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PAIN MEDICINE

The Pharmacokinetics and Efficacy of Ropivacaine Continuous Wound Instillation After Spine Fusion Surgery

Margherita Bianconi, MD^*, Luca Ferraro, PharmD, Riccardo Ricci, MD^*, Gustavo Zanoli, MD, Tiziana Antonelli, MD^,, Bighetti Giulia, MD, Aurelia Guberti, MD^*, and Leo Massari, MD

Departments of *Anesthesiology and Intensive Care and Clinical Pharmacology, St. Anna Hospital, Ferrara, Italy; and Departments of Clinical and Experimental Medicine, Section of Pharmacology, and Biomedical Sciences and Advanced Therapies, Section of Orthopaedics and Traumatology, University of Ferrara, Ferrara, Italy

Address correspondence and reprint requests to Tiziana Antonelli, MD, Department of Clinical and Experimental Medicine, Section of Pharmacology, University of Ferrara, Via Fossato di Mortara 17-19, 44100, Ferrara, Italy. Address e-mail to ant{at}unife.it

	Abstract

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Because local anesthetic continuous wound instillation has not been evaluated after spine fusion surgery, we designed this study to determine whether this technique could enhance analgesia and improve patient outcome after posterior lumbar arthrodesis. Thirty-eight patients undergoing spine stabilization were randomly divided into two groups. The M group received a postoperative baseline IV infusion of morphine plus ketorolac for 24 h, and the R group received IV saline. In both groups, a multihole 16-gauge catheter was placed subcutaneously; in the R group, the wound was infiltrated with a solution of ropivacaine 0.5% 200 mg/40 mL, and infusion of ropivacaine 0.2% 5 mL/h was maintained for 55 h. In the M group, saline infusion was given at the same rate. Pain scores were taken at rest and on passive mobilization by nurses blinded to patient analgesic treatment. The total plasma ropivacaine concentration was evaluated. Pain scores and rescue medication requirements (diclofenac and tramadol) were significantly less in the R group than in the M group. Postoperative blood loss was less and the length of hospital stay was shorter in the R group. The ropivacaine peak total plasma concentration occurred at 24 h during infusion and was within safe limits; no toxic local anesthetic side effects were observed. These results suggest that wound infiltration and continuous instillation of ropivacaine 0.2% is effective for pain management after spine stabilization surgery.

IMPLICATIONS: Postoperative pain after lumbar arthrodesis is related to soft tissue and muscle dissection and to manipulations and removal at the operation site. By blocking noxious stimuli from the surgical area, infiltration and wound perfusion with ropivacaine were more effective in controlling pain than systemic analgesia.

	Introduction

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Postoperative pain after posterior lumbar stabilization surgery is related to soft tissue and muscle dissection and to manipulations and removal at the operation site. Most patients complain of severe pain at rest during the first 12 h after surgery. This pain increases considerably with mobilization because of the reflex spasm of paraspinal muscles that is triggered by the primary wound pain (1). During the following 48–72 h, postoperative back pain is generally moderate at rest, whereas it remains severe on movement and produces discomfort that can interfere with patient mobilization and, possibly, with discharge time. Reuben et al. (2) found that continuous systemic administration of nonsteroidal antiinflammatory drugs (NSAIDs) is effective in controlling pain after lumbar stabilization surgery. Moreover, when associated with centrally acting drugs such as opioids, NSAIDs have an opioid-sparing effect (3,4).

Despite the favorable effects of analgesia in the early postoperative period, this drug association may produce a number of well-known side effects, such as nausea, vomiting, respiratory depression, sedation, renal abnormality, and upper gastrointestinal and operative site bleeding (5). Finally, NSAID administration might have an inhibitory effect on the spinal fusion rate (6,7). Local anesthetic infiltration of the surgical wound is a useful method in the treatment of postoperative pain after various surgical procedures (8–12), but, at present, there is no clinical evidence of real effectiveness and safety of continuous wound perfusion after spinal surgery.

The major limitations of currently available local anesthetics are the relatively short duration of action and the potential risk of systemic toxicity. Furthermore, studies performed so far have not provided definitive data concerning either the evaluation of the optimal method and time for infiltration or the optimal dosage/volume of local anesthetic, particularly regarding its systemic absorption and toxicity (13), which may increase during the large surgical incisions and soft tissue dissection typical of major orthopedic surgery.

