Partial Liquid Ventilation Research Articles

Mechanisms of recruitment in oleic acid-injured lungs.

Lung recruitment strategies, such as the application of positive end-expiratory pressure (PEEP), are thought to protect the lungs from ventilator-associated injury by reducing the shear stress associated with the repeated opening of collapsed peripheral units. Using the parenchymal marker technique, we measured regional lung deformations in 13 oleic acid (OA)-injured dogs during mechanical ventilation in different postures. Whereas OA injury caused a marked decrease in the oscillation amplitude of dependent lung regions, even the most dependent regions maintained normal end-expiratory dimensions. This is because dependent lung is flooded as opposed to collapsed. PEEP restored oscillation amplitudes only at pressures that raised regional volumes above preinjury levels. Because the amount of PEEP necessary to promote dependent lung recruitment increased the end-expiratory dimensions of all lung regions (nondependent AND dependent ones) compared with their preinjury baseline, the "price" for recruitment is a universal increase in parenchymal stress. We conclude that the mechanics of the OA-injured lung might be more appropriately viewed as a partial liquid ventilation problem and not a shear stress and airway collapse problem and that the mechanisms of PEEP-related lung protection might have to be rethought.

Spontaneous breathing during partial liquid ventilation in animals with meconium aspiration.

Partial liquid ventilation (PLV) has been shown to improve gas exchange in paralyzed animals and humans with lung disease. The present study tests the hypothesis that PLV improves gas exchange in spontaneously breathing animals with meconium aspiration supported by proportional assist ventilation. Twenty-five adult anesthetized intubated rabbits with experimental meconium aspiration were randomized to gas ventilation (GV) or PLV while being supported by proportional assist ventilation. Minute ventilation, tidal volume, respiratory rate, mean airway pressure, heart rate, and mean arterial and pulmonary arterial pressure were recorded continuously. Every 30 min, arterial blood gases were obtained, and lung compliance, airway resistance, work of breathing, and cardiac output were measured. Animals were sacrificed after 5 h to obtain lung histology. More PLV animals survived until the end of the study period. PaO(2) (14.5 +/- 4.5 versus 25.6 +/- 6.7 kPa; p < 0.01; GV versus PLV) and lung compliance (4.3 +/- 0.4 versus 6.1 +/- 1.2 mL.kPa(-1).kg(-1); p < 0.001) were improved during PLV, resulting in a lower work of breathing (5.3 +/- 2.8 versus 3.5 +/- 1.5 mL.kPa.kg(-1); p < 0.05) and less need for ventilatory support. Minute ventilation and respiratory rate were higher during GV versus PLV, resulting in a slightly lower PaCO(2) (3.9 +/- 0.5 versus 4.5 +/- 0.7 kPa; p < 0.05). Histologic evaluation showed more atelectasis, inflammatory changes, and hemorrhage in GV animals. Other parameters measured were similar. We conclude that PLV improves oxygenation, lung compliance, and survival and results in less lung injury in spontaneously breathing animals with meconium aspiration when supported by proportional assist ventilation.

Effect of Increasing Perfluorocarbon Dose on ˙Va/˙Q Distribution during Partial Liquid Ventilation in Acute Lung Injury

