JOURNAL HOME CME HOME THIS MONTH PAST ISSUES ETOC COLLECTIONS
AUTHORS REVIEWERS EDITORIAL BOARD FEEDBACK RSS HELP
A&A International Anesthesia Research Society
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a colleague
Right arrow Similar articles in this journal
Right arrow Similar articles in Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowRequest Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Web of Science (9)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Gaitini, L. A.
Right arrow Articles by Zinder, O.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Gaitini, L. A.
Right arrow Articles by Zinder, O.
Anesth Analg 2000;90:1029-1033
© 2000 International Anesthesia Research Society

PEDIATRIC ANESTHESIA

Does the Addition of Fentanyl to Bupivacaine in Caudal Epidural Block Have an Effect on the Plasma Level of Catecholamines in Children?

L. A. Gaitini, MD*, M. Somri, MD*, S. J. Vaida, MD*, B. Yanovski, MD*, G. Mogilner, MD{dagger}, E. Sabo, MD*, S. Lischinsky, MSc{ddagger}, A. Greenberg, MSc{ddagger}, N. Levy, PhD{ddagger}, and O. Zinder, PhD{ddagger}

Departments of *Anesthesiology and {dagger}Pediatric Surgery, B’nai Zion Medical Center; and {ddagger}Department of Clinical Biochemistry, Rambam Medical Center; and B. Rappaport, Faculty of Medicine, Technion, Haifa, Israel

Address correspondence and reprint requests to L. Gaitini, MD, Director, Department of Anesthesiology, Bnai Zion Medical Center, P.O. Box 4940, 31048, Haifa, Israel. Address e-mail to gaitini{at}netvision.net.il


   Abstract
Top
 Abstract
Introduction
 Methods
 Results
 Discussion
 References
 
We evaluated the effect of adding fentanyl to bupivacaine, compared with bupivacaine alone, on the stress response. The effect was evaluated by determining blood levels of epinephrine (E) and norepinephrine (NE) in pediatric patients receiving caudal epidural blocks. Sixty children, 1–8 yr of age, scheduled for elective herniorrhaphy, were randomly allocated to two groups of 30 patients each. Group A received inhaled anesthesia and caudal epidural block with bupivacaine 0.25% alone, 1.0 mL/kg. Group B received identical anesthesia; however, fentanyl 1 µg/kg was added to the bupivacaine in the caudal block. Blood samples for E and NE plasma levels were drawn at induction time (H0), at the end of surgery (H1), and in the postanesthesia care unit (H2). In both groups, there was a significant decrease in the E and NE plasma levels, when comparing H1 and H2 with H0 within the same group (P < 0.001). There were no significant differences in the E and NE plasma levels between the two groups at H0, H1, and H2 (P = 0.5, P = 0.12, P = 0.5, respectively). Pain scores (modified Children’s Hospital of Eastern Ontario Pain Score) were also similar in both groups (P = 0.19). This study suggests that adding fentanyl 1 µg/kg to bupivacaine in the caudal epidural block in children does not influence plasma levels of E and NE, nor does it improve the analgesic intensity of the caudal block.

Implications: This study demonstrates that adding fentanyl to bupivacaine for caudal epidural blocks has no beneficial effect on the stress response in pediatric patients undergoing inguinal herniorrhaphy, as evaluated by plasma epinephrine and norepinephrine values, compared with bupivacaine alone.


   Introduction
Top
 Abstract
 Introduction
Methods
 Results
 Discussion
 References
 
