High-frequency partial liquid ventilation in respiratory distress syndrome: hemodynamics and gas exchange

Partial liquid ventilation using conventional ventilatory schemes improves lung function in animal models of respiratory failure. We examined the feasibility of high-frequency partial liquid ventilation in the preterm lamb with respiratory distress syndrome and evaluated its effect on pulmonary and systemic hemodynamics. Seventeen lambs were studied in three groups: high-frequency gas ventilation (Gas group), high-frequency partial liquid ventilation (Liquid group), and high-frequency partial liquid ventilation with hypoxia-hypercarbia (Liquid-Hypoxia group). High-frequency partial liquid ventilation increased oxygenation compared with high-frequency gas ventilation over 5 h (arterial oxygen tension 253 +/- 21.3 vs. 17 +/- 1.8 Torr; P < 0.001). Pulmonary vascular resistance decreased 78% (P < 0.001), pulmonary blood flow increased fivefold (P < 0.001), and aortic pressure was maintained (P < 0.01) in the Liquid group, in contrast to progressive hypoxemia, hypercarbia, and shock in the Gas group. Central venous pressure did not change. The Liquid-Hypoxia group was similar to the Gas group. We conclude that high-frequency partial liquid ventilation improves gas exchange and stabilizes pulmonary and systemic hemodynamics compared with high-frequency gas ventilation. The stabilization appears to be due in large part to improvement in gas exchange.     

Pressure-controlled, inverse ratio ventilation that avoids air trapping in the adult respiratory distress syndrome

OBJECTIVES: To investigate physiologic and outcome data in patients switched from volume-cycled conventional ratio ventilation to pressure-controlled inverse ratio ventilation that did not produce air trapping and intrinsic positive end-expiratory pressure (PEEP). SETTING: Medical intensive care unit. DESIGN: Retrospective analysis of crossover data and outcome. PATIENTS: Fourteen patients with the adult respiratory distress syndrome who were receiving mechanical ventilation with volume-cycled, conventional ratio ventilation followed by pressure-controlled, inverse ratio ventilation. INTERVENTIONS: Our approach to pressure-controlled, inverse ratio ventilation was to use tidal volumes and applied PEEP values comparable to those volumes and values used on volume-cycled, conventional ratio ventilation, use inspiratory times to increase mean airway pressure instead of additional applied PEEP, and avoid air trapping (intrinsic PEEP). MEASUREMENTS AND MAIN RESULTS: With this approach, there was a reduction in peak airway pressure from 53 +/- 8.5 (SD) to 40 +/- 5.9 cm H2O (p < .01), and an increase in mean airway pressure from 20 +/- 3.9 to 30 +/- 5.2 cm H2O (p < .01). Tidal volume, mean inflation pressure, and compliance did not change. Oxygenation (PaO2) improved from 57 +/- 11.3 torr (7.6 +/- 1.5 kPa) to 94 +/- 40.2 torr (12.5 +/- 5.4 kPa) (p = .01) but the oxygenation index (mean airway pressure x FIO2 x 100/PaO2) did not change significantly (25.9 +/- 10.3 to 27.2 +/- 12.2). There was no significant change in PaCO2 or pH even though delivered minute ventilation decreased from 17.4 +/- 4.3 to 14.8 +/- 5.8 L/min (p = .02). Cardiac index slightly decreased, but hemodynamic values were otherwise stable. Only three of the 14 study patients survived. CONCLUSIONS: These data demonstrate that oxygenation is primarily a function of mean airway pressure, and that longer inspiratory times can be used as an alternative to applied PEEP to increase this oxygenation. If no air trapping develops, lung inflation pressures and delivered volumes remain constant with this approach. Because the technique was used only in patients refractory to conventional techniques, the poor outcome is not surprising.     

Pharmacologic adjuncts to mechanical ventilation in acute respiratory distress syndrome

This article reviews pharmacologic approaches to treating acute respiratory distress syndrome (ARDS). The authors discuss the therapeutic effects of ketoconazole, antioxidants, corticosteroids, surfactant, ketanserin, pentoxifylline, bronchodilators, and almitrine in ARDS. Current animal data and proposed mechanics which may foster future pharmacologic therapies are also examined.     

