Mortality was 2 of 270 patients (0.7%). No risk factors for death were identified. Weight (median 6.8 kg vs 6.2 kg, P = .038) and age (median 186 days vs 159 days, P = .001) at the time of surgery were significantly greater in the bilateral bidirectional Glenn group compared with the unilateral group. However, there was no difference in any of the outcome variables. CONCLUSION Outcomes were adversely affected primarily by prolonged cardiopulmonary bypass time, elevated central venous pressure and transpulmonary gradient, and right ventricular morphology. Specifically, outcomes were unaffected by the presence of a left superior vena cava, cannulation strategy, or antegrade pulmonary blood flow. There were few differences between the unilateral and bilateral groups, none of which were postoperative outcomes.

Effects of cardiopulmonary bypass and circulatory arrest on endothelium-dependent vasodilatation in the lung ☆ ☆☆ ★ ★★ ♢

Endothelial injury with failure of pulmonary endothelium-dependent vasodilatation has been proposed as a possible cause for the increased pulmonary vascular resistance observed after cardiopulmonary bypass, but the mechanisms underlying this response are not understood. An in vivo piglet model was used to investigate the role of endothelium-dependent vasodilatation in postbypass pulmonary hypertension. The pulmonary vascular responses to acetylcholine, a receptor-mediated endothelium-dependent vasodilator, and nitric oxide, an endothelium-independent vasodilator, were studied in one group of animals after preconstriction with the thromboxane A2 analog U46619 (n = 6); a second group was studied after bypass with 30 minutes of deep hypothermic circulatory arrest (n = 6). After preconstriction with U46619, both acetylcholine and nitric oxide caused significant decreases in pulmonary vascular resistance (34% +/- 6% decrease, p = 0.007, and 39% +/- 4% decrease, p = 0.001). After cardiopulmonary bypass with circulatory arrest, acetylcholine did not significantly change pulmonary vascular resistance (0% +/- 8% decrease, p = 1.0), whereas nitric oxide produced a 32% +/- 4% decrease in pulmonary vascular resistance (p = 0.007). These results demonstrate a loss of receptor-mediated endothelium-dependent vasodilatation with normal vascular smooth muscle function after circulatory arrest. Administration of the nitric oxide synthase blocker Ngamma-nitro-L-arginine-methyl-ester after circulatory arrest significantly increased pulmonary vascular resistance; thus, although endothelial cell production of nitric oxide may be diminished, it continues to be a major contributor to pulmonary vasomotor tone after cardiopulmonary bypass with deep hypothermic circulatory arrest. In summary, cardiopulmonary bypass with deep hypothermic circulatory arrest results in selective pulmonary endothelial cell dysfunction with loss of receptor-mediated endothelium-dependent vasodilatation despite preserved ability of the endothelium to produce nitric oxide and intact vascular smooth muscle function.