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Biomedical subjects

R B Hirschl

Publications and source records attributed to R B Hirschl.

At least 73 records · Page 4Linked to original sources

Partial liquid ventilation protects lung during resuscitation from shock.

Preliminary animal experience with partial liquid ventilation (PLV) suggests that this therapy may diminish neutrophil invasion and capillary leak during acute lung injury. We sought to confirm these findings in a model of shock-induced lung injury. Sixty anesthetized rats were studied. After hemorrhage to an arterial pressure of 25 mmHg for 45 min, animals were resuscitated with blood and saline and treated with gas ventilation alone or with 5 ml/kg of intratracheally administered perflubron. Myeloperoxidase activity was used to measure lung neutrophil content. A permeability index (the bronchoalveolar-to-blood ratio of 125I-labeled albumin activity) quantified alveolar leak. Injury caused an increase in myeloperoxidase that was reversed by PLV (injury = 0.837 +/- 0.452, PLV = 0.257 +/- 0.165; P < 0.01). Capillary permeability also increased with hemorrhage, with a strong trend toward improvement in the PLV group (permeability indexes: injury = 0.094 +/- 0.102, PLV = 0.045 +/- 0.045; 95% confidence interval for injury--PLV: -0.024, 0.1219). We conclude that PLV is associated with a decrease in pulmonary neutrophil accumulation and a trend toward decreased capillary leak after hemorrhagic shock.

Airway Resistance↗

Vesicoureteral reflux and ureteropelvic junction obstruction: association, treatment options and outcome.

PURPOSE: We investigated the association, treatment options and outcomes of patients with ureteropelvic junction obstruction and concomitant vesicoureteral reflux. MATERIALS AND METHODS: We analyzed 6,790 consecutive pediatric urology records at our university. Treatment options included observation, and primary pyeloplasty, ureteroneocystostomy and nephroureterectomy. Hydronephrosis, reflux and obstruction were judged as resolved, improved, unchanged or worse. RESULTS: A total of 1,140 patients had vesicoureteral reflux, 224 had ureteropelvic junction obstruction and 41 had both conditions (39 ipsilateral and 6 contralateral kidneys). There was no increased risk of obstruction in patients with reflux when all grades of reflux were grouped (odds ratio 1.26, confidence interval 0.91 to 1.71). In contrast, subgroup analysis of patients with high grade reflux demonstrated a 5-fold increased risk of obstruction (odds ratio 5.0, confidence interval 2.4 to 10.8). One patient was lost to followup. Observation of 6 kidneys led to resolution of reflux in 3 (50%), resolution of obstruction in 3 (50%) and resolution or improvement of hydronephrosis in 4 (67%). Primary pyeloplasty was done on 29 kidneys with 10 (35%) requiring subsequent ureteroneocystostomy. At latest followup hydronephrosis resolved or improved in 24 patients (83%), vesicoureteral reflux resolved or improved in 19 (66%) and ureteropelvic junction obstruction resolved in all. Primary ureteroneocystostomy was performed on 5 kidneys, all of which required subsequent pyeloplasty. Hydronephrosis resolved in 3 patients (60%), and reflux and obstruction resolved in all. Two patients treated with primary nephroureterectomy, and 1 who underwent concomitant pyeloplasty and ureteroneocystostomy have had no subsequent urological problems. One patient awaits primary pyeloplasty. CONCLUSIONS: High grade vesicoureteral reflux is associated with ureteropelvic junction obstruction. No association with low or intermediate grade reflux was demonstrated. While some patients may be monitored expectantly, in our series pyeloplasty or nephrectomy was required in 81% and ureteroneocystostomy was required in 36%. In no case did primary ureteroneocystostomy protect against the subsequent need for pyeloplasty.

Child, Preschool↗

Pulmonary pathology of patients treated with partial liquid ventilation.

