Bronchopulmonary Segmental Lavage with Surfaxin (KL₄-Surfactant) for Acute Respiratory Distress Syndrome

Abstract

We performed a trial to assess the safety and tolerability of sequential bronchopulmonary segmental lavage with a dilute synthetic surfactant (Surfaxin) in 12 adults with ARDS. Patients received one of three dosing regimens in which aliquots of Surfaxin were administered via a wedged bronchoscope to each of the 19 bronchopulmonary segments. Suctioning was performed 10-30 s after instillation of individual aliquots. Group 1 patients (n ϭ 3) received one 30-ml aliquot of a 2.5-mg/ml concentration of Surfaxin in each segment, followed by a second 30-ml aliquot with a 10-mg/ml concentration. Group 2 patients (n ϭ 4) received two 30-ml aliquots of the 2.5-mg/ml concentration followed by a third lavage with the 10-mg/ml concentration. Group 3 patients (n ϭ 5) received therapy identical to that received by patients in Group 2 and were eligible for repeat dosing 6 to 24 h later. All patients tolerated the procedure. There were no serious adverse experiences ascribed to either the procedure or the surfactant. The acute respiratory distress syndrome (ARDS) is a lifethreatening disorder characterized by noncardiogenic pulmonary edema and refractory hypoxemia, with a case fatality rate as high as 40-60% (1-7). The pathophysiology of ARDS involves injury to the alveolar-capillary barrier, lung inflammation, atelectasis, surfactant dysfunction, and intrapulmonary shunting. The disorder typically appears within 12 to 24 h of an identifiable clinical event and may be due to direct lung injury, such as with gastric content aspiration, pneumonia, neardrowning, toxic gas inhalation, or chest/lung trauma. In addition, ARDS may be associated with systemic processes such as sepsis, nonthoracic trauma, acute pancreatitis, major surgery, multiple blood transfusions, fat embolism, or shock. No specific therapy for ARDS currently exists. To date, the numerous treatment strategies for the disorder that have been studied have not reduced associated morbidity or mortality.Pulmonary surfactant lines the alveolar epithelium of mature animal lungs. It is a lipoprotein complex that reduces surface tension to assist alveoli expansion, allowing gas exchange. The endogenous surfactant system of patients with ARDS may be compromised in several ways (7,8): the inciting disorder may directly damage type II pneumocytes and decrease the synthesis, secretion, and composition of surfactant or produce abnormal surfactant aggregate forms; plasma proteins in the pulmonary edema fluid may inhibit surfactant properties; and the products of inflammation, such as proteases and reactive oxygen species, may interfere with surfactant function, as well as processing of the substance in the alveolus (7,8).The major pulmonary consequences of ARDS are decreased compliance, decreased oxygenation, loss of lung vol-

Surfactant for Pediatric Acute Lung Injury

“…A significant number of clinical studies have reported benefits following the instillation of exogenous surfactants to term infants, children, or adults with ALI/ARDS or related acute respiratory failure [25,[120][121][122][123][124][125][126][127][128][129][130][131][132][133][134][135] (Table 4). However, many of these are small case series or pilot studies, and found only improvements in acute lung function (oxygenation).…”

“…Two important conceptual approaches being followed to develop synthetic exogenous surfactants are: (1) Combining human sequence recombinant proteins or synthetic amphipathic peptides with synthetic biological glycerophospholipids; and (2) combining synthetic amphipathic peptides with novel synthetic lipids designed to have favorable physicochemical properties such as high surface activity and structural resistance to inflammatory phospholipases during lung injury. Surfaxin® (KL4) [87,107,123,[189][190][191][192][193][194][195] and Venticute® (recombinant SPC surfactant) [26,[196][197][198][199][200][201] are two current examples of the first of these approaches (Table 3). However, the 21 amino acid KL4 peptide is only a very rough structural analog to native SP-B, and advances in peptide molecular modeling and synthesis technology support the feasibility of preparing new SP-B peptides with significantly greater sequence and molecular folding specificity, and correspondingly higher activity ( [202][203][204] for review).…”

Exogenous Surfactant Treatment in Children with ARDS

“…(29) These animal studies on exogenous surfactant lavages are very impressive but in the literature there are no trials in humans except for a few small studies done in adults and in older children using the bronchoscope. (31)(32)(33) The bronchoscope allows reduction of the total volume of lavages to 1-3 cc/kg, decreasing side effects from larger volumes but it requires a lot of expertise in the management of such respiratory unstable patients during this invasive procedure. Nevertheless, in treated subjects most of the studies showed an improvement in gas exchanges.…”

Lung Surfactant and Its Use in Lung Diseases

“…Сна чала препарат вводят в малой концентрации 2,5 мг/мл, а затем в том же объеме (по 30 мл в каждый сегмент) с концентраци ей 10 мг/мл. Суммарная доза препарата в сутки составляет 120 мг/кг [150]. Необходимо еще раз подчеркнуть, что тера певтические дозы разных препаратов отличаются и потому, что состав препаратов также различен.…”