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PubMed1992

Mucus rheology and transport in neonatal respiratory distress syndrome and the effect of surfactant therapy.

BACKGROUND: Neonatal respiratory distress syndrome (RDS) is caused by a deficiency of pulmonary surfactant. Alveolar collapse and obstruction of conducting airways leads to mismatch of ventilation and perfusion and profound hypoxemia. We postulated that surfactant deficiency could alter the properties of respiratory mucus in such a way that it would be poorly cleared from airways and promote airway luminal obstruction and that these changes might be reversed by the exogenous administration of a synthetic surfactant preparation. METHODS: Respiratory mucus coating an endotracheal tube (ETT) or suction catheter was collected from 14 neonates (gestational age, 24 to 36 weeks; birth weight, 600 to 2,400 g) with RDS who required tracheal intubation and ventilation. Eight of these neonates received 5 ml/kg of an intratracheal artificial surfactant preparation (Exosurf), given between 2 and 10 h of age and six neonates received 5 ml/kg of air. Mucus viscoelasticity, hydration (percentage of solid composition of mucus), and mucociliary clearability (NFPTR) were measured for each specimen. RESULTS: The total volume of mucus collected from the surfactant-treated and control infants was similar, but mucus hydration was significantly less in babies with RDS who did not receive Exosurf (percentage of solid composition of mucus 18.7 vs 11.4; p = 0.013). Ciliary transportability was also less in the untreated babies (NFPTR 0.39 vs 0.86; p = 0.018) and this mucus was more rigid (increased viscoelasticity: log G* 1 rad/s 2.28 vs 1.50; p = 0.0001). CONCLUSIONS: These data suggest that airway obstruction in RDS may be due, in part, to abnormal mucus properties and impaired ciliary transport. Surfactant therapy appears to improve mucus clearability. Exogenously administered surfactant may also be beneficial for the treatment of other selected respiratory conditions associated with impaired mucus clearance.

Drug Combinations↗
PubMed2001

Efficacy of low tidal volume ventilation in patients with different clinical risk factors for acute lung injury and the acute respiratory distress syndrome.

In patients with acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), a recent ARDS Network randomized controlled trial demonstrated that a low tidal volume (VT) mechanical ventilation strategy (6 ml/kg) reduced mortality by 22% compared with traditional mechanical ventilation (12 ml/kg). In this study, we examined the relative efficacy of low VT mechanical ventilation among 902 patients with different clinical risk factors for ALI/ARDS who participated in ARDS Network randomized controlled trials. The clinical risk factor for ALI/ARDS was associated with substantial variation in mortality. The risk of death (before discharge home with unassisted breathing) was highest in patients with sepsis (43%); intermediate in subjects with pneumonia (36%), aspiration (37%), and other risk factors (35%); and lowest in those with trauma (11%) (p < 0.0001). Despite these differences in mortality, there was no evidence that the efficacy of the low VT strategy varied by clinical risk factor (p = 0.76, for interaction between ventilator group and risk factor). There was also no evidence of differential efficacy of low VT ventilation in the other study outcomes: proportion of patients achieving unassisted breathing (p = 0.59), ventilator-free days (p = 0.58), or development of nonpulmonary organ failure (p = 0.44). Controlling for demographic and clinical covariates did not appreciably affect these results. After reclassifying the clinical risk factors as pulmonary versus nonpulmonary predisposing conditions and infection-related versus non-infection-related conditions, there was still no evidence that the efficacy of low VT ventilation differed among clinical risk factor subgroups. In conclusion, we found no evidence that the efficacy of the low VT ventilation strategy differed among clinical risk factor subgroups for ALI/ARDS.

Adult↗
PubMed2026

Interventions with a significant mortality difference in acute respiratory distress syndrome: A systematic review and comparison with Guidelines.

