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Benzamil, a blocker of epithelial Na+ channel-induced upregulation of artery oxygen pressure level in acute lung injury rabbit ventilated with high frequency oscillation

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Abstract

The epithelial Na(+) transport via an epithelial Na(+) channel (ENaC) expressed in the lung epithelium would play a key role in recovery from lung edema at acute lung injury by removing the fluid in lung luminal space. The lung edema causes dysfunction of gas exchange, decreasing oxygen pressure level of artery [P(aO(2))]. To study if ENaC plays a key role in recovering P(aO(2)) from a decreased level to a normal one in acute lung injury, we applied benzamil (20microM, a specific blocker of ENaC) to the lung luminal space in acute lung injury treated with high frequency oscillation ventilation (HFOV) that is a lung-protective ventilation with a lower tidal volume and a smaller pressure swing than conventional mechanical ventilation (CMV). Benzamil facilitated the recovery of P(aO(2)) in acutely injured lung with HFOV but not CMV. The observation suggests that in acutely injured lung treated with HFOV an ENaC blocker, benzamil, can be applied as a therapeutic drug for acute lung injury combing with HFOV.

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... Sodium is absorbed through the basolateral membrane of the epithelial sodium channel (ENaC) and sodium pump (Na + /K + -ATPase)-type cells. The associated chloride transport mechanisms have not yet been elucidated [18]. (iii) Passive water transport is accomplished mainly by aquaporins on type I cells. ...
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... Отек легких нарушает транспорт газов, снижает парциальное давление кислорода в артериальной крови. Применение се лективного блокатора ENaC при ОПЛ, вызванном высокочастотной вентиляцией (ВЧВ), способст вует ликвидации отека и может быть предложено в качестве терапевтического средства при ОПЛ в условиях проведения ВЧВ [18]. ...
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The highly amiloride-sensitive epithelial sodium channel (ENaC) is an apical membrane constituent of cells of many salt-absorbing epithelia. In the kidney, the functional relevance of ENaC expression has been well established. ENaC mediates the aldosterone-dependent sodium reabsorption in the distal nephron and is involved in the regulation of blood pressure. Mutations in genes encoding ENaC subunits are causative for two human inherited diseases: Liddle's syndrome, a severe form of hypertension associated with ENaC hyperfunction, and pseudohypoaldosteronism (PHA-1), a salt-wasting syndrome caused by decreased ENaC function. Transgenic mouse technologies provide a useful tool to study the role of ENaC in vivo. Different mouse lines have been established in which each of the ENaC subunits was affected. The phenotypes observed in these mice demonstrated that each subunit is essential for survival and for regulation of sodium transport in kidney and colon. Moreover, the alpha subunit plays a specific role in the control of fluid absorption in the airways at birth. Such mice can now be used to study the role of ENaC in various organs and can serve as models to understand the pathophysiology of these human diseases.
Article
Lung epithelial ion transport promotes salt and water movement across the fetal and neonatal lung epithelium. The mechanism is dependent on basolateral membrane Na-K-ATPase and the apical membrane Cl(-) and Na(+) channels. During fetal life active secretion of Cl(-) and parallel movement of Na(+) across the epithelium into the developing lung lumen induce accumulation of liquid into the future airspaces. Postnatally, however, absorption of fluid from the airspaces must start. Present evidence suggests that activation of Na(+) transport from the lumen into the basolateral direction drives fluid absorption and results in an essentially dry air-filled alveolus. In laboratory animals amiloride, a Na(+) channel blocker, induces respiratory distress and impedes lung fluid clearance. One of the epithelial amiloride-sensitive Na(+) channels, ENaC, is composed of three homologous subunits that differentially respond to glucocorticoid hormone. In newborn infants an increase in pulmonary fluid and a defective Na(+) transport associate with respiratory distress. The ontogeny, subunit composition and function of ENaC along the respiratory tract are currently under investigation. It will be interesting to find out whether the subunit composition and function of lung ENaC respond to the therapy of the critically ill newborn infant.
