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Biomedical subjects

B L Short

Publications and source records attributed to B L Short.

At least 55 records · Page 3Linked to original sources

Improved pulmonary outcome after exogenous surfactant therapy for respiratory failure in term infants requiring extracorporeal membrane oxygenation.

A blinded, randomized, controlled study was designed to test whether multiple-dose surfactant therapy would improve pulmonary outcome in term infants with respiratory failure, resulting in a shortened period of extracorporeal membrane oxygenation (ECMO). Infants > or = 34 weeks of gestational age in severe respiratory failure and receiving ECMO were stratified by diagnosis and then randomly assigned to the treatment or the control group. Four doses of modified bovine lung surfactant extract (beractant) were administered to the surfactant group (n = 28), and an equal volume of air was administered to the control group (n = 28). Lung compliance was initially low in both groups; after treatment, values were higher with time in the surfactant group (F = 5.40, p = 0.026). The ECMO treatment period was significantly shorter in the surfactant group (mean +/- SD: 107 +/- 33 hours vs 139 +/- 54 hours for the control group; U = 232, p = 0.023). Tracheal aspirate concentrations of surfactant protein A were low in both groups, and then increased steadily to a higher level in the surfactant group (F = 2.58, p = 0.04). The overall incidence of complications after ECMO was decreased in the surfactant group (18% vs 46% for the control group; chi-square value = 5.004, p = 0.025). Radiographic scores, echocardiographic findings, incidence of intracranial or pulmonary hemorrhage and bronchopulmonary dysplasia, time to extubation, duration of oxygen therapy, and duration of hospitalization did not differ between the two groups. Beractant in this population improved pulmonary mechanics, increased surfactant protein A content in tracheal aspirate, decreased time on ECMO duration, and reduced disease complications.

Double-Blind Method↗

Congenital diaphragmatic hernia: long-term outcome in neonates treated with extracorporeal membrane oxygenation.

As more infants with congenital diaphragmatic hernia (CDH) survive with extracorporeal membrane oxygenation (ECMO), it seems prudent to detail the longterm outcome in these medically complex infants. Eighteen children with CDH-treated with postoperative ECMO were recruited for participation in this study. The mean duration of ECMO was 193 hours (range 82 to 493 hours), mean time to extubation after ECMO was 142 hours (range 34 to 312 hours), and median duration of hospitalization was 46 days (range 30 to 181 days). Of the 18 infants, 4 (22%) were discharged home requiring oxygen therapy. At follow-up the notable findings were a high incidence of gastroesophageal reflux and failure to thrive. At both 1 and 2 years of age, 50% of infants were at less than the 5th percentile for weight. At 1 and 2 years of age, 39% and 21%, respectively, were at less than the 5th percentile for weight/length ratio. A total of 16 children (89%) had clinical evidence of reflux, and 8 (44%) were discharged home on a regimen of nasogastric feedings. Reherniation occurred in 4 children (22%) and was more frequent when a patch was used. An electrocardiogram showed right ventricular hypertrophy in 6 (43%); oxygen saturation by pulse oximetry was > 95% in all children, and pulmonary artery pressure was estimated by Doppler echocardiography to be normal in 12 of 14 children examined. The neurodevelopmental outcome (Bayley Scales or Stanford-Binet scale) at 1 to 4 years of age was not dissimilar from that of other ECMO-treated children. Given the severity of illness in the neonatal period, the general health and development of children with CDH surviving after ECMO are good. Surprisingly few children have long-term respiratory complications related to pulmonary hypoplasia. Follow-up in the first few years should be aimed at aggressive nutritional intervention to prevent the growth failure that appears to be prevalent in these children.

Brain Diseases↗

Impairment of cerebral autoregulation during extracorporeal membrane oxygenation in newborn lambs.

