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PubMed2004

Is carbon monoxide-mediated cyclic guanosine monophosphate production responsible for low blood pressure in neonatal respiratory distress syndrome?

Infant respiratory distress syndrome (RDS) involves inflammatory processes, causing an increased expression of inducible heme oxygenase with subsequent production of carbon monoxide (CO). We hypothesized that increased production of CO during RDS might be responsible for increased plasma levels of vasodilatory cGMP and, consequently, low blood pressure observed in infants with RDS. Fifty-two infants (no-RDS, n = 21; RDS, n = 31), consecutively admitted to the neonatal intensive care unit (NICU) between January and October 2003 were included. Hemoglobin-bound carbon monoxide (COHb), plasma cGMP, plasma nitric oxide (NOx), and bilirubin were determined at 0-12, 48-72, and at 168 h postnatally, with simultaneous registration of arterial blood pressure. Infants with RDS had higher levels of cGMP and COHb compared with no-RDS infants (RDS vs. no-RDS: cGMP ranging from 76 to 101 vs. 58 to 82 nmol/l; COHb ranging from 1.2 to 1.4 vs. 0.9 to 1.0%). Highest values were reached at 48-72 h [RDS vs. no-RDS mean (SD): cGMP 100 (39) vs. 82 (25) nmol/l (P < 0.001); COHb 1.38 (0.46) vs. 0.91 (0.26)% (P < 0.0001)]. Arterial blood pressure was lower and more blood pressure support was needed in RDS infants at that point of time [RDS vs. no-RDS mean (SD): mean arterial blood pressure 33 (6) vs. 42 (5) mmHg (P < 0.05)]. NOx was not different between groups and did not vary with time. Multiple linear regression analysis showed a significant correlation between cGMP and COHb, suggesting a causal relationship. Mean arterial blood pressure appeared to be primarily correlated to cGMP levels (P < 0.001). We conclude that a CO-mediated increase in cGMP causes systemic vasodilation with a consequent lower blood pressure and increased need for blood pressure support in preterm infants with RDS.

Biomarkers↗
PubMed1999

Initial serum ferritin levels in patients with multiple trauma and the subsequent development of acute respiratory distress syndrome.

Acute respiratory distress syndrome (ARDS) represents a catastrophic form of inflammatory lung injury that occurs unpredictably in some, but not all, at-risk patients. In this study, we investigated serum ferritin as a marker for ARDS development in a homogenous group of patients at-risk because of multiple trauma. We hypothesized that since ferritin synthesis is increased by proinflammatory cytokines, which are increased and implicated in ARDS, that ferritin levels would increase and that ferritin increases would correlate with the degree of inflammation and therefore the development of ARDS. We studied 42 patients (25 male, 17 female) who as a consequence of multiple trauma became at-risk for developing ARDS. Using the European/American Consensus definition for ARDS, 16 (38%) patients subsequently developed ARDS (11 male and five female). We found that initial serum ferritin levels correlated with the subsequent development of both ARDS (progression to ARDS, median = 638 ng/ml; (range, 70 to 4,500) versus nonprogression to ARDS = 185 ng/ml; range, 12 to 2,850) (p = 0.02, r = -0.27) and multiple organ failure (p < 0.05, r = 0.39). Using our previously established cutoff points for serum ferritin, the positive predictive value was 62% for men and 75% for women. Initial serum ferritin levels also correlated with a measurement of the degree of initial trauma injury, i.e., the injury severity score (ISS) (p < 0.05, r = 0.37). However, there was no correlation between serum ferritin levels and other markers of clinical injury, namely, lowest PaO2/FIO2 ratio (p = 0.67), days requiring ventilation (p = 0.09), or mortality (p = 0.42). A significant association existed between serum ferritin levels and products of endothelial activation, i.e., sE-selectin (p < 0.04, r = 0.37) and sICAM-1 (p < 0.01, r = 0.21). In the future, with the development of novel anti-inflammatory therapies, early identification of specific high-risk patients would allow the institution of these therapies and thereby increase the chances of reducing ARDS morbidity and mortality.

Acute Disease↗
PubMed2000

Diuretics for respiratory distress syndrome in preterm infants.

