Acute respiratory distress syndrome. Inhaled nitric oxide

There is enough evidence to support the short-term beneficial effects and safety of administering inhaled NO to ARDS patients. This effect may be potentiated when inhaled NO is administered in conjunction with other therapies. The full spectrum of effects of inhaled NO remains to be elucidated. Long-term benefit in terms of mortality and duration of mechanical ventilation has not been demonstrated; more randomized trials probing these effects are needed.     

Respiratory mechanics and surfactant in the acute respiratory distress syndrome

1. Although abnormalities in pulmonary surfactant were initially implicated in the pathogenesis of the acute respiratory distress syndrome (ARDS) 30 years ago, most subsequent research has focused on mediators of the parenchymal acute lung injury (ALI) and the associated increase in alveolocapillary permeability. 2. Surfactant is essential for normal breathing and the severity of ALI correlates with surfactant dysfunction and abnormalities in surfactant composition; however, no relationship has been shown with respiratory system compliance. In neonates and most animal models, respiratory system compliance will directly reflect the elastic properties of the lung. However, the greater vertical height of the chest wall in adults, in combination with the increase in lung density due to ALI, results in dependent collapse of alveoli. Because simple, global measurement of compliance is strongly influenced by the volume of aerated lung, alternative measures of respiratory mechanics may reflect surfactant dysfunction. 3. Using a dynamic, volume-dependent model of respiratory mechanics to indirectly reflect this heterogeneous inflation, we have found direct relationships with surfactant composition in patients with ARDS. A failure of surfactant to increase surface tension in large alveoli may also explain why lung overdistension occurs at relatively low pressures. Furthermore, surfactant dysfunction will exaggerate heterogeneous lung inflation, augmenting regional overinflation, and is essential for ALI secondary to repetitive opening and closing of alveoli during tidal ventilation. 4. Ventilation-induced ALI has also been shown to result in massive increases in pro-inflammatory cytokines within the lung. Because ALI itself fails to compartmentalize cytokines, with spillover into the systemic circulation resulting in distant organ dysfunction, surfactant dysfunction may have widespread implications.     

Open-lung biopsy in patients with acute respiratory distress syndrome

Occupational exposures contribute to the morbidity and mortality of many diseases. However, occupational diseases continue to be underrecognized even though they are responsible for an estimated 860,000 illnesses and 60,300 deaths each year. Family physicians can play an important role in improving the recognition of occupational disease, preventing progressive illness and disability in their own patients, and contributing to the protection of other workers similarly exposed. This role can be maximized if physicians raise their level of suspicion for workplace disease, develop skills in taking occupational histories and establish routine access to occupational health resources.     

Current aspects of acute respiratory distress syndrome in children

Acute respiratory distress syndrome (ARDS) is a frequent condition in pediatric intensive care units. The mortality remains high despite advances in conventional mechanical ventilation and aetiological treatment. Several animal studies have documented lung injury during mechanical ventilation with high tidal volume, and clinical investigations have shown that in human ARDS, most ventilation is distributed to the small areas of remaining aerated lung resulting in overdistension of these areas and lung injury ("baby lung" theory). Nevertheless the usefulness of extrapulmonary gas exchange remains much debated. New ventilatory strategies have been developed in order to reduce ventilator-induced lung injury and to improve systemic oxygenation but multicentric randomized clinical trials are needed before these strategies can be validated.     

Nitric oxide in respiratory diseases

Recent reports have described a pathogenic role of nitric oxide in several respiratory disease. It is specially useful in the adult respiratory distress syndrome, where it acts as a selective vasodilator and improves gas exchange, decreasing pulmonary shunting. Although it has a proven bronchodilator effect, its therapeutic role in diseases such as asthma and chronic limitation of airway flow is not well defined. This article review the metabolism, mechanisms of action, potential uses and adverse effects of nitric oxide in respiratory disease.     

Acute respiratory distress syndrome: CT abnormalities at long-term follow-up

Photochemical thrombotic ischemia model was used to study the possible roles of excision repair cross-complementing group 6 (ERCC6), a DNA repair gene, in the neuroprotection of dextromethorphan (DM), a NMDA antagonist, in ischemic brain injury. The results showed that no obvious ERCC6 mRNA expression was found in the perifocal area of irradiated cerebral cortex before 24 h postischemia. Then, the number of ERCC6 mRNA positive cells gradually enhanced, and attained a peak value at 72 h after light irradiation, which followed a declined tendency at 7-day postlesion. These results suggest that DNA repair gene ERCC6 mRNA expression in the perifocal area may be involved in the pathophysiological processes following the photochemical thrombotic cerebral ischemia. By the administration of DM, we observed that it can significantly upregulate the expression of ERCC6 mRNA in the perifocal area at 48 h after ischemic event. The neuroprotective mechanisms of DM may be related to the upregulation of DNA repair gene ERCC6 mRNA.     

