Comparison of 1% and 2% lidocaine epidural anaesthesia combined with sevoflurane general anaesthesia utilizing a constant bispectral index

A. Shono, S. Sakura*, Y. Saito, K. Doi and T. Nakatani

Department of Anesthesiology, Shimane Medical University, 89–1 Enya-cho, Izumo City 693–8501, Japan

*Corresponding author. E-mail: ssakura@med.shimane-u.ac.jp

Accepted for publication: May 9, 2003


    Abstract
 Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
Background. The authors compared the effects of epidural anaesthesia with lidocaine 1% and lidocaine 2% on haemodynamic variables, sevoflurane requirements, and stress hormone responses during surgery under combined epidural/general anaesthesia with bispectral index score (BIS) kept within the range 40–50.

Methods. Thirty-three patients undergoing lower abdominal surgery were randomly divided into two groups to receive lidocaine 1% or 2% by epidural with sevoflurane general anaesthesia. Sevoflurane was adjusted to achieve a target BIS of 40–50 during maintenance of anaesthesia with nitrous oxide 60% in oxygen. Measurements included the inspired (FISEVO) and the end-tidal sevoflurane concentrations (E'SEVO), blood pressure (BP), and heart rate (HR) before surgery and every 5 min during surgery for 2 h. Plasma samples were taken immediately before and during surgery for measurements of catecholamines, cortisol, and lidocaine.

Results. During surgery, both groups were similar for HR, BP and BIS, but FISEVO and E'SEVO were significantly higher and more variable with lidocaine 1% than with 2%. Intraoperative plasma concentrations of epinephrine and cortisol were found to be higher with lidocaine 1% as compared with 2%.

Conclusions. To maintain BIS of 40–50 during combined epidural/general anaesthesia for lower abdominal surgery, sevoflurane concentrations were lower and less variable with lidocaine 2% than with 1%. In addition, the larger concentration of lidocaine suppressed the stress hormone responses better.

Br J Anaesth 2003; 91: 825–9

Keywords: anaesthesia, general; anaesthetic techniques, epidural; anaesthetics local, lidocaine; anaesthetics volatile, sevoflurane; monitoring, bispectral index


    Introduction
 Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
Combined epidural/general anaesthesia technique has widely been used in major abdominal and thoracic surgery for decades. Our clinical experience has shown that there are less general anaesthetic requirements when the two techniques are provided simultaneously. Theoretically, epidural anaesthesia blocks the nociceptive input originating from the surgical site to some degree. In addition, the results of a recent clinical study1 indicate that neuraxial anaesthesia has a supraspinal effect that suppresses the level of consciousness. In our clinical practice, however, the ratio of the two techniques has been arbitrarily determined: varying concentrations of local anaesthetic are used, and general anaesthesia is administered empirically or based on cardiovascular responses during surgery without knowing the depth of anaesthesia. In the literature, the optimal combinations of the two techniques have never been explored. Nor have the concentrations of local anaesthetic for epidural during combined epidural/general anaesthesia been adequately compared.

The bispectral index score (BIS) has recently been introduced as an estimation of anaesthetic effect. According to the results of previous clinical studies,2 3 despite being independent of anaesthetic used, BIS score could indicate adequate depth of anaesthesia during surgery.

In the present study, we compared the effects of epidural anaesthesia using lidocaine 1% and 2% on haemodynamic variables, stress hormone responses, and sevoflurane concentration during surgery under combined epidural/general anaesthesia utilizing a BIS within the range 40–50. Lidocaine was chosen because of its popular use for epidural anaesthesia during surgery in our institution and previous clinical studies.47


    Methods
 Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
After institutional review board approval and written informed consent, we studied 33 patients classified as ASA physical status I or II undergoing elective surgery on the lower abdomen lasting more than 2 h. Patients who were taking regular medications or had a history of major back problems, coagulation abnormality, or neurological disease were excluded.

Atropine 0.005–0.01 mg kg–1 was given i.m. approximately 1 h before anaesthesia. All patients fasted for ~8 h and received no intravascular volume loading before entering an operating room, where an i.v. infusion of Ringer’s acetate solution was initiated at a rate of 10 ml kg–1 h–1. They were placed in the left lateral decubitus position, the skin, subcutaneous tissue, and supraspinous ligament were anaesthetized with 2 ml of mepivacaine 1%. The epidural space was identified with an 18-gauge Tuohy needle with the bevel directed cephalad via the midline approach in the T11–L3 vertebral interspace, and a catheter (Portex) advanced 5 cm into the epidural space. The catheter was aspirated to exclude intrathecal or i.v. placement and then secured. The patient was then returned to the supine position.

