The addition of epinephrine increases intensity of sensory block during epidural anesthesia with lidocaine

Regional Anesthesia and Pain Medicine 24(6): 541-546, 1999

The A d d i t i o n of Epinephrine Increases Intensity of Sensory Block During Epidural Anesthesia With Lidocaine Shinichi Sakura, M.D., Mariko Sumi, M.D., Noriko Morimoto, M.D., and Yoji Saito, M.D.

Background and Objectives. Little is k n o w n about the effect of adding epinephrine to local anesthetic solutions on the intensity of sensory block during epidural anesthesia. This study examined development of sensory block during lumbar epidural anesthesia using a cutaneous current perception threshold (CPT) quantitative sensory testing device. Methods. TWenty ASA I patients w h o were randomly divided to receive 10 mL 1% lidocaine with (group E) or without (group P) epinephrine 1:200,000. Current perception threshold at 2,000, 250, and 5 Hz stimulation at the trigeminal (V), ninth thoracic (T9), and second lumbar (L2) dermatomes, and the dermatomal levels of block of light touch, temperature, and pinprick discrimination were measured before and every 5 minutes, until 60 minutes after injection of epidural lidocaine. Results. After epidural administration of lidocaine with epinephrine, all CPT significantly increased at T9 and L2, whereas no increase was detected after epidural plain lidocaine. Areas under the curves, calculated to express overall magnitude and duration of CPT values, were significantly larger in group E than those in group P at 2,000 and 250 Hz at T9. No differences were observed in the maximal levels of loss of cold, pinprick, and touch sensations between both groups. Conclusions. These results suggest that lumbar epidural anesthesia using 10 mL 1% lidocaine with epinephrine produces a more intense block of both large and small diameter sensory nerve fibers than that with plain lidocaine. It appears, therefore, that the addition of epinephrine improves the quality of sensory block during epidural anesthesia with lidocaine. Reg Anesth Pain Med 1999: 24: 541-546. Key words: epidural, lidocaine, epinephrine, transmission.

E p i n e p h r i n e is c o m m o n l y a d d e d to local a n e s t h e t i c s o l u t i o n s for e p i d u r a l a d m i n i s t r a t i o n to p r o -

l o n g t h e d u r a t i o n of e p i d u r a l b l o c k a n d to r e d u c e t h e p o t e n t i a l for s y s t e m i c t o x i c i t y a f t e r a b s o r p t i o n of t h e local a n e s t h e t i c i n t o t h e g e n e r a l c i r c u l a t i o n ( 1 - 5 ) . It h a s also b e e n b e l i e v e d t h a t t h e a d d i t i o n of e p i n e p h r i n e i m p r o v e s t h e q u a l i t y a n d i n t e n s i t y of e p i d u r a l a n e s t h e s i a (6,7). T h e effects of e p i n e p h r i n e on motor block have been investigated widely; h o w e v e r , little is k n o w n a b o u t t h e effects o n s e n s o r y b l o c k , p r o b a b l y b e c a u s e of a l a c k of a p p r o p r i a t e and reproducible sensory measurements. Recent advances allow quantitative measurement of t h e f u n c t i o n a l i n t e g r i t y of b o t h large a n d s m a l l d i a m e t e r s e n s o r y n e r v e fibers u s i n g a c u t a n e o u s

From the Department of Anesthesiology, Shimane Medical University, Izumo City, Japan. Accepted for publication July 7, 1999. Supported by Grant No. 10770754 from the Ministry of Education, Science, and Culture of Japan. Presented in part at the Annual Meeting of the American Society of Anesthesiologists, Orlando, Florida, October 17-21, 1998. Reprint requests: Shinichi Sakura, M.D., Department of Anesthesiology, Shimane Medical University, 89-1 Enya-cho, Izumo City 693-8501, Japan. Copyright © 1999 by the American Society of Regional Anesthesia. I098-7339/99/2406-001255.00/0

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current perception threshold (CPT) quantitative sensory testing device (8,9). CPT is defined as the minimum amount of current applied transcutaneously that an individual consciously perceives. Using this device, we have demonstrated that dose and concentration of lidocaine administered for lumbar epidural anesthesia affected the intensity of sensory block of nerve fibers of different sizes (10,11). The present study was performed to examine the effects of the addition of epinephrine to lidocaine on the quality of sensory block during lumbar epidural anesthesia selectively and quantitatively.