Acute effects of inhaled nitric oxide in adult respiratory distress syndrome

This study evaluated the dose-response effect of inhaled nitric oxide (NO) on gas exchange, haemodynamics, and respiratory mechanics in patients with adult respiratory distress syndrome (ARDS). Of 19 consecutive ARDS patients on mechanical ventilation, eight (42%) responded to a test of 10 parts per million (ppm) NO inhalation with a 25% increase in arterial oxygen tension (Pa,O2,) over the baseline value. The eight NO-responders were extensively studied during administration of seven inhaled NO doses: 0.5, 1, 5, 10, 20, 50 and 100 ppm. Pulmonary pressure and pulmonary vascular resistance exhibited a dose-dependent decrease at NO doses of 0.5-5 ppm, with a plateau at higher doses. At all doses, inhaled NO improved O2 exchange via a reduction in venous admixture. On average, the increase in Pa,O2, was maximal at 5 ppm NO. Some patients, however, exhibited maximal improvement in Pa,O2 at 100 ppm NO. In all patients, the increase in arterial O2 content was maximal at 5 ppm NO. The lack of further increase in arterial O2 content above 5 ppm partly depended on an NO-induced increase in methaemoglobin. Respiratory mechanics were not affected by NO inhalation. In conclusion, NO doses < or =5 ppm are effective for optimal treatment both of hypoxaemia and of pulmonary hypertension in adult respiratory distress syndrome. Although NO doses as high as 100 ppm may further increase arterial oxygen tension, this effect may not lead to an improvement in arterial O2 content, due to the NO-induced increase in methaemoglobin. It is important to consider the effect of NO not only on arterial oxygen tension, but also on arterial O2 content for correct management of inhaled nitric oxide therapy.     

Pharmacologic adjuncts to mechanical ventilation in acute respiratory distress syndrome

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.     

Eicosanoids and fat emulsions in acute respiratory distress syndrome patients

Laparoscopic splenectomy has been accepted as a feasible extension of minimally invasive surgery, which has undergone dramatic improvements in both technology and instrumentation. We performed a laparoscopic splenectomy in a 7-year-old girl with hereditary spherocytosis. The patient recovered rapidly and returned to unrestricted activities quickly. The appropriate positioning of each laparoscopic port is essential for a good operative view and smooth access. It is also important to dissect the hilum of the spleen meticulously. Laparoscopic splenectomy in the pediatric age group appears to be another promising extension of laparoscopic surgery.     

Rescue therapy for the acute respiratory distress syndrome (ARDS)

The potential risk of feto-maternal haemorrhage following coelocentesis was examined in 17 singleton pregnancies at 6-11 weeks of gestation by measuring maternal serum concentration of alpha fetoprotein (AFP) before and 1 and 10 min after the procedure. There was no significant difference between the maternal serum AFP concentration before coelocentesis (median 7.5, range 4.5-21.5 IU) compared to the values at 1 min (median 8.6, range 3.9-17.8; Z = -0.504, P = 0.614), and 10 min (median 7.5, range 5.7-20.6; Z = -0.432, P = 0.666) after the procedure. These findings demonstrate that coelocentesis is not associated with significant feto-maternal haemorrhage.     

Surfactant replacement therapy in acute respiratory distress syndrome from viral pneumonia

A modified natural surfactant was administered to a patient with life-threatening adult respiratory distress syndrome caused by viral pneumonia. Subsequently, there was a marked improvement in gas exchange. In order to assess the mechanism for improved oxygenation, computed tomography of the lungs was done. Quantitative analysis of the scans taken before and after surfactant administration indicates that improvement in gas exchange was largely due to the expansion of underinflated and collapsed lung areas. Although this is a single case report, it provides insight into the possible beneficial effect of instilled surfactant in severe respiratory distress from viral pneumonia.     

Inhaled nitric oxide for adult respiratory distress syndrome after pulmonary resection

