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Response to E-Letter by Bamgbade et al
- Daniel Bolliger, Miodrag Filipovic, Manfred D. Seeberger (30 March 2007)
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Effects of propofol and sevoflurane on left ventricular diastolic function
- Olumuyiwa A Bamgbade, Angela Chung, Emma Bain, Lee Feddy. (26 February 2007)
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Daniel Bolliger, research fellow Department of Anaesthesia, University Hospital Basel, Switzerland, Miodrag Filipovic, Manfred D. Seeberger
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We are grateful to Dr. Bamgbade and colleagues for their interest in our recent publication on the effects of propofol and sevoflurane on diastolic function in patients with pre-existing diastolic dysfunction (1). The authors of the letter raise many points, some of which are of general importance whenever a clinical research protocol is designed. The sample size calculation, as indicated in their critique, is important with regard to the study design and had been performed as described on page 14 (last sentence of the Methods section) of our article. Although in both important and interesting, a detailed discussion of the general remarks regarding the study design would go beyond the limits of this letter. In short, ethical aspects precluded us from performing the “perfect” study that uses the most valid (invasive) monitors and excludes all confounding factors such as administration of fentanyl prior to tracheal intubation. Our primary responsibility and main goal as clinical researchers is to provide safe anaesthesia to our study patients. This is followed by the goal and responsibility of obtaining the most valid scientific evidence achievable. In the constant effort to better achieve both goals, we are grateful to Bamgbade and colleagues for their thoughts on how the design of our ongoing research can be further improved. The question of equipotency of the two drugs is discussed as a limitation in the Discussion section of our article. We further explained why this limitation does not undermine the validity of the findings. We believe that this limitation is not caused by shortcomings of the study protocol but by the lack of a valid “equipotency monitor”. We purposely decided against titrating anaesthesia levels to bispectral index monitoring (BIS) values as BIS monitoring has never been established for comparing depths of anaesthesia induced by different anaesthetics. In contrast, it has been shown that BIS values are significantly lower during sevoflurane than halothane anaesthesia at 1 MAC and 1.5 MAC (2). Moreover, BIS values as low as 33 and 9 have been found after administration of neuromuscular blocking agents in unanaesthetised volunteers (3). Therefore, we are unaware of the scientific evidence to call BIS values of 36-41 as indicative of “excessive depth” of anaesthesia. Based on the MAC concept, we would even postulate that at least the patients anaesthetized with sevoflurane were given “light” anaesthesia! Another point is that isolated diastolic dysfunction is not uncommon, as Bamgbade et al. state, but is the cause of congestive heart failure in more than one-third of all patients suffering from this disease (4,5). Although it is correct that the diagnosis of diastolic dysfunction is not easy, we were able to reliably assess diastolic function based on established echocardiographic parameters. Many patients with diastolic dysfunction are not, or not yet, symptomatic, as were the patients included in our study. The number of patients with diastolic dysfunction undergoing surgery is substantial, and many questions concerning optimal perioperative treatment of them are unresolved. For instance, the effects of anaesthetics on diastolic function are insufficiently understood. This lack of knowledge is the reason for our studies that are aimed to add a small piece of knowledge to this topic. Daniel Bolliger, Miodrag Filipovic, Manfred D. Seeberger References: 1. Filipovic M, Michaux I, Wang J et al. Effects of sevoflurane and propofol on left ventricular diastolic function in patients with pre- existing diastolic dysfunction. Br J Anaesth 2007;98:12-8. 2. Schwab HS, Seeberger MD, Eger EI, 2nd et al. Sevoflurane decreases bispectral index values more than does halothane at equal MAC multiples. Anesth Analg 2004;99:1723-7, table of contents. 3. Messner M, Beese U, Romstock J et al. The bispectral index declines during neuromuscular block in fully awake persons. Anesth Analg 2003;97:488-91. 4. Bhatia RS, Tu JV, Lee DS et al. Outcome of heart failure with preserved ejection fraction in a population-based study. N Engl J Med 2006;355:260-9. 5. Owan TE, Hodge DO, Herges RM et al. Trends in prevalence and outcome of heart failure with preserved ejection fraction. N Engl J Med 2006;355:251-9. Conflict of Interest:None declared |
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Olumuyiwa A Bamgbade, Consultant Anaesthetist Central Manchester University Hospital, Manchester, UK, Angela Chung, Emma Bain, Lee Feddy.