Article
WEQAS is one of the largest and the most rapidly expanding national EQA Schemes in the UK with over 500 participants. Since April 1995, the Scheme has distributed a tonometered protein-based aqueous material for blood gas analytes (H(+), pCO2, pO2), electrolytes, glucose and lactate. Current performance of the new generation of blood gas analysers show marked bias between analysers which a number of manufacturers have attributed to a "matrix" effect. This study was undertaken to investigate the "true" analytical performance of these analysers utilising a tonometered haemolysate blood product with oxygen saturation kinetics identical to that of fresh blood. One hundred laboratories that represented the major analyzers used in the UK were selected to participate in the study. Participants were asked to analyse the samples within 1 week of tonometry of the material. Performance data, expressed as interlaboratory variation, was compared with concentration matched data from the same group using the aqueous material. Significant improvement in instrument Bias was observed for the AVL Omni and iStat analysers for pO2). Surprisingly, there was also an improvement in bias for the electrolyte parameters on the IL synthesis. However, a significant positive bias was observed for the AVL Opti for Potassium and for the Nova analyzer for glucose using this material. Similar performance was observed for the co-oximetry, parametres for fresh and lyophilised material for the majority of analyzers.
Article
Active transepithelial transport of sodium from the airspaces to the lung interstitium is a primary mechanism driving alveolar fluid clearance. This mechanism depends on sodium uptake by amiloride-sensitive sodium channels on the apical membrane of alveolar type II cells followed by extrusion of sodium on the basolateral surface by the Na-K-ATPase. Injury to the alveolar epithelium can disrupt the integrity of the alveolar barrier or downregulate ion transport pathways thus reducing net alveolar fluid reabsorption, and enhancing the extent of alveolar edema. Endogenous catecholamines upregulate alveolar fluid clearance in several experimental models of acute lung injury, but this upregulation is short-term and often not sufficient to counterbalance alveolar flooding. There is new evidence, however, that pharmacological treatment with beta-adrenergic agonists and/or epithelial growth factors may induce a more sustained stimulation of alveolar fluid reabsorption and in turn facilitate recovery from experimental pulmonary edema. Similar results have been achieved experimentally by gene transfer enhancing the abundance of sodium transporters in the alveolar epithelium. Clinical studies show that impaired alveolar fluid transport mechanisms contribute to the development, severity and outcome of pulmonary edema in humans. Very recent data suggest that mechanisms that augment transepithelial sodium transport and enhance the clearance of alveolar edema may lead to more effective prevention or treatment for pulmonary edema and acute lung injury.
Article
The epithelial sodium channel (ENaC) in the apical membrane of polarized epithelial cells is the rate-limiting step for Na entry into the cell; in series with the basolateral Na pump, it allows the vectorial transepithelial transport of Na ions. ENaC is expressed in different epithelia like the distal nephron or colon, and the airways epithelium. In the lung ENaC controls the composition and the amount of pulmonary fluid, whereas in the distal nephron ENaC under the control of aldosterone and vasopressin, is essential to adapt the amount of Na+ reabsorbed with the daily sodium intake. Activating mutations of ENaC cause severe disturbances of Na+ homeostasis leading to hypertension in human and in mouse models. Functional expression of ENaC in different cell systems allowed the identification of structural domains of the protein that are essential for channel function and/or modulation of channel activity. Site-directed mutations in specific domains of the channel protein lead to channel hyperactivity or channel loss of function. Knowledge about ENaC structure-function relationships opens new opportunities for development of pharmacological tools for controlling ENaC activity, such as channel activators of potential benefit in the treatment of pulmonary edema, or highly potent ENaC blockers with natriuretic effects.
Article
A beta-adrenergic agonist (beta-agonist), terbutaline, stimulated amiloride-sensitive Na(+) absorption in fetal rat alveolar type II epithelium, contributing to the clearance of lung fluid. Cytosolic Ca(2+) plays an important role in terbutaline-stimulated Na(+) absorption, since Ca(2+)-activated, amiloride-sensitive Na(+)-permeable channels are involved in transcellular Na(+) absorption and terbutaline stably elevates the cytosolic Ca(2+) concentration by stimulating Ca(2+) influx. Therefore, we studied whether Ca(2+) channel blockers (Ni(2+), verapamil, and nifedipine) affect terbutaline-stimulated transcellular Na(+) absorption. Ni(2+) partially blocked the channel responsible for the terbutaline-stimulated Na(+) absorption at the Na(+) entry pathway across the apical membrane of the epithelium, but did not diminish the terbutaline-stimulated transcellular Na(+) absorption. By measuring the capacity of the Na(+),K(+)-pump activity, we determined that the rate-limiting step of the terbutaline-stimulated transcellular Na(+) absorption was the extrusion step across the basolateral membrane by the Na(+),K(+)-pump. The other Ca(2+) channel blockers, verapamil and nifedipine, had effects identical to those of Ni(2+). Based upon these observations, we conclude that, in the beta-agonist-stimulated fetal rat alveolar type II epithelium, Ca(2+) channel blockers diminish amiloride-sensitive channels, but do not affect transcellular Na(+) absorption, since under the beta-agonist-stimulated condition the Na(+),K(+)-pump is the rate-limiting step in Na(+) transport.
