Oxygen dynamics during partial liquid ventilation in a sheep model of severe respiratory failure.

BACKGROUND: We evaluated the relationship of dose of perflubron and gas tidal volume to oxygen dynamics during partial liquid ventilation in the setting of respiratory failure. METHODS: Lung injury was induced in 16 sheep by using right atrial injection of 0.15 ml/kg oleic acid. Animals were ventilated with 15 ml/kg gas tidal volume and stabilized. Animals were then divided into three groups: (1) gas ventilation with a tidal volume of 15 ml/kg (control, GV, n = 5); (2) partial liquid ventilation at a gas tidal volume of 15 ml/kg with 10 ml/kg incremental pulmonary dosage of perflubron from 10 to 50 ml/kg (best fill, BF, n = 6); (3) administration of 35 ml/kg perflubron pulmonary dose with 5 ml/kg incremental increase in gas tidal volume from 10 to 30 ml/kg (best tidal volume, BTV, n = 5). RESULTS: Arterial oxygen saturation increased with increasing dose of perflubron and gas tidal volume (BF, p = 0.01; BTV, p = 0.001). A simultaneous trend toward a reduction in cardiac index was observed with increasing dose of perflubron (BF, p = 0.01). Maximal increase in mixed venous oxygen saturation was observed in the BF and BTV groups at a cumulative perflubron dose of 40 ml/kg and a gas tidal volume of 20 ml/kg, respectively. CONCLUSIONS: In this sheep lung injury model oxygenation improves with incremental increases in perflubron dose or gas tidal volume, and the mixed venous oxygen saturation appears to be optimal at a cumulative perflubron dose of 40 ml/kg and a gas tidal volume of 20 ml/kg.

Liquid ventilation provides uniform distribution of perfluorocarbon in the setting of respiratory failure.

BACKGROUND: We evaluated the effect of perfluorocarbon liquid ventilation (LV) on gas exchange and pulmonary function in the setting of respiratory failure and the distribution of the ventilating medium during LV when compared to gas ventilation (GV). METHODS: Ten sheep, 17.3 +/- 4.2 kg in weight, underwent oleic acid induction of lung injury followed by either GV (n = 5) or perfluorocarbon LV (n = 5). After 1 hour animals were killed, and chest computed tomographic (CT) imaging was performed. Average CT attenuation number was assessed as an indicator of the distribution of gas or perfluorocarbon in the dependent (posterior) and nondependent (anterior) zones of the lung (air = -1000; soft tissue = 0; perfluorocarbon = +2300 Hounsfield units [H]). RESULTS: Significant increases in PaO2 (LV = 298 +/- 76 mm Hg, GV = 43 +/- 18 mm Hg, p < 0.001), SvO2 (LV = 74% +/- 6%, GV = 32% +/- 18%, p < 0.01), and lung compliance (LV = 1.65 +/- 0.50 ml/cm H2O/kg, GV = 0.58 +/- 0.06 ml/cm H2O/kg, p < 0.01) were observed. Significant decreases in physiologic shunt (LV = 24% +/- 6%, GV = 62% +/- 14%, p < 0.01) were noted. CT attenuation data showed the presence of minimal gas ventilation in the dependent regions during GV although the nondependent regions remained well aerated (CT attention number during GV: ND = -654 +/- 160 H; D = -92 +/- 160 H, p < 0.0001). During LV, there was a fairly homogenous distribution of perfluorocarbon in the lungs (CT attenuation number during LV: D = 1071 +/- 330 Hounsfield units; ND = 1112 +/- 287 Hounsfield units; p = 0.240). Lung biopsy analysis in the LV animals was consistent with a reduction in intraalveolar hemorrhage, intraalveolar edema, and the inflammatory infiltrate. CONCLUSIONS: On the basis of the data, we conclude that in this lung injury model, (1) the distribution of the ventilating medium is uniform during LV when compared to GV, (2) LV improves gas exchange and pulmonary function, and (3) histologic evidence of lung injury is reduced after LV when compared to GV.

Distribution of pulmonary blood flow and total lung water during partial liquid ventilation in acute lung injury.

BACKGROUND: Gas exchange is improved during partial liquid ventilation (PLV) with perfluorocarbon in animal models of acute lung injury. The mechanisms are not fully defined. We hypothesize that redistribution of pulmonary blood flow (PBF) along with redistribution of, and decrease in, total lung water (TLW) during PLV may improve oxygenation. METHODS: We characterized PBF and TLW in anesthetized adult dogs by using positron emission tomography with H2(15)O. Measurements of gas exchange, PBF, and TLW were made before and after acute lung injury was induced with intravenous oleic acid. The same measurements were made during PLV (with 30 ml/kg perfluorocarbon) and compared with gas ventilated (GV) controls. RESULTS: Oxygenation was significantly improved during PLV. PBF redistributed from the dependent zone of the lung to the nondependent zones, thus potentially improving ventilation/perfusion relationships. However, a similar pattern of PBF redistribution was observed during GV such that there was no significant difference between groups. TLW redistributed in a similar pattern during PLV. By quantitative measurements, PLV ameliorated the continued accumulation of TLW compared with GV animals. CONCLUSIONS: We conclude that PBF and TLW redistribution and attenuation of increases in TLW may contribute to the improvement in gas exchange during PLV in the setting of acute lung injury.

