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[The effect of a nitroglycerin infusion on the hemodynamics, extravascular lung water and gas exchange in patients with adult respiratory distress syndrome].

Nine patients with adult respiratory distress syndrome, stage III, secondary to diffuse peritonitis have been examined. The patients were subject to pulmonary artery and aorta catheterization. Cardiac output, extravascular water in the lungs, the extent of pulmonary shunting were determined; pulmonary artery and aortic pressure were measured. O2 transport parameters, pulmonary capillary pressure (Pc), pressure gradient (Pc-COP) were calculated and arterial and venous blood gases as well as colloid-osmotic pressure (COP) were analysed. Selective hypotension in the pulmonary circulation was performed using an infusion of nitroglycerin solution. Despite differences in the response of patients with ARDS to nitroglycerin, when the drug was injected with optimal positive end-expiratory pressure, it promoted an increase in O2 delivery, normalization of pulmonary hemodynamics and a decrease in extravascular pulmonary water.

Extravascular Lung Water↗

Changing trends in the management of respiratory distress syndrome (RDS).

The management of respiratory distress syndrome (RDS) has advanced because of improvements in mechanical ventilators, promotion of antenatal steroids, availability of surfactant and overall advancements in neonatal intensive care. Intermittent mandatory ventilation still forms the mainstay of assisted ventilation. Newer modes of ventilation have not delivered the results as promised. Because of the continued high incidence of bronchopulmonary dysplasia, there is a renewed interest in non-invasive modes of ventilation like CPAP and nasal IPPV. The present trend is to follow gentle ventilatory strategies accepting higher arterial carbon dioxide and lower oxygen. The role of antenatal steroids has been established beyond doubt but still they fall short of universal acceptance. Surfactant replacement therapy is the standard of care for RDS but beyond the reach of majority in India. Postnatal steroids are out of vogue because of probable links with cerebral palsy and abnormal neurological outcomes.

Bronchopulmonary Dysplasia↗

Upper airway reflexes in newborns with respiratory distress syndrome.

In 16 newborns with respiratory distress syndrome (RDS) not artificially ventilated, oesophageal pressure was recorded with an electromanometer and the reactions to mechanical stimulation of the upper airways by means of a nylon fibre were investigated. The results were compared with the values obtained in 16 newborns without cardiorespiratory disturbances. The reactions were evoked by mechanical stimulation of the airways. Mechanical stimulation of the nasal mucosa produced expulsive reactions only in 45% of cases in newborns with RDS as compared with 95% in healthy newborns (p less than 0.001). Stimulation of the oropharyngeal and laryngeal regions elicited expulsive reactions in 48% of cases in newborns with RDS, but 74% in healthy newborns (p less than 0.001). In other cases, inhibition of breathing or apnoea was the most common reaction. The expulsive component of responses such as sneezing, expiratory reaction and crying was weaker in newborns with RDS than in control infants. The inspiratory component of sneezing and coughing, on the contrary, was stronger in newborns with RDS. These results indicate that active elimination of irritants from the airways is reduced in newborns with RDS.

Apnea↗

Prognosis for infants with idiopathic respiratory distress syndrome.

Infants with the idiopathic respiratory distress syndrome admitted to the intensive care unit during January 1972 to September 1974 were reviewed. The overall mortality rate for infants whose birth weight was 1000 g or more was under 10%, and for those who established spontaneous respiration after birth it was less than 5%. The hyperoxia test was not a useful guide to prognosis. It was possible on the basis of the infants' ability to establish spontaneous ventilation after birth to divide them into two groups. In those who established adequate ventilation the mortality rate was 4-5%; in those who did not it was 57%. This test should be generally applied, since not only does it give an immediate guide to the severity of the disease, which is better than that provided by birth weight, gestational age, or the hyperoxia test, but it may be applied to infants born in and outside a hospital providing neonatal intensive care. Improvement in the outlook for infants with a bad prognosis will be achieved only by improvements in perinatal care designed to minimize severe intrapartum asphyxia in infants of low birth weight.

Birth Weight↗

New therapies for acute respiratory distress syndrome (ARDS):--a review.