Ropivacaine is an interesting molecule for infiltration because of its vasoconstrictive properties and decreased neuro- and cardiotoxicity compared with bupivacaine, and its favorable pharmacodynamic profile could be especially relevant when large doses are required (14,15). The aim of this study was to determine whether local anesthetic continuous wound perfusion could enhance analgesia and improve patient outcome after posterior lumbar arthrodesis.

	Methods

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After we obtained approval from the ethics committee and informed, written consent from patients, ASA status I–II patients undergoing elective posterior lumbar stabilization were enrolled in the study. Inclusion criteria were elective posterior stabilization for lumbar instability due to spinal stenosis, a good understanding of the Italian language and the visual analog pain scale (VAS), and age from 18 to 80 yr. Exclusion criteria included known local anesthetic allergy or NSAID allergy, renal or hepatic insufficiency, coagulation abnormalities, neoplastic disorders, pathologic obesity (body mass index 35%) or weight <60 kg, local sepsis, unbalanced cardiopathy or pneumopathy, severe diabetes, and a history of peptic ulcer or bleeding diathesis.

Patients were randomized with a computer-generated sequence and assigned to one of the two following postoperative analgesia groups after a presealed envelope was opened: the M group received IV analgesic infusion, and the R group received IV saline infusion plus local anesthetic instillation directly into the surgical area. After premedication with IV midazolam 0.02 mg/kg, anesthesia was induced with propofol 2 mg/kg and fentanyl 5 µg/kg, and paralysis was achieved by injection of vecuronium bromide 0.1 mg/kg. After the induction, the patients were placed on the operating table in the prone position. General balanced anesthesia with mild hypotension was performed by the same anesthesiologist for all patients.

For maintenance, a combination of 65% N₂O/35% oxygen and sevoflurane was administered at 1.5%–2% end-tidal concentration to achieve a reduction of mean arterial blood pressure to 50–70 mm Hg on the basis of the patient’s general condition. Fentanyl was administered during the surgical procedure for intraoperative analgesia. Ondansetron (8 mg IV) was given as a prophylactic antiemetic at the end of surgery.

The perioperative monitoring included electrocardiogram (ECG), intraarterial blood pressure, central venous pressure, temperature, neuromuscular blockade, end-tidal carbon dioxide, pulse oximetry, airway pressure, and urinary output. All operations were performed by the same surgeon with a standardized posterior median incision at the level of lumbar vertebra instability. The surgical procedure was performed with decompression and fixation by a metallic internal device with transpedicular screws.

An initial loading dose of IV morphine 10 mg was given to both groups at the end of surgery, and then the M group (19 patients) received a standard baseline IV infusion of morphine at 0.5 mg/h plus ketorolac 3.7 mg/h for 24 h through an elastomeric pump at 2 mL/h (Infusor; Baxter, Deerfield, IL; a total of 50 mL at a flow rate of 2 mL/h), whereas in the R group, a normal saline solution was given IV at 2 mL/h for 24 h.

In the R group (19 patients), after the fascia closure, the surgeon infiltrated all surgical strata and the paraspinal muscles all long the wound bilaterally with a solution of ropivacaine 0.5% 40 mL (200 mg; Naropine®; AstraZeneca, Milano, Italy). Thereafter, in both groups of patients, under direct visualization, a multihole 16-gauge catheter was placed between the muscle fascia and subcutaneous tissues all along the wound, and then it was fixed at the skin by a stitch and the wound was sutured as usual (Fig. 1). A suction drain was placed near the spinal instrumentation level and under the fascia and, according to our standard practice, far away from the indwelling catheter. The 16-gauge catheter was immediately connected to a bacterial filter through which an elastomeric infusion pump (Infusor; a total of 275 mL at a flow rate of 5 mL/h) delivered ropivacaine 0.2% 5 mL/h for 55 h (R group) or saline solution (M group). The catheter was removed with aseptic technique at the end of infusion, and the tip was subjected to microbiological analysis.

