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Sevoflurane progressively prolongs the QT interval in unpremedicated female adults

Kuenszberg, E; Loeckinger, A; Kleinsasser, A; Lindner, K. H; Puehringer, F; Hoermann, C

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European Journal of Anaesthesiology (EJA): November 2000 - Volume 17 - Issue 11 - p 662-664
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The matter of a long QT interval has received considerable attention over the past few years. This cardiac disorder may result in potentially lethal ventricular tachydysrhythmia and specifically in torsade de pointes. Prolongation of the QT interval can be inherited, or acquired following drug administration, or arise from electrolyte disturbances, e.g. potassium depletion or hypomagnesaemia. Many drugs used in anaesthesia interfere with cardiac action and volatile anaesthetics in particular have been recognized to influence the duration of the QT interval [1]. In prospective randomized clinical trials it was demonstrated that inhalational induction and anaesthesia with isoflurane prolongs the QT interval in contrast to halothane, which shortens the QT interval [2,3]. Sevoflurane is the most recently released volatile anaesthetic and is used throughout the world. Compared to isoflurane or halothane, the distinguishing feature of sevoflurane is its low blood-gas partition coefficient allowing rapid induction of and emergence from anaesthesia. Satisfactory pharmacokinetics and the acceptable aroma of sevoflurane make inhalational induction of anaesthesia practicable in both children and adults. Sevoflurane has been shown to prolong the QT interval - corrected for heart rate (QTc) - in diazepam-premedicated patients after 20 min of continuous application [4]. In 1998 Abe and associates presented a case of torsade de pointes ventricular tachydysrhythmia which occurred after the inhalation of sevoflurane and subsided after the sevoflurane effect had disappeared [5].

The objective of this study was to assess time-dependent effects of sevoflurane on the QT interval in unpremedicated female patients in comparison to propofol, which is known to have little effect on the QT interval [6].


After authorization of the institutional ethics committee and after giving written informed consent, 36 female patients, ASA status I or II, admitted for gynaecological surgery were included in this study. Written informed consent was obtained from each patient on the day before surgery. Patients presenting with cardiovascular diseases, congenital or acquired prolongation of the QTc interval (QTc = 440 ms), serum electrolyte abnormalities or patients receiving medication or being suspect for malignant hyperthermia were not studied. No premedication was administered. Patients were randomly allocated into two groups consisting of 18 patients each, one receiving sevoflurane induction and anaesthesia, the other receiving propofol induction and anaesthesia. After venepuncture, Ringer's solution was started at 7 mL kg−1 h−1 in both groups before anaesthesia was induced. In the sevoflurane group induction was managed in a conventional fashion using a facemask, with the inspired concentration of sevoflurane initially set at 0.7% then increased every fifth breath by 0.5% until a maximum concentration of 5% was attained. Precalibrated vaporizers (Vapor 19.3, Dräger, Lübeck, Germany) were used in all patients in the sevoflurane group. After anaesthesia had been induced, the vapour concentration was adjusted to achieve an end-tidal concentration of 2.0% in order to provide an adequate depth of anaesthesia. Manually assisted ventilation of the lungs was carried out to maintain end-tidal carbon dioxide concentration within the normal range. In the propofol group, anaesthesia was induced using 2.5 mg kg−1 over 60 s and maintained by continuous infusion at a rate of 6 mg kg−1 h−1. In both groups of patients the fresh gas flow was set at 6 L min−1 using an oxygen-air mixture with an FiO2 of 0.3. Identical Julian ventilators were used in all patients (Dräger, Lübeck, Germany). A three-lead electrocardiogram (ECG; Cardiosmart, Hellige GmbH, Freiburg, Germany) was recorded before drug administration, then 2, 5 and 10 min after initial drug administration at a paper speed of 50 mm s−1. Heart rate and arterial pressure were recorded at the same time (AS/3 monitor, Datex, Helsinki, Finland). After the measurements were completed anaesthesia was adapted to the requirements of the patient and type of surgery. Three investigators who were blinded with respect to the type of anaesthetic used examined the ECGs. The following ECG parameters were investigated: heart rate, corrected QT interval using Bazett's formula [7]: QTc = QT/vR-R where QT is the measured interval (ms) and R-R is the measured interval between two consecutive R waves (s). Statistical analysis, performed using a two-way analysis of variance for repeated measures, was used to determine intergroup and intragroup differences. P-values < 0.05 were considered significant. Significant post hoc differences were analysed by using the Newman-Keuls test. All values are expressed as mean ± SEM.


There were no differences in the demographic data between the two groups. Data are displayed in Table 1. QTc interval was significantly lengthened 10 min after inhalational induction with sevoflurane, in contrast to the propofol group where the QTc interval remained virtually unchanged (Fig. 1a). This lengthening became visible already after 2 min of inhaling sevoflurane vapour. The critical value of 440 ms in the QT interval was exceeded in four patients in the sevoflurane group 10 min after drug administration but in just in one patient in the propofol group. Systolic arterial pressure was depressed in all measurements after baseline in both sevoflurane and propofol group (Fig. 1b). In the intergroup comparison a significant difference in the measurement made at 2 min became evident. Diastolic arterial pressure was neither significantly depressed by sevoflurane (from 76 ± 2 mmHg to 64 ± 5 mmHg nor by propofol (from 73 ± 2 mmHg to 64 ± 2 mmHg). Heart rate was not significantly affected in either the propofol (from 75 ± 2 beats min−1 to 74 ± 4 beats min−1, or the sevoflurane (from 73 ± 3 to 72 ± 5 beats min−1, groups.

Table 1
Table 1:
Demographic data
Fig. 1
Fig. 1:
(a) The QTc intervals and (b) systolic arterial pressure before and at 2, 5 and 10 min after induction of anaesthesia using sevoflurane or propofol. BL = baseline. Values are mean ± SEM; *P < 0.05, **P < 0.01, in comparison to baseline values.


Inhalational induction and anaesthesia with sevoflurane progressively prolonged the QTc interval in our experiments. Propofol had no influence on the QT interval, which is consistent with previously published work [6]. The fact that four of 18 patients in the sevoflurane group and one of 18 patients in the propofol group developed QTc intervals longer than 440 ms implies that the preoperative ECGs must be explicitly investigated for any QTc prolongation which is already present when the use of sevoflurane is planned. The decrease in systolic arterial pressure which occurred after induction was smoother when sevoflurane was used compared to propofol (Fig. 1b), which is possibly due to the protracted uptake of a vaporized anaesthetic via the alveoli. This method of administration may turn out to be beneficial in patients with cardiovascular impairment. Two limitations of this study should be noted: First, women per se tend to have a longer QT interval [8]. Second, our patients were not premedicated using benzodiazepine as is sometimes usual in clinical practice - a measure that was necessary to identify the unmasked actions of sevoflurane on the QT interval. We conclude that sevoflurane progressively lengthened the QTc interval in unpremedicated female adults and that the QTc prolongation associated with sevoflurane needs to be recognized early in order to prevent the critical ventricular tachycardia, torsade de pointes.


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8 Busjahn A, Knoblauch H, Faulhaber HD et al. QT Interval is linked to 2 long-QT syndrome loci in normal subjects. Circulation 1999; 99: 3161-3164.


© 2000 European Academy of Anaesthesiology