Acute respiratory distress syndrome (ARDS) has been associated with high mortality. Improved understanding of the pathophysiology, recognition of precipitating events and improved management has decreased the mortality over the years. Mechanical ventilation is still the corner stone of the management of the disease. It is well recognised that high tidal volumes and airway pressures increase the morbidity, hence the need to use alternative modes of ventilation like pressure control with or without inverse ratio ventilation. Extracorporeal membrane oxygenation is still experimental and not easily available, whereas prone position to improve oxygenation is simple and inexpensive. The concept of pathological oxygen dependency and therapy aimed at supranormal values has failed to improve survival. Restricting the fluids to prevent further oedema formation in an already wet lung has improved the survival rate. Nitric oxide and surfactant have failed to produce desirable effect in large studies. Pharmacological support to inhibit inflammation with non steroidal anti-inflammatory drugs, antifungal agents, prostaglandin and corticosteroids have all failed. Interestingly corticosteroid rescue treatment in the late phase of ARDS has shown promise. Antiendotoxin and anticytokine studies which began with much enthusiasm is yet to produce desirable results.

Acute Disease↗

[Clinical impact of recruitment maneuvers in patients with acute respiratory distress syndrome].

In patients with acute respiratory distress syndrome (ARDS), recruitment maneuvers have been proposed as an adjunct to mechanical ventilation to open up atelectasis and to keep these alveoli open by the application of adequate high levels of positive end-expiratory pressure (PEEP). Though several studies reported that the responsiveness to recruitment maneuvers resulted in a marked improvement of oxygenation with a concomitant decrease in airway pressure and/or inspiratory fraction of oxygen, the performance of recruitment maneuvers still remains a matter of dispute, especially in patients ventilated with a lung protective ventilation strategy. In this review we discuss the pathophysiological background, factors affecting the responsiveness to recruitment maneuvers and their clinical impact in the light of recently published studies. Successful recruitment depends on several factors like the applied recruitment pressure, the level of PEEP set before and after the recruitment maneuver, the stage and the underlying disease of the ARDS, chest wall mechanics and the transpulmonary pressure as well as the positioning of the patient. Regarding the current literature, recruitment maneuvers may be considered as a rescue therapy in the early stage of severe hypoxemic lung failure, if a lung protective ventilation strategy and other additive adjuncts like prone positioning or the application of inhaled vasodilators failed to induce adequate gas exchange.

Acute Disease↗

[The protease inhibitor potential in newborns with respiratory distress syndrome].

In 70 newborns with respiratory distress syndrome (RDS) and in roughly the same number of eutrophic mature newborns the total antiplasmin, progressive antithrombin and alpha 2-macroglobulin was determined, the latter in an enzymatical as well as immunochemical way. In healthy mature newborns the progressive antithrombin was somewhat below the level of adults, alpha 2-macroglobulin was above it in both methods and total antiplasmin within it. All parameters of protease inhibitory capacity were significantly lowered in newborns with RDS. Smaller values could be found in patients with bleedings and in those who died later on. Even in those patients with a birth weight under 2,000 g there was a tendency to lower values which can only be partially due to the specificity of development of inhibitors. Progressive antithrombin, total antiplasmin and alpha 2-macroglobulin determined enzymatically are correlated in newborns with RDS jointly and with numerous other parameters of the coagulation system. These relations point to the fact that all components are included in the same consumption process, viz. in the process of disseminated intravascular coagulation. Alpha 2-macroglobulin values determined immunochemically do not correlate with coagulation parameters determined enzymatically as well as with other parameters. They lay partially above or below those determined enzymatically. This behaviour can only be explained by a partial enzyme complex binding of alpha 2-macroglobulin in newborns with RDS.

Antithrombins↗

High cord blood IL-10 levels in preterm newborns with respiratory distress syndrome.

