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PubMed1993

Respiratory distress syndrome in the newborn: innovative therapies.

Neonatal respiratory distress syndrome affects 60,000 to 70,000 infants each year in the United States. Although the mortality rate has decreased dramatically over the past 30 years, many infants die or have sequelae from the syndrome. Three innovative techniques are now playing a role in improving the course of neonates with respiratory distress syndrome: surfactant replacement therapy, high-frequency ventilation and extracorporeal membrane oxygenation. Surfactant therapy should be considered the standard of care for infants with respiratory distress syndrome who require mechanical ventilation. Further investigation is needed to define the precise roles of high-frequency ventilation and extracorporeal membrane oxygenation in the management of neonates with respiratory distress syndrome.

Extracorporeal Membrane Oxygenation↗
PubMed1998

Pharmacologic strategies in acute respiratory distress syndrome.

Treatment of the acute respiratory distress syndrome includes both supportive measures and correction of the underlying cause. Various pharmacological interventions have been proposed to limit the severity of lung injury and enhance the healing process, including exogenous surfactant, inhaled vasodilators (mainly nitric oxide), corticosteroids, prostaglandin E1, antioxidants (N-acetylcysteine), ketoconazole and other substances. Some of these interventions are administered via the airways, for example inhaled nitric oxide or liquid ventilation with perfluorocarbons. Some have beneficial effects on surrogate end-points such as pulmonary gas exchange. However, in large prospective trials none of these pharmacological approaches have resulted in significantly improved survival in acute respiratory distress syndrome patients.

Journal Article↗
PubMed1998

Cardiopulmonary effects of aerosolized prostaglandin E1 and nitric oxide inhalation in patients with acute respiratory distress syndrome.

Ten patients with acute respiratory distress syndrome (ARDS) received in random order nitric oxide (NO) inhalation, aerosolized prostaglandin E1 (PGE1), infusion of PGE1, or no intervention. Inhalation of either aerosolized PGE1 (10 +/- 1 ng/kg/min) or NO (7 +/- 1 ppm) reduced pulmonary vascular resistance (PVR) from 158 +/- 14 to 95 +/- 11 dyn . s/cm5/m2 (NO) and 100 +/- 12 dyn . s/cm5/m2 (aerosolized PGE1), and improved PaO2 from 78 +/- 3 to 96 +/- 5 mm Hg (NO) and 95 +/- 4 mm Hg (aerosolized PGE1) (p < 0.05), venous admixture (Q VA/Q T) from 45 +/- 2 to 36 +/- 2% (NO), and 36 +/- 2% (aerosolized PGE1) (p < 0.05), oxygen delivery (DO2) from 711 +/- 34 to 762 +/- 45 ml/min/m2 (NO) and 780 +/- 46 ml/min/m2 (aerosolized PGE1) (p < 0.05), and right ventricular ejection fraction (RVEF) from 32 +/- 6 to 37 +/- 5% (NO), and 36 +/- 4% (aerosolized PGE1) (p < 0.05) at a constant cardiac index (CI). Although infusion of PGE1 (12 +/- 1 ng/kg/min) caused a similar reduction in PVR as aerosolized PGE1 and NO inhalation, it improved RVEF and increased CI but decreased Q VA/Q T and PaO2. These results suggest that in ARDS patients inhalation of aerosolized PGE1 or NO in low concentrations equally improves PVR and gas exchange by selective vasodilation in ventilated areas.

Administration, Inhalation↗
PubMed2001

Effects of inverse ratio ventilation versus positive end-expiratory pressure on gas exchange and gastric intramucosal PCO(2) and pH under constant mean airway pressure in acute respiratory distress syndrome.

