1 Department of Anaesthesiology and Intensive Therapy and 2 Department of Oncological Surgery, Medical University of Gdansk, Debinki str. 7, 80-211 Gdansk, Poland
*Corresponding author. E-mail: r.owczuk{at}wp.pl This study was presented in part at the Euroanaesthesia 2003 Meeting, Glasgow, UK, May 31 to June 3, 2003 [Eur J Anaesth 2003; 20 (Suppl. 30): 126; Abstract 480].
Accepted for publication: December 7, 2003
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Abstract |
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Methods. Forty women undergoing surgery for breast cancer were included in the study. They were divided into two groups: (A) women previously treated with anthracyclines (n=20); and (B) women not treated with antineoplastic drugs (n=20). All patients received a standardized balanced anaesthetic in which isoflurane 0.5 vol% was used. The QT and corrected QT intervals were measured before anaesthesia, after induction and tracheal intubation, after 1, 5, 15, 30, 60 and 90 min of anaesthesia, and during recovery.
Results. In both groups we observed a tendency to QTc prolongation, but statistically significant differences among baseline values and values observed during isoflurane-containing anaesthesia were seen only in group A. During anaesthesia, significant differences in QTc values between the two groups were observed.
Conclusion. In female patients pretreated with anthracyclines for breast cancer, the tendency to QTc prolongation during isoflurane-containing general anaesthesia was more strongly expressed than in patients without previous chemotherapy.
Br J Anaesth 2004; 92: 65861
Keywords: anaesthesia, general; anaesthetics volatile, isoflurane; chemotherapy, anticancer; monitoring, electrocardiography, QT interval; pharmacology, anthracyclines
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Introduction |
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Drugs administered in anaesthesia have diverse effects on the QT interval, some prolonging it (e.g. thiopental, isoflurane, sufentanil)811 and others shortening it (e.g. propofol, halothane)8 12 or not influencing the length of the QT interval (e.g. etomidate, vecuronium, diazepam, midazolam).8 9 The combination of two or more agents prolonging the QT interval is believed to increase the risk of arrhythmia development.1 Therefore, we aimed to analyse the effect of isoflurane, a potent inhalation anaesthetic known to prolong the QT interval, on the QT interval of patients previously treated with anthracyclines.
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Material and methods |
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Patients were excluded if they were receiving Vaughan-Williams class 1 or 3 anti-arrhythmics, if they had a history of heart disease or circulatory insufficiency, or if they were receiving psychotropic or other drugs known to prolong the QT interval. Patients with preoperative electrolyte abnormalities were also excluded, as were those who had a significant arrhythmia or conduction disturbance on their preoperative ECG (excepting four patients in group A with postanthracycline prolongation of QTc interval).
Anaesthetic management was standardized for all patients. They received estazolam 2 mg p.o during the evening before surgery and midazolam 0.10.2 mg kg1 p.o. 1 h before surgery. Before induction of anaesthesia with etomidate 0.2 mg kg1, fentanyl 12 µg kg1 and vecuronium 0.1 mg kg1, all patients breathed oxygen spontaneously through a facemask. After tracheal intubation, the patients lungs were ventilated mechanically using the ADU S/5TM (Datex Ohmeda, Bromma, Sweden) anaesthesia system. A fresh gas mixture of nitrous oxide/oxygen, 2:1 ratio, 3 litres min1, was used and the inspired concentration of isoflurane was adjusted to maintain an end-tidal concentration at 0.5 vol% (AladinTM vaporizer; Datex Ohmeda). During anaesthesia, further doses of fentanyl and vecuronium were given as required. As part of standard non-invasive monitoring, the ECG was recorded with the Agilent Page Writer M1170A ECG device (Agilent Technologies, Andover, MA, USA). QT and QTc measurements were performed automatically (an option of the ECG device), and verified manually according to Malik and Batchvarow.13 The QT interval was measured in lead II of the ECG, and the correction was calculated according to Bazzets formula (QTc = QT RR1/2). Measurements were performed before anaesthesia, before and after tracheal intubation, and subsequently after 1, 5, 15, 30, 60 and 90 min of anaesthesia with isoflurane and after emerging from anaesthesia. QTc values greater than 0.44 s were considered to be prolonged, based on reports by Khan1 and Wisely and Shipton.8
The minimum group size of 18 was calculated in order to achieve a study power of 90% with type I error rate (alpha) of 0.05. For the purposes of the calculation, we used values of the QTc interval (range, mean, standard deviation) from the study of Benhorin and colleagues.14
The data are presented as mean (SD). Statistica 6.0 (Polish version) was used for statistical calculations. The data were tested for normality using the ShapiroWilk test. Statistical analysis of group differences was performed using Students t-test with Bonferroni correction. The differences within groups were analysed using analysis of variance for repeated measurements. Homoscedascity was verified with Levenes test and significant differences were analysed with Fishers post hoc LSD test. P<0.05 was considered to be significant, and P<0.0011 was considered to be significant when a Bonferroni correction was used.
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Results |
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The patients ages, body mass and height and the duration of anaesthesia were similar in the two groups (Table 1). Patey radical mastectomy was the surgical procedure used for all patients.
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Discussion |
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Although the QTc interval exceeded 0.44 s in more than 50% of patients pretreated with anthracyclines, no serious arrhythmias were observed. This finding is in line with other reports of QTc prolongation after administration of various anaesthetics.11 12 16 17 It would appear that the risk of arrhythmias is low unless a QTc value of 0.6 s is exceeded;1 18 we did not observe such long QTc intervals in any patient. It should be emphasized that higher isoflurane concentrations than those used in our study may enhance QTc prolongation towards 0.6 s in women given anthracycline chemotherapy.
Other authors have observed a statistically significant prolongation of the QTc interval in healthy subjects inhaling isoflurane.12 16 In these studies, however, inhalational agents were administered during induction of anaesthesia, whereas we used drugs that do not influence the QTc interval. We also used relatively low concentrations of isoflurane and our patients had received midazolam for premedication, which can reduce QTc prolongation induced by other anaesthetics.16
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Acknowledgements |
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References |
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