Early changes of cTnT and NT-proBNP in neonates underwent ECMO support: a single-center experience

doi:10.21203/rs.3.rs-2613146/v1

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Early changes of cTnT and NT-proBNP in neonates underwent ECMO support: a single-center experience

https://doi.org/10.21203/rs.3.rs-2613146/v1

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Objective: To explore the changes in the absolute value and decline rate of early serum cTnT and NT-proBNP in neonates who underwent V-A ECMO support therapy within one week of birth.

Methods: Clinical data and laboratory test results of 17 neonates who underwent V-A ECMO support therapy within one week of birth from January 2020 to January 2023 were retrospectively collected from the electronic medical record system. The patients were divided into the survival group and the death group. The absolute values and decline rate of cTnT and NT-proBNP were compared between the two groups on the day, 24, 48, and 72 hours after ECMO treatment.

Result: Of the 17 neonates, 10 survived, and 7 died, with a survival rate of 58.8%. The absolute values of cTnT and NT-proBNP in the survival group were significantly lower than those in the death group, and the decline rate was significantly higher than in the death group. In this study, neonates with no early decline in cTnT and NT-proBNP were all in the death group.

Conclusion: The changes in the absolute value and decline rate of early serum cTnT and NT-proBNP in neonates who underwent V-A ECMO may predict their prognosis.

neonates

ECMO

cTnT

NT-proBNP

Neonatal respiratory and circulatory failure is the most common critical illness leading to neonatal death. With the continuous advancement of respiratory support and treatment technologies such as pulmonary surfactant (PS), high-frequency oscillatory ventilation (HFOV), and inhaled nitric oxide (iNO), most neonates can be treated. But many newborns with severe respiratory failure still need extracorporeal membrane oxygenation (ECMO) support. At present, ECMO technology has been widely applied in advanced medical neonatal intensive care units for severe meconium aspiration syndrome (MAS), acute respiratory distress syndrome (ARDS), congenital diaphragmatic hernia (CDH), persistent pulmonary hypertension of the newborn (PPHN), and severe lung infection, and the overall survival rate is between 51% and 95%.^1,2 Cardiac troponin T (cTnT) is a specific marker of myocardial cell injury, which has been widely used clinically and has an excellent predictive value for various diseases that cause primary and secondary myocardial cell injury.^3,4 The increase of N-terminal pro-brain natriuretic peptide (NT-proBNP) has excellent application value in detecting myocardial function and disease progression in cardiovascular patients.⁵ Few articles have reported the changes of the early change of cTnT and NT-proBNP in light-weight neonates within one week of birth who received veno-arterial (V-A) ECMO. Therefore, the purpose of this study is to explore this topic based on our existing clinical experience to provide a reference for the early treatment strategy of these patients.

Patient

This study was a retrospective study and was approved by our hospital’s ethics committee. Neonatal patients receiving V-A ECMO treatment from January 2020 to January 2023 were selected from the electronic medical record system, and their clinical data and laboratory test results were collected. Exclusion criteria: 1) age > seven days at the time of ECMO support; 2) incomplete data; 3) family members refused to participate. Finally, according to the inclusion and exclusion criteria, we selected 17 neonatal patients and divided them into a survival group (n=11) and a death group (n=6) according to their survival status.

ECMO indications and contraindications

ECMO indications: 1) oxygenation index (OI) > 40 for more than 4 hours; 2) OI > 20 for more than 24 hours or dyspnea continues to worsen (OI = mean airway pressure (MAP) × oxygen inhalation concentration (FiO₂) × 100 / arterial partial pressure of oxygen (PaO₂)); 3) with active respiratory support, the condition continues to deteriorate with severe hypoxemia (PaO₂< 40 mmHg); 4) blood gas analysis showed pH < 7.15, blood lactic acid ≥ 5 mmol/L, urine output < 0.5ml/(kg∙ h) lasted for 12-24 hours; 5) pulmonary hypertension lead to right ventricular dysfunction, which required continuous high-dose inotropic drugs to maintain cardiac function (vasoactive inotropic score (VIS) > 40 points). VIS = dopamine (μg/kg/min) + dobutamine (μg/kg/min) +10 × milrinone (μg/kg/min) +100 × epinephrine (μg/kg/min) +100 × norepinephrine (μg/kg/min) +10000× pituitrin (units/kg/min).⁷

