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Anesth Analg 2002;94:1331-1337
© 2002 International Anesthesia Research Society

REGIONAL ANESTHESIA

Isoflurane Requirements During Combined General/Epidural Anesthesia for Major Abdominal Surgery

Luis Casati, MD PhD, Susana Fernández-Galinski, MD PhD, DEAA, Enriqueta Barrera, MD, Olga Pol, PhD, and Margarita M. Puig, MD PhD, DABA

Department of Anesthesiology, Hospital Universitario del Mar, Universidad Autonóma de Barcelona, Barcelona, Spain

Address correspondence and reprint requests to Dr. Margarita M. Puig, Professor and Vice-Chair, Department of Anesthesiology, Hospital Universitario del Mar, Paseo Marítimo 25, 08003 Barcelona, Spain. Address e-mail to MPuigR{at}imas.imim.es


   Abstract
Top
 Abstract
Introduction
 Methods
 Results
 Discussion
 References
 
We evaluated the effects of bupivacaine on the requirements for thiopental and isoflurane during combined general/epidural anesthesia. Sixty patients scheduled for colon resection were randomly distributed into six groups that received, before the induction of anesthesia, an epidural (T9-10) bolus (8 mL) followed by an infusion (8 mL/h) of saline (Groups 1 and 4), bupivacaine 0.0625% plus fentanyl 2 µg/mL (Groups 2 and 5), or bupivacaine 0.125% plus fentanyl 2 µg/mL (Groups 3 and 6). We evaluated the amount of thiopental needed to abolish the eyelid reflex and the percentage of isoflurane required to maintain the bispectral index (BIS) between 50 and 60 (Groups 1–3) or the mean arterial blood pressure (MAP) within 20% of basal values (Groups 4–6). All groups required similar doses of thiopental (5 mg/kg); the time of evaluation, but not epidural treatment, had a significant effect (P < 0.0001) on BIS and MAP. After tracheal intubation, MAP and BIS increased by 18% and 49%, respectively (P < 0.05). In the bupivacaine groups, isoflurane requirements similarly decreased by 35% (P < 0.03). For BIS and MAP, the epidural treatment (P < 0.02) and type of evaluation (P < 0.03) had a significant effect; MAP was lower (P < 0.05) with 0.125% bupivacaine. We conclude that epidural bupivacaine does not alter the thiopental dose, but it decreases isoflurane requirements by 35%. This study demonstrates that both doses of bupivacaine and fentanyl induce similar isoflurane-sparing effects. However, patients receiving 0.125% bupivacaine showed lower values of MAP when compared with controls, and thus bupivacaine 0.0625% should be favored during combined anesthesia.

IMPLICATIONS: In patients undergoing colon resection under combined anesthesia, isoflurane requirements were assessed by changes in blood pressure or bispectral index. Epidural bupivacaine at concentrations of 0.125% or 0.0625% (each with 2 mg/mL of fentanyl) induced the same sparing of isoflurane (35%). The smaller dose produced less hypotension and should be favored.


   Introduction
Top
 Abstract
 Introduction
Methods
 Results
 Discussion
 References
 
The simultaneous administration of epidural local anesthetics (LA) with general anesthetics (IV or inhaled) is frequently used in major abdominal or thoracic surgery. During combined general/epidural anesthesia (CGEA), the nociceptive input originating from the surgical site is blocked at the spinal level, reducing the requirements of general anesthetics (1). Proven advantages of CGEA include early recovery from general anesthesia and postoperative analgesia, together with likely decreases in blood loss, cardiac dysrhythmias, or ischemic events and postoperative deep vein thrombosis (2). The side effects of the technique are related to the dose (hypotension) or site (bradycardia and respiratory distress) of the LA administration and to light general anesthesia, which can result in awareness during surgery (3). In many settings, the use of CGEA is increasing because of the favorable recovery characteristics that facilitate early hospital discharge (4).