BACKGROUND: The development of respiratory distress syndrome (RDS) is closely related to fetal immaturity, although the participation of inflammatory mechanisms also seems to be likely. We previously reported high interleukin-10 (IL-10) levels in cord blood from preterm infants. In the present study, we investigate the possible role of IL-10 and IL-12 in preterm newborns with RDS, a disease that is also closely related to gestational age. PATIENTS AND METHODS: Cord blood levels of IL-10 and IL-12 (p70 + p40) were determined by ELISA in 20 preterm infants who later developed RDS, in 21 preterm infants without RDS and in 31 full term newborns. In 11 patients follow-up samples could be also obtained between 2 and 14 days of life. RESULTS: Preterm infants with RDS showed higher IL-10 (27 vs 10.8 pg/mL; p: 0.0003) and lower IL-12 (188 vs 384; p: 0.002) levels in cord blood than premature infants without RDS and full term newborns (IL-10: 3.2 pg/mL, p: 0.0001; IL-12: 352 pg/mL; p: 0.002). The differences remained statistically significant after correction for the effect of gestational age between both preterm groups. CONCLUSIONS: The results obtained may be related to an immature cytokine response in premature infants, but the IL-12/IL-10 imbalance found in our patients also supports the hypothesis that inflammation plays a role in RDS.

Biomarkers↗

Oxygen delivery and consumption and ventricular preload are greater in survivors than in nonsurvivors of the adult respiratory distress syndrome.

In patients with adult respiratory distress syndrome (ARDS), oxygen consumption (VO2) is pathologically dependent on oxygen delivery (DO2). Because of alterations in ventricular function, DO2 may be inadequate to satisfy oxygen demand and may contribute to multiple-system organ failure (MSOF). To determine whether there are differences in DO2, VO2, ventricular function, and MSOF, between survivors and nonsurvivors of ARDS, we studied 29 patients without cardiac disease early in the course of ARDS (hypoxemia, diffuse bilateral pulmonary infiltrates, and pulmonary artery occlusion pressure less than 18 mm Hg). Simultaneous hemodynamic, radionuclide cineangiographic, and oxygen transport measurements were made within 24 h of onset of ARDS. Thirteen survivors had greater DO2 and VO2 than did 16 nonsurvivors (p = 0.004 and 0.001, respectively). MSOF developed in no survivors and in 63% of nonsurvivors. In four survivors and in six nonsurvivors in whom DO2 was changed acutely, VO2 was dependent on DO2 (p = 0.014). Survivors had greater stroke volume index and right and left ventricular end-diastolic volume indices than did nonsurvivors despite similar right atrial and pulmonary artery occlusion pressures. There were no differences between survivors and nonsurvivors in biventricular ejection fractions. We conclude that survivors of ARDS have greater DO2 and VO2 than do nonsurvivors. Survival may be explained by the strong inverse relation between DO2 and development of MSOF.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Integrated stimulation by CXC chemokines enhances PMN [Ca2+]i signaling in trauma and adult respiratory distress syndrome.

BACKGROUND: Trauma and adult respiratory distress syndrome (ARDS) are associated with increased CXC chemokine (CXC) activity. CXCs such as interleukin (IL)-8 activate polymorphonuclear neutrophils (PMNs) in the lung by means of calcium signals ([Ca2+]i). We studied CXC effects on PMN [Ca2+]i in ARDS and trauma. METHODS: Isolated PMNs were loaded with Fura-2 dye. Normal PMNs were incubated in ARDS plasma or volunteer plasma, with or without blocking antibodies to IL-8, growth-related oncogene alpha (GRO-alpha), or both (n = 6 pairs), and then stimulated with 1 to 10 nmol/L IL-8. PMNs from trauma patients or volunteers (n = 10 pairs) were stimulated with GRO-alpha, or with sequential GRO-alpha/IL-8. [Ca2+]i was measured with spectrofluorometry. RESULTS: [Ca2+]i responses to IL-8 were higher after being incubated in ARDS plasma than in volunteer plasma (251 +/- 33 vs 218 +/- 33 nmol/L, P = .03). Blockade of GRO-alpha or IL-8 reversed ARDS plasma effects. After GRO-alpha/IL-8, PMNs from trauma patients demonstrated more Ca2+ store release than did PMNs from volunteers (235 +/- 13 vs 170 +/- 10 nmol/L, P < .01). Conversely, PMNs from trauma patients lost receptor-operated Ca2+ influex to GRO-alpha. CONCLUSIONS: In traumatic ARDS, plasma CXCs prime PMNs for higher [Ca2+]i flux, making PMN activation more likely. IL-8 and GRO-alpha interact to modulate these PMN [Ca2+]i responses.