Article
The discovery of mechanisms that regulate salt and water transport by the alveolar and distal airway epithelium of the lung has generated new insights into the regulation of lung fluid balance under both normal and pathological conditions. There is convincing evidence that active sodium and chloride transporters are expressed in the distal lung epithelium and are responsible for the ability of the lung to remove alveolar fluid at the time of birth as well as in the mature lung when pathological conditions lead to the development of pulmonary edema. Currently, the best described molecular transporters are the epithelial sodium channel, the cystic fibrosis transmembrane conductance regulator, Na+-K+-ATPase, and several aquaporin water channels. Both catecholamine-dependent and -independent mechanisms can upregulate isosmolar fluid transport across the distal lung epithelium. Experimental and clinical studies have made it possible to examine the role of these transporters in the resolution of pulmonary edema.
Article
In patients with asthma, eosinophils are primed and massively infiltrate lung tissues and migrate across epithelia into airways. Using blocking monoclonal antibodies, we found that eosinophil transmigration across a lung epithelial cell monolayer depended on the functions of alphaMbeta2 integrin CD11b/CD18. To study the role of Ca2+ in eosinophil priming and transepithelial migration, we treated eosinophils with eotaxin or thapsigargin (TG), reagents that increase cytoplasmic free Ca2+ concentrations by receptor- or nonreceptor-mediated mechanisms, respectively. Pretreatment of eosinophils with TG enhanced CD11b/CD18-dependent transmigration across lung epithelium. Within minutes, TG time- and dose-dependently upregulated the expression of CD11b/CD18 but did not upregulate the expression of alphaL (CD11a) or beta1 (CD29) integrin. The upregulation of CD11b/CD18 expression by eotaxin or TG was prevented when Ca2+ entry was blocked. The priming of eosinophil transmigration by TG was also abrogated by the blockade of Ca2+ entry. Our results indicate that induction of Ca2+ entry by the depletion of Ca2+ from intracellular stores upregulates CD11b/CD18 expression on eosinophils and primes eosinophil transmigration across lung epithelium. Both responses are therefore elicited by extracellular Ca2+. We suggest that, as an important priming signal for human eosinophil functional responses, store-operated Ca2+ entry may be one of the underlying mechanisms of eosinophilic inflammation in asthma.