Caudal epidural analgesia, using either local anesthetic alone or a mixture of local anesthetic with opioids, has been increasingly used in the pediatric population, particularly in lower abdominal surgery (1,2). The combinations of these drugs were used in an attempt to reduce local anesthetic requirements and side effects while improving both the quality and duration of the postoperative analgesic effect of the caudal block. Continuous epidural infusion of fentanyl, alone or in combination with local anesthetics, is effective and safe with the least likelihood of causing respiratory depression in the pediatric population (3). This effect is a result of its high lipid solubility, which makes it less likely to migrate rostrally to the brainstem (4). Previous reports have demonstrated that blood levels of epinephrine (E) and norepinephrine (NE) were decreased by caudal epidural analgesia, using local anesthetics alone, caused by afferent neural blockade (5–7). Furthermore, Breslow et al. (8) found a decrease in the level of catecholamines in adult patients undergoing lower extremity surgery when using an epidural mixture of bupivacaine and fentanyl. Nevertheless, other studies show that epidural opiates are not effective in modulating the intraoperative and postoperative stress responses during upper abdominal surgery, despite the good analgesic effect (9,10). No studies have focused on the effect of adding fentanyl to local anesthetics, in caudal epidural block, on the surgical stress response in pediatric populations.

The present prospective, randomized study was designed to determine if adding fentanyl to bupivacaine, compared with bupivacaine alone in the caudal epidural block, has any effect on plasma E and NE levels as a measure of surgical stress response. In addition, we investigated the analgesic effect of the different compositions of the caudal epidural block, in a pediatric population undergoing inguinal herniorrhaphy.


   Methods
Top
 Abstract
 Introduction
 Methods
Results
 Discussion
 References
 
After approval by our local ethics committee and written parental consent, 60 male pediatric patients, ASA physical status I, between 1 and 8 yr of age, all undergoing elective unilateral herniorrhaphy, were randomly assigned to two groups (Group A = bupivacaine alone and Group B = bupivacaine + fentanyl).

Patients were excluded from the study if they had: a failed block, hemoglobin of less than 11 g%, a history of asthma or allergies, episodes of intraoperative hypothermia (less than 35°C), hypoxia (SaO2 of less than 95%), hypercarbia (CO2 more than 50 mm Hg) or hypoxia, or hypothermia (with or without shivering) in the recovery room.

Failed block was defined when it was necessary to add IV fentanyl, or to increase the concentration of the inhaled anesthetics, in response to a 20% increase for more than 5 min of the systolic blood pressure and/or heart rate from the baseline values.

Group A (n = 30) patients were to have inhaled anesthesia combined with a caudal epidural block in which bupivacaine plain 0.25%, 1.0 mL/kg, was injected. Group B (n = 30) patients received an identical inhaled anesthetic combined with a caudal epidural block in which fentanyl 1.0 µg/kg was added to the bupivacaine 0.25% 1.0 mL/kg with a maximum dose of 25 mL.

Anesthesia was induced with N2O/O2 (50%/50%) and halothane, increasing the concentration by 0.5%, each 3–4 breaths up to 4% by mask. A laryngeal mask airway was inserted after disappearance of the eyelash reflex. End-tidal halothane was maintained in both groups at 1.5% minimal alveolar anesthetic concentration. All children were spontaneously breathing a fresh gas flow of three times the minute volume through a Bain circuit. Manual-assisted ventilation was performed to keep end-tidal CO2 between 30–48 mm Hg. After the child was asleep, and before surgery, he was placed in the lateral position and a 23- or 21-gauge needle inserted into the caudal space through the sacrococcygeal membrane, by using an aseptic and nontouch technique. When the aspiration test was negative, either 1 mL/kg of bupivacaine 0.25% (Group A) or bupivacaine 0.25% 1 mL/kg with fentanyl 1 µg/kg (Group B) was injected. All blocks were performed by the same consultant anesthesiologist. The time elapsed from the caudal epidural injection to the start of surgery was 15–20 min.

No patient was premedicated, and all children were anesthetized in the presence of their parents in a special induction room. No opioids or sedative drugs were given preoperatively.

Heart rate (HR), heart sounds, noninvasive systolic and diastolic blood pressure, SaO2, ETCO2, and temperature were monitored in all patients by using an TMAS/3 monitor (Datex, Engestrom, Finland).

An IV catheter was inserted in an antecubital vein, after application of EMLA® cream (ASTRA, Sodertalge, Sweden), containing lidocaine 25 mg/g and prilocaine 25 mg/g, 1 h before the induction of anesthesia. Patients were fasted for a minimum of 6 h from solid food and milk and 2 h from clear fluid. All children were adequately hydrated by using normal saline solution or lactate Ringer’s solution at a rate of 4–6 mL · kg-1 · h-1 using an infusion pump.

