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ORIGINAL ARTICLE
Year : 2022  |  Volume : 25  |  Issue : 6  |  Page : 855-860

The effect of epidural analgesia added to general anesthesia on systemic immune-inflammation index in radical prostatectomy surgery: A retrospective study


1 Department of Anesthesiology and Reanimation, Tekirdag Namık Kemal University, Faculty of Medicine, Tekirdag, Turkey
2 Department of Urology, Tekirdag Namık Kemal University, Faculty of Medicine, Tekirdag, Turkey

Date of Submission01-Oct-2021
Date of Acceptance12-Jan-2022
Date of Web Publication16-Jun-2022

Correspondence Address:
Dr. A Gultekin
Tekirdağ Namık Kemal University Faculty of Medicine, Department of Anesthesiology and Reanimation, 2nd Floor Operating Room, Süleymanpasa, Tekirdag
Turkey
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/njcp.njcp_1858_21

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   Abstract 


Background: Systemic immune-inflammation index (SII) is increasingly valued for its simplicity and predictability. Anesthesia/analgesia technique may affect cancer survey. Aims: The primary aim of this study is to offer a comparative evaluation for the effect of different anesthesia/analgesia techniques employed in radical prostatectomy surgery on SII, a new inflammatory index. Patients and Methods: Eighty-one patients who underwent radical prostatectomy between January 1, 2012, and December 31, 2020, were included in the study. We recorded oncological demographic data of Group G (n = 45) and Group GE (n = 36), preoperative and postoperative (within the first 4 hrs and 24th hr) SII values, perioperative surgical bleeding, and amount of blood transfusion. Results: Despite the lack of significant difference in the SII values between the groups, both the peak SII level and the SII change in the postoperative period became higher in Group G than in Group GE. In addition, the amount of surgical bleeding and blood transfusion was observed to be significantly lower in Group GE (P < 0.001, P = 0.092, respectively). Conclusions: GE in radical prostatectomy surgery in terms of SII, the SII change in the postoperative period was more pronounced in Group G. However, a significant difference was noted in surgical bleeding in Group GE. We can conclude that comparing the SII values of different anesthesia techniques with prospective studies might thus create a difference in survival and metastasis at the micro-level.

Keywords: Epidural analgesia, radical prostatectomy, systemic immune-inflammation index


How to cite this article:
Gultekin A, Sahin A, Akgul M, Yildirim I, Altinoz K, Baran O, Arar C. The effect of epidural analgesia added to general anesthesia on systemic immune-inflammation index in radical prostatectomy surgery: A retrospective study. Niger J Clin Pract 2022;25:855-60

How to cite this URL:
Gultekin A, Sahin A, Akgul M, Yildirim I, Altinoz K, Baran O, Arar C. The effect of epidural analgesia added to general anesthesia on systemic immune-inflammation index in radical prostatectomy surgery: A retrospective study. Niger J Clin Pract [serial online] 2022 [cited 2022 Aug 8];25:855-60. Available from: https://www.njcponline.com/text.asp?2022/25/6/855/347613




   Introduction Top


Inflammatory reaction acts on tumor development in many aspects, ranging from tumor growth to metastasis.[1] Inflammation-induced by inflammatory blood cells (neutrophils, lymphocytes, and platelets) in peripheral blood contributes to tumor development and progression by affecting proliferation and migration of tumor cells, promoting angiogenesis and metastasis, and reducing responses to anti-tumor therapies.[2],[3],[4] Inflammation acts as an essential predictor of tumor invasion, progression, and metastasis. Therefore, these serum markers are increasingly valued for their noninvasiveness, simplicity, and predictability.[5] In addition, epidemiological data derived from noncancer surgeries suggest that increased inflammatory response may be responsible for worse postoperative outcomes.[6] Systemic immune-inflammation index (SII), a new inflammatory index, has been defined as neutrophil (N) * platelet (P)/lymphocyte (L) count in peripheral blood.[7]

As identified by recent clinical research, SII can be a promising tool for the prognosis of some cancer types, including hepatocarcinoma,[7] renal cell carcinoma,[8] colorectal carcinoma,[9] gastric cancer,[10] and prostate cancer.[11] Prostate cancer is known as the most common type of cancer in men and the second most prevalent cause of cancer-induced death in men.[12] In our healthcare facility, general anesthesia and general anesthesia + epidural analgesia are performed for prostate cancer surgeries. The primary aim of this clinical report is to compare the postoperative short-term effects of epidural analgesia on the SII value, which can yield significant results in oncological prognosis and the estimated amounts of surgical bleeding and blood transfusion in prostate cancer.


