Cardiovascular Surgery and Interventions 2020, Vol 7, Num 1 Page(s): 008-013
Effects of systemic inflammatory response on coronary artery bypass grafting
DOI: 10.5606/e-cvsi.2020.760
Nihan Yeşilkaya1, Orhan Gökalp1, Hasan İner1, Yüksel Beşir1, Hüseyin Durmaz2, Yaşar Gökkurt2, İhsan Peker2, Levent Yılık1, Ali Gürbüz1
1Department of Cardiovascular Surgery, Izmir Katip Çelebi University Faculty of Medicine, Izmir, Turkey
2Department of Cardiovascular Surgery, Izmir Katip Çelebi University Atatürk Research and Training Hospital, Izmir, Turkey
Keywords: Cardiopulmonary bypass, coronary artery bypass grafting, systemic inflammatory response syndrome
Objectives: In this study, we aimed to investigate the effects of systemic inflammatory response syndrome (SIRS) on postoperative results of coronary artery bypass grafting (CABG).

Patients and methods: Between April 2016 and April 2018, a total of 287 patients (203 males, 84 females; mean age 62.5 years; range, 21 to 89 years) who underwent CABG were retrospectively analyzed. Data were collected from the medical records. The diagnosis of SIRS was made according to the criteria used by Boehme.

Results: In total, 83.9% of the patients had postoperative SIRS. Univariate analysis revealed that the predictive factors of SIRS were age, preoperative EuroSCORE, on-pump surgery, and preoperative low hemoglobin levels. However, age was detected as the only predictive factor in the multivariate analysis. The diagnosis of SIRS did not affect hospital mortality, neurological complications or length of hospital stay, whereas it prolonged the weaning period and length of intensive care unit stay.

Conclusion: Our study results show that SIRS has no significant effect on mortality and neurological complications in CABG patients. On the other hand, special attention should be given to the inflammatory response, as it prolongs the weaning period and length of intensive care unit stay

  • Top
  • Summary
  • Introduction
  • Methods
  • Results
  • Disscussion
  • References
  • Coronary artery bypass grafting (CABG) is the conventional therapy of coronary artery disease. This procedure became widespread after Gibbon started to use cardiopulmonary bypass (CPB) machines in 1953.[1] Blood contact with non-endothelial surface triggers systemic inflammation through the secretion of mediators. Systemic inflammation during and after cardiac surgery, more particularly in CABG procedures, is related to the secretion of a large number of mediators and to the activation of certain natural defense mechanisms.[1]

    Inflammation is one of the basic parameters that affects postoperative results.[2] The magnitude of the inflammatory reaction varies, although the persistence of any degree of inflammation may be considered potentially harmful to the cardiac patient.[3] In addition, systemic inflammatory response syndrome (SIRS) can lead to pulmonary, renal, gastrointestinal, myocardial, and central nervous system dysfunction as well as coagulopathy, vasoconstriction, increased interstitial fluid, fever, leukocytosis, hemolysis, and an increased susceptibility to infections.[3,4] When CPB is avoided (e.g., off-pump CABG [OPCAB]), however, evidence suggests that activation of inflammation still occurs, but is slightly delayed with respect to on-pump bypass.[4] In the present study, we aimed to evaluate the effects of SIRS on the postoperative results of CABG.

  • Top
  • Summary
  • Introduction
  • Methods
  • Results
  • Disscussion
  • References
  • Between April 2016 and April 2018, a total of 287 patients (203 males, 84 females; mean age 62.5 years; range, 21 to 89 years who underwent CABG were retrospectively analyzed. Medical data including pre-, intra-, and postoperative data of the patients were obtained from the hospital archive department. Patients who underwent emergent surgery or who had concomitant peripheral artery intervention, valve repair/replacement or carotid endarterectomy were excluded. A written informed consent was obtained from each patient. The study protocol was approved by the Izmir Katip Çelebi University Faculty of Medicine Ethics Commitee of Retrospective Studies. The study was conducted in accordance with the principles of the Declaration of Helsinki.