All patients were randomly divided into two groups using a random number table to receive epidural lidocaine 1% (Group 1) or 2% (Group 2) with sevoflurane general anaesthesia. They received a 10 ml bolus injection of either concentration of lidocaine followed by the same solution at a rate of 10 ml h–1 through the epidural catheter. Fifteen minutes after the injection, the dermatomal level of block of light touch, temperature, and pinprick discrimination was evaluated with the dull, hinged end of a safety pin, an alcohol-soaked swab, and the sharp tip of a safety pin, respectively. Monitoring included noninvasive arterial blood pressure (BP), heart rate (HR), pulse oximetry, BIS, end-expired carbon dioxide, and inspired (FISEVO) and end-expired (E'SEVO) sevoflurane concentrations. After a face mask was applied to achieve a tight seal, general anaesthesia was induced using tidal-breathing technique with sevoflurane 5% and nitrous oxide 60% in oxygen. Endotracheal intubation was facilitated with vecuronium 0.15 mg kg–1. During maintenance of anaesthesia, all the patients received vecuronium for neuromuscular block and were mechanically ventilated to maintain end-tidal carbon dioxide between 35 and 40 mm Hg. Sevoflurane levels were adjusted to achieve a target BIS of 40–50. I.V. fluid infusion was at the discretion of the anaesthetist caring for the patient. Hypotension was treated with 5 mg ephedrine i.v. if systolic arterial pressure decreased by >25% of the pre-anaesthetic value. At the completion of surgery, inhalation anaesthetics were discontinued and residual neuromuscular block was antagonized with atropine 1.0 mg and neostigmine 2.5 mg. All the anaesthetic procedures were conducted by an anaesthetist who was blinded to the local anaesthetic solution injected and told to change FISEVO only on the basis of changes in BIS.

Systolic BP (SBP), HR, and BIS were recorded by an independent investigator who was also blinded to the study group before epidural anaesthesia, before surgery, every 5 min for the first 2 h during surgery, and after the completion of surgery until endotracheal extubation. So were FISEVO and E'SEVO except for the time point before induction. Times from start of induction to loss of eyelash reflex (T1) and dropping of a 50 ml syringe held between the thumb and fingertips (T2), as well as times from end of surgery to return of gag reflex (T3) and handshake on verbal command (T4) were also measured. Plasma samples were taken immediately before, and 1 and 2 h after the start of surgery for measurements of catecholamines, cortisol, and lidocaine. Catecholamines were analysed by high performance liquid chromatography (intra- and inter-assay variations of the method, as expressed by coefficient of variation, were 1.4 and 2.7%, respectively); cortisol was determined by radioimmunoassay (intra- and inter-assay variations were 2.8 and 5.6%, respectively); lidocaine, fluorescence polarization immunoassay (coefficient of variation was <5% with controls of 1.55, 3.03, and 7.55 µg ml–1).

Statistical analysis
Sample size was determined by a power analysis based on the variability observed in our pilot study (SD 0.2%) and the ability to detect a difference in FISEVO of 0.25% with beta set at 0.2 and alpha set at 0.05. A minimal sample of 24 patients (12 in each group) met these criteria. Results are expressed as mean (SD) unless otherwise stated. SBP, HR, FISEVO, E'SEVO, and BIS values recorded every 5 min for the first 2 h during surgery were averaged to provide overall means as summary statistics. Changes in SBP, HR, FISEVO, E'SEVO, and BIS were calculated from the absolute values of the changes in corresponding values every 5 min. Patient characteristics and anaesthetic data in both groups were compared using Student’s t-test and {chi}2-test, as appropriate. Mean and change in SBP, HR, FISEVO, E'SEVO, and BIS were analysed using Student’s t-test, and the Mann–Whitney test was used to determine differences in the maximum level of sensory blocks between groups. Plasma concentrations of catecholamines, cortisol, and lidocaine were analysed using repeated-measures analysis of variance and Dunnett’s test or Student’s t-tests for post hoc testing. P<0.05 was considered statistically significant.


    Results
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 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
Patient characteristics and surgical procedures performed were similar in the two study groups (Table 1). Epidural anaesthesia using both lidocaine solutions, which were injected at similar epidural sites, produced a demonstrable block in every patient (Table 2). The upper levels of sensory block to cold and pinprick 15 min after the bolus injection were similar in the two groups, whereas lidocaine 2% produced a significantly higher level of loss of touch sensation. The volumes of i.v. fluid and blood loss for the first 2 h were similar in the two groups, which also showed similar SBP, HR, and BIS before epidural anaesthesia.