Article
To evaluate the survival rate and factors affecting the outcome of pediatric patients treated with high-frequency oscillatory ventilation (HFOV) for diffuse alveolar disease (DAD) compatible with acute respiratory distress syndrome (ARDS). A cohort study was conducted at the pediatric intensive care unit of Queen Siritkit National Institute of Child Health from 1st January 1999 to 31st December 2001. Children who suffered from DAD compatible with ARDS were enrolled. Inclusion criteria were PaO2/FiO2 < 200 and oxygenation index (OI) > 10. High-frequency oscillatory ventilator (3100A Sensor Medics Corp, Yorba Linda, Calif) was used applying high volume strategy of treatment. Patients were weaned to conventional ventilation (CV) once clinical improvement occurred. Demographic data, duration of CV mode before changing to HFOV, duration of HFOV, ventilator parameters and gas exchange variables from beginning and during the course of HFOV were recorded, so patient data could be compared between surviving and non-surviving groups. A total of 21 children were enrolled during the 3 year period. There were 4 patients with simultaneous air leak syndrome and a total of 10 male patients. The average age was 3.58 +/- 3.9 years. There were 11 surviving patients (52.4%). Data of ventilator parameters and gas exchange variables after changing to HFOV for 4-6 hours for the two groups, FiO2 was higher (0.99 +/- 0.32 vs 0.84 +/- 0.18; p = 0.02) and alveolar arterial oxygen gradient [P(A-a)O2] was lower (448.5 +/- 140.8 vs 562.7 +/- 99.9 mmHg; p = 0.047) in the surviving group than in the non-surviving group. Concerning mean airway pressure (Paw), oxygenation index (OI), P(A-a)O2 and PaO2/FiO2 at initiation and during the course of HFOV with comparison of the surviving and non-surviving groups: Paw and OI decreased in the surviving group and was significantly different at 36 and 24 hours respectively. P(A-a)O2 was statistically significantly lower at 6 hours after HFOV initiation in the surviving group. PaO2/FiO2 was statistically significantly increased at 24 hours in the surviving group. Implement of HFOV is useful in patients with DAD, ARDS and air leak syndrome from the initial phase of illness which fulfill criteria for decreasing ventilator induced lung injury and thus decrease the mortality rate from ARDS. Predisposing survival factor showing statistically significant differences was lower Paw during CV before changing to HFOV, lower Paw at 36 hours, lower OI at 24 hours, lower P(A-a)O2 at 6 hours and higher PaO2/FiO2 at 24 hours. These parameters are good indicators for the prognosis of ARDS for patients responding or not responding to HFOV.
Article
Cystic fibrosis (CF) is a lethal genetic disease caused by a mutation in a membrane protein, the cystic fibrosis transmembrane conductance regulator (CFTR), which mainly (but not exclusively) functions as a chloride channel. The main clinical symptoms are chronic obstructive lung disease, which is responsible for most of the morbidity and mortality associated with CF, and pancreatic insufficiency. About 1000 mutations of the gene coding for CFTR are currently known; the most common of these, present in the great majority of the patients (Delta508) results in the deletion of a phenylalanine at position 508. In this mutation, the aberrant CFTR is not transported to the membrane but degraded in the ubiquitin-proteasome pathway. The aim of this review is to give an overview of the pharmacologic strategies currently used in attempts to overcome the ion transport defect in CF. One strategy to develop pharmacologic treatment for CF is to inhibit the breakdown of DeltaF508-CFTR by interfering with the chaperones involved in the folding of CFTR. At least in in vitro systems, this can be accomplished by sodium phenylbutyrate, or S-nitrosoglutathione (GSNO), and also by genistein or benzo[c]quinolizinium compounds. It is also possible to stimulate CFTR or its mutated forms, when present in the plasma membrane, using xanthines, genistein, and various other compounds, such as benzamidizoles and benzoxazoles, benzo[c]quinolizinium compounds or phenantrolines. Experimental results are not always unambiguous, and adverse effects have been incompletely tested. Some clinical tests have been done on sodium phenyl butyrate, GSNO and genistein, mostly in respect to other diseases, and the results demonstrate that these drugs are reasonably well tolerated. Their efficiency in the treatment of CF has not yet been demonstrated, however. An alternative strategy is to compensate for the defective chloride transport by CFTR by stimulation of other chloride channels. This can be done via purinergic receptors. A phase I study using a stable uridine triphosphate analog has recently been completed. A second alternative strategy is to attempt to maintain hydration of the airway mucus by inhibiting Na(+) uptake by the epithelial Na(+) channel using amiloride or stable analogs of amiloride. Clinical tests so far have been inconclusive. A number of other suggestions are currently being explored. The minority of patients with CF who have a stop mutation may benefit from treatment with gentamicin. The difficulties in finding a pharmacologic treatment for CF may be due to the fact that CFTR has additional functions besides chloride transport, and interfering with CFTR biosynthesis or activation implies interference with central cellular processes, which may have undesirable adverse effects.
