Effects Of Nitric Oxide Inhalation On Oxygenation Function And Inflammatory Response In The Treatment Of Newborns With MAS

Objective: Meconium aspiration syndrome(MAS) was the respiratory system serious disease in newborn, also was one of the difficult governing respiratory failure reasons in the perinatal period. It is from the embryo apnea because of the oxygen deficiency in the uterus, the anus sphincter dilatated, discharged the meconium-stained amniotic fluid. When prior to delivery or delivery, meconium inspiration to lungs caused a series of clinical manifestation. MAS mainly occurred in full-term, smaller than the gestational age and post-term infants. In the domestic report, MAS occurred in live-born infants approximately 1.2%-1.6%, case fatality rate approximately 7%-15.8%. The hypoxemia, high carbohemia and the acidosis were clinanical characteristic, and the case fatality rate was high. The pathogenesis of MAS was not yet completely clear. The animal experimentation proved that MAS was possiblly related to the infection and the endothelial cell function disorder. Meconium entered into the lung, induced the serious inflammation responses in bronchiole and the pulmonary alveolus and caused many kinds of cytokine to release. In the fulminating anoxia infants, the pulmonary circulation resistance was higher, and caused the pulmonary artery, the right camara and right antrum pressure continued to advance. And if either the pulmonary artery or right antrum pressure was higher than the pressure of aorta or left atrium, a right-to-left shunt from the ductus arteriosus or the foramen ovale could produce, if the ductus arteriosus and the foramen ovale continued to open, then hypoxemia could be caused and lung blood stream was reduced, formed persistent pulmonary hypertension (PPHN). The treatment methods of MAS included the cleaning up respiratory tract, the conventional monitor, the maintenance of temperature, the blood gas, blood sugar, electrolyte stable, oxygen therapy, the machinery ventilation, the application antibiotic treatment and so on. If concurrent with hypoxemia or PPHN, inspiration nitric oxide (NO) could be utilized to reduce pulmonary artery pressure, and improve the oxygenation function. This experiment was for the purpose of observing how iNO influenced the oxygentation function of infants troubled with MAS, also to observe the cytokine of expression of the lung tissue, thus provided the theory basis for the therapy of MAS.Methods:1 Experiment objectsThe newborns of the intensive care unit in Hebei Province children hospital were selected, who entered newborn department on February, 2005 to March, 2007, the embryo age in 37-43 weeks, the body weight 2.5kilograms-4kilograms. MAS conformed to MAS diagnostic criteria in the practice neonatology in 2004 the 3rd edition. And the partner has II breath failure, (blood gas standard: PH<7.25, PaO2<6.67Kpa, PaCO2>6.67Kpa), need mechanical ventilation to maintain normal PaO2 and PaCO2, or combined with PPHN, All infants were supplied with airtube intubation, irrigation of trachea,application with baby breathing machine, assisted respiration with SIMV mode. 30 healthy full-term newborns borned in the same hospital in the same time were taken to the comparison group.2 The experiment groupsThe MAS infants were divided into the inspiration nitric oxide group (Group A), and the conventional treatment group (Group B), according to the random digits table, conducted foresighted research, Group C for comparison group.2.1 Group A of 25 examples, the embryo age 39.92±1.55weeks, the birth body weight3.19±0.36kg (28 examples were selected, to give up the treatment 1example, to be rejected because of sample haemolysis or absence 2examples);2.2 Group B 0f 30 examples, embryo age 40.14±1.67weeks, birth body weight 3.39±0.46kg (32 examples were selected, to give up the treatment 1example, to be rejected because of sample haemolysis or absence 1example);2.3 Group C of 30 examples, the embryo age 38.58±1.37 weeks, the birthbody weigh 3.28±0.42kg, were selected randomly on the same time of the same hospital, who born in 1 day, and were born in full-term, excepted for in the palace poverty-stricken, the amniotic fluid early broken, the amniotic fluid pollution history, and apnoea, aspirated pneumonia history.3 Laboratory procedure3.1 Group A and Group B infants of selected accepted the standard treatment, included the machinery ventilation, the appropriate fluid infusion, the antibiotic and other medicine treatments. Group A simultaneously accepted the inspiration nitric oxide treatment. The entire journey two groups of infants were observed vital sign in whole range. The average gas channel presses (MAP), the inspiration oxygen concentration (FiO₂), the breath machine parameter were observed too. The blood gas analysis was made using the artery blood from the beginning of treatment (0h) and 24 hours (24h),72hours(72h) after treatment. The artery blood oxygen partial pressure (PaO₂) was determined. The oxygen index (oxygen index, OI) and the artery/pulmonary alveolus oxygen partial pressure ratio (a/APO₂) were figured out. Two groups of tinfants were recorded the machinery ventilation time, around observation treatment pulmonary artery pressure changes were recorded too.3.2 Group A were taken the bronchial alveolus fluid and the venous blood 2ml when the NO treatment (0h) and 24 hours (24h), 72 hours (72h) aftter therapy. With the 3000r/min centrifugalization 10 minutes, blood serum were accepted and set spare to -30℃refrigerator preservation. Group B were taken the bronchial alveolus fluid and the venous blood 2ml when the breathing machine treatment (0h) and 24 hours (24h) ,72 hours (72h) aftter therapy. With the 3000r/min centrifugalization 10 minutes, blood serum were accepted and set spare to -30℃refrigerator preservation. Group C were taken 2ml venous blood when born (0h) and 24hours (24h) ,72 hours (72h) after born and separated blood serum too. The blood serum were put into -30℃refrigerator for preservation.4 The experimental technique IL-8 and IL-10 concentration were monitored before and after therapy. The radio-immunity method was used. The events-per-unit-time meter used for experiment was: FT-630G, MICRO-COMPU TERED MUTIL-PROBγCOUNTER,CHINA BEIJING NUCLEAR INSTRUMENT FACTORY,The reagent kits for IL-8 and IL-10 radiommunoassay were provided by Beijing north biological technology research institute, the examination step and the method carried on according to which the medicine kit showed.5 The statistical analysis SPSS10.0 statistics software was used to carry on statistics processing, P<0.05(double side) had statistical significance.Results:1 Time of using breath machine treatments of Group A was shorter comparied with group B (machinic ventilation time of GroupA(77.38±13.97)h, of GroupB(104.27±10.53h), two groups of statistics had significance differences(P<0.05). There were no significance difference of OI, a/APO₂ on 0h between GroupA and GroupB, But OI of GroupA was lower than GroupB on 24h, 72h. a/APO₂ was higher than GroupB on 24h, 72h. There was significance difference.2 Doppler echocardiography was used to exmine the infants troubled with MAS(GroupA,B), discovered that there were different level PPHN in two groups before therapy. The results of the comparison of two groups post-treatment explained that the degresion of GroupA was more obvious than GroupB, the equation was (38.64±10.03) mmHg. Simultaneously, the right-to-left shunt decreased obviously, substituted with bidirectional shunt or left-to-right shunt. Among two groups, the shunt of 6 examples disappeared. The average time of utilizing iNO was (31.42±13.51)h. Comparison of prognosis and turnover indicated that there were no statistics difference of death rate, and incidence rate of frequent hemorrhoid, pneumonorrhagia, ICH(â…¡-â…£)between GroupA and GroupB.3 Compared with GroupC, blood serum IL-8 and IL-10 advanced in blood serum of GroupA and GroupB on 0h. But there were no significance differences between GroupA and GroupB. On 24 hours and 72 hours after therapy, compared with GroupB, IL-8 in blood serum and in bronchial alveolus fluid of GroupA were decreased, there were significance differences in statistic.But compared with Group C, IL-8 in blood serum in GroupA and GroupB were still increased(P<0.05). Compared with Group B, IL-10 in Group A of blood serum and in bronchial alveolus fluid were increased 24hour and 72hour after treatment. In statistics had significance differences(P<0.05).Conclusions: 1 Conducted as a special therapy method, there were kinds of contributions of inspiration NO such as selectively expanding pneumoangiogram, improving ventilation/perfusion rati, reducing shunt of lung, cutting down PPHN, so as to shorten time of using breathing machine and improved oxygenation condition. Inhaled NO would not increase incidence rate of major concurrent disease such as frequent hemorrhoid, pneumonorrhagia, ICH. 2 Hypoxia, collection of granular leukocytes to lungs and release of cytokine could be caused by MAS. The inflammation response is the MAS important pathology and physiology change. 3 The release of proinflammatory factor IL-8 may be reduced by small dosage inspiration NO to weaken PMN to hasten, gather, mount and attach, finally reducing PMN sequestration in the lung, playing the certain suppression lung inflammation role. Simultaneously the function which anti-inflammation factor IL-10 surrenders was discovered. It explained that inspiration NO possibly could adjust the lung inflammation in the whole, As for did not cause the imbalance of inflammation -anti- inflammation response. There was protective function to the inflammation caused by MAS. But its function possibly affected by the many kinds of factors.