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This article reviews pharmacologic approaches to treating acute respiratory distress syndrome (ARDS). The authors discuss the therapeutic effects of ketoconazole, antioxidants, corticosteroids, surfactant, ketanserin, pentoxifylline, bronchodilators, and almitrine in ARDS. Current animal data and proposed mechanics which may foster future pharmacologic therapies are also examined.
In 17 patients with adult respiratory distress syndrome, we used data derived from computed tomographic (CT) scan densitometric analysis to validate the value of portable chest roentgenograms in objectively estimating the amount of pulmonary edema. Chest roentgenograms and CT scans were taken in the same ventilatory conditions (apnea at 10 cm H2O of positive end-expiratory pressure [PEEP]); blood gas samples and hemodynamic parameters were collected at the same time. Roentgenographic analysis was undertaken by independent observers using two standardized scoring systems proposed in the literature. CT scan analysis was performed using the CT number frequency distribution and the gas lung volume (measured by helium dilution technique) to estimate quantitatively the lung density, the lung weight, and the percentage of normally aerated and nonaerated tissue. Knowing the mean CT number of the pulmonary parenchyma in a group of normal subjects, we also inferred the ideal lung weight expected in the study population and computed the excess tissue mass as the difference between actual and ideal lung weight. Both the roentgenographic scoring systems showed direct correlation with the pulmonary impairment as detected by CT scan densitometric analysis (CT number, percentage of nonaerated tissue, lung weight, and excess tissue mass; p less than 0.01) and inverse relation with the percentage of normally aerated tissue (p less than 0.01). We also found a relationship between roentgenographic scores and the impairment in gas exchange as detected by shunt fraction (p less than 0.05). We conclude that standardized reading of portable chest roentgenograms by means of scoring tables is a valuable tool in estimating the amount of pulmonary edema in a patient with adult respiratory distress syndrome.
Adult respiratory distress syndrome (ARDS) was described in 1971 by Petty and Ashbaugh. Since that time it has been reported in association with many disease entities. We report a case in which a patient with postanginal sepsis, also known as Lemierre's syndrome, had development of ARDS.
Depletion of plasma fibronectin has been observed in certain clinical conditions predisposing to the adult respiratory distress syndrome and has been associated with cardiopulmonary dysfunction in experimental lung injury. We evaluated prospectively the relationship between plasma fibronectin concentration and the development of the adult respiratory distress syndrome in patients known to be at high risk. Although plasma fibronectin levels in participants at study entry were lower in this population (mean 258 +/- 132 micrograms/ml) than in normal volunteers (461 +/- 127 micrograms/ml, p less than 0.0025), there was no difference between patients who subsequently developed the adult distress syndrome (mean 255 +/- 149 micrograms/ml) and those with similar illness or injury who did not develop the syndrome (260 +/- 126 micrograms/ml). Fibronectin concentration was not further depressed even after development of adult respiratory distress syndrome and did not correlate with degree of pulmonary dysfunction. These data suggest that fibronectin depletion is not an important determinant of respiratory failure in humans. Patients with sepsis syndrome had significantly lower plasma fibronectin levels than those without sepsis (187 +/- 119 micrograms/ml vs. 273 +/- 131 micrograms/ml, p less than 0.05), suggesting a possible role for fibronectin in the pathogenesis of sepsis.
The acute respiratory distress syndrome (ARDS) has been recognized for more than three decades as a cause of respiratory failure in patients with a variety of illnesses. Clinically, it is characterized by pulmonary edema, refractory hypoxemia, diffuse pulmonary infiltrates, and altered lung compliance. Pathologically, it is distinguished by infiltration of the lungs with inflammatory cells, interstitial and alveolar edema, hyaline membrane formation, and ultimately fibrosis. Although we have learned much about the pathophysiology of this inflammatory syndrome since its earliest descriptions, ARDS continues to claim the lives of 40%-70% of its victims. Many treatment strategies have been used to prevent or treat ARDS, but thus far the most encouraging strategy to prevent lung injury and improve survival is mechanical ventilation with low tidal volumes and high levels of positive end-expiratory pressure.
