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Plasma Concentrations of Lidocaine and Bupivacaine After Cervical Plexus Block for Carotid Surgery

Tissot, Sylvie MD; Frering, Beatrice MD; Gagnieu, Marie-Claude PhD; Vallon, Jean-Jacques PhD; Motin, Jean MD

Brief Communication

Service (Tissot, Frering, Motin) d'Anesthesie-Reanimation and (Gagnieu, Vallon) de Biochimie, Hopital Edouard Herriot, Lyon, France.

Accepted for publication March 6, 1997.

Address correspondence and requests to Sylvie Tissot, MD, Hopital Edouard Herriot, Service d'Anesthesie-Reanimation, Pavillon M, Place d'Arsonval, 69437 Lyon Cedex 03, France.

Carotid surgery is often performed under cervical plexus block, which allows clinical monitoring of the neurological status during carotid cross-clamping [1,2]. Toxic concentrations of local anesthetic were obtained in a study using lidocaine [3], and convulsion was described during carotid surgery under bupivacaine local anesthesia [4]. A mixture of lidocaine and bupivacaine is often used to combine the theoretically fast onset of lidocaine with long duration of nerve block of bupivacaine. The purpose of this study was to test the hypothesis that a 1:1 mixture of bupivacaine and lidocaine would result in plasma levels of both drugs that are below toxic levels when administered in commonly used volumes for cervical plexus block.

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Methods

After institutional approval and written, informed consent, 15 patients (12 men, 3 women) scheduled for carotid endarterectomy were prospectively included in the study. Mean age was 67 +/- 14 yr, mean body weight was 75 +/- 13 kg, and mean height was 169 +/- 8 cm. Hydroxyzine 1 mg/kg was administered 2 h before surgery. Two electrocardiographic leads, pulse oximetry, and intraarterial blood pressure were continuously monitored during the perioperative period. The deep cervical block was performed as follows [5]: three needles were inserted onto the transverse processes of C2, C3, and C4. Six to eight milliliters of a 1:1 mixture of 0.5% bupivacaine and 2% lidocaine was injected via each needle. Twenty to thirty milliliters of a 1:1 mixture of 0.25% bupivacaine and 1% lidocaine was injected to block the superficial cervical plexus. All injections were carried out slowly (not faster than 6-7 mL/min) after repeated aspirations. During the surgery, the surgeon reinforced the superficial cervical block, if necessary, with a local injection of 1% lidocaine. Informal clinical observation was performed continuously to detect symptoms of local anesthetic toxicity and neurologic complications related to the carotid cross-clamping. If major neurologic complications (loss of consciousness, convulsions) occurred during the 3-min trial of carotid cross-clamping, general anesthesia was induced.

Serial blood samples (5 mL) were withdrawn from the radial arterial catheter immediately after the deep cervical block, i.e., 5 min prior to the superficial block (T-5), immediately after the superficial block (T0) and 10, 20, 30, 60, 120, and 180 min thereafter.

Measurements of plasma lidocaine and bupivacaine concentrations were performed using a highperformance liquid chromatographic method. An internal standard was added to the plasma samples, which were then submitted to a double extraction. First, the compounds were extracted at alkaline pH 12 using dichlorobutane. The hydrochloric acid was then added to the organic layer, and the aqueous phase was back-extracted using chloroform at alkaline pH. After drying, the residual material was dissolved in a 70% water/30% acetonitrile mixture and injected into a liquid chromatograph equipped with a diode array detector. The chromatograms were obtained at three wavelengths: 226, 240, and 270 nm. The chromatographic peak purity of lidocaine and bupivacaine was verified for all samples, and then the concentrations of the two compounds were calculated at two wave-lengths (226 and 240 nm) against lidocaine and bupivacaine standards. These standards were prepared by spiking human drug-free serum (Lyphocheck Drug Free Serum; Biorad, Richmond, CA) with appropriate amounts of lidocaine and bupivacaine and then extracted as previously described. The intraday coefficient of variation of the method was 8% for lidocaine and bupivacaine. For interday series, the coefficient of variation obtained over a 5-m period for 11 calibration curves was 9.1% for lidocaine and 12.9% for bupivacaine. The detection limits of quantification were 0.05 mg/L.

Data are reported as mean +/- SD.