ECMO contraindications: 1) fatal congenital disabilities; 2) grade III or above intraventricular hemorrhage; 3) uncontrolled bleeding; 4) other irreversible brain injuries.⁸

ECMO strategy

All cases used the Medos ECMO system (Beijing Medos Medical Technology Co., Ltd), including the children’s kit, tubing, oxygenator, and centrifugal pump head, which were all heparin-coated. In all cases, veno-artery intubation, sedation, anesthesia, and muscle release were used. Intubation was performed through the right internal jugular vein (10 Fr) and the right common carotid artery (8 Fr) according to operating specifications and aseptic principles. 1000 ml Ringer’s solution pre-filled the pipeline to exhaust, albumin and suspended red blood cells (added heparin 0.5-1 mg/U red blood cells according to the coagulation condition) to drain the crystalloid in the pipeline, then added 5% sodium bicarbonate 5-10 ml, 10% calcium gluconate 3 ml. The procedure of withdrawing ECMO was as follows: reduced the flow rate to 50 ml/kg/min, increased the ventilator parameters to normal mode, and continued to observe for 3-6 hours. The arterial blood gas was used to evaluate lung ventilation and body oxygenation. After the vital signs were stable, ECMO was withdrawn, and the arterial and venous cannula was removed.

Measurement of cTnT and NT-proBNP

Our center routinely measured cTnT and NT-proBNP levels in patients’ venous blood on the day of ECMO treatment, 24 hours, 48 hours, and 72 hours after ECMO treatment. cTnT decline rate = (initial cTnT– 24h or 48h or 72h cTnT) / initial cTnT. NT-proBNP decline rate = (initial NT-proBNP–24h or 48h or 72h of NT-proBNP) / initial NT-proBNP.

Statistical method

The normal test checked all the measurement data; if they conformed to the normal distribution, the t-test was used, and if they did not conform to the normal distribution, the non-parametric test (Mann-Whitney Test U test) was used for comparison and analysis. Count data were analyzed by chi-square test. The statistical software used was SPSS Statistics 26. Statistical data were expressed as mean ± standard deviation, and p <0.05 was considered to have a significant statistical difference.

A total of 17 neonates with respiratory and circulatory failure who received ECMO support were included in this study, of which 10 survived and 7 died, with a survival rate of 58.8%. All 17 Neonatal patients were weaned off the ECMO successfully. Except for the statistical difference in weight between the survival group and the death group, there was no statistically significant difference in gender, gestational age, age at ECMO, OI, VIS, ECMO duration, pulmonary artery pressure, and the length of ICU stay (table 1).

In the survival group, the diseases that led to neonates needing ECMO support were: PPHN (1 case), PPHN combined with ARDS (5 cases), MAS combined with ARDS (2 cases), CDH combined with PPHN (2 cases). In the death group, the diseases requiring ECMO support were: PPHN (2 cases), PPHN combined with ARDS (1 case), MAS combined with ARDS (1 case), CDH combined with PPHN (1 cases), and low cardiac output syndrome (2 cases). (Table 2)

Tables 3 and 4 showed the two groups' changes in serum cTnT and NT-proBNP levels. In terms of absolute values of serum cTnT and NT-proBNP levels, the death group was significantly higher than the survival group, and there were significant statistical differences on the day of ECMO treatment, 24h, 48h, and 72h after ECMO treatment. The serum cTnT and NT-proBNP in the two groups gradually decreased with the prolongation of ECMO time. And in the decline rate, the survival group was significantly higher than the death group, and there were statistical differences. In both groups, cTnT decreased most considerably on the first day of ECMO treatment, while NT-proBNP decreased most significantly on the second day of ECMO support. At the same time, in this study, cTnT and NT-proBNP did not decrease at the early stage in the death group.