Acute lung injury in the form of the acute respiratory distress syndrome (ARDS) continues to carry a high mortality. Recently, inhaled nitric oxide (NO) has been used in ARDS patients with severe hypoxaemia. We present a retrospective analysis concerning 33 ARDS patients treated with inhaled NO during a period of four years from 1994 to 1998. Patients were young, mean 43 years, had poor oxygenation (PaO2/FiO2 index 67 mmHG) and a lung injury score above 2.5. Eighty-two percent responded immediately to NO, 9% at a later challenge and 9% were non-responders. Mortality for the whole group was 67% and to be expected considering the severity of disease. For the group of patients with ARDS as a complication of pneumonia mortality was only 40%. In one patient therapy had to be stopped due to formation of NO2 even at very low concentrations of inhaled NO. We conclude that inhaled NO is effective in improving oxygenation in patients with ARDS. The study does not allow us to conclude anything about mortality, which was probably unchanged by this novel therapy.
A prospective study of 99 premature infants with severe respiratory distress syndrome who were randomly assigned to receive diuretic treatment with either furosemide or chlorothiazide was analyzed to examine the relationship of diuretic administration and diuresis to survival and to the duration and degree of mechanical ventilatory support. Subjects were given a diuretic, usually beginning on the second or third day of life, if they had not initiated the expected spontaneous diuresis and did not show pulmonary improvement. Infants given furosemide experienced a postnatal weight loss nearly identical to that in infants who were deemed not to need a diuretic; infants given chlorothiazide lost weight more slowly and had significantly greater body weight on postnatal days 4 and 5. Four factors were independently correlated with improved survival: furosemide usage, high birth weight, low initial mean airway pressure, and the absence of intraventricular hemorrhage. Ventilator mean airway pressure on the seventh day of life and duration of mechanical ventilation were both related to diuresis. These data provide additional evidence for the importance of water homeostasis in determining the course of respiratory distress syndrome in premature infants and indicate that furosemide administration is beneficial when spontaneous diuresis does not occur. Furosemide may be particularly effective if combined with early closure of the ductus arteriosus.
We assessed pulmonary mechanics in 35 premature infants with respiratory distress syndrome just before and one hour after the administration of 90 mg of surfactant to each infant. Transpulmonary pressure was measured between the airway opening and an esophageal balloon with use of a differential transducer, and flow rates were measured by a pneumotachometer. Values for pulmonary mechanics were then calculated by microcomputer processing. The administration of surfactant produced a large decrease (56 percent) in the mean (+/- SEM) ratio of alveolar to arterial oxygen, from 7.1 +/- 0.5 to 3.1 +/- 0.2 (P less than 0.0001)--a change that indicates improvement in gas exchange. Associated changes in pulmonary mechanics were not demonstrable when 10 of the infants were studied during continuous mechanical ventilation. However, in the 25 infants examined during spontaneous breathing with continuous positive airway pressures (identical airway pressures before and after treatment), large and consistent improvements in pulmonary mechanics were found after the administration of surfactant. Tidal volume increased by 32 percent (P less than 0.03), minute ventilation by 38 percent (P less than 0.02), dynamic compliance by 29 percent (P less than 0.004), and inspiratory flow rates by 54 percent (P less than 0.01). We conclude that significant improvement in pulmonary mechanics results from surfactant-replacement therapy for respiratory distress syndrome, but that these mechanical changes are apparent only during spontaneous respiration and can be masked if measurements are made during mechanical ventilation.
Acute respiratory distress syndrome (ARDS) in the thoracic surgery patient is a dreaded complication that occurs in 4% to 5% of pneumonectomies. This peculiar syndrome is indistinct from other forms of ARDS yet is associated with an exceedingly higher mortality rate. Current management parallels ARDS treatment of other etiologies.
STUDY DESIGN: A case of acute respiratory distress syndrome following percutaneous vertebroplasty is described. OBJECTIVE: To alert clinicians to the potential occurrence of acute respiratory distress syndrome following use of polymethylmethacrylate bone cement. SUMMARY OF BACKGROUND DATA: Noncardiogenic pulmonary edema has not been reported following intravertebral injection of polymethylmethacrylate. METHODS: A 68-year-old woman underwent percutaneous vertebroplasty for a painful L5 compression fracture under local anesthesia. A contralateral transpedicular approach was made to inject polymethylmethacrylate. RESULTS: On the third postoperative day, she developed arthralgia, myalgia, fever, and frequent coughing. Chest radiography revealed bilateral, multifocal, patchy consolidations, suggestive of acute respiratory distress syndrome, and a 5-cm-long tubular radiopacity in the right pulmonary artery. She died 20 days after the vertebroplasty. CONCLUSION: This case illustrates that clinicians must be aware of the potential occurrence of acute respiratory distress syndrome in patients who received percutaneous vertebroplasty.
