S. David Rubenstein

Partial liquid ventilation with perflubron in premature infants with severe respiratory distress syndrome

Background The intratracheal administration of a perfluorocarbon liquid during continuous positive-pressure ventilation (partial liquid ventilation) improves lung function in animals with surfactant deficiency. Whether partial liquid ventilation is effective in the treatment of infants with severe respiratory distress syndrome is not known. Methods We studied the efficacy of partial liquid ventilation with perflubron in 13 premature infants with severe respiratory distress syndrome in whom conventional treatment, including surfactant therapy, had failed. Partial liquid ventilation was initiated by instilling perflubron during conventional mechanical ventilation to a volume approximating the functional residual capacity. Infants were considered to have completed the study if they received partial liquid ventilation for at least 24 hours. Results Ten infants received partial liquid ventilation for 24 to 76 hours. In the other three infants, partial liquid ventilation was discontinued within four hours in fa...

Liquid ventilation of human preterm neonates

This report details the application of liquid perfluorochemical ventilation for investigational therapy in three human preterm neonates (gestational ages 28, 24, and 23 weeks) in whom conventional therapies for severe respiratory distress had failed. Liquid ventilation was performed without difficulty in each infant for two 3- to 5-minute cycles by means of gravity-assisted technique. Marked improvement in lung distensibility, without a change in cardiovascular status, occurred in all three infants after liquid ventilation; oxygenation improved in two. All infants died within 19 hours of liquid ventilation, and there was no evidence of retained perfluorochemical fluid in the lungs or pleural space. Death was probably related to the severity of lung disease before the initiation of liquid ventilation. This satisfactory initial outcome shows the feasibility and potential of this treatment of pulmonary dysfunction in the preterm neonate.

Immediate improvement in lung volume after exogenous surfactant: alveolar recruitment versus increased distention.

To determine whether changes in lung volume may be responsible for the clinical improvement in preterm infants given exogenous surfactant, we measured functional residual capacity (FRC), lung mechanics, and partial pressure of oxygen in seven ventilated neonates (birth weight 1080 +/- 361 gm (mean +/- SD); gestational age 28.3 +/- 2.6 weeks) less than 9 hours of age who had findings typical of hyaline membrane disease. All patients received 100 mg/kg calf lung surfactant extract. FRC was measured by a closed-circuit helium-dilution technique, and lung mechanics were determined by least mean squares analysis. FRC increased in all patients (range 56% to 330%; p less than 0.03). Dynamic lung compliance and total airway conductance did not change. Mean +/- SEM specific lung compliance (dynamic lung compliance/FRC) decreased 55.93% +/- 4.27% (p less than 0.02) and mean specific conductance (total airway conductance/FRC) decreased 45.91% +/- 9.74% (p less than 0.009). Mean alveolar/arterial partial pressure of oxygen ratio decreased 51.0% +/- 8.67% (p less than 0.01). These data indicate that the immediate improvement in oxygenation after surfactant administration is related to increased lung volumes. The decrease in specific lung compliance and specific airway conductance is suggestive of increased distention rather than recruitment of functional alveoli.

Pressure-volume relationships of tracheae in fetal newborn and adult rabbits

The physical properties of the trachea in fetal, newborn, and adult rabbits change with age. Tracheal dimensions and pressure--volume relationships were determined in excised tracheae at a wide developmental age range (from early gestational age to infancy and adulthood). At intraluminal pressures of 0 to 10 cm H2O, the tracheal specific compliance was 0.089 (cm H2O)(-1) for a 21 day old fetus. By adulthood, the tracheal specific compliance decreased five fold to 0.017 (cm H2O)(-1); a dramatic proportion of this reduction occurred during fetal life itself, followed by a steady, progressive decline to adult age. The volume of the tracheal segment, at intraluminal pressure of 20 cm H2O, increased by 29% (adult), 41.5% (31 day fetus) and 113% (21 day fetus). Developmental alterations in the specific airway compliance suggest significant changes in anatomical dead space would occur as a function of maturation and airway transmural pressure.

LIQUID VENTILATION OF PRETERM BABY

SiR,-While advances in gas ventilation and surfactant replacement therapy have improved survival of premature babies, morbidity remains significant. Animal studies have demonstrated that ventilation with an oxygenated liquid perfluorochemical (PFC) supports gas exchange without deleterious consequences at ages where conventional techniques fail.’-3 We report the application of liquid PFC ventilation as an investigational therapy to improve pulmonary gas exchange and mechanics in a newborn baby. A 28-week gestation, 12-day-old girl weighing 980 g with bilateral interstitial parenchymal disease was referred for

Psychological Aspects of Parenting Critically Ill Neonates

This study was designed to objectively examine depression and distress levels in parents of ill versus parents of healthy neonates by utilizing two well-validated questionnaires, the Beck Depression Inventory (BDI) and Kellner Symptom Questionnaire (KSQ). In addition, morbidity of infants was assessed by the Minde-Whitelaw Neonatal Morbidity Scale, and parents completed a socioeconomic questionnaire. Analysis of mean BDI and KSQ scores revealed significant differences between parents of ill neonates and parents of healthy neonates in BDI, total KSQ scores, KSQ anxiety, and depression scale scores. Within these groups, respondents whose scores fell into moderate to severe ranges of distress on either questionnaire were referred for counseling. The BDI and KSQ, can be tools for better understanding about distress levels in parents of ill and healthy neonates.

