Authors: Feride Karacaer, Ebru Biricik, Murat Ilgınel, Demet Laflı Tunay, Yusuf Döğüş, Özlem Görüroğlu Öztürk, Yasin Güzel, Onur Benli, Yasemin Güneş
Journal of Cardiothoracic and Vascular Anesthesia, Volume 37, Issue 1, Pages 65-72
Commentary by:
Manal Mirreh, MD1, Asif Padiyath, MD2
1,2 Children’s Hospital of Philadelphia, Philadelphia, PA
Take Home Points:
- Cardiac surgery with cardiopulmonary bypass (CPB) induces systemic inflammatory response syndrome (SIRS) which can play an integral role in the observed postoperative complications, morbidity, and mortality.
- In patients with cyanotic congenital heart disease (CCHD), the myocardium is more susceptible to oxidative injury due to hypoxia, reduced ATP stores and antioxidant enzymes.
- The authors conducted a single-center, prospective, randomized double-blind study that included CCHD undergoing open heart surgery. Patients were randomized into general anesthesia with either propofol (group P) or sevoflurane (group S).
- SIRS is more common in group S than in group P at all time points.
- Results demonstrated that propofol had a greater antioxidant effect and reduced SIRS occurrence than sevoflurane in this patient population.
Pediatric patients with congenital heart disease (CHD) are particularly vulnerable to Systemic Inflammatory Response Syndrome (SIRS) following Cardiopulmonary Bypass (CPB) for a multitude of reasons. These include the activation of the innate immune system, and exposure to artificial surfaces within the bypass circuit which triggers the complement and coagulation systems, resulting in the production of pro-inflammatory cytokines. Additionally, endothelial dysfunction contributes to increased permeability, while ischemic reperfusion injury exacerbates tissue damage and the subsequent release of inflammatory agents. The immature immune system in pediatric patients further heightens susceptibility to SIRS. This response involves the activation of leukocytes and the subsequent release of inflammatory mediators such as IL-6 and TNF-α1. In the case of patients with CCHD, altered oxygen levels in the blood contribute to heightened oxidative stress and inflammation.
Anesthetics like propofol and sevoflurane apart from their primary role in anesthesia, have been suggested to possess additional properties, including anti-inflammatory and antioxidant effects2. Propofol, for instance, has shown antioxidant properties by scavenging free radicals and reducing lipid peroxidation3. Some studies have suggested that propofol may modulate inflammatory responses, potentially reducing cytokine release and inflammatory markers in various clinical settings4. Sevoflurane, on the other hand, has been investigated for its potential anti-inflammatory effects, demonstrating a capacity to decrease inflammatory markers in certain conditions 3, 5.Its impact on oxidative stress and inflammation in cyanotic congenital heart disease could be of interest due to its widespread use in pediatric anesthesia.
Previous studies have compared propofol and sevoflurane in both pediatric and adult patients undergoing cardiac surgery, but the results were conflicting5. The authors point out that there have been no adequate studies investigating the effect of anesthetics on laboratory biomarkers and clinical parameters of SIRS in children with CCHD undergoing cardiac surgery with CPB. In this study, the authors aimed to compare the anti-inflammatory and antioxidant effects of propofol and sevoflurane in children with CCHD undergoing cardiac surgery with CPB.
The authors conducted a single center, prospective, randomized, controlled study that included children aged 1-to-10 years old with an American Society of Anesthesiologists physical status class II or III undergoing cardiac surgery with CPB for CCHD. Patients were randomized to general anesthesia with sevoflurane (group S) or propofol (group P). The occurrence of SIRS was determined at the end of surgery, and the 6th, 12th, and 24th hour time points postoperatively.