Although gas exchange during partial liquid ventilation (PLV) depends on perfluorocarbon liquid, the effect of perfluorocarbon dose on the ventilation-perfusion (VA/Q) distribution is not known. This study investigated how VA/Q distribution of an acutely injured lung is affected during PLV at increasing perfluorocarbon dose. In eight rabbits (3.2 +/- 0.1 kg), acute lung injury (ALI) was created by repeated saline lavage (arterial oxygen partial pressure/fraction of inspired oxygen, 37 +/- 11 mm Hg). Three different doses of perfluorodecalin (9 ml/kg = low dose; 13.5 ml/kg = medium dose; 18 ml/kg = functional residual capacity [FRC] dose) were applied in random order during PLV. VA/Q distribution at different doses was evaluated by multiple inert gas elimination technique. Inert gas shunt (63 +/- 21% at ALI) decreased with increasing perfluorocarbon dose (43 +/- 21% at low dose, 29 +/- 10% at medium dose, 11 +/- 9% at FRC dose; P = 0.022). Compared with ALI (0%), the proportion of low VA/Q units was higher at all tested doses (19 +/- 10, 25 +/- 12, and 34 +/- 18%, respectively; all P < 0.05). Compared with ALI (27 +/- 14%), the proportion of normal VA/Q units was not increased at low or medium doses but was increased only at the FRC dose (45 +/- 13%; P = 0.027). With increasing perfluorocarbon dose during PLV, shunt was reduced from a small dose. The majority shunt units were converted to units showing low VA/Q ratios rather than normal VA/Q ratios. The presence of considerable amount of low VA/Q units across the varying doses of perfluorocarbon suggested that additional measures are necessary during PLV to augment its effect on gas exchange.

Role of ventilation strategy on perfluorochemical evaporation from the lungs.

To study the effect of ventilation strategy on perfluorochemical (PFC) elimination profile (evaporative loss profile; E(L)), 6 ml/kg of perflubron were instilled into anesthetized normal rabbits. The strategy was to maintain minute ventilation (VE, in ml/min) in three groups: VE(L) (low-range VE, 208 +/- 2), VE(M) (midrange VE, 250 +/- 9), and VE(H) (high-range VE, 293 +/- 1) over 4 h. In three other groups, respiratory rate (RR, breaths/min) was controlled at 20, 30, or 50 with a constant VE and adjusted tidal volume. PFC content in the expired gas was measured, and E(L) was calculated. There was a significant VE- and time-dependent effect on E(L.) Initially, percent PFC saturation and loss rate decreased in the VE(H) > VE(M) > VE(L) groups, but by 3 h the lower percent PFC saturation resulted in a loss rate such that VE(H) < VE(M) < VE(L) at 4 h. For the groups at constant VE, there was a significant time effect on E(L) but no RR effect. In conclusion, E(L) profile is dependent on VE with little effect of the RR-tidal volume combination. Thus measurement of E(L) and VE should be considered for the replacement dosing schemes during partial liquid ventilation.

Efficacy of Specific Perfluorocarbons for Use in Partial Liquid Ventilation

Departments of Physiology and Pediatrics, Temple University School of Medicine, Temple University Hospital, Temple University Children’s Medical Center, Philadelphia, PA

High-frequency oscillatory ventilation of the perfluorocarbon-filled lung: dose-response relationships in an animal model of acute lung injury.