Mechanisms of acute respiratory distress syndrome: role of surfactant changes and mechanical ventilation

Acute respiratory distress syndrome (ARDS) is a condition characterized by a high permeability oedema due to loss of the integrity of the alveolo-capillary barrier with impairment of normal surfactant function, resulting in an increased collapse tendency of the alveoli. Mechanical ventilation on such alveoli with repeated alveolar collapse and subsequent reexpansion results in severe lung parenchymal injury and may induce further surfactant impairment. This cam be prevented by maintaining alveolar volume at end-expiration by means of sufficient levels of positive end-expiratory pressure (PEEP). Recent evidence from experimental studies has shown that ventilator modes which allow end-expiratory collapse can induce bacterial translocation from the lung into the bloodstream and trigger the release of inflammatory mediators, which can also be presented by maintaining end-expiratory alveolar volume. These data suggest that the interaction between surfactant changes and mechanical ventilation may play a role in the transition of ARDS into the systematic inflammatory disease process of multiple system organ failure (MSOF).     

A new view of pulmonary edema and acute respiratory distress syndrome

The old division of lung edema into two categories--cardiogenic (hydrostatic) and noncardiogenic (increased permeability)--is no longer adequate. For instance, it fails to distinguish between the capillary leak caused by acute respiratory distress syndrome from that caused by interleukin-2 treatment. Further, it fails to account for the capillary leak ('stress-failure') that may accompany edema. A modern view of edema must recognize the natural barriers to the formation and spread of edema. These barriers are the capillary endothelium and the alveolar epithelium. Varying degrees of damage to them can account for the varying radiographic and clinical manifestations of lung edema. Thus, interleukin-2 administration causes increased endothelial permeability without causing alveolar epithelial damage. The result is lung edema that is largely confined to the interstitium, causing little hypoxia and clearing rapidly. However, acute respiratory distress syndrome, which is characterized by extensive alveolar damage, causes air-space consolidation, severe hypoxia, and slow resolution. Thus, a reasonable classification of lung edema requires at least four categories: 1) hydrostatic edema; 2) acute respiratory distress syndrome (permeability edema caused by diffuse alveolar damage); 3) permeability edema without alveolar damage; and (4) mixed hydrostatic and permeability edema. The authors emphasize the importance of the barriers provided by the capillary endothelium and the alveolar epithelium in determining the clinical and radiographic manifestations of edema. In general, when the alveolar epithelium is intact, the radiographic manifestations are those of interstitial (not air-space) edema; this radiographic pattern predicts a mild clinical course and prompt resolution.     

Effect of artificial ventilation on pulmonary capillary pressure in acute respiratory insufficiency

To determine the influence of intermittent positive pressure breathing (IPPB), the level of pulmonary capillary wedge pressure (PCWP) was compared during IPPB and after a short period off the respirator in 68 occasions on 42 patients with an acute respiratory failure (ARF) of various etiologies. During IPPB, the average PCWP was in the normal range in patients with toxic or neurologic comas and in cases of increased pulmonary capillary permeability edema (IPCPE), PCWP slightly increased within chronic obstructive pulmonary disease (COPD) complicated with ARF and in hemodynamic acute pulmonary edema (HAPE). During the weaning stage, PCWP decreased in the groups of coma, COPD, and IPCPE, but increased in HAPE. The weaning test demonstrates that IPPB influenced PCWP in all patients. Therefore, PCWP cannot be assumed to represent the left ventricle filling pressure. The weaning test allows differentiation of IPCPE from HAPE. In the event of over-infusion or hypovolemia, PCWP measured under IPPB can lead to misinterpretation if not followed up by a second measurement off the respirator.     

Artificial ventilation in acute respiratory distress syndrome in adults. Towards an individual optimization

Artificial ventilation plays a key role in the treatment of acute respiratory distress syndrome (ARDS). Initially, the goal is to normalize gas exchange compromised by the lung disease. Positive pressure ventilation can however aggravate prior lesions of the pulmonary parenchyma, at least in areas of the lung accessible to ventilation. Computed tomography of the lung has given us a better understanding of the pathogenesis of these ventilation-induced lesions, leading to new ventilatory strategies aimed at assuring adequate oxygenation without damaging the parenchyma. These ventilatory modes may tolerate a certain degree of hypercapnia to avoid lung injury. Improved oxygenation relies on optimizing the ventilation/perfusion ratio, either with inhaled nitric oxide or a supine position to improve alveolar recruitment. In the most severe cases, extra-corporal gas exchange systems have shown their efficacy for patients whose lungs cannot be ventilated. Thus ventilation should be carefully adapted to each patient based on the severity of the ARDS and its clinical course. We present a practical protocol based on a hierarchy rationale for each ventilation mode and indicate the explorations required to adapt each mode to a specific patient.     