BACKGROUND: The adult respiratory distress syndrome (ARDS) developing after pulmonary resection is usually a lethal complication. The etiology of this serious complication remains unknown despite many theories. Intubation, aspiration bronchoscopy, antibiotics, and diuresis have been the mainstays of treatment. Mortality rates from ARDS after pneumonectomy have been reported as high as 90% to 100%. METHODS: In 1991, nitric oxide became clinically available. We instituted an aggressive program to treat patients with ARDS after pulmonary resection. Patients were intubated and treated with standard supportive measures plus inhaled nitric oxide at 10 to 20 parts/million. While being ventilated, all patients had postural changes to improve ventilation/perfusion matching and management of secretions. Systemic steroids were given to half of the patients. RESULTS: Ten consecutive patients after pulmonary resection with severe ARDS (ARDS score = 3.1+/-0.04) were treated. The mean ratio of partial pressure of arterial oxygen to the fraction of inspired oxygen at initiation of treatment was 95+/-13 mm Hg (mean +/- SEM) and improved immediately to 128+/-24 mm Hg, a 31%+/-8% improvement (p<0.05). The ratio improved steadily over the ensuing 96 hours. Chest x-rays improved in all patients and normalized in 8. No adverse reactions to nitric oxide were observed. CONCLUSIONS: We recommend the following treatment regimen for this lethal complication: intubation at the first radiographic sign of ARDS; immediate institution of inhaled nitric oxide (10 to 20 parts per million); aspiration bronchoscopy and postural changes to improve management of secretions and ventilation/perfusion matching; diuresis and antibiotics; and consideration of the addition of intravenous steroid therapy.     

Patients with acute respiratory distress syndrome mechanically ventilated in prone position

Animal experiments and human studies have shown better oxygenation in mechanically ventilated patients with ARDS when the patient is situated in the prone position. In contradiction to former theories of a gravitational gradient of lung perfusion, a number of investigators have found that lung perfusion is preferentially distributed to the dorsal lung regions regardless of body position. The basal atelectasis and oedema in ARDS are resolved and only partly distributed anteriorly in the prone position, and these areas are thereby better ventilated. The combination of better ventilation and unchanged perfusion improves the ventilation/perfusion ratio and decreases the shunt in the prone position. In two cases of prone position in mechanically ventilated patients the PaO2/FiO2 ratio increased from 7.5 to 14.3 and from 8.8 to 19.8 after one hour in the prone position, and some of the improvement was permanent. Prone position has only minor side effects and is recommended as the first choice amongst adjunct therapies in mechanical ventilation in patients with ARDS remaining hypoxic in conventional therapy in the supine position.     

Pustular and erythrodermic psoriasis complicated by acute respiratory distress syndrome

To investigate the mechanisms of the hypolipidemic effect of monatepil, a new class of calcium antagonists with alpha 1-adrenergic blocking activity, we examined the effects of the drug on low-density lipoprotein (LDL) receptor activity and the level of LDL receptor mRNA present in cultured human skin fibroblasts. At concentrations of 2 x 10(-5) M, monatepil increased the binding (248 +/- 43%; mean +/- SD), internalization (374 +/- 18%), and degradation (145 +/- 2%) of 125I-LDL in human skin fibroblasts (n = 3, p < 0.05). Treatment of human skin fibroblasts with 2 x 10(-5) M of monatepil for 6 hours resulted in an increase in LDL receptor mRNA to 163% of the control level (n = 2), as shown by Northern blot analysis. Our results suggest that the hypolipidemic clinical effects of monatepil may be due to increased LDL receptor activity.     

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

Recent studies have shown that tetrafluoroethylene is a renal and hepatic carcinogen in the rat. In this study, we have examined the ability of a single i.p. dose of 1,1,2,2-tetrafluoroethyl-L-cysteine (TFEC), a major metabolite of tetrafluoroethylene, to produce hepatic and renal injury in male and female rats. We have also examined the effect of blocking the renal organic anion transport system with probenecid and of inhibiting the activity of cysteine conjugate beta-lyase with aminooxyacetic acid on the extent of renal injury produced by TFEC. Doses of > or = 12.5 mg/kg TFEC produced renal tubular necrosis to the pars recta of the proximal tubules within 24 h in both male and female rats. This was associated with an increased kidney to body weight ratio and plasma urea at doses of > or = 25 mg/kg. No consistent evidence of liver injury was seen at doses up to 50 mg/kg TFEC in rats of either sex, although occasional vacuolation of hepatocytes and a small dose-related increase in liver to body weight ratio was observed. Prior treatment of female rats with probenecid completely prevented the renal injury produced by either 25 or 50 mg/kg TFEC as judged by plasma urea and histopathology. However, prior treatment of female rats with aminooxyacetic acid afforded no protection against the nephrotoxicity produced by either TFEC or the cysteine conjugate of hexachloro-1,3-butadiene. Thus no major sex difference in nephrotoxicity in the rat was seen with TFEC, while accumulation of TFEC, or its N-acetyl derived metabolite, into renal proximal tubular cells via a probenecid sensitive transport system appears to be a key event in the mechanism of nephrotoxicity. The lack of protection observed with the cysteine conjugate beta-lyase inhibitor, aminooxyacetic acid, may reflect the inability to completely inhibit the mitochondrial form of this enzyme and thereby prevent the formation of the reactive metabolite. Our acute studies provide no insight concerning the liver carcinogenicity of tetrafluoroethylene.