View larger version (92K): [in this window] [in a new window]   Figure 1. Picture showing the placement of the catheter above the fascia in the surgical bed before the suture.

The pharmacokinetic aspects related to the systemic absorption of ropivacaine (infiltrated and perfused in a surgical area) were evaluated. The resulting total plasma concentrations were compared with established toxic thresholds for venous plasma concentrations as reported by Scott et al. (14) and Knudsen et al. (17) in their studies.

In the postoperative period, patients were asked to quantify their pain at rest and on mobilization by using a VAS between 0 and 100, with 0 representing no pain and 100 representing the worst imaginable pain. Mobilization pain was triggered by asking the patient to turn on both sides.

Pain assessment was made 4, 8, 12, 24, 48, and 72 h after surgery. During the entire postoperative period of observation, the patients of both groups were free to ask for a fixed dose of supplemental analgesic. Nurses, who were blinded to patient analgesic treatment, administered rescue analgesia according to the following standard protocol: if VAS was 50, patients received IM diclofenac 75 mg; if the VAS score was 50 mm or if satisfactory pain relief was not achieved with diclofenac, an IV dose of 100 mg of tramadol was given (and repeated if necessary) until a pain score of 30 mm was recorded.

No restriction was placed for drug frequency or dosage in either group. The amount of analgesics required and the local and systemic adverse events were recorded for each patient. The length of wound incision, the number of levels treated, the amount of perioperative fentanyl, the total postoperative blood loss, and the trend of liver and renal function indices were compared between the two groups.

Postoperative bradycardia, hypotension, nausea, vomiting, headache, fever, agitation, drowsiness or confusion were recorded. The appearance of symptoms of central nervous system (CNS) toxicity, such as numbness of the tongue, dizziness, visual disturbances, metallic taste, tinnitus, muscular twitching and dysarthria, or hemodynamic changes, were criteria indicating immediate discontinuation of ropivacaine infusion. According to our standard practice for this kind of surgery, patients were allowed to eat on the second postoperative day if bowel motility was restored. Mobilization on the side was allowed on the same day, and, on the third postoperative day, patients could get up and walk.

Discharge was decided by the surgeons blinded to the analgesic treatment, according to the following discharge criteria: 1) satisfactory pain control for self-mobility; 2) uncomplicated wound-healing process; 3) uncomplicated clinical and radiographic outcome; 4) no evidence of deep vein thrombosis; and 5) no impairments in hemoglobin or liver/kidney function. After 72 h, we recorded patient satisfaction with the analgesia provided by using a scale of poor, satisfactory, or excellent.

Data are expressed as the mean ± standard deviation (SD) or the mean ± SEM. The results were analyzed by using the nonparametric Mann-Whitney U-test, the Student’s t-test, or the ² test, as reported in table and figure legends. A P value <0.05 was considered to represent statistical significance.

Sample-size calculation was based on an expected difference of 20 mm in VAS measurements for pain between group means, on the basis of a reported value of minimal clinically important differences in acute pain (18), on an SD of 16, obtained from previous studies, with P = 0.90 and = 0.05. A sample size of 14 patients per group was obtained. For the same variables, an expected difference in patient satisfaction of 50% between the R and M groups generated a similar sample size. A conservative sample size of 38 patients was then agreed on to overcome any potential dropout. Microsoft Excel for Windows (Microsoft, Redmond, WA) and SAS for Windows (SAS Institute, Cary, NC) were used for data entry and analysis.

	Results

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Thirty-seven patients completed the study protocol: 19 in the M group and 18 in the R group. In fact, in one patient, ropivacaine wound instillation was discontinued at 4 h after surgery because of respiratory difficulties, chest pain, and T-wave abnormality on the ECG because of an acutely low hemoglobin level. No evidence of toxic plasma ropivacaine concentration was found, and the patient was excluded from the study.

Demographic data of the two groups of patients are shown in Table 1. There were no significant differences between the two groups in the reported variables.

View larger version (15K): [in this window] [in a new window]   Figure 2. Mean total plasma concentrations of ropivacaine in patients receiving infiltration and long-term wound perfusion of the drug (for details, see Methods). The total plasma ropivacaine concentration was determined from peripheral venous samples taken at 15, 30, 90, 180, and 360 min and 12, 24, 48, and 72 h after the onset of drug infiltration.

