Extracorporeal membrane oxygenation.

Extracorporeal membrane oxygenation is still a relatively new technology that has recently achieved recognition after initial clinical disappointment in the late 1970s. At present, it is considered standard therapy for the full-term infant with PPHN who fails CMV and extraordinary, heroic therapy for older children and adults with ARF or cardiac failure, or both. Currently, the emphasis is on developing new technologies for increasing safety and effectiveness. Areas of interest include heparinless circuits, carotid artery reconstruction, improved monitoring, and expanding applications of VV ECMO. As ECMO becomes safer and more effective, it is believed that new and expanding patient populations will emerge to include premature infants, earlier intervention in term infants, and more liberal application to pediatric and adult populations.

Pulmonary development in the fetal lamb: morphometric study of the alveolar phase.

The alveolar stage of intra-uterine lung development was analyzed morphometrically in 18 fetal lambs at 112, 124, 142, or 148 (term) days of gestation. The right lungs were fixed at uniform distending pressure and the tissue embedded in Epon for light microscopy. Over the whole period, right lung volume (VL) increased more rapidly than body weight to reach a mean value of 185 cm3 at term. The increase in VL was greatest between 112 and 124 days gestation. Throughout the period of study the distal lung consisted of alveolar-like air-spaces lined by walls with a single capillary system. Despite this mature morphology, further differentiation took place as established by two independent measurements. First, interalveolar wall thickness decreased from 4.12 +/- .03 microns at 112 days to 2.55 +/- .02 microns at term. Secondly, alveolar surface area increased at a greater rate than lung volume (as VL 1.06), suggesting a moderate increase in surface complexity, but not a subdivision of existing air-spaces. This latter finding was supported by numerical density values which remained fairly constant. We conclude that throughout this period active growth involves the addition of alveolar units of basically similar size. This is a similar process to the one noted previously in postpneumonectomy compensatory growth.

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

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

Oxygen extraction in lamb skeletal muscle.

Past studies have found that total-body O2 extraction during hypoxia was less in 1-wk-old lambs than in older animals. It was proposed that reduced O2 extraction was secondary to suppression of growth-related oxygen consumption (VO2) in tissues such as skeletal muscle, bone, kidney, and skin, rather than a defect in peripheral O2 use. To determine the capacity of immature skeletal muscle to extract O2, we isolated the hind limb circulation of eight ketamine-anesthetized, 7- to 18-d-old lambs exposed to stagnant hypoxia by inflation of a right atrial balloon catheter. Femoral arterial and venous PO2, PCO2, pH, Hb concentration, O2 saturation, and femoral arterial blood flow (Q) were measured and hind limb O2 delivery (DO2), extraction ratio, and VO2 calculated. Individual critical levels of DO2 below which VO2 was dependent on O2 supply were determined by dual-line best-fit regression analysis. In six of eight animals, VO2 was clearly independent of supply until DO2 reached critically low levels. However, O2 extraction during extreme hypoxia appeared submaximal (baseline O2 extraction ratio, 0.22 +/- 0.06; at critical levels of DO2, 0.51 +/- 0.11; at the lowest level of Q, 0.64 +/- 0.15). When 2,4-dinitrophenol, an uncoupler of oxidative phosphorylation, was administered to four additional lambs exposed to stagnant hypoxia, O2 extraction below critical levels of DO2 increased from 0.48 +/- 0.15 to 0.79 +/- 0.10 (p less than 0.001, unpaired t test). These data suggest that initial limitations in O2 extraction were a result of the suspension of O2-consuming processes, not an irreversible defect in peripheral O2 use.

Renal and hemodynamic effects of dopamine in infants following cardiac surgery.

The renal and hemodynamic effects of dopamine were measured during the immediate postoperative period in six infants following repair of congenital cardiac defects. Dopamine was infused at rates of 5, 10, and 15 micrograms/kg/min. Cardiac index (CI) increased significantly at a dopamine infusion rate of 15 micrograms/kg/min. The glomerular filtration rate (GFR) and urine output increased at dopamine infusion rates of 5 and 10 micrograms/kg/min and returned to baseline at 15 micrograms/kg/min. No significant changes occurred in right atrial pressure (RAP), left atrial pressure (LAP), systemic artery pressure, systemic vascular resistance (SVR), or pulmonary vascular resistance (PVR). Heart rate (HR) increased slightly at a dopamine infusion rate of 15 micrograms/kg/min. Pulmonary artery pressure (PAP) increased significantly in only one patient. These data demonstrate that infants require high doses of dopamine to produce the hemodynamic effects seen in adults and that these higher doses may be used without adverse renal effects.

