University Department of Anaesthesia and Pain Management, Leicester Royal Infirmary, Leicester LE1 5WW, UK*Corresponding author
Accepted for publication: August 11, 2000
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Abstract |
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Br J Anaesth 2001; 86: 903
Keywords: analgesics opioid, remifentanil; analgesics opioid, alfentanil; intubation, tracheal, responses; cardiovascular system
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Introduction |
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Patients and methods |
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Patients were not premedicated and received their usual antihypertensive drugs on the day of surgery. All patients received Hartmanns solution 5 ml kg1 over 510 min before induction of anaesthesia. Patients lungs were pre-oxygenated for 3 min and glycopyrrolate 200 µg i.v. was administered followed by the study drug and by an infusion, as described below.
At induction of anaesthesia, group 1 (n=20) received a bolus of remifentanil 0.5 µg kg1 over 30 s followed by an infusion of remifentanil at 0.1 µg kg1 min1. Group 2 (n=20) received a bolus of alfentanil 10 µg kg1 over 30 s followed by an infusion of saline at the same rate. Infusions of remifentanil (group 1) and saline (group 2) continued throughout the study period. All study drugs and infusions were prepared by a third party, so that the investigators were unaware of their identity.
Immediately after the bolus of study drug, a standard general anaesthetic was administered, comprising propofol 0.5 mg kg1 followed by 10 mg every 10 s until loss of verbal contact, and rocuronium 0.6 mg kg1 to produce neuromuscular block. Patients lungs were ventilated manually using a Bain circuit with 1% isoflurane and 66% nitrous oxide in oxygen, to an end-tidal carbon dioxide tension of 4.04.5 kPa using a Datex Capnomac. After establishment of neuromuscular blockade, confirmed with a nerve stimulator (Fisher Paykell NS272), laryngoscopy and orotracheal intubation were performed, 3 min after induction.
Heart rate (HR) and systolic, mean and diastolic arterial pressures (SAP, MAP and DAP) were recorded at 1 min intervals from pre-oxygenation to 5 min after intubation. Arterial pressure was measured non-invasively using an automatic oscillometric device (Datex Cardiocap) and ECG was monitored with electrodes in the CM5 position. The duration of laryngoscopy and any difficulties in laryngoscopy or tracheal intubation were noted.
Escape medication (ephedrine 3 mg increments) was administered for hypotension (SAP<100 mm Hg, or a decrease of >30% of baseline for >60 s) and atropine, in 300 µg increments, for bradycardia (HR<45 beats min1). For hypertension (SAP>200 mm Hg, or an increase of >30% above baseline values, for >60 s) or tachycardia (HR>130 beats min1 for >60 s), the inspired isoflurane concentration was increased in increments of 0.5%. Power analysis, based on previous data,3 suggested that 20 patients per group would give an 80% chance of detecting a difference between the groups of 15 mm Hg in the cardiovascular response to intubation. (=0.05, ß=0.2). Statistical analysis was performed using general linear model analysis of variance for repeated measures (with treatment group and time as between- and within-group factors, and Bonferroni testing to adjust for multiple comparisons of each parameter) using SPSS for Windows computer software (release 9.0, 1998).
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Results |
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Changes in HR after induction of anaesthesia were minimal, but there was a significant increase in HR after intubation in both groups (P<0.05). Mean maximum HR occurred 1 min after intubation in both groups, and was 87 beats min1 (12 beats min1 above baseline; P=0.065) in the remifentanil group and 89 beats min1 (15 beats min above baseline; P<0.05) in the alfentanil group. However, there were no overall differences between groups for SAP, DAP, MAP or HR.
Seven patients in the remifentanil group and four in the alfentanil group required ephedrine 39 mg to treat hypotension (SAP<100 mm Hg). Marked hypotension (SAP<80 mm Hg for >1 min) occurred in three patients in the remifentanil group and two in the alfentanil group. There was no clear relationship between type of antihypertensive medication and requirement for escape medication (Table 2). Three patients in the alfentanil group and none in the remifentanil group required an increase in the inspired concentration of isoflurane to treat hypertension. A SAP of >200 mm Hg occurred in only one patient in the alfentanil group. Data from all patients, including those who required escape medication, were analysed. No patient required treatment for bradycardia. Transient ST segment depression associated with tachycardia occurred after intubation in one patient in the remifentanil group. This resolved spontaneously within 3 min without specific treatment. No other ST segment changes were observed.