BACKGROUND: Lung edema may complicate respiratory distress syndrome (RDS) in preterm infants. OBJECTIVES: The aim of this review was to assess the risks and benefits of diuretic administration in preterm infants with RDS. SEARCH STRATEGY: We used the standard search method of the Cochrane Neonatal Review Group. We searched Medline, Embase and the Cochrane Controlled Trials Register from the Cochrane Library, using the following keywords: and . In addition, we searched the abstract books of the American Thoracic Society and Pediatric Research Societies. SELECTION CRITERIA: We only included trials in which preterm infants with RDS and less than 5 days of age were randomly allocated to diuretic administration. Of those trials, we only included studies in which at least one of the following outcomes measures was evaluated: mortality, patent ductus arteriosus, hypovolemic shock, intraventricular hemorrhage, renal failure, duration of oxygen supplementation, duration of mechanical ventilation, need for oxygen supplementation at 28 days of life, oxygen supplementation at 36 weeks of postconceptional age (gestational age + postnatal age), length of stay, number of rehospitalizations during the first year of life, and neurodevelopmental outcome. DATA COLLECTION AND ANALYSIS: We used the standard method for the Cochrane Collaboration which is described in the Cochrane Collaboration Handbook. Two investigators extracted, assessed and coded separately all data for each study. Any disagreement was resolved by discussion. MAIN RESULTS: Six studies met inclusion criteria. Studies available for this systematic review were all done before the current era of prenatal steroids, surfactant, indomethacin and fluid restriction. Furosemide administration had no long-term benefits. Furosemide-induced transient improvement in pulmonary function did not outweigh an increased risk for patent ductus arteriosus and for hemodynamic instability. REVIEWER'S CONCLUSIONS: There are no current data to support routine diuretic administration in preterm infants with RDS. Elective administration of furosemide or any diuretic to any patient with RDS should be carefully weighed against the risk of precipitating hypovolemia. In addition, elective administration of furosemide should be weighed against the risk of developing a symptomatic patent ductus arteriosus.

Diuretics↗
PubMed2001

Immunohistochemistry of pulmonary surfactant-associated protein A in acute respiratory distress syndrome.

Acute respiratory distress syndrome (ARDS) is a fatal complication in severe traumas and diseases. Although the contribution of pulmonary surfactant abnormality to the pathogenesis of ARDS has been clinically fairly well investigated, the histopathological evidence has not been established. The aim of this study was to clarify the immunohistochemical distribution of surfactant-associated protein A (SP-A) for early diagnosis of ARDS with special regard to hyaline membrane (HM) formation. Two-hundred-and-ten autopsy cases of prolonged death from various traumas and diseases were investigated. ARDS were observed in 23 cases, showing speckled SP-A immunostaining. During the early, exudative phase of ARDS, characteristic SP-A distribution showed intense staining in the intra-alveolar massive aggregates and thick 'peeling'-like substances accompanied with a lot of granular staining. During the proliferative phase, localized accumulation of granular SP-A and macrophages containing dense granular SP-A became predominant. During the final fibrotic phase, SP-A staining in HMs became weak, and disseminated granular staining was observed in the alveolar spaces. These findings provide morphological evidence of the increase of SP-A during the early phase of ARDS, including some molecular alteration and its decrease during the late phase. Characteristic SP-A distribution in the exudative phase appeared to be especially useful for early histopathological diagnosis of respiratory distress, even prior to the appearance of typical HMs.

Journal Article↗
PubMed2001

Pulmonary and extrapulmonary forms of acute respiratory distress syndrome.

Acute respiratory distress syndrome (ARDS) is usually viewed as the functional and morphological expression of a similar underlying lung injury caused by a variety of insults. However, the distinction between ARDS due to a direct (ARDSp) versus an indirect (ARDSexp) lung injury is gaining more attention as a means of better comprehending the pathophysiology of ARDS and for modifying ventilatory management. From the few published studies, we can summarize that: (1) the prevalent damage in early stages of a direct insult is intra-alveolar, whereas in indirect injury it is the interstitial edema. It is possible that the two insults may coexist (i.e., one lung with direct injury (as in pneumonia) and the other with indirect injury, through mediator release from the contralateral pneumonia); (2) the radiological pattern, by chest x-ray or computed tomography (CT), is different in ARDSp (characterized by prominent consolidation) and ARDSexp (characterized by prominent ground-glass opacification); (3) in ARDSp lung elastance is more markedly increased than in ARDSexp, where the main abnormality is the increase in chest wall elastance, due to abnormally high intra-abdominal pressure; (4) positive end-expiratory pressure (PEEP), inspiratory recruitment, and prone position are more effective to improve respiratory mechanics, alveolar recruitment, and gas-exchange in ARDSexp. Further studies are warranted to better define if the distinction between ARDS of different origins can improve clinical management and survival.

