Since the sixties of the previous century, propofol and sevoflurane have been effectively competing with older general anaesthetics. Their popularity results from fast and pleasant induction to anaesthesia, fast recovery and manoeuvrability of anaesthesia [1, 2]. However, they also induce some side effects, e.g. depress the cardiovascular system [3, 4]. Slower heart rate or lower arterial pressure observed clinically may result from decreased cardiac output [5] or peripheral vasodilation [6]. Cardiac output is not routinely monitored during general anaesthesia. The knowledge about effects of individual general anaesthetics on cardiac output facilitates proper choices of agents and methods of anaesthesia.

The objective of the present study was to compare the effects of target-controlled infusion (TCI) of propofol vs sevoflurane on haemodynamic parameters during general anaesthesia.

METHODS

After obtaining approval of the Bioethical Committee for Scientific Research, Gdansk Medical University, female patients anaesthetized for elective breast surgery were enrolled in the study. The exclusion criteria included thyroid disease, ß-adrenergic receptor blockers or more than one of other antihypertensive drugs, and contraindications for the agents used in the study. Patients were premedicated with oral midazolam, 7.5mg, one hour before anaesthesia. The following parameters were monitored: ECG, arterial blood pressure (automated non-invasive) and SpO2.  Prior to induction of anaesthesia, patients were intravenously infused with 0.9% NaCl, 250 mL followed by 09% NaCl, 250 mL over the first 30 min of anaesthesia.

Patients were allocated to two groups: group P– anaesthetized with propofol and group S – anaesthetized with sevoflurane. Anaesthesia was induced with i.v. fentanyl 1-2 µg kg-1 and 1% propofol. In group P, propofol was administered using the infusion pump  to obtain target serum concentration of 4 µg mL-1, up to the dose of 1.5--2 mg kg-1. In group S, propofol was injected in a single dose of 1.5-2 mg kg-1. Vecuronium bromide, 0.1 mg kg-1 was given before endotracheal intubation. Lungs were ventilated with the mixture of oxygen and air (FIO2 0,4) using the initial gas flow of 6 L min-1, followed by 3 L min-1, VT  7-8 mL kg -1, f 10-12 min-1. After intubation, the NICO (Novametrix Medical Systems, USA) loop was placed into the system to measure cardiac output using the non-invasive partial CO2  re-breathing method.

During the maintenance of anaesthesia, group P received the TCI of propofol with the target serum concentration of 3 µg mL-1 whereas group S – sevoflurane 1 MAC, adjusted to age. Before the skin incision, both groups received fentanyl, 1-2 µg kg-1 up to the total dose of 3 µg kg-1. Fifteen successive measurements of the following haemodynamic parameters were recorded every 3 min: HR, MAP, SV, CO, CI.

The results were statistically analysed. Data were presented as a mean and 95% confidence interval of a mean (x, 0.95% CI). Distribution was checked using the Shapiro-Wilk-W tests. Data were compared by Student’s t, Mann-Whitney U tests or ANOVA for repeatable measurements. Additionally, the post hoc Tukey test was applied, if required. P<0.05 was considered as statistically significant.

RESULTS

The study involved sixty-four ASA I or II women, aged 25-75 years. A posteriori  7 patients were excluded: 1 – due to difficulties in endotracheal intubation, 1 – hypertension before induction (SAP/DAP – 194/113 mm Hg) and 5 – too short duration of the procedure to perform all 15 planned measurements. Groups were comparable for age, height, body weight and surface.

No significant intergroup differences were found in the values of all haemodynamic parameters before induction of anaesthesia and after intubation (baseline values) (Table 1). During the maintenance of anaesthesia, markedly decreased HR was observed in group P; the intergroup differences in the values of this parameter were not significant (Fig. 1).

There were no differences in MAP and SV at consecutive measurements in both groups or intergroup comparison (Fig. 2 and 3).

In patients anaesthetized with propofol using the TCI method, CO gradually decreased compared to the first and second measurement; CI decreased at the final two measurements. Likewise, in group S, CO and CI decreased yet the changes occurred at different times. The intergroup differences in parameters were not significant (Fig. 4 and 5).

DISCUSSION

Our findings did not demonstrate any significant differences in haemodynamic parameters during maintenance of anaesthesia with the TCI of propofol or sevoflurane. In earlier studies, both agents were compared during monoanaesthesia or combined with opioids (alfentanil, remifentanil) or N2O. Their results are difficult to compare with our observations due to differences in the methods used and the fact that analysis most commonly covered the induction of anaesthesia [1, 2] or recovery [7, 8].

The experimental studies and clinical trials demonstrated that propofol and sevoflurane had multi-directional depressive effects on the cardiovascular system. Our findings do not confirm the reports about various values of mean arterial pressure using those agents and slower heart rate in patients anaesthetized with sevoflurane compared to propofol [1, 9]. The differences are likely to be related to various methods of sevoflurane administration – in the mixture of O2 and N2O and concentration exceeding 2 MAC – in the studies mentioned vs 1 MAC in our study. Moreover, higher decreases in mean arterial pressure in patients anaesthetized with continuous infusions of propofol with the pre-set rate of infusion and dose reported in other studies are likely to result from the differences in the method of propofol administration [10].

One of the mechanisms of depressive effects of anaesthetics on the circulatory system is dose-dependent inhibition of baroreflexes, an important physiological mechanism maintaining haemodynamic stability [11, 12]. It seems, however, that this mechanism was not essential for our patients as breast surgery was not associated with marked loss of circulating blood.

