Apoptosis inhibition in P. aeruginosa-induced lung injury influences lung fluid balance

Objective Pseudomonas aeruginosa-induced lung injury is characterized not only by the alteration in lung fluid movement but also by apoptosis of lung epithelial and endothelial cells. We studied whether inhibition of apoptosis using a broad spectrum caspase inhibitor, benzyloxycarbonyl-Val-Ala-Asp fluoromethylketone (Z-VAD.fmk), would affect lung fluid balance in rat P. aeruginosa pneumonia. Methods Z-VAD.fmk (3 mg/kg) was administered intravenously simultaneously with P. aeruginosa intratracheal instillation (0.5 ml/kg, 2×10⁹ CFU/ml). Apoptosis was evaluated with the TUNEL technique, cytoplasmic oligonucleosome assay, and caspase 3 activation. To evaluate lung permeability, extravascular plasma equivalent (EPE) and lung wet to dry weight ratio (W/D) were measured 4 h after intratracheal instillation of P. aeruginosa. Results We found an increase of lung apoptosis 4 h after P. aeruginosa instillation: cytoplasmic oligonucleosome assay increased from 3.17±0.78 to 26.82±4.67 OD×1000/mg of proteins/ml, Z-VAD.fmk administration decreased this parameter to 10.3±2.98 OD×1000/mg of proteins/ml. Caspase 3 levels followed the same pattern. Apoptosis involved both epithelial cells and endothelial cells. Endothelial permeability was increased after Pseudomonas instillation: W/D increased from 3.75±0.28 in the Co group to 4.42±0.23 in the Pn group; EPE was also higher in the Pn group compared with the Co group (0.125±0.04 and 0.002±0.01 ml, respectively). Both of these parameters were improved after Z-VAD.fmk administration; W/D decreased to 3.36±0.25 and EPE to 0.02±0.02 ml. Conclusion Apoptosis occurs in the early phase of P. aeruginosa pneumonia. Administration of Z-VAD.fmk significantly decreases DNA fragmentation and caspase 3 levels. This is associated with an improvement of endothelial permeability and lung fluid balance.     

Effects of asphyxia on lung fluid balance in baby lambs.

The purpose of this study was to assess the effects of combined hypoxia and hypercapnia and of severe asphyxia on lung water balance and protein transport in newborn lambs. We studied ten 2-4-wk-old anesthetized lambs which were mechanically ventilated first with air for 2-3 h, then with 10-12% oxygen in nitrogen for 2-4 h, and then with 10-12% oxygen and 10-12% carbon dioxide in nitrogen for 2-4 h. Next we stopped their breathing for 1-2 min to produce severe asphyxia, after which we followed their recovery in air for 2-4 h. In 5 of the 10 lambs we intravenously injected radioactive albumin and measured its turnover time between plasma and lymph during the baseline period and after recovery from asphyxia. During alveolar hypoxia alone, mean pulmonary arterial pressure increased 60% and lung lymph flow increased 74%, whereas lymph protein concentration decreased from 3.47 +/- 0.13 to 2.83 +/- 0.15 g/dl. Cardiac output, left atrial pressure, and plasma protein concentration did not change. When carbon dioxide was added to the inspired gas mixture, pulmonary arterial pressure increased 22%, cardiac output increased 13%, lung lymph flow increased 33%, and lymph protein concentration decreased from 2.83 +/- 0.15 to 2.41 +/- 0.13 g/dl. Left atrial pressure and plasma protein concentration did not change. After 60-90 s of induced asphyxia, vascular pressures and lung lymph flow rapidly returned to values the same as those obtained during the baseline period. The turnover time for radioactive albumin between plasma and lymph was the same between the baseline and recovery periods (185 +/- 16 vs. 179 +/- 12 min). The ratio of albumin to globulin in lymph relative to the same ratio in plasma did not change during any phase of these experiments. Five lambs killed after recovery from asphyxia had significantly less blood and extravascular water in their lungs than control lambs had. We conclude that in the newborn lamb both alveolar hypoxia and alveolar hypoxia with hypercapnia increase lung lymph flow by increasing filtration pressure in the microcirculation, but neither hypoxia with hypercapnia nor brief severe asphyxia alters the protein permeability of the pulmonary microcirculation.     

Understanding and managing fluid balance in patients with acute lung injury

PURPOSE OF REVIEW: Acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS) affect hundreds of thousands of people each year worldwide, resulting in a significant healthcare burden. Over the past four decades, much has been discovered regarding the pathophysiology of lung injury, yet little progress has been made in advancing effective treatment strategies. In this article, we discuss the current knowledge as to fluid balance in the pathophysiology of ALI/ARDS and the recent innovations that have been described related to manipulations of hydrostatic or oncotic pressure in this condition. RECENT FINDINGS: Hypoproteinemia is a clear marker for ALI/ARDS and may play a pathophysiologic role given its independent prognostic value. Fluid balance and oncotic pressure alterations induced by diuretic and colloid therapy improve respiratory physiology and likely alter net flux of fluid across the injured capillary-alveolar membrane. Chest radiographs serve as a useful adjunctive tool in monitoring longitudinal fluid balance manipulations in ALI/ARDS. SUMMARY: Manipulation of Starling forces in established ALI/ARDS produces significant physiologic benefit and may influence outcome. Future research should focus on determining a mortality benefit with this readily available intervention.     

