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 ISI 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
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via ISI Web of Science (7)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Szarvas, S.
Right arrow Articles by Shorten, G. D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Szarvas, S.
Right arrow Articles by Shorten, G. D.
Related Collections
Right arrow Postanesthetic Care Unit
Right arrow Regional Anesthesia
Right arrow Pharmacology

Anesth Analg 2003;97:259-263
© 2003 International Anesthesia Research Society

REGIONAL ANESTHESIA

A Comparison of Dexamethasone, Ondansetron, and Dexamethasone plus Ondansetron as Prophylactic Antiemetic and Antipruritic Therapy in Patients Receiving Intrathecal Morphine for Major Orthopedic Surgery

Szilvia Szarvas, MB*, Ramesh S. Chellapuri, MBBS{dagger}, Dominic C. Harmon, MMedSci FCARCSI*, John Owens, FFARCSI{dagger}, Damian Murphy, MD FFARCSI*, and George D. Shorten, MD PhD*

*Department of Anesthesia and Intensive Care Medicine, Cork University Hospital and University College Cork; and {dagger}Department of Anesthesia, Bon Secours Hospital, Cork, Ireland

Address correspondence and reprint requests to Szilvia Szarvas, MB, Department of Anesthesia and Intensive Care Medicine, Cork University Hospital, Wilton Rd., Cork, Ireland. Address e-mail to szarvasszilvia{at}hotmail.com


   Abstract
Top
 Abstract
Introduction
 Methods
 Results
 Discussion
 References
 
In a prospective, double-blinded, randomized trial, we evaluated the efficacy of IV (a) dexamethasone 8 mg, (b) ondansetron 8 mg, and (c) dexamethasone 8 mg plus ondansetron 4 mg for the prevention of postoperative nausea, vomiting (PONV), and pruritus in 130 (ASA physical status I to III) patients undergoing elective major orthopedic surgery after spinal anesthesia with hyperbaric 0.5% bupivacaine and intrathecal morphine. After spinal anesthesia, patients were randomized to one of three groups. Failure of PONV prophylaxis in the 24-h postoperative period occurred more frequently in patients who received dexamethasone alone (29 of 40; 73%) compared with those who received either ondansetron alone (23 of 47; 49%) (P = 0.02) or dexamethasone plus ondansetron together (19 of 43; 44%)(P = 0.01). There was no difference in the incidence of failure of prophylaxis of pruritus (70%, 72%, and 70% in dexamethasone 8 mg, ondansetron 8 mg, and dexamethasone 8 mg plus ondansetron 4 mg, respectively) (P > 0.1) in the 24-h postoperative period. We conclude that the administration of dexamethasone 8 mg with ondansetron 4 mg has no added benefit compared with ondansetron 8 mg alone in the prophylaxis of PONV and pruritus.

IMPLICATIONS: Postoperative nausea and vomiting (PONV) and pruritus are common side effects after spinal opioid administration. In this study, dexamethasone 8 mg plus ondansetron 4 mg was as effective as ondansetron 8 mg. The administration of dexamethasone alone was associated with a frequent incidence of PONV, demonstrating a lack of efficacy. This has important cost implications.


   Introduction
Top
 Abstract
 Introduction
Methods
 Results
 Discussion
 References
 
Intrathecal opioids are frequently administered to patients undergoing major orthopedic operations for postoperative analgesia. The incidence of postoperative nausea and vomiting (PONV) in patients who have received an intrathecal opiate is 60%–80% (1). The reported incidence of intrathecal opioid-induced pruritus is 20%–100% (2,3). Although the prophylactic and therapeutic effects of several antiemetic and antipruritic drugs have been extensively studied, a decrease in the incidence of PONV and pruritus after intrathecal opioids remains a major therapeutic challenge.

Ondansetron and dexamethasone have well recognized roles in the prophylaxis of PONV after obstetric, gynecological, pediatric, and general surgery (4–7). Prophylactic administration of ondansetron 8 mg IV significantly decreases the frequency and the severity of PONV after Cesarean delivery with intrathecal sufentanil-morphine (8). In 120 parturients who received epidural morphine 3 mg for post-Cesarean delivery analgesia, dexamethasone 8 mg significantly decreased the incidence of PONV compared with placebo (4). Ondansetron has been assessed as an antipruritic drug after neuraxial opioid administration in the orthopedic and obstetric patient populations (2,9). Yeh et al. (2) studied the efficacy of ondansetron 0.1 mg/kg on morphine-induced pruritus compared with either placebo or diphenhydramine (30 mg IV) in patients scheduled for elective Cesarean delivery. The incidence of pruritus was significantly less in the ondansetron group (25%) when compared with the placebo (85%) or the diphenhydramine groups (80%) (P < 0.01). The efficacy of dexamethasone as an antipruritic drug after intrathecal opioid administration has not been studied.

