Biochemical markers of surgical stress in endoscopic rhinosinus surgery under combined anesthesia in children

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Introduction.
Endoscopic rhinosinus surgery in children is associated with a high anesthetic risk, which is often underestimated due to the low invasiveness of this surgical method. However, both the area of operation (the area of innervation of the trigeminal nerve and its branches) and the proximity to the main vessels, high vascularization of the nasal area and paranasal sinuses remain the same. Quite often, there is an intraoperative expansion of the operating field, which requires additional anesthesia and the consumption of inhaled anesthetics, which directly affects the systemic hemodynamics. Inadequate anesthesia, intraoperative stress, and hemodynamic instability increase the risks of trigeminocardial reflex, high bleeding from the surgical area, and other pathological processes.
The hormonal response to intraoperative stress is dominated by the effects of catabolic hormones such as catecholamines, cortisol, and glucagon. Provoking stress factors cause a complex reaction of all parts of the neuroendocrine system. Stress stimulation of the sympathetic-adrenal system leads to the centralization of blood circulation, which triggers a cascade of pathological changes [1]. Vasospasm is accompanied by a violation of microcirculation and ischemia of organs and tissues, a violation of the rheological properties of blood, which is aggravated by hypovolemia. The resulting biologically aggressive metabolites disrupt the biological oxidation reactions, causing changes in the acid-base and water-electrolyte states [2, 3]. Hyperlactatemia and lactic acidosis in this case occurs due to tissue hypoxia due to hypoperfusion.
The hormonal response in young children is most intense, but has a shorter duration in comparison with older children and adults [4, 5]. An increase in the level of catabolic hormones leads to the activation of hepatic gluconeogenesis and lipolysis, which is also accompanied by undesirable hyperglycemia [6, 7].
Intraoperative stress directly affects the course of the postoperative period: the need for additional anesthesia after surgery; bleeding from the operation area; the degree of density of the nasal tamponade and paranasal sinuses; the severity of cephalgia; post-sarcosis nausea and vomiting (PTP); the duration of rehabilitation.
The aim of our study was to study the dynamics of biochemical markers of operational stress in assessing the effectiveness of regional methods of combined anesthesia for rhinosinus surgery in children.

Material and methods.
An open-label, comparative, randomized, parallel-group study was performed in 100 patients aged 6-17 years with an ASA I-II physical condition score, who underwent routine endoscopic endonasal surgery lasting up to 2 hours under combined anesthesia. The work was carried out on the basis of the State Budgetary Institution "Morozovskaya DGKB" DZ of Moscow from November 2018 to January 2021. Protocol No. 130 of August 21, 2018 of the positive decision of the local ethics committee.
All patients were given intravenously a 5% solution of tranexamic acid at a dose of 10-15 mg/kg of body weight 30 minutes before surgery, according to the instructions, as a preoperative preparation for prophylactic purposes.
Introductory anesthesia was performed by inhalation of sevoflurane through a face mask with preliminary filling of the respiratory circuit of the anesthesia apparatus with a gas-narcotic mixture with an anesthetic content of 7-8 vol% in a gas stream of 6 l / min of an oxygen-air mixture in a ratio of 1:1 (O2: Air=1:1) and intravenous administration of a propofol solution at a dose of 2 mg/kg of body weight. Tracheal intubation was performed after intravenous administration of rocuronium bromide solution at a dose of 0.6 mg / kg body weight. Artificial lung ventilation (ventilator) was performed using a Primus anaesthetic breathing apparatus manufactured by Dräger (Germany) in the pressure control mode – PCV with a flow of fresh gas of 1 l/min (Low flow anaesthesia) along a closed circuit.
Depending on the method of maintaining anesthesia, the patients were divided into two comparable groups of 50 people (Table 1): Group 1-Gr1 (n=50) - inhalation of sevoflurane in a stream of 1 l / min of O2 gas mixture:Air=1:1 with a target value of the minimum alveolar concentration of the anesthetic (MAK) of 0.7-0.9, performed immediately after the induction of anesthesia regional blockages pterygopalic anesthesia with palatine access (palatinal) and infraorbital intraoral access bilaterally with ropivacaine solution at the rate of V (ml) = age in years/10. The formula is applicable for calculating the volume of ropivacaine for each of the 4 blockades, and the total dose of ropivacaine does not exceed the maximum allowable dose for regional blockades. Ropivacaine concentrations differ depending on the age of the patient (up to 12 years of age, the permissible concentration is 0.5%, over 12 years of age-0.75%); group 2-Gr2 (n=50) - inhalation of sevoflurane in a stream of 1 l / min of O2 gas mixture:Air=1:1 with a target value of 1.5 MAC of the anesthetic, 5% tramadol solution was injected intravenously at the rate of 2 mg/kg of body weight.