This study was designed to evaluate the effect of normothermic partial bypass, or venoarterial extracorporeal membrane oxygenation (ECMO), on cerebral autoregulation. Fourteen newborn lambs, 1-7 d of age, were randomized into two groups: control (ligation of right carotid artery and jugular vein without ECMO; n = 7) and ECMO (ligation with placement on routine venoarterial ECMO at 120-150 mL/kg/min; n = 7). After 1 h of ECMO or stabilization in controls, cerebral autoregulation was evaluated by lowering cerebral perfusion pressure (CPP) by increasing intracranial pressure through infusion of artificial cerebrospinal fluid into the lateral ventricle. Four ranges of CPP were evaluated: 1) baseline, 2) 55-40, 3) 39-25, and 4) < 25 mm Hg. In ECMO animals, cerebral blood flow (CBF) decreased from baseline (39 +/- 7 mL/100 g/min) to 23 +/- 7 and 12 +/- 2 at CPP of 39-25 and < 25 mm Hg. In the control group, CBF was unchanged from baseline (48 +/- 11 mL/100 g/min) until CPP was < 25 mm Hg, at which time it decreased to 27 +/- 16 mL/100 g/min. Cerebral oxygen consumption decreased from baseline (4.2 +/- 1.1 mL/100 g/min) to 4.0 +/- 0.7 and 3.2 +/- 1.3 mL/100 g/min at CPP of 39-25 and < 25 mm Hg, respectively, in the ECMO group. In the control group, cerebral oxygen consumption was unchanged from baseline (4.2 +/- 1.1 mL/100 g/min) until CPP was reduced to < 25 mm Hg (3.2 +/- 1.3 mL/100 g/min). When CBF autoregulation was altered, i.e. when total CBF decreased, right-left hemispheric CBF differences were noted in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Mortality and morbidity rates among lower birth weight infants (2000 to 2500 grams) treated with extracorporeal membrane oxygenation.

To assess the validity of the currently accepted lower weight limit of 2 kg for treatment of neonates with extracorporeal membrane oxygenation (ECMO), we reviewed the outcome of lower birth weight (2.0 to 2.5 kg, n = 29) and higher birth weight (n = 235) for infants treated with venoarterial ECMO at our institution from 1984 through 1990. Newborn infants with congenital diaphragmatic hernia were not included. The mortality rate was significantly greater after venoarterial ECMO in lower than in higher birth weight infants (relative risk 3.45; confidence interval = (1.68, 5.79)). For infants with the diagnosis of respiratory distress syndrome, the mortality rate was 56% (5/9) for lower and 8% (2/25) for higher birth weight infants (p less than 0.01). The most frequent cause of death in lower birth weight infants was intracranial hemorrhage (7/10 deaths). The overall incidence of any neuroimaging abnormality was significantly greater for lower birth weight infants (p = 0.044), primarily because of the higher incidence of major intracranial hemorrhage. Finally, the risk of developmental delay (development quotient less than 70 at 1 to 2 years of age) among survivors available for follow-up was significantly higher among the lower than the higher birth weight infants. These outcome data suggest that further reduction of the current lower weight limit for ECMO should not become standard without prospective research or technologic advances.

Birth Weight↗

In vitro evaluation of the Mera Silox-S 0.5 and 0.8 m 2 silicone hollow-fibre membrane oxygenator for use in neonatal ECMO.