Abnormalities of pulmonary function occur following the adult respiratory distress syndrome (ARDS). To determine if open lung biopsy (OLB) during ARDS predicts late pulmonary function abnormalities, we examined nine survivors of ARDS who had OLB during ARDS. Open lung biopsy was performed within two weeks of the diagnosis of ARDS, and the following were scored by a pulmonary pathologist as to extent and severity: hyaline membranes (HM), interstitial fibrosis (IF), air space organization (AO), interstitial cellularity (IC), and type 2 cell proliferation (T2C). Pulmonary function tests performed at least one year after ARDS were also used for analysis. Percent predicted Dco, TLC, DL/VA, and FVC were regressed against extent, severity, and combined scores. No significant correlation was found despite impressive histologic abnormalities. These data suggest that the severity and extent of HM, IF, AO, T2C, or IC do not correlate with lung function following ARDS.
In the acute respiratory distress syndrome (ARDS), lower lobes appear essentially non-aerated in contrast to upper lobes whose aeration can be preserved in some patients. The aim of this study was to assess the mechanical compression exerted by the heart on lower lobes in patients with ARDS. Fourteen healthy volunteers and 38 patients with ARDS free of left ventricular failure were studied. Cardiorespiratory parameters were recorded and the cardiac dimensions, the pressure exerted by the heart on subjacent lower lobes, and the gas tissue ratio of lower lobes in the supine position were measured using computer tomography and Lungview, a specifically designed software. In patients with ARDS, the heart was larger and heavier than in healthy volunteers. The enlargement of the heart was mainly related to a left cardiac protrusion and the pressure exerted by the left heart on the lower lobes was higher in patients with ARDS than in healthy volunteers (8 +/- 3 g. cm(-)(2) versus 6 +/- 1 g. cm(-)(2), p < 0.01). As a consequence, the faction of gas represented 62% of the left lower lobes in healthy volunteers and 12% only in patients with ARDS. The present study demonstrates that apart from the already known anteroposterior and cephalocaudal gradients of pressure depending on the lung weight and abdominal pressure, the heart plays an important role in the dramatic loss of aeration characterizing lower lobes of patients with ARDS lying in the supine position.
This study examines the growth and development of 37 preterm infants, 20 with respiratory distress syndrome and 17 with bronchopulmonary dysplasia. The groups were balanced by sex, parity, family configuration, and socioeconomic status and were studied at either 12 or 18 months after hospital discharge. Findings indicate that infants with bronchopulmonary dysplasia are at greater risk for growth retardation in their second year than infants with respiratory distress syndrome. Furthermore, results from cognitive, sensorimotor, and language measures (the Bayley, Uzgiris-Hunt, and Receptive-Expressive Emergent Language scales) demonstrate that infants with bronchopulmonary dysplasia perform significantly less well than infants with respiratory distress syndrome. The group performance of the infants with respiratory distress syndrome suggests that their developmental scores are comparable to those of average, healthy full-term infants of the same age. In contrast, the group of infants with bronchopulmonary dysplasia performed in the low-average to delayed range. Moreover, regression analyses show that type of respiratory illness explains more of the variance in cognitive outcomes than such neonatal factors as birth weight or gestational age. Thus, this study demonstrates that infants with bronchopulmonary dysplasia are at high risk for developmental problems in their second year, and that the contribution of bronchopulmonary dysplasia to explanations of differential cognitive outcomes cannot be reduced to between-group differences in perinatal status.
Prolonged hypoxemic respiratory failure and evidence of lung organization and fibrosis are features of an ARDS subgroup that is variably identified as "late," "persistent," or "fibroproliferative" ARDS. Early reports suggested that patients with late ARDS had a high mortality unless treated with corticosteroids. A large recent study with improved methodology has demonstrated that despite improvements of pulmonary physiology, corticosteroids do not change mortality of patients who continue to meet ARDS criteria 7 to 28 days after onset of acute lung injury. Additionally, there is no compelling evidence that persistent ARDS confers a higher mortality than that of ALI/ARDS. Observational and interventional studies are needed to increase understanding of the incidence, best management, and outcomes of patients with persistent ARDS.