Table.1. General characteristics of patients by group, Me (Q1-Q3)

Criteria for inclusion in the study:
- patients of both sexes who are scheduled for otorhinolaryngological surgical interventions, aged from 4 to 18 years with an ASA I-II rating, who do not have violations of laboratory parameters;
- surgical interventions lasting up to 2 hours;
- general and combined anesthesia with the use of inhaled and intravenous anesthetics and hypnotics (sevoflurane, propofol), regional blockades: palatinal, infraorbital;
- pre-issued informed consent (IP) for the patient's participation in the study.
Exclusion criteria from the study:
- infectious process at the site of the regional blockade;
- coagulopathy and anticoagulant treatment;
- lymphadenopathy in the area of regional blockade;
- traumatic brain injuries and mental illnesses;
- individual intolerance to the drugs used in the study;
- severe violations of kidney and liver function, accompanied by changes in laboratory parameters beyond the age reference values;
- the presence of an immunosuppressive condition, both congenital and acquired;
- refusal to participate in the study.
The assessment of biochemical parameters – markers of operational stress (glucose( Glu), lactate (Lac) and cortisol (Coh)) was carried out at the following stages:: 1st – before the start of anesthesia (the patient is on the operating table, at the time of monitoring); 2nd – the most traumatic stage of the operation, determined by the surgeon; 3rd – the end of anesthesia, the time of tamponade of the nose and paranasal sinuses (ONP).
Determination of glucose and lactate values at the study stages was carried out in all patients using a gas analyzer "Gem Premier 4000" (Werfen, USA), cortisol in 8 patients in each study group using an immunochemical analyzer "Beckman Coulter Dx1800" (USA, 2014). Venous blood was collected for the study from the peripheral vein into a marked tube, in which it was mixed with a filler (coagulation activator)by turning the tube 5-6 times at 180°. The sample was then sent to the laboratory. The reference values of the studied parameters had the following range: glucose-3.9-5.8 mmol/l; lactate-0.7-2.2 mmol/l; cortisol 66-644 nmol / l.
Statistical processing was carried out using the program "Statistica", 10.0. The analysis of the distribution of the obtained data was carried out according to the Kolmagorov Smirnov criterion at p<0.05. The data is presented as a median (Me; Me1, Me2, Me3-the median of 1,2,3 study stages) and quartiles (Q₁/Q3). To assess statistically significant inter - group differences, the Mann-Whitney test (U-test) was used, and the Wilcoxon test was used for intra - group inter-stage differences. The level of statistically significant differences was assumed at p<0.05.

Results and discussion.
In dynamics, the values of glucose, lactate and cortisol in the blood plasma did not have statistically significant differences between the groups at all stages of the study, which indicated the effectiveness of both methods of anesthesia and was confirmed by the absence of a stress reaction even in the most traumatic stage of the operation. (Table 2).

Table 2. Dynamics of glucose, lactate, and cortisol levels at the study stages, Me (Q₁-Q3)

Note: p2-1, p3-1 and p3-2 – the level of statistically significant differences between the second-first, third-first and third-second stages within the group, p*1, p*2, p*3 – - the level of statistically significant differences between the groups at the study stages