Extracorporeal membrane oxygenation and conventional medical therapy in neonates with persistent pulmonary hypertension of the newborn: a prospective randomized study.

Thirty-nine newborn infants with severe persistent pulmonary hypertension and respiratory failure who met criteria for 85% likelihood of dying were enrolled in a randomized trial in which extracorporeal membrane oxygenation (ECMO) therapy was compared with conventional medical therapy (CMT). In phase I, 4 of 10 babies in the CMT group died and 9 of 9 babies in the ECMO group survived. Randomization was halted after the fourth CMT death, as planned before initiating the study, and the next 20 babies were treated with ECMO (phase II). Of the 20, 19 survived. All three treatment groups (CMT and ECMO in phase I and ECMO, phase II) were comparable in severity of illness and mechanical ventilator support. The overall survival of ECMO-treated infants was 97% (28 of 29) compared with 60% (6 of 10) in the CMT group (P less than .05).

Role of extracorporeal membrane oxygenation in selected pediatric respiratory problems.

Between 1984 and 1988, 89 infants and children with severe respiratory failure were supported by extracorporeal membrane oxygenation. Major clinical diagnoses included congenital diaphragmatic hernias (34), meconium aspiration syndrome (26), and sepsis (8). Extracorporeal membrane oxygenation was used for patients with a predicted mortality rate of at least 80% based on an oxygenation index greater than 0.4. Venoarterial bypass was accomplished by way of right cervical cannulation of the common carotid artery and internal jugular vein. Overall survival was 71% but varied widely by diagnosis and progressively improved over time. The average extracorporeal membrane oxygenation run was 5.7 days. Intracranial hemorrhage was the most serious complication occurring in 16% of patients. Mechanical circuit complications were seen in 22% but rarely related to significant morbidity. Extracorporeal membrane oxygenation appears to provide effective cardiopulmonary support for selected pediatric respiratory problems. It affords those with potentially reversible pathophysiology the temporal opportunity for successful medical or surgical therapies.

Pulmonary development in the fetal lamb with severe bladder outlet obstruction and oligohydramnios: a morphometric study.

The lethal feature of male newborns with severe bladder outlet obstruction and oligohydramnios is pulmonary hypoplasia. We report a fetal lamb model of bladder outlet obstruction created in the early second trimester, and morphometric analysis of the profound pulmonary hypoplasia that resulted. At 55 to 65 days of gestation 8 consecutive male fetuses underwent surgical clipping of the urethra and urachus near the abdominal wall. A sham operation was performed in 1 female fetus. The lambs were delivered by cesarean section 10 weeks later. The right lungs were immediately fixed at a distending pressure of 25 cm. water. The results of the morphometric studies were compared to control animals from our earlier study of normal fetal lamb lung development; slides for both studies were scored in a blind, randomized fashion by 1 of us (S. G. D.). Although mean body weights for the groups were similar, mean right lung volume in the operated lambs was 63.8 cM.3 compared to 158 cM.3 in the control animals and 137 cM.3 in the sham operated fetus (p less than 0.0005). Relative volume of respiratory tissue was 87 per cent in the operated animals, and 92 per cent in the controls and the sham operated fetus (p less than 0.0005). Microscopic morphometry revealed an increased relative volume of inter-alveolar tissue in the experimental animals (35 compared to 23 per cent in the normal lambs, p less than 0.05), with a corresponding decrease in relative airspace volume. Alveolar numerical density and alveolar surface density were not statistically different between the groups, although total alveolar number and surface area were substantially decreased in the operated lambs due to the reduced mean lung volume. Mean alveolar wall thickness was increased at 3.6 microM. in the operated group versus 2.1 microM. in the normal group (p less than 0.0005) and 2.8 microM. in the sham operated fetus. Thus, the lung in the lamb with severe bladder outlet obstruction is hypoplastic and immature.