Blood samples of 3 mL for cathecolamine plasma levels were drawn through the venous catheter three times: at the induction time (H0), at the end of surgery (H1), and when an Aldrete recovery score (11) of 10 points was obtained in the postanesthesia care unit (PACU) (H2). All samples were centrifuged immediately for 10 min to separate the plasma and stored at -50°C; the assay was performed by reversed-phase high-performance liquid chromatography with electrochemical detection.

The normal ranges for children up to 15 yr are: E = 20–500 pg/mL and NE = 70–1500 pg/mL (12,13).

After surgery, each patient was transferred to the PACU and observed for 11/2–2 h, followed by 10 h in the surgical ward before discharge.

In the PACU, respiratory rate, SaO2, HR, noninvasive blood pressure, and pain score were reported each 15 min, and the time to first IV injection of fentanyl was recorded by the nursing staff. In the surgical ward, the time to the first supplemental analgesia administered—as well as complications such as respiratory depression (respiratory breathing rate < 12/min), nausea, and vomiting or pruritus—were recorded each half hour.

Postoperative pain was assessed every 15 min in the PACU by using a modified Children’s Hospital of Eastern Ontario Pain Score (mCHEOPS) (14). Patients with a pain score greater than 5 were treated with 1 µg/kg IV fentanyl, in fragmental doses in the PACU or 15 mg/kg of paracetamol on the surgical ward. Postoperative follow up was performed by an anesthesiologist unaware of the patient’s group.

Patients were discharged from the hospital when a score of >=9, according to the modified postanesthesia discharge scoring system, was achieved (15).

Statistical analysis for a comparison between the three phases (H0, H1, and H2) of the study in each group was performed by using the analysis of variance test for repeated measurement, followed by the Bonferroni post hoc test. The unpaired Student’s t-test was used when each phase (H0, H1, and H2) was compared between the two groups. The equality of variances was performed by using the Levene’s test. When no significant differences were obtained, a statistical power analysis was performed. The power was computed based on the results of comparisons between the phases (H0, H1, and H2), as reported in our previous study (4). Statistical significance is assumed when the two-tailed P values were <=0.05.


   Results
Top
 Abstract
 Introduction
 Methods
 Results
Discussion
 References
 
Sixty children undergoing elective unilateral herniorrhaphy were entered in this study and randomly assigned to two groups of 30 patients each. There were no differences in the demographic data (Table 1). No child was excluded from the study.


View this table:
[in this window]
[in a new window]
  		Table 1. Demographic Data, Blood Pressure, Heart Rate, and ETCO2 Values
 
In both groups, there was a significant decrease in the mean values of the plasma E levels and NE plasma levels when comparing H0 with H1 and with H2 (repeated-measure analysis of variance, P < 0.001) (Fig. 1). (H0: E, Group A = 231.9 ± 32.8, Group B = 199.2 ± 40.4; NE, Group A = 593.4 ± 56.2, Group B = 591.3 ± 46.4) (H1: E, Group A = 106.3 ± 12.2, Group B = 80.4 ± 11; NE, Group A = 251.3 ± 23.9, Group B = 252.2 ± 23.2) (H2: E, Group A = 76.7 ± 7.7, Group B = 65.3 ± 11.2, NE, Group A = 254.4 ± 42.5, Group B = 258.4 ± 22.5). All catecholamine data are in pg/mL.



View larger version (23K):
[in this window]
[in a new window]
  		Figure 1. Comparison of mean values of epinephrine (E) and norepinephrine (NE) levels between Groups A and B at the induction time (H0), end of surgery (H1), and in the postanesthesia care unit (H2).

 
The cathecolamines values were well within the normal ranges for H0.