Initial trials of partial liquid ventilation (PLV), which is gas ventilation of perfluorocarbon-filled lungs, are underway in patients with severe respiratory failure. We report the first study of the effects of the perfluorocarbon, perflubron, on the lung. Necropsies were conducted in nine patients (seven adults and two neonates; mean adult age, 31 +/- 5 yr) managed with PLV (average number of doses, 4 +/- 1). All of the patients required extracorporeal life support. The patients had pneumonia with the acute respiratory distress syndrome (six patients), trauma/capillary leak syndrome (one patient), congenital diaphragmatic hernia (one patient), and primary pulmonary hypertension (one patient). Nine adult patients (mean age, 37 +/- 5 yr) with acute respiratory distress syndrome requiring extracorporeal life support served as a control. Pathologic findings were evaluated in both groups. Lung weights in the adult patients of both groups were elevated (mean weight of PLV-treated right lung, 1401 +/- 186 g; mean weight of PLV-treated left lung, 1131 +/- 177 g; mean weight of control right lung, 1018 +/- 91 g; mean weight of control left lung, 988 +/- 80 g). There was no significant difference between the two groups (right lung, P = .066; left lung, P = .436). Frequent gross findings included focal consolidation, patchy hemorrhage, and glassy cut surfaces. The histologic findings were similar in both groups. Diffuse alveolar damage (either proliferative phase or mixed proliferative and exudative phases) was seen in all nine of the study patients. Eight of the nine control patients had diffuse alveolar damage (five had proliferative phase only, one had mixed proliferative and exudative phases, and two had exudative phase only). One other patient had extensive parenchymal necrosis. Other frequent findings were intra-alveolar hemorrhage, numerous intra-alveolar macrophages, and organization of exudate. PLV with perflubron in patients with adult and neonatal respiratory distress syndromes is not associated with unique pathologic findings in the human lung.

Administration, Inhalation↗

Initial experience with partial liquid ventilation in adult patients with the acute respiratory distress syndrome.

OBJECTIVE: To evaluate the safety and efficacy of partial liquid ventilation (PLV). DESIGN: Before-after trial. SETTING: The surgical intensive care unit at the University of Michigan, Ann Arbor, from April to December 1994. PATIENTS: A consecutive sample of 10 patients aged 19 to 55 years with the acute respiratory distress syndrome who were receiving extracorporeal life support. INTERVENTION: Perflubron was administered into the trachea until the dependent zone of the lung was filled. Gas ventilation of the perflubron-filled lung was then performed (PLV). Volatilized perflubron replacement was repeated daily for from 1 to 7 days with a median cumulative dose of 38 mL/kg (range, 15 to 62 mL/kg). MAIN OUTCOME MEASURES: Physiologic shunt and static pulmonary compliance. RESULTS: Physiologic shunt decreased from a median of 0.72 (range, 0.37 to 1.0) to 0.46 (range, 0.21 to 0.96) over the 72 hours following initiation of PLV (P = .01 by repeated measures analysis of variance). Static pulmonary compliance corrected for patient weight increased from a median of 0.16 mL/cm H2O per kilogram (range, 0.01 to 0.48 mL/cm H2O per kilogram) to 0.27 mL/cm H2O per kilogram (range, 0.05 to 1.11 mL/cm H2O per kilogram) over the same time period (P = .04 by repeated measures analysis of variance). Overall survival was five (50%) of 10 patients. Complications that were potentially associated with PLV included pneumothorax development in one patient and mucus plug formation in one patient. CONCLUSIONS: Perflubron may be safely administered into the lungs of patients with severe respiratory failure receiving extracorporeal life support and may be associated with improvement in gas exchange and pulmonary compliance.

Adult↗

Measuring functional residual capacity in normal and oleic acid-injured lungs.

Functional residual capacity (FRC) is an important oxygen reserve that is often depleted in acute respiratory failure. Recent interest in the mechanisms of liquid ventilation and limited experience in measuring FRC in paralyzed, mechanically ventilated, normal and lung-injured animal models have mandated development of accurate laboratory techniques. Eight sheep, from 17 to 27 kg, were anesthetized and instrumented to provide a tracheostomy, a pulmonary artery catheter, and carotid arterial line. They were randomized to two groups, one of which received 0.07 ml/kg of intravenous oleic acid to induce lung injury. Gas ventilation of both groups was identical except for respiratory rate, which was adjusted to normalize PaCO2. FRC was measured in duplicate by both helium dilution (HD) and body plethysmography (BP). When measurements were completed, the animals were euthanized and their endotracheal tubes clamped at end expiration. The lungs were then removed and their water displacement (WD) FRC values were measured. FRC was the difference between WD and tissue weight assuming 1 ml = 1g. Pearson's correlation coefficient (R(2)) was calculated. During in vitro measurement of test lungs, HD had an R(2) value of 0.99 and BP had an R(2) value of 0.98. When compared to WD, in vivo measurement of FRC by HD had an R(2) value of 0.94 while the value for BP was 0.97. In conclusion, both HD and BP are accurate methods of determining FRC in an uninjured and injured lung model when compared to postmortem WD. Documenting changes in FRC will aid in elucidating the mechanisms of alternative ventilatory techniques.

