Patterns of Brain Injury in Newborns Treated with Extracorporeal Membrane Oxygenation.

BACKGROUND AND PURPOSE: Neonates treated with extracorporeal membrane oxygenation are at risk for brain injury and subsequent neurodevelopmental compromise. Advances in MR imaging and improved accessibility have led to the increased use of routine MR imaging after extracorporeal membrane oxygenation. Our objective was to describe the frequency and patterns of extracorporeal membrane oxygenation-related brain injury based on MR imaging findings in a large contemporary cohort of neonates treated with extracorporeal membrane oxygenation. MATERIALS AND METHODS: This was a retrospective study of neonatal patients treated with extracorporeal membrane oxygenation from 2005-2015 who underwent MR imaging before discharge. MR imaging and ultrasound studies were reviewed for location and type of parenchymal injury, ventricular abnormalities, and increased subarachnoid spaces. Parenchymal injury frequencies between patients treated with venoarterial and venovenous extracorporeal membrane oxygenation were compared by χ2 tests. RESULTS: Of 81 neonates studied, 46% demonstrated parenchymal injury; 6% showed infarction, mostly in vascular territories (5% anterior cerebral artery, 5% MCA, 1% posterior cerebral artery); and 20% had hemorrhagic lesions. The highest frequency of injury occurred in the frontal (right, 24%; left, 25%) and temporoparietal (right, 14%; left, 19%) white matter. Sonography had low sensitivity for these lesions. Other MR imaging findings included volume loss (35%), increased subarachnoid spaces (44%), and ventriculomegaly (17% mild, 5% moderate, 1% severe). There were more parenchymal injuries in neonates treated with venoarterial (49%) versus venovenous extracorporeal membrane oxygenation (29%, P = .13), but the pattern of injury was consistent between both modes. CONCLUSIONS: MR imaging identifies brain injury in nearly half of neonates after treatment with extracorporeal membrane oxygenation. The frontal and temporoparietal white matter are most commonly affected, without statistically significant laterality. This pattern of injury is similar between venovenous and venoarterial extracorporeal membrane oxygenation, though the frequency of injury may be higher after venoarterial extracorporeal membrane oxygenation.

Validation of a noninvasive neonatal optical cerebral oximeter in veno-venous ECMO patients with a cephalad catheter.

INTRODUCTION: Cerebral Oximetry is an optical technique that allows for noninvasive and continuous monitoring of brain oxygenation by determining tissue oxygen saturation (SctO2). In conjunction with pulse oximetry, cerebral oximetry offers a promising method to estimate cerebral venous oxygen saturation (SvO2). OBJECTIVE: The aim of this study was to validate the cerebral oximetry measurements with the cerebral oxygen saturation measured from blood drawn in neonates on veno-venous ECMO with existing cephalad catheter with a prototype neonatal cerebral oximeter developed by CAS Medical Systems (Branford, CT, USA). STUDY DESIGN: After obtaining informed consent, neonates undergoing VV-ECMO with cephalad catheterization were monitored by the CAS cerebral oximeter. Cephalad blood samples were periodically obtained to validate the monitor's accuracy. RESULTS: Seventeen neonates were studied with 1718 h of cerebral oximetry data collected. Compared to the reference values, the bias+/-precision for cerebral oximetry SctO2 was 0.4+/-5.1% and derived SvO2 was 0.6+/-7.3%. CONCLUSION: We recommend the use of this noninvasive method as an alternative to blood draws for cerebral venous saturation measurements in neonates requiring extracorporeal life support.

Predicting death or extended length of stay in infants with congenital diaphragmatic hernia.