Influence of feed deprivation on ventilation and gas exchange in broilers: relationship to pulmonary hypertension syndrome

Fast-growing broiler chickens not uncommonly exhibit elevated pulmonary vascular resistance that leads to pulmonary hypertension and right ventricular failure. We tested the hypothesis that a distended gastrointestinal tract in these full-fed birds results in an abnormally low tidal volume and minute ventilation that could lead to pulmonary hypoxia, pulmonary arterial vasoconstriction, right ventricular failure, and ascites. Tidal volume, respiratory frequency, heart rate, percentage saturation of hemoglobin with oxygen (HbO2), O2 consumption, and carbon dioxide elimination were measured on fast-growing broiler chickens when full-fed and after 3, 6, and 9 h of feed deprivation. Tidal volume of full-fed birds was not abnormally low despite HbO2 values varying from above 80% to nearly 60%. Importantly, HbO2 was found to be markedly increased in the hypoxemic birds at and beyond a 3-h period without feed, despite a reduction in minute ventilation. This response was not caused by a decrease in O2 consumption. Thus, limitation of gas intake at the mouth was not the cause of the hypoxemia. The data suggest that feed deprivation results in an increase in parabronchial ventilation, possibly from improvement in aerodynamic valving, which would reduce pulmonary hypoxic vasoconstriction and right ventricular failure.     

Effect of a protective-ventilation strategy on mortality in the acute respiratory distress syndrome

Recent studies have shown that tetrafluoroethylene is a renal and hepatic carcinogen in the rat. In this study, we have examined the ability of a single i.p. dose of 1,1,2,2-tetrafluoroethyl-L-cysteine (TFEC), a major metabolite of tetrafluoroethylene, to produce hepatic and renal injury in male and female rats. We have also examined the effect of blocking the renal organic anion transport system with probenecid and of inhibiting the activity of cysteine conjugate beta-lyase with aminooxyacetic acid on the extent of renal injury produced by TFEC. Doses of > or = 12.5 mg/kg TFEC produced renal tubular necrosis to the pars recta of the proximal tubules within 24 h in both male and female rats. This was associated with an increased kidney to body weight ratio and plasma urea at doses of > or = 25 mg/kg. No consistent evidence of liver injury was seen at doses up to 50 mg/kg TFEC in rats of either sex, although occasional vacuolation of hepatocytes and a small dose-related increase in liver to body weight ratio was observed. Prior treatment of female rats with probenecid completely prevented the renal injury produced by either 25 or 50 mg/kg TFEC as judged by plasma urea and histopathology. However, prior treatment of female rats with aminooxyacetic acid afforded no protection against the nephrotoxicity produced by either TFEC or the cysteine conjugate of hexachloro-1,3-butadiene. Thus no major sex difference in nephrotoxicity in the rat was seen with TFEC, while accumulation of TFEC, or its N-acetyl derived metabolite, into renal proximal tubular cells via a probenecid sensitive transport system appears to be a key event in the mechanism of nephrotoxicity. The lack of protection observed with the cysteine conjugate beta-lyase inhibitor, aminooxyacetic acid, may reflect the inability to completely inhibit the mitochondrial form of this enzyme and thereby prevent the formation of the reactive metabolite. Our acute studies provide no insight concerning the liver carcinogenicity of tetrafluoroethylene.     