Recent studies suggest that epidural LA diminishes the requirements of inhaled anesthetics evaluated by the bispectral index (BIS) by a direct effect on the brain, an effect that is not related to plasma levels of the LA (1). Although the BIS is widely used to establish depth of anesthesia, it essentially measures the degree of sedation and does not directly reflect the antinociceptive component of anesthesia; thus, it is possible that at supraspinal sites, epidural LA could have only sedative effects or no effect at all. LAs are often combined with opioids to enhance analgesia and decrease adverse events. In our study we evaluated the anesthetic-sparing effects of LA plus fentanyl at the doses that are routinely used during labor (5) or postoperative analgesia (6). In these circumstances, small doses of LA are adequate because of the characteristics and intensity of the nociceptive stimulus; thus, motor block and cardiovascular instability can be reduced. The effects of small concentrations of LA plus fentanyl on inhaled anesthetic requirements during CGEA have not been evaluated. We hypothesized that by using small concentrations of epidural LA plus fentanyl, we could reduce general anesthetic requirements without cardiovascular depression or residual motor block. Because opioids have an inconsistent effect on the BIS (7), we compared isoflurane requirements when depth of anesthesia was evaluated by the BIS or cardiovascular variables. Postoperative recall when using CGEA was also assessed.


   Methods
Top
 Abstract
 Introduction
 Methods
Results
 Discussion
 References
 
Sixty ASA status II–III patients scheduled for colon resection under CGEA were randomly assigned to one of six groups (Table 1) by using random permutations generated by the Microsoft Excel (Microsoft, Redmond, WA) computer program. The Ethical Committee of our institution approved the protocol, and all patients gave informed consent. Patients with known cardiovascular, neurologic, or metabolic disease, those receiving ß-blockers, and those with a history of drug allergy or abuse were excluded. Premedication consisted of 5 mg of oral diazepam the night before surgery and again on call to the operating room (OR). On arrival at the OR, patients were monitored as usual and received 8 mL/kg of IV lactated Ringer’s solution. An epidural catheter was inserted through a 17-gauge Tuohy needle at T9-10 and advanced 3–4 cm; afterward, a test dose of 3 mL of saline with 1:200,000 epinephrine was administered to exclude intravascular location. With the patients supine, a bolus of 8 mL of one of the epidural solutions was administered in a double-blinded manner. We used three solutions: saline (Groups 1 and 4), bupivacaine 0.0625% plus fentanyl 2 µg/mL (Groups 2 and 5), or bupivacaine 0.125% plus fentanyl 2 µg/mL (Groups 3 and 6). Fifteen minutes later, motor and sensory blocks were assessed by a Bromage scale (0–4) and pinprick.


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  		Table 1. Requirements of Isoflurane (% MEC) in the Different Groups of Study (n = 10 per group)
 
After the BIS electrodes were placed, IV general anesthesia was induced with midazolam (0.04 mg/kg), lidocaine (1 mg/kg), atracurium (0.3 mg/kg), and thiopental. An initial bolus of 3 mg/kg of thiopental was administered to all patients; then incremental doses of 50 mg every 20 s were given until the eyelid reflex was abolished. After endotracheal intubation (ETI), the epidural catheter was connected to an infusion pump that delivered 8 mL/h of the same solution as the bolus. General anesthesia was maintained with oxygen/N2O (40%/60%), isoflurane, and atracurium (0.3 mg · kg-1 · h-1). All patients were mechanically ventilated to an ETCO2 of 32–35 mm Hg. An arterial line was also inserted to obtain mean arterial blood pressure (MAP) and blood gas analysis. Values of MAP during induction were obtained noninvasively, whereas during surgical anesthesia they were registered from the arterial line.