Article
In a recent review of the data for fluid strategies and ARDS, fluid restriction or diuretic use was graded as "reasonably justifiable by available scientific evidence" and as "strongly supported by expert critical care opinion". Until the ARDS Network trial is published, only general guidelines regarding fluid management with or without specific vascular filling pressures from a pulmonary artery catheter can be made. Ultimately, the rationale for restricting fluid is to reduce hydrostatic pressures as much as possible. It seems most reasonable to maintain the lowest PAOP in ARDS patients that still maintains adequate circulating blood volume, mean arterial perfusion pressures, and cardiac output to provide sufficient oxygen delivery. Other clinical variables such as central venous pressure, urinary output, acid-base status, and lactate, serum urea nitrogen, and serum creatinine levels may help in judging the adequacy of a patient's intravascular volume, especially if central vascular pressure measurements are not available. Measures to reduce total body water, including flood restriction and diuretic use, seem to be of some benefit. Vasopressor use is especially important when systemic perfusion pressures are inadequate to maintain organ blood flow but should not be used to create supranormal levels of oxygen delivery.
Article
In the experimental setting, repeated derecruitments of the lungs of ARDS models accentuate lung injury during mechanical ventilation, whereas open lung concept strategies can attenuate the injury. In the clinical setting, recruitment manuevers that use a continuous positive airway pressure of 40 cmH2O for 40 secs improve oxygenation in patients with early ARDS who do not have an impairment in the chest wall. High intermittent positive end-expiratory pressure (PEEP), intermitent sighs, or high-pressure controlled ventilation improves short-term oxygenation in ARDS patients. Both conventional and electrical impedance thoracictomography studies at the clinical setting indicate that high PEEP associated with low levels of pressure control ventilation recruit the collapsed portions of the ARDS lungs and that adequate PEEP levels are necessary to keep the ARDS lungs opened allowing a more homogenous ventilation. High PEEP/low tidal volume ventilation was seen to reduce inflammatory mediators in both bronchoalveolar lavage and plasma, compared to low PEEP/high tidal volume ventilation, after 36 hours of mechanical ventilation in ARDS patients. Recruitment maneuvers that used continuous positive airway pressure levels of 35-40 cmH2O for 40 secs, with PEEP set at 2 cmH2O above the lower inflection point of the pressure-volume curve, and tidal volume < 6 mL/kg were associated with a 28-day intensive care unit survival rate of 62%. This contrasted with a survival rate of only 29% with conventional ventilation (defined as the lowest PEEP for acceptable oxygenation without hemodynamic impairment with a tidal volume of 12 mL/kg), without recruitment manuevers (number needed to treat = 3; p < 0.001). In the near future, thoracic computed tomography associated with high-performance monitoring of regional ventilation may be used at the bedside to determine the optimal mechanical ventilation of the ARDS keeping an opened lung with a homogenous ventilation.
Article
Amiloride-sensitive sodium channels in the lung play an important role in lung fluid balance. Particularly in the alveoli, sodium transport is closely regulated to maintain an appropriate fluid layer on the surface of the alveoli. Alveolar type II cells appear to play an important role in this sodium transport, with the role of alveolar type I cells being less clear. In alveolar type II cells, there are a variety of different amiloride-sensitive, sodium-permeable channels. This significant diversity appears to play a role in both normal lung physiology and in pathological states. In many epithelial tissues, amiloride-sensitive epithelial sodium channels (ENaC) are formed from three subunit proteins, designated alpha-, beta-, and gamma-ENaC. At least part of the diversity of sodium-permeable channels in lung arises from the assembling of different combinations of these subunits to form channels with different biophysical properties and different mechanisms for regulation. This leads to epithelial tissue in the lung, which has enormous flexibility to alter the magnitude and regulation of salt and water transport. In this review, we discuss the biophysical properties and occurrence of these various channels and some of the mechanisms for their regulation.
