1Service of Anaesthesiology, Resuscitation and Pain Clinic, Hospital Universitario Sant Joan de Reus, Reus, Tarragona, Spain. 2Service of Anaesthesiology, Resuscitation and Pain Clinic, 3Laboratory of Clinical Analysis and 4Research Unit, Department of Internal Medicine, Pius Hospital de Valls, Valls, Tarragona, Spain*Corresponding author: Passatge dels Grallers 24, E-43205 Reus, Tarragona, Spain
Accepted for publication: November 22, 2001
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Abstract |
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Methods. Forty-two adult patients were randomly allocated to receive either a 0.5% lidocaine solution 3 mg kg1 (n=20) or mepivacaine 5 mg kg1 (n=22). Plasma concentrations of both anaesthetic agents were measured at 5, 10, 20, 30, 45, and 60 min after deflation of the tourniquet by gas chromatography.
Results. Although plasma concentrations of mepivacaine and lidocaine were comparable 5 min after deflation, concentrations of lidocaine decreased significantly thereafter, whereas plasma concentrations of mepivacaine were similar over the 60-min study period. Supplementary analgesia during the intraoperative period was required by 45% of patients in the lidocaine group as compared with 9% in the mepivacaine group (P=0.02). No adverse effects were observed in patients given mepivacaine. In the lidocaine group, adverse effects were observed in 10% of the patients. The total ischaemia time, volume of the local anaesthetic, and duration of the surgical procedure were not significantly different between the two groups.
Conclusions. Mepivacaine 5 mg kg1 ensured better intraoperative analgesia than lidocaine 3 mg kg1 when used for IVRA. Plasma concentrations of lidocaine decreased significantly between 5 and 60 min following tourniquet deflation, whereas blood concentrations of mepivacaine remained below the toxic concentration.
Br J Anaesth 2002; 88: 51619
Keywords: anaesthetic techniques, i.v., regional; anaesthetics local, lidocaine; anaesthetic local, mepivacaine
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Introduction |
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Methods |
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Patients 50 kg and/or with respiratory disease were premedicated with diazepam 5 mg, whereas patients weighing greater than 50 kg were given diazepam 10 mg. A 20-gauge catheter was introduced into a vein on the dorsum of the hand to be operated upon and another 16-gauge catheter was inserted into a vein of the arm not requiring surgery for fluid infusion and blood sampling. The operative arm was exanguinated by elevating it and wrapping it with a rubber Esmarch bandage. The proximal cuff of a double tourniquet was then inflated to 350 mm Hg and 20 ml min1 of either mepivacaine or lidocaine was injected in a double-blind fashion into the indwelling cannula. After approximately 15 min, the distal cuff was inflated to the same pressure. A minimum total ischaemia time of 40 min was established for safety reasons because of the use of mepivacaine in doses much larger than those reported in the literature. Midazolam 1 mg every 10 min up to a maximum of 5 mg was used for intraoperative sedation trying to maintain the patient at level 23 on the Ramsay sedation scale.7 Supplementary intraoperative analgesia consisted of intravenous boluses of fentanyl 50 µg every 10 min up to a total dose of 150 µg. Boluses of fentanyl were provided whenever there was a 20% increase in baseline values of arterial pressure and/or heart rate or when analgesia was graded as poor by the patient. Patients vital signs (arterial pressure, ventilatory frequency, pulse oximeter), analgesic request, and presence of adverse events related to unexpected deflation of the tourniquet were assessed intraoperatively.
Venous blood samples were obtained from the opposite arm at 5, 10, 20, 30, 45, and 60 min after release of the tourniquet. The samples were centrifuged and the plasma frozen at 20°C and stored. Plasma concentrations of local anaesthetics were analysed by gas chromatography/mass spectrometry.
After tourniquet release and at the end of surgery, patients were asked to report any adverse effects. Symptoms of dizziness, nystagmus, tinnitus, facial dysaesthesia, convulsions, depression of the central nervous system, bradypnoea (ventilatory frequency 10 breaths min1), bradycardia (heart rate
50 beats min1), and cardiovascular depression (
25% decrease in baseline arterial pressure) were noted, if present. Patients vital signs and time to the first analgesic request after cuff release (time of residual analgesia) were recorded in the postanaesthesia care unit.
The sample size was calculated according to the main objective of the study, that is adequate intraoperative analgesia with mepivacaine for IVRA, which was determined by the need for supplementary medication intraoperatively, for a sensitivity of 20%, beta error of 0.10 and an alpha error of 0.05. Patient characteristics and data related to the anaesthetic technique and the surgical procedure were recorded in both groups. Comparison of categorical variables was carried out with the Pearsons chi-squared test. All quantitative variables with the exception of time of residual analgesia were normally distributed and were analysed using the Students t-test if variances were comparable or with the MannWhitney U test if variances were not comparable. Paired data were analysed with the paired t-test. KaplanMeier survival analysis was performed for time of residual analgesia. Statistical analysis was performed with the SPSS/PC+ (version 8.0, SPSS Inc., Chicago, IL) software programme. Data are expressed as mean (SD) unless indicated otherwise.
