The Application Of Non-invasive Cardiac Output Parameters、Perfusion Index And Pleth Variability Index In Premature Infants With Patent Ducts Arteriosus

1、Background and Objection1.1 BackgroundWith the rapid development of medical and neonatal medicine and the change of environment, economy and social factors,the survival rate of premature babies has been increased significantly recent years. Patent ductus arteriosus(PDA) is a early common disease in premature babies.It is a hot issue that how to find signs of illness timely during the growth in the premature palace,in order to take measures in advance.Cardiac output parameters and perfusion index, the index of perfusion variation have been studied more and more for its easy access, the continuous observation and the large clinical significance.Classified by gestational age, the ones whose birth gestational age is less than 37 weeks of are called premature infants.Epidemiological data show:in Europe, the incidence of preterm infants was about 5%～9% in the total number of all the newborn birth.In the United States, the incidence of preterm infants was 12.7%.In China, especially Beijing, Shanghai, Guangzhou, Shenzhen and other cities), the proportion of the total number of birth was about 7.8%～8.1%,it means that not less than 1.5 million premature babies are born each year in our nation.In Shenzhen, birth population is about 210000 a year in recent years, and about 15000 premature babies are born each year.Cardiac output (CO) is one of the most direct indicators reflect the heart function.cardiac output and its related hemodynamic indexes were measured timely,accurately by ultrasonic method or electrode method.It is an advantage that data can get by the bed monitoring at any time.Noninvasive cardiac output ultrasonic Monitoring technique adopts the mature technology of continuous wave doppler, to measure hemodynamic status precisely when the heart beats each time.Cardiac output is monitored by its unique design probe which percutaneous aortic blood flow measurement (sternal elevation nest or supraclavicular fossa), and pulmonary artery blood flow (breastbone left edge rib 2～4 gap). Probe ponits to the head, and maintain the probe parallel to the frame. We collect the most accurate doppler blood flow spectrum by paying attention to listen to the loudest and strongest signal, and then select the most appropriate location.In operation,we should keep the beam parallel to the direction of blood flow, and make the probe be in alignment with the blood flow from aortic valve/pulmonary valve injection, in order to obtain the most satisfactory spectrum.Perfusion index (PI) and pleth variability index (PVI) is a kind of monitoring which reflects peripheral circulation change in early postnatal, and it possesses the advantages of convenient and noninvasive method.In recurring obstacle, blood flow from the important organs, tissues, skin, muscle, digestive tract) to vital organs (heart, brain, kidney), it monitors the blood perfusion of unimportant organization, and is conductive to early detection of low perfusion of important organs.The arterial catheter between the aorta and pulmonary artery catheter often cannot effectively shut down when Premature babies are born, and it brings increased pulmonary blood flow, lung blood much, pulmonary edema, etc, which makes premature originally immature lungs adapt to postnatal oxygenation function needed more difficultly.Blood perfusion changes because of the open artery catheter.The blood discharge from left heart into the aorta oxygenation parts back into the lung oxygenation by the arterial catheter, which adds to the burden of the heart, also affects the heart coronary artery perfusion, and then make the premature heart prone to heart failure.In the same way,the changes of blood flow in brain, kidney, and gastrointestinal tract,make the premature babies prone to intracranial hemorrhage, oliguria,necrotizing enterocolitis, and so on.So the patent ductus arteriosus(PDA) has seriously increased the occurrence of complications and prognosis in preterm infants.As part of the open artery catheter closes naturally in postnatal days or even months,especially for the arterial catheter for with small duct diameter or less blood flow in premature infants, too early or excessive intervention will increase the intervention side effects.The prostacycline inhibitors are commonly used to Close arterial duct in clinical practice.and its side effects that oliguria, hemorrhage and so on drug that may occur.Some infants needs surgical ligation treatment,and it also brings related side effects. Therefore there is a controversy that whether or when to close the artery catheter.Currently,whether close the opening artery catheter in preterm infants depends on clinical cardiac ultrasound results combined with clinical Manifestation.Clinical manifestations are mainly:heart murmur, water hammer pulse, tachycardia, the stronger precordialbeat, the increased Pulse pressure, the worse breathing,etc.Ultrasonography standards include:(1) confirm left to right shunt. (2) the ratio of the diameter in left atrial and aortic root>1.3. (3) catheter diameter>1.5 mm. Standard is relatively complex, and the results are conformed especially by the examination of B ultrasonic doctor or specially trained doctor.Some infants who did not reach this standard but with evident clinical hemodynamic change also receive treatment according to clinicians experience.Noninvasive cardiac output monitor examination is easy, and the doctor who masters the inspection method only needs after a short-term