There were no significant differences in the baseline (H0) of E and NE plasma levels between the two groups (P = 0.5, P = 0.9). Also, there were no significant differences in the E plasma levels between the two groups at H1 (P = 0.12) and at H2 (P = 0.5) or in the NE plasma levels between the two groups at H1 (P = 0.9) and H2 (P = 0.9) (Fig. 1). The power of the statistical tests in all the above comparisons was greater than 80%. No statistically significant differences were found in the blood pressure or the HR between the two groups at the three phases of the study (SBP: P = 0.79, P = 0.56, P = 0.77) and (DBP: P = 0.045, P = 0.18, P = 0.72). The P values of the HR at the three phases were (0.25, 0.38, and 0.73) (Table 1).

Pain score using (mCHEOPS) was similar in both groups. No statistically significant differences between the two groups were found regarding either the time of the first IV fentanyl administration or the number of patients who required fentanyl. There were also no significant differences between the two groups regarding the time of the first dose and the number of patients who received paracetamol in the ward (Table 2).


View this table:
[in this window]
[in a new window]
  		Table 2. Timing and Patient Need for Postoperative Analgesia and Pain Score (mCHEOPS)
 
Nausea and/or vomiting was experienced by three patients in Group A and four patients in Group B; they were treated effectively with IV metoclopramide. No child demonstrated respiratory frequency of less than 12 breaths/min. Nasal pruritus occurred in one patient in Group A and two patients in Group B.


   Discussion
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
References
 
For reduction of the stress response as measured by plasma catecholamine levels, we found no advantage of adding 1 µg/kg fentanyl to bupivacaine over bupivacaine alone in the caudal epidural block in infraumbilical surgery in children.

Reduction of the stress response is highly dependent on the surgical site and the analgesic technique used. Caudal epidural analgesia/anesthesia inhibits the stress response, particularly during surgery in the lower part of the body in a pediatric population (16). It has been demonstrated that the addition of caudal block to general anesthesia significantly reduces the neurohormonal response in children undergoing ilioinguinal herniorrhaphy (5).

In contrast, the use of epidural anesthesia for upper abdominal and thoracic surgery failed to prevent the surgical stress response, despite excellent analgesia (17). Epidural morphine did not augment the effectiveness of epidural bupivacaine in suppressing postoperative elevation of cortisol, despite providing good analgesia in thoracic surgery (18). The surgical site may influence the residual afferent nociceptive activity, without conscious perception of pain, although still evoking the surgical stress response.

Our results revealed the same analgesic intensity of the caudal block whether using the mixture of fentanyl and bupivacaine or bupivacaine alone. Campbell et al. (19) had similar results when evaluating the analgesic efficacy and safety of a single caudal injection of bupivacaine 0.125%-epinephrine 1:200,000 with fentanyl 1 µg/kg, compared with bupivacaine 0.125%-epinephrine 1:200,000 in children undergoing elective urological surgery. They found no advantages to the mixture of bupivacaine-epinephrine 1:200,000 with fentanyl over the bupivacaine-epinephrine 1:200,000 without fentanyl, based on the number of patients receiving morphine within eight hours after surgery and the time of the first morphine administration.

Our results also agreed with those of Jones et al. (20), who found in a controlled study that the addition of fentanyl 1 µg/kg to lidocaine 2% placed in the caudal epidural seems to convey no benefit to postoperative analgesia in children who underwent circumcision.

Pain is the main determinant of the early catecholamine response to surgery in the lower extremity (8); however, pain measurement in children is difficult and unreliable. Each of the methods of rating pain has its limitations, particularly in the nonverbal children (20). The mCHEOPS is a valid and reliable method of assessing immediate postoperative pain for the ages of children participating in our study (14). Stress response hormone levels can therefore be used as an objective method to assess the analgesic efficacy of local anesthetics injected into the extradural space before infraumbilical or lower extremity surgery in both adult and pediatric populations.