    The patients were divided into two groups according to the SIRS status: the SIRS-positive group (n=241) and SIRS-negative group (n=46). The two groups were compared in terms of pre-, intra, and postoperative parameters. The diagnosis of SIRS was made according to the criteria used by Boehme.[5] According to these criteria, at least two of the followings were required: fever >38°C or <36°C, heart rate >90 bpm, respiratory rate >20 bpm or partial pressure of carbon dioxide (pCO2) <32 mmHg, leucocyte >12¥103/μL-1 or <4×103/μL-1.

    Statistical analysis
    Statistical analysis was performed using the IBM SPSS version 22.0 software (IBM Corp., Armonk, NY, USA). Descriptive data were expressed in mean ± standard deviation (SD), median (min-max) or number and frequency. Categorical data were compared using the Pearson’s chi-square and Fisher's exact tests. The Mann-Whitney U test was used for the comparison of the study groups. The correlation between SIRS and demographic and clinical characteristics of the patients was analyzed using univariate and multivariate regression analyses. A p value of <0.05 was considered statistically significant.

  • Top
  • Summary
  • Introduction
  • Methods
  • Results
  • Disscussion
  • References
  • In terms of preoperative parameters, the mean age and EuroSCORE were higher and the mean preoperative hemoglobin levels were lower in the SIRS group (p<0.001 and p=0.009, respectively). However, there were no statistically significant differences in the other preoperative parameters (Table 1).

    Table 1: Pre- and intraoperative data

    In terms of intraoperative data, the use of on-pump surgery and intra-aortic balloon pump (IABP) was statistically significantly higher in the SIRS group (p=0.001 and p=0.026, respectively). On the other hand, there were no statistically significant differences in the cross-clamp and CPB time (Table 1).

    In terms of postoperative data, the length of intensive care unit stay and the weaning period were statistically longer in the SIRS group (p<0.001 and p=0.004, respectively). However, there were no statistically significant differences in the incidence of postoperative neurological complications and mortality rates between the groups (Table 2).

    Table 2: Postoperative data

    Univariate regression analysis was carried out to identify possible variables for SIRS. The analysis revealed that age, EuroSCORE, preoperative low hemoglobin level, and on-pump surgery positively affected SIRS (p<0.001, p=0.001, p=0.015, and p=0.001, respectively). On the contrary, off-pump CABG adversely affected SIRS (p=0.003). The remaining variables were not found to be significant predictors of SIRS (Table 3). Factors which were statistically significant in the univariate analysis were included in the multivariate analysis. Accordingly, age was the only factor which had a significant effect on SIRS prediction (p=0.009) (Table 4). A regression analysis was performed to identify whether SIRS had an effect on the postoperative results, and SIRS was found to have no significant effect on neurological complications or mortality (p=0.998 and p=0.289, respectively) (Table 5). A single linear regression analysis revealed that the length of ICU stay and the weaning period were longer in the patients with SIRS (p=0.022 and p=0.002, respectively) (Table 6).

    Table 3: Univariate logistic regression analysis for predictors of SIRS

    Table 4: Multivariate logistic regression analysis for predictors of SIRS

    Table 5: Univariate regression analysis

    Table 6: Single linear regression analysis

  • Top
  • Summary
  • Introduction
  • Methods
  • Results
  • Disscussion
  • References
  • As one of the most common operations, particularly after the introduction of CBP machine, CABG surgery is subject to much interest, as it may lead to prolonged weaning times, increased renal dysfunction, stroke, deep sternal infections, and death.[6] These results are thought to be related to systemic inflammation, which is most probably caused by CBP machines.[7,8] Nevertheless, systemic inflammation which occurs after CABG procedures is affected by many factors other than CPB machines. Tissue damage, endotoxemia, and contact of blood with non-endothelial surfaces are the main known triggers of SIRS.[9,10]