The Mera Silox-S is a silicone hollow-fibre membrane oxygenator made up of thousands of fibres in a clear polycarbonate housing. Being a silicone membrane it does not have the plasma leakage problem associated with conventional microporous hollow fibres when used in a long-term application. This device (Mera Senko Medical Instrument Co., Japan) is made in three sizes: 0.3, 0.5 and 0.8 m 2. The performance of the 0.5 m 2 and 0.8 m 2 Silox-S membrane oxygenators was tested in vitro using filtered ovine blood and a customized test circuit designed to provide a continuous source of de-oxygenated, CO 2-laden blood, according to the AAMI standard for oxygenator performance. The 0.8 m 2 membrane provided excellent oxygenation, with a transfer rate of 13.0-43.5 ml/min for blood flows of 200-800 ml/min. CO 2 transfer over the same range of flows measured 32.3-40.8 ml/min. Flow rates of 100-500 ml/min for the 0.5 m 2 membrane provided an oxygen transfer of 6.8-28.3 ml/min and would probably not be suited for the existing neonatal ECMO population. A matter of concern with both oxygenators was an increased pressure drop for blood flow through the devices. The delta P for the 0.5 m 2 for flows of 100-500 ml/min ranged from 155 +/- 7 mmHg to 516 +/- 6 mmHg. For the 0.8 m 2, delta P was 194 +/- 39 mmHg to 492 +/- 53 mmHg for flows of 200-800 ml/min. Overall, favourable results support further long-term evaluation for potential use in neonatal ECMO.

Evaluation Studies as Topic↗

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.

Echocardiography↗

Cardiac performance in infants referred for extracorporeal membrane oxygenation.

We performed cardiac evaluations in 59 infants referred for severe lung disease to determine whether cardiac performance was impaired in those requiring extracorporeal membrane oxygenation (ECMO). Infants were divided into two groups: group 1 (n = 25) received conventional therapy and group 2 (n = 34) received ECMO therapy after meeting established criteria. Ventilatory and oxygenation indexes and estimates of right ventricular systolic pressure were measured. Load-dependent and load-independent echocardiographic indexes of cardiac performance were also measured. The infants in the two groups had similar diagnoses, age, weight, inotropic support, ventilator and oxygenation indexes on admission, and survival. Heart rate and estimates of preload and afterload were similar in the two groups. Ventricular shortening fraction was 36.1 +/- 7.6% in group 1 and 40.5 +/- 8.8% in group 2 (p value was not significant). Velocity of circumferential fiber shortening (VCF/sec) was 1.41 +/- 0.35 in group 1 and 1.58 +/- 0.39 in group 2 (p value was not significant). The relationship between wall stress and ventricular shortening was similar in the two groups. There were no differences in cardiac output. Pulmonary artery pressure was estimated to be 56 +/- 13 mm Hg in group 1 and 63 +/- 10 mm Hg in group 2 (p = 0.017). Thus no significant differences were found in load-dependent or load-independent measures of cardiac performance in infants with severe lung disease treated with ECMO or conventional therapy. We conclude that cardiac failure is not the primary cause of clinical deterioration in infants with severe lung disease who require ECMO therapy.

Blood Pressure↗

Effects of hydralazine on cardiac performance in infants receiving extracorporeal membrane oxygenation.

To determine the effects of afterload reduction on cardiac performance during partial cardiopulmonary bypass, we administered hydralazine to infants who were either normotensive (n = 11) or hypertensive (n = 12) 1 hour after extracorporeal membrane oxygenation (ECMO) was begun. Load-dependent and load-independent measures of cardiac performance and indexes of cerebral blood flow were measured. Infants in both groups had similar weight, heart rate, blood pressure, and inotropic support before ECMO. Shortening fraction was normal in both groups before ECMO (47 +/- 11% vs 49 +/- 10%; p greater than or equal to 0.05), decreased during ECMO (31 +/- 18% vs 39 +/- 12%; p greater than or equal to 0.05), and did not change after administration of hydralazine (31 +/- 12% vs 37 +/- 8%; p greater than or equal to 0.05). Cardiac output was normal in both groups before ECMO (176 +/- 71 vs 157 +/- 72 ml/kg per minute; p greater than or equal to 0.05), decreased during ECMO (120 +/- 80 vs 105 +/- 64 ml/kg per minute; p greater than or equal to 0.05), and did not change after hydralazine administration. Velocity of circumferential fiber shortening, an index of contractility (circumference per second), was normal in both groups before ECMO (1.96 +/- 0.57 vs 1.90 +/- 0.43 circ/sec; p greater than or equal to 0.05), decreased during ECMO (1.18 +/- 0.83 vs 1.56 +/- 0.58 circ/sec; p greater than or equal to 0.05), and did not change after hydralazine administration. The relationship between velocity of circumferential fiber shortening and wall stress was similar in both groups before ECMO, during ECMO, and after hydralazine administration. The cerebral blood flow resistance index was similar in both groups before ECMO (0.70 +/- 0.16 vs 0.70 +/- 0.20; p greater than or equal to 0.05), decreased during ECMO (0.45 +/- 0.13 vs 0.43 +/- 0.09; p greater than or equal to 0.05), and did not change after administration of hydralazine. We conclude that hydralazine does not improve cardiac performance during ECMO.