Fetal diaphragmatic hernia: ultrasound diagnosis and clinical outcome in 38 cases.

A previously published survey has evaluated the natural history and clinical outcome of fetal diaphragmatic hernia (CDH) in 94 cases. This study showed that the prenatal diagnosis is accurate, the mortality is high (80%), and polyhydramnios is a prenatal predictor of poor clinical outcome. As a follow-up study, 38 consecutive cases of CDH diagnosed in utero were evaluated and treated by the same surgical team. This permitted detailed assessment of prognostic factors and evaluation of the impact of extracorporeal membrane oxygenation (ECMO) on outcome. We found the following. (1) Survival is poor despite optimal postnatal therapy including ECMO. (2) Polyhydramnios is both a common prenatal marker for CDH (present in 69% of fetuses) and a predictor for poor clinical outcome (only 18% survival), but tends to occur after the second trimester. (3) Amniocentesis is indicated to rule out chromosomal abnormalities that were present in 16% of fetuses. (4) All 14 fetuses diagnosed prior to 25 weeks' gestation died. Improved postnatal therapy or surgical intervention before birth will be necessary to salvage the CDH fetus with an early gestational diagnosis or associated polyhydramnios.

Effect of pentoxiphylline on oxygen transport during hypothermia.

At least two investigators have demonstrated a reduction in O2 extraction during induced hypothermia (Cain and Bradley, J. Appl. Physiol. 55: 1713-1717, 1983; Schumacker et al., J. Appl. Physiol. 63: 1246-1252, 1987). We hypothesized that administration of pentoxiphylline (PTX), a theobromine that lowers blood viscosity and has vasodilator effects, would increase O2 extraction during hypothermia. To test this hypothesis, we studied O2 transport in anesthetized, paralyzed, mechanically ventilated beagles exposed to hypoxic hypoxia during either 1) normothermia (38 degrees C), 2) hypothermia (30 degrees C), or 3) hypothermia + PTX (30 degrees C and PTX, 20 mg.kg-1.h-1). Measurements included arterial and mixed venous PO2, hemoglobin concentration and saturation, cardiac output, systemic vascular resistance (SVR), blood viscosity, and O2 consumption (VO2). Critical levels of O2 delivery (DO2, the product of arterial O2 content and cardiac output) were determined by a system of linear regression. Hypothermia significantly decreased base line cardiac output (-35%), DO2 (-37%), and VO2 (-45%), while increasing SVR and blood viscosity. Addition of PTX increased cardiac output (35%) and VO2 (14%), and returned SVR and blood viscosity to normothermic levels. Hypothermia alone failed to significantly reduce the critical level of DO2, but addition of PTX did [normothermia, 11.4 +/- 4.2 (SD) ml.kg-1.min-1; hypothermia, 9.3 +/- 3.6; hypothermia + PTX, 6.6 +/- 1.3; P less than 0.05, analysis of variance]. The O2 extraction ratio (VO2/DO2) at the critical level of DO2 was decreased during hypothermia alone (normothermia, 0.60 +/- 0.13; hypothermia, 0.42 +/- 0.16; hypothermia + PTX, 0.62 +/- 0.19; P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Use of the postductal PaO2 as a predictor of pulmonary vascular hypoplasia in infants with congenital diaphragmatic hernia.

Infants with congenital diaphragmatic hernia (CDH) demonstrate a wide range of anatomic and physiologic abnormalities that result in decreased pulmonary perfusion. We have used the patients' ability to achieve at least one postductal PaO2 greater than 100 torr while on maximal ventilation with 100% oxygen during the first 24 hours of life as the clinical marker to identify the degree of pulmonary perfusion. Patients were grouped as follows: group 1 had at least one postductal PaO2 greater than 100 torr, and group 2 patients never had a postductal PaO2 above 100 torr. To see if this classification did reflect pulmonary vascular abnormalities, we compared the pulmonary arteriograms of these two groups of CDH infants for size of the main pulmonary arteries (PAs), size of the lungs, and degree of peripheral vascular obstructive disease (PVO). Infants in group 2 had significantly smaller ipsilateral and contralateral main PAs, as well as smaller ipsilateral lungs with more severe PVO. We propose the postductal PaO2 as the clinical marker for identification of the degree of pulmonary perfusion.