    There are two major ways to investigate SIRS both in cardiac surgery and other fields. One is through the use of laboratory parameters such as tumor necrosis factor or interleukins. The other way is with clinical criteria such as hypotension, hyperthermia, leukocytosis.[5,11] Unfortunately, according to the global studies, the number of patients who develop SIRS after cardiac surgery cannot be neglected. In the study of Sasse et al.,[12] the postoperative SIRS ratio was 39% among the patients undergoing cardiac surgery, including pediatric cases. In another study, MacCallum et al.[13] reported that the postoperative SIRS ratio was 96.2% using clinical parameters for patients in an adult cardiothoracic ICU.[13] We used the same method in our study and the postoperative SIRS ratio was found to be 83.9%.

    Although previous studies have investigated the risk factors of SIRS in many settings, only a few have evaluated the risk factors of SIRS after CABG procedures. However, as a major factor affecting postoperative outcomes of patients undergoing CABG, many studies regarding the causes of SIRS and related precautions for its avoidance SIRS are expected. One of these studies was by Ferraris et al.,[14] which revealed a relation between the intraoperative blood use and SIRS. According to their study, intraoperative blood use led to negative changes in the immune system and induced SIRS. The authors also reported that other factors which caused SIRS were low preoperative functional capacity, liver dysfunction, chronic obstructive pulmonary disease, male sex, preoperative steroid therapy, preoperative dialysis history, and age above 74 years. In another study, Sinning et al.[15] investigated the postoperative effects of SIRS on patients undergoing transaortic valve implantation. Their results showed that risk factors for SIRS were the amount of contrast agents used, major bleeding, major vascular trauma, and blood transfusion. In a similar study by Lindmann et al.,[16] 747 patients who underwent aortic valve implantation or transaortic valve implantation were included to investigate the relationship between SIRS and mortality. The authors found that the predictors of SIRS were high preoperative hemoglobin and leucocyte count, cerebrovascular disease, and preoperative dialysis history. Another study examining SIRS in pediatric patients undergoing cardiac surgery in the postoperative period revealed that predictors of SIRS were age, low weight, CPB time, and cross-clamp time.[9] In a study by Güvener et al.,[17] 246 pediatric patients were retrospectively evaluated to identify the effects of SIRS on the postoperative results. The study revealed that predictors of SIRS were CPB time, low weight (<10 kg), and right-to-left shunt before surgery. In the present study, preoperative EuroSCORE, on-pump CABG, and IABP use were found to be SIRS predictors. In contrary to aforementioned studies, CPB time was not found to be among the SIRS predictors. Another factor different from other studies was hemoglobin level, as such we found that low hemoglobin levels, but not high hemoglobin levels, were the predictor of SIRS.

    Although it is well-known that SIRS is one of the main reasons for adverse postoperative outcomes after cardiac interventions, only a few studies have addressed into this problem. In one of these studies made by Sinning et al.,[15] 152 patients who underwent transcatheter aortic valve implantation (TAVI) were evaluated to question the effects of SIRS on the postoperative results. According to this study, SIRS affected early postoperative results and postoperative first-year mortality rates; however, it had no effect on postoperative stroke. Güvener et al.[17] also evaluated the effects of SIRS on postoperative results of pediatric cardiac operations and SIRS was found to be a strong predictor of postoperative mortality. As mentioned above, Lindmann et al.[16] evaluated 747 patients undergoing postoperative TAVI in terms of SIRS predictors. Clinical parameters were used in their study and the patients with SIRS had a longer ICU length of stay, more frequent ICU admission, longer hospitalization period, and higher acute renal failure incidence. The authors also found that SIRS had no significant effect on postoperative stroke and mortality in the early postoperative period. Subgroup analysis revealed that SIRS was a predictor of mortality in cardiac patients with diabetes in the postoperative period. In another study, Soares et al.[9] evaluated 101 patients who underwent open heart surgery. It was shown that SIRS prolonged the weaning period and the length of ICU and hospital stay. The authors also reported that SIRS had no significant effect on mortality. Our results are consistent with previous studies. According to the present study, SIRS prolonged the weaning period and the length of ICU stay; however, it did not increase neurological outcomes or mortality.