Journal Article↗
PubMed1979

Evaluation of the progress and prognosis of adult respiratory distress syndrome. Simple respiratory physiologic measurement.

In our study of 14 patients with adult respiratory distress syndrome (ARDS), we measured A-aDO2, VD/VT, arterial-to-end tidal PCO2 ), effective dynamic compliance, and pulmonary vascular resistance on a daily basis. At the onset of ARDS, all patients showed bilateral interstitial edema on the chest X-ray films, P(A-a)O2 of more than 500 mm Hg, marked decrease in effective dynamic compliance, a moderate increase in VD/VT, and a normal value of a-etPCO2. Pulmonary vascular resistance was low. After seven days, all of those who subsequently died and developed persistent elevation of P(A-a)O2, significant increase in VD/VT, a-etPCO2 and pulmonary vascular resistance, and significant decrease in effective dynamic compliance compared to the values at the onset of ARDS. Those abnormalities diverged significantly from the findings in those who survived. By evaluating sequential changes of those parameters, we might be able to predict an accurate prognosis of ARDS.

Acute Disease↗
PubMed1993

Approach to adult respiratory distress syndrome and respiratory failure in elderly patients.

Because of physiologic changes associated with aging and the development of chronic illness, the elderly will continue to be at risk for catastrophic illnesses including adult respiratory distress syndrome (ARDS). Current management of elderly patients with ARDS is only supportive and focused on avoiding complications. Truly successful management of these patients requires therapies directed at pathophysiologic initiators and mediators of ARDS.

Aged↗
PubMed1995

Surfactant replacement therapy for non-respiratory distress syndrome neonatal respiratory disease--research or clinical application?

Research studies have highlighted both physiological and pathological evidence to incriminate surfactant abnormality and/or deficiency in many neonatal respiratory diseases. Data from animal models and clinical studies support the concept that surfactant replacement therapy (SRT) may have a role to play in such problems. There is now, therefore, a need to perform further randomized controlled trials to assess the appropriate clinical application of SRT in non-respiratory distress syndrome neonatal respiratory disease.

Hernia, Diaphragmatic↗
PubMed2003

Management of respiratory distress syndrome: an update.

Respiratory distress syndrome is the most common respiratory disorder in preterm infants. Over the last decade, because of improvements in neonatal care and increased use of antenatal steroids and surfactant replacement therapy, mortality from respiratory distress syndrome has dropped substantially. However, respiratory morbidity, primarily bronchopulmonary dysplasia, remains unacceptably high. The management of respiratory distress syndrome in preterm infants is based on various modalities of respiratory support and the application of fundamental principles of neonatal care. To obtain best results, a multidisciplinary approach is crucial. This review discusses surfactant replacement therapy and some of the current strategies in ventilatory management of preterm infants with respiratory distress syndrome.

Disease Management↗
PubMed1977

[Prevention of idiopathic respiratory distress syndrome. Influence of betamethasone on the frequency of respiratory distress syndrome in a premature infant collective at the Bonn University Gynecologic Clinic].

Out of a group of 189 pregnant women, who were in the 28th to 37th week of gestation, 57 women received i.m. injections of betamethasone. 132 premature infants whose mothers were not treated served as controls. Betamethasone caused a significant decrease in established respiratory distress syndrome (RDS). In the betamethasone group there was an incidence of 7% of respiratory distress syndrome as compared to 23,5% in the control group. Neonatal mortality was 1,8% in the treated group versus 10,6% in the control group. The occurrence of suspected respiratory distress syndrome also was significantly lowered after betamethasone. In the control group premature rupture of membranes or administration of tocolytic drugs did not have any effect on the frequency of respiratory distress syndrome. However, the premature babies who were delivered by caesarian section had a significantly higher incidence of respiratory distress syndrome than those who were delivered vaginally. After betamethasone treatment the occurrence of respiratory distress syndrome after caesarian section was as low as in the group with vaginal delivery. The present study of a larger group of premature babies has confirmed previous positive results of betamethasone treatment.

Apgar Score↗
PubMed2000

Natural surfactant extract versus synthetic surfactant for neonatal respiratory distress syndrome.