INTRODUCTION: Acute respiratory distress syndrome (ARDS) has a high mortality rate. European Society of Intensive Care Medicine (ESICM) and American Thoracic Society (ATS) Guidelines are the worldwide reference for clinicians in management of ARDS. Mortality represents one of the most important outcomes in intensive care practice and randomized controlled trials (RCTs) the highest level of evidence. We compared Guidelines recommendations with RCT results to highlight differences and find potential new therapeutic opportunities. METHODS: We performed a systematic review of all RCTs reporting a statistically significant mortality difference in ARDS and a subsequent comparison with ESICM and ATS Guidelines recommendations. RESULTS: We identified 33 RCTs and 23 interventions with mortality difference in ARDS patients. Seven interventions relate to invasive ventilation strategies, two to noninvasive ventilation strategies, one to extracorporeal membrane oxygenation (ECMO), 12 to drugs and one to nutritional support. In 25/33 (76%) RCTs the intervention was associated with mortality reduction and in 8/33 with mortality increase (24%). Multicenter studies were 24/33 (73%) while blinding was adopted in 19/33 (58%) studies. Guidelines recommendations supported by RCTs with mortality impact include: the use of low tidal volume ventilation, prone positioning, venovenous ECMO, steroids and the avoidance of high frequency oscillatory ventilation. Eight of the interventions identified were not mentioned by Guidelines but demonstrated reduced mortality, and five further interventions demonstrated increased mortality. CONCLUSIONS: This systematic review highlights potential gaps between RCTs results and Guidelines that could be used to plan future research or highlight topics to be discussed in future Guidelines.

Humans↗
PubMed1981

The role of megakaryocytes and tissue mast cells in the respiratory distress syndrome of adults.

The pathological role of megakaryocytes has been studied during adult respiratory distress syndrome (ARD) in the formation of intraalveolar oedema, microthrombi and hyaline membranes. The giant cells of the bone marrow are also thought to be involved in the development of peribronchial, perivascular and interalveolar oedemas. Heparin produced by tissue mast cells appears to counteract the clotting disturbances and to promote fibrinolysis in the acute phase of ARD. Vasoactive substances liberated from mast cells enhance oedema formation. Heparin has an influence on the lipid metabolism of type II pneumocytes. During regeneration the stimulating effect of heparin on fibrosis becomes predominant in the connective tissue ground substance. No fundamental morphological difference was found between ARD and the infantile respiratory distress syndrome.

Heparin↗
PubMed1981

Treatment of postoperative respiratory distress syndrome.

We have studied 45 patients with postoperative adult respiratory distress syndrome (ARDS) who were treated by mechanical ventilation during the last four years. This period was divided into two periods, and the mortality and progress after treatment were analysed. The overall, mortality was 56%. In the first period this rate was as high as 76%, while in the second period this rate improved to 43%. This improvement in the second period was thought to have resulted from aggressive cardiorespiratory treatment and the diminution of infection. According to the course of ARDS after treatment, four types could be classified. Type 1 showed rapid improvement in respiratory function. Type 2 showed gradual improvement. Type 3 showed relapse of respiratory failure. Type 4 resisted mechanical ventilation. Patients of types 3 and 4 had extremely poor prognoses. Stricter management to avoid infection, specific treatment of multiple organ failure (which was seen frequently) seemed advantageous. High frequency positive pressure ventilation (HFPPV) may have some role in improving the respiratory function of the patients with ARDS.

Adult↗
PubMed2003

Continuous veno-venous hemofiltration may improve survival from acute respiratory distress syndrome after bone marrow transplantation or chemotherapy.

PURPOSE: Acute respiratory distress syndrome (ARDS) may result from immunologic activity triggered by irradiation and/or chemotherapy. Hemofiltration removes plasma water and soluble components below 25 kilodaltons. The authors hypothesized that early hemofiltration might attenuate the inflammatory component of ARDS, resulting in increased survival in immunocompromised children and young adults. METHODS: Ten children (6 bone marrow transplantation, 3 chemotherapy, 1 lymphoma/hemophagocytosis) with ARDS (Pao2/Fio2 94 +/- 37 torr) received early continuous veno-venous hemodiafiltration as adjunctive therapy for respiratory failure, regardless of renal function. Six children had normal urine output and initial serum creatinine (range 0.1-1.2 mg/dL); four had renal insufficiency (initial creatinine 1.7-2.4 mg/dL). Hemofiltration was instituted coincident with intubation. Respiratory failure was precipitated by Enterobacter sepsis in two patients and by Aspergillus in one. RESULTS: Hemodiafiltration was performed for 13 +/- 9 days. A high rate of clearance was achieved (52 +/- 17 mL/min/1.73 m2). Duration of mechanical ventilation was 14 +/- 9 days. Nine of the 10 children were successfully extubated; 8 survived. CONCLUSIONS: Early hemofiltration may improve survival from ARDS following bone marrow transplantation or chemotherapy. Possible mechanisms include strict fluid balance, immunomodulation through filtration of inflammatory constituents, and immunomodulation through intensive extracellular water exchange that delivers biochemicals to organs of metabolism as well as the hemofilter.

