Marla R. Wolfson

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...

Research in high flow therapy: Mechanisms of action

Recently, heater/humidifier devices that use novel methods to condition breathing gases from an external source have been introduced. The addition of sufficient warmth and high levels of humidification to breathing gas has allowed for higher flow rates from nasal cannula devices to be applied to patients (i.e., high flow therapy). This article provides a review of the proposed mechanisms behind the efficacy of high flow therapy via nasal cannula, which include washout of nasopharyngeal dead space, attenuation of the inspiratory resistance associated with the nasopharynx, improvement in conductance and pulmonary compliance, mild distending pressure and reduction in energy expenditure for gas conditioning.

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.

Liquid ventilation improves pulmonary function, gas exchange, and lung injury in a model of respiratory failure.

ObjectiveThe authors evaluated gas exchange, pulmonary function, and lung histology during perfluorocarbon liquid ventilation (LV) when compared with gas ventilation (GV) in the setting of severe respiratory failure. BackgroundThe efficacy of LV in the setting of respiratory failure has been evaluated in premature animals with surfactant deficiency. However, very little work has been performed in evaluating the efficacy of LV in older animal models of the adult respiratory distress syndrome (ARDS). MethodsA stable model of lung injury was induced in 12 young sheep weighing 16.4 ± 3.0 kg using right atrial injection of 0.07 mL/kg of oleic acid followed by saline pulmonary lavage and bjjugular venovenous extracorporeal life support (ECLS). For the first 30 minutes on ECLS, all animals were ventilated with gas. Animals were then ventilated with either 15 mL/kg gas (GV, n = 6) or perflubron([PFC], LV, n = 6) over the ensuing 2.5 hours. Subsequently, ECLS was discontinued in five of the GV animals and five of the LV animals, and GV or LV continued for 1 hour or until death. Main FindingsPhysiologic shunt (Qps/Q1) was significantly reduced in the LV animals when compared with the GV animals (LV = 31 ± 10%; GV = 93 ± 4%; p < 0.001) after 3 hours of ECLS. At the same time point, pulmonary compliance (Cγ) was significantly increased in the LV group when compared with the GV group (LV = 1.04 ± 0.19 mL/cm H2O/kg; GV = 0.41 ± 0.02 mL/cm H2O/kg; p < 0.001). In addition, the ECLS flow rate required to maintain the PaO2 in the 50− to 80-mm Hg range was substantially and significantly lower in the LV group when compared with that of the GV group (LV =14 ± 5 mL/kg/min; GV = 87 ± 15 mL/kg/min; p < 0.001). All of the GV animals died after discontinuation of ECLS, whereas all the LV animals demonstrated effective gas exchange without extracorporeal support for 1 hour (p < 0.01). Lung biopsy light microscopy demonstrated a marked reduction in alveolar hemorrhage, lung fluid accumulation, and inflammatory infiltration in the LV group when compared with the GV animals.

Mechanics and energetics of breathing helium in infants with bronchopulmonary dysplasia.

The mechanics and energetics of breathing were studied in preterm infants with bronchopulmonary dysplasia while spontaneously breathing control gas and helium-oxygen (Heliox) gas mixtures. During Heliox breathing, there was a significant decrease in pulmonary resistance, resistive work of breathing, and mechanical power of breathing, whereas ventilation remained unchanged. Breathing a lower density gas mixture (Heliox) may have therapeutic value by decreasing the demands on the respiratory muscles and the caloric requirements for breathing. Therefore, this modality may reduce potential respiratory muscle fatigue and avail additional calories for growth and recovery in the preterm infant with bronchopulmonary dysplasia.

Lung lavage with oxygenated perfluorochemical liquid in acute lung injury.