To examine dose-response relationships regarding the efficiency of gas exchange and hemodynamic function during high-frequency oscillation and partial liquid ventilation (HFO-PLV) of the perfluorocarbon (PFC)-treated lung in a model of acute lung injury. An animal research laboratory in a university medical center. A prospective, randomized study comparing animals receiving varying doses (0, 5, 15, and 20 mL/kg) of perflubron during high-frequency oscillatory ventilation (HFOV) with mean airway pressure (Paw) optimized to achieve a minimal percutaneous oxygen saturation (Spo2). Nineteen healthy swine (mean weight 28.9 kg) with saline lavage-induced acute lung injury. Animals were treated with repetitive saline lavage to achieve a uniform degree of acute lung injury (Spo2 < or =90% on an Fio2 of 1.0). After lung injury, subjects were converted to HFOV, and lung volume was optimized. HFO-PLV was initiated by instillation of perflubron at a rate of 0.5 mL.kg-1.min-1 to achieve total doses of 5, 15, and 20 mL/kg. After PFC dosing, the only experimental manipulation consisted of adjustment of Paw to achieve an Spo2 of 90% +/- 2% with Fio2 of 0.6. Gas exchange, hemodynamic variables, and pulmonary mechanics data were collected over a 1-hr period. Five control animals were not dosed with perflubron and remained on HFOV for the 1-hr period of data collection. After lung volume recruitment with HFOV, the initiation of HFO-PLV was best tolerated with the two lower doses in our protocol. There were essentially no changes in Paco2 or pH between groups over the dosing interval. After dosing, analysis of variance demonstrated a PFC dose-dependent effect for oxygenation index (p =.01) only; the lowest oxygenation index was found in the 15 mL/kg group (p =.01). In the 15 mL/kg group, the Paw decreased steadily from 20.6 +/- 3.4 cm H2O at the end of dosing to 18.0 +/- 4.9 cm H2O at 60 mins. The Pao2 increased from 113 +/- 51 torr (15.06 +/- 6.79 kPa) to 134 +/- 49 torr (17.86 +/- 6.53 kPa) during this period and was associated with a decreasing oxygenation index (from 11.4 +/- 2.0 to 9.3 +/- 1.5). The cardiac index and pulmonary vascular resistance did not change significantly during the dosing period and were relatively stable after the completion of dosing. The combination of HFOV and perflubron administration was well tolerated hemodynamically and was not associated with deterioration of gas exchange during dosing. Our data suggest that the optimal dose of perflubron to achieve the lowest oxygenation index during HFO-PLV is between 5 and 15 mL/kg. The combination of HFOV and perflubron administration is a novel strategy in the treatment of acute lung injury that shows some promise and merits additional investigation. We hope in future studies to address the histopathologic effects of varying perflubron doses during HFOV in a long-term study of the lung-protective effects of HFO-PLV.

Effects of combined high-dose partial liquid ventilation and almitrine on pulmonary gas exchange and hemodynamics in an animal model of acute lung injury.

To determine possible additive effects of combined high-dose partial liquid ventilation (PLV) and almitrine bismesylate (ALM) on pulmonary gas exchange and hemodynamics in an animal model of acute lung injury (ALI). Prospective, controlled animal study in an animal research facility of a university hospital. ALI was induced in 12 anesthetized and mechanically ventilated pigs by repeated wash-out of surfactant. After initiation of PLV with 30 ml/kg perfluorocarbon the animals were randomly assigned to receive either accumulating doses of ALM (0.5, 1.0, 2.0, 4.0, 8.0, and 16.0 micrograms/kg per minute) for 30 min each (n = 6) or the solvent malic acid (n = 6). Pulmonary gas exchange and hemodynamics were measured at the end of each infusion period. Compared to ALI, PLV alone significantly increased arterial oxygen partial pressure (PaO2) and decreased venous admixture (QVA/QT) and mean pulmonary artery pressure (MPAP). Administration of ALM did not result in a further improvement in PaO2, QVA/QT or MPAP compared to PLV alone but decreased PaO2 and increased QVA/QT and MPAP when 16 micrograms/kg per min ALM was compared to PLV alone. In an animal model of surfactant depletion induced ALI the combined treatment of PLV and ALM induced no significant improvement in pulmonary gas exchange or hemodynamics when compared to PLV alone. Moreover, high-dose ALM significantly impaired gas exchange and pulmonary hemodynamics.

Effects of perfluorochemical distribution and elimination dynamics on cardiopulmonary function.

Based on a physicochemical property profile, we tested the hypothesis that different perfluorochemical (PFC) liquids may have distinct effects on intrapulmonary PFC distribution, lung function, and PFC elimination kinetics during partial liquid ventilation (PLV). Young rabbits were studied in five groups [healthy, PLV with perflubron (PFB) or with perfluorodecalin (DEC); saline lavage injury and conventional mechanical ventilation (CMV); saline lavage injury PLV with PFB or with DEC]. Arterial blood chemistry, respiratory compliance (Cr), quantitative computed tomography of PFC distribution, and PFC loss rate were assessed for 4 h. Initial distribution of PFB was more homogenous than that of DEC; over time, PFB redistributed to dependent regions whereas DEC distribution was relatively constant. PFC loss rate decreased over time in all groups, was higher with DEC than PFB, and was lower with injury. In healthy animals, arterial PO(2) (Pa(O(2))) and Cr decreased with either PFC; the decrease was greater and sustained with DEC. Lavaged animals treated with either PFC demonstrated increased Pa(O(2)), which was sustained with PFB but deteriorated with DEC. Lavaged animals treated with PFB demonstrated increased Cr, higher Pa(O(2)), and lower arterial PCO(2) than with CMV or PLV with DEC. The results indicate that 1) initial distribution and subsequent intrapulmonary redistribution of PFC are related to PFC properties; 2) PFC distribution influences PFC elimination, gas exchange, and Cr; and 3) PFC elimination, gas exchange, and Cr are influenced by PFC properties and lung condition.