OBJECTIVE: To predict mortality or length of stay (LOS) >109 days (90th percentile) among infants with congenital diaphragmatic hernia (CDH). STUDY DESIGN: We conducted a retrospective analysis using the Children's Hospital Neonatal Database during 2010 to 2014. Infants born >34 weeks gestation with CDH admitted at 22 participating regional neonatal intensive care units were included; patients who were repaired or were at home before admission were excluded. The primary outcome was death before discharge or LOS >109 days. Factors associated with this outcome were used to develop a multivariable equation using 80% of the cohort. Validation was performed in the remaining 20% of infants. RESULTS: The median gestation and age at referral in this cohort (n=677) were 38 weeks and 6 h, respectively. The primary outcome occurred in 242 (35.7%) infants, and was distributed between mortality (n=180, 27%) and LOS >109 days (n=66, 10%). Regression analyses showed that small for gestational age (odds ratio (OR) 2.5, P=0.008), presence of major birth anomalies (OR 5.9, P<0.0001), 5- min Apgar score ⩽3 (OR 7.0, P=0.0002), gradient of acidosis at the time of referral (P<0.001), the receipt of extracorporeal support (OR 8.4, P<0.0001) and bloodstream infections (OR 2.2, P=0.004) were independently associated with death or LOS >109 days. This model performed well in the validation cohort (area under curve (AUC)=0.856, goodness-of-fit (GF) χ(2), P=0.16) and acted similarly even after omitting extracorporeal support (AUC=0.82, GF χ(2), P=0.05). CONCLUSIONS: Six variables predicted death or LOS ⩾109 days in this large, contemporary cohort with CDH. These results can assist in risk adjustment for comparative benchmarking and for counseling affected families.

Short-term outcomes after perinatal hypoxic ischemic encephalopathy: a report from the Children's Hospitals Neonatal Consortium HIE focus group.

OBJECTIVE: To characterize infants affected with perinatal hypoxic ischemic encephalopathy (HIE) who were referred to regional neonatal intensive care units (NICUs) and their related short-term outcomes. STUDY DESIGN: This is a descriptive study evaluating the data collected prospectively in the Children's Hospital Neonatal Database, comprised of 27 regional NICUs within their associated children's hospitals. A consecutive sample of 945 referred infants born ⩾36 weeks' gestation with perinatal HIE in the first 3 days of life over approximately 3 years (2010-July 2013) were included. Maternal and infant characteristics are described. Short-term outcomes were evaluated including medical comorbidities, mortality and status of survivors at discharge. RESULT: High relative frequencies of maternal predisposing conditions, cesarean and operative vaginal deliveries were observed. Low Apgar scores, profound metabolic acidosis, extensive resuscitation in the delivery room, clinical and electroencephalographic (EEG) seizures, abnormal EEG background and brain imaging directly correlated with the severity of HIE. Therapeutic hypothermia was provided to 85% of infants, 15% of whom were classified as having mild HIE. Electrographic seizures were observed in 26% of the infants. Rates of complications and morbidities were similar to those reported in prior clinical trials and overall mortality was 15%. CONCLUSION: Within this large contemporary cohort of newborns with perinatal HIE, the application of therapeutic hypothermia and associated neurodiagnostic studies appear to have expanded relative to reported clinical trials. Although seizure incidence and mortality were lower compared with those reported in the trials, it is unclear whether this represented improved outcomes or therapeutic drift with the treatment of milder disease.

Improved survival in the suckling rat model of group B streptococcal sepsis after treatment with nonsteroidal anti-inflammatory drugs.

The nonsteroidal anti-inflammatory drugs, indomethacin and ibuprofen, have been shown to increase survival in various animal models of Gram-negative or endotoxin shock. To evaluate the use of these drugs in group B streptococcal sepsis, a clinically similar disease state, a newborn suckling rat model (4 to 5 days old) designed to simulate early-onset group B streptococcal sepsis was used. Sepsis was induced by a subcutaneous injection of group B streptococcal organisms (type III). A mortality ranging from 30% to 90% was used for the study. Indomethacin (3 mg/kg) or ibuprofen (4 mg/kg) treatment was administered by an intraperitoneal injection either at the time of the bacterial injection or after bacteremia (four hours) had occurred. Indomethacin clearly improved survival rates, even when given after bacteremia. Ibuprofen also clearly increased survival when given at the same time as the bacterial injection. Ibuprofen was more effective than indomethacin in the high mortality model (lethal dose for 90% survival of group). These drugs alter mechanisms that may be important in the irreversibility of sepsis and they may become useful adjuvants to our present treatment of early onset group B streptococcal sepsis.

Doppler echocardiographic evaluation of cardiac performance in infants on prolonged extracorporeal membrane oxygenation.

