Can Systemic Immune Inflammatory Index Predict Nosocomial Infection in Term Newborns who Underwent Congenital Cardiac Surgery?

doi:10.21203/rs.3.rs-4896275/v1

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Can Systemic Immune Inflammatory Index Predict Nosocomial Infection in Term Newborns who Underwent Congenital Cardiac Surgery?

https://doi.org/10.21203/rs.3.rs-4896275/v1

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Background: In this study, the aim was to investigate the contribution of early-stage systemic immune inflammatory index(SII) and acute phase reactants to predict nosocomial infections in term newborns who underwent congenital heart surgery.

Methods: This study was carried out retrospectively in newborns who were followed up in the pediatric cardiac intensive care unit between November 1, 2021 and December 1, 2022 and had had cardiac surgery. Demographic and clinical features, changes in systemic inflammatory index (platelet count x neutrophil count/lymphocyte count) and acute phase reactants in the preoperative and postoperative first 72 hours were evaluated in patients with or without nosocomial infection.The results were analyzed statistically.

Results: During the study period, cardiac surgery was performed in 160 neonates. Median age was 10 days(IQR 6 days -15 days) and median weight was 3 kg(IQR 2.8 kg -3.2 kg).Eighty of the patients were male(50%).55 different nosocomial infections were detected in 44 patients(27.5%). Bloodstream infections were the most common with 62%, followed by lower respiratory tract infections in 23% and wound infections in 15%.Mortality due to nosocomial infection was determined as 34%.SII and NLR values measured on the 2nd and 3rd postoperative days were significantly higher in patients with nosocomial infection (p< 0.05). SII value >510((72% specificity 85% sensitivity) on postoperative 2nd day and SII >730(72% specificity 80% sensitivity) on postoperative 3rd day were predicting nosocomial infection strongly.

Conclusion: Nosocomial infections are an important cause of mortality and morbidity in newborns with congenital heart surgery. Easy-to-use systemic inflammatory index measurement can help to predict nosocomial infections.

Cardiac & Cardiovascular Systems

newborn

infections

congenital heart disease

systemic inflammatory index

Congenital heart disease (CHD) is a common disease with a general incidence of 4 to 10 per 1000 live births. In the neonatal period, 25% of the cases require surgical and/or interventional palliative and corrective procedures due to critical nature of the heart disease (1).

Immaturity of the immune system in the newborn period, the uncontrolled systemic inflammatory response as a result of interactions in the cellular and humoral systems in cases underwent cardiopulmonary bypass, and the complexity of the operation may cause different complications in organ systems. Infections are one of the most important complications observed, and it has been stated in some studies that it can be seen at a rate of 20–50% after neonatal cardiac surgery. Catheter-associated and bloodstream infections, ventilator-associated pneumonia, nosocomial pneumonia, urinary tract-related infections and surgical site infections can create predisposition to nosocomial infections (2–4).

Early diagnosis and treatment of nosocomial infection may be insufficient in newborns due to the difficulties in figuring clinical findings in the postoperative period and the effects of cardiopulmonary bypass.Prompt diagnosis and appropriate antibiotic treatment are essential even long before blood culture results are obtained, suspicion based on clinical and laboratory parameters should be generated.This spesific period of life is also limited in availability of biomarkers with high diagnostic confirmation, non-invasive, and easily applicable attribute. For this purpose, different tests such as complete blood count, C-reactive protein, procalcitonin, neutrophil-lymphocyte ratio can be used (5–6). Systemic immune-inflammation index (SII) is recently being used as a new index that comprehensively reflects the state of inflammation and immune balance in the body (7). SII can be obtained from routine complete blood cell count analysis.

In this study, it was aimed to evaluate the contribution of SII and acute phase reactants drawn in the preoperative and first 72 hours in the prediction of possible nosocomial infection in cases undergoing neonatal cardiac surgery in the pediatric cardiac intensive care unit.

This retrospective study involved the newborns who were followed up in the pediatric cardiac intensive care unit between November 1st 2021 -December 1st 2022 and underwent cardiac surgery. After approval of the local ethics committee, the study was carried out in accordance with the Declaration of Helsinki. Inclusion criteria were those who were diagnosed with congenital heart disease by a pediatric cardiologist and had undergone cardiac surgery in the neonatal period. Exclusion criteria were defined as death within 48 hours of the operation, having an infection within the first 48 hours after hospitalization, to be transferred to another unit, and prematurity.