Rucci et al. (22) reported that a mixture of bupivacaine with fentanyl prolonged the block only when a large dose (3 µg/kg) of fentanyl was used, but not with 1 or 1.5 µg/kg, in extradural block in an adult population. Welchew (23) found that both the intensity and duration of pain relief were increased as larger doses of fentanyl were added to lidocaine 1%, up to a maximum of 10 µg/kg given epidurally. Neither Rucci et al. (22) nor Welchew (23) measured catecholamine plasma levels. Their findings, however, could explain the lack of benefit we observed by adding fentanyl 1 µg/kg to bupivacaine over bupivacaine alone in the caudal block. The small dose of fentanyl, which is the common and accepted dose, is probably the reason why this mixture had an inconsequential effect on the pain scores and catecholamine plasma level and, therefore, should be increased in the routine use of caudal epidural analgesia in children.

Complete postoperative pain relief cannot be achieved by a single drug or method without significant side effects; therefore, efforts have been focused on improving pain relief by a combination of bupivacaine 0.5% and opioids such as morphine (24,25). These combinations provide effective pain relief even after upper abdominal surgery, but at the cost of motor block of the lower extremity or respiratory depression. A smaller concentration of local anesthetic or morphine leads to less pain relief. We chose the mixture of bupivacaine 0.25% and fentanyl because of the latter’s high lipid solubility, which offers a rapid onset of action while being less likely than morphine to migrate rostrally to the brainstem (4).

The present study demonstrates that there is no beneficial effect to the mixture of small-dose fentanyl (1 µg/kg) and bupivacaine 0.25%, compared with bupivacaine 0.25% alone when used for caudal epidural, based on pain score and catecholamine levels. The reduction of the stress response reflected by plasma catecholamines concentration could influence the clinical outcome in high-risk children. Future studies should examine the influence of larger doses of fentanyl added to local anesthetics on postoperative pain scores and catecholamine blood levels.


