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ORIGINAL ARTICLE
Year : 2022  |  Volume : 6  |  Issue : 3  |  Page : 152-156

Efficacy of preoperative oral glucose on blood glucose response and neutrophil–lymphocyte ratio in patient undergoing brain tumor resection: Randomized controlled trial study


Faculty of Medicine, Department of Anesthesiology and Intensive Care, Udayana University, Bali, Indonesia

Date of Submission19-Mar-2022
Date of Decision01-Jun-2022
Date of Acceptance04-Jun-2022
Date of Web Publication27-Jul-2022

Correspondence Address:
Christopher Ryalino
Faculty of Medicine, Department of Anesthesiology and Intensive Care, Udayana University, Jl. PB Sudirman, Denpasar 80232, Bali
Indonesia
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/bjoa.bjoa_89_22

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  Abstract 

Background: Hyperglycemia and inflammatory conditions due to surgical stress response in conventional brain tumor resection can increase the morbidity and mortality of neurosurgery patients. Enhanced recovery after surgery (ERAS) protocol has been widely used in various types of surgery, but data on the neurosurgery are still limited. The aim of this study was to analyze the role of preoperative oral glucose administration in attenuating surgical stress response in patients undergoing brain tumor resection. Materials and Methods: Thirty-four elective craniotomy brain tumor resection patients underwent a double-blind, randomized controlled trial. Patients were divided into two groups: one group that received oral carbohydrate (CHO; maltodextrin 12.5% 50 g in 400 ml water) 2 h preoperatively and a control group that only received water. Blood glucose level and neutrophil–lymphocyte ratio (NLR) were obtained preoperatively, before induction, and 6 h and 24 h postoperatively. Results: Blood glucose was better in the CHO group at 6 h (117.18 ± 16.25 mg/dl vs. 154.88 ± 28.22 mg/dl, P < .001) and 24 h (118.05 ± 13.89 mg/dl vs. 153.76 ± 34.81 mg/dl, P < .001) postoperatively compared to that in the control group. NLR in the CHO group showed a lower value compared to that in the control group at 6 h (8.21 ± 6.20 vs. 15.47 ± 6.76, P < .001) and 24 h (9.43 ± 7.35 vs. 20.04 ± 10.99, P < .001) postoperatively. Conclusion: Preoperative oral glucose administration can help reduce the stress response in brain tumor resection by maintaining blood glucose level and attenuating the increase of NLR postoperatively better than in routine preoperative fasting.

Keywords: Craniotomy, fasting, maltodextrin, neurosurgery


How to cite this article:
Senapathi TG, Tanoto F, Widnyana I M, Suarjaya I P, Hartawan I G, Ryalino C. Efficacy of preoperative oral glucose on blood glucose response and neutrophil–lymphocyte ratio in patient undergoing brain tumor resection: Randomized controlled trial study. Bali J Anaesthesiol 2022;6:152-6

How to cite this URL:
Senapathi TG, Tanoto F, Widnyana I M, Suarjaya I P, Hartawan I G, Ryalino C. Efficacy of preoperative oral glucose on blood glucose response and neutrophil–lymphocyte ratio in patient undergoing brain tumor resection: Randomized controlled trial study. Bali J Anaesthesiol [serial online] 2022 [cited 2022 Aug 10];6:152-6. Available from: https://www.bjoaonline.com/text.asp?2022/6/3/152/352406




  Introduction Top


The high perioperative stress in conventional craniotomy surgery results in increasing the risk of cerebrovascular and cardiovascular complications and impairs postoperative nutritional intake.[1] In addition, perioperative hyperglycemia and inflammation caused by surgical stress response have an impact especially in neurosurgery patients and are associated with poor outcome, increasing morbidity, and increasing mortality in this population.[2] Enhanced recovery after surgery (ERAS) principle in attenuation of surgical stress response has been widely implemented in various disciplines of elective surgery, including neurosurgery recently.[3]

Preoperative oral carbohydrate (CHO) as one of the key components in ERAS protocol is believed to suppress the surgical stress response by preventing insulin resistance and hyperglycemia, maintaining glucose homeostasis.[2],[3] This study aims to analyze the effect of preoperative oral glucose administration on blood glucose and neutrophil–lymphocyte ratio (NLR) response in patients undergoing brain tumor resection.