Acute lung injury: outcomes and new therapies

Mortality rates in ARDS are improving, with several recent studies reporting mortality in the order of 20-40% rather than the early descriptions of this disease in which a mortality of 40-60% or higher was frequently cited. The ability to accurately predict outcomes plays an important role in the assessment of the impact of new therapies. Traditionally clinicians have relied on simple respiratory indices to assess mortality risk; however, the predictive ability of such indices, particularly early in the course of the disease, is somewhat limited. Adult data suggest that improved prediction not only of the outcome of established ARDS but also of the development of ARDS in at-risk patients may be obtained by measuring the concentrations of inflammatory mediators and/or surfactant-associated proteins in plasma or bronchoalveolar lavage samples. A bewildering array of therapies for ARDS is available; in many cases the benefits are uncertain. Treatments of proven value in adults include using PEEP beyond the lower inflection point of the pressure-volume curve and limiting tidal volumes to 6 ml/kg. Nitric oxide appears to offer no benefit to outcomes, although it does improve oxygenation in some patients. Surfactant is still undergoing assessment in randomised controlled trials; however, the use of aerosolised surfactant has been recently shown to be ineffective in adult patients with ARDS. Perfluorocarbon-assisted gas exchange (PAGE) or partial liquid ventilation is similarly still being assessed in randomised controlled trials in adults.

The Pulmonary and Systemic Distribution and Elimination of Perflubron From Adult Patients Treated With Partial Liquid Ventilation

To assess the pulmonary and systemic distribution and elimination of perflubron (C(8)F(17)Br(1); LiquiVent; Alliance Pharmaceutical; San Diego, CA) during and following the period of partial liquid ventilation. Prospective phase I and II clinical trial. Adult surgical ICU. Eighteen adult patients (mean +/- SEM age, 37.9 +/- 3.4 years) with severe respiratory failure, some of whom required extracorporeal life support (72%), and who were managed with partial liquid ventilation with perflubron. Perflubron was administered into the trachea, and gas ventilation of the perfluorocarbon-filled lung (partial liquid ventilation) was then performed. Additional doses were administered daily for from 1 to 7 days, with a median cumulative dose of 31 mL/kg (range, 3 to 60 mL/kg). Patient blood samples were evaluated by gas chromatography for serum perflubron levels. Sequential lateral and anteroposterior radiographs were assessed, using a 5-point rating scale, for the degree of perflubron fill following the final dose. Samples of expired gas were collected, and the rate of loss of perflubron in the expired gas was measured by gas chromatography. Mean serum perflubron levels increased to 0.16 +/- 0.05 mg/dL at 24 h following administration of the initial dose. A mean maximum level of 0.26 +/- 0.05 mg/dL of perflubron was present in the serum 24 h following the administration of the last dose. This level slowly trended downward to 0.18 +/- 0.06 mg/dL over the ensuing 7 days (p = 0.281). Perflubron elimination via expired gas occurred at a mean rate of 9.4 +/- 3.0 mL/h at 1 h, and 1.0 +/- 0.4 mL/h at 48 h after the last dose (p = 0.012). By radiologic evaluation, perflubron was eliminated from the lungs progressively from 4.2 +/- 0.2 at the time of administration of the last dose, to 2.8 +/- 0.3 at 4 days later (p < 0.001). Perflubron tended to distribute and remain for longer periods in the dependent regions of the lung when compared to the nondependent regions (96-h perflubron fill score: posterior, 3.8 +/- 0.5; anterior, 1.9 +/- 0.4; p = 0.004). Perflubron is eliminated at a maximum rate of 9.4 +/- 3.0 mL/h by evaporative loss from the airways and is retained in greater amounts in the dependent lung regions when compared to the nondependent lung regions. There is a low but measurable maximum blood concentration of 0.26 +/- 0.05 mg/dL in patients after perflubron administration, which did not decrease significantly after cessation of partial liquid ventilation.

