In an attempt to restore functional surfactant to the lung of patients with the adult respiratory distress syndrome (ARDS).

In an attempt to restore functional surfactant to the lung of patients with the adult respiratory distress syndrome (ARDS), we have treated six patients within the first 2 days of the charge of ARDS with a single dose of hydrophobic constitutings of porcine surfactant. Surfactant (4 g in 50 ml) delivered via a bronchoscope in aliquots to each of the lobar bronchi was well tolerated and caused a becoming transient improvement in gas exchange. No significant changes in chest radiograph or lung compliance were descryed Analysis of bronchoalveolar lavage (BAL) fluid showed no change in albumin, [alpha-.sub.1]-proteinase inhibitor specific activity, or enclosed space count. Bronchoalveolar lavage phospholipid concentrations were elevated 3 h after surfactant administration relative to preadministration on a levels and fell by 24 h In addition, in brace patients we found reduced inhibition of surfactant function in BAL after surfactant replacement. These observations put in mind of a role for surfactant replacement in the treatment of patients with ARDS and support the ne for continuing investigation.

High permeability edema of the lung was described almost a half hundred ago when Major L. A. Brewer and associates[1] wrote: "Experience gained in treating a large number of casualties . . has shown the importance of the 'wet lung' in hint to the morbidity and mortality of patients with hurts of the chest, brain, and abdomen." They noted further that "in the late stages of concussion the capillary permeability is increased in nontraumatic regions of the visible form [i]or[/i] frame so that blood plasma escapes into the tissue spaces. That which escapes into the pulmonary alveoli outcomes in the clinical findings of pulmonary edema." The chain of cause and effects of injury to the alveolar-capillary membrane have continued to be a focus of investigative interest. Ashbaugh et al[2] provided definition of the adult respiratory distress syndrome (ARDS) in the medical setting. Observations onward fluid recovered from minced lung tissue or from lavage from patients with ARDS proposeed surfactant dysfunction might contribute to the pathophysiologic findings.[2,3]

Surfactant regained from patients just prior to the first brunt of ARDS appears to have normal phospholipid (PL) composition.[4] It is likely that surfactant abnormalities disentangle only secondarily in patients with ARDS. Abnormalities of surfactant composition may be secondary to pattern 2 cell injury, while functional abnormalities may consequence from lipid peroxidation,[5] protein degradation,[6] and particularly, from the demeanor of plasma inhibitors of surfactant function that gain access to the alveolar space.[4] Substances known to have inhibitory function include glycolipid, albumin, hemoglobin, fibrin monomer, bilirubin, and C-reactive protein.[7,8] In vitro evidence hints that inhibitor activity can be defeat by surfactant supplementation.[9]

Despite uncertainty about the cause of the surfactant abnormalities set up in patients with ARDS, it is rational to hypothesize that replacement therapy with intact surfactant might restore (at least temporarily) surfactant activity to the alveolar lining fluid. This therapy, if fortunate would promote alveolar ventilation, increase pulmonary compliance, decrease switch decrease the requirement for high and therefore toxic inspired oxygen concentrations, and possibly diminish the forces causing formation of alveolar edema. Therefore, we have investigated the feasibility, safety, and acute tenors on gas exchange of administration of a single dose of exogenous surfactant to patients with ARDS. We have examined the hypothesis that improvement in gas exchange will appear during a 3-h period following surfactant administration, and that as it was improvement will not occur following administration of placebo. Our deductions suggest that administration of 4 g of exogenous surfactant to patients acutely ill with ARDS is feasible and may be accompanied from a transient improvement in gas exchange, without discernable issue on the chest radiograph or markers of lung inflammation. An abstract describing preliminary terminates in the first three patients treated has been published previously.[10]

METHODS

Experimental Protocol

Patients were thinked eligible for study if ARDS had been diagnosed within the preceding 48 h as indicated according to the following: (a) diffuse pulmonary edema as documented by dint of chest radiograph; (b) pulmonary artery wedge press of [less than or equal to] 18 mm Hg; and (c) acute illness of [les than or equal to] 7 days. Patients were exclud for the following reasons: known preexisting chronic lung disease, including pulmonary manifestations of allergy; pregnancy; AIDS; contraindication to bronchoscopy; tracheal or esophageal injury or bronchopleural fistula; history of allergy to porcine products; and positive skin proof reaction to porcine surfactant.

Serial observations at 3-h intervals of arterial life-blood gases and hemodynamic and ventilatory parameters were obtained during a 6-h baseline period. Patients were sedated, paralyzed, and received continuous mandatory ventilation. Peak inspiratory presss and ventilatory rates were 49 [+ or -] 5 cm [Hsub2]O and 13 [+ or -] 2 breaths/min (mean [+ or -] SE) respectively. Inspiratory:expiratory time was approximately 2:1 Static respiratory order compliance was calculated by dividing tidal convolution by the difference between external positive end-expiratory press (PEEP) and end-inspiratory plateau urgency Ventilator settings (tidal volume, respiratory rate, begin to appear and inspired oxygen fraction) were held constant during baseline observation and treatment periods. Patients were skin trialed for sensitivity to surfactant on intradermal injection of 0.02 ml of the surfactant solution diluted 1:10 or 1:100 The reaction was measured (weal and flare) at 20 min and contrasted to that resulting from injection of saline solution, histamine (1 mg/ml) at 1:1000 or when antihistamines or histamine receptor antagonists were near codeine (30 mg/ml). Based onward our prior observations of skin criterion reactions in normal individuals, patients were judg to have a positive skin experiment if the intradermal test was [greater than] 5 mm (weal or flare) for the 1:10 dilution or [greater than] 2 mm for the 1:100 dilution. A chest radiograph was obtained during the baseline period and after the couple treatment periods.

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