Craig W. Lillehei

Mortality of necrotizing enterocolitis expressed by birth weight categories

PURPOSE Low birth weight is the most important risk factor for developing necrotizing enterocolitis (NEC). We aimed to establish birth weight-based benchmarks for in-hospital mortality in neonates with NEC. METHODS Five hundred eleven centers belonging to the Vermont Oxford Network prospectively evaluated 71,808 neonates with birth weight of 501 to 1500 g between January 2005 and December 2006. The primary outcome variable was in-hospital mortality. RESULTS Birth weight was divided into 4 categories by 250-g increments. The NEC risk (P < .001) and mortality (P < .001) decreased with higher birth weight category. Necrotizing enterocolitis was associated with a significant odds ratio for death for each category (P < .001). Across groups, the odds ratio for NEC mortality increased with higher birth weight category (category 1 = 1.6 vs category 4 = 9.9; P < .001). CONCLUSION The in-hospital mortality rate of neonates with NEC remains high and is significantly related to birth weight category. Although the risk and absolute mortality of NEC decrease with higher birth weight, the odds ratios indicate that NEC has a relatively greater impact upon mortality at higher birth weight. These data afford birth weight-based mortality benchmarks that may be useful in assessing single center NEC outcomes and facilitating comparisons between centers.

Congenital diaphragmatic hernia--a tale of two cities: the Boston experience.

Infants with congenital diaphragmatic hernia (CDH) show a wide range of anatomic and physiological abnormalities, making it difficult to compare the efficacy of management protocols between institutions. The purpose of this study was twofold: (1) to analyze the results of treatment of CDH in a large tertiary care pediatric center using conventional mechanical ventilation (CMV) with extracorporeal membrane oxygenation (ECMO) as rescue therapy, and (2) to compare these results with those of a parallel study by a similar large urban center that used high-frequency oscillating ventilation (HFOV) as rescue therapy without ECMO. All patients who had CDH diagnosed within the first 12 hours of life and were referred for treatment before repair (between 1981 and 1994) were included in the analysis (n = 196). CMV was used initially in all patients, with conversion to ECMO for refractory hypoxemia or hypercapnea. Between 1981 and 1984, ECMO was not available. Between 1984 and 1987, ECMO was offered postoperatively. Between 1987 and 1991, ECMO was offered preoperatively. In all three groups, aggressive hyperventilation and alkalosis was the norm. Since 1991, permissive hypercapnia has been used. HFOV was used in three patients as stand-alone therapy with one survivor. Twenty patients died without repair: Ten had other lethal anomalies, eight died before ECMO could be instituted, and two died of ECMO-related complications. Overall, 104 patients (53%) survived and 92 (47%) died. Ninety-eight patients (50%) received ECMO, and 43 (44%) survived. Survivors had significantly higher 1- and 5-minute Apgar scores and higher postductal Po2s than did nonsurvivors. Associated anomalies were present in 39%, who had a significantly lower survival than those with isolated CDH. Antenatal diagnosis and side of the defect had no impact on outcome. Survival was not improved with the institution of ECMO or delayed repair but rose significantly to 69% (84% with isolated CDH, P = .007) with the introduction of permissive hypercapnea. Autopsy results from nonsurvivors showed other lethal anomalies and significant barotrauma as the primary causes of death. Comparisons between the Boston and Toronto series showed similar patient demographics and no significant differences in survival in any time period. The two series differed in the number of associated anomalies, their impact on survival, and in the prognosis of right-sided CDH. From the individual and combined analyses the authors concluded: (1) CMV with ECMO as rescue produced an overall survival in CDH patients equivalent to CMV with HFOV in a parallel series, (2) neither HFOV nor ECMO has significantly improved outcome in CDH patients, (3) institution of permissive hypercapnia has resulted in a significant increase in survival, and (4) the leading causes of death in CDH patients appear to be associated anomalies and pulmonary hypoplasia, which are currently untreatable. Barotrauma, which may contribute in up to 25% of deaths in CDH patients is avoidable.