Liquid ventilation.

Partial liquid ventilation (PLV) developed considerably in the clinical and experimental fields during the past few years. In addition to improved oxygenation and lung mechanics by perfluorocarbon (PFC) administration, recent animal studies have tried to optimize PLV by evaluating the most appropriate ventilatory mode to use during PLV and by adjusting the best level of positive end-expiratory pressure (PEEP). Other pathophysiological aspects of acute lung injury that may be positively affected by liquid ventilation have been studied, including regional blood flow redistribution, reduction in ventilator-induced lung injury, and antiinflammatory properties of PFC. Although the precise dosing of PFC is debated, evidence from several experimental studies supports the use of smaller doses of PFC because larger doses increase the occurrence of baro- and volutrauma. In the clinical field, after promising data from preliminary studies, an international randomized controlled trial is on the verge of completion.

Pulmonary administration of prostacyclin (PGI2) during partial liquid ventilation in an oleic acid-induced lung injury: inhalation of aerosol or intratracheal instillation?

The purpose of this study was to investigate the effects of aerosolized prostacyclin (A-PGI2) and intratracheally instilled prostacyclin (I-PGI2) during partial liquid ventilation (PLV) on gas exchange and pulmonary circulation in rabbits with acute respiratory distress. Prospective control study. A research laboratory at a university medical centre. Sixty-nine Japanese white rabbits. Lung injury was induced by oleic acid and the animals were divided into five groups of ten each: a mechanical gas ventilation (GV) group, an A-PGI2 group, a PLV group, an A-PGI2+PLV group and an I-PGI2+PLV group. PLV, A-PGI2+PLV and I-PGI2+PLV groups received 15 ml/ kg perflubron intratracheally while receiving mechanical GV. A-PGI2 and A-PGI2+PLV groups received aerosolized PGI2 (50 ng/kg/min) in combination with GV or PLV, respectively. The I-PGI2+PLV group was instilled 50 ng/kg/min PGI2 intratracheally in combination with PLV. After lung injury, all animals developed hypoxia, hypercarbia and pulmonary hypertension. The improvement of partial pressure of arterial oxygen (PaO2) in the A-PGI2 and PLV groups was transient, whereas the A-PGI2+PLV and I-PGI2+PLV groups showed consistent improvement throughout the experiment. The PaO2 values of the I-PGI2+PLV group were significantly higher than those of the other groups 120 min after treatment. The mean pulmonary artery pressure (PAP) significantly decreased after treatment in the A-PGI2, APGI2+PLV and I-PGI2+PLV groups. The results suggest that both aerosolized and intratracheally instilled PGI2 improve oxygenation and reduce PAP during PLV in oleic acid lung injury.

Cerebral blood flow during partial liquid ventilation in surfactant-deficient lungs under varying ventilation strategies.

