A multi-tiered time-series modelling approach to forecasting respiratory syncytial virus incidence at the local level.

Respiratory syncytial virus (RSV) is the most common cause of documented viral respiratory infections, and the leading cause of hospitalization, in young children. We performed a retrospective time-series analysis of all patients aged <18 years with laboratory-confirmed RSV within a network of multiple affiliated academic medical institutions. Forecasting models of weekly RSV incidence for the local community, inpatient paediatric hospital and paediatric intensive-care unit (PICU) were created. Ninety-five percent confidence intervals calculated around our models' 2-week forecasts were accurate to ±9·3, ±7·5 and ±1·5 cases/week for the local community, inpatient hospital and PICU, respectively. Our results suggest that time-series models may be useful tools in forecasting the burden of RSV infection at the local and institutional levels, helping communities and institutions to optimize distribution of resources based on the changing burden and severity of illness in their respective communities.

Effects of MK-801 and NBQX on acute recovery of piglet cerebral metabolism after hypothermic circulatory arrest.

Brain protection during open heart surgery in the neonate and infant remains inadequate. Effects of the excitatory neurotransmitter antagonists MK-801 and NBQX on recovery of brain cellular energy state and metabolic rates were evaluated in 34 4-week-old piglets (10 MK-801, 10 NBQX, 14 controls) undergoing cardiopulmonary bypass and hypothermic circulatory arrest at 15 degrees C nasopharyngeal temperature for 1 h, as is used clinically for repair of congenital heart defects. MK-801 (dizocilpine) (0.75 mg/kg) or NBQX [2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(F)quinoxaline] (25 mg/kg) was given intravenously before cardiopulmonary bypass. Equivalent doses were placed in the cardiopulmonary bypass prime plus continuous infusions after reperfusion (0.15 mg kg-1h-1 and 5 mg kg-1h-1). Changes in high-energy phosphate concentrations and pH were analyzed by magnetic resonance spectroscopy in 17 animals until 225 min after reperfusion. Cerebral blood flow determined by radioactive microspheres as well as cerebral oxygen and glucose consumption were studied in 17 other animals. Cerebral blood flow and oxygen consumption were depressed relative to control by both MK-801 and NBQX at baseline. Recovery of phosphocreatine (p = 0.010), ATP (p = 0.030), and intracellular pH (p = 0.004) was accelerated by MK-801 and retarded by NBQX over the 45 min of rewarming reperfusion and the first hour of normothermic reperfusion. The final recovery of ATP at 3 h and 45 min reperfusion was significantly reduced by NBQX (46 +/- 26% baseline, mean +/- SD) versus control (81 +/- 19%) and MK-801 (75 +/- 8%) (p = 0.030). Cerebral oxygen consumption recovered to 105 +/- 30% baseline in group MK-801 and 94 +/- 31% in control but only to 61 +/- 22% in group NBQX (p = 0.070). Cerebral blood flow stayed significantly lower in group NBQX relative to control. Thus, MK-801 accelerates recovery of cerebral high-energy phosphates and metabolic rate after cardiopulmonary bypass and hypothermic circulatory arrest in the immature animal. At the dosage used NBQX exerts an adverse effect.

Predicting death in pediatric patients with acute respiratory failure. Pediatric Critical Care Study Group. Extracorporeal Life Support Organization.