All these study data were obtained from the hospital’s electronic medical record. The onset of nosocomial infection occurred between 48 hours post-surgery and the discharge date from the intensive care unit.The cases were divided into two groups as those with and without nosocomial infections. Nosocomial infections were defined according to the Centers for Disease Control and Prevention criteria and the National Health Care Safety Network (8). The following infections were included:Central line-associated blood stream infection, clinical sepsis, pneumonia, ventilator-associated pneumonia (VAP), and surgical-site infection. Sepsis was defined coherently to the proposed definition in the International Sepsis Forum for infection in the intensive care unit.

Cefazolin was given within 0.5–1 hour before surgery and within 72 hours after surgery to prevent infection.A study form was created for each patient, including demographics, perinatal- catheter and postoperative characteristics, type of surgery, laboratory data, isolated microorganisms, etc. Peripheral venous blood samples were drawn from all cases 24 hours before and 1,2 and 3 days after the operation. Samples were sent to the laboratory for routine examination. White blood cell ( neutrophil- lymphocyte) counts, platelets, albumin, C-reactive protein (CRP), procalcitonin levels were obtained. The SII value of the cases was calculated and recorded on the form. SII was calculated as follows: SII = neutrophil count × platelet count/lymphocyte count (10). The results were evaluated statistically.

Statistical analysis

Continuous variables were described as Mean ± SD or Median (IQR) according to their distributions andcategorical data were presented as frequency (%). For between group comparison, T tests or Mann-Whitney U tests were used for continuous variables and Chi-squared tests or Fisher’s exact tests for categorical data,as appropriate. Receiver operating characteristic (ROC) curve and the area under the curve (AUC) were used to evaluate the cut-off values between SII and nosocomial infection. The final model for the estimation of SII parameters affecting nosocomial infection was expressed as Odds ratio with 95% confidence interval. p < 0.05 was considered statistically significant.

We have 160 newborns during the study period. Nosocomial infections were detected in 44 (25,7%) of the patients. Demographic characteristics of newborn cases with and without nosocomial infection are shown in Table 1.

There were fifty different nosocomial infections were detected. Thirty one of these cases had only one infection, eleven of them had two infections and two cases had three infections. Blood stream infections were the most common in 62% (sepsis n = 22, catheter-associated blood stream infection n = 12), followed by lower respiratory system infections in 23% (ventricular-associated pneumonia n = 9, pneumonia n = 4) and wound site infections in 15% (n = 8).

Of the detected infectious agents; 55% were gram (-), 30% were gram (+) and 15% were fungal organisms. The most common agents detected in all three blood, lung and wound swab cultures were gram(-) organisms. Detected infections and their sites are shown in Table 2.The overall mortality was 16% (n = 26/140). In 15 cases, the main cause of death was the NI (15/44, 34%). The difference (p = 0.01) in the mortality rate between the patients with nosocomial infections and without nosocomial infections was attributable to the infections.

The results of preoperative and postoperative 1st, 2nd 3rd day of hemogram and acute phase reactants in cases with and without nosocomial infections were shown in Table 3. NLR and SII values were detected significantly high in patients with nosocomial infections according to these results (p < 0,05).

Postoperative 2nd day SII c index = 0.80 (CI: 0.72–0.88, p = 0.02), postoperative 3rd day NLR value c index = 0.78 (CI: 0.66–0.88 p = 0.04), postoperative 3rd day SII value c index = 0.80 (CI: 0.72–0.88, p = 0.001) could predict nosocomial infection.

Cut-off points were postoperative 2nd day SII > 630 ( 72% specificity 85% sensitivity) and postoperative 3rd day SII > 720 (75% specificity, 80% sensitivity) and postoperative 3rd day NLR > 3.8 (70% specificity 70% sensitivity) predicted nosocomial infection.