Our study did not demonstrate decreased stroke volume at successive measurements in both groups, which may evidence the lack of changes in myocardial contractility during maintenance of anaesthesia. Decreased heart rate observed in group P at consecutive measurements did not reduce cardiac output or cardiac index almost throughout the study period, which may result from higher activity of the sympathetic system during combined anaesthesia with sevoflurane compared to entirely intravenous anaesthesia [13]. Slight inotropic effects of propofol observed in experimental studies seem less likely explanations of such events [14].

The lack of simultaneous changes in cardiac output and cardiac index values in group S may indicate randomness of the differences observed.  

The available literature lacks studies directly comparing effects of sevoflurane and propofol on cardiac output during the maintenance of anaesthesia. According to the study assessing haemodynamic parameters in patients anaesthetized with both these agents for cardiac surgery, there were no significant differences in cardiac output index during the maintenance of anaesthesia, which is consistent with our findings. Moreover, in the propofol group, the number of interventions necessary to achieve the haemodynamic parameters assumed was higher, which was interpreted as lower haemodynamic stability during anaesthesia. It should be stressed, however, that groups of patients, their preoperative status (ASA III or IV), types of surgery, methods of induction and maintenance of anaesthesia differed [16].

Cardiac output was determined non-invasively measuring the concentration of expiratory carbon dioxide during a single re-breathing; calculations were based on the Fick`s law [17, 18]. NICO monitoring is limited by the fact that cardiac output may be assessed after intubation; therefore, effects of propofol and sevoflurane on haemodynamic parameters were compared only during the maintenance of anaesthesia.

Another drawback of the method is selective assessment of cardiac performance, in which the diastolic function cannot be determined.  Anaesthetic-induced impaired heart work can manifest itself only during the diastole. The study assessing the diastolic heart function in patients anaesthetized with propofol, with target serum concentration up to 6 µg mL-1, halothane or sevoflurane, up to 1.5 MAC demonstrated slightly impaired diastolic function at higher serum levels of propofol, which was not considered clinically relevant [19].

In our study, patients of both groups received fentanyl during the induction and before skin incision. The use of opioids decreases the dose of propofol required for general anaesthesia [20] as well as MAC of sevoflurane [4]. The dose of fentanyl was identical in both groups, so its use did probably not affect the values of examined parameters.

The key limitation of the present study is its population consisting only of patients without impaired circulatory function. Our findings cannot be directly referred to patients with myocardial dysfunction; further observations are needed. An additional difficulty in comparing intravenous and inhaled general anaesthetics is the determination of equivalent doses of anaesthetics. Our results concern only concentrations of propofol or sevoflurane.

CONCLUSIONS

During the maintenance of anaesthesia with TCI of propofol 3 µg mL-1 or sevoflurane 1 MAC with fentanyl, the values of stroke volume, cardiac output and cardiac index are comparable.

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REFERENCES

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12.Umehara S, Tanaka M, Nishikawa T: Effects of sevoflurane anesthesia on carotid-cardiac baroreflex responses in humans. Anesth Analg 2006; 102: 38-44.

13.  Ledowski T, Bein B, Hanss R, Paris A, Fudickar W, Scholz J, Tonner PH: Neuroendocrine stress response and heart rate variability: aof total intravenous versus balanced anesthesia. Anesth Analg 2005; 101:1700-1705.

14.  Gable BD, Shiga T, Murray PA, Damron DS: Propofol increases contractility during alpha 1a-adrenoreceptor activation in adult rat cardiomiocytes. Anesthesiology 2005; 103: 335-343.

15.  Gravel NR, Seatle NR, Taillefer J, Carrier M, Roy M, Gagnon L: Comparison of the hemodynamic effects of sevoflurane anesthesia induction and maintenance vs TIVA in CABG surgery. Can J Anesth 1999; 46: 240-246.

16.  Haryadi DG, Orr JA, Kuck K, McJames S, Westenskow DR: Partial CO2 rebreathing indirect Fick technique for non-invasive measurement of cardiac output. J Clin Monit Comput 2000; 16: 361-374.

17.  Gueret G, Kiss G, Khaldi S, Le Jouan R, Le Grand A, Perrament Y, Lefèvre C, Arvieux CC: Comparison of cardiac output measurements between NICO and the pulmonary artery catheter during repeat surgery for total hip replacement. Eur J Anaesth 2007; 24: 1028-1033.

18.  Filipovic M, Wang J, Michaux I, Hunziker P, Skarvan K, Seeberger MD: Effects of halothane, sevoflurane and propofol on left ventricular diastolic function in humans during spontaneous and mechanical ventilation. Br J Anaesth 2005; 94: 186-192.

19.  Kazama T, Ikeda K, Morita K: Reduction by fentanyl of the Cp50 values of propofol and hemodynamic responses to various noxious stimuli. Anesthesiology 1997; 87: 213-227.

20.  Lysakowski C, Daumont L, Pellegrini M, Clergue F, Tassonyi E: Effects of fentanyl, alfentanil, remifentanil and sufentanil on loss of consciousness and bispectral index during propofol induction of anaesthesia. Br J Anaesth 2001; 86: 523-527.

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Address:

*Magdalena Łasińska-Kowara
Katedra i Klinika Anestezjologii
i Intensywnej Terapii Gdańskiego UM
ul. Dębinki 7, 80-211 Gdańsk
tel.: 0-58 349 24 06, 0-695 641 648
fax: 0-58 349 11 82
e-mail: magda@amg.gda.pl

Received: 27.02.2009
Accepted: 07.05.2009