BACKGROUND: In patients with acute respiratory distress syndrome, whether inverse ratio ventilation differs from high positive end-expiratory pressure (PEEP) for gas exchange under a similar mean airway pressure has not been adequately examined. The authors used arterial oxygenation, gastric intramucosal partial pressure of carbon dioxide (PiCO(2)), and pH (pHi) to assess whether pressure-controlled inverse ratio ventilation (PC-IRV) offers more benefits than pressure-controlled ventilation (PCV) with PEEP. METHODS: Seventeen acute respiratory distress syndrome patients were enrolled and underwent mechanical ventilation with a PCV inspiratory-to-expiratory ratio of 1:2, followed by PC-IRV 1:1 initially. Then, they were randomly assigned to receive PC-IRV 2:1, then 4:1 or 4:1, and then 2:1, alternately. The baseline setting of PCV 1:2 was repeated between the settings of PC-IRV 2:1 and 4:1. Mean airway pressure and tidal volume were kept constant by adjusting the levels of peak inspiratory pressure and applied PEEP. In each ventilatory mode, hemodynamics, pulmonary mechanics, arterial and mixed venous blood gas analysis, PiCO(2), and pHi were measured after a 1-h period of stabilization. RESULTS: With a constant mean airway pressure, PC-IRV 2:1 and 4:1 decreased arterial and mixed venous oxygenation as compared with baseline PCV 1:2. Neither the global oxygenation indices with oxygen delivery and uptake nor PiCO(2) and pHi were improved by PC-IRV. During PC-IRV, applied PEEP was lower, and auto-PEEP was higher. CONCLUSION: When substituting inverse ratio ventilation for applied PEEP to keep mean airway pressure constant, PC-IRV does not contribute more to better gas exchange and gastric intramucosal PiCO(2) and pHi than does PCV 1:2 for acute respiratory distress syndrome patients, regardless of the inspiratory-to-expiratory ratios.

APACHE↗
PubMed1986

Incidence, site, and outcome of infections in patients with the adult respiratory distress syndrome.

Bacterial infection in the adult respiratory distress syndrome (ARDS) is associated with the occurrence of multiple organ failures and death. We studied 108 infections in 129 patients with ARDS and evaluated the organisms responsible, the body sites involved, and the outcomes of therapy. Gram-negative bacilli represented 57% of the microbial pathogens and gram-positive cocci 36%. Only 7% of infections were caused by other organisms (fungi, viruses, Pneumocystis, Legionella). Gram-negative organisms were more common in the lung, abdomen, and pleura. Bacteremia was more common in abdominal infections (11 of 17, 67%) than in infections at other sites (18 of 65, 28%), (p less than 0.01); ;9 patients were bacteremic from clinically undetected sites. Ten of 17 (59%) patients with abdominal infections survived compared with 7 of 56 (13%) patients with lung infections (p less than 0.001). A retrospective review of in vitro organism susceptibility and the antibiotics administered revealed that the patients who received adequate antibiotic therapy did not have a higher survival rate (20 of 69, 29%) than those who received inadequate antibiotic therapy (3 of 13, 23%). These data suggest that further investigation of infections in patients with ARDS is required and that emphasis should be placed on pathogenesis, prevention, and host responses.

Adult↗
PubMed1990

Perinatal factors associated with the respiratory distress syndrome.

Perinatal factors related to the incidence of respiratory distress syndrome were analyzed by the multiple logistic regression statistical method in 263 mothers and their 298 offspring delivered between 24 and 35 weeks' gestation in a 1-year period in a regional referral perinatal center. The risk of respiratory distress syndrome in white infants rose with decreasing gestational age (p less than 0.0001) while prolonged rupture of membranes of greater than 24 hours in the absence of maternal infection (28% of cases) was highly protective (p less than 0.0001). Compared with vaginal delivery, cesarean delivery without labor increased the risk of respiratory distress syndrome (p = 0.03). The administration of tocolytic drugs was unrelated to the incidence of respiratory distress syndrome, but corticosteroid therapy given at least 72 hours before delivery was protective (p = 0.03). Male and female infants were equally at risk for respiratory distress syndrome as were black and white infants, but other races had a lower incidence (p = 0.004). Infants with respiratory distress syndrome were on mechanical ventilators longer than those with other respiratory illnesses.

Adrenal Cortex Hormones↗
PubMed2005

Ventilatory management of acute lung injury and acute respiratory distress syndrome.