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Table 1 Patient characteristics and surgical procedures. Data are presented as mean (SD or range) or absolute number. There were no statistical differences between two groups
 

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Table 2 Perioperative data. Data are presented as mean (SD), absolute number or median (10th, 90th percentiles). I.V. fluid and blood loss represent the values for the first 2 h during surgery. Baseline SBP=systolic blood pressure before epidural anaesthesia; baseline HR=heart rate before epidural anaesthesia; baseline BIS=bispectral index before epidural anaesthesia. *P<0.05 between two groups
 
Two groups were similar for the timings of special events for induction including T1 or T2 (Table 3). During surgery, both groups were similar for both mean and change per 5 min in BIS, SBP and HR, but mean and change per 5 min in FISEVO and E'SEVO were significantly higher and larger, respectively, in Group 1 than in Group 2 (Table 4). Plasma lidocaine concentration was significantly higher in Group 2 than in Group 1 (Fig. 1). Plasma epinephrine and cortisol in Group 1 were significantly increased during surgery and became significantly higher than those in Group 2 (Fig. 2). Plasma norepinephrine and dopamine concentrations were similar in the two groups.


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Table 3 Anaesthetic induction and recovery. Data are presented as mean (SD). T1, time from start of induction to loss of eyelash reflex; T2, from start of induction to drop a syringe; T3, time from end of surgery to return of gag reflex; and T4, time from end of surgery to handshake on verbal command. There were no differences between two groups
 

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Table 4 BIS, FISEVO and E'SEVO, SBP, HR and dose of ephedrine during surgery. Data are presented as mean (SD). Mean BIS, FISEVO, E'SEVO, SBP, and HR reflect the average of corresponding values recorded every 5 min for the first 2 h during surgery. Changes in BIS, FISEVO, E'SEVO and SBP were calculated from the absolute values of the changes in respective values every 5 min. *P<0.05 between groups
 


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Fig 1 Plasma lidocaine concentration immediately before, 1 and 2 h after the start of surgery in patients given lidocaine 1% and 2%. Data are presented as mean (SD). *P<0.05 vs lidocaine 1%. #P<0.05 vs before surgery and lidocaine 1%.

 


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Fig 2 Plasma concentrations of (A) epinephrine and (B) cortisol. Data are presented as mean (SD). *P<0.05 vs before surgery and lidocaine 2%.

 
After completion of surgery, BIS gradually returned to baseline values in both groups similarly. The timings of special events for recovery from general anaesthesia, as shown in T3 and T4, were similar in the two groups (Table 3).


    Discussion
 Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
To the best of our knowledge, this is the first study to examine the effects of epidural anaesthesia on haemodynamics, stress hormone responses, and sevoflurane requirements during surgery. A recent study1 demonstrated that lidocaine epidural anaesthesia reduced the minimum alveolar concentration (MAC) of sevoflurane from 1.18% to 0.52%, which they speculated was attributable to indirect central effects of spinal deafferentation. However, they only assessed the MAC by applying a tetanic electrical stimulation to the fifth cervical dermatome that was cephalad to the upper level of epidural anaesthesia and, thus, did not reveal the sevoflurane sparing effect on stimulation where the surgical procedure was being performed. They subsequently found that lidocaine epidural anaesthesia decreased the general anaesthetic requirements to produce a BIS value <50 by 35%.4 However, they assessed the values before starting the operation and, thus, did not reveal the sevoflurane sparing effect when the surgical stimulation was being applied.

Although previous researchers have sought to determine the effects of epidural anaesthesia on BIS during surgery, their results appear to be inconclusive and differ from ours. For example, Casati and colleagues8 demonstrated that epidural bupivacaine and fentanyl decreased insoflurane requirements during combined general/epidural anaesthesia for colon resection. However, since fentanyl alone should decrease the anaesthetic requirement, the effects of epidural bupivacaine were obscure. Hans and colleagues9 found that epidural anaesthesia did not affect BIS during desflurane anaesthesia. However, they enrolled patients undergoing lumber disc surgery, which often does not require profound epidural anaesthesia.

The differences in sevoflurane requirements and stress hormone responses observed between epidural lidocaine 1% and 2% are probably attributable to the difference in extent and/or intensity of the block. Although the two lidocaine solutions were similar for upper level of sensory blocks to cold and pinprick before the induction of general anaesthesia, the higher concentration of lidocaine produced a higher level of loss of touch sensation. The two groups differed in dosage and concentration of lidocaine, both of which have been demonstrated to affect the extent and intensity of the epidural block.5 6 10

In the present study, the concentration of sevoflurane was adjusted to obtain a target BIS of 40–50 regardless of other variables. Previous studies2 3 have demonstrated that the BIS is a highly predictive monitor for depth of sedation, and that the probability of responsiveness becomes small at a BIS value of 50 or less. Thus, two groups of patients in the present study appear to have been kept constantly in a similarly adequate depth of anaesthesia throughout surgery.