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Results |
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Plasma concentrations of both local anaesthetic agents are shown in Table 2. Five minutes after cuff deflation, plasma concentrations of mepivacaine and lidocaine were comparable. However, plasma concentrations of lidocaine decreased significantly between 5 and 60 min following tourniquet deflation (P<0.001), whereas blood concentrations of mepivacaine did not change during the observation period. At 60 min, plasma concentrations of mepivacaine were significantly higher than those of lidocaine (P<0.001).
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Discussion |
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The dose of lidocaine recommended for classical IVRA technique (3 mg kg1 as a 0.5% lidocaine solution) was used. With respect to mepivacaine, we used a dose of 5 mg kg1 with which consistent satisfactory results had been obtained by our group as well as by others.16 17 According to the study of Rawal and co-workers18 in which plasma concentrations of mepivacaine, lidocaine, and prilocaine when given at the 3 mg kg1 dose peaked within 5 min after tourniquet release, we decided to start measurements of plasma drug concentrations at 5 min following tourniquet deflation, with the last measurement at 60 min because in the pharmacokinetic study of Simon and associates8 less than 1 µg ml1 of lidocaine was measured from that time. Although in the case of mepivacaine for IVRA, no previous studies have evaluated plasma concentrations of this agent at 60 min after deflation, a pharmacokinetic behaviour similar to that of lidocaine was assumed as in the study of Rawal and co-workers,18 mepivacaine and lidocaine showed similar pharmacokinetics 5 min after tourniquet release.
As compared with lidocaine, mepivacaine 5 mg kg1 provided better intraoperative analgesia with no adverse effects on release of the tourniquet. Moreover this finding is supported by plasma concentrations of the drugs that were comparable 5 min after deflation (1.68 (0.73) µg ml1 for lidocaine and 1.62 (0.52) µg ml1 for mepivacaine), whilst plasma concentrations of lidocaine decreased significantly (0.81 (0.21) µg ml1) at 60 min as opposed to plasma concentrations of mepivacaine that did not vary (1.68 (0.41) µg ml1). The observation of similar plasma concentrations of both anaesthetic agents despite the use of almost double concentrations of mepivacaine may be explained by the vascular effects of mepivacaine (vasoconstriction) in IVRA19 and a much more sustained release to the systemic circulation as compared with the predominatly vasodilatory effects of lidocaine.20 Therefore, toxic plasma concentrations of mepivacaine are not reached rapidly as opposed to lidocaine 3 mg kg1 when adverse events may appear within the first minute after tourniquet release as reported by Simon and associates.8 On the other hand, the relatively prolonged nature of the increase in systemic mepivacaine concentrations might produce longer term psychometric effects. However, we did not examine this in our study.
Up to the present time, toxic plasma concentrations of local anaesthetics greater than 4 µg ml1 for lidocaine and between 5 and 6 µg ml1 for mepivacaine have been quoted.15 In our study, however, plasma drug concentrations within the first 5 min after tourniquet release were not measured but in that interval a case of dizziness and a case of bradycardia occurred. No patient in the lidocaine group showed plasma concentrations greater than 3 µg ml1, although there was a greater dispersion of lidocaine values at 5 min (predominately 23 µg ml1). In our study, there were no statistically significant differences in the occurrence of adverse events, probably because of the small sample size. In the study of Simon and co-workers,8 five of the 10 patients showed plasma concentrations of lidocaine greater than 4 µg ml1 during the first minute after release of the tourniquet. This is in contrast to findings of Rawal and associates18 who reported plasma concentrations of lidocaine less than 1 µg ml1 at this time. It should be noted, however, that in the first study8 high-performance liquid chromatography was used for the assessment of plasma drug concentrations in 10 patients, whereas in the second study18 gas chromatography in 20 patients. In the study of Simon and co-workers,8 although toxic plasma concentrations were obtained in half of the patients, none of them experienced any adverse effect. In contrast, in the study of Rawal and colleagues,18 four patients in the lidocaine group experienced dizziness as compared with none in the mepivacaine group.
This preliminary study in a small number of patients indicates that mepivacaine 5 mg kg1 has a closer profile of the ideal local anaesthetic agent for IVRA than lidocaine 3 mg kg1. Mepivacaine offered adequate intraoperative analgesia with no incidence of adverse effects on release of the tourniquet despite persistence of plasma drug concentrations during the 60-min study period.
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Acknowledgement |
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References |
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