Pulmonary fluid balance and hemodynamics after perfluorocarbon infusion in the dog lung

Perfluorocarbon (PFC) emulsions are promising oxygen-carrying blood supplements for the treatment of shock and in organ preservation for transplantation. We used the isolated, blood-perfused, canine right lower lung lobe (RLL) to determine the effect of a PFC emulsion, Oxypherol (FC-43), upon lung fluid balance and hemodynamics. Eighteen RLLs were divided into three equal groups, one of which was infused with a bovine serum albumin (BSA) solution to 10% of the total perfusate volume, and two of which were infused with Oxypherol to 10% and 20% of the final blood volume, respectively. At 145 min after infusion, there was no significant difference among the three groups in pH, blood gases, and lobar compliance. Arterial pressure and lobar vascular resistance were significantly (p less than .05) greater in the 20% Oxypherol group than in the BSA group. PFC-related changes in lobar permeability were determined by measuring the pulmonary filtration coefficient (Kf), which was not significantly different among groups. Thus, Oxypherol did not increase microvascular permeability (i.e., lung edema).     

Reversible adsorption by a pH- and temperature-sensitive acrylic hydrogel

Thermo- and pH-sensitive hydrogels were synthesized using N-isopropylacrylamide (NIPA) and N-aminopropylmethacrylamide, cross-linked with N,N′-methylenebis(acrylamide). The dependence of the degree of swelling on the cross-linking density was analyzed according to the Flory-Huggins theory and a master curve obtained. To optimize the efficiency of these hydrogels in controlled release, we studied the loading and release of a divalent molecule (naphthalenedisulfonic acid, NS-2) in media of different ionic strengths and pH. The uptake process followed the Langmuir adsorption isotherm model. The highest loading occurred when the amino groups in the gel were protonated (acidic pH) and could come close each other to form a binding site for the two sulfonic groups of NS-2, i.e. low degree of cross-linking and collapsed state. Below the phase transition temperature (33 °C), NS-2 loaded hydrogels quickly released a significant amount of adsorbate until a new equilibrium between free NS-2 and adsorbed NS-2 was achieved. Above that temperature, hydrogels not only stopped the release but were even able to take free NS-2 up again from the medium, showing that the loading/release process was reversible and reproducible after several temperature cycles. At 37 °C, the release rate was independent of the degree of cross-linking (NIPA caused the hydrogel to collapse), but was strongly affected by the pH and salt concentrations of the medium, which condition the strength of the interaction between the hydrogel amino groups and the NS-2 sulfonic groups. In an acidic medium, the protonated amino groups bind NS-2 strongly and the amount released is small. In contrast, at pH 7.4 or in the presence of a high salt concentration, the hydrogel loses its affinity for NS-2 and the release rate increases, giving pH- or salt-sensitive delivery systems. Additionally, since the hydrogel is collapsed, the release can be prolonged for a long period of time.     

Effects of intravascular volume expansion on lung fluid balance in a canine model of septic shock

We tested the early effects of endotoxin on both the permeability of capillary membranes and microvascular pressure. One group of dogs (n = 8) were fluid loaded (30 ml/kg dextran-40) after having been subjected to a 2-h Escherichia coli endotoxin infusion (0.25 micrograms/kg X min). A second control group of animals (n = 6) was submitted to a similar (25 ml/kg) volume loading over an equivalent 30-min period. We estimated extravascular lung water (EVLW), calculated the effective pulmonary capillary pressure, and determined the alveolar-capillary filtration coefficient (Kf) after volume loading. Only the septic animals consistently showed elevated EVLW values consistent with pulmonary edema. The results showed, however, that the Kf calculated for the dogs that received endotoxin was no different from that of control group (Kf = 0.005 ml/kg X min X mm Hg). Instead, endotoxin constricted the pulmonary veins which led to a considerable rise in microvascular hydrostatic pressure above the level at which the lungs could not resist edema formation. We conclude that acute pulmonary edema that follows endotoxin insult and subsequent therapeutic volume replacement is due to an increased filtration force instead of an alteration in the microvascular permeability.     

Measuring and managing fluid balance

Ensuring patients are adequately hydrated is an essential part of nursing care, yet a recent report from the Care Quality Commission found "appalling" levels of care in some NHS hospitals, with health professionals failing to manage dehydration. This article discusses the importance of hydration, and the health implications of dehydration and overhydration. It also provides an overview of fluid balance, including how and why it should be measured, and discusses the importance of accurate fluid balance measurements.     