We hypothesized that IV dexamethasone 8 mg plus ondansetron 4 mg, administered in combination to patients undergoing major orthopedic surgery who received intrathecal morphine, would decrease the incidence of PONV and pruritus compared with either ondansetron 8 mg or dexamethasone 8 mg alone. PONV and pruritus are recognized complications of major orthopedic surgery performed under spinal anesthesia including intrathecal morphine administration. Therefore, we considered the inclusion of a placebo group to be unethical.


   Methods
Top
 Abstract
 Introduction
 Methods
Results
 Discussion
 References
 
With institutional ethics committee approval and having obtained written informed consent from each, we studied 130 adult ASA physical status I to III patients undergoing major orthopedic surgery. Patients who received opiates or antiemetic therapy within 48 h before surgery, those known to have a history of motion sickness, pruritic skin disorder or hypersensitivity to dexamethasone or ondansetron, and patients on current steroid medication were excluded. Patients were allocated by using computer random-generated numbers to receive one of three treatment regimens: dexamethasone 8 mg, ondansetron 8 mg, or dexamethasone 8 mg plus ondansetron 4 mg. Patients, anesthesiologists involved in intraoperative care, and investigators who collected postoperative data were unaware of patient group allocation. The study drugs were administered by slow (30 s) IV injection immediately after performing spinal anesthesia. An anesthesiologist who was not an investigator prepared syringes containing the study drugs. The drugs were diluted with normal saline in identical syringes to achieve a volume of 5 mL. A standardized anesthetic technique was used as follows. Premedication consisted of diazepam 10 mg administered orally 60–90 min before performance of the spinal anesthetic. After the institution of monitoring, including the placement of electrocardiogram leads, a noninvasive blood-pressure monitor, and pulse oximetry (DATEX AS3, Datex Inc, Mission Hills, CA), an 18-gauge IV cannula was inserted, and Hartmann’s solution 500 mL was administered before the start of spinal anesthesia. Anesthesia was instituted in the left lateral position. Using an aseptic technique, a 25-gauge Whit-acre needle was inserted via a midline approach into the L2-3 or L3-4 interspace. Anesthesia was established with a single bolus of 0.5% hyperbaric bupivacaine (17.5 mg if >70 kg and 15 mg if ≤70 kg) and preservative-free morphine 0.01 mg/kg (up to 0.7 mg). The level of sensory blockade was assessed by the level of touch sensation before surgical incision (T6-8 was considered adequate). Midazolam 1–2 mg IV prn was administered for intraoperative sedation. Supplemental oxygen 6 L/min (35%) via a vent mask was administered during and after surgery.

Postoperatively, all patients were admitted to a high-dependency unit. A standard postoperative analgesic regimen of tramadol 100 mg IM as required was prescribed for postoperative pain relief. Nausea was defined as the unpleasant sensation associated with awareness of the urge to vomit; vomiting was defined as the forceful expulsion of gastric contents from the mouth; and pruritus was defined as the sensation that provokes the desire to scratch. Failure of PONV prophylaxis was defined as any episode of nausea, retching, vomiting, or use of rescue antiemetic. Failure of pruritus prophylaxis was defined as any episode of itching that provoked the desire to scratch or use of rescue antipruritic. Cyclizine 50 mg IM and chlorpheniramine 4 mg orally prn was prescribed for rescue treatment of PONV and pruritus, respectively. PONV, pruritus, and pain were assessed at 30 min and 2, 4, 8, and 24 h after surgery by a blinded investigator. The severity of PONV and pruritus was assessed via a visual analog scale (VAS) ranging from no symptom (0 cm) to worst possible symptoms (10 cm). The VAS was divided into 4 scores: 0 cm = no symptoms; 1–3 cm = mild symptoms; 3–7 cm = moderate symptoms, and 7–10 cm = severe symptoms. Pain was assessed using a similar VAS.

A sample size of 45 patients per group was required to detect a difference in response rates of 20% from a baseline prevalence of 50% with 80% power at a significance level of 5%. We chose a 50% baseline prevalence because a previous pilot study in our department (unpublished) showed that the incidence of PONV in our patient population was approximately 50%. A series of two-way analysis of variance was conducted to examine the difference among the three groups with respect to parametric variables. If a significant difference was found, Student’s t-test with Bonferroni correction was used to detect the intergroup differences. Nonparametric data were analyzed by Kruskal-Wallis, followed by Mann-Whitney U-test, as appropriate. A P value < 0.05 was considered significant.