training,its results have good repeatability.Especially the cardiac output index, such as heart around each cardiac output, cardiac index, the blood flow velocity peak, peripheral vascular resistance reflects to the large vascular hemodynamic changes.Combined with peripheral blood perfusion index,pleth variability index(be read on pulse oxygen saturation monitor) can better reflect the systemic circulation.Our initial preliminary study found that open artery catheter in premature babies might affect these parameters.We conduct a study to compared noninvasive cardiac related parameters combined with perfusion index with the traditional ultrasound in diagnosis, and to determine the clinical value of the new index, which will make premature PDA treatment simpler and more convenient, and take timely treatment, shorter hospital stay, reduce hospitalization expenses, and improve the prognosis of premature infants.1.2 Research purposesIn this study,PDA that needs to be closed by drugs is defined as Clinical handle PDA;PDA that don’t needs to be closed by drugs is defined as the untreated PDA; The ones whose artery catheter close within 3 days after birth are defined as normal preterm infants.These premature infants were divided into the PDA treated group,the PDA untreated group and the normal infants group by the results of echocardiogram in the first three days and the use of drugs. We collected all the subjects’non-invasive cardiac output parameters and PI, PVI data in the first three days,then compare the difference between groups by Statistical analysis. The cut-off value of the parameters related to the Clinical handle PDA by diagnosis will provide quantitative indicators for clinical treatment.Discussion related cut-off value’s application worth in treatment of PDA.Observe the changes of related parameters before and after arterial catheter’s close, and explore the predict meaning of the effectiveness of the treatment.2. Materials and Methods2.1 Research objectThe clinical data of the premature infants with a gestational age of 28-31 weeks.6 weeks or birth weight of 1000-1799 g admitted to the neonatal intensive care unit from January,2015 to December,2015 was collected.Exclusion criteria:(1) ultrasound confirmed that the infants have congenital heart disease (2) antenatal examinations show clear birth defects and other chromosomal abnormalities (3) needs to have a breathing machine auxiliary support, severe asphyxia, severe infection and unstable circulation. (4) be diagnosed as intraventricular hemorrhage(IVH)Ⅲ, Ⅳ by head color Doppler ultrasound in the first three days.2.2 Experimental methods2.2.1 Grouping:These premature infants were divided into the PDA treated group,the PDA untreated group and the normal infants group by the results of echocardiogram in the first three days and the use of drugs.According to the average value of the aorta and pulmonary artery CI, MD, (three times/day 3 days) measured by the ultrasonic monitoring cardiac output in the first 3 days,the studying objects are divided into clinical handle patent ductus arteriosus(Clinical handle PDA)and no clinical handle patent ductus arteriosus(no Clinical handle PDA).2.2.2 Grouping method:1)the PDA treated group:Conventional echocardio-graphy examination within 3 days after birth, Reference to the criteria defined by Malviya and so on, one of clinical signs:heart murmur, water hammer pulse, tachycardia, the stronger precordialbeat, the increased Pulse pressure, the worse breathing, combined with all the following ultrasonics standards:(1) confirm left to right shunt. (2) the ratio of the diameter in left atrial and aortic root>1.3.(3) catheter diameter>1.5 mm.(4) the ventricular diastolic blood flow to the main pulmonary artery mixed with catheter under aortic blood flow backwards and forward catheter on aortic blood flow (can be considered a two-way shunt exists).The premature babies satisfying the above diagnosis criteria are all using drugs to close artery catheter; Another infants with PDA who don’t fully achieve the above standard, but clinical doctors still close artery catheter by use of drugs according to the severity of the disease and clinical symptoms.All the infants using drugs to close artery catheter are defined as clinical handle PDA.2)the PDA untreated group:The patent ductus arterious do not meet the above clinical diagnostic criteria,so it does not require the use of drugs.3)the normal infants group:the results of echocardiography show that artery catheter is closed.2.2.3 Noninvasive cardiac output check:all the premature infants are checked the cardiac output by using ultrasonic monitor cardiac output (USCOM 1 a, Australia) every day in the first three days, at the same time every morning and repeat 3 times each time, so each noninvasive cardiac output parameter has a total of nine numerical (three times/day 3 days), and then each parameter has the final average. The data will be collected until on the day of drug use to close arterial duct within 3 days after birth.Operations are completed by a neonatal doctor who is trained rigorously.2.2.3.1 Noninvasive cardiac output measurement :maintain the infants in horizontal position and be quiet. The probe in sternal elevation nest or supraclavicular fossa is in alignment with of the blood flow from aortic valve/pulmonary valve injection to measure related parameters.In operation,we should pay attention to listen to the loudest and strongest signal, and then select the most appropriate location.keeping the beam parallel to the direction of blood flow to obtain the most satisfactory spectrum.The