Continuous positive airways pressure treatment by a face chamber in idiopathic respiratory distress syndrome. During a 3-year period 45 infants with idiopathic respiratory distress syndrome (IRDS) requiring ventilatory support were treated in the neonatal unit. Continuous positive airways pressure (CPAP) via the face chamber was applied as initial therapy in 39 infants and during weaning from initial intermittent positive pressure ventilation (IPPV) treatment in 5 infants, whereas 1 infant received IPPV only. Among the 39 infants initially treated with CPAP 9 required IPPV as well. The overall survival rate was 37/45 or 82%. Incapacity to hyperoxygenate while breathing 100% oxygen was the indication for CPAP while occurrence of apnoeic attacks was the indication for IPPV. Pao2 during the hyperoxia test before ventilatory support was less than 50 mmHg in 10 infants and between 50 and 105 mmHg in 35 infants. Surviving infants were followed up with neurological and developmental control examinations as well as chest x-ray, and in several infants pulmonary function tests. 3/37 infants had moderate neurological sequelae and only 1/37 infants developed bronchopulmonary dysplasia. No deleterious effects of the face chamber were seen. As the face chamber is a noninvasive and easily applied technique for CPAP therapy without hazards, it is proposed that it should be used at a still earlier stage of IRDS in order to lesson the need for IPPV treatment and to increase the neurological and lung functional quality of survival.
OBJECTIVES: To review the physiologic approach to setting mechanical ventilation in acute lung injury/acute respiratory distress syndrome. DATA SOURCES: MEDLINE search from 1979 to the present. DATA SELECTION: Personal selection of some articles we believe relevant for understanding acute lung injury/acute respiratory distress syndrome physiopathology and its physiologic management. DATA SUMMARY: Knowing the underlying pathology is key to estimating the potential for recruitment. The potential for recruitment is rather low when the consolidation of pulmonary units exceeds collapse, as in diffuse pneumonia. In contrast, when pulmonary unit collapse exceeds consolidation, as in acute lung injury/acute respiratory distress syndrome from extrapulmonary origin, the potential for recruitment may be high. To exploit the potential for recruitment, a transpulmonary pressure greater than the opening pressure must be applied to the lung. To do so, chest wall elastance must be measured or estimated. To avoid collapse after recruitment, a positive end-expiratory pressure greater than the compressive forces operating on the lung and an alveolar ventilation sufficient to prevent absorption atelectasis must be provided. Indeed, avoidance of stretch (low airway plateau pressure) and prevention of cyclic collapse and reopening (adequate positive end-expiratory pressure and alveolar ventilation) are the physiologic cornerstones of mechanical ventilation in acute lung injury/acute respiratory distress syndrome. When considering all the randomized clinical trials reported so far, it is tempting to speculate that transpulmonary pressure and stresses, rather than tidal volume per se, are the key factors that may have an impact on mortality. CONCLUSIONS: The majority of physiologic, experimental, and clinical trial data converge on one simple concept: treat the lung gently.
CONTEXT: Severe acute respiratory syndrome (SARS) is an emerging infectious disease with a 25% incidence of progression to acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) and mortality exceeding 10%. OBJECTIVE: To describe the clinical spectrum and outcomes of ALI/ARDS in patients with SARS-related critical illness. DESIGN, SETTING, AND PATIENTS: Retrospective case series of adult patients with probable SARS admitted to the intensive care unit (ICU) of a hospital in Singapore between March 6 and June 6, 2003. MAIN OUTCOME MEASURES: The primary outcome measure was 28-day mortality after symptom onset. RESULTS: Of 199 patients hospitalized with SARS, 46 (23%) were admitted to the ICU, including 45 who fulfilled criteria for ALI/ARDS. Mortality at 28 days for the entire cohort was 20 (10.1%) of 199 and for ICU patients was 17 (37%) of 46. Intensive care unit mortality at 13 weeks was 24 (52.2%) of 46. Nineteen of 24 ICU deaths occurred late (> or =7 days after ICU admission) and were attributed to complications related to severe ARDS, multiorgan failure, thromboembolic complications, or septicemic shock. ARDS was characterized by ease of derecruitment of alveoli and paucity of airway secretion, bronchospasm, or dynamic hyperinflation. Lower Acute Physiology and Chronic Health Evaluation II scores and higher baseline ratios of PaO2 to fraction of inspired oxygen were associated with earlier recovery. CONCLUSIONS: Critically ill patients with SARS and ALI/ARDS had characteristic clinical findings, high rates of complications; and high mortality. These findings may provide useful information for optimizing supportive care for SARS-related critical illness.
