Bronchoalveolar lavage with pulmonary surfactant/dextran mixture improves meconium clearance and lung functions in experimental meconium aspiration syndrome

Abstract

Surfactant lung lavage is a promising approach in the treatment of meconium aspiration syndrome (MAS). We hypothesise that the enrichment of modified natural surfactant with dextran will enhance meconium clearance from the airspaces during lung lavage and improve lung function in experimental MAS. Human meconium (30 mg/ml; 4 ml/kg) was instilled into the tracheal cannula of anaesthetised and paralysed adult rabbits to induce respiratory failure. The animals were then lavaged with saline (Sal), surfactant without (Surf) and with dextran (Surf+dex). Lung lavage (10 ml/kg in three portions) was performed with diluted surfactant (Curosurf, 10 mg/ml, 100 mg/kg) without or with dextran (3 mg/mg of surfactant phospholipids) or saline and the animals were conventionally ventilated with 100% O(2) for an additional hour. Lung functions were measured prior to and after meconium instillation, and 10, 30 and 60 min after lavage. The recovery of meconium in bronchoalveolar lavage (BAL) fluid was quantified. More meconium solids was recovered in the surfactant-lavaged than in the saline-lavaged groups (Surf: 12.4 +/- 3.9% and Surf+dex: 17.5 +/- 3.5% vs. Sal: 4.8 +/- 1.0%; both P < 0.01). Moreover, more meconium solids was obtained by Curosurf/dextran than by Curosurf-only lavage (P < 0.05). In the Surf group, the values for PaO(2)/FiO(2) were significantly higher than in the controls (at 60 min: 24.5 +/- 4.2 kPa vs.9.1 +/- 2.2 kPa, P < 0.01). An additional increase in oxygenation was seen in the Surf+dex group (at 60 min: 34.2 +/- 8.1 kPa, P vs. Surf group <0.01). The lung-thorax compliance was higher in the Surf+dex group in comparison with the Sal and Surf groups (at 60 min: 9.6 +/- 0.9 vs.7.6 +/- 1.2, P < 0.01 and 8.0 +/- 0.7 ml/kPa/kg, P < 0.05). The enrichment of Curosurf with dextran improves meconium clearance and lung functions in surfactant-lavaged rabbits with meconium aspiration.

Effective Lavage Volume of Diluted Surfactant Improves the Outcome of Meconium Aspiration Syndrome in Newborn Piglets

“…Although various reports have shown some merits in surfactant-lavaged animals than saline-lavaged or nonlavaged animals (23,(25)(26)(27)30,(32)(33)(34)(35), it is still not conclusive in the therapeutic techniques. This study focused on comparing the effects of different lavage volumes separated in two aliquots and suggested the use of a relative large lavage volume (20 -30 mL/kg) in treating MAS.…”

“…However, the techniques of therapeutic BAL are quite different among reported animal (Table 1) (23,(25)(26)(27)30,(32)(33)(34)(35)40) and neonatal studies (Table 2) (24,28,29,31,36 -39). The biggest difference was the lavage volume of each aliquot (range: 2 mL/aliquot to 20 mL/ kg/aliquot) and lavage frequencies (range, 2-30 aliquots), thus resulting in a large difference in total lavage volume (range, 9 mL totally to 80 mL/kg) ( Tables 1 and 2).…”

“…Intervention to treat progressive MAS using BAL with saline has not proved to be clinically useful (15,16) and may even be detrimental as the volume of saline can further impede gas exchange and worsen lung mechanics. Some authors have tried to use bolus surfactant given after saline lavage (15,(17)(18)(19)(20), but the surfactant distribution was not uniformly obtained in the same manner as when using surfactant lavage (21,22).Recently, technique of therapeutic BAL with diluted exogenous surfactant has been tried and shown some promising benefits in improving pathophysiological responses, increasing meconium removal amount, lowering ventilation duration, and decreasing the severity of illness (12,(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40). However, the techniques of therapeutic BAL are quite different among reported animal (Table 1) (23,(25)(26)(27)30,(32)(33)(34)(35)40) and neonatal studies (Table 2) (24,28,29,31,36 -39).…”

Continuous renal replacement therapy to reduce inflammation in a piglet hemorrhage–reperfusion extracorporeal membrane oxygenation model

“…The use of non-bronchoscopic BAL for treatment of meconium aspiration syndrome to improve oxygenation with a targeted volume of 10-15 ml/kg diluted surfactant saline suspension has been reported with modest success in both animal and human models (24,25). Non-bronchoscopic BAL has also been reported in ECMO patients on lung rest who are not dependent on native pulmonary function for gas exchange (26).…”

Experimental Models of Acute Lung Injury in the Newborns

“…The later possibility resembles better the situation of meconium aspiration in the neonates; however, it is associated with increase in PaCO 2 because of significant airway obstruction by meconium particles (Tyler et al 1978). Various animal species have been utilized for creation of the MAS model: piglets (Kuo and Chen 1999, Aaltonen et al 2005, Colvero et al 2008), rabbits (Krause et al 1998, Lam et al 2000, Zagariya et al 2010), rats (Calkovska et al 1999, Turhan et al 2012 Calkovska et al 2008, Mikolka et al 2013 and of more than 50 % in the studies by other authors (Robinson andRoberts 2002, Li et al 2015). Serious decline in the lung compliance after meconium instillation was observed also in other animal species (Wiswell et al 1994, Cochrane et al 1998, Zagariya et al 2010, Rey-Santano et al 2011, Renesme et al 2013.…”