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ANESTHETIC PHARMACOLOGY

The Influence of Desflurane on QTc Interval

Radoslaw Owczuk, MD^*, Magdalena A. Wujtewicz, MD^*, Wioletta Sawicka, MD^*, Jerzy Lasek, MD, PhD, and Maria Wujtewicz, MD, PhD^*

Departments of *Anaesthesiology and Intensive Therapy, and Trauma Surgery, Medical University of Gdansk, Gdansk, Poland

Address correspondence and reprint requests to Radoslaw Owczuk, MD, Department of Anaesthesiology and Intensive Therapy, Medical University of Gdansk, Debinki 7 str., 80-211 Gdansk, Poland. Address e-mail to r.owczuk{at}amg.gda.pl.

	Abstract

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Volatile anesthetics may prolong the QTc interval and this may result in grave cardiac arrhythmias. We assessed the effect of desflurane on the QTc interval in 40 ASA physical status I or II patients. Volatile anesthetic induction with desflurane was performed, and after obtaining adequate level of anesthesia, QTc interval, heart rate, and noninvasive arterial blood pressure were measured. Prolongation of the QTc interval was observed within the first minute of anesthesia. There were no differences in QTc interval changes between sexes at any time. We conclude that desflurane prolongs the QTc interval, but that there are no differences between genders in sensitivity to this action.

	Introduction

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Prolongation of QT interval in the electrocardiogram (ECG) may cause cardiac electrical instability and result in polymorphous ventricular tachycardia of the "torsade de pointes" (TdP) type as well as ventricular fibrillation (1–4). Apart from the rare cases of congenital long QT syndrome, secondary prolongation of the interval is often observed (1,2). Anesthetics may have various influences on the duration of QT interval. The most frequently used volatile anesthetics, sevoflurane and isoflurane, prolong QT, whereas the influence of halothane is controversial (5–8). There are reports of severe complications after administration of these anesthetics, including TdP and ventricular fibrillation (9).

The effect of desflurane on the cardiovascular system has been reported in numerous publications. However, there are no reports concerning the influence of this anesthetic on the QTc interval and its potential proarrhythmogenic effect.

	Methods

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Approval from the institutional bioethics committee was obtained for the study and informed written consent was obtained from each patient.

The study group included 20 women and 20 men, admitted for elective surgery including orthopedic interventions or resections of benign tumors. Inclusion and exclusion criteria are presented in Table 1.

Anesthetic procedure was standardized for all the patients. In the evening preceding anesthesia, patients were premedicated with 2 mg of estazolam orally. One hour before anesthesia, patients were given 0.15–0.2 mg/kg oral midazolam. On arrival to the operating room, patient variables were monitored (ECG, pulse oximetry, noninvasive arterial blood pressure [NIBP] measurement) (AS/5 monitors; Datex Ohmeda, Bromma, Sweden). A cannula was inserted into a peripheral vein and infusion of 0.9% NaCl was started. Oxygen was administered for at least 3 min with the flow of 8 L/min. The ADU S/5^TM (Datex Ohmeda) device was used for anesthesia with a precalibrated Aladin^TM vaporizer (Datex Ohmeda) for desflurane. The anesthetic circuit was filled with desflurane (6 vol %) and 94% oxygen (fresh gas flow of 8 L/min). Inhaled induction was initiated with 6 vol % of desflurane (Suprane^TM; Baxter International Inc., Lessines, Belgium). The desflurane concentration was gradually increased by 1 vol % for each 3–5 inspirations up to 8–12.5 vol %. After an adequate depth of anesthesia was achieved, the desflurane concentration was reduced to 6 vol %. Manually controlled ventilation was performed to maintain the end-tidal CO₂ level within the normal values. Before tracheal intubation, 0.1 mg of fentanyl and 0.1 mg/kg vecuronium were administered. Heart rate (HR), ECG, and NIBP were recorded at the same time points: before induction of anesthesia, after 1, 3, and 5 min of adequate anesthesia, and after tracheal intubation.