selection criteria of the optimal signal graphics about blood flow is: isosceles triangle, smooth line, a sharp peak, fill full, shown as figure 1-2.2.2.3.2 Data collection:Record 38 data including aortic and pulmonary cardiac index (CI) and minutes distance (MD) measured by cardiac output ultrasound monitor.2.2.4 Perfusion index,pleth variability index data collection methods:We monitor the infants’peripheral perfusion circulation situation by pulse oxygen saturation monitor (Masimo Rainbow SET Radical-7) at the fixed time(9:00-11:00 am). maintaining the premature infants in quiet state, we record 10 minutes.And after being waveform is stable,we read the average of perfusion index and pleth variability index, recording the heart rate, blood oxygen saturation and other indexes at the same time.2.3 Statistical methods:Statistical analysis by SPSS20.0 software.Measurement data in the normal distribution Expressed as mean±standard deviation (x±s),comparison between two groups by t test.Comparison among groups by one-way ANOVA,and between two groups by SNK-q test.preliminary analysis of noninvasive cardiac output parameters by receiver operating characteristic curve(ROC curve)to select two representative parameters,and then analyze the diagnostic value of the two parameters for Clinical handle PDA.Difference was statistically significant (P< 0.05).3. Results3.1 The ROC curve analysis of noninvasive cardiac output parameters:firstly, through the preliminary analysis,the results of the area under the ROC curve (AUC)of noninvasive cardiac output 38 parameter show that of the aorta CI and the aorta MD were 0.86 and 0.82 respectively,and that of the pulmonary artery CI and the pulmonary artery MD were 0.86 and 0.84 respectively (only list top 5),suggesting that the two parameters are the most representative parameter of the diagnosis of clinical handle PDA, so we choose the two parameters as a research object.3.2 The aorta and pulmonary artery CI, MD test results:The aorta, pulmonary artery CI and MD in the PDA treated group were significantly higher than that in the PDA untreated group and the normal infants premature group, with significant difference (P<0.05). There were no significant difference between the PDA untreated group and the normal infants premature group in the aorta, pulmonary artery CI and MD(P>0.05).3.3 The ROC curve analysis of the aorta and pulmonary artery CI, MD:The cut-off value of the aorta CI, MD are 2.95 L/(min-m2) and 21.50 m/min respectively,the combination of the two can improve specificity,reaching up to the highest sensitivity of 0.90.The combination of pulmonary and aorta artery CI, MD has the highest specificity of 0.88 in clinical handle PDA.3.4 The closure of arterial duct in the PDA treated group and the PDA untreated group:the closure rate of the overall premature infants was 85.07%(57/67). The closure rate of premature infants in the PDA treated group was 70.83%(17/24),and that of premature infants in the PDA untreated group was 93.02%(40/43).There were significant difference between the PDA treated group and the PDA untreated group in closure rate(P<0.05).3.5 The change of the noninvasive cardiac output parameters after arterial duct’s closure in the PDA treated group :considering the heart rate (HR) has no actual meaning, this parameter is excluded in the analysis.The results show that only pulmonary artery FT and aortic artery SVI, SV, vti have significant difference was significant(P<0.05),in noninvasive cardiac output 36 parameters,and there is no significant difference in the other 32 parameters(P>0.05).the aorta and pulmonary artery CI, MD decreased after arterial duct’s closure in the PDA treated group,but there is no statistical significance.3.6 The comparison of perfusion index and pleth variability index among the PDA treated group,the PDA untreated group and the normal infants premature group:there is no statistical significance among the three groups in perfusion index and pleth variability index(P>0.05).Pleth variability index in the PDA treated group is significantly higher than that in the PDA untreated group and the normal infants premature group (P<0.05).However,there is no statistical significance between the PDA untreated group and the normal infants premature group.3.7 The change of perfusion index and pleth variability index after arterial duct’s closure in the PDA treated group:The results show that there is no significant difference after arterial duct’s closure in the PDA treated group(P>0.05).4.Conclusion4.1 It is a preliminary judgment for the preterm infants with clinical handle PDA that the aortic artery CI no less than 2.95I/min m2 and the aortic MD no less than 21.50 m/min。We should take measures timely to close the arterial duct if the pulmonary artery CI no less than 4.55 L/(min·m2) and the pulmonary artery MD no less than 26.50 m/min simultaneously.4.2 The accuracy of diagnosis cut-off value of noninvasive cardiac output parameters CI, MD for PDA is high.It is a reference method for Its high true negative rate and true positive rate.There is no significant difference in noninvasive cardiac output parameters CI, MD after arterial duct’s closure in the PDA treated group,suggesting that we estimate artery catheter closure still depend on the results of echocardiography,not the change of the pulmonary the aortic artery CI and MD.4.3 Whether or not hemodynamic significant PDA will not affect the peripheral blood perfusion,but hemodynamic significance of PDA may make blood flow volatility increased.There is no obvious change after arterial duct’s closure by drugs(P>0.05).