Abstract
Introduction:
Heart rate variability which denotes variations of the length of consecutive heart cycles has been suggested to reflect the modulation of heart rate by autonomic nervous system.
Methods:
Sixty four patients of ASA I and ASA II status scheduled for elective abdominal surgical procedures were randomly allocated to group 1 and group 2. Premedication and induction of anaesthesia were performed with same agents. After orotracheal intubation maintenance of balanced anaesthesia was based on administration of same induction agents,opioids and muscle relaxant while delivery of gaseous mixture with sevoflurane in the group 1 (n=32) and isoflurane in the group 2(n=32). Haemodynamic parameters were monitored in perioperative and electrocardiogram was recorded by holter ECG recorder, while the analysis of the parameters were performed by corresponding softwares . Data were presented as mean values of logarithmic (natural logarithm) values of the power of the total spectrum of heart rate variability(TP), mean values of the logarithmic values of low frequency band (LF), mean values of the logarithmic values of high frequency range(HF), and mean values of SD1 and SD2 parameters.
Results:
Analysis of the values of hemodynamic parameters has shown changes of haemodynamic parameters during perioperative period without significant statistical differences between the groups. Analysis of the logarhitmic values of parameters of heart rate variability of frequency domain has shown changes of the total spectrum power and LF and HF spestra with variations of the values of total power spectrum and individual components of the spectrum of heart rate variability during the balanced anaesthesia with administration of two different inhalation anaesthetics, without statistically significant differences between the groups.
Conclusion:
The results have shown that during balanced anaesthesia with two different inhalation anaesthetics there are variations of haemodynamic variables and parameters of heart rate variability without statistically significance that could show the difference between the groups and different agents administered.
Keywords: heart rate variability, balanced anaesthesia, inahalation anaesthetics
1. INTRODUCTION
Variability of the complex systems enable those systems to respond to different environmental and intrinsic inputs in a whole spectrum of reactions and effects. Heart rate variability reflects the possibility of the cardiovascular system to adapt to the whole spectrum of different more or less demanding tasks and situations. Heart rate variability is reduced in many pathological conditions and most altered after myocardial infarction and in the failing heart,besides the other pathological conditions (1, 2). It is an important predictor in risk stratification and early prediction of cardiac autonomic neuropathy (3, 4). The importance of the monitoring of heart rate variability during surgical procedures and anaesthesia have been recognized. Poincaré plot is a visual presentation of time series of signal and has been used for quantifying of the parameters of heart rate variability (5). Standard descriptors of the Poincaré plot have been introduced, SD1 and SD2. SD1 represents the standard deviation of the variability of the signal in short terms, while SD2 represents standard deviation of the long term RR interval (6).
Proposed physiological explanations of the significance of parameters are listed elsewhere (1, 7).
There have been many clinical trials performed aiming to assess if there could be found significant differences of the effects of different anaesthetic agents (8,9,10). Besides two main linear methods of analysis (time –domain indices and frequency-domain indices) there have been many new nonlinear methods of analysis evolving. Some linear measures appropriate for short-time recordings are shown in the Table 1.
Table 1.
Linear measures of HRV in Time-domain and Frequency–domain analysis (modified from „Heart rate variability: standards of measurement, physiogical interpretation and clinical use ”Circulation 1996)

Surgery and anaesthetics influence significat changes of homeostasis what is reflected in changes of haemodynamic variables (9, 10, 11).
2. PATIENTS AND METHODS
After obtaining approval of Ethics Committee and informed consent sixtyfour patients of ASA I and ASA II status,who were scheduled for elective abdominal surgery were randomized to two groups : group 1(balanced anaesthesia with inhalatory anaesthetic sevoflurane) and group 2 (balanced anaesthesia with inhalatory anaesthetic isoflurane). Patients with cardiovascular disease, diabetes mellitus,arrhythmias,endocrine and neurologic conditions and therapy with medications that may affect heart rhythm were not included in the trial. Exclusion criteria were recordings with many artifacts. Monitoring of haemodynamic parameters and recording of the electrocardiogram were performed during perioperative period. Fortyfive minutes before induction of anaesthesia patients were given midazolam (Dormicum, F. Hoffman-La Roche Ltd Basel, Switzerland) in the dosis of 7,5 mg. In the preinduction period patients were given opioid fentanyl 2µgkg-1 (Fentanyl –Janssen-Cilag,Belgium). Five minutes later induction was started by thiopentone (Thiopental sodium, Rotexmedica GMBH Germany) which was administered in the doses range of 4-6 mg kg-1. Upon induction of anaesthesia and ventilation by face mask for five minutes orotracheal intubation was performed after administration of tracrium (Tracrium,GlaxoSmithKline UK) in the dosis of 0,5 mg kg -1, and later on maintenance of anaesthesia was performed by balanced technique. The recordings of electrocardiogram, recorded by Holter ECG recorder (Trillium 3000 Holter System, Forest Medical,USA), and after excluding artifacts were put to analysis by Trillium HrvFreq 4.01, 2006 software (ForestMedical, LLC,East Syracuse, USA). Upon obtaining time series of the signal by exporting NN intervals it was possible to perform analysis with Kubios HRV software v.2.1, 2012 (Biosignal Analysis and Medical Imaging Group,Department of Applied Physics ,University of Eastern Finland, Kuopio,Finland) for nonlinear indices. Interpolating rate was 4Hz, window width 256s and window overlap of 50%.
Power spectra were determined in nine 5-minutes segments, in preinduction period-Tpre, after administration of opioid -T1, after induction–T2, after orotracheal intubation-T3 period, during balanced anaesthesia with administration of two different inhalation anaesthetics :sevoflurane or isoflurane –(T4-T7), and in postoperative period two hours after emergence –Tpost. Spectral analysis was calculated with application of Hanning window. Data were presented as mean values of logarhitmic values of the total power spectrum values (TP), mean values of the logarhitmic(nautural logarhitm) values of power spectrum of low frequencies (LF), mean values of the logarithmic values of power spectrum of high frequencies (HF). Descriptors of Poincare plots were presented for each patients and correlated. Data were expressed as the means+-SDE. Statistical analysis was performed with χ2-test for gender, Student t-test for age, Mann-Whitney test for BMI data, and one-way repeated analysis of variance (ANOVA) for parameters of hemodynamic and heart rate variability parameters. P value <0,05 was considered as statistically significant.
3. RESULTS
Analysis was performed by statistical package IBM Statistics SPSS v22.0 (Chicago,Illinois,USA). Results of analysis of demographic data have not shown statistically significant differences between the groups (Table 2). Results of the analysis of haemodynamic parameters have shown variations of hemodynamic variables in both groups, with slight decrease of the values of mean arterial pressure in both groups after administration of induction agent thiopental and changes in heart rate, but there was no statistically significant differences (Table 3).
Table 2.
Demographic data. CH=Cholecystectomy ,H=Hernioplasty

