EFFICACY OF INHALED NITRIC OXIDE IN PIGLET WITH MECONIUM ASPIRATION

Hua ZY¹, Wang DH²,Xu JZ²,et al

¹ Children’s Hospital, Chongqing University of Medical Sciences, Chongqing, China

² Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking, China

Objective: Meconium-stained amniotic fluid is found in 9%-20% of births, and meconium aspiration occurs in 2%－4% of all live births. Furthermore, mortality of severe meconium aspiration syndrome（MAS）is about 25%, these patients are rescued by extracorporal membrane oxygenation （ECMO）. ECMO is too expensive to be taken in developing countries. Severe MAS is characterized by pulmonary hypertension, persistent fatal circulation and severe hypoxemia. Nitric oxide（NO）is known as endothelium-derived relaxation factor. It has a vital role in blood pressure control as well as neurotransmitter and immune function. Inhaled NO produces pulmonary vasodilation near gas-exchanging alveoli, causing selective pulmonary vasodilation. MAS and other diseases complicated with pulmonary hypertension may be the best clinical targets for inhaled NO therapy. However, prolonged therapy of inhaled NO is costly and not safe. This study aims at evaluating and predicting efficacy of inhaled NO in meconium aspiration.

Methods: Thirty white strain newborn piglets weighing 1.8 to 2.3㎏ were obtained on the second to sixth day of life. Four to six ml/㎏ of 20% human meconium in normal saline were instilled into the trachea when animal was placed on the animal ventilator. Severe MAS was produced, partial pressure of arterial oxygen（PaO₂）<60mmHg, pulmonary arterial pressure（PAP）>25mmHg, and arterial/Alveolar ratio of oxygen pressure（a/APO₂）<0.2. Animals were randomly grouped into routine-therapy group and inhaled-NO group, the later received 20 per parts million NO inhaling therapy. To observe the efficacy at 5minutes(mins), 15mins,30mins,60mins,120mins after therapy, linear regression was used to identify correlation between various physiological parameters and the change in oxygenation index（PaO₂/FiO₂）, PAP and shunt fraction（Qs/Qt）due to inhalation of NO.

Results: The physiological changes of persistent pulmonary hypertension and hypoxemia in routine-therapy group couldn’t be improved,. Some piglets died of tension pneumothorax, pulmonary hemorrage and heart failure. 5mins after initiation of inhaled NO led to significant increases in PaO₂（from 50.1mmHg, SD 6.6 to 78.9mmHg, SD 7.7, P<0.01）and a/APaO₂（from 0.18, SD 0.03 to 0.26, SD 0.02, P<0.01）. At 15mins after NO inhalation a statistically significant decreases in PAP（from 31.8mmHg, SD 5.8 to 21.0mmHg, SD 3.3, P<0.01）and Qs/Qt（from 0.181, SD 0.039 to 0.134, SD 0.030, P<0.05）. Systemic blood pressure and heart rate did not change. Within 3mins of NO withdrawn, pulmonary arterial pressure increased to the level before NO inhalation. At 5mins after inhaled NO, the decrease in PAP did correlate with the Qs/Qt before NO inhalation（r=0.93, P<0.05）, the increase in PaO₂/FiO₂ at 30mins, the decrease in Qs/Qt at 60mins and the decrease in PAP at 90mins did correlate with the PAP before NO inhalation（r=0.94, r=0.94, and r=0.89, respectively, P<0.05）. After 120mins of NO inhalation, the change in PAP, Qs/Qt and PaO₂/FiO₂ did correlate with PAP before NO inhalation（r=0.90, r=0.96, and r=0.95, respectively, P<0.05）.

Conclusion: These results suggest that inhaled NO may be beneficial in meconium aspiration syndrome in neonates, decreasing pulmonary arterial pressure by selectively pulmonary vasodilation, improving oxygenation by decreasing extrapulmonary shunting and by improving ventilation/perfusion ratio. However, prolonged inhalation of NO may cause some severe side effects, such as methemoglobinemia, toxication of nitric dioxide and so on. Furthermore, prolonged therapy is costly.It is significant that we can predict efficacy of inhaled NO at the acute stage of therapy. In our study, the changes in PAP, Qs/Qt and PaO₂/FiO₂ at different therapy time correlate with PAP and PaO₂/FiO₂ before NO inhalation. It suggests that the efficacy of inhaled NO may be predicted after short-time therapy. However, our results couldn’t be repeated in other experiments, such as inhalation of NO 40 parts per million. More animal experiments and retrospective multi-center clinical studies are needed for finding out how to predict efficacy of NO inhalation.

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