Effect of pulmonary hypertension on gas exchange

This paper reviews the effects of pulmonary artery hypertension on gas exchange by exploring three different issues, namely: 1) how does gas exchange behave in diseases characterized by increased vascular tone (primary pulmonary hypertension (PPH), chronic obstructive pulmonary disease (COPD) and interstitial pulmonary fibrosis (IPF)) or decreased vascular tone ("hepatopulmonary syndrome"); 2) how does exercise, as a non-pharmacological tool of increasing pulmonary blood flow, modify gas exchange in these diseases; and 3) how do several drugs that lower (vasodilators) or increase (almitrine) the active component of pulmonary hypertension interact with gas exchange. Available data show that: 1) in PPH a high pulmonary vascular tone enhances gas exchange and when it is lowered, either by oxygen or vasodilators, ventilation perfusion (VA/Q) distributions deteriorate; 2) in COPD a lowered (vasodilators) or augmented (almitrine) active vascular tone is almost invariably paralleled by a deterioration or enhancement of ventilation-perfusion matching, respectively; 3) in IPF an adequate active response of the pulmonary vasculature is essential to maintain gas exchange, both at rest and during exercise; and 4) in patients with liver cirrhosis a low pulmonary vascular tone induces an abnormal VA/Q distribution. In summary, these data show that any situation and/or therapeutic intervention that lowers the active vascular tone deteriorates VA/Q relationships and vice versa. The final effect of pulmonary vascular tone on arterial oxygen tension (PaO2) is less predictable. The reason for this uncertainty is that the actual PaO2 value depends on the interplay of the intra- and extrapulmonary factors that control gas exchange in humans, and not only on the degree of VA/Q mismatching.     

Current aspects of acute respiratory distress syndrome in children

Acute respiratory distress syndrome (ARDS) is a frequent condition in pediatric intensive care units. The mortality remains high despite advances in conventional mechanical ventilation and aetiological treatment. Several animal studies have documented lung injury during mechanical ventilation with high tidal volume, and clinical investigations have shown that in human ARDS, most ventilation is distributed to the small areas of remaining aerated lung resulting in overdistension of these areas and lung injury ("baby lung" theory). Nevertheless the usefulness of extrapulmonary gas exchange remains much debated. New ventilatory strategies have been developed in order to reduce ventilator-induced lung injury and to improve systemic oxygenation but multicentric randomized clinical trials are needed before these strategies can be validated.     

Open-lung biopsy in patients with acute respiratory distress syndrome

Occupational exposures contribute to the morbidity and mortality of many diseases. However, occupational diseases continue to be underrecognized even though they are responsible for an estimated 860,000 illnesses and 60,300 deaths each year. Family physicians can play an important role in improving the recognition of occupational disease, preventing progressive illness and disability in their own patients, and contributing to the protection of other workers similarly exposed. This role can be maximized if physicians raise their level of suspicion for workplace disease, develop skills in taking occupational histories and establish routine access to occupational health resources.     

Experiences with high-frequency oscillatory ventilation in premature infants with respiratory distress syndrome

BACKGROUND: High-frequency oscillatory ventilation (HFOV) has been used in treating premature infants with respiratory distress syndrome who have a low incidence of ventilation-associated lung injury. Herein, we report our initial clinical experience in using HFOV to treat such infants. METHODS: From October 1996 to February 1997, 10 premature infants with severe respiratory distress syndrome treated with HFOV were retrospectively evaluated. Clinical course and laboratory data collected during treatment were analyzed. Parameters evaluated included patient survival rate, incidence of chronic lung disease and morbidity associated with HFOV usage. RESULTS: The mean gestational age was 29 +/- 2 weeks; mean birth weight, 1,182 +/- 342 g; and mean period of HFOV treatment, 3.4 +/- 1.9 days. One patient died of sepsis due to infective pancarditis. Two patients developed moderate chronic lung disease at 30 days post delivery and in one of these patients, the disease persisted at 36 weeks' of age. The overall survival rate was 90%. No patient developed air-leak syndrome during the course of treatment. CONCLUSIONS: Our initial experience demonstrated that using HFOV in treating premature infants with severe respiratory distress syndrome was safe and effective. The incidence of moderate to severe chronic lung disease or air-leak syndrome following HFOV was low.     