View larger version (27K): [in this window] [in a new window]   Figure 3. Visual analog scale (VAS) scores (100 mm) for pain at rest (A) and during passive mobilization (B) in the M group and R group at 4, 8, 12, 24, 48, and 72 h after surgery (x axes). Data are reported as mean ± SEM. **P < 0.01, significantly different from the control group according to the nonparametric Mann-Whitney U-test.

View larger version (14K): [in this window] [in a new window]   Figure 4. Rescue medication requirements (mg) in the M group and R group. The mean tramadol and diclofenac doses were significantly increased in the M group compared to the R group during the time interval. Data are reported as mean ± SEM. *P < 0.05; **P < 0.01, significantly different from the control group according to the nonparametric Mann-Whitney U-test.

	Discussion

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Peripheral pain modulation by incisional local anesthesia is a useful method in the treatment of postoperative pain after various surgical procedures. However, it has been previously reported (19) that local anesthetic infiltration into the operative incision after spine fusion surgery fails to provide any advantages in postoperative pain relief after single-shot infiltration of bupivacaine 0.25% (100 mg). Both the small dose of the local anesthetic used in that study and the single-infiltration procedure could have contributed to the negative result (13). More recently, Pobereskin and Sneyd (20) reported that triamcinolone, infiltrated at the end of surgery, reduced postoperative pain scores, morphine consumption, and LOS after shorter and less invasive lumbar spine surgical procedures, suggesting a potential for the use of this method and also for major spine surgery.

None of the ropivacaine-treated patients experienced any serious side effects because of local anesthetic toxicity. In this context, it is worth noting that although a threshold for CNS toxicity has been reported at a ropivacaine venous C_max ranging from 1 to 2 µg/mL (14,16), many other studies have failed to observe the occurrence of adverse events even at larger ropivacaine plasma concentrations. For instance, Pettersson et al. (9) measured a ropivacaine C_max of 3 µg/mL after infiltration of 375 mg of ropivacaine for hernia repair surgery without any adverse events. In addition, Horn et al. (8) reported a peak ropivacaine C_max of 2.7 µg/mL after wound infiltration and drain lavage with 225 mg of ropivacaine 7.5 mg/mL for major shoulder surgery, and no neurological or cardiac complications occurred. The pharmacokinetics of different concentrations of ropivacaine have also been evaluated after peripheral nerve blocks by Wulf et al. (21), who reported a C_max of 3.70 µg/mL and no adverse reaction. Finally, ropivacaine pharmacokinetics during long-term epidural infusion have also been studied by many authors (21–24).

In particular, Wiedermann et al. (22) observed during 120 hours of ropivacaine epidural infusion that the anesthetic C_max increased steadily from 2.39 to 6.8 µg/mL with no symptoms of systemic toxicity. It should be considered that, although after IV administration of ropivacaine in nonoperated volunteers, ropivacaine-induced CNS toxicity occurred at ropivacaine C_max ranging from 1 to 2 µg/mL (14–15,17), Wiedermann et al. (22) suggested that large increases in ropivacaine C_max during long-term epidural infusion reflect changes in plasma protein binding related to an increased ₁-acid glycoprotein plasma concentration after surgery. It seems likely that after surgery, increased ropivacaine C_max is not accompanied by similar increases in the free-drug (i.e., unbound) concentration, thus also possibly explaining the lack of symptoms for relatively high levels of total ropivacaine plasma. Finally, the observation that plasma ropivacaine levels decreased significantly after 24 hours and continued to decrease until the end of the infusion suggests that ropivacaine would not accumulate in the plasma.

Fredman et al. (25) found that patient-controlled ropivacaine wound instillation decreased postcesarean delivery pain and opioid requirements and reported good pain relief with patient-controlled analgesia ropivacaine wound instillation even in the first hours after cesarean delivery. In our study, the poor pain control at four hours after surgery was likely ascribable to unblocked afferents from deep in the wound, in conjunction with decreasing systemic morphine levels and waning of the surgically infiltrated local anesthetic. However, in the following 24–48 hours, when postoperative pain is usually worsened by mobilization because of reflex spasm of paraspinal muscles (1), the R group reported significantly better pain relief and fewer differences in pain intensity, both at rest and mobilization. Interestingly, at 72 hours after surgery, the pain was still reduced in R group despite discontinuation of the ropivacaine infusion.