Adult↗

A retrospective analysis of the effect of antenatal steroid administration on the incidence of respiratory distress syndrome in preterm twin pregnancies.

Respiratory distress syndrome (RDS) is the major cause of morbidity and mortality in preterm twin deliveries. Therapy with corticosteroids has been shown to reduce the incidence of RDS in preterm singleton gestations but similar reductions in twin pregnancies have not been demonstrated. Maternal and neonatal medical records were reviewed from twins delivered between 24 to 34 weeks gestation over the period of January 1, 1990 to December 31, 1994. Twenty-one pairs of twins received optimal steroid treatment defined as the use of two 12 mg doses of betamethasone, with birth occurring between 24 hours and 7 days after the first dose. Sixty-three pairs received no treatment. The mean gestational age at delivery was 29.9 +/- 2.6 weeks. No decrease was seen in the incidence of RDS (optimal steroid 70.7% versus no treatment 68.0%, unadjusted odds ratio [OR] 1.14, 95% confidence interval [CI] 0.49 to 2.65). Multivariate logistic regression showed no statistical difference in the incidence of RDS in the optimal steroid compared to the no treatment group (adjusted OR 0.63, 95% CI 0.2 to 1.95). No statistical differences were noted in the incidence of mechanical ventilation (58.6% versus 55.4%, p = 0.83), median duration of intubation (5.0 versus 5.0 days, p = 0.47), the median maximum inspiratory pressure requirements (20.0 versus 22.0 mm Hg; p = 0.15) in the optimal treatment versus no treatment group, respectively. The current regimen of antenatal corticosteroids utilized in twin pregnancies does not reduce the incidence of RDS.

Betamethasone↗

Acute respiratory distress syndrome: 30 years later.

Acute respiratory distress syndrome (ARDS) was first described about 30 years ago. Modern definitions and statements have recently been proposed to describe ARDS accurately, but none is perfect. Diffuse alveolar damage is the basic pathological pattern most commonly observed in ARDS, and the term includes permeability edema. The alveolar epithelium of the alveolar-capillary barrier is clearly a key component requiring repair, given its multipotent functional activity. Lung inflammation and neutrophil accumulation are essential markers of disease in ARDS, and a wide variety of pro- and anti-inflammatory cytokines have been described in the alveolar fluid and blood of patients. These molecules still have to prove their value as diagnostic or prognostic biomarkers of ARDS. Supportive therapy in ARDS improved in the past decade; mechanical ventilation with lung protective strategies and patient positioning are gaining interest, but the indications for corticosteroids for ARDS are still debated. Nitric oxide may have a place in the treatment of one-third of patients. Novel approaches, such as surfactant replacement and liquid ventilation, may further improve supportive therapy. Innovative interventions may be on the horizon in treatments that help to resolve or modulate common pathways of ARDS, such as inflammation (eg, granulocyte-colony stimulating factor) or epithelial repair (eg, keratinocyte growth factor).

Adrenal Cortex Hormones↗

High concentrations of plasminogen activator inhibitor-1 in lungs of preterm infants with respiratory distress syndrome.