Pressure support ventilation in adult respiratory distress syndrome: short-term effects of a servocontrolled mode

PURPOSE: To assess the short-term effects of pressure support ventilation in adult respiratory distress syndrome (ARDS), we studied 17 patients with moderate to severe ARDS using mandatory rate ventilation (MRV), a servocontrolled mode of PSV having respiratory rate as the targeted parameter. MATERIALS AND METHODS: Based on the duration of ARDS, the patients were divided into two groups: Group 1, early ARDS (duration up to 1 week), 10 patients; Group 2, intermediate ARDS (duration between 1 and 2 weeks). The patients were initially ventilated with assisted mechanical ventilation then with MRV, and finally with controlled mechanical ventilation. After a 20-minute period allowed for stabilization in each mode, ventilatory variables, gas exchange, hemodynamics, and patient's inspiratory effort were evaluated. RESULTS: During MRV blood gases, airway pressures and hemodynamic variables remained within acceptable limits in all patients. Compared with assisted mechanical ventilation, during MRV, patients of group 1 decreased their VT and V (from 0.64 +/- 0.04 to 0.42 +/- 0.03 L/sec) and increased their TI/TT (from 0.39 +/- 0.03 to 0.52 +/- 0.03). f did not change. PAO2 - PaO2 and QS/QT decreased (from 306 +/- 16 to 269 +/- 15 mm Hg, and from 20.2 +/- 1.4 to 17.5 +/- 1.1, respectively), while PaCO2 increased (from 44 +/- 3 to 50 +/- 3 mm Hg). On the contrary, patients of group 2 increased their VT (from 0.69 +/- 0.02 to 0.92 +/- 0.09 L), decreased their f (from 22.3 +/- 0.5 to 19.3 +/- 0.3 b/min), although they did not change their V and TI/TT. PAO2 - PaO2 and QS/QT remained stable. PaCO2 diminished (from 39 +/- 3 to 34 +/- 3 mm Hg). Pressure support level was higher in group 2 than in group 1 (29.4 +/- 3.0 v 19.8 +/- 2.9 cm H2O). CONCLUSIONS: We conclude that (1) PSV delivered by MRV may adequately ventilate patients with moderate to severe ARDS, preserving gas exchange and hemodynamics, at least for the short period tested; (2) early and intermediate ARDS respond in a different manner to MRV in terms of breathing pattern, gas exchange, and level of pressure assistance; and (3) patients with early ARDS are those who have an improvement in intrapulmonary oxygenation probably due, at least in part, to alveolar recruitment augmented by active diaphragmatic contraction.     

Eicosanoids and fat emulsions in acute respiratory distress syndrome patients

Laparoscopic splenectomy has been accepted as a feasible extension of minimally invasive surgery, which has undergone dramatic improvements in both technology and instrumentation. We performed a laparoscopic splenectomy in a 7-year-old girl with hereditary spherocytosis. The patient recovered rapidly and returned to unrestricted activities quickly. The appropriate positioning of each laparoscopic port is essential for a good operative view and smooth access. It is also important to dissect the hilum of the spleen meticulously. Laparoscopic splenectomy in the pediatric age group appears to be another promising extension of laparoscopic surgery.     

Respiratory mechanics and surfactant in the acute respiratory distress syndrome

1. Although abnormalities in pulmonary surfactant were initially implicated in the pathogenesis of the acute respiratory distress syndrome (ARDS) 30 years ago, most subsequent research has focused on mediators of the parenchymal acute lung injury (ALI) and the associated increase in alveolocapillary permeability. 2. Surfactant is essential for normal breathing and the severity of ALI correlates with surfactant dysfunction and abnormalities in surfactant composition; however, no relationship has been shown with respiratory system compliance. In neonates and most animal models, respiratory system compliance will directly reflect the elastic properties of the lung. However, the greater vertical height of the chest wall in adults, in combination with the increase in lung density due to ALI, results in dependent collapse of alveoli. Because simple, global measurement of compliance is strongly influenced by the volume of aerated lung, alternative measures of respiratory mechanics may reflect surfactant dysfunction. 3. Using a dynamic, volume-dependent model of respiratory mechanics to indirectly reflect this heterogeneous inflation, we have found direct relationships with surfactant composition in patients with ARDS. A failure of surfactant to increase surface tension in large alveoli may also explain why lung overdistension occurs at relatively low pressures. Furthermore, surfactant dysfunction will exaggerate heterogeneous lung inflation, augmenting regional overinflation, and is essential for ALI secondary to repetitive opening and closing of alveoli during tidal ventilation. 4. Ventilation-induced ALI has also been shown to result in massive increases in pro-inflammatory cytokines within the lung. Because ALI itself fails to compartmentalize cytokines, with spillover into the systemic circulation resulting in distant organ dysfunction, surfactant dysfunction may have widespread implications.