Methods After receiving institutional review board approval and written informed consent from each patient, we studied 20 unpremedicated ASA Physical Status I patients presenting for elective gynecologic surgery. None of the patients was taking regular medications or had evidence of neurologic disease. The study was performed in a quiet room on the day ot surgery prior to the surgical procedure. Noninvasive arterial blood pressure, heart rate, and pulse o x imetr y were m o n i t o r e d continuously throughout the study. After local anesthesia with 0.1 mL 1% lidocaine, an intravenous infusion of acetated Ringer's solution was started in a hand or forearm vein at a rate of 10 mL/kg/h. Patients were then placed in the left lateral decubitus position, and the skin, subcutaneous tissue, and supraspinous ligament at the L1-L2 vertebral interspace were anesthetized with 2 mL 1% lidocaine. The epidural space was identified using an 18-gauge Tuohy needle with the bevel directed cephalad via the midline approach, and an epidural catheter (Portex) was advanced 5 cm into the epidural space. The catheter was aspirated to minimize the possibility of intrathecal or intravenous placement and then secured. The patient was then returned to the supine position. Patients were trained to perceive perception thresholds to transcutaneous constant sine wave electrical currents at 2,000, 250, and 5 Hz with a commercially available device (Neurometer CPT, Neurotron, Inc., Baltimore, MD) before the baseline measurements began. The current was delivered to the skin by a pair of 1 cm diameter gold surface electrodes that were separated by 1.7 cm with a clear Mylar spreader (Neurotron, Inc., Baltimore, MD). The stimulating surface of each electrode was covered by a thin layer of electroconductive gel. CPT testing was performed at the trigeminal (V; in front of the ear), ninth thoracic (T9; above umbilicus on

the anterior axillary line), and second lumbar (L2; above knee) dermatomes, on the left side using the rapid screening procedure. Perception thresholds at each frequency were determined by stepwise increasing the current (controlled by the device) to a m axi m um of 9.99 mA (cut-off) until the patient reported sensation. The current was terminated and then repeated. The procedure for all three frequencies at all the test sites required approximately 4-5 minutes. Patients were randomly divided into two equal groups to receive 10 mL 1% lidocaine with (group E) or without (group P) epinephrine 1:200,000. After baseline measurements were obtained, patients were given the local anesthetic through the epidural catheter, and the CPT and the upper dermatomal levels of block of light touch, temperature and pinprick discrimination were measured every 5 minutes, until 60 minutes after the epidural lidocaine by an investigator blinded to the local anesthetic solution injected. The dull, hinged end of a sterile safety pin was used to examine light touch, an alcohol-soaked swab for temperature, and the sharp tip ot a safety pin for pinprick. Loss of each sensory modality was determined by the patient's verbal response to the stimulus applied to the left anterior axillary line starting caudad and moving cephalad. Results are expressed as m ean +_ SD unless otherwise stated. CPT data were converted to percent m axi m um possible effect (%MPE), calculated as [(CPT value-baseline)/(cut-off-baseline)] × 100. Thereafter, area under the time-effect curve (AUC) at all three frequencies at all test sites of each subject was calculated by accumulating the effect (%MPE) for 60 minutes using the trapezoidal integration method. Significant increases in %MPE above baseline values were determined by calculating 95% confidence intervals for mean differences between values obtained before versus after epidural lidocaine. Differences in AUC between the groups were analyzed using the Mann-Whitney U test. Other continuous variables were analyzed using repeatedmeasures analysis of variance (ANOVA). The maxim u m levels of sensory blocks were compared between the groups and among the three modalities in each group using the Mann-Whitney U test and the Friedman test, followed by the Wilcoxon's signed rank test with Bonferroni's adjustment w h e n appropriate, respectively. In addition, differences in the time course of dermatomal level of analgesia to pinprick between the two solutions were assessed with repeated-measures ANOVA. P < .05 was considered significant.