In our clinical practice, we do not change an inspired anaesthetic concentration only on the basis of BIS values. Thus, the significance of the difference in variability of anaesthetic requirements may be questionable, and less variable sevoflurane concentration with higher concentration of lidocaine may not seem to be an advantage. However, in view of similar changes in SBP and HR during surgery between the two groups, it is likely that the depth of general anaesthesia is more variable with the use of lower concentration of lidocaine in a situation where an anaesthetist provides general anaesthesia relying on haemodynamic values without a BIS monitor.

Possible criticisms of the study include the fact that the dosage of lidocaine administered in the two groups differed. Thus, as observed in the plasma concentration of lidocaine, the differences in effects between the groups might have been associated with a difference in the systemic effects of lidocaine. However, the results of a study by Hodgson and colleagues1 showed that the MAC sparing was not caused by systemic effects of lidocaine. Another group of researchers11 found that i.v. lidocaine resulting in a plasma concentration of lidocaine twice that associated with epidural administration did not affect the recovery time. Thus, it is unlikely that the addition of i.v. lidocaine to a group of patients given epidural lidocaine 1% would have led to different conclusions.

As previous studies have shown that epidural lidocaine 3 mg kg–1 shortens induction with sevoflurane7 and delays arousal from isoflurane anestheisia,11 our finding that the two groups were similar for both induction and recovery times was surprising. However, although the mechanism is not clear, the present results favour the use of higher concentrations of local anaesthetic solutions.


    References
 Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
1 Hodgson PS, Liu SS, Gras TW. Does epidural anesthesia have general anesthetic effects? A prospective, randomized, double-blind, placebo-controlled trial. Anesthesiology 1999; 91: 1687–92[ISI][Medline]

2 Glass PSA, Bloom M, Kearse LAJ, Rosow CE, Sebel PS, Manberg P. Bispectral analysis measures sedation and memory effects of propofol, midazolam, isoflurane, and alfentanil in healthy volunteers. Anesthesiology 1997; 86: 836–47[ISI][Medline]

3 Katoh T, Suzuki A, Ikeda K. Electroencephalograhic derivatives as a tool for predicting the depth of sedation and anesthesia induced by sevoflurane. Anesthesiology 1998; 88: 642–50[ISI][Medline]

4 Hodgson PS, Liu SS. Epidural lidocaine decreases sevoflurane requirement for adequate depth of anesthesia as measured by the Bispectral Index monitor. Anesthesiology 2001; 94: 799–803[ISI][Medline]

5 Sakura S, Sumi M, Yamada Y, Saito Y, Kosaka Y. Quantitative and selective assessment of sensory block during lumbar epidural anaesthesia with 1% or 2% lidocaine. Br J Anaesth 1998; 81: 718–22[Abstract/Free Full Text]

6 Sakura S, Sumi M, Kushizaki H, Saito Y, Kosaka Y. Concentration of lidocaine affects intensity of sensory block during lumbar epidural anesthesia. Anesth Analg 1999; 88: 123–7[Abstract/Free Full Text]

7 Nakatani T, Kushizaki H, Doi K, Sakura S, Saito Y. The influence of epidural anesthesia on the inhalation induction with sevoflurane. Anesthesiology 2001; 93: A294

8 Casati L, Fernandez-Galinski S, Barrera E, Pol O, Puig MM. Isoflurane requirements during combined general/epidural anesthesia for major abdominal surgery. Anesth Analg 2002; 94: 1331–7[Abstract/Free Full Text]

9 Hans P, Lecoq JP, Brichant JF, Dewandre PY, Lamy M. Effect of epidural bupivacaine on the relationship between the bispectral index and end-expiratory concentrations of desflurane. Anaesthesia 1999; 54: 899–908[CrossRef][ISI][Medline]

10 Liu SS, Ware PD, Rajendran S. Effects of concentration and volume of 2-chloroprocaine on epidural anesthesia in volunteers. Anesthesiology 1997; 86: 1288–93[CrossRef][ISI][Medline]

11 Inagaki Y, Mashimo T, Kuzukawa A, Tsuda Y, Yoshiya I. Epidural lidocaine delays arousal from isoflurane anesthesia. Anesth Analg 1994; 79: 368–72[Abstract]





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