To guarantee an adequate depth of anesthesia at surgical incision, all patients received isoflurane 1.2%–2% (fresh gas flow 5 L/min) for 15 min. Immediately after incision, the isoflurane was turned off and then was administered at the required concentrations to maintain the BIS number between 50 and 60 (Groups 1–3) or the MAP within 20% of preoperative values (Groups 4–6). These end points were achieved by increasing or decreasing the end-tidal isoflurane by 0.2%. If hypotension persisted, a fluid challenge of 300 mL of lactated Ringer’s solution followed by boluses of ephedrine (5 mg) could be administered. Hydralazine was used for the treatment of hypertension. At peritoneal closure, the epidural treatment was stopped and replaced in all groups by an infusion of 0.125% bupivacaine plus 2 µg/mL of fentanyl (5 mL/h), administered to provide postoperative analgesia. The inhaled anesthetics were discontinued on completion of skin closure, and patients were tracheally extubated in the OR.

During surgery, the expired concentrations of isoflurane were monitored every 90–120 s by mass spectrometry. Individual values were sequentially stored on a computer disk and used for calculation of the isoflurane requirements. Results are expressed as percentage mean expired concentration (% MEC) of isoflurane; they are the weighted means of the overall concentrations obtained during surgical anesthesia.

For the purpose of the study, MAP and heart rate (HR) were registered at the following time points: the night before surgery (baseline), on arrival to the OR, just before ETI, and 3 min after ETI. The BIS values were measured at the same time points except on the night before surgery. During surgical anesthesia, MAP, HR, and BIS were registered every 5 min, and the mean values were obtained for the first hour, second hour, and >2 h. Values after tracheal extubation and before leaving the OR were also registered.

Patients and investigators were blinded to the treatment received by the epidural route. The epidural solutions were prepared by a different anesthesiologist, who did not participate in the anesthetic care or evaluation of the patients. When isoflurane requirements were established on the basis of changes in MAP (Groups 4, 5, and 6), the principal investigator was blinded to the BIS number, which was registered by another anesthesiologist. In Groups 1, 2, and 3, anesthetic requirements were titrated to maintain a BIS number between 50 and 60. All patients were visited 72 h after surgery to evaluate intraoperative recall by using the following questionnaire: (1) What is the last event that you remember before going to sleep? (2) What is the first thing that you remember when you woke up? (3) Do you remember anything between these moments? (4) Do you remember having dreams? (5) Were the dreams pleasant?

Statistical analysis was performed with SPSS/PC (SPSS Inc., Chicago, IL). The two main variables of the study were the dose of thiopental needed to abolish the eyelid reflex and the isoflurane required to maintain a BIS of 50–60 (Groups 1–3) or the MAP within 20% of preoperative values (Groups 4–6). For thiopental, we used a one-way analysis of variance (ANOVA) to establish differences between groups, whereas a two-way ANOVA was used to establish the evolution of BIS and MAP over time; to analyze differences between times of evaluation, we used Student’s t-test. Isoflurane requirements were evaluated by a two-way ANOVA: the epidural treatment and the type of evaluation of isoflurane requirements (BIS and MAP). The evolution of the MAP, HR, and BIS during surgical anesthesia was compared by multivariate ANOVA. Intragroup and intergroup evaluations were performed by one-way ANOVA followed by a post hoc Newman-Keuls test. P < 0.05 was considered significant. For the correlations between BIS and MAP, a Pearson test was used. Comparison of demographic data, duration of surgery, and Bromage and sensory testing were established by one-way ANOVA, whereas for qualitative variables we used the {chi}2 test.


   Results
Top
 Abstract
 Introduction
 Methods
 Results
Discussion
 References
 
The groups were comparable regarding demographic data, baseline hemodynamic variables, and the duration of surgery (Table 2). Fifteen minutes after the epidural bolus, no motor block in the lower extremities could be established in any of the groups. The upper level of sensory block was T5 (T4 to T6) in the groups receiving epidural 0.125% bupivacaine (Groups 3 and 6), whereas no definite changes were observed in the groups treated with 0.0625% bupivacaine (Groups 2 and 5) or saline (Groups 1 and 4). Thiopental requirements during induction were approximately 5 mg/kg, without significant differences among groups (Table 3). A two-way ANOVA showed that for BIS and MAP, the time of evaluation, but not the epidural treatment, had a significant effect (P < 0.0001); in all groups, both variables increased after ETI, and most reached statistical significance (P < 0.05; Student’s t-test). Thus, when depth of anesthesia was evaluated by the loss of the eyelid reflex, the epidural treatment did not alter thiopental requirements, MAP, or BIS.