OBJECTIVE: To estimate mortality risk in pediatric patients with acute hypoxemic respiratory failure (AHRF). DESIGN: Retrospective chart review. SETTING: Forty-one pediatric ICUs. SUBJECTS: Four hundred seventy children with AHRF. We defined AHRF as mechanical ventilation with positive end-expiratory pressure > or = 6 cm H2O and fraction of inspired oxygen greater than or equal to 0.5 for 12 or more hours. MEASUREMENTS: Physiologic and treatment variables were recorded every 12 h for 14 days. Cases were randomly assigned to score development and score validation subsets. Variables were assessed for their association with mortality in the development subset by logistic regression analysis. The analysis generated a series of logistic equations, which we called the Pediatric Respiratory Failure (PeRF) score, to estimate mortality risk at 12-h intervals over the first 7 days of treatment for AHRF. The predictive ability of the score was assessed in the validation subset by receiver operating characteristic curve area and goodness-of-fit chi 2. RESULTS: Mortality of the collected cases was 43%. The PeRF score included age, operative status, Pediatric Risk of Mortality score, fraction of inspired oxygen, respiratory rate, peak inspiratory pressure, positive end-expiratory pressure, PaO2, and PaCO2. Area under the receiver operating characteristic curve was 0.769 at entry and increased to greater than 0.8 after 36 h. When the score was applied to the validation subset of patients, goodness-of-fit chi 2 showed no significant difference between estimated and actual mortality between 0 and 96 h. CONCLUSIONS: The PeRF Score accurately estimated mortality risk in this retrospectively sampled group of high-risk pediatric patients with AHRF. This score may be useful in studies of newer therapies for pediatric AHRF, though prospective validation is necessary before it could be used to make clinical decisions.

Recovery of cerebral blood flow and energy state in piglets after hypothermic circulatory arrest versus recovery after low-flow bypass.

A miniature piglet model that replicates clinical hypothermic (14 degrees C nasopharyngeal) circulatory arrest and low-flow (50 ml/kg per minute) bypass was used to study carotid blood flow with electromagnetic flow probe, cerebral blood flow by microsphere injection, cerebral metabolic rate by arteriovenous oxygen and glucose extractions, lactate production by cerebral arteriovenous difference, and cerebral edema. Data from five animals that underwent circulatory arrest and five animals that underwent low-flow bypass (aged 28.8 +/- 0.4 [mean +/- standard error of the mean] days) were analyzed. The duration of circulatory arrest and low-flow bypass was 1 hour. In a parallel study with the same animal model, phosphorus 31 magnetic resonance spectroscopy was used to assess cerebral phosphocreatine, nucleoside triphosphate (adenosine triphosphate), and intracellular pH. Five animals (aged 31.8 +/- 1.1 days) underwent circulatory arrest, and five underwent low-flow bypass. A brief phase of hyperemic carotid blood flow was seen immediately after the onset of reperfusion in the circulatory arrest group but not in the low-flow group. In the circulatory arrest and low-flow bypass groups, cerebral blood flow (percentage of baseline 71.2% +/- 8.3% and 69.1% +/- 5.8%, respectively), cerebral oxygen consumption (45.6% +/- 10.0%, 44.5% +/- 7.6%), and cerebral glucose consumption (31.5% +/- 30.7%, 83.5% +/- 24.2%) remained depressed after 45 minutes of reperfusion and rewarming to normothermia. However, after 3 more hours of pulsatile normothermic reperfusion, cerebral oxygen consumption and cerebral glucose consumption had returned to baseline. Phosphocreatine, adenosine triphosphate, and pH were maintained at or above baseline levels throughout low-flow bypass and throughout 3 hours of normothermic reperfusion. In contrast, both phosphocreatine and adenosine triphosphate became undetectable 32 +/- 3.7 minutes after onset of circulatory arrest. During and early after circulatory arrest, pH decreased to a minimum of 6.506 +/- 0.129 at 40 minutes after reperfusion. After 3 hours of normothermic reperfusion, phosphocreatine and adenosine triphosphate recovered to 98.6% +/- 9.0% and 90.1% +/- 13.5% of baseline, respectively, and pH was 7.087 +/- 0.051, similar to baseline (7.1755 +/- 0.041). In the low-flow bypass group, the disparity between the depressed level of cerebral oxygen consumption and normal high-energy phosphate levels may reflect incomplete cerebral rewarming or decreased energy consumption. In the circulatory arrest group, the parallel recovery of oxygen consumption and high-energy phosphates eventually achieving baseline levels suggests that the degree of hypothermia used provides adequate protection for acute cerebral recovery after 1 hour of circulatory arrest.(ABSTRACT TRUNCATED AT 400 WORDS)

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.