Inhaled nitric oxide in the treatment of postoperative graft dysfunction after lung transplantation

Pulmonary hypertension and transient graft dysfunction may complicate the postoperative course of patients undergoing lung transplantation. We report the acute effect of inhaled nitric oxide (80 ppm) on hemodynamics and gas exchange in 6 patients (median age, 14 years; range, 5 to 21 years) after lung transplantation as well as the effect of extended treatment over 40 to 69 hours in 2 patients. In 5 patients with pulmonary hypertension nitric oxide lowered mean pulmonary artery pressure (from 38.4 +/- 1.6 to 29.4 +/- 3.1 mm Hg; p < 0.05), pulmonary vascular resistance index (from 9.3 +/- 1.4 to 6.4 +/- 1.3 Um2; p < 0.05), and intrapulmonary shunt fraction (from 28.6% +/- 8.3% to 21.0% +/- 5.7%; p < 0.05). There was a 28.4% +/- 7.2% reduction in transpulmonary pressure gradient with only minor accompanying effects on the systemic circulation. Mean arterial pressure decreased only 2.7% +/- 5% (from 76.4 +/- 2.2 to 74 +/- 2.3 mm Hg; p = not significant), and systemic vascular resistance index by 4.2% +/- 9.7% (from 21.7 +/- 3.1 to 20.6 +/- 3.6 Um2; p = not significant). Cardiac index was unchanged (from 3.5 +/- 0.8 to 3.6 +/- 0.7 L.min-1.m-2; p = not significant). Nitric oxide caused a sustained improvement in oxygenation and pulmonary artery pressure during extended therapy at doses of 10 ppm. There were no major side effects. However, transient methemoglobinemia (9%) developed in 1 patient after 10 hours of nitric oxide treatment. Nitric oxide may be useful in the treatment of pulmonary hypertension and the impaired gas exchange that occurs after lung transplantation.

Congenital diaphragmatic hernia. Stabilization and repair on ECMO.

Availability of extracorporeal membrane oxygenation (ECMO) support and the potential advantages of delayed repair of congenital diaphragmatic hernia (CDH) have led several centers to delay CDH repair, using ECMO support if necessary. This study reviews the combined experience of five ECMO centers with infants who underwent stabilization with ECMO and repair of CDH while still on ECMO. All infants were symptomatic at birth, with a mean arterial oxygen pressure (PaO2) of 34 mmHg on institution of bypass despite maximal ventilatory support. A total of 42 infants were repaired on ECMO, with 18 (43%) surviving. Seven infants had total absence of the diaphragm, and 28 required a prosthetic patch to close the defect. Only five infants ever achieved a best postductal PaO2 over 100 mmHg before institution of ECMO. Prematurity was a significant risk factor, with no infants younger than 37 weeks of age surviving. Significant hemorrhage on bypass was also a hallmark of a poor outcome, with 10 of the 24 nonsurvivors requiring five thoracotomies and six laparotomies to control bleeding, whereas only one survivor required a thoracotomy to control bleeding. In follow-up, nine of the 18 survivors (50%) have developed recurrent herniation and seven (43%) have significant gastroesophageal reflux. Importantly, five of the 18 survivors were in the extremely high-risk group who never achieved a PaO2 over 100 mmHg or an arterial carbon dioxide pressure (PaCO2) less than 40 mmHg before the institution of ECMO. In conclusion, preoperative stabilization with ECMO and repair on bypass may allow some high-risk infants to survive. Surviving infants will require long-term follow-up because many will require secondary operations.

Delayed repair and preoperative ECMO does not improve survival in high-risk congenital diaphragmatic hernia