Effect of exchange transfusion with a red blood cell substitute on neonatal hemodynamics and organ blood flows.

The present study was designed to evaluate the effect of a perfluorocarbon erythrocyte substitute on hemodynamics in the newborn lamb. Isovolumic double volume exchange transfusions were performed with perfluorocarbon emulsion (FC-43) on lambs who were ventilated to maintain normal acid base status. Hematocrit, fluorocrit, viscosity, arterial gas tensions, mean arterial pressure, and heart rate were determined before (control) and after (exchange) exchange transfusion. A radiolabeled microsphere technique was used and cardiac output, organ blood flow, organ vascular resistance, and oxygen delivery were calculated. As the hematocrit and viscosity decreased and the fluorocrit increased, there was a significant increase in PaO2 as well as a significant decrease in A-a gradient and oxygen content. There was no significant change in the acid-base status or the hemodynamic profile (heart rate, stroke volume, cardiac output, and mean arterial pressure). Blood flow to the heart and brain showed a significant increase, whereas flow to the cortex of the kidney showed a significant decrease. There was no significant change in flow to the gastrointestinal tract. Organ vascular resistance in the brain significantly decreased, increased in the kidney, and showed no significant change in the heart and gastrointestinal tract. Oxygen delivery significantly decreased in all organs except the heart. These data suggest that perfluorocarbon emulsions can acutely maintain hemodynamic stability in the newborn lamb and that the intrinsic properties of perfluorocarbons allow for the preservation of adequate oxygenation and acid-base status.

PARTIAL LIQUID VENTILATION FOR INFANTS FAILING ON EXTRACORPOREAL MEMBRANE OXYGENATION (ECMO). † 1251

A trial of partial liquid ventilation (PLV) with sterile perflubron(LiquiVent©; Alliance Pharmaceutical, San Diego CA.) is being conducted for infants with severe respiratory failure requiring ECMO support. Infants are enrolled, following informed parental consent, if they have been on ECMO for at least 48 hours, and are not responding to therapy. The lungs are filled with an FRC of perflubron and the infant is maintained on ECMO support and conventional ventilation. Evaporative losses of perflubron are replaced. PLV is continued for up to 96 hours if improvement is noted. To assess the effect of PLV on lung function, compliance (CL, ml/cmH2O/kg,) is determined by airway manometry and pneumotachography. Six infants (ARDS = 4, CDH = 2) have been studied (Mean ± SE age 3 ± 1.6 months) following prolonged periods of ECMO without improvement (mean ± SE 13± 3.3 days on ECMO, range 5 to 21 days). The infants tolerated PLV well, with volume recruitment observed on chest radiograph, and debris removal occurring on suctioning. The total amount of perflubron instilled varied with each infant (mean ± SE 64 ± 19 ml/kg, range 16 to 125 ml/kg). Compared to pre-PLV, all infants demonstrated improvements in Cl during PLV, ranging from 24 to 344% increase (Mean ± SE 186 ± 51%). Four of 6 infants weaned from ECMO to conventional ventilation for at least 3 days. One infant with CDH died of respiratory failure and one infant died from generalized Herpes soon after ECMO was withdrawn. Two infants died at 4 and 68 days post-PLV, and two are long term survivors. None of the deaths were related to PLV. These data demonstrate that PLV recruits lung volume and improves CL in critically ill infants on ECMO. The impact of PLV on long term outcome in these critically ill infants, however, will need to be evaluated. Supported in part by NIH MO1RR00240.

AN EXPERIMENTAL PRETERM MODEL OF EXTRAUTERINE DEVELOPMENT

Liquid ventilation (LV) with oxygenated fluorocarbon (RIMAR 101R) was utilized to develop an extrauterine preterm lamb model. Fifteen preterm lambs ranging in age from 106 to 142 days gestation (0.70 to 0.95 gestation) were studied. At elective cesarean section, the fetal carotid artery, jugular vein and trachea were cannulated. The umbilical cord was clamped and the lamb was liquid ventilated through the tracheostomy. Controlled LV was delivered over 2 hrs at an FRC = 30 ml/kg; tidal volume = 15 ml/kg; frequency = 5-9 brth/min. Normothermia was maintained by radiant (heat lamp) and convective (warmed liquid fluorocarbon) heat exchange. Dextrose (6 mg/kg/min) and bicarbonate (1 mEq/kg/hr) were continuously infused. Hemodynamic parameters during LV ranged from: heart rate = 146-202 b/min; mean arterial pressure = 40-80 mmHg; central venous pressure = 0.7-9.8 mm/Hg; O2 consumption = 1.38-11.8 ml/min/kg. Stable gas exchange was demonstrated with; PaO2 = 158-222 mmHg; PaCO2 = 34-38 mmHg; and pH = 7.28-7.39. The extrauterine model provides general accessibility of the preterm animal thus enabling the necessary instrumentation for comprehensive evaluation. Of further importance, the viability of preterm animals is extended to an earlier gestational age, thereby enlarging the scope of developmental research. (Supported by NIH Grant HL22843 and 5T32HL0741405)