Safety And Feasibility Of Inhaled Carbon Monoxide In Neonatal Diseases

Objective:Neonatal persistent pulmonary hypertension (PPHN) is due to continuously increased Pulmonary vascular pressures after birth, so the infant can not be transferred from the fetal circulation to neonatal circulation, when pulmonary vascular pressure exceeds systemic pressure, a lot of none-oxygenated blood can shunt from right to left through arterial catheter and foramen ovale. It causes neonatal cyanosis, persistent hypoxemia, High concentration oxygen inhalation cannot alleviate cyanosis. PPHN is one of serious common diseases in neonatal intensive care unit (NICU),The incidence of PPHN in live births is0.1%-0.2%, and the mortality rate is as high as25%-50%, so it is one of the hotspot of medical problems.Nitric oxide (NO) inhalation therapy could reduce pulmonary hypertension, because of its non-invasive, good effect, NO inhalation therapy has became the main means of treatment and the most commonly used therapy for PPHN at home and abroad.Nevertheless, there are still nearly40%of patients is invalid with NO inhalation, searching for a new treatment is urgent.Since the middle of the twentieth Century, the domestic and foreign researches have discovered that carbon monoxide (CO), the double atomic combustible gas, could be produced from heme by heme oxygenase (HO) oxidation in vivo, thus, the researches on mechanism and effects of endogenous CO have been launched. In recent years, studies have found that CO has a cell protection function with anti-inflammatory, oxidation, proliferation, apoptosis, its inhibition of proliferation of vascular smooth muscle cells and vascular dilation function may have an effect for PPHN, the formation of endogenous HO/CO may be involved in the formation of hypoxic pulmonary hypertension. However, as everyone knows, CO is also one kind of chemical asphyxiants, its affinity with hemoglobin is much stronger than that of oxygen affinity with hemoglobin, thereby preventing hemoglobin transport oxygen to the tissues and organs, and then leads to hypoxia asphyxia.There is a tradeoff between the important potential utility of CO on neonatal critical illness and its toxicity, It is necessary to explore the safety and feasibility of application of CO in neonates. This study is based on this purpose, to explore the feasibility and safety of inhaled CO therapy applied in neonates, and also to explore the anti-inflammatory and antioxidant benefits of the CO on the body, so we can provide the prerequisites for further study of CO inhalation as a new therapy treatment for neonatal critically ill.Considering the neonatal critical illness such as PPHN or bronchopulmonary dysplasia (BPD) and CO poisoning may require ventilator, this study also try to compare the efficacy of respiratory support between nasal continuous positive airway pressure (nCPAP) and nasal intermittent positive pressure ventilation (nIPPV). after ventilator extubation at the same time.Methods:Part Ⅰ:Safety and feasibility of inhaled carbon monoxide in infants with stabilized pneumonia1. Twenty-four term infants with stabilized neonatal pneumonia were distributed into4groups using randomly blind method, respectively inhaled50,60,70,100ppm CO2h, continuous monitoring their vital signs and carboxyhaemoglobin (COHb) concentration was used to evaluate the feasibility and safety of CO inhalation;2. Determined inflammation and oxidative parameters of blood, explored the effect of CO on anti-inflammatory and antioxidant.Part Ⅱ:Nasal positive pressure ventilation versus after extubation:a retrospective analysisFor a retrospective study, in accordance with the respiratory support mode after extubation,196patients were randomly divided into two groups between January,2011and December,2012, respectively was group nIPPV (n=102); group nCPAP (n=94), The ratio of requirement for endotracheal ventilation and the outcome were investigated.Results:Part Ⅰ:Safety and feasibility of inhaled carbon monoxide in infants with stabilized pneumonia1. No patients needed to be terminated because of adverse effect;2. There were no significant changes of carboxyhaemoglobin (COHb) concentrations during the course of CO inhalation with50or60or70ppm groups; 3. Serum inflammation and oxidant parameters including advanced oxidation protein products (AOPPs), malondialdedyde (MDA), total antioxidant capacity (TAOC),and macrophage inflammatory protein-2(MIP-2) showed decreasing trends with the increase of CO concentrations, but no significant differences were found in different times and groups.Part II:Nasal positive pressure ventilation versus after extubation:a retrospective analysis1. Group nIPPV respiratory support after extubation:days (6.3±2.8) d, the successful rate was88.2%(90/102); group nCPAP:(7.1±2.4) d, the rate was75.5%(71/94);2. After extubation, group nIPPV needed a shorter time, and has a more successful rate (p<0.05).Conclusion:Part Ⅰ:Safety and feasibility of inhaled carbon monoxide in infants with stabilized pneumonia1. Vital signs were unaffected in the group of CO inhalation with50or60or70ppm, and CO Inhalation in term infants with neonatal pneumonia in a stable phase was feasible and safe;2. There was a reduction trend of inflammation and an improvement of oxidative stress during the course of CO inhalation;3. Further studies are needed to confirm the safety and efficacy of long-time CO inhalation in newborn infants.Part Ⅱ:Nasal positive pressure ventilation versus after extubation:a retrospective analysis1. nIPPV not only can be used as the initial model of respiratory support, but also can be applied to treat children with respiratory support after extubation;2. The time of nIPPV group with extubation respiratory treatment is shorter than nCPAP group;3. The success rate of extubation in nIPPV group is higher than in nCPAP group.