  Materials and Methods Top


Our study was a double-blind, randomized controlled trial. The study protocol was reviewed and approved permission by the institutional review board (registry number 76/UN14.2.2.VII.14/LT/2022) issued on January 12, 2022. Inclusion criteria included adult patients with single intracranial space occupying lesion with physical status ASA I-II and aged between 18 and 60 years admitted for elective craniotomy brain tumor resection. Patients with diabetes mellitus, pregnancy, consciousness deficit, cognitive impairment, and swallowing and gastrointestinal abnormalities were excluded. Patients with intraoperative bleeding more than 30% of estimated blood volume, incidence of adverse event, surgery duration >4 h, and postoperative ventilator use were excluded from the study. Written informed consent was obtained from all patients or their legal guardian.

A total of 98 patients were assessed for eligibility, of whom 30 patients were excluded [Figure 1]. All eligible subjects were randomly divided into two groups: CHO group (n = 34) and control group (n = 34). Solid food should not be taken 6 h prior to surgery as per our hospital preoperative fasting protocol. We divided the subjects randomly into two groups. Group T received 400 ml of CHO (maltodextrin 12.5% 50 g–0.5 kcal/ml) 2 h prior to surgery as in the ERAS protocol. Group C (control) received 400 ml of water 2 h instead as preoperative routine care in our center.
Figure 1: CONSORT flow diagram

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In the operating room, all patients were placed under standard monitoring with electrocardiogram, arterial line, oxygen saturation, and end-tidal CO2. For both groups, standard general anesthesia protocol was performed with induction of fentanyl, propofol using target-controlled infusion, and rocuronium. Maintenance of anesthesia was given oxygen mixed with air, propofol, fentanyl, and rocuronium. Both groups were given local anesthetic infiltration at the incision site by our neurosurgeon. At the end of the surgery, all patients were extubated uneventfully and transferred to the intensive care unit (ICU) for 1 day monitoring as per our hospital protocol. Both groups received intravenous paracetamol 1000 mg, non-steroidal anti-inflammatory drugs, and intravenous fentanyl for postoperative multimodal analgesia. Random blood glucose and NLR were recorded at an hour preoperative, before anesthesia induction, and 6 h and 24 h after surgery by venous blood sampling.

Descriptive statistics were used to compare the patient baseline characteristics. All data that were normally distributed were analyzed using the t test, and statistical significance was defined as P < .05. All the statistical tests were performed using the SPSS software (IBM Corp. Released 2020, IBM SPSS Statistics for Windows, Version 27.0; IBM Corp, Armonk, New York).


  Results Top


A total of 68 eligible patients completed the study and further data will be analyzed. No dropout subjects were found in this study. Characteristics of our subjects were comparable between CHO and control groups [Table 1].
Table 1: Subject baseline characteristics

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There was no significant difference of the glucose levels at 1-h preoperative (103.76 ± 15.26 vs. 115.18 ± 24.52 mg/dl, P = .057) and before induction of anesthesia (98.64 ± 12.11 vs. 104.76 ± 20.11 mg/dl, P = .145). Significant differences of glucose level were found at 6 h (95% CI: 21.61–53.79 mg/dl, P < .001) and 24 h postoperatively (95% CI: 17.18–55.22 mg/dl, P < .001). We found that the mean glucose level of the control group was significantly higher (154.88 ± 28.22 mg/dl) than that of the CHO group (117.18 ± 16.25 mg/dl) at 6 h postoperatively. We also found that the mean glucose level of the control group was significantly higher (153.76 ± 34.81 mg/dl) than that of the CHO group (118.05 ± 13.89 mg/dl) 24 h postoperatively [Figure 2].
Figure 2: Changes in the blood glucose level between groups