Article
Numerous studies suggest setting positive end-expiratory pressure during conventional ventilation according to the static pressure-volume (P-V) curve, whereas data on how to adjust mean airway pressure (P(aw)) during high-frequency oscillatory ventilation (HFOV) are still scarce. The aims of the current study were to (1) examine the respiratory and hemodynamic effects of setting P(aw) during HFOV according to the static P-V curve, (2) assess the effect of increasing and decreasing P(aw) on slice volumes and aeration patterns at the lung apex and base using computed tomography, and (3) study the suitability of the P-V curve to set P(aw) by comparing computed tomography findings during HFOV with those obtained during recording of the static P-V curve at comparable pressures. Saline lung lavage was performed in seven adult pigs. P-V curves were obtained with computed tomography scanning at each volume step at the lung apex and base. The lower inflection point (Pflex) was determined, and HFOV was started with P(aw) set at Pflex. The pigs were provided five 1-h cycles of HFOV. P(aw), first set at Pflex, was increased to 1.5 times Pflex (termed 1.5 Pflex(inc)) and 2 Pflex and decreased thereafter to 1.5 times Pflex and Pflex (termed 1.5 Pflex(dec) and Pflex(dec)). Hourly measurements of respiratory and hemodynamic variables as well as computed tomography scans at the apex and base were made. High-frequency oscillatory ventilation at a P(aw) of 1.5 Pflex(inc) reestablished preinjury arterial oxygen tension values. Further increase in P(aw) did not change oxygenation, but it decreased oxygen delivery as a result of decreased cardiac output. No differences in respiratory or hemodynamic variables were observed when comparing HFOV at corresponding P(aw) during increasing and decreasing P(aw). Variation in total slice lung volume (TLVs) was far less than expected from the static P-V curve. Overdistended lung volume was constant and less than 3% of TLVs. TLVs values during HFOV at Pflex, 1.5 Pflex(inc), and 2 Pflex were significantly greater than TLVs values at corresponding tracheal pressures on the inflation limb of the static P-V curve and located near the deflation limb. In contrast, TLVs values during HFOV at decreasing P(aw) (i.e., 1.5 Pflex(dec) and Pflex(dec)) were not significantly greater than corresponding TLV on the deflation limb of the static P-V curves. The marked hysteresis observed during static P-V curve recordings was absent during HFOV. High-frequency oscillatory ventilation using P(aw) set according to a static P-V curve results in effective lung recruitment, and slice lung volumes during HFOV are equal to those from the deflation limb of the static P-V curve at equivalent pressures.
Article
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. 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. 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.
Article
Acute respiratory failure requiring mechanical ventilation continues to contribute to mortality and affect long-term functional outcomes in patients admitted to the pediatric intensive care unit (ICU). Studies in adults with acute respiratory distress syndrome (ARDS) far outnumber those conducted in the pediatric age group, and pediatric intensivists are left with the task of carefully selecting and critically appraising relevant adult data and extrapolating results to their domain of practice. The recent ARDSNet study reinforces the use of low tidal volumes. Administration of surfactant is safe, but once again its beneficial effect was not sustained in a randomized trial. Surfactant proteins A and D have been shown to be of prognostic value in cases of acute lung injury. The effect of inhaled nitric oxide (NO) in patients with ARDS can be enhanced by aggressive lung recruitment strategies such as can be achieved using high-frequency oscillatory ventilation (HFOV). A recent adult trial shows good response rates but no significant long-term outcome benefit from prone positioning in patients with ARDS. Routine scheduled assessments of readiness for weaning and extubation may be more important than specific weaning modes and weaning criteria for children. A recent meta-analysis suggests that prophylactic dexamethasone use may decrease postextubation stridor and possibly reduce the need for reintubation in selected patients. Outcome data in children requiring mechanical support is encouraging, especially for high-risk groups such as bone marrow transplant (BMT) recipients, and may guide ethically challenging decision-making for these patients. Mechanical ventilation strategies aiming for optimal alveolar recruitment with the judicious use of positive end-expiratory pressure (PEEP) and low tidal volumes will remain the mainstay for managing respiratory failure in children. Dexamethasone may prevent postextubation stridor. Prone positioning, surfactant therapy, HFOV, and inhaled NO are used sporadically and need to be evaluated for their effect on mortality and duration of ventilation.
Article
Acute lung injury remains a major cause of morbidity and mortality in paediatric intensive care units. Research over the past decade has altered our understanding of the pathophysiology of acute lung injury and the effects of mechanical ventilation on the lung. As a result, approaches to conventional mechanical ventilation of the injured lung are now largely centred around preservation of adequate gas exchange while protecting the lung from further ventilator-induced lung injury. Current techniques for accomplishing these goals include adjusting the ventilator based on the measurement and interpretation of pressure-volume curves, limitation of inspiratory tidal volumes, use of elevated levels of positive end-expiratory pressure, recruiting manoeuvres and prone positioning. The currently available data regarding the efficacy and appropriate use of these techniques are reviewed.
Biophysical properties of sodium channels in lung alveolar epithelial cells
  • Matalon