Effects of pH on brain energetics after hypothermic circulatory arrest.

The pH management that provides optimal organ protection during hypothermic circulatory arrest is uncertain. Recent retrospective clinical data suggest that the pH-stat strategy (maintenance of pH at 7.40 corrected to core temperature) may improve brain protection during hypothermic cardiopulmonary bypass with a period of circulatory arrest in infants. The impact of alpha-stat (group A) and pH-stat (group P) strategies on recovery of cerebral high-energy phosphates and intracellular pH measured by magnetic resonance spectroscopy (A, n = 7; P, n = 5), organ blood flow measured by microspheres, cerebral metabolic rate measured by oxygen and glucose extraction (A, n = 7; P, n = 6), and cerebral edema was studied in 25 4-week-old piglets undergoing core cooling and 1 hour of circulatory arrest at 15 degrees C. Group P had greater cerebral blood flow during core cooling (54.3% +/- 4.7% versus 34.2% +/- 1.5% of normothermic baseline, respectively; p = 0.001). The intracellular pH during core cooling showed an alkaline shift in both groups but became more alkaline in group A than in group P at the end of cooling (7.08 to 7.63 versus 7.09 to 7.41, respectively; p = 0.013). Recovery of cerebral adenosine triphosphate (p = 0.046) and intracellular pH (p = 0.014) in the initial 30 minutes of reperfusion was faster in group P. The cerebral intracellular pH became more acidotic during early reperfusion in group A, whereas it showed continuous recovery in group P. Brain water content postoperatively was less in group P (0.8075) than in group A (0.8124) (p = 0.05). These results suggest that compared with alpha-stat, the pH-stat strategy provides better early brain recovery after deep hypothermic cardiopulmonary bypass with circulatory arrest in the immature animal. Possible mechanisms include improved brain cooling by increased blood flow to subcortical areas, improved oxygen delivery, and reduction of reperfusion injury, as well as an alkaline shift in intracellular pH with hypothermia in spite of a stable blood pH.

Weaning from mechanical ventilation: patterns in young children recovering from acute hypoxemic respiratory failure.

OBJECTIVE: The purpose of the study was to describe the patterns of weaning from mechanical ventilation in young children recovering from acute hypoxemic respiratory failure. METHODS: Decision-making rules on progressive weaning were developed and applied to existing data on 82 patients 2 weeks to 6 years old in the Pediatric Acute Respiratory Distress Syndrome Data Set. RESULTS: Three patterns of weaning progress were detected: sprint, consistent, and inconsistent. Length of ventilation and weaning progressively increased from the sprint, to the consistent, to the inconsistent subset. Patients in the inconsistent subset were most likely to have a systemic (sepsis or shock) trigger of acute respiratory distress syndrome and to be rated as having at least moderate disability at discharge. Hypothesis-generating univariate and then multivariate logistic regression analyses indicated that patients who experienced more days of mechanical ventilation before the start of weaning and who had a higher oxygenation index during the weaning process were most likely to have an inconsistent pattern of weaning. CONCLUSION: Patterns of weaning are discernible in a population of young children and indicate a subset at risk for inconsistent weaning. Knowing the patterns of weaning may help clinicians anticipate, perhaps plot, and then modulate a patient's weaning trajectory.

ECMO in evolution: the impact of changing patient demographics and alternative therapies on ECMO.