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  		Table 2. Demographic Data and Duration of Surgery
 

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  		Table 3. Thiopental Requirements, Mean Arterial Blood Pressure, and BIS Number During the Induction of General Anesthesia (n = 10 per group)
 
Isoflurane requirements were established by changes in the BIS number (Groups 1–3) or the MAP (Groups 4–6) (Table 1). A two-way ANOVA demonstrated that the epidural treatment (but not the type of evaluation) had a significant effect (P < 0.042) on isoflurane requirements. The similarity of the results when isoflurane requirements were evaluated by MAP or BIS permitted the combination of the groups that received the same epidural treatment (Fig. 1). One-way ANOVA demonstrated significant differences between the saline and bupivacaine groups (P < 0.03), but not between the two bupivacaine groups. When the values (% MEC) of isoflurane evaluated by BIS or MAP were plotted, we obtained a straight line with a correlation coefficient of 0.935 (Fig. 2, upper panel). Thus, epidural LA decreased isoflurane MEC for both LA concentrations and both types of evaluation (BIS or MAP).



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  		Figure 1. Isoflurane requirements (percentage mean expired concentration [% MEC]) when patients were grouped according to epidural treatment. Each point represents mean values of the % MEC of isoflurane, and the vertical lines represent the SEM; n = 20 patients in each group. *P < 0.03 when compared with the Saline group (one-way analysis of variance). Bupi = bupivacaine.

 


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  		Figure 2. Upper panel, Correlation between the values of isoflurane obtained by bispectral index (BIS) or mean arterial blood pressure (MAP) during surgical anesthesia. The line has a correlation coefficient of 0.935. Lower panel, Line derived from plotting the individual values of MAP and BIS in the groups that received epidural saline (Groups 1 and 4). For each variable (BIS and MAP), values obtained during the induction (before and after endotracheal intubation), surgical anesthesia (1, 2, and >2 h), and extubation were plotted (60 values for each group). Thus, 120 points are included in the figure, and the line has a correlation coefficient of 0.85 (Pearson’s correlation coefficient). Bupi = bupivacaine.

 
Table 4 shows the mean values of MAP and BIS during surgery. We used a three-factor multivariate ANOVA, in which the effects of the method of evaluation of isoflurane requirements (BIS and MAP), the epidural treatment (saline, bupivacaine 0.0625%, and bupivacaine 0.125%), and the time (basal, 1 h, 2 h, and >2 h), as well as their interactions, were assessed. For the MAP, we observed an effect of treatment (P < 0.0001) and method of evaluation (P < 0.003) related to decreased MAP in the groups receiving 0.125% bupivacaine at 1 h (P < 0.05, ANOVA and Student-Newman-Keuls) and to overall decreased MAP in the groups evaluated by BIS (1–3).


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  		Table 4. Mean Arterial Blood Pressure and BIS Values Before Surgery (Basal) and During Surgical Anesthesia (n = 10 per group)
 
The analysis of BIS showed a significant effect of treatment (P < 0.024) and method of evaluation (P < 0.017), as well as their interaction (P < 0.029). In Group 6, the BIS was lower during 1 and >2 h of anesthesia (P < 0.05). BIS values were also lower in Groups 1–3. Thus, patients who received epidural 0.125% bupivacaine and those evaluated by BIS showed lower values of MAP. By using the values of MAP and BIS obtained in the OR at each time of evaluation (pre-ETI, post-ETI, 1 h, 2 h, >2 h, and postextubation), we evaluated the correlation between these two variables in each group of study (Groups 1–6). The results show that in all groups, the r2 values were >0.847 (0.847–0.923). Figure 2 (lower panel) shows the line derived from plotting the individual values of MAP and BIS in the groups that received epidural saline (Groups 1 and 4).