ObjectiveTo investigate the effects of lung lavage with oxygenated liquid perfluorochemical on gas exchange, lung mechanics, and cardiac function in animals with acute lung injury. DesignProspective, randomized, controlled trial. SettingAnimal laboratory. SubjectsEight adult cats (2 to 4 kg, random sex). InterventionsTwo insults were combined to cause lung injury: oleic acid infusion and saline whole-lung wash. Animals were assigned to either the control or treatment group which consisted of a perfluorochemical liquid (Rimar 101) lavage. Perfluorochemical liquid lavage was performed three times at hourly intervals after lung injury. Three other cats with identical injury but no perfluorochemical liquid lavage served as control animals. All cats were ventilated with an Fio2 of 0.95 and positive end-expiratory pressure of 2 cm H2O continuously. Measurements and Main ResultsArterial blood gas tensions and pH, dynamic pulmonary compliance were measured at 15-min intervals. Cardiac index was assessed hourly, and lung fluid was collected after each of the three perfluorochemical liquid lavages. Arterial oxygen tension and pulmonary compliance deteriorated abruptly after lung injury in all cats, and improved significantly (p < .001, two-way analysis of variance) 15 mins after perfluorochemical liquid lavage. These parameters gradually returned to their baseline over 60 mins. Arterial blood pressure and cardiac index decreased after injury in all cats, and were not significantly changed after perfluorochemical liquid lavage. Hemorrhagic fluid was recovered from distal airways by perfluorochemical liquid lavage, despite prior suctioning of the airway. ConclusionsPerfluorochemical liquid lavage removes pulmonary edema fluid and improves gas exchange and the mechanical properties of the lung, after acute severe lung injury. (Crit Care Med 1993; 21:768–774)

Liquid assisted ventilation: An alternative ventilatory strategy for acute meconium aspiration injury

Evidence of surfactant inactivation by meconium has led to the use of exogenous surfactant therapy in the management of meconium aspiration syndrome (MAS). Liquid assisted ventilation has been shown to improve the cardiopulmonary function in lungs with high surface tension. We compared exogenous surfactant therapy with liquid assisted ventilation in the management of experimental acute meconium aspiration injury. Thirty‐two newborn lambs were ventilated at peak inspiratory pressures of 13–16 cm H2O, positive end expiratory pressure of 3–4 cm H2O, fractional inspired oxygen concentration (F1O2) of 1.0, and a respiratory frequency range between 30 and 35 breaths/min. Baseline arterial blood gases, pulmonary function, and arterial blood pressure measurements were taken. All lambs were given 2–3 ml/kg of an unfiltered 25% meconium solution. Lambs were then randomized into either gas‐ventilated meconium control, or one of three treatment groups: 1) surfactant; 2) partial liquid ventilation (PLV); or 3) total liquid ventilation (TLV) for 4 hours after meconium injury. All treated groups demonstrated a significant increase in arterial oxygenation (P < 0.05); surfactant and PLV‐treated lambs demonstrated significantly decreased arterial PCO2 (P < 0.05). Compliance in all groups increased compared with injury values; compliance of the TLV group increased more than in all other treatment groups (P < 0.05). In addition, lung histology of the TLV group demonstrated clear, intact alveolar epithelium and homogeneously expanded alveoli, while no such improvement was evident in the other groups. These data suggest roles for both exogenous surfactant therapy and liquid assisted ventilation techniques in the management of MAS. Pediatr Pulmonol. 1996; 21:316–322.

Fluorocarbon ventilation: maximal expiratory flows and CO2 elimination.