Reversible cortical blindness after lung transplantation

Cyclosporine (CYA) is a calcineurin inhibitor widely used in immunosuppressive regimens after organ transplantation. Several neurologic side effects are frequently associated with CYA use; however, reversible cortical blindness is a rare manifestation of CYA toxicity traditionally seen after liver and bone marrow transplantation. This report presents a case of reversible cortical blindness after lung transplantation, then details the risk factors and clinical course of 28 previously well-documented cases of CYA-induced cortical blindness after transplantation. Identification of known risk factors, clinical clues, and typical radiographic findings may aid in the diagnosis of CYA-induced cortical blindness, since reduction in CYA dose or cessation of CYA therapy usually permits resolution of the neurologic effects.     

Echocardiography to predict tolerance to negative fluid balance in acute respiratory distress syndrome/acute lung injury

Purpose

In acute respiratory distress syndrome (ARDS) and acute lung injury (ALI), a conservative fluid management strategy improves lung function but could jeopardize extrapulmonary organ perfusion. The objective was to evaluate the diagnostic accuracy of echocardiography to predict tolerance of negative fluid balance (NFB) in patients with ARDS/ALI.

Materials and Methods

A prospective and observational study in an adult intensive care unit of a university hospital was conducted. All hemodynamically stable patients with ARDS/ALI were included. Echocardiography was performed before NFB and again after 24 hours. Tolerance of NFB was evaluated by the presence of hypotension, acute kidney injury, or need for fluid expansion. The 2 patient groups (tolerating and not tolerating NFB) were compared.

Results

Forty-five patients were included. Median age (Q1-Q3) was 58 (52-66) years, and the ratio of partial pressure of arterial oxygen to the fraction of inspired oxygen was 205 (163-258) mm Hg. Negative fluid balance was 1950 (1200-2200) mL within 24 hours in the tolerant group. Complications of NFB were observed in 35% cases. After univariate and multivariate logistic regression analyzes, 2 criteria was independently associates with poor tolerance: mitral inflow E wave to early diastolic mitral annulus velocities ratio (E/Ea ratio; odds ratio, 2.02 [1.02-4.02]; P = .04) and weight gain (odds ratio, 1.2 [1.03-1.4]; P = .02). The area under receiver operating characteristic curves was 0.74 for E/Ea and 0.77 for weight gain.

Conclusions

The ratio of E/Ea accurately predicted tolerance of NFB in patients with ARDS/ALI.     

The sauna and body fluid balance

Sauna bathing may affect the fluid, electrolyte and acid-base balance. In addition to sweating and thirst, a sauna bath also has effects on many endogenous regulatory mechanisms maintaining the balance between the fluid compartments and appropriate distribution of the circulating blood. Although the sauna-induced fluid loss is usually not very severe, its adequate replacement as early as possible is important. In practice, the most convenient and effective way is to replace the fluid loss by small liquid doses repeated frequently during the bathing. If a sauna bath is taken after heavy physical activity, the fluid compensation may be necessary already before bathing.     

The importance of fluid balance in clinical practice

This article reviews the physiology that underpins normal fluid balance and discusses how fluid balance can be affected by illness. Clinical assessment of hydration and the importance of fluid balance record keeping are explained. Recommendations are made to improve fluid balance management in clinical practice and the professional importance of record keeping is highlighted.     

Acute effects of tidal volume strategy on hemodynamics, fluid balance, and sedation in acute lung injury

OBJECTIVE: To examine the effects of mechanical ventilation with a tidal volume of 6 mL/kg compared with 12 mL/kg predicted body weight on hemodynamics, vasopressor use, fluid balance, diuretics, sedation, and neuromuscular blockade within 48 hrs in patients with acute lung injury and acute respiratory distress syndrome. DESIGN: Retrospective analysis of a previously conducted randomized, clinical trial. SETTING: Two adult intensive care units at a tertiary university medical center and a large county hospital. PATIENTS: One hundred eleven patients who were enrolled in the National Institutes of Health ARDS Network trial at the University of California, San Francisco. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Compared with 12 mL/kg predicted body weight, treatment with a tidal volume of 6 mL/kg predicted body weight had no adverse effects on hemodynamics. There were also no differences in the need for supportive therapies, including vasopressors, intravenous fluids, or diuretics. In addition, there were no differences in body weight, urine output, and fluid balance. Finally, there was no difference in the need for sedation or neuromuscular blockade between the two tidal volume protocols. CONCLUSIONS: When compared with ventilation with 12 mL/kg predicted body weight, patients treated with the lung-protective 6 mL/kg predicted body weight tidal volume protocol had no difference in their supportive care requirements. Therefore, concerns regarding potential adverse effects of this protocol should not preclude its use in patients with acute lung injury or the acute respiratory distress syndrome.