BACKGROUND: This section is under preparation and will be included in the next issue. OBJECTIVES: To compare the effect of synthetic surfactant to natural surfactant in premature infants with established respiratory distress syndrome. SEARCH STRATEGY: Searches were made of the Oxford Database of Perinatal Trials, Medline (MeSH terms: pulmonary surfactant; limits: age groups, newborn infant; publication type, clinical trial), previous reviews including cross references, abstracts, conference and symposia proceedings, expert informants, and journal hand searching in the English language. SELECTION CRITERIA: Randomized controlled trials comparing administration of synthetic surfactants to administration of natural surfactant extracts in premature infants with respiratory distress syndrome were considered for this review. DATA COLLECTION AND ANALYSIS: Data regarding clinical outcomes including pneumothorax, patent ductus arteriosus, necrotizing enterocolitis, intraventricular hemorrhage (all intraventricular hemorrhage and severe intraventricular hemorrhage), chronic lung disease, retinopathy of prematurity, and mortality were excerpted by the primary reviewer (R. Soll). Data analysis was conducted according to the standards of the Neonatal Cochrane Review Group. MAIN RESULTS: The meta-analysis supports a significant reduction in the risk of pneumothorax (typical relative risk 0.68, 95% CI 0.56, 0.83; typical risk difference -0.04 95% CI -0.06, -0.02). No disadvantages to natural surfactant extract treatment are noted regarding other outcomes. A trend towards reduced mortality is noted in association with natural surfactant extract treatment. REVIEWER'S CONCLUSIONS: Both natural surfactant extracts and synthetic surfactant extracts are effective in the treatment of established respiratory distress syndrome. Comparative trials demonstrate greater early improvement in the requirement for ventilatory support and fewer pneumothoraces associated with natural surfactant extract treatment. On clinical grounds, natural surfactant extracts would seem to be the more desirable choice.

Biological Products↗
PubMed1997

Acute respiratory distress syndrome caused by respiratory syncytial virus.

Acute respiratory distress syndrome (ARDS) complicating severe respiratory syncytial virus (RSV) infection has been described in only a few infants. In contrast to the low mortality rates usually associated with RSV infections (< 5%), mortality rates in the range of 40-70% have been reported in pediatric patients with ARDS. However, studies on patients with ARDS are usually lumped with respect to causation, and the disease course of RSV-induced ARDS has not been previously studied. We examined the pulmonary function abnormalities of 37 infants with RSV-induced respiratory failure who were admitted to our pediatric intensive care unit for assisted ventilation. Measurements included respiratory mechanics, maximum expiratory flow-volume curves, and lung volumes. These allowed the calculation of a Murray lung injury score (modified for pediatric use) in which radiographic findings, ventilator settings, lung compliance, and blood gas results were considered. We identified ten infants with severe restrictive lung disease who fulfilled the clinical criteria for classification as ARDS. All had lung injury scores above 2.5, compatible with a diagnosis of ARDS. Twenty-seven infants had obstructive patterns of lung function consistent with a clinical diagnosis of RSV bronchiolitis. The patients with RSV-induced ARDS were significantly younger, and had a longer time on assisted ventilation (P < 0.05) and a higher proportion of predisposing illnesses (P < 0.05, odds ratio = 6.67, two-tailed Fisher's exact test) when compared with the patients who had obstructive disease. Only one patient (who had immunodeficiency) died, and all others were successfully managed on conventional mechanical ventilation. We conclude that RSV-induced respiratory failure represents a relatively benign cause of ARDS in pediatric patients. Our observations support the notion of differentiating ARDS with respect to causation, especially when novel and experimental therapy is considered and mortality rates are analyzed.

Causality↗
PubMed1989

Exogenous surfactant treatments for neonatal respiratory distress syndrome and their potential role in the adult respiratory distress syndrome.

Exogenous surfactant therapy has been recognised as an approach to alleviating the surfactant-deficine state for 3 decades. Natural and lipid-extracted surfactants derived from amniotic fluid, lung lavage, or lung homogenates are being used in worldwide clinical trials in premature infants. These studies are demonstrating a generally favourable influence on lung function by improving oxygenation and reducing the risk for pneumothorax and pulmonary interstitial emphysema. In some studies, reduction in death and the occurrence of bronchopulmonary dysplasia have been found. Numerous questions are unresolved and pharmacokinetic data are limited in preterm infants. Artificial surfactants are similarly under evaluation but current data demonstrate less overall effect. Adult respiratory distress syndrome has also been treated with exogenous surfactants. Although complex in terms of multiple initiating factors and in terms of high permeability of surfactant inhibitors, further studies are under way to determine the ideal methods of administration to enhance distribution and to monitor surfactant function in vivo.

Humans↗
PubMed2006

Acute lung injury and acute respiratory distress syndrome: extracorporeal life support and liquid ventilation for severe acute respiratory distress syndrome in adults.