Blood Flow Velocity↗

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.

Aorta↗

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.

6-Ketoprostaglandin F1 alpha↗

Extracorporeal membrane oxygenation therapy in neonates with septic shock.

Neonatal septic shock has significant morbidity and mortality with current therapeutic measures. At Children's National Medical Center, from June 1984 to October 1986, 10 of 100 patients treated with venoarterial extracorporeal membrane oxygenation (ECMO) had a documented diagnosis of septic shock. All of these infants fulfilled criteria consistent with 80% mortality using conventional intensive medical management. However, the survival rate for the septic neonates in this study was 100%. Compared with other groups of infants treated with ECMO, these septic neonates required significantly more ventilatory support after ECMO and had a higher incidence of chronic lung disease (30% v 12%). The septic neonates were also at higher risk for intracranial hemorrhage than the other infants treated with ECMO (40% v 26%). The necessity for prolonged intubation after ECMO for patients with septic shock suggests that this condition may be associated with additional structural damage not seen with meconium aspiration syndrome or respiratory distress syndrome. Nevertheless, for neonatal patients with septic shock unresponsive to conventional medical management, ECMO must be considered a viable alternative treatment.

Cerebral Hemorrhage↗

Effect of extracorporeal membrane oxygenation on survival of infants with congenital diaphragmatic hernia.

To determine the effect of extracorporeal membrane oxygenation (ECMO) on the survival of infants with congenital diaphragmatic hernia, we undertook a retrospective review of 31 infants with congenital diaphragmatic hernia treated at Children's National Medical Center. Infants were categorized by means of the Bohn quadrant analysis to determine the impact of ECMO on infants with congenital diaphragmatic hernia and a "poor prognosis." All infants assigned to the Bohn 100% mortality quadrant required ECMO. The survival rate in this group was 86% (6/7) when assessed preoperatively and 67% (6/9) when assessed postoperatively. Comparison of the change occurring in ventilation index and arterial carbon dioxide pressure demonstrated that after repair the clinical condition of 48% of infants deteriorated, 40% improved, and 12% remained unchanged. Of the 12 infants whose condition was worse after surgery, 11 eventually required ECMO. Our review demonstrates that ECMO improved survival significantly in infants with congenital diaphragmatic hernia who had a "poor prognosis" by the criteria of Bohn et al. We recommend consideration of ECMO for all infants with congenital diaphragmatic hernia for whom maximal medical therapy has failed.

Evaluation Studies as Topic↗

Surfactant protein A concentrations in tracheal aspirate fluid from infants requiring extracorporeal membrane oxygenation.

To understand the lung abnormalities leading to respiratory failure in infants, we measured 35,000-dalton surfactant protein A concentrations in tracheal aspirate fluid collected daily from 25 infants receiving extracorporeal membrane oxygenation (ECMO). Surfactant protein A concentrations were standardized per milligrams of total protein present in the aspirate. Among the 23 survivors with complete data, the surfactant protein A concentration increased significantly with time (p less than 0.0001). Concurrent increases in lung compliance (p less than 0.0001) and radiographic scores (p less than 0.0001) were also observed. This increase in surfactant protein A content may reflect lung recovery from barotrauma and oxygen toxic effects or be a response to the primary pulmonary disease process. The two infants who did not survive extracorporeal membrane oxygenation failed to demonstrate these trends.