The incidence of neonatal extracorporeal membrane oxygenation (ECMO) is decreasing nationally. This decrease is presumed to be a result of the emergence of alternative technologies such as high-frequency oscillatory ventilation (HFOV), nitric oxide (NO), and surfactant therapy as well as others. The purposes of the present report were to determine just how rapidly the demographics of ECMO are changing and to determine the impact of competing technologies on ECMO use. The authors reviewed their entire ECMO experience of 455 cases (370 neonatal, 38 pediatric, and 47 cardiac). The neonatal cases also were separated into diagnostic groups: MAS (meconium aspiration syndrome), PPHN (persistent pulmonary hypertension of the newborn), RDS (respiratory distress syndrome), and sepsis. To allow statistical comparison, the patients were divided into four chronological groups, of equal 3-year duration, spanning the 12 years that ECMO has been available. The results of the analysis demonstrated four principle findings. (1) The total number of patients receiving ECMO per year was declining (P = .0001). This decline was attributable to a reduction in the total number of neonatal patients, with the exception of cases of congenital diaphragmatic hernia. (2) The complexity of each ECMO run was increasing, as evidenced by substantial increases in mean ECMO duration per patient and an increase in the incidence of patient complications on ECMO (P = .0001). (3) There has been a significant decrease in the overall survival rate for patients treated with ECMO (P = .0001). (4) The ECMO population mix has shifted away from straightforward neonatal cases and toward the more complex pediatric and cardiac cases. This demographic shift has occurred as a result of improvements in pre-ECMO management of neonatal patients, and is primarily responsible for the findings noted above. However, there also has been a worsening of condition severity within each diagnostic group, which also is partly responsible for the changes noted. If these trends continue, pediatric, cardiac, and CDH patients will likely account for the majority of ECMO patients. Consequently, existing ECMO centers must be prepared to adapt to the changing demographics by evolving programs that support pediatric, cardiac, and adult patients, in addition to neonates. Furthermore, the complexity associated with transporting these unstable older patients and the likelihood that the number of active ECMO centers will decline may require remaining ECMO centers to develop long-distance ECMO transport capabilities.

Experimental fetal tracheal ligation reverses the structural and physiological effects of pulmonary hypoplasia in congenital diaphragmatic hernia.

Infants with congenital diaphragmatic hernia (DH) and profound pulmonary hypoplasia are currently unsalvageable. The authors previously demonstrated that tracheal ligation (TL) accelerates fetal lung growth and reverses the pulmonary hypoplasia of fetal nephrectomy. The purpose of this study was to determine if the pulmonary hypoplasia of experimental DH could be similarly reversed and, if so, whether the resulting lungs would show better function than those of their DH counterparts. Eighteen fetal lambs were divided into three experimental groups of six animals each. In group 1, DH was created at 90 days' gestation. In group 2, DH was created at 90 days' gestation and TL performed during the same operation. Group 3 consisted of sham-operated controls. These animals were delivered near full-term, and their lungs analyzed by standard morphometric techniques. Ten additional fetal lambs were divided into two experimental groups of five animals each. In group 4, DH was created at 90 days' gestation. In group 5, DH was created at 90 days' gestation and TL performed 20 days later, at 110 days' gestation. These animals were pressure-ventilated via tracheostomy over a 2-hour period in which PaO2, PaCO2, and compliance were measured. Intratracheal pressure (ITP) was measured at the time of delivery in all groups. Upon retrieval, DH animals had abdominal viscera in the chest and small lungs; in contrast, DH/TL animals had the herniated viscera reduced from the chest by enlarged lungs. DH/TL lungs showed markedly increased growth, with significant increases in lung volume:body weight ratio (LV:BW; P = .0001), alveolar surface area (ALV.SA; P = .0001), and alveolar number (ALV#) (P = .0001) when compared with those of the DH or control group. This growth was associated with a normal maturation pattern based on histological appearance, normal airspace fraction, and normal alveolar numerical density. ITP in the DH/TL group was increased when compared with that of DH and control animals (P = .0001). Total lung DNA and protein were both elevated in the DH/TL animals (P = .0001). However, the DNA:protein ratio remained normal, suggesting lung growth had occurred through cell proliferation, not by hypertrophy. When ventilated over a range of settings, DH/TL lungs were more compliant (P = .0001) and achieved higher PaO2s (P < .003) and lower PaCO2s (P = .0001) than their DH counterparts. From these data, the authors conclude: (1) Experimental fetal DH produces hypoplastic lungs that are not capable of adequate gas exchange with conventional ventilation.(ABSTRACT TRUNCATED AT 400 WORDS)

Aminocaproic acid decreases the incidence of intracranial hemorrhage and other hemorrhagic complications of ECMO.

