Serum Inflammatory Cytokines and Peritoneal Dialysis in Infants with Acute Renal Failure Following Open Heart Surgery

Research Article

Austin J Clin Cardiolog. 2022; 8(3): 1098.

Serum Inflammatory Cytokines and Peritoneal Dialysis in Infants with Acute Renal Failure Following Open Heart Surgery

Liu Y, Mao Y, Ma Y, Zhai M, Li L, Jin P, and Yang J*

Department of Cardiovascular Surgery, Xijing Hospital, Air Force Medical University, Xi’an, China

*Corresponding author: Jian Yang, Department of Cardiovascular Surgery, Xijing Hospital, Air Force Medical University, 127 Changle West Road, Xi’an 710032, Shaanxi, China

Received: October 12, 2022; Accepted: November 11, 2022; Published: November 18, 2022

Abstract

Background: Acute Renal Failure (ARF) is a common complication after open heart surgery with Cardiopulmonary Bypass (CPB) because of the capillary leak syndrome. Peritoneal Dialysis (PD) has been widely used to treat ARF after CPB. In this study, the clearance of inflammatory cytokines of PD in infants with ARF following open heart surgery was investigated.

Methods: Twenty-nine infants with ARF following open heart surgery who underwent PD were divided into survival and nonsurvival groups. Clinical records were reviewed to document clinical features, operative procedures, and perioperative courses. The serum inflammatory cytokine levels, including those of Tumor Necrosis Factor (TNF)-a, interleukin (IL)-6, IL-8, and IL-10, were measured perioperatively.

Results: There was no difference in the preoperative characters between the 2 groups. Longer CPB time, duration of mechanical ventilation, duration from surgery to the beginning of PD, and higher central venous pressure appeared in the nonsurvival group. The serum concentrations of IL-6 and IL-8 were significantly higher in the nonsurvival group than in the survival group before PD and on PD 1 day, PD 4 days, and PD 7 days, respectively. The serum concentrations of IL-10 were higher in the nonsurvival group than in the survival group on PD day 4 and PD day 7, respectively. There were no significant differences of TNF-a between the 2 groups during the perioperative period and PD.

Conclusion: PD could eliminate inflammatory cytokines effectively in patients with mild ARF after open heart surgery.

Keywords: Inflammatory cytokines; Peritoneal dialysis; Acute renal failure; Cardiopulmonary bypass; Infant

Bulleted Clinical Perspectives

Acute renal failure is a common complication after open heart surgery with cardiopulmonary bypass.

In the group with mild acute renal failure, for example, the patients in the survival group, adequate amounts of the inflammatory cytokines could be removed cytokines could be moved from the blood to the peritoneal fluid.

In patients who died, for example, the patients in the non-survival group, the quantity of inflammatory cytokines removed might not be enough or might continue to increase even with Peritoneal dialysis therapy.

Introduction

Acute Renal Failure (ARF) is a frequently reported complication after open heart surgery with Cardiopulmonary Bypass (CPB) in infants. The reported incidence of ARF ranged from 2.4% to 8%. Previous studies have reported a high mortality rate ranging from 30% to 79% [1-3]. According to previous reports, the application of CPB relates directly to the occurrence of ARF. Longer CPB time and longer aortic clamp time corresponded with a higher incidence of ARF and higher mortality [4-6]. A probable mechanism of ARF after CPB is that CPB induced an acute systemic inflammatory response characterized by complement activation, adhesion molecule upregulation, neutrophil activation, and release of the proinflammatory cytokines, which are associated with pulmonary and myocardial dysfunction, neurological injury, and renal failure [3,7].

Peritoneal Dialysis (PD) is frequently used for ARF following open-heart surgery in pediatric patients. Compared to hemofiltration, which has some disadvantages including requirements for systemic anticoagulation and vascular access, PD represents a simple, safe system for fluid removal, especially in newborns and infants. According to some reports, PD resulted in satisfactory outcomes in the therapy of ARF after open heart surgery in pediatric patients [8-12]. Some previous reports also indicated that PD could remove proinflammatory cytokines effectively, including interleukin (IL)-6, IL-8, and IL-10, which could lead to the occurrence and development of ARF [13,14]. However, deaths of ARF after open heart surgery were still high with a range from 32% to 57%, even with PD. Whether removing proinflammatory cytokines by PD could decrease the number of deaths is still under discussion. Our goal was to investigate the impact of PD on cytokine homeostasis and mortality at our institution.

Patients and Methods

Study Population

From July 2018 to May 2022, a total of 29 pediatric patients (body weight <10 kg) who experienced ARF after open heart surgery with CPB in the Xijing Hospital underwent PD. All children were diagnosed by echocardiography, computed tomography scan or angiography, and cardiac catheterization. These examinations assessed cardiac function and associated anomalies. Clinical records were reviewed to document clinical features, operative procedures, and perioperative courses. A total of 15 patients (51.7%) died after PD, and 14 patients (48.3%) were weaned successfully from PD and survived after PD. These patients were divided into 2 groups, survivors and nonsurvivors. This study was approved by the ethics committee of Xijing Hospital and was performed in accordance with the Declaration of Helsinki and all relevant Chinese laws. All participants provided written informed consent from the children’s guardians before inclusion in the study.