The important finding of this study is that analgesia provided by wound infiltration and perfusion with ropivacaine was more effective than systemic analgesia in controlling mobilization pain, especially during the 48–72 hours after surgery, thus improving early patient rehabilitation, hastening convalescence, and shortening LOS.

It is evident that persistent postoperative low back pain results in a forced stay in bed, an increased rate of complications, delayed rehabilitation, and prolonged LOS. In this context, as Capdevilla et al. (26) pointed out, functional recuperation is accelerated and the overall LOS is shortened by an early intensive rehabilitation program, which is possible only if the patients are pain free. Thus, better pain control in the R group may have played a role in improving early patient rehabilitation, in hastening convalescence, and in enabling a more rapid achievement of postoperative discharge criteria. Another positive outcome was the significant reduction in postoperative blood loss in the R group compared with the M group, an effect that could be relevant in reducing the need for homologous blood transfusions and related costs and morbidity. From the available data, it is difficult to propose any explanations, except speculative hypotheses, for the finding of decreased postoperative blood loss in ropivacaine-treated patients. Other factors (not considered in this study), such as platelet count, bleeding time, and previous NSAID consumption, might have played a role, and further investigations will therefore be necessary to clarify this point.

In conclusion, our data suggest that infiltration and wound perfusion of ropivacaine is a safe and effective choice as a part of a multimodal analgesic regimen for the management of postoperative pain after spine fusion surgery. The satisfaction and compliance of our patients is further evidence of an improved quality of care after anesthesia and surgery.

	Acknowledgments

 
Supported by AstraZeneca SpA, Basiglio, Milano, Italy.

	References

Top Abstract Introduction Methods Results Discussion References

 