ABSTRACT: Elimination of CO2 during liquid ventilation is dependent on flow, diffusion, and the liquids capacitance for CO2. Maximum expiratory flow (Vmax) and diffusion dead space were measured in vivo in 12 young cuts during liquid fluorocarbon (FC-80) ventilation to determine the effect of breathing frequency on maximum CO2 elimination. All animals were maintained (PaO2, = 255 ± 19 SEM mm Hg, PaCO2, = 35 ± 1 SEM mm Hg, pH = 7.31 ± 0.01 SEM) within physiologic range during 1–4 h of liquid ventilation. The Vmax in air (26 ± 1 SEM liter/min) and in liquid (1.2 ± 0.2 SEM liter/min) was determined by volume displacement plethysmography. Diffusion dead space (VDdiff) during liquid ventilation as a ratio of alveolar volume (VA) was well correlated (r = 0.84, p < 0.005) with the average time (tav) the liquid was in the lung [VDdiff/VA = 0.89 e(-0.053 tav)]. Alveolar ventilation, CO2 elimination (VCO2 and PaCO2 were not affected by breathing frequency (f) when tidal volume was adjusted appropriately during steady state liquid ventilation. Predicted maximum CO2 elimination (VCO2max) determined from Vmax and VDdiff was 24 ml/min at a f of 3–3.5 breaths/min. The maximum was found to be strongly dependent on f with much less dependency on fixed dead space (anatomic plus equipment) and wave shape characteristics. Elimination of CO2 decreased at low values of f due to inadequate ventilation and at high values of f due to inadequate diffusion time. From a comparison of experimentally determined steady state VCO2 to theoretically predicted VCO2max, the results demonstrate a f-related functional reserve capacity for CO2 elimination during liquid ventilation. These findings suggest that by optimizing the liquid ventilatory pattern it should be possible to maintain adequate CO2 elimination and physiologic PaCO2 in the presence of pulmonary dysfunction and/or elevated metabolic states.

Pregnancy and outcome of uterine allotransplantation and assisted reproduction in sheep.

This pilot study was performed from March 2008 through February 2010 to demonstrate that pregnancy can be achieved in a uterine allograft in the sheep model with the guidance of assisted reproductive technology. Uterine allotransplantation was performed in 12 sexually mature African sheep (Sudanese and Ethiopian). All animals underwent uterine transplantation via a minilaparotomy incision using a Mobius retractor device. A control group of pregnant Romney Marsh sheep with nontransplanted uteri were used to compare fetal development, uterine and placental histologic findings, and blood samples of progeny of the uterine transplant recipient sheep. Fetal size was obtained from ultrasound measurements during the early (crown-rump length) and late (biparietal diameter and abdominal circumference) gestational periods. The primary end point variables included preoperative and postoperative management, embryo transfer protocol, intraoperative assessments, and physiologic cardiopulmonary changes in the lamb during the first 5 hours of life. Four months after the initial uterine transplantation, 5 of 12 uterine allografts were considered candidates for the embryo transfer procedure. Fresh and frozen blastocyst donors were transferred accordingly to the remaining 5 uterine allografts via a minilaparotomy incision. Three of these resulted in pregnancies. One was an ectopic gestation, 1 sheep carried the pregnancy to 105 days, and 1 delivered a fully developed lamb from the transplanted uterus that was delivered via cesarean section. Neonatal lamb blood gas values and chemistry, gross organ examination, and ventilation and respiratory compliance studies yielded results normal for gestational age. This first reported case demonstrates that pregnancy can be carried in an allotransplanted uterus, with the end result a successful delivery.

In Vivo Mechanical Properties of the Developing Airway

ABSTRACT: The inherent mechanical characteristics of the airways are determined in part by their elastic and viscoelastic properties. As compliant structures during early development, the airways are susceptible to significant distention and collapse, depending on the proportionality between airway volume and transmural pressure. To characterize the age-related changes in airway mechanical properties, the elastic and viscoelastic behavior of in vivo trachea! segments were evaluated in preterm and newborn lambs over a wide range of developmental age (108 to 154 days postconceptional age). Tracheal pressure-vol relationships and concomitant airway compliance measurements were used to determine elastic behavior. Calculations of the tracheal relaxation time constant on the same tracheal segments were used to evaluate airway viscoelastic behavior. Data demonstrated a significant (p<0.01) correlation with developmental age. With increasing age, the airways were found to be less compliant, and the tracheal relaxation time constant was observed to decrease. The difference in elastic properties of the trachea, in vivo compared to in vitro, suggest that neural-humoral and surrounding connective tissue factors may affect the elasticity of the developing airway. Although the modulating effects of smooth muscle tone and supporting connective tissue assist in the control of airway dimension and resistance to airflow in the intact airway, the age-related differences in the elastic properties may be a factor that predisposes the more immature airway to positive pressure-induced damage.