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Results

Local anesthetic doses used for cervical block were 343 +/- 35 mg of lidocaine and 87 +/- 8 mg of bupivacaine. The mean peak concentrations (Cmax) of lidocaine and bupivacaine were 5.14 +/- 1.20 mg/L (range 3.03-7.32 mg/L) and 1.59 +/- 0.63 mg/L (range 0.82-3.02 mg/L), respectively (Figure 1). The time to reach the Cmax was equal to 10 +/- 9 min (range -5 to 20 min) for both lidocaine and bupivacaine after superficial cervical injection.

Figure 1

Figure 1

Additional doses of lidocaine (mean 139 +/- 12 mg) were injected by the surgeon in nine patients between 25 and 50 min after the superficial cervical plexus block. An increase in lidocaine concentration (0.56 +/- 0.65 mg/L) was observed in the blood sample after this injection, 30 min after superficial block in two patients, and 60 min after superficial block in the seven other patients. The concentrations remained lower than the Cmax, except in one patient (Figure 2), after the injection of 150 mg of lidocaine 45 min after superficial block.

Figure 2

Figure 2

No toxic cardiovascular reactions were observed after administration of the local anesthetics. In one patient, transient drowsiness and slurring of speech was observed 15 min after the superficial block. The concentrations of lidocaine and bupivacaine were 2.85 mg/L and 0.91 mg/L, respectively, 10 min after the superficial block. They decreased to 1.91 mg/L and 0.64 mg/L, respectively, 20 min after superficial block. The Cmax values, reached at T-5, i.e., just after the deep block, were 3.53 mg/L for lidocaine and 1.22 mg/L for bupivacaine.

Carotid shunting was necessary in four patients because of new onset of neurologic symptoms after carotid clamping. Two patients presented a decrease in contralateral grip strength, and the surgery was continued under local anesthesia. In the two other patients, a loss of consciousness was observed, and general anesthesia was performed. General anesthesia was also necessary for another patient just after incision due to lack of patient cooperation.

The time between the block and the beginning of surgery was 36 +/- 12 min, the duration of surgery was 95 +/- 12 min, and the duration of the carotid cross-clamping was 48 +/- 13 min.

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Discussion

Cervical plexus block for carotid endarterectomy appears to be a safe technique, as described in several studies [2,6,7]. In this study, no major complications related to the systemic effects of local anesthetics were observed despite high C (max) values for lidocaine and bupivacaine. Six patients had Cmax levels for lidocaine higher than 6 mg/L, and in these patients, two had a Cmax higher than 2.5 mg/L for bupivacaine, concentrations that are considered toxic for each anesthetic administered alone [8]. The risk of toxic effects could be even higher for two reasons. A mixture of local anesthetics can result in cumulative toxicity [9-11], and the Cmax was reached rapidly, possibly increasing the risk of adverse effects [12]. Only one patient presented mild and transient symptoms of central nervous system toxicity, but in this case, the local anesthetic concentrations were very much lower than toxic levels. The patient did not have any underlying pathology that might explain a higher sensitivity to the toxic effects of the local anesthetics, e.g., renal failure, acidosis or cirrhosis [13].

In this study, concomitant peak concentrations of lidocaine and bupivacaine were observed early (about 10 min) after the injection of the superficial cervical plexus block. In some patients, local anesthetic concentrations increased rapidly to the peak value, and for one patient, the Cmax was reached just after the injection of the deep cervical plexus block. The speed of injection was probably not a factor because it was very slow in this technique. Rapid absorption has been reported after stellate ganglion block [14] and could be explained by the increased vascularization of the cervical region. Early peak values have also been described after intercostal blocks [13,15]. The injection of lidocaine by the surgeon led to a second increase of the lidocaine concentrations. In one case in this study (Figure 2), the second peak was higher than the Cmax related to the cervical block. It exceeded the theoretical toxic concentrations, although the lidocaine injection was limited (150 mg) and carried out 45 minutes after the block.

In conclusion, during cervical plexus block, plasma concentrations of local anesthetics reached an early peak, which neared toxic thresholds. Although no toxic systemic effects were observed, the doses of local anesthetic used were maximal. Additional doses of local anesthetics must be injected carefully and at least 40 minutes after the initial block to avoid the period of peak concentrations. The usual recommendations (multiple aspiration, slow injection) must be emphasized.

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