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Discussion |
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We have recently shown that in young adults a bolus dose of remifentanil 0.5 µg kg1 followed by an infusion at 0.25 µg kg min1 is as effective as a remifentanil bolus of 1.0 µg kg1 followed by an infusion at 0.5 µg kg min1, in attenuating the haemodynamic response to intubation.10 The increase in SAP, DAP and MAP after intubation in young adults was approximately 10 mm Hg, compared with 30 mm Hg in the present study. This may reflect the fact that hypertensive patients demonstrate a greater cardiovascular response to laryngoscopy and orotracheal intubation, but could be related to the lower infusion regimen used in this study. However, the incidence of hypotension observed in the present study (7/20 patients in the remifentanil group required escape medication for hypotension) implies that higher doses of remifentanil would have been inappropriate in this patient population.
Previous studies have shown an unacceptable incidence of bradycardia associated with the use of remifentanil in the absence of a vagolytic drug.3 In this study, glycopyrrolate 200 µg was given before induction of anaesthesia and no patient required treatment for bradycardia. Seven patients in the remifentanil group and four in the alfentanil group were treated for hypotension. In most cases the hypotension was moderate (i.e. SAP>80 mm Hg) and responded well to small doses of ephedrine. The incidence of hypotension in this study confirms the view that hypertensive patients demonstrate exaggerated swings in arterial pressure and HR in response to induction of anaesthesia and tracheal intubation.2 However, hypotension occurred despite i.v. fluid preloading and glycopyrrolate, and may have been related to the use of propofol in combination with remifentanil or to the effects of antihypertensive medication.
Bolus doses of alfentanil 1015 µg kg1 have previously been shown to be effective in modifying the cardiovascular response to intubation.4 5 Higher doses of alfentanil (40 µg kg1) have been used in some studies, but these were in healthy young adult patients and such doses have been associated with bradycardia and hypotension.4 In elderly patients, a dose of alfentanil 10 µg kg1 was effective,11 so this dose was chosen for our study. Pharmacokinetic modelling indicates a 20- to 30-fold greater potency for remifentanil than for alfentanil.12 A bolus dose of alfentanil 10 µg kg1 approximates to remifentanil 0.5 µg kg1 based on relative potencies of 20:1. We chose a lower infusion rate of remifentanil than in our previous study because in the elderly the clearance and volume of distribution of remifentanil are reduced, and the pharmacodynamic effects are greater.13 The similarity in results between the two groups suggests that the doses of remifentanil and alfentanil chosen were comparable.
Recent data have again highlighted the problem of hypotension after induction of anaesthesia in patients receiving antihypertensive medication, in particular angiotensin-converting enzyme (ACE) inhibitors.14 A possible criticism of this study is that the patients were receiving different types of antihypertensive medication, and this was not controlled between groups. However, Sear and colleagues found no difference in the cardiovascular response to intubation in patients receiving different monotherapies for mild to moderate hypertension,15 and the distribution of type of antihypertensive medication between groups in this study was similar. Furthermore, the aim of this study was to establish whether remifentanil was as effective as alfentanil in a cohort of hypertensive patients, rather than examine the effects in those taking particular types of antihypertensive drugs. Although no firm conclusions can be made from a study of this size, escape medication for hypotension was required by patients taking beta blockers, ACE inhibitors, diuretics and combination therapy, with no clear association between type of antihypertensive treatment and hypotension after induction of anaesthesia. Further studies might assess the effects of opioids and specific antihypertensive medication.
This study supports the notion that hypertensive patients have an exaggerated cardiovascular response to laryngoscopy and tracheal intubation and are susceptible to episodes of hypotension after induction of anaesthesia. The occurrence of transient ST depression despite treatment measures confirms that this group is at risk of myocardial ischaemia. In conclusion, remifentanil and alfentanil in the doses described were similarly effective in reducing the cardiovascular response to laryngoscopy and orotracheal intubation.
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Acknowledgement |
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References |
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