   Material and Methods Top


The ethics approval was granted by the medical ethics committee of Tekirdag Namık Kemal University (dated January 26, 2021, and protocol number 2021.21.01.21), and the research was carried out in collaboration with the Department of Anaesthesiology and Reanimation and the Department of Urology. This retrospective study was planned by scanning the files of patients who had undergone elective radical prostatectomy between January 1, 2012, and December 31, 2020. Patients who were diagnosed with prostate cancer and over the age of 18 who underwent elective radical prostatectomy under general anesthesia were included in the study. Among the cases, cases with hematological malignancies other than prostate cancer or with additional malignancies expected to directly affect SII, and cases requiring surgical intervention within 24 hrs postoperatively were excluded from the study. We divided the eligible patients into two cohorts as general anesthesia (Group G) and general anesthesia + epidural group (Group GE). Group G's perioperative and postoperative analgesia was maintained with nonsteroidal anti-inflammatory analgesics and narcotic drugs. In contrast, Group GE was provided with local anesthetics and epidural catheters perioperatively and up to 12 hrs postoperatively. For general anesthesia, infusion of fentanyl (Johnson & Johnson, Belgium) 1–2 μg/kg, propofol (Frenius Kabi, Sweden) 1.5–2.5 μmg/kg, and rocuronium (Merck Sharp Dohme, Germany) 0.6 μg/kg Anesthesia was induced. In addition, general anesthesia was continued with sevoflurane inhalation anesthesia (and if necessary, remifentanil infusion).

In contrast, nonsteroidal anti-inflammatory and weak narcotic agents (tramadol) were utilized for postoperative analgesia in Group G. On the other hand, perioperative and postoperative analgesia in Group GE (After the epidural space was identified using the loss-of-resistance technique, athe epidural catheter (B. Braun, Germany) was inserted into the epidural space.) was maintained by administering a local anesthetic of 5cc 0.25% bupivacaine bolus (bupivacaine 0.5 – 1/1 diluted in physiological saline) through an hourly epidural catheter, depending on the patients' hemodynamics. It was established during the clinical procedure that the patients were given intermittent bolus doses of a local anesthetic (bupivacaine 0.25%) agent through the epidural catheter for the following 12 hrs for postoperative analgesia, based on their hemodynamics.

In addition to demographic information extracted from the patient files, the following parameters were recorded based on the first preoperative and postoperative (within the first 4 hrs and at the 24th hr) hemogram results in the hospital: SII values, the status of the surgical margin, the ISUP grade[13] score (from 1 to 5) accepted by the International Society of Urological Pathology (ISUP), preoperative PSA (prostate-specific antigen), tumor stage based on the extent of the tumor limited to or outside the prostate capsule (<pT3b), and the amount of surgical bleeding (ml) and transfusion (number of erythrocyte suspension packages).

All these research data were collected to investigate regional anesthesia and its effects on cancer prognosis (micro-level) with SII values in patients exposed to radical prostatectomy.

Statistical analysis

Descriptive statistics were expressed as mean ± standard deviation and median with interquartile range (IQR) of 25% to 75% for continuous variables depending on their distribution. Numbers and percentages were used for categorical variables. The normality of the numerical variables was checked by the Shapiro–Wilk, Kolmogorov–Smirnov, and Anderson–Darling tests. The independent samples t-test was performed in comparing two independent groups where numerical variables had a normal distribution. For variables with nonparametric distribution, the Mann–Whitney U test was used. The Pearson's Chi-squared test was performed to compare the differences between categorical variables. The Friedman test was conducted in examining the changes of numerical variables (hemoglobin and the SII score) over different study intervals (preoperative, early postoperative, postoperative 24 hr). The Durbin Conover test determined the measurements causing the significance. Spearman correlation coefficients were calculated to analyze the relationships between numerical variables. “Jamovi project (2020), Jamovi (Version 1.6.13.0) [Computer Software] (Retrieved from https://www.jamovi.org), and JASP (Version 0.14.1.0) (Retrieved from https://jasp-stats.org) software programs were utilized for statistical analysis. In a separate analysis of each group, P values were corrected using Bonferroni Correction in evaluating changes over time. The significance level (P-value) was set at 0.05 in all statistical analyses.


