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From the Department of Anesthesiology Yale University School of Medicine New Haven Connecticut USA.
Address correspondence to: Dr. Peter G. Atanassoff, Yale University School of Medicine, Department of Anesthesiology, P.O. Box 208051, 333 Cedar Street, New Haven, Connecticut 06520, USA. Phone: 203-785-2802; Fax: 203-785-6664; E-mail: peter.atanassoff{at}yale.edu
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Abstract |
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Methods: In a double-blind, cross-over study, ten volunteers received IVRA with 40 mL ropivacaine 0.2% or lidocaine 0.5% at least four days apart. Both cuffs of a double-cuff tourniquet remained inflated until they could no longer be tolerated. The incidence, duration and intensity of CNS side effects were recorded at three, ten, and 30 min after tourniquet release and correlated with simultaneous venous blood samples.
Results: There was a lower incidence of CNS side effects with ropivacaine (6/10 volunteers) when compared to lidocaine (10/10 volunteers). There was also less duration of these side effects (mean ± SD, 5.1 ± 5.2 min vs 11.7 ± 6.7 min). Measured total plasma levels were highest at ten minutes with ropivacaine 0.2% (1.2 ± 0.3 µg•mL-1) and at three minutes with lidocaine 0.5% (1.7 ± 0.6 µg•mL-1). Peak CNS symptoms correlated with measured venous plasma levels for lidocaine, but occurred earlier with ropivacaine.
Conclusions: We observed a lower incidence of CNS side effects with ropivacaine as compared to lidocaine. Although ropivacaine's greater lipid solubility should, theoretically, lead to more CNS side effects, this was, likely, offset by slower release from tissues and lesser percentage of unbound (free) drug.
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Introduction |
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Reports of major complications such as seizures, cardiac arrest or death following intravenous regional anesthesia (IVRA) are scarce in the literature, but exist.2,3 In a prospective investigation4 of complication rates, three of 11,229 patients after IVRA developed a seizure after deflation of the tourniquet. A survey5 among North American anesthesiologists who frequently use IVRA confirmed that severe CNS and cardiovascular side effects do occur.
Lidocaine 0.5% is used frequently for IVRA. By the mid-eighties the longer-lasting local anesthetic ropivacaine was introduced into clinical practice. In contrast to currently used local anesthetics, ropivacaine is not prepared as a racemic mixture but as a pure left enantiomer. It is structurally related to mepivacaine and bupivacaine, with a clinical profile similar to the latter. The s-enantiomers have been shown to substantially reduce systemic toxicity when compared to their racemic counterparts. Four volunteer studies compared ropivacaine to lidocaine or bupivacaine and found potential advantages of ropivacaine over the other two local anesthetics.6–9 All noted less CNS and absent serious cardiac side effects with ropivacaine. These studies did not investigate, however, the quantification of CNS effects and their correlation to local anesthetic plasma levels. The present investigation examines duration, intensity, and the correlation of CNS side effects to venous plasma levels following IVRA with lidocaine and ropivacaine as local anesthetics.
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Methods |
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Following exsanguination by gravity, the proximal cuff of a double-cuff tourniquet placed on the subject's upper arm was inflated to a pressure of 250 mmHg. Limb occlusion pressure was verified by loss of pulse oximetry tracing; local anesthetic (40 mL) was then injected over one minute. When the proximal tourniquet pressure became unbearable (verbal numerical pain score, VNPS=10), the distal cuff was inflated followed by release of the proximal tourniquet. During inflation and following deflation of the distal tourniquet, the volunteers were questioned about CNS side effects and asked to rate them on a verbal numerical intensity scale between 0–10. The incidence, duration, and intensity of CNS side effects were recorded at three, ten, and 30 min post tourniquet release and correlated with venous local anesthetic plasma levels which were sampled at the same time points. Local anesthetic plasma levels were determined by means of gas chromatography. After completion of the experiment, on study-day two, volunteers were asked to compare the intensity of CNS side effects between the two days.
Data are expressed as mean ± SD and were analyzed using Wilcoxon rank and paired t tests for non-parametric and parametric data, respectively; P <0.05 was considered statistically significant.
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Results |
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During tourniquet inflation, no CNS side effects were reported by the volunteers, no cardiac arrhythmias were observed. Following deflation of the distal tourniquet there was a lower incidence of CNS side effects with ropivacaine as compared to lidocaine. While all volunteers receiving lidocaine reported lightheadedness, dizziness, metallic taste, or tinnitus, only six of ten subjects with ropivacaine experienced these mild CNS side effects. Duration of the side effects was shorter with ropivacaine as compared to lidocaine (5.1 ± 5.2 min vs 11.7 ± 6.7 min, P=0.028). Also, when asked for intensity, perceived CNS symptoms were markedly less intense after ropivacaine. A statistically significant difference was noted for verbal numerical intensity scores for dizziness, lightheadedness, tinnitus, and metallic taste at three minutes, and for lightheadedness and tinnitus after ten minutes following tourniquet release (Figure 1
).
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). Peak CNS symptoms correlated with measured venous plasma levels for lidocaine, but occurred earlier with ropivacaine (Figures 1 and 2
). In both groups no cardiac arrhythmias were observed in the two ECG leads.