CONTEXT: The acute lung injury and acute respiratory distress syndrome are critical illnesses associated with significant morbidity and mortality. Mechanical ventilation is the cornerstone of supportive therapy. However, despite several important advances, the optimal strategy for ventilation and adjunctive therapies for patients with acute lung injury and acute respiratory distress syndrome is still evolving. EVIDENCE ACQUISITION: To identify reports of invasive ventilatory and adjunctive therapies in adult patients with acute lung injury and acute respiratory distress syndrome, we performed a systematic English-language literature search of MEDLINE (1966-2005) using the Medical Subject Heading respiratory distress syndrome, adult, and related text words, with emphasis on randomized controlled trials and meta-analyses. EMBASE and the Cochrane Central Register of Controlled Trials were similarly searched. The search yielded 1357 potential articles of which 53 were relevant to the study objectives and considered in this review. EVIDENCE SYNTHESIS: There is strong evidence to support the use of volume- and pressure-limited lung-protective ventilation in adult patients with acute lung injury and acute respiratory distress syndrome. The benefit of increased levels of positive end-expiratory pressure and recruitment maneuvers is uncertain and is being further evaluated in ongoing trials. Existing randomized controlled trials of alternative ventilation modes, such as high-frequency oscillation and adjunctive therapies, including inhaled nitric oxide and prone positioning demonstrate no significant survival advantage. However, they may have a role as rescue therapy for patients with acute respiratory distress syndrome with refractory life-threatening hypoxemia. CONCLUSIONS: Volume- and pressure-limited ventilation strategies should be used in managing adult acute lung injury and acute respiratory distress syndrome patients. Further research is needed to identify barriers to widespread adoption of this strategy, as well as the role of alternative ventilation modes and adjunctive therapies.

Humans↗
PubMed1998

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

BACKGROUND: In patients with the acute respiratory distress syndrome, massive alveolar collapse and cyclic lung reopening and overdistention during mechanical ventilation may perpetuate alveolar injury. We determined whether a ventilatory strategy designed to minimize such lung injuries could reduce not only pulmonary complications but also mortality at 28 days in patients with the acute respiratory distress syndrome. METHODS: We randomly assigned 53 patients with early acute respiratory distress syndrome (including 28 described previously), all of whom were receiving identical hemodynamic and general support, to conventional or protective mechanical ventilation. Conventional ventilation was based on the strategy of maintaining the lowest positive end-expiratory pressure (PEEP) for acceptable oxygenation, with a tidal volume of 12 ml per kilogram of body weight and normal arterial carbon dioxide levels (35 to 38 mm Hg). Protective ventilation involved end-expiratory pressures above the lower inflection point on the static pressure-volume curve, a tidal volume of less than 6 ml per kilogram, driving pressures of less than 20 cm of water above the PEEP value, permissive hypercapnia, and preferential use of pressure-limited ventilatory modes. RESULTS: After 28 days, 11 of 29 patients (38 percent) in the protective-ventilation group had died, as compared with 17 of 24 (71 percent) in the conventional-ventilation group (P<0.001). The rates of weaning from mechanical ventilation were 66 percent in the protective-ventilation group and 29 percent in the conventional-ventilation group (P=0.005): the rates of clinical barotrauma were 7 percent and 42 percent, respectively (P=0.02), despite the use of higher PEEP and mean airway pressures in the protective-ventilation group. The difference in survival to hospital discharge was not significant; 13 of 29 patients (45 percent) in the protective-ventilation group died in the hospital, as compared with 17 of 24 in the conventional-ventilation group (71 percent, P=0.37). CONCLUSIONS: As compared with conventional ventilation, the protective strategy was associated with improved survival at 28 days, a higher rate of weaning from mechanical ventilation, and a lower rate of barotrauma in patients with the acute respiratory distress syndrome. Protective ventilation was not associated with a higher rate of survival to hospital discharge.

Adult↗
PubMed1985

Long-term sequelae in children surviving adult respiratory distress syndrome.