Animals↗

The effect of pre-ECLS ventilation time on survival and respiratory morbidity in the neonatal population.

Although mechanical ventilation for more than 7 to 10 days has been considered a contraindication to the application of extracorporeal life support (ECLS) in neonates, the outcome and respiratory morbidity for newborns placed on ECLS after more than 7 days of ventilation have not been well characterized. The purpose of this study was to determine the impact of pre-ECLS ventilation time on the rate of survival, the likelihood of the development of bronchopulmonary dysplasia (BPD), and the need for supplemental oxygen at the time of discharge. Examination of the Extracorporeal Life Support Organization (ELSO) Registry showed that 6,110 neonates were treated for respiratory failure with a pre-ECLS ventilation time of less than 14 days between January 1990 and May 1995. Gestational age (GA), birth weight (BW), indication for ECLS, and diagnosis were compared with the rate of survival, the discharge diagnosis of BPD, and the need for home oxygen. The GA and BW of neonates placed on ECLS during the first week of life (n = 5,888) did not differ significantly from those of neonates whose ECLS was begun in the second week of life (n = 222). The neonates were divided into two groups (early, ventilation time of 3 to 6 days; late, ventilation time of 7 to 10 days) to determine the odds ratios for survival, BPD, and home oxygen. Logistic regression analysis was used to develop a model to predict the rate of survival, the risk for the development of BPD, and the need for home oxygen given the length of pre-ECLS ventilation time. The late group was less likely to survive (odds ratio, 1.8; 95% confidence interval [CI], 1.21 to 2.68). The late group also had approximately twice the risk for the development of BPD (odds ratio, 1.9; 95% CI, 1.2 to 3.04) and a trend toward an increased incidence of home oxygen use (odds ratio, 1.55; 95% CI, 0.92 to 2.60). The authors conclude that (1) there is a greater risk of mortality and BPD and a trend toward an increased need for home oxygen with increased time on the ventilator before ECLS; (2) at 14 days the predicted probability of survival is still 53% (95% CI, 31% to 74%); (3) at 14 days the predicted probability of BPD is 54% (95% CI, 28% to 78%); and (4) based on these data, it is reasonable to consider application of ECLS to patients who have had mechanical ventilation for up to 14 days.

Bronchopulmonary Dysplasia↗

Partial liquid ventilation in newborn patients with congenital diaphragmatic hernia.

The authors evaluated the safety and efficacy of liquid ventilation with perfluorocarbon in four newborns with congenital diaphragmatic hernia and severe respiratory failure, who were on extracorporeal life support (ECLS). After 2 to 5 days on the ECLS, perflubron was administered into the trachea until the dependent zone of the lung was filled. The first dose was 6 +/- 1 mL/kg (range, 5 to 8 mL/kg). Gas ventilation of the perflubron-filled lung was performed (partial liquid ventilation). The administration of perflubron was repeated daily for 5 to 6 days, with total cumulative doses of 36 +/- 8 mL/kg (range, 26 to 44 mL/kg). A significant increase in PaO(2) (P = .027 by repeated-measures analysis of variance [ANOVA]), a trend toward an increase in arterial oxygen content (P = .052 by repeated-measures ANOVA), and a significant increase in specific static total pulmonary compliance (P = .007 by repeated-measures ANOVA) were observed after administration of the daily dose of perflubron. PaCO(2) data showed a decreasing trend (P = .08 by repeated measures ANOVA). The authors conclude that perflubron can be safely administered into the lungs of newborn patients with congenital diaphragmatic hernia and severe respiratory failure, and it may be associated with improvement in gas exchange and pulmonary compliance.

Dose-Response Relationship, Drug↗

Effect of very delayed repair of congenital diaphragmatic hernia on survival and extracorporeal life support use.