Since the inception of extracorporeal membrane oxygenation (ECMO), hemorrhage has been a major complication often limiting its usefulness. This study was undertaken to evaluate the effect of aminocaproic acid (AMICAR), an inhibitor of fibrinolysis, on all hemorrhagic complications of ECMO including intracranial hemorrhage (ICH). In 1990, 49 neonates and 5 older children received ECMO therapy. None of these patients received AMICAR. In 1991, 51 neonates and 5 older children received ECMO. Forty-two of these patients who were considered to be at high risk for bleeding complications (preexisting or anticipated surgical procedures, preexisting ICH, or profound hypoxia, acidosis, coagulopathy, or prematurity) were given AMICAR. The remaining 14 low-risk neonates did not receive AMICAR, and for purposes of analysis were combined with the 1990 group. AMICAR was administered just prior to or after cannulation (100 mg/kg, intravenously) and was infused continuously at 30 mg/kg/h until decannulation. Except for the addition of AMICAR, the ECMO protocol was identical for these two patient groups. Patients who received AMICAR had significantly less bleeding while on ECMO (P = .03) and required fewer blood transfusions (P = .01) than patients not receiving AMICAR. This difference was most significant in the congenital diaphragmatic hernia and cardiac subgroups (P = .0001) and was not significant in the meconium aspiration subgroup (P = .1). The incidence of ICH in the neonatal subgroup was also significantly reduced with no patient on AMICAR developing a new or extending a preexisting ICH (P = .007). Reexploration of the cannulation site for bleeding was also reduced in the AMICAR-treated group but the difference failed to reach statistical significance.(ABSTRACT TRUNCATED AT 250 WORDS)

Continuous intrapulmonary distension with perfluorocarbon accelerates neonatal (but not adult) lung growth.

BACKGROUND/PURPOSE: We have previously demonstrated that experimental fetal tracheal ligation reverses the structural and physiological effects of pulmonary hypoplasia associated with congenital diaphragmatic hernia. The purpose of this study was to determine if lung growth could be similarly accelerated postnatally by continuous liquid-based intrapulmonary distension. METHODS: Ten neonatal lambs were divided into two experimental groups. Five neonatal animals underwent a right thoracotomy with isolation of the anterior superior segment of the right upper lobe. A pressure monitoring catheter was introduced and perfluorocarbon (PFC) was instilled into the segment. Animals were subjected to a 21-day distention period with continuous maintenance of 7 to 10 mm Hg intrabronchial pressure. Five other neonatal animals used as age- and weight-matched controls were killed immediately after distension with PFC to 7 to 10 mm Hg. To evaluate the effect of age on postnatal growth, identical procedures were performed on seven mature sheep. Four adult animals underwent a 21-day distension with PFC, and three animals were killed immediately after PFC distension. RESULTS: Neonatal animals who underwent distension showed a significant acceleration of lung growth based on right upper lobe volume to body weight ratio (P = .0019), total alveolar number (P = .003), and total alveolar surface area (P = .006), when compared with controls. Alveolar growth was attributed to an increased alveolar number rather than increased alveolar size based on a normal histological appearance, normal airspace fraction (P = NS), and normal alveolar numerical density (P = NS). In contrast, no significant differences in lung growth or maturation indices were present in adult animals. CONCLUSIONS: From this preliminary data we conclude: (1) Liquid-based airway distension does accelerate postnatal lung growth, (2) lung architecture remains normal during this period of accelerated growth, (3) adult sheep do not respond to liquid-based airway distension with lung growth, and (4) prolonged exposure to intrapulmonary PFC appears to be safe. We speculate that stretch is the stimulus for lung growth because there are no known growth factors present in PFC.

Poor prognosis for existing monitors in the intensive care unit.