   Results
Top
 Abstract
 Introduction
 Methods
 Results
Discussion
 References
 
The three groups were similar in terms of age, sex ratio, weight, intrathecal opioid dose, and duration of surgery (Table 1). No significant opioid or study drug-related adverse effects were reported within the 24-h observation period. All patients completed a VAS score for pruritus, PONV, and pain at each period studied. The overall incidence of PONV in the first 24-h postoperative period was 67%, 47%, and 40% in the dexamethasone alone, ondansetron alone, and dexamethasone plus ondansetron groups, respectively. Failure of prophylaxis of PONV during the first 4 h (0–4 h) after surgery occurred in 53%, 28%, and 33% of patients; during the subsequent 4 h (4–8 h), it was 43%, 34%, and 35%. The next 16 h (8–24 h) was 48%, 43%, and 42% in the dexamethasone alone, ondansetron alone, and dexamethasone plus ondansetron groups, respectively (Table 2). The overall failure of prophylaxis of PONV during the 24-h observation period was 73%, 49%, and 44%, respectively.


View this table:
[in this window]
[in a new window]
  		Table 1. Patient Characteristics
 

View this table:
[in this window]
[in a new window]
  		Table 2. Nausea, Vomiting, use of Rescue Antiemetics, and Proportion of Patients in Whom Prophylaxis Failed
 
Failure of prophylaxis of PONV during the 24-h observation period occurred less often in patients who received either dexamethasone plus ondansetron or ondansetron alone compared with those who had received dexamethasone alone (P = 0.01 and 0.02, respectively). Furthermore, in the first 4 h after surgery, ondansetron alone was significantly better (P = 0.02) than dexamethasone alone in decreasing the incidence of PONV in this patient population.

The incidence of pruritus for the 24 h after surgery was 70%, 73%, and 72% in the dexamethasone, ondansetron, and dexamethasone-ondansetron groups, respectively. There was no significant difference in the incidence of failure of prophylaxis of pruritus among the groups at each of the time periods examined.

There was no significant difference in pain scores at any assessment interval. The opioid analgesic consumption (tramadol 100 mg IM) in the dexamethasone-ondansetron group (39.5 mg) was significantly less than in the ondansetron alone group (68.0 mg)(P = 0.04).


   Discussion
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
References
 
This study shows that compared with ondansetron 8 mg alone, dexamethasone 8 mg plus ondansetron 4 mg IV, administered in combination to patients undergoing major orthopedic surgery including intrathecal morphine, does not significantly decrease the incidence of PONV. The overall (0–24 hours) incidence of failure of prophylaxis of PONV in the dexamethasone 8 mg-ondansetron 4 mg and ondansetron 8 mg alone groups was less compared with the dexamethasone alone group.

We chose 8 mg of ondansetron as monotherapy because it is the standard antiemetic in our institution. This dose prevents PONV successfully after Cesarean delivery, laparoscopic, and day case surgery (10–12). Dexamethasone 8 mg administered alone has been used in the adult population for prophylaxis of PONV after general surgery and chemotherapy (7,13). A smaller dose of ondansetron (4 mg) was chosen in this study combination with dexamethasone 8 mg because (a) previous data indicated that ondansetron either 4 mg or 8 mg were equally effective in the prophylaxis of PONV (12), (b) both doses were reported to be equally safe after rapid IV administration in terms of the cardiovascular adverse effects (14), and (c) the incorporation of ondansetron 4 mg in the combination may offer a more cost-effective option.

Dexamethasone has been postulated to be an effective antiemetic after pediatric and general surgery (6,7). It has been suggested that dexamethasone decreases the incidence of PONV after neuraxial opioid (4). In a study with 120 parturients who received epidural morphine (3 mg), dexamethasone 8 mg IV significantly decreased the incidence of PONV compared with placebo (18% and 51%, respectively) (4). There is substantial evidence that dexamethasone, alone or in combination, may possess antiemetic effects during the postoperative period (15,16). In our study, it was not possible to determine if dexamethasone monotherapy had an antiemetic effect because no placebo group was included. The frequent incidence (67%) of PONV with dexamethasone monotherapy in our study would suggest a lack of efficacy. Historical data indicate that 80% of patients who receive no antiemetic prophylaxis after undergoing total joint replacement procedures with neuraxial anesthesia have PONV (17).