Nine children surviving severe adult respiratory distress syndrome were studied 0.9 to 4.2 years after the acute illness. They had received artificial ventilation for a mean of 9.4 days, with an Fio2 greater than 0.5 during a mean time of 34 hours and maximal positive end expiratory pressure levels in the range of 8 to 20 cm H2O. Three children had recurrent respiratory symptoms (moderate exertional dyspnea and cough), and two had evidence of fibrosis on chest radiographs. All patients had abnormal lung function; the most prominent findings were ventilation inequalities, as judged by real-time moment ratio analysis of multibreath nitrogen washout curves (abnormal in eight of nine patients) and hypoxemia (seven of nine). Lung volumes were less abnormal; one patient had restrictive and two had obstructive disease. A significant correlation between intensive care measures (Fio2 greater than 0.5 in hours and peak inspiratory plateau pressure) and lung function abnormalities (moment ratio analysis and hypoxemia) was found. A possibly increased susceptibility of the pediatric age group to the primary insult or respiratory therapy of adult respiratory distress syndrome is suggested.

Adolescent↗
PubMed1993

Prediction of survival and mortality in patients with adult respiratory distress syndrome.

The adult or acute respiratory distress syndrome (ARDS) is an increased permeability pulmonary edema that occurs most often as a complication of bacterial sepsis, aspiration of gastric contents, or massive trauma. Clinically, the syndrome is recognized as acute respiratory failure with bilateral infiltrates on chest radiograph, a marked oxygenation defect, and normal or nearly normal cardiac function. Since its first comprehensive description > 25 yrs ago, the reported mortality rate of ARDS has remained high. Current series describe mortality rates in the range of 50% to 60%. The major cause of death in patients with ARDS seems to be bacterial sepsis and multiple organ dysfunction. Predictors of survival and mortality have been studied. Older patients (> or = 60 yrs) who develop bacterial sepsis and multiple organ dysfunction are at high risk to die. Younger patients who develop ARDS from trauma or other noninfectious causes have a better prognosis. Persistent metabolic acidosis on the first day of ARDS is a particularly poor prognostic sign.

Acidosis↗
PubMed1984

Air leak in neonatal respiratory distress syndrome.

A review of 9401 consecutive live births at the Mercy Maternity Hospital, Melbourne, was performed to determine the incidence of air leak in those with respiratory distress syndrome. Respiratory distress was detected in 552 (5.9%) infants and hyaline membrane disease was the most common cause occurring in 238 (2.5%) infants. Air leak developed in 22% of infants with respiratory distress, 8% had pulmonary interstitial emphysema alone, 14% had pneumomediastinum or pneumothorax and 7% had emphysema with pneumomediastinum or pneumothorax. Mortality increased from 12% in infants without air leak to 31% (p less than 0.001) in infants with air leak. Ninety-five per cent of air leak developed in infants with hyaline membrane, and these were smaller, less mature and sicker than those without air leak. Eighty-seven per cent of air leak developed in infants treated with assisted ventilation and was commoner with mechanical ventilators with a more rapid rise in inspiratory pressure.

Humans↗
PubMed2003

Enteral nutrition with eicosapentaenoic acid, gamma-linolenic acid, and antioxidants reduces alveolar inflammatory mediators and protein influx in patients with acute respiratory distress syndrome.