Acute respiratory distress syndrome (ARDS) has many underlying causes and carries an overall mortality of 40 to 60%. For those patients with severe ARDS who have a predicted mortality of 80 to 100%, extracorporeal life support (ECLS) can provide an extraordinary means of support. We recently demonstrated a survival to hospital discharge of 52% in this subset of patients. ECLS is capable of providing full respiratory and cardiac support, allowing time for the patient to recover from the underlying disease process. Additionally, ventilator settings are reduced to "rest" settings, avoiding the consequences of ventilator-induced lung injury that can contribute to a worse outcome. Systemic heparinization is a mainstay of ECLS therapy because of platelet activation in the circuit. Mechanical complications and significant bleeding can occur in up to one quarter of patients, requiring close attention and prompt intervention should they occur. Although not currently in clinical practice, liquid ventilation using perfluorocarbons to provide gas exchange in the lungs is a potentially useful adjunct in the management of severe respiratory failure.

Extracorporeal Membrane Oxygenation↗
PubMed1987

Evaluation of routine lumbar punctures in newborn infants with respiratory distress syndrome.

Infants with respiratory distress syndrome are routinely evaluated for infection which commonly includes a lumbar puncture. In this study cerebrospinal fluid (CSF) examination failed to elicit evidence for meningitis in 238 consecutively admitted infants with respiratory distress syndrome evaluated during the first 24 hours of life. Blood cultures were obtained in all; suprapubic or catheterized urine was obtained in 163 infants; CSF was collected successfully in 203 infants. Seventeen infants demonstrated positive blood cultures: 7 Streptococcus, 5 Staphylococcus, 3 Haemophilus influenzae, 1 Bacillus subtilis and 1 diphtheroid infection. CSF obtained from 14 of those infants had normal examinations and sterile cultures. Factors associated with bacteremia were birth weight (P less than 0.01), gestational age (P less than 0.01), prolonged rupture of membranes (P less than 0.05) and leukopenia below 10 000/mm3 (P less than 0.05). In view of the negative CSF examinations in infants with positive blood cultures and the potential complications of lumbar puncture (hypoxia, trauma, infection, epidermoid tumor), the potential risks of CSF evaluation may exceed the assessed benefit for the infant with respiratory distress syndrome.

Humans↗
PubMed2004

High-frequency percussive ventilation: an alternative mode of ventilation for head-injured patients with adult respiratory distress syndrome.

BACKGROUND: Adult respiratory distress syndrome develops in up to 20% of patients with severe head injury. This complicates the treatment of head-injured patients because lung-protective strategies such as high positive end-expiratory pressure (PEEP) and permissive hypercapnia may increase intracranial pressure (ICP) and reduce cerebral perfusion pressure. The use of high-frequency percussive ventilation (HFPV) is an alternate mode of ventilation that may improve oxygenation for head-injured patients while also lowering ICP. METHODS: Clinical data were collected retrospectively over a 1-year period. Patients were included if they had a severe traumatic brain injury with a Glasgow Coma Score (GCS) of 8 or lower, a ventriculostomy drain for ICP measurement and cerebral spinal fluid drainage, and adult respiratory distress syndrome. Patients were switched from conventional mechanical ventilation to HFPV at the discretion of the attending trauma surgeon. Data for partial pressure of oxygen to fraction of inspired oxygen (PF) ratio, peak inspiratory pressure (PIP), ICP, partial pressure of carbon dioxide level (PCO2), PEEP, and mean airway pressure were compared before and then 4 and 16 hours after institution of HFPV therapy. RESULTS: A total of 10 patients met study criteria. Data were expressed as mean +/- standard error. There was an increase in PF ratio (91.8 +/- 13.2 vs. 269.7 +/- 34.6; p < 0.01), PEEP (14 +/- 2.5 vs. 16 +/- 3.5), and mean airway pressure (20.4 +/- 4.8 vs. 23.6 +/- 6.8) 16 hours after institution of HFPV. There was a decrease in ICP (30.9 +/- 3.4 vs. 17.4 +/- 1.7; p < 0.01), PC02 (37.7 +/- 4.1 vs. 32.7 +/- 1.1; p < 0.05), and PIP (49.4 +/- 10 vs. 41 +/- 7.9; p < 0.05) at 16 hours. Overall mortality was 10%. CONCLUSIONS: Therapy with HFPV produced a significant improvement in oxygenation with a concomitant reduction in ICP during the first 16 hours. This therapy may represent an important new method for the management of adult respiratory distress syndrome among head-injured trauma patients, although the long-term outcome of HFPV still needs evaluation.

Adult↗