Bovine surfactant therapy for patients with acute respiratory distress syndrome.

Abstract

Lung surfactant is deficient in patients with acute respiratory distress syndrome (ARDS). We performed a randomized, prospective, controlled, open-label clinical study of administration of a bovine surfactant to patients with ARDS to obtain preliminary information about its safety and efficacy. Patients received either surfactant by endotracheal instillation in addition to standard therapy or standard therapy only. Three different groups of patients receiving surfactant were studied: patients receiving up to eight doses of 50 mg phospholipids/kg, those receiving up to eight doses of 100 mg phospholipids/kg, and those receiving up to four doses of 100 mg phospholipids/kg. Outcome measures included ventilatory support parameters, arterial blood gases, organ system failures, bronchoalveolar lavage (BAL) analyses, immunologic analyses, survival, and adverse events during the 28-d study period. Fifty-nine study patients were evaluable; 43 in the surfactant group and 16 in the control group. The FI(O2) at 120 h after treatment began was significantly decreased only for patients who received up to four doses of 100 mg phospholipids/kg surfactant as compared with control patients (p = 0.011). Mortality in the same group of patients was 18.8%, as compared with 43.8% in the control group (p = 0.075). The surfactant instillation was generally well tolerated, and no safety concerns were identified. This pilot study presents preliminary evidence that surfactant might have therapeutic benefit for patients with ARDS, and provides rationale for further clinical study of this agent.

Surfactant for Pediatric Acute Lung Injury

“…However, interpretation of these negative results is confounded because both laboratory and clinical studies have documented that Exosurf® has low activity compared to animal-derived surfactants [51, [113][114][115][116][117][142][143][144][145], and aerosolization has not been shown to be as effective as airway instillation in delivering surfactant. Gregory et al [137] reported small benefits in oxygenation in a controlled trial in adults with ARDS who received four 100 mg/kg doses of Survanta®, but with no overall advantage in survival in the 43 surfactant-treated patients studied. A more recent study by Spragg et al [26] using recombinant SP-C surfactant (Venticute®) in adults with ARDS showed immediate improvements in oxygenation, but no longer-term improvement in duration of mechanical ventilation, lengths of stay, or mortality.…”

“…However, many of these are small case series or pilot studies, and found only improvements in acute lung function (oxygenation). Controlled trials of surfactant therapy in patients with ALI/ARDS have met with mixed success, particularly in adults with sepsis-associated ARDS [136,137]. A summary of the clinical experience with exogenous surfactant therapy in term infants, children and adults is given below.…”

“…The addition of bovine SP-B or synthetic SP-B peptides to Survanta® significantly improves its surface and physiological activity towards that of Infasurf and whole surfactant [106,118,175] (Figure 5)‥ Despite its lack of SP-B, other active components such as SP-C in Survanta® allow it to have significant efficacy in some forms of ALI/ARDS as noted earlier (e.g., [130,131,133]). Treatment with Survanta® has not been found to give substantial improvements in adult patients with ARDS [137], but Category I exogenous surfactants with the complete mix of surfactant lipids and near-endogenous amounts of both SP-B and SP-C may prove to have increased efficacy.…”

Exogenous surfactant instillation attenuates inflammatory response to acid-induced lung injury in rat

“…Instillation of surfactant into sepsis-induced ARDS patients improved gas exchange and mortality rate only in the group receiving four doses of 100 mg/kg compared with other groups receiving eight doses of 50 mg/kg or 100 mg/kg, respectively [8], suggesting that the benefits of subsequent dosing regimens are random. Spragg et al [9] evaluated the anti-inflammatory effects of SP-C-based surfactant in patients with ARDS.…”

Polyethylene Glycol-Surfactant for Lavage Lung Injury in Rats

“…In turn, injury predisposes the patient to acute (or adult) respiratory distress syndrome (ARDS) (1)(2)(3)(4). Pulmonary surfactant replacement, now a mainstay in the treatment of respiratory distress syndrome in premature infants, has not enjoyed comparable success in treating ARDS (5)(6)(7). Inadequate dosage or distribution, and inactivation of surfactant have been postulated for its poor performance in treating these injuries (8 -11).…”