Table 3.
Hemodynamic variables in periprocedural period. Results are presented as means and standard deviation in brackets

Table 4.
Logarithmic values (native logarithm) of the TP,LF,HF spectra and SD1 and SD2 value. Results are presented as means and standard deviation in brackets.

Analysis of the changes of the values of the power of total spectrum (TP), low frequency (LF) and high frequency (HF) spectra, demonstrated alterations of the power of all spectral parameters in both groups,which was most visible after induction, without statistically significant differences between the groups. Results of anlysis of hamodynamic parameters are shown in the diagrams in Figure 1, results of the analysis of heart rate variability and Poincaré plot descriptors (SD1 and SD2) in Figure 2, while some of the diagrams of Poincaré plot from different periods of perioperative time are shown in Figure 3.
Figure 1.

Diagram of hamodynamic parameters (mean arterial pressure and heart rate)
Figure 2.

Diagram of the spectral components and nonlinear geometric measures in time periods : a) logarithmic values of TP spectrum ,b) logaritmic values c) logaritmic values of HF spectrum, d) values of SD1 and SD2 for both groups
Figure 3.

Poincaré plot in different perioperaive periods in different subjects :a)preinduction period,b)immediately after induction,(c,d,e,f,g) intraoperatively,h) in the early postoperative period
4. DISCUSSION
Monitoring of heart rate variability could show clinical usefullness during perioperative period. Stress reaction to surgical procedure and general anaesthesia have strong impact on the dynamic stability of the variability of physiological functions.
There have been numerous published papers on the topic of possible influence of different anaesthetic agents on the parameters of heart rate variability (8,9,10,11,12).
Huang HH. and coworkers who studied the effects of induction of anaesthesia by thiopentone have shown decrease of the power of total spectrum and individual components of the spectrum but no significant changes in the relationship between the spectral components, what suggested that there were no changes in the balance of autonomic nervous system(9).
Latson TW. and coworkers also examined the effects of three induction anaesthetic techniques on heart rate variability (10). They have shown that induction of anaesthesia both with thiopental and nitrous oxide and etomidate and nitrous oxide were associated with decrease of the powers of total spectrum, low frequency and high frequency spectra, with more evident decrease of low frequency spectrum (LF) with thiopental in regard to etomidate (10).
Tanaka S. and coworkers investigated effects of different inhalation anaesthetics and did not find sympathetic activation in patients who were administered sevoflurane unlike to those who received desflurane and isoflurane (11) . In the trial performed by Kato M. and coworkers, who investigated the effects of inhalation anaesthesia with isoflurane with different inhalatory concentrations it was shown that all components of the heart rate variability were decreased in dose depnedent manner,but with more effects on the high-frequency and mid-frequency components (12). Ebert TJ et al. described that sevoflurane could have such pharmacological profile that does not elict profound heart rate changes (13, 14). According to the findings of the Wodey E. et al. variations of heart rate in children who were administered sevoflurane as inhalation anaesthesia during induction could be described as withdrawal of parasympathetic tone (15).
Results of our trial have shown variations of hemodynamic variables in both groups, with decrease of the values of mean arterial pressure in both groups after administration of induction agent, thiopental and consecutive changes in heart rate,with no statistically significant difference between the groups. Analysis of the changes of the logarhitmic values of power of total spectrum, of low frequency (LF) and high frequency (HF) spectra, has shown reductions of the power of all spectral parameters in both groups, with most visible decrease after induction, without statistically significant differences between the groups.
Analysis of the descriptors of Poincaré plot, SD1 and SD2 demonstrated variations of the values of the descriptors SD1 and SD2 without statistically significant differences between the groups.
5. CONCLUSION
Short- term heart rate variability parameters measured in frequency-domain,
in perioperative period in patients who underwent elective abdominal surgical procedures of moderate stress while general anaesthesia was performed using balanced technique in which the induction agent was the same (thiopentone) while the inhalatory components were two different anaesthetic agents: sevoflurane and isoflurane, have shown variable changes of all spectral components of the total spectrum of heart rate variability in both groups. The most visible changes of HRV parameters were evident in periinduction period, without statistically significant differences between the groups.
Footnotes
CONFLICT OF INTEREST: NONE DECLARED.
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