The current study was designed to show the role of SII and acute phase reactants in predicting nosocomial infections in the early period after cardiopulmonary bypass. The frequency of nosocomial infection was 27.5%. We observed that high SII values on postoperative day two and day 3 increased the likelihood of nasocomial infection. Our study is one of the limited studies in the literature underscoring SII and acute phase reactants in predicting nosocomial infection.

Nosocomial infection is a serious morbidity that may result in lethal complications after cardiac surgery for congenital heart disease, and it is even more critical in newborns. The incidence of nasocomial infection in patients with CHD has been reported at different rates. Yu et al. (11) reported a nosocomial infection rate of 10.8% for all patient groups, according to the newborn, infants and children subgroups were 32.9%, 15.4% and 5.2%, respectively. In a different study, the rate of nasocomial infection in newborns was 25.3%whic was five times higher than in other age groups (12). Our nosocomial infection incidence was 27.5% and was consistent with the literature.

The leading complications at the postoperative period of the newborns with CHD requiring surgical intervention are infectious complications. Bloodstream, lower respiratory tract, wound site and urinary tract infections are major sites for postoperative infections. Pasquali et al. reported sepsis, wound infection and pneumonia as the most prevalent sites of nosocomial infection, accounting for 51%, 35% and 10% of patients, respectively (13). Likewise, we identified bloodstream infections as the most common type of nasocomial infection.

Mortality rate was higher in patients with nosocomial infections. Magliola et al. (14) and Garcia et al. (3) reported 14% and 17.8% mortality rates, respectively. In our study, mortality in patients with infection was 34% and 10% in those without infection, and the difference was significantly higher. According to other studies, the complexity of the patient’s pathology may contribute to the high mortality rate.

Systemic inflammatory response syndrome, that can affect mortality and morbidity negatively in newborns, can be triggered by surgical trauma or cardiopulmonary bypass (CPB) during cardiac surgery or in the early postoperative period. Contact of CPB equipment with blood cells initiates the inflammatory cascade with the release of cytokines and activation of the complement and coagulation systems. In this complex process, hypothermia and ischemia-reperfusion injury, impair tissue oxygenation further; as a result, hemodynamics get worse. Different biomarkers are used in the diagnosis and management of this process. However, none of them is easily found, or reproducible or useful in clinical practice (15–16).

CRP is one of the most reliable parameters for detecting nosocomial sepsis, with its level rising significantly during infections, particularly in gram-negative bacterial sepsis (17). Some of the rapidly available parameters, as the platelet/lymphocyte ratio and neutrophil/lymphocyte ratio (NLR), calculated from routine complete blood count, were investigated as potential indicators of infection. These ratios have been suggested to be potentially more sensitive biomarkers of inflammation than absolute levels of each blood cell component (18).

Nowadays, NLR is accepted as a more valuable marker of inflammation than lymphocytopenia or neutrophilia alone, specially to detect bacterial infection (19–20). NLR and SII have been used to predict disease activity, prognosis, and survival rates in diseases with systemic inflammation, particularly in many clinical cancer scenarios, hepatocellular carcinoma, breast and colorectal cancers, and bacterial and bloodstream infections (7, 19–22).

NLR and SII have also been recognized as inflammatory markers of neonatal sepsis due to inflammation-induced changes in neutrophil, platelet, and lymphocyte counts. (7, 19–22).

Inflammation and ischemia risks are high in conditions of nosocomial infection and CHD. SII has also been investigated in cardiac morbidities with ischemia (21). Aydoğan et al. found significantly higher SII values, where the cut-off value was 517 in CHD patients with sepsis (7). In our study, postoperative 2nd and 3rd day NLR and SII values were higher in nosocomial infections.

Limitation

Firstly, it was a retrospective study with a limited number of patients performed in a single center. Another limitation is that the patient's underlying pathologies were heterogeneous, which could significantly impact consequences. Unfortunately, we did not have a separate population to validate the cutoff values.

In conclusion, nosocomial infections cause significant mortality and morbidity in newborns undergoing congenital cardiac surgery. SII could help early detection of postoperative nosocomial infections.

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Tables 1 to 3 are available in the Supplementary Files section

The authors declare no competing interests.

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Can Systemic Immune Inflammatory Index Predict Nosocomial Infection in Term Newborns who Underwent Congenital Cardiac Surgery?

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Introduction

Method

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