Partial liquid ventilation improves lung function in ventilation-induced lung injury.

Disturbances in lung function and lung mechanics are present after ventilation with high peak inspiratory pressures (PIP) and low levels of positive end-expiratory pressure (PEEP). Therefore, the authors investigated whether partial liquid ventilation can re-establish lung function after ventilation-induced lung injury. Adult rats were exposed to high PIP without PEEP for 20 min. Thereafter, the animals were randomly divided into five groups. The first group was killed immediately after randomization and used as an untreated control. The second group received only sham treatment and ventilation, and three groups received treatment with perfluorocarbon (10 mL x kg(-1), 20 mL x kg(-1), and 20 ml x kg(-1) plus an additional 5 mL x kg(-1) after 1 h). The four groups were maintained on mechanical ventilation for a further 2-h observation period. Blood gases, lung mechanics, total protein concentration, minimal surface tension, and small/large surfactant aggregates ratio were determined. The results show that in ventilation-induced lung injury, partial liquid ventilation with different amounts of perflubron improves gas exchange and pulmonary function, when compared to a group of animals treated with standard respiratory care. These effects have been observed despite the presence of a high intra-alveolar protein concentration, especially in those groups treated with 10 and 20 mL of perflubron. The data suggest that replacement of perfluorocarbon, lost over time, is crucial to maintain the constant effects of partial liquid ventilation.

Treatment of ventilation-induced lung injury with exogenous surfactant.

OBJECTIVE: It has been demonstrated that pulmonary surfactant plays a role in the pathophysiology of ventilation-induced lung injury (VILI). Therefore, we investigated whether exogenous surfactant might restore lung function and lung mechanics in an established model of VILI. DESIGN: Prospective, randomized, animal study. SETTING: Experimental laboratory of a university. SUBJECTS: Twenty-four adult male Sprague-Dawley rats. INTERVENTIONS: First, a group of six animals were killed immediately after induction of anesthesia and used as healthy controls. Then, in 18 rats, VILI was induced by increasing peak inspiratory pressure (PIP) to 45 cmH2O without positive end-expiratory pressure (PEEP) for 20 min. Thereafter, animals were randomly divided into three groups of six animals each: one group was killed immediately after VILI and served as VILI-control. In the other two groups, ventilator settings were changed to a PIP of 30 cmH2O and a PEEP of 10 cmH2O, and a respiratory rate of 40 bpm. One group received a bolus of surfactant and the other group received no treatment. MEASUREMENTS AND RESULTS: Blood gas tension and arterial blood pressures were recorded every 30 min for 2 h. After the study period, a pressure-volume curve was recorded. Then, a broncho-alveolar lavage (BAL) was performed to determine protein content, minimal surface tension, and surfactant composition in the BAL fluid. Oxygenation, lung mechanics, surfactant function and composition were significantly improved in the surfactant-treated group compared to the ventilated and non-ventilated control groups. CONCLUSION: We conclude that exogenous surfactant can be used to treat VILI.

Treatment and prevention of acute respiratory failure: physiological basis.

Acute respiratory failure is caused by many factors and remains one of the most common reasons for admission to the intensive care unit (ICU). In all cases of acute respiratory failure, there is a shortage of surfactant at the alveolar level. This deficit of surfactant leads to an increase in alveolar surface tension that increases the retraction forces of the lung, leading to end-expiratory alveolar collapse, finally resulting in respiratory dysfunction, which includes hypoxemia, low lung compliance, increase of intrapulmonary shunts, low functional residual capacity, atelectasis, and pulmonary edema. The goal of the treatment and prevention of acute respiratory failure is therefore based on the following three main items: re-opening the collapsed alveolar units; preserving the active surfactant component in the remaining functional alveolar units, and preventing end-expiratory collapse. The following strategies can be used to prevent and/or treat acute respiratory failure: counterbalancing the retraction forces of the lung by applying sufficiently high external pressures; and/or decreasing the surface tension at the air-liquid interface by means of exogenous surfactant, and/or eliminating the air-liquid interface by filling the lung with perfluorocarbons. By applying these therapeutic strategies in routine clinical practice, we should achieve a reduction in the mortality rate of patients suffering from acute respiratory failure.

Mechanical ventilation with high positive end-expiratory pressure and small driving pressure amplitude is as effective as high-frequency oscillatory ventilation to preserve the function of exogenous surfactant in lung-lavaged rats.