Adolescent↗
PubMed1984

Elevated concentrations of leukotriene D4 in pulmonary edema fluid of patients with the adult respiratory distress syndrome.

The possible contribution of metabolites of arachidonic acid to the increased permeability of the alveolar-capillary barrier in the adult respiratory distress syndrome was examined by quantifying the pulmonary edema fluid concentrations of lipoxygenase and cyclooxygenase products. The concentration of leukotriene D4 in pulmonary edema fluid of 10 patients with the adult respiratory distress syndrome (18.5 +/- 6.8 pmol/ml; mean +/- SD), assessed by specific radioimmunoassay after isolation of the mediator, was significantly higher (P less than 0.001) than that of five patients with cardiogenic pulmonary edema (4.4 +/- 1.1 pmol/ml). The concentrations of leukotrienes B4 and C4, prostaglandin E2, and thromboxane B2 in edema fluid were not significantly different in the adult respiratory distress syndrome patients than in the other subjects with pulmonary edema. The edema fluid concentration of leukotriene D4 correlated with the ratio of edema fluid to plasma concentrations of albumin (r = 0.64). Leukotriene D4 thus may contribute to the permeability defect which allows an accumulation of protein-rich alveolar fluid in the adult respiratory distress syndrome.

Adolescent↗
PubMed1975

[Membrane oxygenator for the treatment of respiratory distress syndrome (author's transl)].

This report deals with the extracorporeal oxygenation in the respiratory distress syndrome. Investigations were performed with a membrane oxygenator. If one considers the present results, one might suppose an extracorporeal oxygenation without pumping-system to be ineffective. There are many different complications. It is doubtful whether this method will ever be an effective and sufficient therapy in respiratory distress syndrome.

Animals↗
PubMed1986

The effects of prostaglandin E1 on the adult respiratory distress syndrome in septic primates.

The effects of prostaglandin E1 (PGE1) on the adult respiratory distress syndrome were studied in the septic primate (Macaca fascicularis). A 30-min infusion of Escherichia coli (1 X 10(10)/kg) resulted in severe septic shock and adult respiratory distress syndrome. Primates, if living, were killed 4 h after completion of the E. coli infusion. Three groups of primates were studied (n = 4 in each group). The control group (Group 1) received PGE1 at 100 ng/kg/min throughout the experiment. The septic group (Group 2) received a 30-min infusion of E. coli. The treatment group (Group 3) received a continuous PGE1 infusion (100 ng/kg/min) along with the E. coli infusion which was begun 30 min after the PGE1 infusion was started. Control primates had hemodynamic changes consistent with the vasodilatory effect of PGE1 (heart rate and cardiac output increased; blood pressure and systemic vascular resistance (SVR) decreased). All control animals survived the experiment and had no evidence of pulmonary damage. Primates given E. coli developed severe hypotension, decreased SVR, and lung injury evidenced by pulmonary edema, decreased oxygenation, and increased extravascular lung water. Primates treated with both PGE1 and E. coli developed similar cardiovascular and pulmonary changes as the septic group. There was no statistically significant difference between Group 2 and Group 3 animals with regard to mean arterial blood pressure, SVR, extravascular lung water, alveolar-arterial oxygen difference, or survival.(ABSTRACT TRUNCATED AT 250 WORDS)

Alprostadil↗
PubMed1992

Randomized European multicenter trial of surfactant replacement therapy for severe neonatal respiratory distress syndrome: single versus multiple doses of Curosurf.

There is now convincing evidence that the severity of neonatal respiratory distress syndrome can be reduced by surfactant replacement therapy; however, the optimal therapeutic regimen has not been defined. This randomized European multicenter trial was designed to determine whether the beneficial effects of a single large dose of Curosurf (200 mg/kg) in babies with severe respiratory distress syndrome (arterial to alveolar oxygen tension ratio approximately 0.10) could be enhanced by using multiple doses of surfactant. Preterm neonates (birth weight 700 to 2000 g) with severe respiratory distress syndrome requiring artificial ventilation with fraction of inspired oxygen greater than or equal to 0.6 were randomized into two groups at an age of 2 to 15 hours. Both groups received the usual dose of Curosurf (200 mg/kg) immediately after randomization. In neonates randomized to receive multiple-dose treatment, two additional doses of Curosurf (100 mg/kg each) were instilled into the airways (12 and 24 hours after the initial dose) provided that the patients still needed artificial ventilation with fraction of inspired oxygen greater than 0.21. In both groups (single dose: n = 176, multiple doses: n = 167) there was a rapid improvement in oxygenation as reflected by a threefold increase in arterial to alveolar oxygen tension ratio within 5 minutes after surfactant instillation (P less than .001), and peak inspiratory pressure and mean airway pressure could be reduced significantly during the first 6 hours after surfactant treatment. In addition, ventilatory requirement (peak inspiratory pressure, ventilatory efficiency index) was reduced in the multiple-dose group 2 to 4 days after randomization (P less than .05 to .01).(ABSTRACT TRUNCATED AT 250 WORDS)