Epidural Lidocaine and Epinephrine

Results Patient characteristics and baseline CPT did not differ b e t w e e n the two study groups (Table 1). All patients had CPT values within n o r m a l range before the epidural administration of lidocaine solutions. Neither solution had any effect o n CPT at cranial nerve V. Time course of effect of epidural block on CPT at T9 and L2 is displayed in Fig. 1. After epidural administration of lidocaine with epinephrine, all CPT significantly increased at T9 and L2, whereas no increase was detected after epidural plain lidocaine. Patients in group E t e n d e d to develop greater increases in CPT t h a n those in group P at T9, and statistical significance was achieved in AUC at 2,000 and 250 Hz. There were n o differences in the maximal d e r m a t o m a l levels of loss of cold, pinprick and t o u c h sensations b e t w e e n the two groups (Fig. 2). Maximal level of loss of touch sensation was significantly lower t h a n that of cold and pinprick sensation in both groups. In addition, the two solutions produced similar time course of dermatomal level of analgesia to pinprick (Fig. 3). No significant changes were observed in arterial blood pressure, heart rate, or pulse oximetry after epidural block with either lidocaine solution. After completion of the study, all patients were given 10-15 mL 2% mepivacaine which p r o d u c e d satisfactory anesthesia for surgery.

Discussion The addition of epinephrine intensified sensory block during lumbar epidural anesthesia with lidoT a b l e 1. P a t i e n t C h a r a c t e r i s t i c s a n d B a s e l i n e C u r r e n t P e r c e p t i o n T h r e s h o l d s for E a c h Site Tested

Age (y) Weight (kg) Height (cm) Baseline CPT (mA) Trigeminal 2,000 Hz 250 Hz 5 Hz Th9 (above umbilicus) 2,000 Hz 250Hz 5 Hz L2 (above knee) 2,000 Hz 250 Hz 5 Hz

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45 _+ 4 51 ± 4 157 -4- 5

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1.037 ± 0.383 0.298 + 0.168 0.196 ± 0.144

1.131 _+ 0.362 0.244 ± 0.149 0.158 _+ 0.121

1.297 ± 0.385 0.312 ± 0.107 0.215 _+ 0.115

1.087 _+ 0.372 0.253 _+ 0.141 0.163 ± 0.107

0.868 ± 0.216 0.298 ± 0.057 0.146 +_ 0.080

0.679 ± 0.247 0.235 ± 0.126 0.163 ± 0.103

Data are m e a n ± SD. No significant differences were observed b e t w e e n groups. Patients in groups E and P received 10 mL 1% lidocaine with and w i t h o u t epinephrine, respectively. CPT, current perception threshold.

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caine. Despite no differences in the extent of sensory block to cold, pinprick, and t o u c h b e t w e e n the two solutions, lidocaine with epinephrine p r o d u c e d a more intense sensory block t h a n lidocaine alone, with all CPT values at T9 and L2 increasing significantly after the former solution but not after the latter one. These results provide further evidence that co-administration of a vasoconstrictor improves the quality of epidural anesthesia. Although the effects of adding epinephrine to local anesthetic agents for epidural anesthesia have b e e n studied widely, to our knowledge this is the first comparative study investigating its effects on the intensity of sensory block. In previous studies, the quality of epidural block has only b e e n assessed with rate of onset and duration and degree of m o t o r block (6,7,12,13). For example, Bromage et al. (6) found that epinephrine doubled the duration, trebled the intensity of m o t o r block, and irregularly affected latency of onset of sensory block during epidural anesthesia with 1-5% lidocaine. M u r p h y et al. (7) s h o w e d that the addition of epinephrine to 1% etidocaine significantly shortened the onset time for sensory and m o t o r block and that there was a greater length of time until t w o - s e g m e n t regression of sensory block and a more p r o f o u n d and longerlasting m o t o r block with an epinephrine-containing 2 % lidocaine solution. Recently, it has b e c o m e possible to perform quantitative m e a s u r e m e n t of the functional integrity of sensory nerve fibers using CPT testing (8,9). The electrical stimulus selectively excites distinct subpopulations of nerve fibers as a function of the sinusoid frequency. Correlation b e t w e e n lowf r e q u e n c y stimulation and activation of small nerve fibers and that b e t w e e n higher f r e q u e n c y stimulation and activation of large nerve fibers have been demonstrated with thermal perception threshold testing and quantitative vibration testing, respectively (14). In the present study, patients given lidocaine with epinephrine developed significant increases in all CPT values at T9 and L2, whereas no significant alteration in CPT values was detected in those given lidocaine alone. In addition, significant differences were observed in AUC for CPT values at 2000 and 250 Hz at T9 b e t w e e n the two solutions. Thus, it appears that the addition of epinephrine to 1% lidocaine increases intensity of sensory block of b o t h small and large diameter nerve fibers during lumbar epidural anesthesia. It is generally t h o u g h t that a vasoconstrictor decreases local blood flow, slowing the systemic absorption of local anesthetic agents and allowing more anesthetic molecules to diffuse to the nerve m e m b r a n e t h a n w i t h o u t added vasoconstrictive