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There was no significant difference of NLR levels at preoperative baseline (3.99 ± 2.50 vs. 4.89 ± 2.93) and before induction of anesthesia (4.49 ± 2.81 vs. 6.10 ± 4.2, P = .103). Significant differences of NLR levels were found at 6 h (95% CI = 2.71–11.79, P < .001) and 24 h (95% CI = 4.08–17.14, P < .001) postoperatively. We found that the mean NLR level of the control group was significantly higher (15.47 ± 6.76) than that of the CHO group (8.21 ± 6.20) at 6 h postoperatively. We also found that the mean glucose level of the control group was significantly higher (20.04 ± 10.99 mg/dl) than that of the CHO group (9.43 ± 7.35) 24 h postoperatively [Figure 3].
Figure 3: Changes in the NLR level between groups

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  Discussion Top


Hyperglycemia and inflammation as body responses from surgical stress are associated with deleterious clinical effects, especially in neurosurgical patients, resulting in increase in morbidity and mortality, longer ICU stay, and poor functional recovery.[2] There is a strong correlation between hyperglycemia and inflammation and outcome in a neurosurgical patient (subarachnoid/intracranial hemorrhage, ischemic stroke, brain tumor) that has shown an increasing risk of poor outcome, neurological insults, and even death. NLR as a novel systemic inflammatory predictor and blood glucose as an indicator of stress response level are easy and readily available routine markers. Combined NLR and blood glucose can better predict the unfavorable outcome than any biomarker alone.[2],[4]

The metabolic effects of fasting are different between a physiological patient and a patient undergoing a major surgery. When body is under fasting condition, glucose production results mainly from glycogenolysis from liver and gluconeogenesis from muscle proteolysis to fulfil cell’s glucose demand. To reduce glucose demand in limited supply condition, the body’s response tries to lower the metabolism rate. Whereas in patients undergoing surgery, this adaptation does not occur and the rate of metabolism increases significantly instead, leading to more profuse catabolism situation, insulin resistance, and hyperglycemia. Activation of hypothalamus–pituitary–adrenal axis induces release of catecholamines, cortisol, glucagon, and inflammation cytokines as body under major stress because of surgical trauma.[5]

The main principle of ERAS protocol is to attenuate surgical stress response by multidisciplinary approach, including preoperative, intraoperative, and postoperative areas. In the preoperative setting, the concept of preoperative CHO 2 h before surgery is to prepare the human body for obtaining an endogenous release of insulin from the fasting state, resulting in a less catabolic state, thus reducing insulin resistance and hyperglycemia under stress conditions.[3],[6] Neurosurgical patients are more prone to neurological insults because of their vulnerable blood brain barrier caused not only by proinflammatory molecules, coagulation, and thrombosis from inflammation, hyperglycemia, and bleeding but also from direct sterile trauma itself, leading to neuroinflammation.

The result of our study showed that in both groups, the NLR level increases at 6 h and 24 h postoperatively, and this result confirms the previous study that NLR level will increase at day 2 until day 4 postoperatively.[4],[7] Although NLR levels increased in both groups, the increase in the CHO group was lower than that in the control group (P < .001), indicating that the acute stress response caused by surgery in the CHO group was not as severe as that in the control group. Perioperative multimodal analgesia also plays an important role in attenuating surgical stress response.

Recent studies found that preoperative CHO loading in the ERAS protocol for brain tumor surgery in China and India has shown better functional recovery and reduced hospital length of stay without increasing complication compared to that in the standard protocol.[1],[6],[8],[9],[10] Liu et al. found that preoperative CHO 2 h before surgery in patients undergoing elective craniotomy improves glucose homeostasis, lowers postoperative insulin level, and provides better handgrip strength and pulmonary functions postoperatively.[6] Widnyana et al. found 54 patients undergoing major oncology surgery who were given preoperative CHO twice (evening and morning) more effective to attenuate increase in cortisol and blood glucose level compared with patients under routine care fasting protocol.[11] In our study, the changes in blood glucose were found similar between both groups at preinduction of anesthesia (P = .145), but at 6 h and 24 h postoperatively, the blood glucose was significantly higher in the control group compared to that in the CHO group (P < .001). Results of this study are consistent with those of the previous studies. Godoy et al. have shown that the optimal glucose level in neurosurgery and neurocritical care needed to be maintained is between 100 and 150 mg/dl.[12] There were no serious complications detected in our study, but hyperglycemia (blood glucose > 180 mg/dl) was found in the control group and treated with intravenous insulin and needed to be monitored for few more days in the ICU.