Through retrospective research, this study focused on the changes in the absolute value and decline rate of early serum cTnT and NT-proBNP in neonates less than 4kg and within one week after birth, which required ECMO treatment for neonatal respiratory and circulatory failure. This study showed that the absolute values of early cTnT and NT-proBNP in the death group were significantly higher than those of surviving patients, and the decline rate was significantly lower than that of surviving patients. The ECMO technology application ensures circulation and gas exchange and gains time to recover the failing respiratory and circulatory function. Many articles have focused on the research of cTnT and NT-proBNP in the ECMO treatment of fulminant myocarditis.^9,10 However, few relevant reports focus on neonates weighing less than 4 kg and receiving ECMO within one week after birth. And clinically commonly used cTnT and NT-proBNP indicators are studied based on adults. However, there are relatively few reports on the changes of cTnT and NT-proBNP in newborns with small body weights after receiving ECMO treatment. Therefore, this study's highlight focused on light-weight newborns treated with ECMO, which was where other studies needed to pay more attention.

Some studies have confirmed that myocardial cell ischemia and hypoxia caused by various reasons can lead to elevated serum cTnT levels.^11,12 PPHN and ARDS lead to respiratory and circulatory failure, myocardial damage is diffused and progressively aggravated, and cTnT often shows a persistent increase in the early stage. ECMO treatment uses a centrifugal pump to draw blood from the vena cava, reduce cardiac preload, reduce left ventricular end-diastolic volume, and reduce cardiac oxygen consumption. Increase blood pressure, ensure cardiac oxygen supply, and avoid myocardial damage caused by hypoperfusion so that cTnT can be decreased earlier.¹³ These results were similar to our findings. In our cases, serum cTnT decreased significantly after ECMO treatment. In addition, we found that cTnT increased on the second day after ECMO treatment, and death occurred, which might indicate that cTnT did not decrease after ECMO treatment, leading to a poor prognosis. At the same time, it was interesting that we observed a significant increase in serum cTnT after weaning off ECMO, which might be related to the increase in cardiac work and oxygen consumption after weaning off the machine, which needed to be further studied. Therefore, in addition to the absolute value of serum cTnT, we should pay more attention to the decline rate. It might be a good predictor of neonatal ECMO prognosis.

BNP is a polypeptide neurohormone that is mainly synthesized in the ventricle. It first synthesizes a physiologically inactive hormone precursor by ventricular myocytes; then, it can be cleaved into BNP and NT-proBNP under endonuclease action. When the patient’s ventricular volume load increases, it can increase the wall tension and reduce the systolic or diastolic function of the ventricle, thereby causing the synthesis and release of NT-proBNP and increasing the level of NT-proBNP.1^4,15 Neonatal respiratory and circulatory failure leads to weakened cardiac contractility and blood stasis in the heart, resulting in increased wall tension and stimulated NT-proBNP increase. While, ECMO support, cardiac work, oxygen consumption, and mechanical shear force are all reduced, which may be the reason for the decrease of NT-proBNP under ECMO support. In this study, NT-proBNP decreased significantly under ECMO support. Falkensammer et al. reported that BNP levels might indicate left ventricular stretch and are a valuable indicator of monitoring left ventricular dilation.¹⁶ Reynolds et al. believed that the level of BNP was related to the function of the right heart, and in children with PPHN, BNP could also be used to predict the survival rate.¹⁷ Baptista and his colleagues evaluated NT-proBNP in 13 neonates with CDH and found that high levels predicted death.¹⁸ And our study also found that the NT-proBNP of the death group was significantly higher than that of the survival group, and the decline rate was significantly slower than that of the survival group. This result was similar to the findings of the appeals study. Those patients who did not decrease in NT-proBNP 24 hours after ECMO treatment were all in the death group, which indicated that no decrease in NT-proBNP after ECMO treatment might lead to a poor prognosis. This finding suggested that not only the absolute levels of cTnT and BNP should be paid attention to in clinical work but also their dynamic change trends, which might be more effective in predicting the prognosis than the absolute values.

Limitation

The study still had certain limitations. The first limitation was that the sample size was small. To focus on underweight neonates who received ECMO treatment within one week after birth, the incidence of neonates who needed ECMO treatment was relatively low, so the sample size was limited. Secondly, the limited sample size made it impossible to conduct an effective statistical analysis of the factors related to prognosis. In addition, this study was a single-center retrospective study. In the future, we plan to adopt a joint multi-center survey to analyze further the factors related to the prognosis of under-weight newborns who receive ECMO treatment one week after birth.