BACKGROUND: Since November 1992, operative repair in neonates with congenital diaphragmatic hernia (CDH) at this institution was delayed until respiratory insufficiency had resolved. METHODS: A retrospective analysis was performed (n = 33) comparing delayed repair with our previously reported institutional experience with immediate repair from January 1988 to October 1992 (n = 66). Infants with severe genetic defects or moribund conditions or who were premature were not considered candidates for repair or extracorporeal life support (ECLS), but they were included in the survival analysis. Survival was defined as hospital discharge. Data were compared with an independent t test or Pearson chi-squared test. RESULTS: Mean age at repair was 8.9 +/- 4.5 days (range, 3 to 20 days). Eleven infants in the study group were placed on ECLS (33% versus 68% in the comparison group; p = 0.001). Six of these infants survived (55% versus 58% in the comparison group; p = 0.846). Of these survivors, one patient was repaired while on ECLS, and the remainder underwent repair after decannulation from ECLS. All 20 of the remaining candidates for repair survived without need for ECLS. Overall survival was 79% versus 56% in the comparison group (p = 0.027). CONCLUSIONS: Our current data suggest that very delayed repair of newborns with CDHs is associated with an increase in the overall survival and a decrease in the use of ECLS when compared with previous experience at this institution.

Extracorporeal Membrane Oxygenation↗

Partial liquid ventilation provides effective gas exchange in a large animal model.

PURPOSE: The purpose of this study was to show the ability of partial liquid ventilation (PLV) to sustain gas exchange in normal large (50 to 70 kg) adult animals. METHODS: Ten adult sheep (53.7 +/- 2.8 kg) were anesthetized and mechanically ventilated. Sequential dosing of perflubron (LiquiVent, Alliance Pharmaceutical Corp, San Diego, CA) was performed to cumulative doses of 10 mL/kg, 20 mL/kg, 40 mL/kg, and 60 mL/kg. Physiological data were assessed at baseline and after each dose. Five animals were rotated through the left decubitus, right decubitus, supine, and prone positions while five animals remained prone throughout the experiment. RESULTS: PaO2 and PaCO2 did not change significantly from baseline during administration of perflubron except for the PaO2 in rotated animals when supine (rotated-supine PaO2: baseline = 519 +/- 64 mm Hg; 60 mL/kg = 380 +/- 109 mm Hg, P = .0131). In both groups, static lung compliance (CT) decreased steadily with each successive perflubron instillation (nonrotated CT: baseline = 1.55 +/- 0.22 mL/cm H2O/kg; 60 mL/kg = 0.52 +/- 0.10 ml/cmH2O/kg, P = .0003). CONCLUSIONS: These data show that during PLV in this normal animal model, effective gas exchange is sustained and CT decreases with increasing perflubron dose.

Animals↗

Initial experience with partial liquid ventilation in pediatric patients with the acute respiratory distress syndrome.

OBJECTIVE: Liquid ventilation with perfluorocarbon previously has not been reported in pediatric patients with respiratory failure beyond the neonatal period. We evaluated the technique of partial liquid ventilation in six pediatric patients with the acute respiratory distress syndrome of sufficient severity to require extracorporeal life support (ECLS). DESIGN: This study was a noncontrolled, phase I/II experimental study with a single group pretest/posttest design. SETTING: All studies were performed at a tertiary, pediatric referral hospital at the University of Michigan Medical School. PATIENTS: Six pediatric patients, from 8 wks to 5 1/2 yrs of age, with severe respiratory failure requiring ECLS to support gas exchange. INTERVENTIONS: After 2 to 9 days on ECLS, perfluorocarbon was administered into the trachea until the dependent zone of each lung was filled. The initial administered was 12.9 +/- 2.3 mL/kg (range 5 to 20). Gas ventilation of the perfluorocarbon-filled lungs (partial liquid ventilation) was then performed. The perfluorocarbon dose was repeated daily for a total of 3 to 7 days, with a cumulative dose of 45.2 +/- 6.1 mL/kg (range 30 to 72.5). MEASUREMENTS AND MAIN RESULTS: All measurements of native gas exchange were made during brief periods of discontinuation of ECLS and include PaO2 and the alveolar-arterial oxygen gradient, P(A-a)O2. Static pulmonary compliance, corrected for weight, was also measured directly. The mean PaO2 increased from 39 +/- 6 to 92 +/- 29 torr (5.2 +/- 0.8 to 12.2 +/- 3.9 kPa) over the 96 hrs after the initial dose (p = .021 by repeated-measures analysis of variance). The average P(A-a)O2 decreased from 635 +/- 10 to 499 +/- 77 torr (84.7 +/- 1.3 to 66.5 +/- 10.3 kPa) over the same time period (p = .059), while the mean static pulmonary compliance (normalized for patient weight) increased from 0.12 +/- 0.02 to 0.28 +/- 0.08 mL/cm H2O/kg (p = .01). All six patients survived. Complications potentially associated with partial liquid ventilation were limited to pneumothoraces in two of six patients. CONCLUSIONS: Perfluorocarbon may be safely administered into the lungs of pediatric patients with severe respiratory failure on ECLS and may be associated with improvement in gas exchange and pulmonary compliance.