Cardiac performance was evaluated by Doppler echocardiography in 19 infants with persistent pulmonary hypertension before, during and after prolonged extracorporeal membrane oxygenation (ECMO). Systemic arterial pressure was normal before ECMO (67 +/- 12 mm Hg), increased during ECMO (78 +/- 13 mm Hg) and decreased to baseline after ECMO (p less than or equal to 0.01). Heart rate was normal before ECMO and did not change during or after ECMO. The left ventricular shortening fraction was normal before ECMO (37 +/- 11%), decreased after beginning ECMO (25 +/- 11%) and returned to baseline 72 hours after beginning ECMO (p less than or equal to 0.01). Pulmonary arterial and aortic blood flow velocities were normal before ECMO, decreased 30 to 50% during ECMO and increased to baseline 72 hours after beginning ECMO (p less than or equal to 0.01). Stroke volume had an identical trend (p less than or equal to 0.01). Left ventricular velocity of circumferential shortening--an index of contractility--decreased after beginning ECMO (p less than or equal to 0.05). Left ventricular systolic wall stress--an index of systemic afterload--increased after beginning ECMO (p less than or equal to 0.01). A patent ductus arteriosus was present in 13 of 19 infants before ECMO, 16 of 19 infants during ECMO and in none of 19 infants after ECMO. Pulmonary arterial systolic pressure was high before ECMO (72 +/- 25 mm Hg), began to decrease after 48 hours on ECMO (59 +/- 24 mm Hg) and was normal after ECMO (38 +/- 18 mm Hg), p less than or equal to 0.05.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac stun in infants undergoing extracorporeal membrane oxygenation.

Previous studies have shown that cardiac performance decreases in infants undergoing extracorporeal membrane oxygenation (ECMO). Some infants have an exaggerated decrease in cardiac performance during ECMO. This syndrome has been called cardiac stun. To better understand this phenomenon, we reviewed the records of infants with cardiac stun and compared them with infants who did not have the syndrome. Cardiac stun was detected in 12 of 240 infants (5.0%) undergoing ECMO. The diagnoses were congenital diaphragmatic hernia (7/12), meconium aspiration syndrome (3/12), respiratory distress syndrome (1/12), and persistent pulmonary hypertension of the newborn (1/12). The weight, gestational age, inotropic support, and time to start of ECMO were similar to infants without cardiac stun. Arterial oxygen tension was lower, carbon dioxide tension was higher, and pH was lower before ECMO in infants in whom cardiac stun developed (p less than or equal to 0.03). Cardiac arrests were more common, before ECMO, in infants in whom cardiac stun developed (6/12; p less than or equal to 0.01). Cardiac stun began at an average 2 1/2 hours after beginning ECMO (range 0.1 to 7 hours). Pulse pressure decreased from 20 mm Hg (range 10 to 45 mm Hg) before stun to 8 mm Hg (range 4 to 12 mm Hg) after stun. Heart rate did not change. Cardiac stun lasted for 33 hours (range 1 to 64 hours) on ECMO and recurred in three infants. Decreases in pump flow and increases in preload, afterload reduction, and inotropic agents did not improve cardiac performance. Survival was lower in the infants in whom cardiac stun developed (p less than or equal to 0.001). Only 5 of 12 infants (42%) survived ECMO when cardiac stun occurred. Our findings show that cardiac stun occurs infrequently during ECMO and is transient in most infants. Infants in whom cardiac stun develops appear to be more ill before ECMO and have a higher mortality after ECMO.

Plasma thromboxane and pulmonary artery pressure in neonates treated with extracorporeal membrane oxygenation.

To examine whether neonates with persistent pulmonary hypertension are subject to a thromboxane-mediated exacerbation of their pulmonary hypertension during extracorporeal membrane oxygenator therapy (a form of partial cardiopulmonary bypass), we performed serial measurements of plasma thromboxane B2 and pulmonary artery pressure before, during, and after extracorporeal membrane oxygenation. Pulmonary artery pressure was high before extracorporeal membrane oxygenation, did not increase after the start of this therapy, but began to decrease after 48 hours of extracorporeal membrane oxygenation. During the course of extracorporeal membrane oxygenation, mean pulmonary artery pressure decreased by 50% and mean plasma thromboxane B2 levels decreased by 70%. In addition, serial plasma thromboxane B2 levels were significantly correlated with pulmonary artery pressures in individual infants with a primary diagnosis of meconium aspiration (r = 0.965 to 0.723). We speculate that the decrease in pulmonary artery pressure and plasma thromboxane B2 levels over time may reflect resolution of acute lung injury and that thromboxane B2 may play a role in regulating pulmonary artery pressure in infants with meconium aspiration.