BACKGROUND: Acute respiratory failure in both pediatric and adult patient populations has been extensively studied with recent emphasis on ventilation strategies that can effect mortality outcome. This research in adults has focused on definitive trials of lung protective strategies that have been proposed following preliminary reports of their potential benefits. High frequency oscillatory ventilation has also been described as a lung protective strategy. For many institutions HFOV is today considered a routine therapy as a "rescue" method in acute pediatric respiratory failure. Because HFOV is considered to be a "rescue" therapy, intervention with HFOV is usually in the later stages of acute respiratory failure and consideration of the time to intervention has not been previously examined. OBJECTIVE: To evaluate the effect of time to intervention with high-frequency oscillatory ventilation (HFOV) on the survival of children with severe acute hypoxemic respiratory failure who were managed with lung protective strategies on conventional mechanical ventilation (CMV). METHODS: Twenty-six consecutive patients older 1 month of age with severe hypoxemic respiratory failure and ARDS who at some point in their management were treated with HFOV were evaluated. The mean age was 3.7 years and included three patients treated in the Pediatric Intensive Care Unit (17, 19 and 24 years). Mean weight was 13.8 kg and there were 17 males and 9 females. Nine patients met Extracorporeal Membrane Oxygenation (ECMO) criteria, although only two patients were cannulated. Upon admission to the PICU, patients were initially managed with lung protective strategies using Pressure Controlled Ventilation (PCV) or Pressure Regulated Volume Control (PRVC) modes with limited peak inspiratory pressure, high positive end-expiratory pressure, and permissive hypercapnia. If a Pa-CO2 reached > 75 torr (10.0 kPa) and/or pH < 7.20, tracheal gas insufflation (TGI) was instituted. If FiO2 remained above 0.6 and mean airway pressure (Paw) exceeded 15 cmH2O in order to maintain arterial saturation above 89% or if hypercapnia and/or acidosis on CMV with TGI persisted, the patients were switched to HFOV. An "Optimal Volume Strategy" with HFOV was utilized to recruit alveoli and optimize lung volume. Patients were returned to CMV when their mean airway pressure were between 15 and 20 cmH2O, FiO2 < 0.6, had no evidence of air-leak and/or improved chest X-rays, and did not desaturated during airway suctioning. Patients were offered ECMO if the hypoxemia persisted on HFOV and there were no contraindications to its use. The patients were stratified for analysis by the time to intervention with HFOV. Early intervention was defined as within the first 24 hours of mechanical ventilation (17 patients) and late intervention defined patients beyond 24 hours (9 patients). Demographic data (gender, age, weight, admission PRISM score), time of each mode of ventilation, oxygenation indices and outcomes were recorded for both groups of patients. MAIN RESULTS: The severity of respiratory failure at the time of HFOV intervention was comparable in both early and late groups (PaCO2/FiO2 83 vs. 79 torr, oxygenation index 27 vs. 33, AaDO2 421 torr (56 kPa) vs. 413 torr (55 kPa)). There were no differences in mean age, weight, admission PRISM score length of HFOV, length of CMV after HFOV (CMV post-HFOV) and the total duration of mechanical ventilation between the groups. We found a statistically significant difference in mortality with 58.8% of the early intervention patients surviving while only 12.5% of the late intervention patients survived. The overall survival rate was 42% (11/26 patients). CONCLUSION: Early use of HFOV within the first 24 hours of acute hypoxic respiratory failure in pediatric patients is associated with better survival. Use of this therapy should be considered early in the course of treatment of any pediatric patient meeting this definition. (Tab. 2, Fig. 1, Ref. 28.)