   References
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 

  1. Pietropaoli JA, Keller MS, Smail DF, et al. Regional anesthesia in pediatric surgery: complications and postoperative comfort level in 174 children. J Pediatr Surg 1993;4:560–4.
  2. Dalens B, Hasnaoui A. Caudal anesthesia in pediatric surgery: success rate and adverse effects in 750 consecutive patients. Anesth Analg 1989;68:83–9.[Web of Science][Medline]
  3. Caudle CL, Freid EB, Bailey AG, et al. Epidural fentanyl infusion with patient-controlled epidural analgesia for postoperative analgesia in children. J Pediatr Surg 1993;28:554–9.[Web of Science][Medline]
  4. De Leon-Casasola OA, Lema MJ. Postoperative epidural opioid analgesia: what are the choices? Anesth Analg 1996;83:867–75.[Abstract]
  5. Gaitini L, Somri M, Vaida S, et al. Effect of caudal block on the epinephrine and norepinephrine in paediatric patients undergoing ilioinguinal herniorrhaphy. Eur J Anaesthesiol 1999;16:92–7.[Web of Science][Medline]
  6. Nakamura T, Takasaki M. Metabolic and endocrine responses to surgery during caudal analgesia in children. Can J Anaesth 1991;38:969–73.[Web of Science][Medline]
  7. Dupont D, Velin P, Cabour F, et al. Influence de l’anesthésie caudale sur la sécrétion des catécholamines chez l’enfant. Ann Fr Anesth Réanim 1987;6:156–8.[Medline]
  8. Breslow MJ, Parker SD, Frank SM, et al. Determinant of catecholamine and cortisol responses to lower extremity revascularization. Anesthesiology 1993;79:1202–9.[Web of Science][Medline]
  9. Normandale JP, Schmulian C, Paterson JL, et al. Epidural diamorphine and the metabolic response to upper abdominal surgery. Anaesthesia 1985;40:748–53.[Web of Science][Medline]
  10. Rutberg H, Hakanson E, Anderberg B, et al. Effect of the extradural administration of morphine or bupivacaine on the endocrine response to upper abdominal surgery. Br J Anaesth 1984;56:233–8.[Abstract/Free Full Text]
  11. Aldrete JA, Kroulik D. A postanesthetic recovery score. Anesth Analg 1970;49:924–34.[Free Full Text]
  12. Goldstein DS, Feuerstein G, Izzo JL, et al. Validity and reliability of liquid chromatography with electrochemically detection for measuring plasma levels of norepinephrine and epinephrine in man. Life Sci 1981;28:467–75.[Web of Science][Medline]
  13. Candito M, Albertini M, Politano S, et al. Plasma catecholamine levels in children. J Chrom Biomed Appl 1993;617:304–7.
  14. Splinter WM, Semelhago L, Chou S. The reliability and validity of a modified CHEOPS pain score. Anesth Analg 1994;78:S413.
  15. Chung F. Discharge criteria—a new trend. Can J Anaesth 1995;42:1056–8.[Web of Science][Medline]
  16. Murat I, Walker J, Esteve C, et al. Effect of lumbar epidural anesthesia on plasma cortisol levels in children. Anaesth 1988;35:20–3.
  17. Traynor C, Paterson JL, Ward ID, et al. Effects of epidural analgesia and vagal blockade on the metabolic and endocrine response to upper abdominal surgery. Br J Anaesth 1982;54:319–23.[Abstract/Free Full Text]
  18. Scott NB, Mogensen T, Bigler D, et al. Continuous thoracic extradural 0.5% bupivacaine with or without morphine: effect on quality of blockade, lung function and the surgical stress response. Br J Anaesth 1989;62:253–7.[Abstract/Free Full Text]
  19. Campbell FA, Yentis SM, Fear DW, Bissonnette B. Analgesic efficacy and safety of a caudal bupivacaine-fentanyl mixture in children. Can J Anaesth 1992;39:661–4.[Web of Science][Medline]
  20. Jones RD, Gunawardene WM, Yeung CK. A comparison of lignocaine 2% with adrenaline 1: 200000 and lignocaine 2% with adrenaline 1:200000 plus fentanyl as agents for caudal anesthesia in children undergoing circumcision. Anaesth Intensive Care 1990;18:194–9.[Web of Science][Medline]
  21. Fell D. Postoperative analgesia in children [editorial]. Br J Anaesth 1993;70:4–5.[Free Full Text]
  22. Rucci FS, Cardamone M, Migliori P. Fentanyl and bupivacaine mixtures for extradural blockade. Br J Anaesth 1985;57:275–84.[Abstract/Free Full Text]
  23. Welchew EA. The optimum concentration for epidural fentanyl. A randomised, double-blind comparison with and without 1: 200,000 adrenaline. Anaesthesia 1983;38:1037–41.[Web of Science][Medline]
  24. Wolf AR, Huges D, Wade A, et al. Postoperative analgesia after paediatric orchidopexy: evaluation of a bupivacaine-morphine mixture. Br J Anaesth 1990;64:430–5.[Abstract/Free Full Text]
  25. Krane EJ. Delayed respiratory depression in a child after caudal epidural morphine. Anesth Analg 1988;67:79–82.[Free Full Text]
Accepted for publication January 19, 2000.




This article has been cited by other articles:


Home page
 Anesth. Analg.Home page
T. R. Vetter, D. Carvallo, J. L. Johnson, M. S. Mazurek, and R. G. Presson Jr
A Comparison of Single-Dose Caudal Clonidine, Morphine, or Hydromorphone Combined with Ropivacaine in Pediatric Patients Undergoing Ureteral Reimplantation
Anesth. Analg., June 1, 2007; 104(6): 1356 - 1363.
[Abstract] [Full Text] [PDF]

Home page
 Br J AnaesthHome page
Y. Kawaraguchi, T. Otomo, C. Ota, N. Uchida, A. Taniguchi, and S. Inoue
A prospective, double-blind, randomized trial of caudal block using ropivacaine 0.2% with or without fentanyl 1 {micro}g kg-1 in children
Br. J. Anaesth., December 1, 2006; 97(6): 858 - 861.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a colleague
Right arrow Similar articles in this journal
Right arrow Similar articles in Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowRequest Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Web of Science (9)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Gaitini, L. A.
Right arrow Articles by Zinder, O.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Gaitini, L. A.
Right arrow Articles by Zinder, O.

Lippincott, Williams & Wilkins Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins and Stanford University Libraries' HighWire Press®. Copyright 2000 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999 HighWire Press