Plasma prostanoids in neonatal extracorporeal membrane oxygenation. Influence of meconium aspiration.

Thromboxane B2 may be a mediator of neonatal persistent pulmonary hypertension. Elevated levels of plasma thromboxane and prostacyclin have been described previously in hypoxic newborn infants with neonatal pulmonary hypertension. We measured serial plasma levels of thromboxane B2 and 6-keto-prostaglandin F1 alpha (stable metabolite of prostacyclin) in 21 newborn infants with severe respiratory failure and pulmonary hypertension who required extracorporeal membrane oxygenation support. We sought to study (1) the evolution of plasma prostanoids in pulmonary hypertensive infants treated with extracorporeal membrane oxygenation and (2) whether different pulmonary hypertensive diagnostic subgroups have distinctive prostanoid profiles. Our data indicated that infants with meconium aspiration had significantly lower levels of plasma thromboxane B2 and 6-keto-prostaglandin F1 alpha while receiving extracorporeal membrane oxygenation than did infants with persistent pulmonary hypertension but no meconium aspiration. Levels of all infants decreased progressively as extracorporeal membrane oxygenation support continued.

Cardiac determinants of cerebral blood flow during extracorporeal membrane oxygenation.

Doppler recordings of the pericallosal artery (PCA) and echocardiographic examinations were performed on nine infants before, and at 24-, 72-, and 96-hour intervals during extracorporeal membrane oxygenation (ECMO). Systolic indices of left ventricular (LV) function, as well as mean blood flow velocity and pulsatility in the PCA, were measured. Arterial blood gases and blood pressure were monitored. LV cardiac output and LV stroke volume decreased during early ECMO and returned toward baseline as ECMO flow rates decreased. In the PCA, changes in pulsatility paralleled changes in ventricular performance. Pulsatility decreased during early ECMO and returned toward baseline with time. There was an inverse relationship between mean blood flow velocity in the PCA and ventricular function during early ECMO. Mean blood flow velocity increased during early ECMO and returned toward baseline as ECMO flow rates decreased. Early changes in mean blood flow velocity were associated with an initial increase in arterial pO2, pCO2, and mean blood pressure. Total aortic flow (ECMO flow + LV cardiac output in cc/kg), arterial blood gases, and mean blood pressure remained unchanged during prolonged ECMO. These data suggest that the pulsatility of cerebral blood flow is related to cardiac function during partial bypass and that the regulation of cerebral blood flow during prolonged bypass may be dependent on the presence of pulsatile flow.

Congenital diaphragmatic hernia survival and use of extracorporeal life support at selected level III nurseries with multimodality support.

BACKGROUND: Congenital diaphragmatic hernia (CDH) has been cited to have a mortality rate of 50%. There have been multiple studies at individual institutions demonstrating potential benefits from various strategies including extracorporeal life support (ECLS), delayed repair, and lower levels of ventilator support. There has been no multicenter survey of institutions offering these modalities to describe the current use of ECLS and survival of these infants. In addition, the relationship between the number of patients with CDH managed at an individual institution and outcome has not been evaluated. METHODS: We queried 16 level III neonatal intensive care centers on the use of ECLS and survival of infants with CDH who were treated during 2 consecutive years (1993 to 1995). Data are presented as mean +/- SEM, median, and range. RESULTS: Data were collected on 411 patients. Of these, 71% +/- 8% were outborn and 8% +/- 3% were considered nonviable. Overall survival of CDH infants was 69% +/- 4% (range, 39% to 95%). The survival rate of infants on ECLS was 55% +/- 4%, whereas survival of infants not requiring ECLS was significantly increased at 81% +/- 5% (p = 0.005). The mean rate of ECLS use was 46% +/- 2%. There was no correlation between the number of cases per year at an individual institution and overall survival, ECLS survival, or ECLS use (r = 0.341, 0.305, and 0.287, respectively). There was also no correlation between case volume at an individual institution and ECLS survival (r = 0.271). CONCLUSIONS: The current survival rate and rate of ECLS use in infants with CDH at level III neonatal intensive care units in the United States are 69% +/- 4% and 46% +/- 2%, respectively. There is no correlation between the yearly individual center experience with managing CDH and rate of ECLS use or outcome.

Intracranial abnormalities in infants treated with extracorporeal membrane oxygenation: update on sonographic and CT findings.