The HR remained stable during the study, without significant changes related to treatment, time, or method of evaluation. No differences were observed regarding the number of patients per group who required ephedrine (range, 5–7). A two-way ANOVA showed an effect of the treatment (P < 0.001), but not of the type of evaluation; thus, patients could be grouped according to the epidural treatment. The results show that patients who received saline required significantly less ephedrine (8.37 ± 1.2 mg; P < 0.02) than those in the Small-Dose (16.67 ± 3.2 mg) and Large-Dose (18.0 ± 2.1 mg) bupivacaine groups. On the postoperative visit (72 h after surgery), none of the patients had recall of intraoperative events, and the degree of satisfaction was consistently acceptable.


   Discussion
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
References
 
We evaluated the effects of the epidural administration of small doses of bupivacaine (0.0625% or 0.125%) plus fentanyl (2 µg/mL) on the requirements of general anesthetics (thiopental and isoflurane) in patients undergoing colon resection under CGEA. The protocol allowed for the comparison with a nonactive treatment group (saline), because in all instances our patients received the required doses of anesthetics (thiopental or isoflurane) to provide an adequate depth of anesthesia.

During the induction of anesthesia, requirements for thiopental were similar in all groups, demonstrating that small doses of epidural bupivacaine did not alter depth of anesthesia in the presence of strong nociceptive stimuli (ETI). Thus, the reported general anesthetic effect of epidural LA (1,8) was not observed in our study when depth of anesthesia was evaluated by loss of the eyelid reflex, a territory not blocked by the epidural LA (9). The upper limit of sensory block in our patients never reached above T4 and could be determined only in those patients receiving 0.125% bupivacaine. The divergence between our results and those of Hodgson and Liu (1) could be explained by the method of evaluation of depth of anesthesia, the low doses of LA used, or both of these. During induction, MAP and BIS significantly increased after intubation, by 18% and 49%, respectively, showing a larger increase in the latter. Changes in MAP reflect the neuroendocrine response to pain, which in our patients was for the most part blocked by the induction drugs (thiopental or IV lidocaine). However, the same drugs did not prevent the increase in BIS (arousal), showing that the BIS does not monitor the analgesic component of anesthesia. Although the BIS reached 65 in some of our patients, none had postoperative recall.

During surgical anesthesia, isoflurane requirements in patients receiving bupivacaine were similarly reduced by approximately 35%. The two doses of bupivacaine (0.0625% and 0.125%) had the same efficacy in reducing the % MEC of isoflurane. This, together with lower values of MAP in patients receiving 0.125% bupivacaine, would favor the use of the 0.0625% concentration during CGEA. When plotting the values of BIS and MAP according to isoflurane requirements in each patient, a correlation coefficient of 0.94 was obtained, showing that similar quantities of isoflurane were administered when the requirements were evaluated by either variable.

Our protocol compares two small doses of bupivacaine (0.125% and 0.0625%), each with fentanyl (2 µg/mL), and demonstrates for the first time that very small concentrations of bupivacaine plus fentanyl (0.0625% and 2 µg/mL, respectively) produce the same anesthetic-sparing effect as larger doses of epidural LAs. The results show that this concentration is adequate to induce the maximal anesthetic-sparing effect reported in the literature (approximately 35%), suggesting that this may be the greatest that can be achieved by epidural LA. The work of Hodgson and Liu (1) shows a decrease in sevoflurane requirements of approximately 35% after the administration of a single bolus of 300 mg of lidocaine (15 mL of 2% lidocaine), a dose that could be considered average. The main differences between our work and that of Hodgson and Liu (1) are the type, dose, and mode of the administration of the LA, in addition to the use of 2 µg/mL of fentanyl, as already mentioned. Lidocaine is less potent than bupivacaine (approximately 10:1) and has a shorter duration of action. Regarding the dose, in our study we used a bolus of 5 mg followed by an infusion of 5 mg/h (bupivacaine 0.0625%) or twice as much when testing the effects of bupivacaine 0.125%. Thus, taking into account the potency ratio of the two drugs, we used approximately one to two thirds of the dose of LA used in the Hodgson study. Moreover, we administered a constant epidural infusion of bupivacaine and fentanyl, thus reducing nociceptive input throughout surgery. It is possible that the synergistic interaction between epidural LA and opioids (10) is responsible for the efficacy of the epidural treatments observed in our study. Our results cannot exclude that the spinal analgesia induced by fentanyl is the main critical factor reducing isoflurane requirements. This seems unlikely because small doses of epidural fentanyl by itself have been proven to be inadequate to induce postoperative analgesia, and only its combination with LA is clinically effective (11). However, regardless of the contribution of fentanyl to the antinociceptive effects of the combination, our results show that an infusion of 5 mg/h of bupivacaine 0.0625% plus 2 µg/mL fentanyl induced the same isoflurane-sparing effects as twice the dose of bupivacaine plus 2 µg/mL fentanyl.