OBJECTIVE: To test the hypothesis that cerebral and other regional organ blood flow would be maintained during partial liquid ventilation (PLV) in an animal model of acute lung injury during different ventilation strategies. DESIGN: A prospective, randomized study. SETTING: Animal research facility. SUBJECTS: Sixteen piglets, 2 to 4 wks of age. INTERVENTIONS: Severe lung injury was induced in infant piglets by repeated saline lavage and high tidal volume ventilation. Animals were then randomized to either conventional volume-controlled ventilation or PLV. MEASUREMENTS AND MAIN RESULTS: Organ blood flow was determined in both groups using radiolabeled microspheres under four conditions: high mean airway pressure, Paw; high Paco(2), high Paw; normal Paco(2); low Paw, high Paco(2); low Paw, normal Paco(2). There were no differences in cerebral blood flow during conventional ventilation and PLV, regardless of ventilation strategy. CONCLUSIONS: These results suggest in an acute lung injury model, PLV does not affect cerebral blood flow or other regional organ blood flow over a range of airway pressures.

The use of intratracheal pulmonary ventilation and partial liquid ventilation in newborn piglets with meconium aspiration syndrome.

OBJECTIVE: To determine whether intratracheal pulmonary ventilation (ITPV) combined with partial liquid ventilation (PLV) improves oxygenation and ventilation at lower mean airway and peak inspiratory pressures when compared with conventional mechanical ventilation in a piglet model of meconium aspiration syndrome. DESIGN: Prospective, randomized, interventional study. SETTING: Animal Research Laboratory at the Children's National Medical Center, Washington, DC. SUBJECTS: Twenty newborn piglets, 1 to 2 wks of age, 1.8-2.8 kg in weight. INTERVENTION: The animals were anesthetized, paralyzed, and intubated with a 4.0 mm (internal diameter) endotracheal tube via a tracheostomy and were ventilated. Catheters were placed in the femoral artery and vein. Seven milliliters per kilogram of 20% human meconium was insufflated into the lungs over 30 mins. Dynamic pulmonary compliance was measured before and after instillation of meconium. Animals were ventilated to maintain arterial blood gases in a normal range, that is, pH = 7.35-7.45, Paco(2) = 40-45 torr (5.3-6.0 kPa), and Pao(2) = 70-90 torr (9.3-12.0 kPa). Ventilator settings were increased as needed to a maximum setting of Fio(2) = 1.0, peak inspiratory pressure (PIP) = 40 cm H(2)O, positive end-expiratory pressure = 5 cm H(2)O, and intermittent mandatory ventilation = 60 bpm. After a period of stabilization, 30 mL/kg of perflubron (Liquivent; Alliance Pharmaceutical Corp., San Diego, CA) was given intratracheally over 30 mins and the animals were randomized to either ITPV or control group. Measurements and RESULTS: Arterial blood gases were taken every 30 mins, and ventilatory settings were adjusted to achieve the targeted blood gas parameters. The animals' temperature, arterial blood pressure, heart rate, and oxygen saturation were monitored continuously. There was a significant decrease in the dynamic pulmonary compliance measurements in both groups immediately after meconium instillation. Compliance measurements after meconium instillation were similar in both groups (0.67 +/- 0.23 mL/cm H(2)O/kg ITPV; 0.88 +/- 0.46 mL/cm H(2)O/kg conventional, p =.17), indicating a similar degree of injury before the administration of perflubron. PIP and mean airway pressures were not significantly different at baseline; however, there was significant difference in PIP at 0, 2, and 4 hrs after administration of perflubron (p <.05). The maximum PIP and mean airway pressure were seen in both groups after meconium instillation before perflubron administration, with a mean PIP of 29.0 +/- 4.6 cm H(2)O in ITPV and 28.8 +/- 2.1 cm H(2)O in control. Mean airway pressure was significantly different between the two groups at 0, 1, 2, 3, and 4 hrs after perflubron administration. Lung pathology showed a uniform distribution of meconium in animals of both groups. The alveolar spaces were relatively clear of meconium and appeared to be well preserved. CONCLUSION: The results of this study indicate that ITPV combined with PLV allows for effective ventilation and oxygenation in piglets with meconium aspiration syndrome at lower mean airway pressure and PIP compared with conventional ventilation combined with PLV.