Body Fluids↗

Intracranial blood flow: quantification with duplex Doppler and color Doppler flow US.

The authors compared changes in cerebral blood flow (CBF), determined by means of injection of radiolabeled microspheres, with Doppler blood flow measurements obtained simultaneously in the middle (n = 9) and anterior cerebral arteries (n = 3) in 12 newborn lambs. Doppler estimates of blood flow and mean blood flow velocity correlated well with changes in CBF. However, with changes in mean blood flow velocity, the degree of change in CBF tended to be underestimated. The resistive index correlated well with perfusion pressure but correlated weakly with cerebrovascular resistance and poorly with changes in CBF. Doppler blood flow estimates and mean blood flow velocities correlate well with changes in CBF and allow significant improvement in accuracy over instantaneous velocity or pulsatility measurements alone. Determination of absolute blood flow remains difficult due to systolic and diastolic differences in vessel diameter and intrinsic error in true diameter measurement with currently available color flow technology.

Animals↗

Effect of extracorporeal membrane oxygenation on cerebral blood flow and cerebral oxygen metabolism in newborn sheep.

Extracorporeal membrane oxygenation (ECMO) supplies respiratory support to term or near-term infants with respiratory failure. Although infants requiring this therapy may have already sustained significant hypoxia and/or ischemia predisposing them to neurologic injury, the high incidence of neuroimaging abnormalities in the ECMO population raises concerns about the additional neurologic risk associated with the ECMO procedure itself. Our study was undertaken to evaluate the effects of ECMO on the normal neonatal cerebral circulation. Thirteen newborn lambs (1-7 d of age) were placed on normothermic venoarterial ECMO using a silicone membrane oxygenator and roller occlusion pump. Regional brain blood flows, cerebral oxygen consumption, fractional oxygen extraction, and oxygen transport were determined 30 and 120 min after initiation of ECMO. Neither cerebral blood flow (baseline, 60.2 +/- 23.6; 30 min, 56.1 +/- 18.1; 120 min 56.1 +/- 12.9 mL/100 g/min) nor oxygen metabolism (cerebral oxygen consumption: baseline, 4.48 +/- 1.48; 30 min, 3.86 +/- 1.53; 120 min, 4.10 +/- 1.32 mL/100 g/min and oxygen extraction: baseline, 0.52 +/- 0.09; 30 min, 0.47 +/- 0.14; 120 min, 0.46 +/- 0.14 mL/100 g/min) changed after the initiation of ECMO. Regional and left/right blood flow differences were not noted. These findings suggest that in healthy newborn lambs, initiation of ECMO does not alter cerebral blood flow or oxygen metabolism.

Animals↗

Cerebral blood flow and metabolism during and after prolonged hypocapnia in newborn lambs.

We studied the effects of prolonged (6 hours) hypocapnia and the abrupt termination thereof on cerebral blood flow and metabolism in six paralyzed, sedated (but not anesthetized) newborn lambs. Thirty minutes after institution of hyperventilation to an arterial carbon dioxide pressure of 15 +/- 2 torr, hyperventilation, cerebral blood flow had returned to baseline. Abrupt termination of hyperventilation after 6 hours resulted in a 110 +/- 71% increase in cerebral blood flow over baseline after 30 minutes of normocapnia. This cerebral hyperemia persisted for at least 90 minutes after hyperventilation was discontinued. Cerebral oxygen consumption did not change throughout the study. The posthypocapnia hyperemia noted in these animals after abrupt normalization of arterial carbon dioxide pressure may contribute to the increased risk of intracranial hemorrhage in newborn infants who are treated similarly in the management of pulmonary hypertension.

Animals↗