   Results Top


A total of 89 files dated between January 1, 2012, and December 31, 2020, were included for analysis in our study. However, the files of 8 patients were excluded owing to the missing data, and thus those of 81 eligible patients were taken into consideration in the final analysis. There were 45 (55.6%) patients in Group G and 36 (44.4%) patients in Group GE. The groups turned out to be similar with respect to age (P = 0.255), preoperative PSA (P = 0.362) and hemoglobin levels (P = 0.676), preoperative SII scores (P = 0.638), distribution of ISUP grades (P = 0.202), surgical margins (P = 0.731), and tumor stage (P = 0.866). Preoperative SII index scores in Group G and in Group GE were calculated as 385 and 413.5, respectively, which yielded no significant difference (P = 0.638).

The demographic and clinical characteristics of the patients are summarized in [Table 1]. The median value of intraoperative blood loss was 900 ml, and red blood cell transfusions were performed in 52 (64.2%) patients. Negative margins for tumors were seen in 65 (80.2%) patients, while the tumor stage was localized in the prostate gland in 68 (84.0%) patients.
Table 1: Demographic and clinical characteristics of the patients

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Another aspect deserving attention is that the mean intraoperative blood loss was 1100 ml in Group G and 500 ml in Group GE, which indicated a significant difference (P < 0.001). Though the proportion of patients exposed to transfusion in Group G was higher than that of their counterparts in Group GE, this difference was not significant (73.3% vs 52.8%, respectively, P = 0.092). However, a significant difference was noted in the number of transfused packed red blood cells between the two groups (P = 0.025) [Table 1]. [Table 2] compares the results obtained from hemoglobin levels and perioperative SII scores in both groups.

Significant decreases were observed in postoperative hemoglobin levels in comparison to preoperative measurements in both groups. Hemoglobin levels in Group G fell from 14.4 g/dL to 11.4 g/dL until the postoperative 4th hour and to 10.6 g/dL in the postoperative 24 hrs (P < 0.001). Early and postoperative 24-hr hemoglobin measurements were also significantly lower than those in the preoperative period in Group GE (P < 0.001). Nevertheless, the changes in hemoglobin levels in the postoperative periods were established to be similar between the groups [Table 3].
Table 2: Measurements of perioperative and postoperative hemoglobin levels and SII scores in the groups

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Table 3: Comparison of the perioperative changes in hemoglobin levels and SII scores

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SII scores in the postoperative 4th hr and 24th hr significantly increased in both groups compared to preoperative SII scores (P < 0.001 for both groups). Comparing the SII scores between the postoperative 4th hr and 24th hr revealed that the peak values reached in the postoperative 4th hr period plummeted in the postoperative 24th hr [Table 3]. Although the SII change in the postoperative period was more significant in Group G, SII scores did not show significant between-group changes.


   Discussion Top


The systemic immune-inflammation index, a new inflammatory index that can broadly represent the balance of host immunity and inflammatory status, refers to neutrophil (N) * platelet (P)/lymphocyte (L) count in peripheral blood.[7] Published research provides clinical evidence that platelets may promote the formation of micrometastases, that neutrophils can enhance tumor-induced angiogenesis, and that both platelets and neutrophils may even facilitate the disguise of the host from the immune system by creating a barrier to circulating tumor cells. Tumor proliferation and migration can be suppressed by lymphocytes which induce cytotoxic cell death.[14] In this context, SII can account for why high neutrophil and platelet counts and low lymphocyte counts bring about an inadequate immune response but a robust inflammatory response.[15],[16] Previous literature reports suggest that SII has a clear association with the number of circulating tumor cells involved in the poor prognosis and metastasis of cancer[17] and can also shed new light on the prognosis of hepatocarcinoma,[7] renal cell carcinoma,[8] colorectal carcinoma,[9] gastric cancer,[10] and prostate cancer.[11] Our study mainly focused on prostate cancer because prostate cancer is the most common type of cancer among men and ranks second in cancer-related deaths in men.[12]

