Surfactant lavage with lidocaine improves pulmonary function in piglets after HCl-induced acute lung injury

Abstract

Acute respiratory distress syndrome (ARDS) is associated with significant morbidity and mortality. The pathophysiology of ARDS includes abnormalities of surfactant function as well as pulmonary inflammation. Immunomodulating drugs, like Lidocaine, have shown some success in decreasing inflammation in ARDS. We attempted to combine surfactant lavage's ability to reverse the surfactant dysfunction, while acting as a vehicle to deliver Lidocaine. Gravity-driven surfactant (Infasurf) lavage (35 ml/kg) was administered alone or mixed with Lidocaine after severe HCl acid injury (0.3 N; 3 cc/kg) in neonatal piglets. Treatment groups included: control (C) ( n = 5), surfactant lavage (SL) (35 ml/kg-diluted Infasurf) ( n = 7) and SL mixed with Lidocaine (SL+L) ( n = 7). About 26-27% of the lavage was retained (phospholipid 73-74 mg/kg; Lidocaine 1.8 mg/kg). Oxygenation progressively increased in the SL and SL+L groups over the 4-hour period (at 240 min: C = 99 +/- 14; SL = 154 +/- 39; SL+L = 230 +/- 40 mmHg) ( p < 0.05). PaCO(2) increased in all groups from 43 +/- 0.3 to 55 +/- 0.7 mmHg. Only SL+L showed a reduction in PaCO(2) (at 240 min: C = 54 +/- 4; SL = 53 +/- 7; SL+L = 49 +/- 2 mmHg) ( p < 0.05). Finally, SL and SL + L had superior characteristics during the quasi-static pressure volume (PV) procedure as compared to Control ( p < 0.05). In our HCl ALI model, SL improved oxygenation and quasi-static lung compliance over C. The pulmonary function effects of SL were further enhanced by the addition of Lidocaine to the surfactant suspension. Combining therapeutic agents with surfactant lavage may be an effective strategy in ALI.

Fig. 1

Effects of HCl instillation and subsequent treatment with surfactant lavage on PaO₂ in Control, SL and SL+L groups. All data are presented as mean ± standard error. SL and SL+L groups showed improvement in oxygenation with time starting at 90 min (*p < 0.05). Further, oxygenation in the SL group was better than Controls starting at 120 min (^†p < 0.05). Oxygenation in the SL+L group was better than the other two groups starting at 90 min (^§p < 0.05).

Fig. 2

Effects of HCl instillation and subsequent treatment with surfactant lavage on PaCO₂ in Control, SL and SL+L groups. All data are presented as mean ± standard error. PaCO₂ decreased only in the SL+L group with time starting at 120 min (*p < 0.05) and this was significantly different compared to the other groups (^†p < 0.05).

Fig. 3

Results of Quasi-static pressure volume measurements in the Control, SL and SL+L groups. Improvement in pressure volume characteristics are seen on inflation (15–35 cm H₂O), early deflation (35–20 cm H₂O), and steep deflation (15–0 cm H₂O) portions in SL+L and SL over Controls (*p < 0.05).