OBJECTIVE: To identify areas requiring the most urgent improvement in the intensive care unit (ICU); and to accurately determine the positive predictive value of routine critical care patient monitoring alarms, as well as the common causes for false-positive alarms. DESIGN: Prospective, observational study. SETTING: A multidisciplinary ICU in a university-affiliated children's hospital (excluding children with primary heart disease). INTERVENTIONS: The occurrence rate, cause, and appropriateness of all alarms from tracked monitors were recorded by a trained observer and validated by the bedside nurse over a 10-wk period for a single bedspace at a time. MEASUREMENTS AND MAIN RESULTS: After 298 monitored hrs, 86% of a total 2,942 alarms were found to be false-positive alarms, while an additional 6% were classified as clinically irrelevant true alarms. Only 8% of all alarms tracked during the study period were determined to be true alarms with clinical significance. Alarms were also classified according to whether they were clearly associated with a "patient intervention" (18%), were clearly not associated with a patient intervention (74%), or had unclear association to interventions (8%). While 11% of "nonpatient intervention" alarms were clinically significant true alarms, only 2% of "patient intervention" alarms were so. Positive predictive values for the various devices ranged from < 1% for the pulse oximeter's heart rate signal to 74% for the arterial catheter's mean systemic blood pressure signal during periods free from patient interventions. The pulse oximeter caused false-positive alarms most frequently, with common reasons being bad data format/bad connection and poor contact. CONCLUSION: Efforts to develop intelligent monitoring systems have more potential to deliver significantly improved patient care by initially targeting especially weak areas in ICU monitoring, such as pulse oximetry reliability.

Rethinking brain death.

OBJECTIVE: To evaluate whether current criteria for the diagnosis of brain death fulfill the requirement for the "irreversible cessation of all functions of the entire brain, including the brainstem." DATA SOURCES: Clinical, philosophical, legal, and public policy literature on the subject of brain death. DATA EXTRACTION/SYNTHESIS: We advance four arguments to support the view that patients who meet the current clinical criteria for brain death do not necessarily have the irreversible loss of all brain function. First, many clinically brain-dead patients maintain hypothalamic-endocrine function. Second, many maintain cerebral electrical activity. Third, some retain evidence of environmental responsiveness. Fourth, the brain is physiologically defined as the central nervous system, and many clinically brain-dead patients retain central nervous system activity in the form of spinal reflexes. We explore options for resolving these inconsistencies between the conceptual definition and the clinical criteria used to make the diagnosis of brain death. CONCLUSIONS: Brain death is a valid conception of death because it signifies the permanent loss of consciousness. Brain death criteria should therefore be based on the diagnosis of the permanent loss of consciousness rather than that of the loss of vegetative brain functions. Revision of our current "whole brain" definition of brain death to a "higher brain" standard should be considered.

Predictors of intracranial hemorrhage during neonatal extracorporeal membrane oxygenation.

OBJECTIVE: To identify independent predictors of intracranial hemorrhage (ICH) during neonatal extracorporeal membrane oxygenation (ECMO). STUDY DESIGN: This retrospective cohort consisted of all neonates who did not have an ICH before treatment with ECMO identified in the Extracorporeal Life Support Organization Registry from 1992 to 1995 (n = 4550). Multiple logistic regression analysis was used to identify factors independently correlated with ICH and to develop a model that could be used to predict the risk of ICH in neonates treated with ECMO. RESULTS: ICH was identified in 9.9% of patients. The factors associated with ICH remaining after adjusting for other significant variables (P <.01) were gestational age (GA) <34 weeks (odds ratio [OR] 12.1, 95% confidence intervals [CI] [6.6, 22]), GA 34 to <36 weeks (OR 4.1, CI [2.9, 5.8]), GA 36 to <38 weeks (OR 2.1, CI [1.6, 2.8]) primary diagnosis of sepsis (OR 1.8, CI [1.4, 2.3]), epinephrine use (OR 1.9, CI [1.5, 2.5]), coagulopathy (OR 1. 6, CI [1.1, 2.2]), arterial pH <7.0 (OR 2.5, CI [1.6, 3.9]), and arterial pH 7.0 to <7.2 (OR 1.8 CI [1.3, 2.5]). ICH rates for neonates receiving venovenous versus venoarterial ECMO and for those treated with or without cephalic jugular venous drainage were not significantly different. CONCLUSIONS: Gestational age, acidosis, sepsis, coagulopathy, and treatment with epinephrine are major independent factors associated with ICH in neonates treated with ECMO. In particular, GA <34 weeks remains a major barrier for use of current ECMO technologies.