Acute Renal Failure and Indications for Peritoneal Dialysis

ARF was defined as a serum creatinine level of more than 1.2 mg/dL or oliguria (< 0.5 mL/kg/hour) for more than 4 hours despite aggressive diuretic therapy and optimization of the inotropic support or a combination of both. The indications for PD were (1) anuria or oligoanuria (<0.5 mL/kg/hour for more than 4 hours) resistant to controlled volume expansion, inotropes, vasodilators, and diuretics; (2) fluid overload; (3) hyperkalemia (> 5.5 mmol/L); (4) metabolic acidosis (serum pH < 7.3, HCO3 < 18 mmol/L); and (5) a serum creatinine level greater than 1.2 mg/dL. Fluid overload was defined as edema, increase of body weight in serial measurements, and difference between fluid uptake and urine output.

Peritoneal Dialysis Procedures

All these patients underwent PD in the intensive care unit postoperatively. In brief, a standard Dacron-cuffed silicone rubber peritoneal catheter (Tenckhoff, Sherwood Medical GmbH, Schwalbach, Germany) was inserted surgically through an infraumbilical midline or a paraumbilical left-sided approach in the intensive care unit when postoperative hemodynamic and renal complications were anticipated according to previous indications for PD.

The PD catheter was connected to a closed system for peritoneal drainage. Standard dialysate solutions were prepared under sterile conditions at our pharmacy. The dextrose concentration varied from 1.5 to 4.5%. A 2.5% solution was used initially. A low-volume dialysis technique was used that included 10 minutes of indwelling time and 20 to 50 minutes of drainage time in one cycle with 10 mL/kg body weight irrigation. The recovery of urine output was defined as urine output > 1 mL/kg/hour, and the recovery of serum creatinine was defined as a decline in serum creatinine to preoperative levels. Indications for stopping PD included a return to a sufficient urine output, maintaining a negative fluid balance, and normalization of the serum electrolyte and acid-base status.

Clinical Data

The data related to age, weight, sex, and diagnosis were recorded for all patients. The Risk Adjustment for Congenital Heart Surgery-1 was used to categorize the surgical intervention. Total duration of CPB, aorta clamp time, and the lowest temperature during CPB were recorded. The perioperative inotropic score for each patient was calculated in accordance with the previously published equation: inotropic score = 1 × dopamine (mg/kg/minute) + 1× dobutamine (mg/kg/minute) + 10 × milrinone (mg/kg/minute) + 100 × epinephrine (mg/kg/minute). The duration of the mechanical ventilation, duration of PD, time to onset of ARF, time interval between the beginning of PD and ARF, incidence of complications during PD, all kinds of hemodynamic data, and other perioperative data were collected. Blood urea nitrogen and serum creatinine levels were measured in the pre- and postoperative periods. Arterial blood gas analysis and electrolyte analysis were performed routinely preoperatively. These clinical data were obtained retrospectively from medical records.

Proinflammatory Cytokines Detections

For all patients who needed PD with ARF after open heart surgery, the venous blood samples (1 mL) were taken under sterile conditions from the patients before the beginning of PD, the first day after PD, and then every 3 days. Added preoperative and postoperative blood samples were centrifugated at 1500 g ×15 minutes at room temperature and at 14000 g ×15 minutes at 4°C. After centrifugation, all serum samples were quickly frozen at -70°C and stored until processed.

Serum proinflammatory cytokine levels, including TNF-a, IL-6, IL-8, and IL-10, were measured by the Enzyme-Linked Immunosorbent Assay (ELISA) technique (Enzyme-Amplified Sensitivity Immunoassay kits, BioSource Europe SA, 8 B-1400, Nivelles, Belgium) according to the manufacturer’s directions. These assays detected only human cytokines, and the minimum detectable concentrations were 5 pg/ml for TNF-a, less than 3 pg/ml for IL-10, less than 2 pg/ml for IL-8, and less than 1 pg/ml for IL-6.

Statistical Analyses

All data were analyzed on the computer using the IBM SPSS Statistics 13.0 for Windows program (IBM SPSS Statistics, Armonk, NY, USA). All data were given as mean ± Standard Deviation (SD). The Χ² test was used to compare differences between the frequencies. Serum cytokine levels were analyzed using the normality test. The Mann- Whitney U test and the Student t-test were used to compare mean values between groups. The Spearman rank correlation test was used for the assessment of correlation. The statistical significance was accepted as P value < 0.05.

Results

All patients were similar in weight and age (Table 1). All patients had congenital heart disease and needed surgical correction. Most patients’ congenital cardiac malformations were more severe than tetra logy of Fallot (Table 2). CPB time was significantly longer in the nonsurvival group than in the survival group. The total number of blood transfusions was significantly higher in the nonsurvival group than in the survival group. All other demographic and operative data are summarized in Table 1; all postoperative data are summarized in (Table 3).