The amount of surgical bleeding in Group GE was lower. A significant difference was evident in terms of the estimated amount of bleeding during surgery (P < 0.001), also validated by published clinical reports.[18],[19],[20],[21] This situation arises due to hypotension caused by epidural analgesia added to general anesthesia.[21] Consequently, the amount of blood transfusion performed on the patients in Group GE perioperatively (P = 0.025) and the proportion of patients receiving perioperative transfusion remained lower (P = 0.092).

Though both groups had similar preoperative SII values, a significant difference was noted between the postoperative 4th hr and 24th-hr SII and the preoperative SII, which might have resulted from the surgical procedure and the stress it caused. The change in SII proved to be more significant in the postoperative period in Group G, yet this did not yield a significant difference.

According to the data issued by the World Health Organization, cancer is still the second leading cause of death in the world.[22] Prostate cancer is the most prevalent cancer in men,[12] and conditions that will affect the prognosis and survival of the patient are of great importance. Indeed, the association between SII and cancer prognosis remains controversial. However, there are some lines of evidence suggesting that SII is correlated with the circulating tumor cell count of the gastric tumor metastasis.[17] Furthermore, a meta-analysis documents that high SII values may be a prognostic indicator in urological cancers.[15],[16] No significant difference was detected in terms of the effect of anesthesia type on SII change. However, it should be noted that the postoperative peak level of SII and the amount of change in the postoperative period were higher in Group G.

The treatment of a substantial number of cancer types is conducive to surgery, and over 60% of cancer patients are most likely to undergo tumor resection. Moreover, 80% of patients have to undergo anesthetic procedures for diagnostic, therapeutic, or palliative intervention.[6] Intraoperative anesthetic management and postoperative analgesic strategies may facilitate the spread and/or elimination of micrometastases and residual tumor cells following oncologic surgery.[23] Recently, a substantial body of clinical research has addressed the survival or recurrence impact of anesthetic techniques in cancer surgery.[24],[25],[26],[27],[28],[29] However, while some metanalyses based on retrospective data of neuraxial anesthesia techniques in prostate cancer surgery report conflicting results concerning recurrence,[25],[26] other studies document favorable effects of these techniques on overall survival.[30] In line with the studies mentioned above, no significant difference is evident between Group G and Group GE during the postoperative short-term concerning SII in our study. However, the peak level of SII and the amount of change in the postoperative period was observed to be higher in Group G. The relationship between short or long-term SII studies scheduled postoperatively and oncological results of neuraxial anesthesia can be investigated at the micro-level in cancer surgeries, other than prostate cancer, performed with regional anesthesia.

The most important limitation of our study; the study method is retrospective. We believe that if our study had been conducted with a prospective design, it would have yielded more insightful outcomes. As a result, even though our cohorts were similar in terms of postoperative evaluation of SII, we suggest that opioid use, if any, can be minimized by extending the duration of postoperative epidural analgesia. If we had administered continuous infusion and more prolonged epidural analgesia instead of bolus epidural doses, the SII values could have been more discriminating. SII can be considered as a predictive factor for prognosis in some types of oncology, and prospective studies may enable clinicians to re-assess the effects of anesthesia techniques on prognosis and survival at the micro-level in oncological surgeries.

SII, a new inflammatory index, may have clinical utility as a prognostic indicator of some cancer types, including hepatocarcinoma, renal cell carcinoma, colorectal carcinoma, gastric, and prostate cancer. Although our findings did not signal any significant difference between the groups exposed to general anesthesia and general + epidural analgesia, we suggest that prospective studies on other oncological cancer surgeries and further studies on the effect of anesthesia techniques on SII in the short and long term are warranted. In that regard, a micro-level investigation into the effect of anesthesia techniques upon survival and recurrence could yield fruitful and insightful results.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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    Tables

  [Table 1], [Table 2], [Table 3]



 

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