Another question that arises is how to properly evaluate the level or depth of anesthesia in clinical practice. There are no simple tools available that can distinctly and independently assess antinociception and hypnosis, because these variables are closely interrelated and the degree of analgesia may affect the level of hypnosis. Thus, in our study we were unable to directly evaluate antinociception and used the requirements of isoflurane (evaluated by BIS or MAP) as an indirect measurement of the depth of anesthesia. We kept the BIS values between 50 and 60 and MAP within 20% from baseline—values that, even if they are not very precise, are those routinely used in clinical practice.

Intraoperatively, changes in the hemodynamic variables and the BIS number were similar in all groups. However, patients who received epidural bupivacaine required two times more ephedrine (P < 0.02), showing that hypotension still occurs even with small doses of LA. The large number of patients (37 of 60) receiving ephedrine in our study could be related to the type of surgery (bowel preparation), to overzealous administration by the investigators, or both.

The correlation between the hemodynamic responses and the BIS remains controversial (12). After ETI, both variables increased, but the BIS experienced greater changes. In the OR we could establish a good correlation (r2 > 0.85) between mean values of MAP and BIS at the different times of evaluation (pre- and post-ETI, one hour, two hours, more than two hours, and postextubation), as well as for isoflurane requirements (r2 > 0.9). Thus, blockade of nociceptive input by LA did not alter the BIS/MAP correlation, because the groups treated with saline showed similar values (r2 = 0.91 and 0.92 for Groups 1 and 4, respectively). Several reports in the literature have shown that the minimum alveolar anesthetic concentration of inhaled anesthetics and anesthetic requirements is significantly reduced when evaluated by BIS, as compared with standard clinical practice (13). However, in this investigation, we could not replicate these results, even in the saline control group that received no LA by the epidural route. We do not have a definite explanation for the discrepancy, although the small doses of inhaled anesthetics required in our study, the careful titration of isoflurane to the preestablished end points, and the administration of muscle relaxants may have been implicated. The isoflurane requirements in patients receiving epidural saline were very small (% MEC = 0.43), a finding previously reported by our group (14). Epidural saline has been claimed to improve labor analgesia (15), but the analgesic effect of epidural saline remains highly controversial (16) and cannot acceptably explain the small concentration of isoflurane required by the control groups in our study. It could be postulated that at small concentrations of inhaled anesthetics, there is a better correlation between BIS and MAP.

Our results show that thoracic epidural bupivacaine plus fentanyl does not alter the requirements of thiopental for ETI when depth of anesthesia is evaluated by the loss of eyelid reflex. However, both concentrations of bupivacaine (0.0625% and 0.125%) similarly decreased the intraoperative requirements of isoflurane by 35%. Patients receiving bupivacaine required two times more ephedrine than controls, but all groups had good hemodynamic stability during the study. From the results we conclude that 0.0625% bupivacaine plus 2 µg/mL of fentanyl is adequate to provide intraoperative analgesia during CGEA.


   Acknowledgments
 
Supported in part by grants from Fundació La Marató de TV3 (2032/98) and Generalitat de Catalunya (1999SGR00244), Barcelona, Spain. Dr. Casati had a fellowship from the Mutis Program, Agencia Española de Cooperación Internacional, Ministerio de Asuntos Exteriores, Madrid, Spain.