When analyzing the dynamics of glucose values within the groups at different stages of the study, there were no significant differences in both groups between stages 3 and 2 (Gr1, p3-2=0.071; Gr2, p3-2=0.309). Between stages 2 and 1 of the study (Gr1, p2-1=0.001; Gr2, p2-1=0.051), the indicators had statistically significant differences in Gr1, and between stages 3 and 1 (Gr1, p3-1=0.001; Gr2, p3-1=0.006), the indicators were statistically significantly different in both groups. Despite the significant differences at these stages of the study, the plasma glucose concentration remained within the reference values (N=3.9-5.8 mmol/l). A comparative analysis of the median (Iu) values of glucose showed a tendency to an insignificant increase in it by the end of the operation in both groups (Gr1-Me1=4.85; Me2=5.2; Me3=5.35 / Gr2-Me1=4.85; Me2=5.0; Me3=5.15), which indicated the stability and effectiveness of the performed anesthetic support, a sufficient level of anesthesia in both groups.
When analyzing the dynamics of lactate values within groups at different stages of the study, there were no significant differences in both groups between stages 2 and 1, as well as stages 3 and 1 (Gr1, p2-1=0.558; Gr2, p2-1=0.833), (Gr1, p3-1=0.397; Gr2, p3-1=0.603). Between the 3 and 2 stages of the study (Gr1, p3-2=0.037; Gr2, p3-2 0.428), the indicators were statistically significantly different in Gr1. Despite the significant differences between the 3 and 2 stages in Gr1, the lactate indicators remained within the reference values (N= 0.7-2.2 mmol/l). In the comparative analysis of the median (Iu) values of plasma lactate, there were slight fluctuations in the normal values (Gr1-Me1=1.5; Me2=1.3; Me3=1.5 / Gr2-Me1=1.6; Me2=1.68; Me3=1.6), which indicated adequate tissue perfusion, CBS stability, and the effectiveness of anesthesia in both groups. However, in Hr1, there was a tendency to reduce lactate by the traumatic stage of the operation with a return to the initial values by the end of the operation , in contrast to Hr2, in which the lactate level tended to increase to the traumatic peak of the operation, which may indicate a more reliable protection of the patient from hypoperfusion in the conditions of peak stress in the group of regional pain management methods.
The dynamics of cortisol values was characterized by a tendency to decrease its level by the most traumatic stage of the operation, followed by a return to the initial values by the end of the study in both groups (Gr1-Me1=369.28; Me2=273.40; Me3=322.00 / Gr2 - Me1=288.61; Me2=181.27; Me3=308.59). At the same time, significant differences between stages 2 and 1 were noted in Gr1 (Gr1, p2-1=0.011; Gr2, p2-1=0.326), but the detected changes were within the reference boundaries and indicated the stability and effectiveness of the performed anesthesia. There were no statistically significant differences between the other stages of the study in both groups (p>0.05) (see Table 2).
The obtained data on the dynamics of glucose, lactate and cortisol in both groups indicated the effectiveness and stability of the anesthesia methods used. At the same time, the concentration of the inhaled anesthetic in the group where tramadol was used was twice as high as the concentration of the anesthetic in comparison with the group where regional methods were used to ensure and maintain the desired level of anesthesia. Taking into account the sufficient number of available studies on the negative effect of general anesthetics, including inhaled ones, on the developing brain and their toxic effects on neurons [8-15, 17], the use of regional anesthesia techniques with local anesthetics seems preferable, since it allows reducing the doses of general anesthetics used, providing prolonged analgesia, earlier recovery and comfort in the postoperative period [16, 18-21].

Conclusion.
The dynamics of the biochemical markers of operational stress did not show their significant inter-group stage and intra-group inter-stage statistically significant differences and deviations beyond the reference values, which confirms the absence of stress reactions to surgery, the adequacy and effectiveness of the anesthesia methods in both groups.

 

About the authors

Tatiana A. Ovchar

Morozov Children’s City Clinical Hospital

Author for correspondence.
Email: shadum@yandex.ru
ORCID iD: 0000-0001-5764-4016
SPIN-code: 8387-5141

anesthesiologist-intensivist, neonatologist

Россия, 1 Dobryninsky 4th lane, Moscow, 119049

Vladimir V. Lazarev

N.I. Pirogov Russian National Research Medical University

Email: lazarev_vv@inbox.ru
ORCID iD: 0000-0001-8417-3555
SPIN-code: 4414-0677

Dr. Sci. (Med.), Professor

Россия, 1 Dobryninsky 4th lane, Moscow, 119049

Lyudmila S. Korobova

Morozov Children’s City Clinical Hospital

Email: lydmil@bk.ru
ORCID iD: 0000-0003-3047-412X
SPIN-code: 6197-8273

Cand. Sci. (Med.), anesthesiologist-intensivist

Россия, 1 Dobryninsky 4th lane, Moscow, 119049

References

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