OBJECTIVE: Previously, we showed that acute respiratory distress syndrome patients fed an enteral diet containing eicosapentaenoic acid and gamma-linolenic acid and elevated antioxidants (EPA+GLA; Oxepa) had significantly reduced pulmonary inflammation, increased oxygenation, and improved clinical outcomes. In a subset of acute respiratory distress syndrome patients from this trial, we performed a preliminary examination of the potential mechanisms underlying these clinical improvements by retrospectively testing the hypothesis that enteral feeding with EPA+GLA could reduce alveolar-capillary membrane protein permeability and the production of interleukin (IL)-8, IL-6, tumor necrosis factor-alpha, and leukotriene B4 that are responsible, in part, for pulmonary inflammation. DESIGN: Prospective, randomized, double-blind, controlled clinical trial. SETTING: Intensive Care Unit of the Ohio State University Medical Center. PATIENTS: A total of 67 patients were enrolled who met defined criteria for acute lung injury/acute respiratory distress syndrome. INTERVENTIONS: A total of 43 of 67 evaluable patients randomly received either EPA+GLA or an isonitrogenous, isocaloric standard diet that was tube fed at a minimum caloric delivery of 75% of basal energy expenditure times 1.33 for at least 4 to 7 days. MEASUREMENTS AND MAIN RESULTS: Bronchoalveolar lavage (BAL) was performed at baseline and study days 4 and 7 to obtain BAL fluid (BALF) for measurement of total protein, ceruloplasmin, and transferrin, total neutrophil count, IL-8, IL-6, tumor necrosis factor-alpha, and leukotriene B4. Oxygenation, measured as Pao2/Fio2, was assessed before BAL. Patients fed EPA+GLA had a significant reduction in BALF ceruloplasmin and IL-8 during the study as compared with patients fed the control diet. BALF levels of total protein, neutrophils, and leukotriene B4 tended to decrease in EPA+GLA patients over the course of the study as compared with control patients. BALF levels of IL-6 declined similarly during the study in both groups. A trend toward a reduction in BALF tumor necrosis factor-alpha was observed on study day 7 in the EPA+GLA group as compared with control patients. Significant improvements in oxygenation (Pao2/Fio2) occurred in EPA+GLA patients on study day 4 as compared with controls. Correlation analysis revealed significant relationships between BALF neutrophil counts and indices of alveolar-capillary membrane protein permeability, IL-8, and leukotriene B4. CONCLUSIONS: This preliminary investigation showing a decrease in BALF levels of IL-8 and leukotriene B4 and the associated reduction of BALF neutrophils and alveolar membrane protein permeability in acute respiratory distress syndrome patients fed EPA+GLA support, in part, the potential mechanisms underlying the previously described clinical improvements with this diet. Additional controlled studies are needed to confirm these findings.

Antioxidants↗
PubMed2006

Long-term outcome of acute respiratory distress syndrome caused by severe acute respiratory syndrome (SARS): an observational study.

OBJECTIVE: We examined long-term outcome of pulmonary function, exercise capacity and health-related quality of life (HRQoL) in patients with acute respiratory distress syndrome (ARDS) caused by severe acute respiratory syndrome (SARS). METHODS: 59 critically ill patients with ARDS caused by SARS between March and July 2003 were studied prospectively and followed up for 1 year. Thirty-six underwent pulmonary function testing and a 6-minute walk test, and 35 underwent HRQoL evaluation by Short Form-36 questionnaire at 3, 6, and 12 months after illness onset. RESULTS: Mean age was 47 (SD, 15.7) years. Median APACHE II score was 10 (interquartile range [IQR], 7-12). Only 47% required invasive mechanical ventilation. Median admission and worst PaO2/FIO2 ratio were 142 (IQR, 94-177) mmHg and 86 (IQR, 66-122) mmHg, respectively. Median stay in ICU and hospital were 9 (IQR, 5-20) and 31 (IQR, 20-54) days, respectively. Mortality was 24% at hospital discharge and at 1 year. Mean lung volumes and spirometric measurements were nearly normal by 6 months. Except for diffusion capacity adjusted for haemoglobin concentration (DLCO) measured at 12 months, there was no significant difference in pulmonary function measurement between those who had mechanical ventilation and those who did not. The 6-minute walk distance (6MWD) improved from 3 to 6 months, with no further significant change. Younger patients had near normal HRQoL by 6 months. Those aged over 40 years had impaired HRQoL at multiple domains even at 12 months. At 12 months, forced expiratory volume in 1 second, forced vital capacity and 6MWD correlated significantly with multiple SF-36 domain scores. DLCO correlated significantly only with domain scores reflecting physical function. CONCLUSIONS: The mortality of SARS-related ARDS is similar to the mortality of ARDS from other causes. A substantial number of patients with SARS-related ARDS survived without receiving mechanical ventilation. Patients had good recovery of pulmonary function and HRQoL.