Partial liquid ventilation - effects of intrapulmonary perfluorocarbon volume and respiratory settings on bronchial elimination

Partial liquid ventilation - effects of intrapulmonary perfluorocarbon volume and respiratory settings on bronchial elimination

Partial pressure of oxygen and partial pressure of carbon dioxide of perfluorocarbon liquid during partial liquid ventilation: their regional difference and their dependence on tidal volume and positive end-expiratory pressure level.

To investigate the regional partial pressure of oxygen (PO2) and partial pressure of carbon dioxide (PCO2) of the perfluorocarbon liquid (PpfcO2, PpfcCO2) during partial liquid ventilation (PLV). Prospective, controlled study. A research laboratory at a university medical center. Thirteen Japanese white rabbits. After the tracheostomy, PLV was started with perflubron (15 ml/kg) following saline lung lavage. Fractional inspired oxygen (FIO2) was 1.0, respiratory rate was 30 bpm and tidal volume (VT) was 30 ml. Two epidural catheters (18 gauge) were inserted from the rubber diaphragm interposed in the respiratory circuit to sample perflubron. One catheter was inserted into the left lower lobe bronchus and placed at 5-6 cm distal from the carina (DISTAL). The other one was inserted at the tip of the endotracheal tube (PROXIMAL). Then the effect of the larger VT (50 ml) or positive end-expiratory pressure (PEEP; 10 cmH2O) to the gas tension in perflubron was examined. (1) In the lower VT (30 ml) with 0 cmH20 PEEP, DISTAL PpfcO2 was significantly lower than PROXIMAL PpfcO2 (265 72 vs 386 +/- 47 mmHg, p < 0.0001), and DISTAL PpfcCO2 was significantly higher than PROXIMAL PpfcCO2 (51.1 +/- 14.4 vs 42.4 +/- 11.8 mmHg (p = 0.0007)), (2) the higher VT setting increased PpfcO2 (p = 0.0001) and decreased PpfcCO2 (p < 0.0001), although the gas tension gradient was significant, (3) 10 cmH2O PEEP increased PpfcO2 (p = 0.0004) and decreased PpfcCO2 (p = 0.0089) in the DISTAL sample. There was a difference in gas tension in perflubron between the central airway and the peripheral dependent lung region, and gas tension in perflubron was affected by the VT and the PEEP level.

Acute respiratory distress syndrome: pharmacological treatment options in development.

The acute respiratory distress syndrome (ARDS) is a clinical syndrome with primarily supportive management options. Despite extensive basic and clinical investigations, multiple pharmacological and nonpharmacological modalities have been unsuccessful in decreasing mortality. Nonetheless, these efforts have substantially heightened our understanding of ARDS pathophysiology. Investigators continue to create new and more complex therapeutic strategies that may have significant clinical impact. Several pharmacological agents for ARDS are in development and have shown either great promise or are at most, under phase II evaluation. The order in which therapeutic options are presented in this review highlights therapeutic options other than the anti-inflammatory approach. In addition to the anti-inflammatory category, vasodilators, surfactant therapy, immunonutrition and partial liquid ventilation are all being evaluated. Within the anti-inflammatory category. new mechanistic approaches include the 'anti-inflammatory nature' of interleukin-10, the inhibitory aspects of lysophosphatidic acid on endothelial cell permeability, and the use of recombinant human anti-coagulant proteins (activated protein C and tissue factor pathway inhibitor) to reduce the inflammatory cycle that contributes to microvascular thrombi. Previous work with surfactant in ARDS had its limitations, however, these trials were of sufficient success to spawn 2 new synthetic compounds. These new synthetic surfactants incorporate mixtures of phosphatidylcholine and phosphatidylglycerol (the key phospholipids within endogenous surfactant) and either recombinant surfactant protein C or an analogue of surfactant protein B. Recently, the ARDS Network's low tidal volume study has broken the cycle of decades of negative ARDS trials and demonstrated an improvement in mortality. Through better mechanistic approach and study design, investigator compliance with exclusion criteria, and better understanding of the complexities of patient management, the next pharmacological ARDS trials will hopefully be successful and lead to further reductions in patient mortality.