Child, Preschool↗

Total liquid ventilation with perfluorocarbons increases pulmonary end-expiratory volume and compliance in the setting of lung atelectasis.

OBJECTIVE: To compare compliance and end-expiratory lung volume during reexpansion of normal and surfactant-deficient ex vivo atelectatic lungs with either gas or total liquid ventilation. DESIGN: Controlled, animal study using an ex vivo lung preparation. SETTING: A research laboratory at a university medical center. SUBJECTS: Thirty-six adult cats, weighing 2.5 to 4.0 kg. INTERVENTIONS: Heparin (300 U/kg) was administered, cats were killed, and lungs were excised en bloc. Normal lungs and saline-lavaged, surfactant-deficient lungs were allowed to passively collapse and remain atelectatic for 1 hr. Lungs then were placed in a plethysmograph and ventilated for 2 hrs with standardized volumes of either room air or perfluorocarbon. Static pulmonary compliance and end-expiratory lung volume were measured every 30 mins. MEASUREMENTS AND MAIN RESULTS: Reexpansion of normal atelectatic lungs with total liquid ventilation was associated with an 11-fold increase in end-expiratory lung volume when compared with the increase in end-expiratory lung volume observed with gas ventilation (total liquid ventilation 50 +/- 14 mL, gas ventilation 4 +/- 9 mL, p < .0001). The difference was even more pronounced in the surfactant-deficient lungs with an approximately 19-fold increase in end-expiratory lung volume observed in the total liquid ventilated group, compared with the gas ventilated group (total liquid ventilation 44 +/- 17 mL, gas ventilation 2 +/- 8 mL, p = .0001). Total liquid ventilation was associated with an increase in pulmonary compliance when compared with gas ventilation in both normal and surfactant-deficient lungs (normal: gas ventilation 6 +/- 1 mL/cm H2O, total liquid ventilation 14 +/- 4 mL/cm H2O, p < .0001; surfactant-deficient: gas ventilation 4 +/- 1 mL/cm H2O, total liquid ventilation 9 +/- 3 mL/cm H2O, p < .01). CONCLUSIONS: End-expiratory lung volume and static compliance are increased significantly following attempted reexpansion with total liquid ventilation when compared with gas ventilation in normal and surfactant-deficient, atelectatic lungs. The ability of total liquid ventilation to enhance recruitment of atelectatic lung regions may be an important means by which gas exchange is improved during total liquid ventilation when compared with gas ventilation in the setting of respiratory failure.

Animals↗

Evaluation of gas exchange, pulmonary compliance, and lung injury during total and partial liquid ventilation in the acute respiratory distress syndrome.