The 12-lead ECG was recorded with an Agilent Page Writer M1170 A device (Agilent Technologies, Andover, MA). QTc measurements were performed automatically and verified manually according to the principles described by Moss (10). QT correction for HR was calculated using the formula of Bazett (QTc = QT · RR^–1/2).

Statistica 6.0 (StatSoft Inc., Tulsa, OK) was used for statistical calculations. The minimal group size of 18 was calculated to achieve a study power 90% with type I error rate of 0.05. The data are presented as mean ± sd. The data were tested for normality using Shapiro-Wilk test. Differences between subgroups were tested with Student’s t-test. Results were analyzed with two-way analysis of variance for repeated measurements. Significant differences were analyzed with post hoc Newman-Keuls test. P < 0.05 was considered to be significant.

	Results

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Table 2 summarizes patients’ characteristics. Changing QTc values over time are depicted in Figure 1. Prolongation of the QTc interval was observed within the first minute of adequate anesthesia. Statistically longer QTc intervals were observed after tracheal intubation, compared both with initial values and the values recorded after 5 min of anesthesia (P = 0.00002 and P = 0.00003, respectively). There were no differences in the patterns of QTc changes between men and women. Table 3 presents values of HR and NIBP after administration of desflurane.

View larger version (22K): [in this window] [in a new window]   Figure 1. Changes of QTc value (milliseconds). *P < 0.00001, **P < 0.0001 compared with baseline.

	Discussion

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The principal finding of this study is that desflurane causes prolongation of the QTc interval in patients without cardiovascular diseases. Similar effects have been noted with sevoflurane (11–13) and isoflurane (6,14,15).

In this study, the adverse effect of desflurane on ventricular repolarization was observed within the first minute of anesthesia. We did not observe progressive prolongation of the QTc interval as has been reported for sevoflurane (16). The most marked QTc prolongation was observed after tracheal intubation which itself prolongs the QT interval despite an adequate level of anesthesia. This time in general anesthesia seems of importance in induction of malignant arrhythmias in patients affected by other pathologies influencing the QT interval.

We observed no differences in the pattern of QTc prolongation after administration of desflurane between men and women, although it is believed that females are more susceptible to QT prolongation after medication, and this can result in a more frequent incidence of the TdP-type arrhythmias in women compared with men (4,17,18).

Sympathetic activation is one of the factors interfering with duration of the QTc interval. This activation has been observed after desflurane administration (19) and has been attributed to the release of epinephrine, norepinephrine, and vasopressin (20). The irritating effect of desflurane on the respiratory tract mucosa is another phenomenon responsible for adrenergic stimulation (21).

The observed QTc prolongation after inhaled desflurane was not accompanied by parallel changes in HR or mean arterial blood pressure values, which possibly may be explained by premedication with midazolam. This drug has no effect on the QT interval (22) but may inhibit sympathetic stimulation caused by volatile anesthetics (15,23). Furthermore, animal studies have revealed the influence of desflurane on cardiac function (induction of tachycardia), which is independent from sympathetic stimulation and is related to vagal blockade by the anesthetic (24).

The lack of contemporaneous sympathetic stimulation and parasympathetic inhibition observed in our patients, which manifested as lack of HR and mean arterial blood pressure variability, and the significant QTc prolongation may have been attributable to the direct effect of the anesthetic on the myocardium.

We conclude that desflurane prolonged the QTc interval in our patients with no differences between the two sex subgroups. Midazolam may prevent sympathetic stimulation induced by desflurane.

We thank all the nurses from our department for their assistance during the study; special thanks to Ms. Iza Rudzinska, Mrs. Michalina Szczukowska, Mrs. Edyta Wojcik, and Mrs. Ewa Morzuch.

	Footnotes

 
Accepted for publication December 8, 2004.

	References

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This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (12) Citing Articles via Google Scholar Google Scholar Articles by Owczuk, R. Articles by Wujtewicz, M. Search for Related Content PubMed PubMed Citation Articles by Owczuk, R. Articles by Wujtewicz, M. Related Collections Monitoring (Cardiac) Pharmacology