Traumatic rupture of a cervical parathyroid adenoma.

BACKGROUND: Spontaneous rupture of a hyperplastic parathyroid gland or adenoma resulting in extracapsular hemorrhage is extremely rare. METHODS: We report a case of traumatic rupture of a cervical parathyroid gland adenoma. RESULTS: The patient had progressive stridor, neck swelling, and chest and back pain with evidence of ongoing blood loss resulting in airway compromise. Exploration of the neck and superior mediastinum revealed hypercellular parathyroid tissue consistent with adenoma or hyperplasia. CONCLUSIONS: Traumatic rupture of an enlarged parathyroid gland is a distinct and potentially lethal cause of unexplained cervical or mediastinal hemorrhage after blunt neck trauma. Failure to consider the diagnosis may result in delayed operative intervention with persistent hemorrhage resulting in airway compromise.

Partial liquid ventilation improves gas exchange and increases EELV in acute lung injury.

Gas exchange is improved during partial liquid ventilation with perfluorocarbon in animal models of acute lung injury. The specific mechanisms are unproved. We measured end-expiratory lung volume (EELV) by null-point body plethysmography in anesthetized sheep. Measurements of gas exchange and EELV were made before and after acute lung injury was induced with intravenous oleic acid to decrease EELV and worsen gas exchange. Measurements of gas exchange and EELV were again performed after partial liquid ventilation with 30 ml/kg of perfluorocarbon and compared with gas-ventilated controls. Oxygenation was significantly improved during partial liquid ventilation, and EELV (composite of gas and liquid) was significantly increased, compared with preliquid ventilation values and gas-ventilated controls. We conclude that partial liquid ventilation may directly recruit consolidated alveoli in the lung-injured sheep and that this may be one mechanism whereby gas exchange is improved.

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.

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.

Effect of independent changes in mixed-venous PCO2 or PO2 on cardiac output in anesthetized sheep.

To determine whether changes mixed-venous PCO2 or PO2 affect cardiac output independent of changes in arterial blood gases, we used extracorporeal gas exchange to increase mixed-venous PCO2 or decrease mixed-venous PO2 in adult sheep. Sheep were anesthetized, mechanically ventilated, and connected to a veno-venous extracorporeal circuit. The circuit included a gas exchanger which was used to increase mixed-venous PCO2 or decrease mixed-venous PO2; the native lungs were ventilated to maintain arterial PCO2 and PO2 at control levels. When mixed-venous PCO2 was increased by 32% above control levels for a period of 60 min, cardiac output increased significantly to 28% above control levels. Cervical vagotomy abolished this response. In contrast, decreasing mixed-venous PO2 by 29% did not increase cardiac output. These results demonstrate that increasing mixed-venous PCO2 can increase cardiac output independent of changes in arterial blood gases and that intact vagus nerves are necessary for this response to occur.

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.

Extracorporeal life support for neonatal respiratory failure. A 20-year experience.

OBJECTIVE: The authors reviewed their experience with extracorporeal life support (ECLS) in neonatal respiratory failure; they define changes in patient population, technique, and outcomes. SUMMARY BACKGROUND DATA: Extracorporeal life support has progressed from laboratory research to initial clinical trials in 1972. Following a decade of clinical research, ECLS is now standard treatment for neonatal respiratory failure refractory to conventional pulmonary support techniques. Our group has the longest and largest experience with this technique. METHODS: Between 1973 and 1993, 460 neonates with severe respiratory failure were treated using ECLS. The records of all patients were reviewed. RESULTS: Overall survival was 87%. Primary diagnoses were meconium aspiration syndrome (MAS; 169 cases [96% survival]), respiratory distress syndrome/hyaline membrane disease (91 cases [88% survival]), persistent pulmonary hypertension of the newborn (37 cases [92%]), pneumonia/sepsis (75 cases [84% survival]), congenital diaphragmatic hernia (CDH; 67 cases [67% survival]), and other diagnoses (21 cases [71% survival]). Common mechanical complications included clots in the circuit (136; 85% survival); air in the circuit (67; 82% survival); cannula problems (65; 83% survival) and oxygenator failure (34; 65% survival). Patient-related complications included intracranial infarct or bleed (54 cases; 61% survival), major bleeding (48 cases; 81% survival), seizures (88 cases; 76% survival), metabolic abnormalities (158 cases; 71% survival) and infection (21 cases; 48% survival). Since 1989, treatment groups have been expanded to include premature infants (13 cases; 62% survival), infants with grade I intracranial hemorrhage (28 cases; 54% survival) and "non-honeymoon" CDH patients (15 cases; 27% survival). Since 1990, single-catheter venovenous access has been used in 131 patients (97% survival) and currently is the preferred mode of access. Follow-up ranges from 1 to 19 years; 80% of patients are growing and developing normally. CONCLUSIONS: Extracorporeal life support has become standard treatment for severe neonatal respiratory failure in our center (460 cases; 87% survival), and worldwide (8913 cases; 81% survival). The availability of ECLS makes the evaluation of other innovative methods of treatment, such as late elective repair of diaphragmatic hernia and new pulmonary vasodilators, possible. The application of ECLS is now being extended to premature and low-birth weight infants as well as older children and adults.

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.