OBJECTIVE: To investigate whether pulmonary compliance and gas exchange will be sustained during "total" perfluorocarbon liquid ventilation followed by "partial" perfluorocarbon liquid ventilation when compared with gas ventilation in the setting of the acute respiratory distress syndrome (ARDS). STUDY DESIGN: A prospective, controlled, laboratory study. SETTING: A university research laboratory. SUBJECTS: Ten sheep, weighing 12.7 to 25.0 kg. INTERVENTIONS: Lung injury was induced in ten young sheep, utilizing a right atrial injection of 0.07 mL/kg of oleic acid followed by saline pulmonary lavage. Bijugular venovenous extracorporeal life support access, a pulmonary artery catheter, and a carotid artery catheter were placed. When the alveolar-arterial O2 gradient was >/= 600 torr and PaO2 </= 50 torr (</= 6.7 kPa) with an FIO2 of 1.0, extracorporeal life support was instituted. For the first 30 mins on extracorporeal life support, all animals were ventilated with gas. Animals were then ventilated with equal tidal volumes of 15 mL/kg during gas ventilation (n=5) over the ensuing 2.5 hrs, or with total liquid ventilation for 1 hr, followed by partial liquid ventilation for 1.5 hrs (total/partial liquid ventilation, n=5). MEASUREMENTS AND MAIN RESULTS: An increase in physiologic shunt (gas ventilation = 69 +/- 11%, total/partial liquid ventilation = 71 +/- 3%) and a decrease in static total pulmonary compliance measured at 20 mL/kg inflation volume (gas ventilation = O.48 +/- 0.03 mL/cm H2O/kg, total/partial liquid ventilation = 0.50 +/- 0.17 mL/cm H2O/kg) were observed in both groups with induction of lung injury. Physiologic shunt was significantly reduced during total and partial liquid ventilation when compared with physiologic shunt observed in the gas ventilation animals (gas ventilation = 93 +/- 8%, total liquid ventilation = 45 +/- 11%, p<.001; gas ventilation = 95 +/- 3%, partial liquid ventilation = 61 +/- 12%, p<.001), while static compliance was significantly increased in the total, but not the partial liquid ventilated animals when compared with the gas ventilated group (gas ventilation = 0.43 +/- 0.03 mL/cm H2O/kg, total liquid ventilation = 1.13 +/- 18 mL/cm H2O/kg, p <.001; gas ventilation = 0.41 +/- 0.02 mL/cm H2O/kg, partial liquid ventilation = 0.47 +/- 0.08, p = .151). In addition, the extracorporeal life support flow rate required to maintain adequate oxygenation was significantly lower in the total/partial liquid ventilation group when compared with that of the gas ventilation group (gas ventilation = 89 +/- 7 mL/kg/min, total liquid ventilation = 22 +/- 10 mL/kg/min, p <.001; gas ventilation = 91 +/- 12 mL/kg/min, partial liquid ventilation = 41 +/- 11 mL/kg/min, p < .001). Lung biopsy light microscopy demonstrated a marked reduction in alveolar hemorrhage, lung fluid accumulation, and inflammatory infiltration in the total/partial liquid ventilation animals when compared with the gas ventilation animals. CONCLUSIONS: In a model of severe ARDS, pulmonary gas exchange is improved during total followed by partial liquid ventilation. Pulmonary compliance is improved during total, but not during partial liquid ventilation. Total followed by partial liquid ventilation was associated with a reduction in alveolar hemorrhage, pulmonary edema, and lung inflammatory infiltration.

Animals↗

Efficacy of perfluorocarbon partial liquid ventilation in a large animal model of acute respiratory failure.

OBJECTIVE: To demonstrate the efficacy of partial perfluorocarbon liquid ventilation in large animal model of acute respiratory failure. DESIGN: Prospective, randomized, controlled trial. SETTING: Animal laboratory at a university medical center. SUBJECTS: Ten adult sheep, weighing 53.0 +/- 2.8 kg. INTERVENTIONS: After assessment of baseline physiologic data, acute respiratory failure was induced by right atrial injection of oleic acid (0.2 mL/kg). Five animals (partial liquid ventilation group) underwent sequential intratracheal dosing of 10 mL/kg of perflubron at 30-min intervals to the following cumulative doses: 10, 20, 30, 40, and 50 mL/kg. The remaining five animals were gas ventilated (control group). Physiologic data were assessed at 30-min intervals in both groups for the 2.5-hr experimental period or until death. MEASUREMENTS AND MAIN RESULTS: When compared with control animals, intratracheal perfluorocarbon instillation resulted in significant improvements in arterial oxygen saturation (arterial oxygen saturation after 50 mL/kg: partial liquid ventilation, 96 +/- 3%; control, 55 +/- 8%; p = .001) and physiologic shunt (physiologic shunt after 50 mL/kg dose: partial liquid ventilation, 2 +/- 8%; control, 64 +/- 5%; p = .004). Oxygen delivery improved with perfluorocarbon instillation, but this improvement was not significant. No significant difference in pulmonary compliance was observed during partial liquid ventilation when compared with controls (pulmonary compliance: partial liquid ventilation, 0.43 +/- 0.04 mL/ cm H2O/kg; control, 0.53 +/- 0.03 mL/cm H2O/kg; p = .102). CONCLUSIONS: Partial liquid ventilation with perflubron provides effective improvement in gas exchange in an adult animal model of respiratory failure.