Age-specific characteristics of brain death in children.

Clinical and neuropathologic characteristics of 45 children who met criteria for brain death were analyzed. Children between 2 months and 1 year of age were compared with children older than 1 year and children older than 5 years. The observation period to fulfill brain death criteria was not different between the age groups. Deep tendon and spinal reflexes were preserved significantly less frequently in children younger than 1 year old. Diabetes insipidus and the necessity of inotropic support were significantly more frequent in children older than 5 years. Fifty-eight percent (26/45) of patients had no cerebral perfusion pressure before death. However, 18% (8/45) of patients never had a cerebral perfusion pressure below 40 mm Hg. No relationships could be shown between the clinical or physiologic factors and neuropathologic findings. We found no support for using different brain-death criteria for children between 2 months and 1 year of age.

Retinal hemorrhages in newborn piglets following cardiopulmonary resuscitation.

OBJECTIVE: To determine whether conventional cardiopulmonary resuscitation causes retinal hemorrhages in piglets. DESIGN: Nonrandomized observations. SETTING: Animal physiology laboratory. PARTICIPANTS: Six 3.5- to 4.5-kg piglets. INTERVENTIONS: Fifty minutes of conventional, closed chest cardiopulmonary resuscitation. MEASUREMENTS/MAIN RESULTS: Intrathoracic venous pressure (right atrium) and intracranial venous pressure (sagittal sinus) were directly measured. At 5 minutes of cardiopulmonary resuscitation, the mean (+/- SEM) sagittal sinus pressure was 41 +/- 8 mm Hg and the mean right atrial pressure was 58 +/- 9 mm Hg. The pressures were sustained throughout the 50 minutes of cardiopulmonary resuscitation. At autopsy, there was no gross or microscopic evidence of retinal hemorrhages. CONCLUSION: These results support the conclusion that cardiopulmonary resuscitation does not cause retinal hemorrhages.

High-frequency oscillatory ventilation in pediatric respiratory failure.

OBJECTIVE: To evaluate the safety and effectiveness of high-frequency oscillatory ventilation using a protocol designed to achieve and maintain optimal lung volume in pediatric patients with respiratory failure. SETTING: Tertiary care pediatric ICU in a university hospital. DESIGN: A prospective, clinical study. PATIENTS: Seven patients aged 1 month to 15 yrs with diffuse alveolar disease and airleak with a variety of primary diagnoses, including pneumonia, adult respiratory distress syndrome, and pulmonary hemorrhage. INTERVENTIONS: After varying periods of conventional mechanical ventilation (16 to 216 hrs), patients were managed with high-frequency oscillatory ventilation using a "high-volume" strategy that consisted of incremental increases in mean airway pressure and lung volume to achieve an arterial oxygen saturation of > or = 90%, with an FIO2 of < or = 0.6. MEASUREMENTS AND MAIN RESULTS: Ventilatory settings, including FIO2 and mean airway pressure, hemodynamic parameters (cardiac index, systemic and pulmonary vascular resistance indices, oxygen delivery [DO2] and oxygen extraction ratio) and the oxygenation index (oxygenation index = [FIO2 x mean airway pressure x 100]/PaO2) were monitored during the transition to high-frequency oscillation and throughout the course of the high-frequency oscillatory ventilation with rapid and sustained reductions in mean airway pressure (p = .0001, repeated-measures analysis of variance [ANOVA]) and a trend toward decreasing oxygenation index (p = .08, repeated-measures ANOVA). In the four patients from whom hemodynamic data were obtained, there were no compromises of cardiac index or DO2 despite a significant increase in mean airway pressure (26 +/- 2 to 35 +/- 2 cm H2O) during conversion from conventional ventilation to high-frequency oscillation. CONCLUSIONS: High-frequency oscillatory ventilation, using a high-volume strategy, may be used safely and effectively in pediatric patients with respiratory failure and with high predicted mortality rates. High mean airway pressure during oscillatory ventilation does not appear to compromise DO2. Whether this technique can alter morbidity or mortality rates in this population awaits prospective randomized study.