OBJECTIVE: To demonstrate that under well-defined conditions, pressure-controlled ventilators (PCV) allow settings that are as good as high-frequency oscillatory ventilators (HFOV) at preserving the function of exogenous surfactant in lung-lavaged rats. DESIGN: Experimental, comparative study. SETTING: Research laboratory of a large university. SUBJECTS: Sixteen adult male Sprague-Dawley rats (280-310 g). INTERVENTIONS: Lung injury was induced by repeated lavage. After last lavage, all animals received exogenous surfactant and were then randomly assigned to two groups (n = 8 per group). The first group received PCV with small pressure amplitudes and high positive end-expiratory pressure. The second group received HFOV. In both groups, an opening maneuver was performed by increasing airway pressure to improve PaO2/F(IO2) to > or =500 torr. MEASUREMENTS AND MAIN RESULTS: Blood gases were measured every 30 mins for 3 hrs. Airway pressures were measured with a tip catheter pressure transducer. At the end of the study period, a pressure-volume curve was recorded and a broncho-alveolar lavage was performed to determine protein content and surfactant composition. The results showed that arterial oxygenation in both groups could be kept >500 torr during the 3-hr study period by using a mean airway pressure of 13+/-3 cm H2O in PCV and 13+/-2 cm H2O in HFOV. Further, there were no differences in the Gruenwald index, protein influx, or ratio of small to large aggregates between the study groups. CONCLUSION: PCV with sufficient level of positive end-expiratory pressure and small driving pressure amplitudes is as effective as HFOV to maintain optimal gas exchange, to improve lung mechanics, and to prevent protein influx and conversion of large into small aggregates after exogenous surfactant therapy in lung-lavaged rats.

At surfactant deficiency, application of "the open lung concept" prevents protein leakage and attenuates changes in lung mechanics.

OBJECTIVE: To evaluate whether mechanical ventilation using "the open lung concept" during surfactant depletion can attenuate the deterioration in pulmonary function. DESIGN: Experimental, comparative study. SETTING: Research laboratory of a large university. SUBJECTS: Eighteen adult male Sprague-Dawley rats, weighing 280-340 g. INTERVENTIONS: Twelve rats were anesthetized, mechanically ventilated with 100% oxygen, and randomly divided into two groups (n = 6 each). The open lung group underwent six saline lavages at different ventilator settings that prevented alveolar collapse. The settings (expressed as frequency/peak inspiratory pressure/positive end-expiratory pressure/inspiratory:expiratory ratio) were 30/26/6/1:2 during the first lavage, 100/27/10/1:1 during the next two lavages, and 100/33/15/1:1 during the last three lavages and during the remaining ventilation period. The ventilated control group underwent six saline lavages with settings at 30/26/6/1:2. After the lavages, peak inspiratory pressure and positive end-expiratory pressure were increased in this group by 2 cm H2O each for the remaining study period. An additional group of six animals were killed immediately after induction of anesthesia and served as healthy controls. Blood gases were measured before lavage, immediately after the last lavage, and thereafter hourly. At the end of the 4-hr study period, we constructed pressure-volume curves from which we determined total lung capacity at a distending pressure of 35 cm H2O (TLC35). Subsequently, total lung volume at a distending pressure of 5 cm H2O (V5) was determined, followed by bronchoalveolar lavage. RESULTS: In the ventilated control group, PaO2, V5, and TLC35 were significantly decreased and protein concentration of bronchoalveolar lavage was significantly increased compared with the healthy control group. In the open lung group, PaO2 did not decrease after the lavage procedure, and V5, TLC35, and the protein concentration of bronchoalveolar lavage were comparable with the healthy controls. CONCLUSION: We conclude that application of the open lung concept during surfactant depletion attenuates deterioration in pulmonary function.

The open lung concept: pressure-controlled ventilation is as effective as high-frequency oscillatory ventilation in improving gas exchange and lung mechanics in surfactant-deficient animals.

OBJECTIVE: To demonstrate in experimental animals with respiratory insufficiency that under well-defined conditions, commercially available ventilators allow settings which are as effective as high-frequency oscillatory ventilators (HFOV), with respect to the levels of gas exchange, protein infiltration, and lung stability. DESIGN: Prospective, randomized, animal study. SETTING: Experimental laboratory of a university. SUBJECTS: 18 adult male Sprague-Dawley rats. INTERVENTIONS: Lung injury was induced by repeated whole-lung lavage. Thereafter, the animals were assigned to pressure-controlled ventilation (PCV) plus The Open Lung Concept (OLC) or HFOV plus OLC (HFO(OLC)). In both groups, an opening maneuver was performed by increasing airway pressures to improve the arterial oxygen tension/fractional inspired oxygen (PaO(2)/FIO(2)) ratio to L 500 mm Hg; thereafter, airway pressures were reduced to minimal values, which kept PaO(2)/FIO(2) L 500 mm Hg. Pressure amplitude was adjusted to keep CO(2) as close as possible in the normal range. MEASUREMENTS AND RESULTS: Airway pressure, blood gas tension, and arterial blood pressure were recorded every 30 min. At the end of the 3-h study period, a pressure-volume curve was recorded and bronchoalveolar lavage was performed to determine protein content. After the recruitment maneuver, the resulting mean airway pressure to keep a PaO(2)/FIO(2) L 500 mm Hg was 25 +/- 1.3 cm H(2)O during PCV(OLC) and 25 +/- 0.5 cm H(2)O during HFOV(OLC). Arterial oxygenation in both groups was above L 500 mm Hg and arterial carbon dioxide tension was kept close to the normal range. No differences in mean arterial pressure, lung mechanics and protein influx were found between the two groups. CONCLUSIONS: This study shows that in surfactant-deficient animals, PCV, in combination with a recruitment maneuver, opens atelectatic lung areas and keeps them open as effectively as HFOV.