Group S was induced with Sevoflurane (2-8%), 5µg/kg fentanyl, 0.6 mg/kg of rocuronium then 2% sevoflurane and 5 µg/kg/h fentanyl infusion were used for maintenance anesthesia. Group P was induced with 2-to-3 mg/kg of propofol, fentanyl 5 mcg/kg, and rocuronium 0.6 mg/kg. Then, a 10 mg/kg/hr propofol infusion and 5 µg/kg/h fentanyl infusion were used for maintenance of anesthesia. Blood samples were obtained at four time points: after induction anesthesia (T0) after release of the aortic cross clamp (T1), at the end of the surgery (T2), and postoperative 24th hour (T3). Primary outcomes were perioperative serum levels of interleukin 6 (IL-6), tumor necrosis factor-alpha(TNF-α), total antioxidant status (TAS), and total oxidant status (TOS). IL-6 and TNF-α were determined with enzyme-linked immunosorbent assays as indicators of the systemic inflammatory reaction. TAS and TOS of samples were measured with a colorimetric assay.
The occurrence of SIRS was assessed based on sepsis consensus criteria6.Diagnosis of SIRS occurred when at least two of the following clinical parameters were present, one of which must be an abnormal leukocyte count or body temperature: (1) core body temperature > 38.5 C or <36; (2) tachycardia or for children < 1 year of age bradycardia; (3) a mean respiratory rate above normal for age or mechanical ventilation not related to neuromuscular disease or general anesthesia; and (4) leukocyte count elevated or depressed for age. The occurrence of SIRS was assessed at the end of surgery (S1) and the sixth (S2), 12th (S3) and 24th (S4) postoperative hours. T-test or Mann-Whitney U-test was used to analyze the data.
Forty children were enrolled in the study. Six children were excluded because of missing blood samples therefore 34 patients were analyzed: 16 in group P and 18 in group S. There was no difference between the groups regarding baseline demographic data, intraoperative variables, and Risk Adjusted Classification for Congenital Heart Surgery (RACHS1) categorization of cardiac diseases.
The clinical occurrence of SIRS was more common in group S than in group P at all control times (p = 0.020, p = 0.036, p = 0.004, p = 0.008). There were no significant differences in the mean TNF-α levels at any time between the groups. The TAS level at T2 was higher in group P than in group S (p = 0.036). The serum TAS level increased at T2 compared with T0 in group P, but it decreased in group S (p = 0.041). The results suggest that propofol was superior to sevoflurane in reducing SIRS and oxidative stress in children with CCHD undergoing cardiac surgery with CPB. However, the authors point out that sevoflurane and propofol were comparable in terms of plasma IL-6 and TNF-α concentrations and clinical outcomes.
Several limitations should be considered when interpreting the findings. First, it was a single-center study. Second, the study did not measure concentrations of sevoflurane and did not use target-controlled infusion for propofol due to technical restrictions thus could not compare total intravenous anesthesia with total inhalational anesthesia. Finally, the relatively small sample size complicates the analysis of clinical outcomes.
Despite the above limitations and the inability to demonstrate differences in clinical outcomes, this study is the first to compare the anti-inflammatory effects of propofol and sevoflurane in cyanotic children undergoing cardiac surgery with CPB. If these drugs demonstrate significant secondary benefits by modulating oxidative stress and inflammation, they could potentially be used strategically to improve outcomes or mitigate complications associated with cyanotic congenital heart disease.
References:
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2. Cruz FF, Rocco PR and Pelosi P. Anti-inflammatory properties of anesthetic agents. Crit Care. 2017;21:67.
3. Suleiman MS, Zacharowski K and Angelini GD. Inflammatory response and cardioprotection during open-heart surgery: the importance of anaesthetics. Br J Pharmacol. 2008;153:21-33.
4. Samir A, Gandreti N, Madhere M, Khan A, Brown M and Loomba V. Anti-inflammatory effects of propofol during cardiopulmonary bypass: a pilot study. Ann Card Anaesth. 2015;18:495-501.
5. Bettex DA, Wanner PM, Bosshart M, Balmer C, Knirsch W, Dave H, Dillier C, Burki C, Hug M, Seifert B, Spahn DR and Beck-Schimmer B. Role of sevoflurane in organ protection during cardiac surgery in children: a randomized controlled trial. Interact Cardiovasc Thorac Surg. 2015;20:157-65.
6. Goldstein B, Giroir B, Randolph A and International Consensus Conference on Pediatric S. International pediatric sepsis consensus conference: definitions for sepsis and organ dysfunction in pediatrics. Pediatr Crit Care Med. 2005;6:2-8.
