الفهرس 
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Abstract
SUMMARY
N
eonatal sepsis defines a complex syndrome characterized by systemic inflammatory response arising from the bacterial, viral or fungal origin, associated with hemodynamic changes and clinical findings and causing severe morbidity and mortality. The high mortality rate of neonatal sepsis is contributed to late diagnosis and improper management. The clinical manifestations range from subclinical infection to severe focal or systemic disease.
One of the major organs that can be affected by sepsis is the heart. Myocardial dysfunction has been attributed to the high mortality associated with sepsis. It results from circulating myocardial depressants including TNF and IL-1A. It usually starts during the first 24 hours of sepsis, and it is reversible in survivors within 7 to 10 days.
Echocardiography is an important tool for the diagnosis of cardiac dysfunction that can influence the outcome of septic newborns in the NICUs. A wealth of hemodynamic information can be derived from echocardiography as without its use, physicians are left to speculate the underlying pathophysiology of circulatory compromise, and the assumptions they make may be incorrect.
Copeptin is a stable by-product of arginine-vasopressin AVP (or antidiuretic hormone; ADH) synthesis, which acts as a main regulator in the homeostasis of the cardiovascular and renal system. It is produced by the hypothalamus and secreted in the posterior lobe of the pituitary gland upon hemodynamic or osmotic stimuli. Copeptin directly reflects the concentration of ADH as a marker of endogenous stress and ischemia; it is synthesized after 5-20 minutes of acute myocardial damage and remains stable for several days.
Ischemia-modified albumin (IMA) is a marker of oxidative stress related to different clinical conditions such as myocardial ischemia. The modified form of albumin related to ischemia, called ischemia-modified albumin (IMA), is incapable of binding to metallic ions. Its concentration rises already in 6-10 minutes from the moment of development of ischemia, and returns to the initial level in 6-24 hours, that is, even before the increase of levels of cardiac troponin, creatine kinase isoform (CK-MB) or myoglobin.
Our study aimed to measure the levels of copeptin and ischemia-modified albumin in septic neonates and to detect their correlation to cardiac dysfunction by echocardiography in these infants, to detect the reliability of plasma copeptin and ischemia-modified albumin as indicators of cardiac affection in neonatal sepsis.
This cross-sectional study was conducted on 70 near term neonates from NICU of Ain Shams University hospital and permitted by Ain Shams Ethical Committee. Neonates were classified into three groups; group 1 included 30 neonates diagnosed with sepsis having echocardiographic findings, group 2 included 20 neonates diagnosed with sepsis free of echocardiographic findings and group 3 included 20 matched neonates free of sepsis and echocardiographic findings. In consideration, these neonates’ gestational age was ≥ 34weeks and < 37 weeks, they had no congenital anomalies, heart defects, inborn errors of metabolism or conditions that increase level of serum copeptin or IMA.
Detailed history taking, full examination and laboratory investigations were obtained. Serum Copeptin level and serum IMA level were measured using commercially available ELISA kits. Transthoracic echocardiogram and Tissue Doppler imaging were used for the assessment of systolic and diastolic cardiac functions in studied neonates.
As regards echocardiographic findings in cases and control; LVESD and LVEDD were significantly lower in cases compared to controls, this may be related to hemodynamic alteration and profound hypovolemia due to sepsis, which can induce myocardial depression and dysfunction. Regarding LV function by echocardiographic findings; fractional shortening FS% and ejection fraction EF% (measuring LV systolic function) were significantly lower in cases than in control. Furthermore, it was noticed that MAPSE was significantly lower in preterm septic patients group compared to control group. This indicated impaired longitudinal myocardial functions of left ventricle. The LV Tei index ” MPI ” significantly increased in the cases. The higher myocardial performance index (MPI) compared to control group indicates impaired diastolic function. Regarding mitral inflow: preterm septic patients’ group had significantly lower E/A ratio across mitral valve compared to control group, indicating left ventricular diastolic dysfunction.
Regarding right ventricular function detected by echocardiographic findings in our study; pulmonary artery pressure was substantially higher in cases than in control. Also, septic patients’ group had significantly higher left atrial diameter compared to control group. It was noticed that TAPSE was significantly lower in pre term septic patients group compared to control group. This indicated impaired longitudinal myocardial functions of right ventricle. In our investigation, cases had a greater RV tei index than controls. The higher myocardial performance index (MPI) compared to control group indicates impaired global diastolic function of RV in septic patients’ group. According to tissue Doppler analysis, the right ventricle’s diastolic function represented by the tricuspid E/A ratio, was found to be considerably poorer in the examined neonates with sepsis than in the control group indicating right ventricular diastolic dysfunction.
Regarding Copeptin (ng/ml), it was significantly higher in group 1 (12.26±4.06), followed by group 2 (4.25±1.56), then group 3 (2.17±0.79). Using ROC curve, the best cut off value of Copeptin >8.17 (ng/ml) for discrimination between septic neonates with and without cardiac affection groups with sensitivity 73.3% and specificity 95%. Furthermore, we found that Copeptin can also differentiate between septic and healthy neonates. This can be done using ROC curve where the best cut off value using Copeptin (ng/ml) to detect sepsis is >1.83 with sensitivity 60% and specificity 75%.
Furthermore, regarding ischemia-modified albumin (IMA) (ng/ml) in our study, there was significantly higher mean value of IMA in group 1 (263.97±81.49), followed by group 2 (68.62±22.08), then group 3 (35.94±10.94). While, regarding ROC curve for the neonates with sepsis and echo findings group, and the neonates with sepsis and echo free group, the best cut off value for discrimination between group 1 vs. group 2 using IMA (ng/ml) to detect cardiac affection was >170.2 with sensitivity 66.7% and specificity 100%. Furthermore, Regarding ROC curve in the neonates with sepsis group, vs the healthy control group, the best cut off value for discrimination between group 2 vs. group 3 using IMA (ng/ml) to detect sepsis was >38.4 with sensitivity 60% and specificity 70%.
We concluded that serum IMA and Copeptin levels are good predictors of sepsis. Furthermore, among septic neonates they were found to differentiate between those with and without cardiac affection. Further studies are needed to confirm their reliability