PURPOSE: To determine the frequency of intracranial lesions in infants treated with extracorporeal membrane oxygenation (ECMO), to evaluate trends in frequency during an 8-year period, and to determine which infants are at highest risk for intracranial injury. METHODS: Daily sonograms were obtained in 386 infants during treatment with ECMO. Cranial CT scans were acquired after decannulation in 286 of 322 survivors. Abnormalities were classified as major or minor and hemorrhagic or nonhemorrhagic. Results were correlated with infant demographic data. RESULTS: Intracranial abnormalities were detected in 203 (52%) of the 386 infants; 73 (19%) hemorrhagic, 86 (22%) nonhemorrhagic, and 44 (11%) combined lesions. Eighty-two lesions (21%) were classified as major. Forty-six (94%) of 49 major hemorrhages were identified at sonography. CT contributed additional information in 73% of neonates with intracranial abnormalities, of which 17 were major lesions not identified at sonography. The frequency of intracranial hemorrhage was increased in infants who were septic or premature or weighed less than 2.5 kg. An increase in time spent on ECMO bypass increased the risk for nonhemorrhagic injury. During an 8-year period, the frequency of hemorrhagic and major nonhemorrhagic lesions remained constant, whereas minor nonhemorrhagic abnormalities increased significantly. CONCLUSION: Infants treated with ECMO continue to be at high risk for cerebrovascular injury. Although daily sonograms are useful in identifying major hemorrhages, follow-up CT scans are crucial for accurate evaluation of intracranial abnormalities.

The current status of neonatal extracorporeal membrane oxygenation.

Marked changes have occurred in the practice of neonatal extracorporeal membrane oxygenation (ECMO) since the first survivor in 1975. Coagulation management has been markedly refined, new catheters allow ECMO to be done either in a venoarterial or venovenous (VV) mode, depending on cardiac function in the infant. A new design of the VV catheter will allow this technique to be used in more infants in the future. New therapies for respiratory failure have changed the complexion of the population being treated with ECMO. The 34 to 36 week gestation infant with respiratory distress syndrome and/or pulmonary hypertension rarely needs ECMO therapy due to the effectiveness of surfactant and high frequency oscillation. Present day survival for infants treated with ECMO for many diagnostic categories ranges between 90% to 100%. The effects of new interventions must be evaluated with regard to their effect on morbidity when being considered prior to ECMO. Neuro-developmental outcome is encouraging, but does indicate that ECMO and the near-miss ECMO patients need to be followed closely into school age. The number of patients being treated per ECMO center has dropped significantly over the last 10 years from 18 to 9. This brings forward the question about regional needs for ECMO Centers and how to assure that centers have enough patients to maintain their clinical competencies. The challenge for the future is where to place ECMO as a therapy. Should it remain a rescue therapy? Or should there now be a trial comparing ECMO to conventional therapies, with morbidity and cost of care as the outcome variables?

Venoarterial extracorporeal membrane oxygenation impairs basal nitric oxide production in cerebral arteries of newborn lambs.

OBJECTIVE: Based on previous studies in our laboratory showing that exposure of newborn lambs to venoarterial extracorporeal membrane oxygenation (ECMO) alters cerebral blood flow autoregulation, we postulated that this altered vascular reactivity is mediated through changes in endothelial function caused by the pumping systems used in venoarterial ECMO. We tested that hypothesis in this study. DESIGN: Prospective, controlled, laboratory trial. SETTING: Animal research laboratory. SUBJECTS: Two groups of newborn lambs. INTERVENTIONS: One group of animals was exposed to venoarterial ECMO (n = 6) and another group of control animals (n = 5) was maintained under similar conditions for 2 hrs on the ventilator without ECMO. MEASUREMENTS AND MAIN RESULTS: Third-order branches of the middle cerebral arteries (140-300 microm diameter) were isolated from animals at the end of the experiment, mounted on glass cannulae in an arteriograph, and superfused with Krebs-Ringer buffer. Decrease in the diameter of the arteries induced by exposure of the vessels to nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (200 micromol/L) for 30 mins was significantly less (p <.05) in arteries from lambs exposed to ECMO compared with control animals. There were no significant differences between the two groups in myogenic response or in the contractile activity of the arteries to increasing concentrations of serotonin. CONCLUSIONS: These results demonstrate that 2 hrs of exposure of newborn lambs to venoarterial ECMO leads to a decrease in basal production of nitric oxide in cerebral arteries, and suggest that venoarterial ECMO selectively impairs cerebral arterial endothelial function.