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The article by Filipovic et al (1) on the effects of propofol and sevoflurane on left ventricular (LV) diastolic function is interesting, but generates some debate. Although uncommon, isolated diastolic dysfunction is a recognized cause of cardiac failure and the prevalence increases with old age, cardiovascular disease, diabetes and obesity (2). Most patients have combined systolic and diastolic LV dysfunction, which reduces the clinical impact of this study. The basis for this study by Filipovic et al was their findings in a previous similar study of healthy subjects, and this is valid (3). This current study was prospective, randomised, single-blinded and has valid patient exclusion criteria. However, patient inclusion was based on a clinical assumption, and an echocardiographic criterion that may not be validated. It will be useful to know if the echocardiographic diagnosis of diastolic dysfunction was clinically significant or symptomatic. Although Filipovic et al (1) discussed their study limitations, there are other points that require clarification. The sample size of 22 is small and there was no study power calculation; which undermines the significance of the results. What is the basis for the regimen of fluid replacement during the study? Is this a validated rehydration regimen, and is this a study of drug effects and/or fluid effects on LV function? Patient monitoring included two-lead electrocardiography which may be inadequate to detect ischaemia. Bispectral index (BIS) monitoring showed excessive depths of anaesthesia; and it will be useful to know if anaesthesia was titrated to BIS, and what the target BIS values were. What was the induction target level of propofol infusion before reducing to 4mcg/ml. Clinical doses of propofol preserves LV systolic and diastolic function (4), but the high doses that might have been used in this study could affect cardiac function. What dose of sevoflurane was used for induction, and was induction smooth in these adult patients? Sevoflurane induction preserves LV diastolic function, but causes negative inotropism (5). The addition of fentanyl during the IPPV phase would have impacted on anaesthesia and affected BIS values (6). Fentanyl causes hypotension and may affect LV function; which may confound the effects of propofol or sevoflurane. It will be interesting to do a cross-over study of sevoflurane and propofol on left ventricular diastolic function, to see how both anaesthetics affect the same patient. References: 1) Filipovic M, Michaux I, Wang J, et al. Effects of sevoflurane and propofol on left ventricular diastolic function in patients with pre- existing diastolic dysfunction. Br J Anaesth 2007; 98:12-18. 2) Redfield MM, Jacobsen SJ, Burnett JC Jr, et al. Burden of systolic and diastolic ventricular dysfunction in the community: appreciating the scope of the heart failure epidemic. JAMA 2003; 289:194-202. 3) Filipovic M, Wang J, Michaux I, et al. Effects of halothane, sevoflurane, and propofol on left ventricular diastolic function in humans during spontaneous and mechanical ventilation. Br J Anaesth 2005; 94:186- 92. 4) Kato H, Sasaoka N, Yositani K, et al. The effects of propofol on left ventricular systolic and diastolic function during induction of anaesthesia. Masui 2004; 53:761-6. 5) Kato H, Sasaoka N, Yoshitani K, et al. The effect of inhalation induction with sevoflurane on left ventricular systolic and diastolic function. Masui 2004; 53:34-9. 6) Mi WD, Sakai T, Kudo T, et al. Performance of bispectral index and auditory evoked potential monitors in detecting loss of consciousness during anaesthetic induction with propofol with and without fentanyl. Eur J Anesthesiol 2004; 21:807-11. Conflict of Interest:None declared |
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