BACKGROUND: Among preterm infants, respiratory distress syndrome (RDS) is characterized by the presence of intraalveolar fibrin deposition. Fibrin monomers inhibit surfactant function effectively. However, little is known about potential disturbances of intraalveolar fibrinolysis in RDS. We studied levels of major plasminogen activator inhibitor-1 (PAI-1), tissue-type plasminogen activator (tPA), and urokinase-type plasminogen activator (uPA) in lungs of preterm infants with RDS. METHODS: The antigen levels of PAI-1, tPA, and uPA were measured in 262 samples of tracheal aspirate fluid collected from 37 intubated preterm infants during the first 2 postnatal weeks. To examine the expression of PAI-1, tPA, and uPA in lung tissue, immunohistochemical analyses were performed on autopsy specimens from 7 preterm infants with RDS and 6 newborn infants without pulmonary pathologic conditions. RESULTS: For infants with an immature surfactant profile, as indicated by lecithin/sphingomyelin ratios in tracheal aspirate fluid of < 10, PAI-1 levels and ratios of PAI-1 to uPA and tPA were significantly higher during postnatal days 1 to 2, compared with infants with lecithin/sphingomyelin ratios of > or = 10. Moreover, infants who subsequently developed bronchopulmonary dysplasia (BPD) (n = 15) had higher PAI-1 levels on days 3 to 4 and days 7 to 8 than did those who survived without BPD. For preterm infants with RDS, immunohistochemical analyses demonstrated increased expression of PAI-1, tPA, and uPA predominantly in alveolar epithelium. CONCLUSIONS: High concentrations of PAI-1 and an increased ratio of PAI-1 to uPA, with a concurrently less-increased ratio of PAI-1 to tPA, are associated with the severity of RDS among preterm infants during the first postnatal days. Pulmonary inhibition of fibrinolysis is a pathophysiologic feature of RDS and may play a role in the development of BPD.

Enzyme-Linked Immunosorbent Assay↗

[Gas exchange in acute respiratory distress syndrome].

The hypoxemia of acute respiratory distress syndrome (ARDS) depends chiefly upon shunt and ventilation-perfusion (VA/Q) inequality produced by fluid located in the interstitial space, alveolar collapse and flooding. Variables other tham inspired oxygen fraction and the underlying physiological abnormality can influence arterial oxygen partial pressure (PaO2). Changes in cardiac output, hemoglobin concentration, oxygen consumption and alcalosis can cause changes in PaO2 through their influence on mixed venous PO2. Gas exchange (GE) in ARDS may be studied using the inert gas elimination technique (MIGET) which enables to define the distribution of ventilation and perfusion without necessarily altering the FIO2 differentiating shunt from lung units with low VA/Q ratios and dead space from lung units with high VA/Q ratios. Different ventilatory strategies that increase mean airway pressure (positive end-expiratory pressure, high tidal volumes, inverse inspiratory-expiratory ratio, etc) improve PaO2 through increasing lung volume by recruiting new open alveoli and spreading the intra-alveolar fluid over a large surface area. Also prone-position ventilation would result in a marked improvement in GE enhancing dorsal lung ventilation by the effects on the gravitional distribution of pleural pressure and the reduction in the positive pleural pressure that develops in dorsal regions in ARDS. Inhaled nitric oxide (NO) has been shown to increase PaO2 in ARDS patients by inducing vasodilation predominantly in ventilated areas redistributing pulmonary blood flow away from nonventilated toward ventilated areas of the lung thus resulting in a shunt reduction. On the same way inhaled prostaglandins (PGI2 or PGE1) causes selective pulmonary vasodilation improving pulmonary GE. Intravenous almitrine, a selective pulmonary vasoconstrictor, has been shown to increase PaO2 by increasing hypoxic pulmonary vasoconstriction. A synergistic effect was found between inhaled NO and almitrine. In spite of the improval of GE shown by these different techniques on ARDS, no effect was demonstrated on mortality or duration of mechanical ventilation.

Acute Disease↗

Surfactant protein (SP) B associations and interactions with SP-A in white and black subjects with respiratory distress syndrome.