Effect of nitric oxide and high-frequency oscillatory ventilation in meconium aspiration syndrome.

OBJECTIVE: To test the hypothesis that inhaled nitric oxide, when combined with high-frequency oscillatory ventilation, is an effective therapeutic agent in meconium aspiration syndrome. DESIGN: Prospective, interventional study. SETTING: The animal research laboratory at The Children's National Medical Center. SUBJECTS: Five newborn piglets, 1-2 wks old, weighing 3.6 +/- 0.2 kg. INTERVENTION: Animals were anesthetized, paralyzed, intubated, and ventilated. Catheters were placed in the femoral vein and artery and the pulmonary artery. After 1 hr of recovery, 10 mL/kg of 20% meconium in normal saline solution was insufflated into the lungs. Animals were ventilated with a SensorMedics oscillator to maintain arterial blood gases in a normal range (pH, 7.35-7.45; Paco2, 40-45 mm Hg [5.3-6.0 kPa]; Pao2, 70-90 mm Hg [9.3-12.0 kPa]). Ventilator settings were increased as needed until maximum settings as follows: Fio2, 1.00; proximal oscillatory pressure amplitude, 36 cm H2O; mean airway pressure, 25 cm H2O; frequency, 10 Hz. After a short period of stabilization, inhaled nitric oxide was administered. Concentrations of 40, 20, and 10 ppm were given and measurements were taken after each exposure to inhaled nitric oxide and after its discontinuation. To assure that there was no additive effect of inhaled nitric oxide, each dose was given for 20 mins followed by a 15-min normalization period at 0 ppm. MEASUREMENTS AND MAIN RESULTS: Physiologic measurements, ventilatory settings, arterial blood gases, and methemoglobin were recorded at each study period. Measurements were taken after each exposure to inhaled nitric oxide and after its discontinuation. Arterial saturation and partial pressure of arterial oxygen (Pao2) were significantly lower after meconium aspiration when compared with baseline. Administration of inhaled nitric oxide improved oxygenation without a significant decrease in pulmonary artery pressure. CONCLUSION: In this model of meconium aspiration syndrome, short-term exposure to inhaled nitric oxide when combined with high-frequency oscillatory ventilation improved oxygenation secondary to better distribution of inhaled nitric oxide. The increase in oxygenation may be secondary to improved ventilation perfusion mismatch, as the primary etiology of hypoxia in this model may be a combination of parenchymal lung disease and pulmonary hypertension.

Outcome of perforated necrotizing enterocolitis in the very low-birth weight neonate may be independent of the type of surgical treatment.

Perforated necrotizing enterocolitis (NEC) in the low-birth weight infant is now one of the most common surgical problems encountered in contemporary neonatal intensive care units. However, morbidity and mortality from NEC remain high, and the optimal surgical management of these infants remains controversial. Currently few data exist comparing the factors influencing outcome in very low-birth weight infants with perforated NEC treated by either local drainage or exploration. We hypothesize that survival of very low-birth weight neonates with perforated NEC may be more dependent on clinical status than on treatment modality. We present our experience treating a large cohort of infants weighing less than 1000 g with perforated NEC. A retrospective cohort study describes our experience with perforated NEC in very low-birth weight infants in a Level III neonatal intensive care unit. Between January 1991 and May 1998 a total of 70 newbo infants weighing less than 1000 g were evaluated and managed for perforated NEC. Comorbid factors were identified and calculated for each infant. Primary treatment was either local drainage or laparotomy. Statistical analysis was performed by Student's t test and multiple logistic regression. A multiple logistic regression model examined factors (comorbidities, number of comorbidities, and mode intervention) influencing outcome. A Kaplan-Meier survival analysis comparing survival versus number of comorbidities was performed. Twenty-two infants with an average weight of 679 g were treated by local drainage. Forty-eight infants with an average weight of 756 g were treated with exploratory laparotomy. Infants treated by local drainage had a higher cumulative number of comorbid factors (5.2+/-0.50 vs 3.7+/-0.29; P < 0.05) than those managed by operative exploration. Fourteen infants (63%) initially undergoing local drainage for perforated NEC survived. Of the 48 infants 36 operated on survived (75%). No single factor or combination of any comorbid factors was predictive of outcome. The total number of comorbidities for each neonate did reach statistical significance (P < 0.05). A greater likelihood of death was associated with a higher number of comorbidities. Survival with four or fewer comorbidities was 84 per cent, whereas survival with greater than six comorbidities was 30 per cent. The mean number of comorbidities was greater for drainage than for surgery, and for the same number of comorbidities the probability of survival tended to be greater for those treated with drainage than for those undergoing surgery. Multiple logistic regression analysis identified the total number of comorbidities as affecting outcome rather than treatment choice. This suggests therefore that selection of therapeutic options for the patient requires evaluating all factors that may impact survival rather than applying a single treatment strategy for all patients.