It is noteworthy that the dexamethasone 8 mg-ondansetron 4 mg antiemetic combination costs less than ondansetron 8 mg alone (24.89 versus 41.57 Euros), and their efficacy as prophylactic therapy of PONV seems to be similar in this setting. If patients are not at risk of drug interaction because of polypharmacy, it is reasonable to take cost-effectiveness into account.

The absence of a significant difference in this study between the ondansetron 8 mg IV and dexamethasone 8 mg plus ondansetron 4 mg IV groups as PONV prophylaxis may be because of the fact that in previous studies, 4 mg and 8 mg of ondansetron proved to be similarly effective in either the prevention (12) or the treatment (18) of PONV. Dexamethasone has a long biological half-life of 36 to 72 hours and is suggested to provide better control of delayed PONV (i.e., beyond 24 hours) after chemotherapy (19). In this study, the 24-hour observation period may not have been sufficiently long enough to identify a difference between the two regimens.

The second objective of this trial was to compare the antipruritic effects of the three regimens. Ondansetron, a specific 5-hydroxytryptamine3 antagonist, has been shown to decrease the incidence of pruritus after intrathecal morphine injection associated with elective Cesarean delivery (2). Dexamethasone has not been studied as an antipruritic drug after neuraxial opioid administration. Colbert et al. (20,21) reported that diclofenac and tenoxicam had antipruritic effects in patients after epidural (20) and intrathecal (21) opioid administration. Because of possible antipruritic effects of the two study drugs, we postulated that the combination of dexamethasone 8 mg plus ondansetron 4 mg would decrease the incidence of intrathecal morphine-induced pruritus compared with dexamethasone 8 mg or ondansetron 8 mg alone. We failed to demonstrate a significant difference in the incidence of failure of pruritus prophylactic therapy among the three groups.

Our study showed that patients in the dexametha-sone-ondansetron group required less opioid analgesia than those receiving monotherapy. Afferent nerve fibers mediating pain are a subset of the large population of polymodal C-nociceptors, and their transmission to the central nervous system may be enhanced by prostaglandins (PGE2) (10). Dexamethasone inhibits PGE2 synthesis and may provide analgesia by this mechanism. 5-Hydroxytryptamine3 is also implicated in the central processing of pain (22). In this study, the decreased analgesic consumption in the dexamethasone-ondansetron group have been because of the analgesic properties of these two drugs.

This study demonstrated that dexamethasone 8 mg IV and ondansetron 4 mg IV was as effective as ondansetron 8 mg alone in the prophylaxis of PONV in patients undergoing major orthopedic operation with spinal morphine. The incidence of pruritus was also similar in each group during the 24-hour observation period.

In conclusion, dexamethasone 8 mg plus ondansetron 4 mg in the prophylaxis of PONV in patients undergoing major orthopedic operation with spinal morphine was not more effective than the standard antiemetic therapy, ondansetron 8 mg. Dexamethasone alone was associated with a frequent failure rate of PONV prophylaxis.