  Conclusion Top


Preoperative oral glucose administration can help reduce the stress response in brain tumor resection by maintaining stable blood glucose level and attenuating the increase in NLR postoperatively better than in routine care fasting procedure. This procedure may be considered in the development of elective preoperative fasting protocol, particularly in neurosurgical population. Further studies are needed to provide more data and their relationship to patient clinical outcome.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Wang Y, Liu B, Zhao T, Zhao B, Yu D, Jiang X, et al. Safety and efficacy of a novel neurosurgical enhanced recovery after surgery protocol for elective craniotomy: A prospective randomized controlled trial. J Neurosurg 2018;130:1680-91.  Back to cited text no. 1
    
2.
Atkins JH, Smith DS A review of perioperative glucose control in the neurosurgical population. J Diabetes Sci Technol 2009;3:1352-64.  Back to cited text no. 2
    
3.
Sarin A, Chen LL, Wick EC Enhanced recovery after surgery—Preoperative fasting and glucose loading—A review. J Surg Oncol 2017;116:578-82.  Back to cited text no. 3
    
4.
Chen J, Qu X, Li Z, Zhang D, Hou L Peak neutrophil-to-lymphocyte ratio correlates with clinical outcomes in patients with severe traumatic brain injury. Neurocrit Care 2019;30:334-9.  Back to cited text no. 4
    
5.
Nygren J The metabolic effects of fasting and surgery. Best Pract Res Clin Anaesthesiol 2006;20:429-38.  Back to cited text no. 5
    
6.
Liu B, Wang Y, Liu S, Zhao T, Zhao B, Jiang X, et al. A randomized controlled study of preoperative oral carbohydrate loading versus fasting in patients undergoing elective craniotomy. Clin Nutr 2019;38:2106-12.  Back to cited text no. 6
    
7.
Yombi JC, Schwab PE, Thienpont E Neutrophil-to-lymphocyte ratio (NLR) distribution shows a better kinetic pattern than C-reactive protein distribution for the follow-up of early inflammation after total knee arthroplasty. Knee Surg Sports Traumatol Arthrosc 2016;24:3287-92.  Back to cited text no. 7
    
8.
Hagan KB, Bhavsar S, Raza SM, Arnold B, Arunkumar R, Dang A, et al. Enhanced recovery after surgery for oncological craniotomies. J Clin Neurosci 2016;24:10-6.  Back to cited text no. 8
    
9.
Liu B, Liu S, Wang Y, Zhao B, Zhao T, Zhao L, et al. Neurosurgical enhanced recovery after surgery (ERAS) programme for elective craniotomies: Are patients satisfied with their experiences? A quantitative and qualitative analysis. BMJ Open 2019;9:e028706.  Back to cited text no. 9
    
10.
Sriganesh K, Syeda S, Shanthanna H, Venkataramaiah S, Palaniswamy SR Effect of opioid versus non-opioid analgesia on surgical pleth index and biomarkers of surgical stress during neurosurgery for brain tumors: Preliminary findings. Neurol India 2020;68:1101-5.  Back to cited text no. 10
    
11.
Widnyana IMG, Senapathi TGA, Aryabiantara IW, Wiryana M, Sinardja K, Budiarta IG Metabolic stress response attenuate by oral glucose preoperatively in patient underwent major surgery with general anesthesia. Int J Anesth Pain Med 2017;3:1-5.  Back to cited text no. 11
    
12.
Godoy DA, Di Napoli M, Biestro A, Lenhardt R Perioperative glucose control in neurosurgical patients. Anesthesiol Res Pract 2012;2012:690362.  Back to cited text no. 12
    


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