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Fig. 1. Time course of effect of epidural block using 10 mL 1% lidocaine with (group E) or without (group P) epinephrine on current perception thresholds (CPT) at T9 and L2. The current perception threshold neurometer selectively stimulates A-beta, A-delta, and C-fibers using a 2000-, 250-, and 5-Hz stimulus, respectively. Current perception threshold values are expressed as percent m a x i m u m possible effect (%MPE), where %MPE = [(CPT v a l u e - baseline)/ (cutoff - baseline)] × 100. Data reflect the m e a n + SE. Area u n d e r the curve was calculated to perform statistical analysis between groups. *Significant increase from baseline (P < .05). l-Significant difference from group P (P < .05).

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Fig. 2. Maximal cephalad spread of epidural block using I0 mL of I% lidocaine with (group E) or without (group P) epinephrine as determined by loss of sensation to cold, pinprick, and touch (n = 10). Boxplot displays median and 10th, 25th, 75th, and 90th percentiles for values. *Significant difference from cold or pinprick sensation

(P< .o5). (15). Thus, it w o u l d be logical to predict that added e p i n e p h r i n e e n h a n c e s the block of sensory n e r v e fibers during epidural anesthesia in the p r e s e n t study. In addition, e p i n e p h r i n e m a y intensify analgesia by stimulating a l p h a - 2 - a d r e n e r g i c receptors in the dorsal h o r n of the spinal cord, exerting an antinociceptive effect t h r o u g h the spinal descending inhibitory p a t h w a y w h i c h is m o d u l a t i n g sensory processing (16). Published data regarding the effect of e p i n e p h r i n e o n the e x t e n t of sensory block are conflicting (6,7,17). In the p r e s e n t study, no differences w e r e

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f o u n d b e t w e e n the two solutions in the spread of loss of three sensory modalities. However, because of the small n u m b e r of patients studied, statistical p o w e r m i g h t h a v e b e e n insufficient to detect a significant difference in the variables, in w h i c h wide individual variability is c o m m o n l y observed. Neither m o t o r block n o r caudal sensory levels w e r e e x a m i n e d in the present study. Because w e p e r f o r m e d sensory m e a s u r e m e n t s e v e r y 5 minutes, there was little time left after the e x a m i n a t i o n of CPT a n d u p p e r d e r m a t o m a l levels of block to light touch, t e m p e r a t u r e , and pinprick discrimination at each time point. The duration of sensory block was not evaluated in this study. Because w e p e r f o r m e d m e a s u r e m e n t s only until 60 m i n u t e s after epidural lidocaine, time to t w o - s e g m e n t regression was not obtained f r o m all patients. However, it is interesting to note that there was a trend t o w a r d m o r e p r o l o n g e d elevation of %MPE for CPT values at L2 w i t h the e p i n e p h r i n e containing solution (Fig. 1). We only e x a m i n e d one local anesthetic a n d thus the e n h a n c e m e n t of sensory block b y e p i n e p h r i n e m a y n o t apply to other c o m m o n l y used local anesthetics (18). We conclude that l u m b a r epidural anesthesia using 10 m L 1% lidocaine w i t h e p i n e p h r i n e produces m o r e intense block of b o t h large a n d small d i a m e t e r sensory n e r v e fibers t h a n that w i t h plain lidocaine. Therefore, it appears that the addition of e p i n e p h r i n e i m p r o v e s the quality of sensory block during epidural anesthesia w i t h lidocaine.

References

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Fig. 3. Time course of dermatomal level of loss of pinprick sensation after epidural block using 10 mL 1% lidocaine with (group E) or without (group P) epinephrine. Data reflect the mean -SE. No significant difference was observed between groups.

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