The changes in the absolute value and decline rate of early serum cTnT and NT-proBNP in neonates who underwent V-A ECMO may predict their prognosis, but this result requires further study.

Data Sharing and Data Accessibility

The data supporting this study’s findings are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.

Competing Interests

All authors declare that they have no competing interests.

Funding

There is no funding.

Author Contributions

Jiang-Shan Huang and Qiang Chen designed the study, performed the statistical analysis, participated in the operation, and drafted the manuscript. Xiu-Hua Chen, and Si-Jia Zhou collected the clinical data. Yi-Rong Zheng and Hua Cao supervised the study. All authors read and approved the final manuscript.

Acknowledgments

We highly acknowledge the following researchers’ contributions: Qi-Liang Zhang, Ze-Wei Lin, Wang-Sheng Dai, Li-Wen Wang, Zeng-Chun Wang, and Ling-Shan Yu. Hope humans eventually defeat COVID-19.

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Table 1: General clinical data of patients

	survival group	death group	P
number	10	7	-
Male / female	6/4	6/1	0.278
gestational age (weeks)	37.8±2.4	35.9±2.9	0.150
age at ECMO (d)	1.8±0.74	3.1±2.5	0.150
weight (kg)	3.4±0.40	2.6±0.47	0.001
OI	55.2±14.9	75.1±44.8	0.237
VIS	53.6±3.8	70.0±24.5	0.069
ECMO duration (h)	83.4±9.9	68.9±19.6	0.078
pulmonary artery pressure	67.2±13.1	62.9±21.0	0.630
ICU (d)	23.5±14.6	16.0±12.2	0.353

Table 2 Disease distribution of the two groups

	survival group	death group
PPHN	1	2
PPHN+ARDS	5	1
MAS+ARDS	2	1
CDH+PPHN	2	1
LCOS	0	2

PPHN: persistent pulmonary hypertension of the newborn

ARDS: acute respiratory distress syndrome

MAS: meconium aspiration syndrome

CDH: congenital diaphragmatic hernia

Table 3 Comparison of two groups of cTnT

	survival group	death group	P
cTnT0	410.4±365	756.2±105.3	0.047
cTnT1	381.2±745.9	636.7±214.6	0.006
cTnT2	259.9±507.7	524.2±284.4	0.011
cTnT3	237.9±494.4	521.8±197.7	0.000
ΔcTnT1-0	0.48±0.13	0.17±0.16	0.001
ΔcTnT2-1	0.61±0.16	0.31±0.33	0.026
ΔcTnT3-2	0.68±0.23	0.29±0.28	0.010

cTnT0= initial cTnT; cTnT1= 24h cTnT; cTnT2= 48h cTnT; cTnT3= 72h cTnT

ΔcTnT1-0=(initial cTnT–24h cTnT) / initial cTnT.

ΔcTnT2-1=(24h cTnT–48h cTnT) / 24h cTnT.

ΔcTnT3-2=(48h cTnT–72h cTnT) / 48h cTnT.

Table 4 Comparison of two groups of NT-proBNP

	survival group	death group	P
NT-proBNP0	21505±8486	31955±9374	0.003
NT-proBNP1	15664±8193	35983±3946	0.002
NT-proBNP2	9144±8303	26375±7677	0.000
NT-proBNP3	5323±7664	18129±9848	0.000
ΔNT-proBNP1-0	0.29±0.22	-0.04±0.18	0.011
ΔNT-proBNP2-1	0.77±0.13	0.13±0.17	0.000
ΔNT-proBNP3-2	0.84±0.11	0.47±0.30	0.002

NT-proBNP0= initial NT-proBNP; NT-proBNP1= 24h NT-proBNP; NT-proBNP3= 72h NT-proBNP

ΔNT-proBNP1-0= (initial NT-proBNP–24h NT-proBNP) / initial NT-proBNP.

ΔNT-proBNP2-1= (24h NT-proBNP–48h NT-proBNP) / 24h NT-proBNP.

ΔNT-proBNP3-2= (48h NT-proBNP–72h NT-proBNP) / 48h NT-proBNP.

No competing interests reported.

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Early changes of cTnT and NT-proBNP in neonates underwent ECMO support: a single-center experience

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