It has been suggested that delayed repair with preoperative stabilization might improve survival in high-risk (symptomatic within 6 hours of birth) congenital diaphragmatic hernia (CDH). This study compares the results of immediate operation versus delayed repair using extracorporeal membrane oxygenation (ECMO) when necessary. Since we first used ECMO in 1984, 101 high-risk CDH infants have been treated. Prior to 1987, we used immediate repair and postoperative ECMO if necessary. Between 1987 and 1990 we combined delayed operation (24 to 36 hours) with preoperative ECMO as necessary. No infant in this series was excluded from ECMO therapy unless absolute contraindications existed (prematurity, intracranial hemorrhage, or other major anomalies). Fifty-five patients received immediate operation and 46 had delayed repair. The two groups were comparable populations based on gestational age, birth weight, age at onset of symptoms, Apgar scores, best postductal PO2 (BPDPO2), and frequency of antenatal diagnosis. There was no statistically significant difference in overall survival between the two groups. Differences in survival among subpopulations (BPDPO2 greater than 100 or less than 100, antenatal diagnosis, inborn v outborn) also are not significant. The requirement for ECMO was similar in both groups. Survivors in the delayed repair group were ventilated longer and on ECMO longer, but had fewer late deaths (greater than 21 days) and fewer pulmonary sequelae (O2 dependency at discharge) than infants in the immediate repair group (P less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Bronchial Atresia Is Common to Extralobar Sequestration, Intralobar Sequestration, Congenital Cystic Adenomatoid Malformation, and Lobar Emphysema

Congenital cystic adenomatoid malformation (CCAM), intralobar sequestration (ILS), extralobar sequestration (ELS), and lobar emphysema (LE) are well-accepted entities; however, certain findings are common to all, particularly the parenchymal maldevelopment characterizing CCAM. Isolated reports have described bronchial atresia (BA) in some specimens in all 4 entities, but this finding has not been evaluated in a prospective manner. With the aid of a dissecting microscope, we prospectively examined 47 lung specimens resected during the past 4 years and submitted with the clinical impression of ELS (n = 11), ILS (n = 11), CCAM (n = 20), LE (n = 4), and airway-esophageal communication (n = 1). Most lesions were detected by prenatal ultrasound and were resected during infancy. The clinical impression and pathologic findings were compared. Pathologic examination revealed atresia of a lobar, segmental, or subsegmental bronchus in 100% of ELS, 82% of ILS, 70% of CCAM, and 50% of LE (those clinically recognized to have BA or minor CCAM) cases. Parenchymal maldevelopment that characterizes CCAM was present in 100% of CCAM cases (as expected by definition) as well as in 91% of ELS, 91% of ILS, and 50% of LE (those with BA) cases. Bronchial atresia is present in all ELS, most ILS and CCAM, and some LE cases, and its detection is greatly enhanced with the dissecting microscope. Bronchial atresia and CCAM nearly always coexist. It may be that both have the same etiopathogenesis with anatomic differences accounted for by aberrant genetic programs or other insults, perhaps modified by time of onset or duration.

Congenital diaphragmatic hernia: Predictors of severity in the ECMO era

Infants with congenital diaphragmatic hernia (CDH) demonstrate a wide range of anatomic and physiologic abnormalities, making it difficult to compare the efficacy of new forms of therapy such as extracorporeal membrane oxygenation (ECMO) among institutions. This study was undertaken to determine whether any predictors of severity could be identified in the ECMO era. The charts of all patients with CDH treated at this institution since 1984, when ECMO became available. (n = 110), were reviewed. Infants were considered high risk and included in this study if they presented with respiratory distress within the first 6 hours of life (n = 94). In order to focus on predictors of pulmonary insufficiency, patients who died of nonpulmonary causes or had other significant congenital anomalies were excluded from this review, leaving 59 patients for analysis. All the infants during this period had intensive pharmacological and ventilatory support. When needed, ECMO was offered postoperatively from 1984 to 1987, and preoperatively from 1987 to the present. Forty-five of 59 had a best postductal PO2 (BPDPO2) greater than 100 mm Hg, and 41 of these responders survived (91%). Fourteen patients had a BPDPO2 less than 100 mm Hg and only one survived (7%) (P = .0001). Mean BPDPO2 between survivors with or without ECMO, and nonsurvivors were also significantly different (P = .001). To incorporate ventilatory information, an oxygenation/ventilation index was devised: [OVI = PO2/(mean airway pressure x respiratory rate) x 100]. Differences in OVI between these three groups were also significant. When analyzing the data by the method proposed by Bohn (PCO2 v VI), no correlation between ventilatory parameters and outcome was found.(ABSTRACT TRUNCATED AT 250 WORDS)

Acalculous cholecystitis in children.

