Stress Response » of the Organism During Oncosurgery Depending on Different Types of Anesthesia

Материалы и методы. Пациентов, перенесших резекционные операции на толстой кишке по поводу зло качественных заболеваний, разделили на 2 группы: основную (n=57) и группу сравнения (n=35). В основной группе проводили мультимодальную анестезию, включавшая неглубокую симпатическую блокаду в сочета нии с поверхностной ингаляционной анестезией. В группе сравнения была проведена ингаляционно внутри венная анестезия на основе системного введения фентанила в условиях миоплегии и инсуффляции севоф люрана. В трех исследовательских точках (перед индукцией в анестезию, в травматичный момент операции и в момент окончания операции) в сыворотке крови определяли содержание инсулина, адреналина, норадре налина, дофамина, кортизола и глюкозы. Проверка статистических гипотез проведена с помощью непараме трических методов, данные обработаны с использованием программы Statistica 6.


Materials and Methods
During the period from 2011 to 2013 in the Omsk Regional Clinical Oncology Dispensary 92 patients, 57 to 74 years old, were examined.Patients with colon cancer were treated by a surgery.The study was approved by the ethics committee; the patients were informed about the upcoming surgery and anesthesia and provided the written informed consent.All patients had anesthesia risk of 3 rd class (ASA).Patients with a blood loss of over 500 ml (as determinjed by an aspiration gravimetric method), and patients who received inotropic support, or those who suf fered from diabetes were excluded from the study.Endoscopic interventions were excluded.All patients were discharged from the hospital without any assessment of the duration of stay.There was no gender preferential for inclusion into the study group.The patients were divided into 2 groups: study group and comparison group.Patients of comparison group (n=35) received a combined inhala tion intravenous anesthesia under myoplegia and mechan ical ventilation as an anesthesia care.All patients received oral sedative drugs and 2500 IU of dalteparin subcuta neously the evening before the surgery.On the day of oper ation premedication was prescribed that included anti his tamines (diphenhydramine 20 mg intramuscularly, IM) and treatment for prevention of infectious and inflamma tory complications (ceftriaxone 1 g administered 40 min utes before skin incision).Induction of anesthesia was per formed by intravenous bolus administration of solution of fentanyl (0.0014 mg/kg) and propofol lipuro (2.14 mg/kg) (B.Braun, Gеrmany).Myoplegia was performed with lis tenon (2.5 mg/g) and pipecuronium (0.06 mg/kg).Anesthesia was maintained by fractional introducing of fentanyl (0.003-0.004 mg/kg/h) with sevoflurane inhala tion (MAC to 1) based on the low flow technique with the fresh gas flow (at least 0.5 l/h).Ventilation was carried out with Aespire (J.Electricians, USA) with control by volume and 40% FiO 2 .We controlled the blood pressure, heart rate, capnogram, the depth of neuromuscular block, and the ECG without BIS monitoring.
Концентрация кортизола во 2 й исследова тельской точке (момент операции) в основной группе оказалась статистически значимо ниже (на 21,1%), чем в группе сравнения, в которой от мечалось увеличение этого показателя на 38,2% по сравнению с исходным, что превышало верх abdomen revision and intestinal traction, as the most trau matic moment, and the end of operation.The study of early postoperative period in these groups is beyond the scope of this study.Cortisol and insulin levels were determined by ELISA with automatic analyzer IMMULITE 1000 (USA) using standard reagents (Siemens Healthcare Diagnostics Prodacts Ltd.UK).Adrenaline, noradrenaline, dopamine in the plasma was determined by ELISA with a microplate photometer Multiskan FC (Finland) using standard kits (3 CATELISA, Germany).Statistical data processing was performed in Statistica 6 program.The distribution of a number of variations was assessed using the Kolmogorov Smirnov test, as well as histograms and frequency analysis.Because the studied parameters were not the subject of normal (Gaussian) distribution, the nonparametric Mann Whitney test (for comparison of two independent sam ples) and Wilcoxon (to compare two dependent samples) were employed for testing the statistical hypothesis, and quantitative data were expressed as median (Me) and interquartile amplitude.