    The main limitations of the present study are its retrospective design and the evaluation of clinical parameters only, but not proinflammatory markers. Nevertheless, our study is one of the rare studies which address into the relationship between SIRS and CABG.

    In conclusion, the relationship between SIRS and CABG outcomes is still an obscure subject to be elucidated. In our study, mean age and EuroSCORE were higher and preoperative hemoglobin levels were lower in patients with SIRS. On-pump surgery and IABP use were also significantly higher in the SIRS group, while the length of ICU stay and the weaning period were significantly longer in the SIRS group. Based on these results, we can speculate that age is the only factor which has a significant effect on SIRS prediction. Although SIRS seems not to have an evident effect on neurological complications or mortality, it may prolong the length of ICU stay and the weaning period. Further prospective, large-scale, randomized-controlled studies are needed to confirm these findings.

    Declaration of conflicting interests
    The authors declared no conflicts of interest with respect to the authorship and/or publication of this article.

    Funding
    The authors received no financial support for the research and/or authorship of this article.

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  • Summary
  • Introduction
  • Methods
  • Results
  • Discussion
  • References
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    2) Asimakopoulos G. Systemic inflammation and cardiac surgery: an update. Perfusion 2001;16:353-60.

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    7) Brewer R, Theurer PF, Cogan CM, Bell GF, Prager RL, Paone G; Membership of the Michigan Society of Thoracic and Cardiovascular Surgeons. Morbidity but not mortality is decreased after off-pump coronary artery bypass surgery. Ann Thorac Surg 2014;97:831-6.

    8) Bicer M, Senturk T, Yanar M, Tutuncu A, Oral AY, Ulukaya E, et al. Effects of off-pump versus on-pump coronary artery bypass grafting: apoptosis, inflammation, and oxidative stress. Heart Surg Forum 2014;17:E271-6.

    9) Soares LC, Ribas D, Spring R, Silva JM, Miyague NI. Clinical profile of systemic inflammatory response after pediatric cardiac surgery with cardiopulmonary bypass. Arq Bras Cardiol 2010;94:127-33.

    10) Laffey JG, Boylan JF, Cheng DC. The systemic inflammatory response to cardiac surgery: implications for the anesthesiologist. Anesthesiology 2002;97:215-52.

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    12) Sasse M, Dziuba F, Jack T, Köditz H, Kaussen T, Bertram H, Beerbaum P, Boehne M. In-line Filtration Decreases Systemic Inflammatory Response Syndrome, Renal and Hematologic Dysfunction in Pediatric Cardiac Intensive Care Patients. Pediatr Cardiol 2015;36:1270-8.

    13) MacCallum NS, Finney SJ, Gordon SE, Quinlan GJ, Evans TW. Modified criteria for the systemic inflammatory response syndrome improves their utility following cardiac surgery. Chest 2014;145:1197-203.

    14) Ferraris VA, Ballert EQ, Mahan A. The relationship between intraoperative blood transfusion and postoperative systemic inflammatory response syndrome. Am J Surg 2013;205:457-65.

    15) Sinning JM, Scheer AC, Adenauer V, Ghanem A, Hammerstingl C, Schueler R, Müller C, Vasa-Nicotera M, Grube E, Nickenig G, Werner N. Systemic inflammatory response syndrome predicts increased mortality in patients after transcatheter aortic valve implantation. Eur Heart J 2012;33:1459-68.

    16) Lindman BR, Goldstein JS, Nassif ME, Zajarias A, Novak E, Tibrewala A, et al. Systemic inflammatory response syndrome after transcatheter or surgical aortic valve replacement. Heart 2015;101:537-45.

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  • Top
  • Summary
  • Introduction
  • Methods
  • Results
  • Discussion
  • References