'Alveolar recruitment strategy' improves arterial oxygenation during general anaesthesia.

Abnormalities in gas exchange during general anaesthesia are caused partly by atelectasis. Inspiratory pressures of approximately 40 cm H2O are required to fully re-expand healthy but collapsed alveoli. However, without PEEP these re-expanded alveoli tend to collapse again. We hypothesized that an initial increase in pressure would open collapsed alveoli; if this inspiratory recruitment is combined with sufficient end-expiratory pressure, alveoli will remain open during general anaesthesia. We tested the effect of an 'alveolar recruitment strategy' on arterial oxygenation and lung mechanics in a prospective, controlled study of 30 ASA II or III patients aged more than 60 yr allocated to one of three groups. Group ZEEP received no PEEP. The second group received an initial control period without PEEP, and then PEEP 5 cm H2O was applied. The third group received an increase in PEEP and tidal volumes until a PEEP of 15 cm H2O and a tidal volume of 18 ml kg-1 or a peak inspiratory pressure of 40 cm H2O was reached. PEEP 5 cm H2O was then maintained. There was a significant increase in median PaO2 values obtained at baseline (20.4 kPa) and those obtained after the recruitment manoeuvre (24.4 kPa) at 40 min. This latter value was also significantly higher than PaO2 measured in the PEEP (16.2 kPa) and ZEEP (18.7 kPa) groups. Application of PEEP also had a significant effect on oxygenation; no such intra-group difference was observed in the ZEEP group. No complications occurred. We conclude that during general anaesthesia, the alveolar recruitment strategy was an efficient way to improve arterial oxygenation.

Comparison of exogenous surfactant therapy, mechanical ventilation with high end-expiratory pressure and partial liquid ventilation in a model of acute lung injury.

We have compared three treatment strategies, that aim to prevent repetitive alveolar collapse, for their effect on gas exchange, lung mechanics, lung injury, protein transfer into the alveoli and surfactant system, in a model of acute lung injury. In adult rats, the lungs were ventilated mechanically with 100% oxygen and a PEEP of 6 cm H2O, and acute lung injury was induced by repeated lung lavage to obtain a PaO2 value < 13 kPa. Animals were then allocated randomly (n = 12 in each group) to receive exogenous surfactant therapy, ventilation with high PEEP (18 cm H2O), partial liquid ventilation or ventilation with low PEEP (8 cm H2O) (ventilated controls). Blood-gas values were measured hourly. At the end of the 4-h study, in six animals per group, pressure-volume curves were constructed and bronchoalveolar lavage (BAL) was performed, whereas in the remaining animals lung injury was assessed. In the ventilated control group, arterial oxygenation did not improve and protein concentration of BAL and conversion of active to non-active surfactant components increased significantly. In the three treatment groups, PaO2 increased rapidly to > 50 kPa and remained stable over the next 4 h. The protein concentration of BAL fluid increased significantly only in the partial liquid ventilation group. Conversion of active to non-active surfactant components increased significantly in the partial liquid ventilation group and in the group ventilated with high PEEP. In the surfactant group and partial liquid ventilation groups, less lung injury was found compared with the ventilated control group and the group ventilated with high PEEP. We conclude that although all three strategies improved PaO2 to > 50 kPa, the impact on protein transfer into the alveoli, surfactant system and lung injury differed markedly.

[Acute fatty liver of pregnancy complicated by pancreatitis]. / Hígado graso agudo del embarazo complicado con pancreatitis.

A woman with acute fatty liver of pregnancy developed fulminant hepatic failure after delivery, a time when spontaneous recovery was expected. Pancreatitis and multiple organ failure was documented and intensive treatment in a critical care unit was needed to support organ function. She underwent plasmapheresis due to extreme hyperbilirubinemia and coma. She recovered completely.