Acute Disease↗

Perfluorocarbon protects lung epithelial cells from neutrophil-mediated injury in an in vitro model of liquid ventilation therapy.

Liquid ventilation with perfluorocarbon has been effective in improving gas exchange and pulmonary function in the setting of acute respiratory failure. How improvement is brought about remains unknown. In the present study, we examined perfluorocarbon for effects on neutrophil function and for effects on neutrophil-epithelial cell interactions that could underlie its in vivo activity. Exposure of neutrophils in vitro to perfluorocarbon followed by washing did not interfere with their ability to generate oxidants or release proteolytic enzymes upon subsequent stimulation. Likewise, such treatment did not interfere with subsequent adhesion of the neutrophils to monolayers of epithelial cells or with neutrophil-induced injury to these cells. In contrast, when perfluorocarbon was added to neutrophils and epithelial cells together and the neutrophils then stimulated, it reduced their adhesive interaction with the target cells and concomitantly reduced target cell injury. In companion studies, cells were obtained by bronchial lavage of perfluorocarbon-treated patients with acute respiratory distress syndrome (ARDS) and analyzed for oxidant production. Oxidant-generating capacity by the cells obtained from the bronchial lavage fluid was similar to that of peripheral blood neutrophils. These data are consistent with the suggestion that perfluorocarbon protects cells in vitro from neutrophil-mediated injury, at least in part, by acting as a mechanical barrier. These findings are consistent with a potential mechanism of action in vivo.

Bronchoalveolar Lavage Fluid↗

Partial liquid ventilation with perflubron during extracorporeal life support in adults: radiographic appearance.

PURPOSE: To describe the radiographic appearance of perflubron-filled lungs during partial liquid ventilation (PLV). MATERIALS AND METHODS: Supine chest radiographs (391 anteroposterior, 154 lateral radiographs) were obtained before and after daily perflubron instillation in 13 adults undergoing PLV who were receiving extracorporeal life support. Perflubron distribution, barotrauma, and inability to discern catheters were evaluated. RESULTS: Immediately after instillation of perflubron, opacification of more than two-thirds of the lungs was shown in 12 of 13 patients. A gravity-dependent distribution of perflubron was shown on 146 (95%) of 154 lateral radiographs. Perflubron gradually cleared until it filled less than one-third of the lungs 6.8 days later (range, 2-20 days). In the five survivors, minimal perflubron was visible up to 138 days. In five patients, perflubron increased the visibility of small pneumothoraces present before PLV. Location of intrathoracic catheters was obscured on 44 radiographs. CONCLUSION: Perflubron symmetrically opacifies the lungs in a gravity-dependent distribution during PLV and clears to minimal levels within 3 weeks.

Adult↗

Neonates with congenital diaphragmatic hernia: radiographic findings during partial liquid ventilation.

PURPOSE: To determine the serial radiographic appearance of the lungs of neonates who underwent partial liquid ventilation with perflubron because of congenital diaphragmatic hernia (CDH) or primary pulmonary hypertension. MATERIALS AND METHODS: Bedside anteroposterior (AP) and lateral chest radiographs (n = 235) were scored for percentage of lung opacification by perflubron during partial liquid ventilation (PLV) and extracorporeal membrane oxygenation (ECMO). Five neonates participated in the study; four had CDH, and one had primary pulmonary hypertension. RESULTS: The lungs were opacified nearly completely after each dose of perflubron. The degree of opacification was the same on 117 of 169 (69%) AP radiographs and within one point on another 40 (24%). A gravity-dependent distribution was shown on 58 of 66 (88%) lateral radiographs. A minimal amount of perflubron remained in the lungs after 5.2 days. A hypoplastic bronchus and ipsilateral lung were manifest in all four of the patients with CDH after the airway and lung were filled with radiopaque perflubron. CONCLUSION: Lungs filled with perflubron were opacified to a similar degree in a gravity-dependent distribution. Evaporation of perflubron from the lungs of neonates is relatively rapid. The size of the ipsilateral bronchus and lung may be estimated by comparison of radiographs taken before and after the lungs were filled with perflubron.

Extracorporeal Membrane Oxygenation↗