1. Bonica JJ. Postoperative Pain. In: Bonica JJ, ed. The management of pain. Philadelphia: Lea-Febiger, 1990: 461–80.
2. Reuben SS, Connelly NR, Lurie S, et al. Dose-response of ketorolac as an adjunct to patient controlled analgesia: morphine in patients after spinal fusion surgery. Anesth Analg 1998; 87: 98–102.[Abstract/Free Full Text]
3. Ready LB, Brown CR, Stahlgren LH, et al. Evaluation of intravenous ketorolac administered by bolus or infusion for treatment of postoperative pain. Anesthesiology 1994; 80: 1277–86.[Web of Science][Medline]
4. Aubrun F, Langeron O, Heitz D, et al. Randomized, placebo-controlled study of the postoperative analgesic effects of ketoprofen after spinal fusion surgery. Acta Anaesthesiol Scand 2000; 44: 934–9.[Web of Science][Medline]
5. Souter AJ, Fredman B, White PF. Controversies in the perioperative use of non steroidal anti-inflammatory drugs. Anesth Analg 1994; 79: 1178–90.[Free Full Text]
6. Martin GJ, Boden SD, Titus L. Recombinant human bone morphogenetic protein-2 overcomes the inhibitory effect of ketorolac, a nonsteroidal anti-inflammatory drug (NSAID), on posterolateral lumbar intertransverse process spine fusion. Spine 1999; 24: 2188–94.[Web of Science][Medline]
7. Glassman SD, Mattew-Rose S, Dimar JR, et al. The effect of postoperative non steroidal anti-inflammatory drug administration on spinal fusion. Spine 1998; 23: 834–8.[Web of Science][Medline]
8. Horn EP, Schroeder F, Wilhelm S, et al. Infiltration and drain lavage with ropivacaine after major shoulder surgery. Anesth Analg 1999; 89: 1461–6.[Abstract/Free Full Text]
9. Pettersson N, Emanuelsson BM, Reventlid H, Hahn RG. High-dose ropivacaine wound infiltration for pain relief after inguinal hernia repair: a clinical and pharmacokinetic evaluation. Reg Anesth Pain Med 1998; 23: 189–96.[Web of Science][Medline]
10. Rawal N, Axelsson K, Hylander J, et al. Postoperative patient-controlled local anesthetic administration at home. Anesth Analg 1998; 86: 86–9.[Web of Science][Medline]
11. Karsten A, Galatius H, Hansen A, et al. Preoperative wound infiltration with bupivacaine reduces early and late opioid requirement after hysterectomy. Anesth Analg 1996; 83: 376–81.[Abstract]
12. Partridge BL, Stabile BE. The effect of incisional bupivacaine on postoperative narcotic requirements, oxygen saturation and length of stay in the post-anesthesia care unit. Acta Anaesthesiol Scand 1990; 34: 486–91.[Medline]
13. Dahl JB, Moiniche S, Kehlet H. Wound infiltration with local anaesthetics for postoperative pain relief. Acta Anaesthesiol Scand 1994; 38: 7–14.[Web of Science][Medline]
14. Scott DB, Lee A, Fagan D, et al. Acute toxicity of ropivacaine compared with that of bupivacaine. Anesth Analg 1989; 69: 563–9.[Abstract/Free Full Text]
15. Sztark F, Malgat M, Dabadie P, Mazat JP. Comparison of the effects of bupivacaine and ropivacaine on heart cell mitochondrial bioenergetics. Anesthesiology 1998; 88: 1340–9.[Web of Science][Medline]
16. Reif S, Le Corre P, Dollo G, et al. High-performance liquid chromatographic determination of ropivacaine, 3-hydroxy-ropivacaine, 4-hydroxy-ropivacaine and 2',6'-pipecoloxylidide in plasma. J Chromatogr B Biomed Sci Appl 1998; 719: 239–44.[Medline]
17. Knudsen K, Beckman-Suurkula M, Blomberg S, et al. Central nervous and cardiovascular effects of i.v. infusion of ropivacaine, bupivacaine and placebo in volunteers. Br J Anaesth 1997; 78: 507–14.[Abstract/Free Full Text]
18. De Loack LJ, Higgins MS, Caplan AB, Stiff JL. The visual analog scale in the immediate postoperative period: intrasubject variability and correlation with a numeric scale. Anesth Analg 1998; 86: 102–6.[Abstract]
19. Chaddduck JB, Sneyd JR, Pobereskin LH. The role of bupivacaine in early postoperative pain after lumbar decompression. J Neurosurg 1999; 90 (1 Suppl): 67–72.[Medline]
20. Pobereskin LH, Sneyd JR. Does wound irrigation with triamcinolone reduce pain after surgery to the lumbar spine? Br J Anaesth 2000; 84: 731–4.[Abstract/Free Full Text]
21. Wulf H, Worthmann F, Behnke H, Bohle AS. Pharmacokinetics and pharmacodynamics of ropivacaine 2 mg/mL, 5 mg/mL, or 7.5 mg/mL after ilioinguinal blockade for inguinal hernia repair in adults. Anesth Analg 1999; 89: 1471–4.[Abstract/Free Full Text]
22. Wiedermann D, Muhlnickel B, Staroske E, et al. Ropivacaine plasma concentration during 120-hour epidural infusion. Br J Anesth 2000; 85: 830–5.[Abstract/Free Full Text]
23. Scott DA, Emanulesson BM, Mooney PH, et al. Pharmacokinetic and efficacy of long term epidural ropivacaine infusion for postoperative analgesia. Anesth Analg 1997; 85: 1322–30.[Abstract]
24. Burm AGL, Stienstra R, Browwer R, et al. Epidural infusion of ropivacaine for postoperative analgesia after major orthopaedic surgery. Anesthesiology 2000; 93: 395–403.[Web of Science][Medline]
25. Fredman B, Shapiro A, Zohar E, et al. The analgesic efficacy of patient-controlled ropivacaine instillation after cesarean delivery. Anesth Analg 2000; 91: 1436–40.[Abstract/Free Full Text]
26. Capdevilla X, Barthelet Y, Biboulet P, et al. Effects of perioperative analgesic technique on the surgical outcome and duration of rehabilitation after major knee surgery. Anesthesiology 1999; 91: 8–15.[Web of Science][Medline]

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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