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Discussion |
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Lidocaine IVRA is safe and effective, being associated with rapid onset of anesthesia after injection and termination of analgesia after release of the tourniquet. Deflation of the tourniquet five minutes after administration of 2.5 mg•kg-1 of lidocaine 0.5% resulted in no signs of cardiac or serious CNS effects,10 yet symptoms of tinnitus between 20 and 70 sec after deflation were noted. In the present study, peak symptoms occurred three minutes after deflation. However, the tourniquet had been inflated on an average for approximately one to one and a half hours. Presumably more lidocaine is bound to tissue proteins (Na+ receptors) during this longer tourniquet time, and is then released slowly after deflation. This aspect is underlined by an investigation showing that approximately 70% of lidocaine remains within the tissues of the previously isolated limb after tourniquet release, the remainder entering the systemic circulation in the subsequent 45 min.11 Release of tissue-bound lidocaine is increased when the limb is exercised, emphasizing the necessity of keeping the previously anesthetized extremity quiescent after tourniquet deflation.
Pharmacokinetic washout data are available for lidocaine following IVRA,11,12 but do not exist for ropivacaine. Ropivacaine is structurally related to bupivacaine; its ability to bind to proteins as well as its pKa are also very similar if not equivalent to bupivacaine. Bupivacaine, however, binds tightly to activated sodium channels at low plasma concentrations (<0.2 µg•mL-1) displaying fast on - slow off kinetics. Consequently, the release of a bolus of bupivacaine as it occurs on deflation of the tourniquet has been associated with the occurrence of toxic ventricular dysrhythmias including ventricular fibrillation resistant to conventional therapy.13,14 Due to the lower lipophilicity and thereby lower overall toxicity of ropivacaine, it may be more suitable for IVRA than bupivacaine. Its margin of safety was found to be approximately 25% higher than bupivacaine following continuous iv infusion.8 Two articles reported of patients accidentally receiving high dosages of ropivacaine intravascularly and the patients failed to develop life-threatening cardiovascular side effects.15,16 More recently, after sciatic nerve block with presumable intravascular injection of 30 mL of ropivacaine 0.75%, bradycardia with QRS enlargement and inversion of T-waves were reported.17 Still, no ventricular tachycardia or fibrillation developed after ropivacaine which was the case in patients accidentally receiving bupivacaine intravascularly. These latter patients could not be successfully resuscitated.
Ropivacaine's higher ability to bind to tissue proteins, leading eventually to delayed release from its binding sites after tourniquet release, may be the principal reason why there was a lower incidence, duration, and intensity of CNS side effects in patients, when compared to lidocaine. Further studies are required to clarify if ropivacaine is an alternative to lidocaine for IVRA.
Revision received November 16, 2001. Accepted for publication September 12, 2001.
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References |
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2 Heath ML. Deaths after intravenous regional anaesthesia. Br Med J 1982; 285: 913–4.
3
Davis NL, de Jong RH. Successful resuscitation following massive bupivacaine overdose. Anesth Analg 1982; 61: 62–4.
4 Auroy Y, Narchi P, Messiah A, Litt L, Rouvier B, Samii K. Serious complications related to regional anesthesia: results of a prospective survey in France. Anesthesiology 1997; 87: 479–86.[Medline]
5 Henderson CL, Warriner CB, McEwen JA, Merrick PM. A North American survey of intravenous regional anesthesia. Anesth Analg 1997; 85: 858–63.[Abstract]
6 Chan VW, Weisbrod MJ, Kaszas Z, Dragomir C. Comparison of ropivacaine and lidocaine for intravenous regional anesthesia in volunteers: a preliminary study on anesthetic efficacy and blood level. Anesthesiology 1999; 90: 1602–8.[Medline]
7
Hartmannsgruber MW, Silverman DG, Halaszynski TM, et al. Comparison of ropivacaine 0.2% and lidocaine 0.5% for intravenous regional anesthesia in volunteers. Anesth Analg 1999; 89: 727–31.
8
Scott DB, Lee A, Fagan D, Bowler GM, Bloomfield P, Lundh R. Acute toxicity of ropivacaine compared with that of bupivacaine. Anesth Analg 1989; 69: 563–9.
9
Knudsen K, Beckman Suurkula M, Blomberg S, Sjovall J, Edvardsson N. Central nervous and cardiovascular effects of i.v. infusions of ropivacaine, bupivacaine and placebo in volunteers. Br J Anaesth 1997; 78: 507–14.
10 Smith CA, Steinhaus JE, Haynes CD. The safety and effectiveness of intravenous regional anesthesia. South Med J 1968; 61: 1057–60.[Medline]
11 Tucker GT, Boas RA. Pharmacokinetic aspects of intravenous regional anesthesia. Anesthesiology 1971; 34: 538–49.[Medline]
12
Hoffmann AC, van Gessel E, Gamulin Z, Ryser JE, Forster A. Quantitative evaluation of tourniquet leak during i.v. regional anaesthesia of the upper and lower limbs in human volunteers. Br J Anaesth 1995; 75: 269–73.
13
Long WB, Rosenblum S, Grady IP. Successful resuscitation of bupivacaine-induced cardiac arrest using cardiopulmonary bypass. Anesth Analg 1989; 69: 403–6.
14 Reynolds F. Bupivacaine and intravenous regional anaesthesia. Anaesthesia 1984; 39: 105–7.[Medline]
15
Abouleish EI, Elias M, Nelson C. Ropivacaine-induced seizure after extradural anaesthesia. Br J Anaesth 1998; 80: 843–4.
16 Korman B, Riley RH. Convulsions induced by ropivacaine during interscalene brachial plexus block. Anesth Analg 1997; 85: 1128–9.[Medline]
17 Ruetsch YA, Fattinger KE, Borgeat A. Ropivacaine-induced convulsions and severe cardiac dysrythmia after sciatic block. Anesthesiology 1999; 90: 1784–6.[Medline]
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