Acalculous cholecystitis (AC) is a rare disease in children, and its spectrum has not been well established. Twenty-five children with AC were identified (treated between 1970 and 1994) by retrospective clinical and pathological review. The authors recognized two distinct forms of this disease: acute (duration of symptoms < 1 month) and chronic (duration > 3 months). Thirteen children had acute AC. Seventy-five percent were males; the age range was from 2 months to 20 years. Of these cases, six occurred in the immediate postoperative period, five were in association with a systemic medical illness, and two had an infectious cause (Salmonella). The mean time of onset of symptoms ranged from 4 to 30 days after surgery or hospitalization (mean, 16 days). All children presented with fever, right-upper-quadrant pain, and vomiting. Other manifestations included jaundice (38%) and right-upper-quadrant mass (23%). Most had leukocytosis (76%) and abnormal liver function test results (62%). Ultrasonography was the most commonly used radiological test, and all 10 cases tested met the ultrasonographic criteria for acute AC. Cholecystectomy was performed in nine children, and pathological examination confirmed cholecystitis. No postoperative complications occurred. The other four children were managed nonoperatively with intravenous antibiotics. One died, but the other three recovered fully. Twelve children had chronic AC. Sixty-seven percent were females; the age range was 7 to 18 years. All presented with chronic symptoms of right-upper-quadrant pain and nausea or vomiting. The leukocyte count and results of liver function tests were normal. Seventy-five percent had evidence of abnormal gallbladder function (noted by a radionuclide hepatobiliary scan or cholecystography). All children in this group underwent cholecystectomy, with pathological confirmation of chronic inflammation. No complications occurred, and all patients had complete resolution of symptoms. The authors conclude that AC in children occurs in two distinct patterns. The acute and chronic forms differ in their clinical setting and presentation. Cholecystectomy is effective treatment of AC, although there may be a role for nonoperative management in selected cases.

The therapy of biliary atresia combining the Kasai portoenterostomy with liver transplantation: A single center experience***

Survival has improved dramatically for children with extrahepatic biliary atresia (EHBA), but optimal surgical management remains controversial. We have studied 28 infants born between June 1981, and April 1988, who underwent Kasais portoenterostomy as primary surgical treatment. Those with evidence of subsequent hepatic decompensation were evaluated for liver transplantation (LT). All were cared for by surgeons who perform both the Kasai portoenterostomy and LT. Following the Kasai operation, 16 of 28 patients (57.1%) have achieved total biliary drainage, while 5 of 28 (17.9%) achieved partial drainage, and 7 of 28 (25%) achieved no drainage. Nine of 28 (32.1%) have undergone LT, 4 of whom were transplanted at greater than 2 years of age. To date, 25 of 28 (89.3%) are alive. Twenty three of 25 (92%) living are jaundice-free, 65% of whom have undergone the Kasai operation only. We project that 5 of 28 (17.8%) will come to transplantation, and 12 of 28 (43%) have no current indication that they are likely to come to transplantation. We conclude that combining Kasais portoenterostomy with LT as needed is an effective therapy for children with EHBA, that the Kasai operation offers significant benefit by delaying LT in many, and that the long-term results of management remain to be determined.

The effect of extracorporeal membrane oxygenation on the survival of neonates with high-risk congenital diaphragmatic hernia: 45 cases from a single institution.

At The Childrens Hospital, Boston (TCH), in the 3 years before extracorporeal membrane oxygenation (ECMO) was available, infants with high-risk congenital diaphragmatic hernia (CDH) had a 47% survival rate. In February 1984, ECMO was introduced and offered to all high-risk CDH infants with a 100% predicted mortality. Since February 1984, 45 infants with high-risk CDH presented to TCH. Twenty-six (58%) were supported with ECMO; 19 (42%) never met the criteria for 100% predicted mortality and were supported with conventional mechanical ventilation (CMV). Overall survival was 49%. Nine (35%) of the 26 ECMO patients survived. Thirteen (68%) of the 19 CMV patients survived. Although there was no change in survival, there was a change in the cause of death. Deaths in the ECMO group were either early (n = 8, secondary to a complication of ECMO or lack of pulmonary improvement) or late (n = 9). The late deaths were infants who were successfully weaned from ECMO, never weaned from CMV, and who died secondary to complications of chronic lung disease.