Citrobacter sepsis and severe newborn respiratory failure supported with extracorporeal membrane oxygenation.

An infant with fulminant Citrobacter sepsis and respiratory failure is presented. The severity of respiratory failure and the need for systemic heparinization on extracorporeal membrane oxygenation delayed the opportunity of initial lumbar puncture to rule out meningitis. The infant was successfully treated with extracorporeal membrane oxygenation and long-term antibiotics. Repeated cranial computed tomography scans remained negative for intracerebral abscesses, and the infant is within normal limits for growth, neurologic status, and developmental status.

Extracorporeal membrane oxygenation in the management of respiratory failure in the newborn.

The history of ECMO and the development of its present-day use is discussed. The results of the National ECMO Registry and the first 100 patients at Children's Hospital National Medical Center are presented. Future developments and directions of ECMO are presented.

The cerebrovascular response to prolonged hypoxia with carotid artery and jugular vein ligation in the newborn lamb.

This study was designed to evaluate the effect of ligation of the carotid artery and/or jugular vein, after exposure to prolonged (4 hours) hypoxia, and the effect of acute normalization of PaO2 after prolonged hypoxia with vessel ligation, on the cerebral circulation. Twelve 1- to 7-day-old lambs were anesthetized with pentobarbital. Catheters were placed in the femoral artery and vein, left ventricle, lingual artery, and sagittal sinus. Cerebral blood flow (CBF) was determined using the radiolabeled microsphere technique. After baseline studies, the animals were made hypoxic with a nitrogen/air mixture, to lower PaO2 to 36 +/- 5 mm Hg for 4 hours, followed by 1 hour of normoxia. After four hours of hypoxia, studies were performed. The animals were divided into two groups to evaluate carotid artery and jugular vein ligation separately. In group I, the carotid artery was ligated first, with studies performed after 5 minutes; this was followed by ligation of the jugular vein, with studies after 5 minutes. In group II, the jugular vein was ligated first, with studies after 5 minutes; this was followed by ligation of the carotid artery, with studies after 5 minutes. With regard to physiological variables, there were no differences between the groups. CBF increased 106% (P < .001 compared with the baseline value) after 4 hours of hypoxia, maintaining cerebral oxygen consumption (CMRO2) and oxygen transport (OT) constant in both groups. Ligation of either the carotid artery or jugular vein after 4 hours of hypoxia, did not alter CBF responses to hypoxia.(ABSTRACT TRUNCATED AT 250 WORDS)

Criteria for extracorporeal membrane oxygenation in a population of infants with persistent pulmonary hypertension of the newborn.

Extracorporeal membrane oxygenation (ECMO) has been available since 1975 as a therapy of last resort to provide adequate oxygenation for term infants with acute lung disorders that do not respond to maximal medical therapy. Virtually all term infants with serious lung disease have persistent pulmonary hypertension of the newborn (PPHN) characterized by significant right-to-left shunting of blood and severe diffusion defects manifested as increased alveolar-arterial oxygen gradients (AaDO2). Criteria for initiation of ECMO therapy have been developed in several institutions but at the present time there are no universal criteria applicable to all infants with PPHN. We have attempted to establish entry criteria that may be used for different populations of infants with PPHN. Based on a retrospective review of 30 infants with PPHN in our institution, we have defined standards of maximal medical therapy. An alveolar-arterial oxygen difference (AaDO2) of greater than or equal to 610 for 8 hours has been shown to be associated with 79% mortality in this population. This AaDO2/time interval is established as a major criterion for institution of extracorporeal membrane oxygenation.