Adult↗
PubMed1992

Adult respiratory distress syndrome: a review for the clinician.

Adult respiratory distress syndrome is a common respiratory problem with a wide array of precipitating causes and an overall mortality rate of more than 50%. Signs on physical examination tend to be nonspecific as do laboratory findings associated with the syndrome. Because of its diverse etiology, there is no one specific treatment for adult respiratory distress syndrome. Therapy is primarily supportive and centers around the use of mechanical ventilator support. The authors discuss the pathogenesis and management of this syndrome together with some of the newer approaches to mechanical ventilation.

Adrenal Cortex Hormones↗
PubMed2004

Late-stage adult respiratory distress syndrome caused by severe acute respiratory syndrome: abnormal findings at thin-section CT.

PURPOSE: To evaluate thin-section computed tomographic (CT) abnormalities in patients in the intensive care unit during the late stage of adult respiratory distress syndrome (ARDS) caused by severe acute respiratory syndrome (SARS). MATERIALS AND METHODS: Eight patients in the late stage of ARDS (ie, more than 2 weeks after onset) were imaged with thin-section CT. Images were evaluated for ground-glass opacification, consolidation, interstitial thickening, evidence of fibrosis, and any other abnormalities. Patient records were reviewed, and relevant respiratory and ventilatory parameters, total steroid dose, and outcome were recorded. RESULTS: All patients received high-dose pulse methylprednisolone (minimum, 2.5 g total), and all patients who received ventilation received low-pressure, low-volume ventilation. Five patients received prolonged mechanical ventilation (for more than 14 days), one received ventilation for 72 hours, and two patients did not receive ventilation. Three patients died, four were discharged from the hospital, and one continued to require ventilation. Ground-glass opacification and interstitial thickening were present at CT in all eight patients. Consolidation was present in six patients. Three patients had evidence of fibrosis. Patients who received long-term ventilation, those who received short-term ventilation, and those who did not receive ventilation had similar pulmonary changes at CT. Pulmonary cysts, most of which were small (<1 cm), were present in five patients. Cysts were present in one patient who received only short-term low-pressure and low-volume ventilation and in one patient who received no mechanical ventilation. CONCLUSION: The CT features of late-stage ARDS caused by SARS are similar to those seen in late-stage ARDS of other causes, with no apparent differences between patients who do and patients who do not receive prolonged mechanical ventilation. The presence of cysts in one patient who received short-term and one patient who received no mechanical ventilation suggests that severe SARS-induced ARDS may independently result in cyst formation.

Adult↗
PubMed1986

An index to predict outcome in adult respiratory distress syndrome.

Thirty patients with adult respiratory distress syndrome required intermittent positive pressure ventilation; 15 survived. In 25 the syndrome followed bacterial infection or multiple injuries. From the peak upper airway pressure, the oxygen gradient and the age of the patient, an index was obtained which discriminated between the survivors and those who died from the pulmonary lesion of the syndrome.

Humans↗
PubMed1977

[Prevention and therapy of respiratory distress syndrome in premature infants by means of bromhexine metabolite VIII. Animal experimental studies on the therapeutic efficacy of bromhexine metabolite VIII in premature respiratory distress syndrome].

In preparing a clinical study 14C-labelled bromhexine metabolite VIII was applied intraamnially in animal experiments. The distribution was measured in different maternal and fetal organs by thinlayer chromatography and autoradiography. A complete placental passage was found in both directions. An organspecific accumulation in the fetal lungs could not be demonstrated.

Ambroxol↗
PubMed2000

Acute respiratory distress syndrome in adults.

The acute respiratory distress syndrome (ARDS) can arise from a range of predisposing insults. Mortality rates are high for patients with ARDS and survivors require extended and expensive intensive care treatment. This article presents evidence that implicates the production of toxic and damaging reactive oxygen species in the pathogenesis of ARDS.

Adult↗