Epstein-Barr virus infection in a child with acquired immunodeficiency syndrome.

A 3-year-old girl, born to an intravenous-drug-dependent mother, had protracted diarrhea, failure to thrive, generalized lymphadenopathy, and recurrent fevers during the first six months of life. At 7 months of age, the Epstein-Barr virus (EBV) genome was detected in her saliva by DNA dot-blot hybridization using a cloned EBV probe. Spontaneous EBV+ lymphoblastoid cell lines had repeatedly developed from her peripheral blood lymphocytes over the subsequent 2 1/2 years. At 11 months of age, persistent tachypnea and a diffuse pulmonary infiltrate developed. Lung biopsy demonstrated a florid, peribronchiolar lymphocytic infiltrate and the EBV genome was identified in the lung tissue. Serum anti-EBV antibodies remained undetectable until 14 months of age. She had a T4+/T8+ ratio of less than 0.8 and serum antibody to human T-cell lymphotropic virus type III. The delayed seroresponse of this patient to symptomatic EBV infection suggests that reliance on EBV serology to diagnose EBV infection in immunocompromised hosts may be inappropriate, and other methods such as DNA probes should be used.

The impact of extracorporeal membrane oxygenation on survival in pediatric patients with acute respiratory failure. Pediatric Critical Care Study Group.

OBJECTIVE: Extracorporeal membrane oxygenation (ECMO) has been used with increasing frequency in the treatment of acute respiratory failure in pediatric patients. Our objective in this study was to test the hypothesis that ECMO improves outcome in pediatric patients with acute respiratory failure. DESIGN: Multicenter, retrospective cohort analysis. SETTING: Forty one pediatric intensive care units participated in the study under the auspices of the Pediatric Critical Care Study Group. PATIENTS: All pediatric patients admitted to the participating institutions with acute respiratory failure during 1991 were included. Patients with congenital heart disease, contraindications to ECMO, or incomplete data were excluded, yielding a data set of 331 patients from 32 hospitals. INTERVENTIONS: Conventional mechanical ventilation, high-frequency ventilation, and extracorporeal membrane oxygenation. MEASUREMENTS AND MAIN RESULTS: Multivariate logistic regression analysis was used to identify factors associated with survival. In a second analysis, pairs of ECMO and non-ECMO patients, matched by severity of disease and respiratory diagnosis, were compared. The use of ECMO (p = .0082), but not the use of high-frequency ventilation, was associated with a reduction in mortality. Other factors independently associated with mortality included oxygenation index (p < .0001), Pediatric Risk of Mortality score (PRISM) (p < .0001) and the Paco2 (p = .045). In 53 diagnosis- and risk-matched pairs, there was a significantly lower mortality rate (26.4% vs. 47.2%; p < .01) in the ECMO-treated patients. When all patients were stratified into mortality risk quartiles on the basis of oxygenation index and PRISM score, the proportion of deaths among ECMO-treated patients in the 50% to 75% mortality risk quartile was less than half the proportion in the non-ECMO treated patients (28.6% vs. 71.4% p < .05)> No effect was seen in the other quartiles. CONCLUSIONS: The use of ECMO was associated with an improved survival in pediatric patients with respiratory failure. The lack of association of outcome with treatment in the ECMO-capable hospital or with another tertiary technology (i.e. high-frequency ventilation) suggests that ECMO itself was responsible for the improved outcome. Further studies of this procedure are warranted but require broad-based multi-institutional participation to provide sufficient statistical power and sensitivity to demonstrate efficacy.