1 Department of Anaesthesiology, University Hospital Ghent, Ghent, Belgium. 2 Department of Anaesthesiology and CCM, OLV Hospital, Aalst, Belgium. 3 Department of Paediatric Cardiology, University Hospital Ghent, Ghent, Belgium. 4 Department of Anaesthesiology, H.H.R.M. Hospital, Menen, Belgium
* Corresponding author. E-mail: k.reyntjens{at}ugent.be
Accepted for publication August 31, 2005.
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Abstract |
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Methods. Forty-five children undergoing general anaesthesia with remifentanil and sevoflurane were randomly allocated to receive either saline, glycopyrrolate 6 µg kg1 or glycopyrrolate 12 µg kg1. After induction of anaesthesia with sevoflurane, i.v. placebo or glycopyrrolate was administered. An infusion of remifentanil at the rate of 0.15 µg kg1min1 was started, sevoflurane continued at 0.6 MAC and cisatracurium 0.2 mg kg1 was given. Heart rate (HR) and non-invasive arterial pressures were monitored and noted every minute for the first 10 min and then every 2.5 min for subsequent maximum of 45 min.
Results. Baseline HR [mean (SD)] of 117 (20) beats min1 decreased significantly from 12.5 min onwards after starting the remifentanil infusion in the control group [106 (18) at 12.5 min and 99 (16) beats min1 at 45 min]. In the groups receiving glycopyrrolate, no significant decrease in HR was noticed. Glycopyrrolate at 12 µg kg1 induced tachycardia between 5 and 9 min after administration. Systolic and diastolic arterial pressures decreased gradually, but there were no significant differences in the pressures between groups.
Conclusion. I.V. glycopyrrolate 6 µg kg1 prevents bradycardia during general anaesthesia with remifentanil and sevoflurane for cardiac catheterization in children with congenital heart disease. Administering 12 µg kg1 of glycopyrrolate temporarily induces tachycardia and offers no additional advantage.
Keywords: analgesics opioid, remifentanil ; children, congenital heart disease ; complications, bradycardia ; procedure, cardiac catheterization
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Introduction |
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Vasodilatation and bradycardia associated with the use of remifentanil are possible drawbacks in a patient population in whom ventricular filling pressure and rate dependency of cardiac output are critical determinants of haemodynamic stability.1
The aim of this study was to investigate whether previously reported bradycardia during remifentanilsevoflurane anaesthesia for cardiac catheterization can be prevented by administration of i.v. glycopyrrolate at induction of anaesthesia.2
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Methods |
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Statistical analysis was performed using repeated measures analysis of variance (ANOVA) with a Dunnett multiple comparisons post-hoc test for within-group evaluation. Differences between groups were analysed with a one-way ANOVA and a Bonferroni multiple comparisons test. P<0.05 was considered significant.
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Results |
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The groups were matched for patient characteristics and duration of procedure (Table 1). Induction of anaesthesia and tracheal intubation did not alter HR and mean arterial pressure (MAP) during the first 10 min of starting remifentanil infusion in the three groups, except for an increase in HR starting between 1 and 5 min following tracheal intubation in Group G12 (Table 2). In Group G0, HR decreased significantly from the baseline value from between 12.5 and 45 min. In contrast to the placebo group, HR was preserved in both the glycopyrrolate groups (Fig. 1); HR was significantly lower in Group G0 compared with Group G6 or Group G12 from 3 min after starting the remifentanil infusion (Fig. 1 and Table 2). No significant difference in HR between Group G6 and Group G12 was seen.
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Discussion |
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The major finding of our study is that glycopyrrolate 6 or 12 µg kg1 administered as an i.v. bolus after induction of anaesthesia, prevents bradycardia during remifentanilsevoflurane anaesthesia for catheterization of children with congenital heart disease. In the placebo group, bradycardia occurred from 12.5 min after the start of the remifentanil infusion, whereas in both glycopyrrolate groups no bradycardia was noticed during 45 min of study period. Also, the HR changes were qualitatively similar in both the glycopyrrolate groups in this time course (Fig. 1), suggesting no benefit of using the higher dose. In quantitative terms, the higher dose of glycopyrrolate caused tachycardia 1 min after tracheal intubation and this was significant until 5 min after intubation. The clinical relevance of this tachycardia is uncertain as maximal mean HR was only 140 beats min1 (Table 2). The time course of this HR increase coincided with the pressor response to tracheal intubation, which typically peaks at 12 min after laryngoscopy and usually subsides within 56 min, whereas tachycardia may persist for 10 min.5 Because the stress response to tracheal intubation was blunted in Group G0 and Group G6, and the anaesthetic regimen was the same in the three groups, the bolus effect of glycopyrrolate is a plausible explanation for the tachycardia seen in Group G12. Whereas a bolus of remifentanil can induce severe bradycardia and hypotension,5 6 even our technique of using low concentrationhigh flow continuous infusion of remifentanil induced bradycardia (Group G0). At the infusion rate set in our study, patients received a total of remifentanil 0.6 µg kg1, in the time period of 4 min, before tracheal intubation; this dose is sufficient to prevent stress response.5 The addition of glycopyrrolate 6 µg kg1 not only prevented bradycardia during induction of anaesthesia, but also kept HR virtually constant during 45-min study period.
We preferred giving glycopyrrolate by i.v. route as compared with the rectal route because the latter route can be associated with variable and/or incomplete gastrointestinal absorption.7 In a previous study in a similar population, rectal glycopyrrolate could not prevent bradycardia, albeit higher doses of remifentanil were used.2 After i.v. bolus, the mean distribution phase half-life of glycopyrrolate is 2.22 (1.26) min and mean elimination phase half life is 0.83 (0.27) h.7 Nevertheless, in the present study it protected against bradycardia for a prolonged period of time. It should also be noted that there is no linear relationship between the plasma level of glycopyrrolate and the HR response after i.v. administration.6 We preferred glycopyrrolate to atropine because the latter has central effects and leads to more prolonged impairment of parasympathetic nervous system control of HR than equipotent doses of glycopyrrolate.8
Although the use of glycopyrrolate efficiently prevented bradycardia, there was a significant, but clinically acceptable decrease in arterial pressure in all study groups. The decrease in MAP (between 15 and 20%) in this study was consistent with the findings of other studies in paediatric patients.2 9 10 In children undergoing general surgery, Chanavaz and colleagues studied the effect of atropine during remifentanilsevoflurane anaesthesia using echocardiography.9 They described a reduction in cardiac index related to a decrease in HR in the placebo group and a decrease in stroke volume in atropine-treated patients, without changes in myocardial contractility. Although we did not study myocardial contractility in our study, the effect of remifentanilsevoflurane on myocardial contractility is likely to be as small in our study as in the study by Chanavaz and colleagues. Because glycopyrrolate kept HR virtually unchanged in our patients, this raises the question whether the decrease in MAP in our patients was related to a decrease in preload and/or a decrease in afterload with this anaesthetic technique.
In conclusion, remifentanilsevoflurane is a safe and feasible anaesthetic technique for paediatric cardiac catheterization, but is associated with bradycardia and a moderate degree of hypotension. We have shown that i.v. glycopyrrolate 6 µg kg1 at induction of anaesthesia effectively prevents bradycardia, but not a moderate degree of hypotension.
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Acknowledgments |
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References |
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