   Footnotes
 
Presented in part at the European Society of Anaesthesiologists meeting, Vienna, Austria, April 1–4, 2000.


   References
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 

  1. Hodgson PS, Liu SS. Epidural lidocaine decreases sevoflurane requirements for adequate depth of anesthesia as measured by the bispectral index monitor. Anesthesiology 2001; 94: 799–803.[ISI][Medline]
  2. Rodgers A, Walker N, Schug S, et al. Reduction of postoperative mortality and morbidity with epidural or spinal anaesthesia: results from overview of randomised trials. BMJ 2000; 321: 1–12.[Abstract/Free Full Text]
  3. Domino KB, Posner KL, Caplan RA, Cheney FW. Awareness during anesthesia: a closed claims analysis. Anesthesiology 1999; 90: 1053–61.[ISI][Medline]
  4. Senagore AJ, Whalley D, Delaney CP, et al. Epidural anesthesia-analgesia shortens length of stay after laparoscopic segmental colectomy for benign pathology. Surgery 2001; 129: 672–6.[ISI][Medline]
  5. Fernandez-Guisasola J, Serrano ML, Cobo B, et al. A comparison of 0.0625% bupivacaine with fentanyl and 0.1% ropivacaine with fentanyl for continuous epidural labour analgesia. Anesth Analg 2001; 92: 1261–5.[Abstract/Free Full Text]
  6. Hodgson PS, Liu SS. A comparison of ropivacaine with fentanyl to bupivacaine with fentanyl for postoperative patient-controlled epidural analgesia. Anesth Analg 2001; 92: 1024–8.[Abstract/Free Full Text]
  7. Barr G, Anderson RE, Owall A, Jakobsson JG. Effects on the bispectral index during medium-high dose fentanyl induction with or without propofol supplement. Acta Anaesthesiol Scand 2000; 44: 807–11.[ISI][Medline]
  8. 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]
  9. Licker M, Farinelli C, Klopfenstein CE. Cardiovascular reflexes during anesthesia induction and tracheal intubation in elderly patients: the influence of thoracic epidural anesthesia. J Clin Anesth 1995; 7: 281–7.[ISI][Medline]
  10. Maves TJ, Gebhart GF. Analgesic synergy between intrathecal opioids and local anesthetics. Anesth Analg 1991; 73: 365–6.
  11. Cohen S, Lowenwirt L, Pantuck CB, et al. Bupivacaine 0.01% and/or epinephrine 0.5 microgr/ml improve epidural fentanyl analgesia after cesarean section. Anesthesiology 1998; 89: 1354–61.[ISI][Medline]
  12. Driessen JJ, Harbers JB, van Egmond J, Booij LH. Evaluation of the electroencephalographic bispectral index during fentanyl-midazolam anaesthesia for cardiac surgery: does it predict haemodynamic responses during endotracheal intubation and sternotomy? Eur J Anaesthesiol 1999; 16: 622–7.[ISI][Medline]
  13. Song D, Joshi GP, White PF. Titration of volatile anesthetics using bispectral index facilitates recovery after ambulatory anesthesia. Anesthesiology 1997; 87: 842–8.[ISI][Medline]
  14. Samsó E, Vallés J, Pol O, et al. Comparative assessment of the anaesthetic and analgesic effects of intramuscular and epidural clonidine in humans. Can J Anaesth 1996; 43: 1195–202.[Abstract/Free Full Text]
  15. Beilin Y, Arnold I, Telfeyan C, et al. Quality of analgesia when air versus saline is used for identification of the epidural space in the parturient. Reg Anesth Pain Med 2000; 25: 596–9.[ISI][Medline]
  16. Trautman WJ III, Liu SS, Kopacz DJ. Comparison of lidocaine and saline for epidural top-up during combined spinal-epidural anesthesia. Anesth Analg 1997; 84: 574–7.[Abstract]
Accepted for publication January 14, 2002.




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Lippincott, Williams & Wilkins Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999 HighWire Press