Partial liquid ventilation (PLV) vs conventional mechanical ventilation (CMV) with high PEEP and moderate tidal volume (Vt) in acute lung injury in piglets

Partial liquid ventilation (PLV) vs conventional mechanical ventilation (CMV) with high PEEP and moderate tidal volume (Vt) in acute lung injury in piglets

Changes in pulmonary blood flow during gaseous and partial liquid ventilation in experimental acute lung injury.

It has been proposed that partial liquid ventilation (PLV) causes a compression of the pulmonary vasculature by the dense perfluorocarbons and a subsequent redistribution of pulmonary blood flow from dorsal to better-ventilated middle and ventral lung regions, thereby improving arterial oxygenation in situations of acute lung injury. After induction of acute lung injury by repeated lung lavage with saline, 20 pigs were randomly assigned to partial liquid ventilation with two sequential doses of 15 ml/kg perfluorocarbon (PLV group, n = 10) or to continued gaseous ventilation (GV group, n = 10). Single-photon emission computed tomography was used to study regional pulmonary blood flow. Gas exchange, hemodynamics, and pulmonary blood flow were determined in both groups before and after the induction of acute lung injury and at corresponding time points 1 and 2 h after each instillation of perfluorocarbon in the PLV group. During partial liquid ventilation, there were no changes in pulmonary blood flow distribution when compared with values obtained after induction of acute lung injury in the PLV group or to the animals submitted to gaseous ventilation. Arterial oxygenation improved significantly in the PLV group after instillation of the second dose of perfluorocarbon. In the surfactant washout animal model of acute lung injury, redistribution of pulmonary blood flow does not seem to be a major factor for the observed increase of arterial oxygen tension during partial liquid ventilation.

Intrapulmonary Instillation of Perfluorocarbon in Experimental Acute Lung Injury

Intrapulmonary Instillation of Perfluorocarbon in Experimental Acute Lung Injury Max et al.(page 1437) Max et al. used an experimental model to induce acute lung injury in 20 pigs to study the effects of partial liquid ventilation (PLV) with perfluorocarbon on the distribution of pulmonary blood flow. Gas exchange and hemodynamic and pulmonary blood flow were assessed in all animals before and after induction of acute lung injury with use of a saline lavage. Then, the animals were assigned randomly to one of two groups: a group of 10 who were submitted to PLV by administering 15 ml/kg of perfluorocarbon through the endotracheal tube at 1 and 2 h after injury, and a group of 10 in whom controlled mechanical ventilation was continued with no changes in respirator settings. Measurements were performed 1 and 2 h after injury in the latter group, as well. At specific points in the study protocol, researchers also injected radioactive-labeled macroaggregates of human serum albumin to enable measurement of pulmonary blood flow using single photon emission computed tomography. With use of specialized software, they generated 12 lung segments (four transaxial slices consisting of ventral, middle and dorsal segments) for each animal to be examined for distribution of blood flow. Arterial carbon dioxide tension increased from 32 ± 4 to 57 ± 13 mmHg after acute lung injury was induced, but, after the initial changes, arterial carbon dioxide tension and pH remained constant in groups 1 and 2. When all 20 pigs, either in gaseous ventilation or in PLV groups, were analyzed together, acute lung injury was shown to cause an increase of pulmonary blood flow to the ventral segment of slice 2 and to the middle segments of slices 1 and 2. Blood flow increased in the combined middle segments but decreased in the dorsal ones. Neither PLV nor gaseous ventilation resulted in a redistribution of blood flow to any of the 12 segments when values at 1 and 2 h after injury were compared with those measured immediately after acute lung injury. In a third group of five pigs, the attenuation control group, a similar number of lung lavages (11 ± 2) were needed to induce acute lung injury with an arterial oxygen tension of 52 ± 14 mmHg. Arterial oxygenation improved significantly after PLV with perfluororcarbon, which may be caused by an improvement in ventilation/perfusion ratios.