BACKGROUND: The etiology of respiratory distress syndrome (RDS) is multifactorial and/or multigenic. Surfactant protein A (SP-A) and/or SP-B genetic variants have been identified as risk or protection factors for RDS. METHODS: We genotyped subjects with and without RDS for the SP-B intron 4 size variants (invariant (inv), deletion (del), insertion (ins) and for four (-18 (A/C), 1013 (A/C), 1580 (C/T), 9306 (A/G)) SP-B single nucleotide polymorphisms (SNP), to study case-control associations in black and white subjects. We also determined whether specific SP-B variants interact with RDS susceptibility or protective SP-A variants to enhance or reduce risk for RDS. RESULTS: Based on odds ratio: (1) the SP-B intron 4 del variant in white subjects is more of an RDS risk factor for males and for subjects of 28 weeks <gestational age (GA)<33 weeks; (2) the SP-B intron 4 ins variant in black subjects is more of an RDS risk factor in females; (3) in white subjects, SP-A1 (6A(2)/6A(2)) or SP-A2 (1A(0)/1A(0) or 1A(0)/*) genotypes in subjects of certain GA and with a specific SP-B genotype (9306 (A/G) or del/*) are associated with an enhanced risk for RDS; (4) in black subjects, SP-A1 (6A3/6A(3) or 6A(3)/*) genotypes in subjects of 31 weeks < or = GA < or = 35 weeks and with the SP-B (1580 (T/T)) genotype are associated with a reduced risk for RDS. CONCLUSIONS: The SP-B polymorphisms are important determinants for RDS. These may identify differences between black and white subjects, as well as, between males and females regarding the risk for RDS. Furthermore, SP-A susceptibility or protective alleles, in specific SP-B background, are associated, based on OR, with an increased or reduced risk for RDS.

Alleles↗

Functional residual capacity and severity of respiratory distress syndrome in infants.

Infants with respiratory distress syndrome (RDS) have insufficient surfactant systems and decreased functional residual capacity (FRC). This study attempts to relate FRC with severity of disease course. Measurements were made on 36 newborn infants with clinically diagnosed RDS. All infants were intubated and breathing on continuous positive airway pressure (CPAP) at the time studied. Infant CPAP levels were adjusted to 10 cm H2O; then FRC and arterial blood gas measurements were made. The infants were grouped according to their FRC per birth weight (BW). Volumes larger than or equal to 2 SD (larger than or equal to 42 ml/kg) of normal term infants not on CPAP were placed in the "large FRC" group. Volumes within +/- 2 SD (15-41 ml/kg) were in the "medium FRC: group, and infants smaller than or equal to 2 SD (< 14 ml/kg) of normal were in the "small FRC" group. The severity of RDS disease course was judged by the time duration the infants were managed on CPAP and FIO2 > 0.21 and by the maximum CPAP and FIO2 levels used. Twelve infants (33%) had small FRC, 18 (50%) medium FRC, and 6 (17%) large FRC. The time duration the infants with large FRC were on CPAP was significantly less than infants with medium FRC and the medium FRC group time was less than the small FRC group. The time duration on increased FIO2 and maximum FIO2 level used on the large FRC group was less than the medium and small FRC groups. Thus, FRC/BW appears related to the severity of RDS disease course. It is possible that the infants with FRC/BW larger than or equal to 42 ml/kg had pneumonia and were misdiagnosed as RDS. If so, FRC monitoring could have assisted in their diagnosis. BW and gestational ages of the groups were not different. Thus, variables other than these two play an important role in the degree of atelectasis occurring in infants with RDS. In patient management, where frequent changes in airway pressure and FIO2 are made, knowing the FRC/BW as well as blood gas values could aid the clinician in his choice of CPAP and FIO2 levels.

Birth Weight↗

The regulation of interleukin-8 by hypoxia in human macrophages--a potential role in the pathogenesis of the acute respiratory distress syndrome (ARDS).