Biological Products↗
PubMed1984

Association between ruptured membranes, tocolytic therapy, and respiratory distress syndrome.

Two hundred ninety-seven patients from the placebo group of the National Institutes of Health Collaborative Study on Antenatal Steroid Therapy for prevention of respiratory distress syndrome were selected for analysis to investigate a possible association between premature rupture of the membranes, tocolytic therapy, and respiratory distress syndrome. Both premature rupture of the membranes and tocolytic therapy with isoxsuprine were individually associated with a lowered incidence of respiratory distress syndrome. However, when present together, their protective effect was not additive and resulted in a higher incidence of respiratory distress syndrome. It is suggested that the use of tocolytic therapy with beta-adrenergic agents be restricted to patients with intact membranes.

Amniotic Fluid↗
PubMed1992

A 2-year follow up of babies enrolled in a European multicentre trial of porcine surfactant replacement for severe neonatal respiratory distress syndrome. Collaborative European Multicentre Study Group.

The postnatal growth, respiratory status and neurodevelopmental outcome of surviving babies enrolled in the first European multicentre trial of porcine surfactant (Curosurf) replacement for severe neonatal respiratory distress syndrome, were assessed at corrected ages of 1 and 2 years. Follow up rates of survivors were 93% at 1 year and 89% at 2 years. Treated and control groups were similar at both 1 and 2 years in terms of physical growth, the prevalence of persistent respiratory symptoms and the occurrence of major and minor disability. Serum antibodies recognising Curosurf and surfactant-anti-surfactant immune complexes were detected in both treated and control babies, the titres showing no difference between groups. Examination of histological lung sections from non-survivors revealed a higher incidence of severe pulmonary interstitial emphysema in control babies than in those treated with surfactant. Surfactant treatment for severe respiratory distress syndrome reduces neonatal mortality and air leaks and is not associated with an increase in disability 2 years later.

Antibodies↗
PubMed1990

Adult respiratory distress syndrome after limited resection of adenocarcinoma of the lung.

Two cases of the adult respiratory distress syndrome developed after limited resection for lung carcinoma. No other known precipitants were evident. The adult respiratory distress syndrome is a clinical expression of acute lung injury that may arise from various insults and include air and blood borne factors. Tumour related blood borne factors may have contributed to lung injury in these cases.

Adenocarcinoma↗
PubMed1987

Miliary tuberculosis and adult respiratory distress syndrome.

Although, miliary tuberculosis is an unusual cause of severe acute respiratory failure, we describe nine patients with miliary tuberculosis who developed adult respiratory distress syndrome. This complication occurred in seven patients despite treatment with antituberculous drugs. In two patients who developed the syndrome, miliary tuberculosis was diagnosed only at postmortem. The presence of pulmonary hypertension in all cases and disseminated intravascular coagulation in seven cases suggests a possible pathophysiologic relationship with severe pulmonary vascular damage. The high mortality rate (88.8%) was associated with nonpulmonary organ system failure. Miliary tuberculosis should be considered in patients with adult respiratory distress syndrome of unknown etiology, and simple diagnostic procedures such as sputum, bronchial brushing, and gastric examination should be followed by invasive diagnostic procedures to confirm this etiology. Since untreated miliary tuberculosis is usually fatal, early recognition of this disease is of great importance, and specific therapy may play a lifesaving role.

Adult↗
PubMed1984

Severe hypoxemia without evidence of tissue hypoxia in adult respiratory distress syndrome.

A patient with severe arterial hypoxemia in adult respiratory distress syndrome (ARDS) secondary to a fractured femur is reported. A marked discrepancy between the clinical condition and laboratory findings was observed. At one point, PaO2 was below 4 kPa (30 mm Hg) on F1O2 0.21 without signs of tissue hypoxia. This patient illustrates beneficial effects of a leftward shift of the oxyhemoglobin dissociation curve.

Adult↗