Results and Discussion
The results are presented in the table and fig ure .Before surgery, there were no statistically signif icant differences in studied parameters between groups.At the time of and after the surgery the sta tistically significant differences during the observa tion (1 st , 2 nd , 3 rd study points) were defined (Table ).
As shown in the Table, cortisol level at the 2 nd study point (the time of a surgery) in the study group was significantly lower (21.1%)than in the comparison group that demonstrated an increase in this parameter by 38.2% compared to a baseline exceeding the upper normal values.At the 3rd study point (at the end of operation), the cortisol level in the comparison group had a tendency to further increase (by 46.8% compared to baseline), and in the study group hypercortisolemia was not observed.The difference between groups was 32.3%.
Insulin level in the 2 nd study point was signifi cantly higher (by 21.5%) in the study group than in the comparison group.The level of adrenaline in the 2 nd study point was lower than the initial one by 35.9% for patients of the study group, whereas in the comparison group it was higher by 35.9% exceeding 2 fold the level of adrenaline of the study group patients.At the end of operation (3 rd study point) the level of adrenaline continued to increase in the comparison group, and the same indicator in the study group decreased (the difference was 65.8%).
Level of glucose in serum of patients of the study group and the comparison group during the traumatic moments of operations significantly exceeded the initial values by 16.4 and 23.6%, respectively.After the operation, the level of glucose in both groups did not change demonstrating persis tence of hyperglycemia.
Therefore, the study of 'stress' hormones, insulin and glucose indicates activation of 'hypothal amic pituitary adrenal cortex' system under the stress caused by a traumatic surgical procedure in cancer patients.Hypercortisolemia in the compari son group at the traumatic moment of operation is explained by the fact that the targets of systemic anesthesia analgesia are supraspinal structures.Lack of hypercortisolemia at this moment in the study group demonstrates the reliable prevention of sym pathetic afferentation from the injury site, even with a low concentration of local anesthetic solution.
One of the major signs of the severity of the «stress response» to injury is the level of plasma cat echolamines.Hypercatecholaminemia (mainly due to adrenaline) in the comparison group at the trau matic time and further growth of indicators point to the failure of systemic administration of drugs for anesthesia to prevent sympathetic afferentation fol lowed by «stress response».At the same time, the absence of catecholamine level drift in the study group indicates the ability of multimodal anesthesia to prevent hypermetabolic response to stress [18].
The main reason for insulin resistance (the key anabolic hormone) is considered to be a high level of serum cortisol, which indirectly promotes gluconeo genesis in the later period presumably due to the amino acids of skeletal muscle proteins.Dynamics of insulin levels in our patients suggest the ability of multimodal anesthesia to maintain a high level of insulin in serum at traumatic moment in conjunction with the lack of hyperglycemia.To ensure a stable glycemic profile after operation in patients with an epidural catheter less insulin is needed.Thereby, the multimodal anesthesia prevents possible insulin resistance.Postoperatively even a slight hyper glycemia may contribute to unfavorable outcome after surgery on the colon (the results of a retrospec tive analysis of more than 7,500 colectomies) [19].
Thus, the effectiveness of various methods of anesthesia can be judged by hormonal background of intraoperative period, but these studies are quite time consuming and expensive for anesthesiologists to use on a daily basis.Based on these data it can be argued that multimodal anesthesia is more effective method for traumatic surgery on the colon than modern inhalation intravenous anesthesia [20,21].Interrupting sympathetic afferentation from the injury site, multimodal anesthesia reduces the sever ity of metabolic reactions to surgical stress and thereby has a stress limiting and stress modeling effect [22,24].вает на способность мультимодальной анестезии предотвращать гиперметаболическую реакцию на стресс [18].