BACKGROUND: The acute respiratory distress syndrome (ARDS) represents a form of severe acute inflammatory lung disease. We have previously demonstrated significantly raised interleukin-8 (IL-8) levels in the lungs of at-risk patients that progress to ARDS, and identified the alveolar macrophage as an important source of this chemokine. We wished to extend this study in a well-defined group of patients with major trauma, and to investigate potential mechanisms for rapid intrapulmonary IL-8 generation. MATERIALS AND METHODS: Patients with major trauma underwent bronchoalveolar lavage (BAL) and IL-8 levels were measured in BAL fluid by ELISA. Human macrophages were derived from peripheral blood monocytes from healthy volunteers. Rabbit alveolar macrophages were obtained from ex-vivo lavage of healthy rabbit lungs. Macrophages were culture under normoxic or hypoxic (PO2 26 mmHg) conditions. IL-8 and other proinflammatory mediator expression was measured by ELISA, northern blotting or multi-probe RNase protection assay. RESULTS: In patients with major trauma, IL-8 levels were significantly higher in patients that progressed to ARDS compared to those that did not (n = 56, P = 0.0001). High IL-8 levels negatively correlated with PaO2/FiO2 (r = -0.56, P < 0.001). In human monocyte derived macrophages hypoxia rapidly upregulated IL-8 protein (within 2 hours) and mRNA expression (within 30 mins). Acute hypoxia also increased rabbit alveolar macrophage IL-8 expression. Hypoxia increased DNA binding activity of AP-1 and C/EBP but not NF-kappaB. Hypoxia induced HIF-1 expression, but cobaltous ions and desferrioxamine did not mimic hypoxic IL-8 induction. Hypoxia downregulated a range of other proinflammatory mediators, including MCP-1 and TNF-alpha. Both the pattern of cytokine expression and transcription factor activation by hypoxia was different to that seen with endotoxin. CONCLUSIONS: Rapidly raised intrapulmonary IL-8 levels are associated with ARDS progression in patients with major trauma. Acute hypoxia, a clinically relevant stimulus, rapidly and selectively upregulates IL-8 in macrophages associated with a novel pattern of transcription factor activation. Acute hypoxia may represent one of potentially several proinflammatory stimuli responsible for rapid intrapulmonary IL-8 generation in patients at-risk of ARDS.

Adolescent↗

Ventilation with lower tidal volumes versus traditional tidal volumes in adults for acute lung injury and acute respiratory distress syndrome.

BACKGROUND: Patients with acute respiratory distress syndrome (ARDS) and acute lung injury (ALI) require mechanical ventilatory support. ALI/ARDS is further complicated by ventilator-induced lung injury. Lung-protective ventilation strategies may lead to improved survival. OBJECTIVES: To assess the effects of ventilation with lower tidal volume (Vt) on morbidity and mortality in adults patients affected by ALI/ARDS. A secondary objective was to determine whether the comparison between low and conventional Vt is different if a plateau airway pressure of greater than 30 to 35 cm H20 was used. SEARCH STRATEGY: We searched The Cochrane Central Register of Controlled Trials (CENTRAL), The Cochrane Library issue 3, 2002; MEDLINE (1966 to June 2002); EMBASE and CINAHL (1982 to June 2002); intensive care journals and conference proceedings; databases of ongoing research, reference lists and 'grey literature'. SELECTION CRITERIA: Randomized trials comparing ventilation using lower Vt and/or low airway driving pressure (plateau pressure 30 cm H2O or less), resulting in Vt of 7 ml/kg or less versus ventilation that uses Vt in the range of 10 to 15 ml/kg, in adults (16 year-old or greater). DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and extracted data. Wherever appropriate, results were pooled. Fixed and random effects models were applied. MAIN RESULTS: Five trials, involving 1202 patients, were eligible. The test for heterogeneity gave a P-value of 0.12. Ventilation with lower Vt was associated with a decreased mortality at the end of the follow up period for each trial: 216/605 (35.7%) versus 249/597 (41.7%), relative risk (RR) 0.85 (CI 0.74 to 0.98). The effect of the intervention was not statistically significant when a random effects model was used: RR 0.91 (CI 0.72 to 1.14). Mortality at day 28 was significantly reduced by lung-protective ventilation: RR 0.74 (CI 0.61 to 0.88). The comparison between low and conventional Vt was not significantly different if a plateau pressure less than or equal to 31 cm H2O in control group was used: RR 1.13 (CI 0.88 to 1.45). There was insufficient evidence about morbidity and long term outcomes. REVIEWER'S CONCLUSIONS: Clinical heterogeneity, such as different lengths of follow up and higher plateau pressure in control arms in two trials make the interpretation of the combined results difficult. Mortality is significantly reduced at day 28 and the effects on long term mortality are uncertain, although the possibility of a clinically relevant benefit cannot be excluded. There is no evidence that low Vt ventilation is beneficial in patients where hypercapnia is potentially harmful.

Adult↗