   References
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 

  1. Dahl JB, Jeppesen IS, Jorgensen H, et al. Intraoperative and postoperative analgesic efficacy and adverse effects of intrathecal opioids in patients undergoing cesarean section with spinal anesthesia. Anesthesiology 1999; 91: 1919–27.[ISI][Medline]
  2. Yeh HM, Chen LK, Lin CJ, et al. Prophylactic intravenous ondansetron reduces the incidence of intrathecal morphine-induced pruritus in patients undergoing cesarean delivery. Anesth Analg 2000; 91: 172–5.[Abstract/Free Full Text]
  3. Krajnik M, Zylicz Z. Understanding pruritus in systemic disease. J Pain Symptom Manage 2001; 21: 151–68.[ISI][Medline]
  4. Tzeng JI, Wang JJ, Ho ST, et al. Dexamethasone for prophylaxis of nausea and vomiting after epidural morphine for post-cesarean section analgesia: comparison of droperidol and saline. Br J Anaesth 2000; 85: 865–8.[Abstract/Free Full Text]
  5. Helmers JH, Briggs L, Abrahamsson J, et al. A single i.v. dose of ondansetron 8 mg prior to induction of anaesthesia reduces postoperative nausea and vomiting in gynaecological patients. Can J Anaesth 1993; 40: 1155–61.[Abstract/Free Full Text]
  6. Aouad MT, Siddik SS, Rizk LB, et al. The effect of dexamethasone on postoperative vomiting after tonsillectomy. Anesth Analg 2001; 92: 636–40.[Abstract/Free Full Text]
  7. Lee Y, Lin PC, Lai HY, et al. Prevention of PONV with dexamethasone in female patients undergoing desflurane anesthesia for thyroidectomy. Acta Anaesthesiol Sin 2001; 39: 151–6.[Medline]
  8. Yazigi A, Chalhoub V, Madi-Jebara S, et al. Prophylactic ondansetron is effective in the treatment of nausea and vomiting but not on pruritus after cesarean delivery with intrathecal sufentanil-morphine. J Clin Anesth 2002; 14: 183–6.[ISI][Medline]
  9. Borgeat A, Stirnemann HR. Ondansetron is effective to treat spinal or epidural morphine-induced pruritus. Anesthesiology 1999; 90: 432–6.[ISI][Medline]
  10. Pan PH, Moore CH. Intraoperative antiemetic efficacy of prophylactic ondansetron versus droperidol for cesarean section patients under epidural anesthesia. Anesth Analg 1996; 83: 982–6.[Abstract]
  11. Koivuranta M, Laara E, Ranta P, et al. Comparison of ondansetron and droperidol in the prevention of postoperative nausea and vomiting after laparoscopic surgery in women: a randomised, double-blind, placebo-controlled trial. Acta Anaesthesiol Scand 1997; 41: 1273–9.[ISI][Medline]
  12. Pearman MH. Single dose intravenous ondansetron in the prevention of postoperative nausea and vomiting. Anaesthesia 1994; 49: 11–5.
  13. Munstedt K, Muller H, Blauth-Eckmeyer E, et al. Role of dexamethasone dosage in combination with 5-HT3 antagonists for prophylaxis of acute chemotherapy-induced nausea and vomiting. Br J Cancer 1999; 79: 637–9.[ISI][Medline]
  14. Heyman JS, Young ML, Bagshaw RJ, et al. Cardiovascular stability with rapid intravenous infusion of ondansetron. Can J Anaesth 1993; 40: 448–52.
  15. Coloma M, White PF, Markowitz SD, et al. Dexamethasone in combination with dolasetron for prophylaxis in the ambulatory setting. Anesthesiology 2002; 96: 1346–50.[ISI][Medline]
  16. Sukhani R, Pappas AL, Lurie J, et al. Ondansetron and dolasetron provide equivalent postoperative vomiting control after ambulatory tonsillectomy in dexamethasone-pretreated children. Anesth Analg 2002; 95: 1230–5.[Abstract/Free Full Text]
  17. Chen JJ, Frame DG, White TJ. Efficacy of ondansetron and prochlorperazine for the prevention of postoperative nausea and vomiting after total hip replacement or total knee replacement procedures. Arch Intern Med 1998; 158: 2124–8.[Abstract/Free Full Text]
  18. Claybon L. Single dose intravenous ondansetron for the 24-hour treatment of postoperative nausea and vomiting. Anaesthesia 1994; 49: 24–9.
  19. The Italian Group for Antiemetic Research. Dexamethasone alone or in combination with ondansetron for the prevention of delayed nausea and vomiting induced by chemotherapy. N Engl J Med 2000; 342: 1554–9.[Abstract/Free Full Text]
  20. Colbert S, O’Hanlon DM, Chambers F, Moriarty DC. The effect of intravenous tenoxicam on pruritus in patients receiving epidural fentanyl. Anaesthesia 1999; 54: 76–80.[ISI][Medline]
  21. Colbert S, O’Hanlon DM, Galvin S, et al. The effect of rectal diclofenac on pruritus in patients receiving intrathecal morphine. Anaesthesia 1999; 54: 948–52.[ISI][Medline]
  22. Bunce KT, Tyers MB. The role of 5-HT in postoperative nausea and vomiting. Br J Anaesth 1992; 69: 60–2.
Accepted for publication February 25, 2003.




This article has been cited by other articles:


Home page
 Br J AnaesthHome page
M.-P. Bonnet, E. Marret, J. Josserand, and F. J. Mercier
Effect of prophylactic 5-HT3 receptor antagonists on pruritus induced by neuraxial opioids: a quantitative systematic review
Br. J. Anaesth., September 1, 2008; 101(3): 311 - 319.
[Abstract] [Full Text] [PDF]

Home page
 The Annals of PharmacotherapyHome page
A. L Kovac
Meta-Analysis of the Use of Rescue Antiemetics Following PONV Prophylactic Failure with 5-HT3 Antagonist/Dexamethasone Versus Single-Agent Therapies
Ann. Pharmacother., May 1, 2006; 40(5): 873 - 887.
[Abstract] [Full Text] [PDF]

Home page
 Anesth. Analg.Home page
A. Pirat, S. F. Tuncay, A. Torgay, S. Candan, and G. Arslan
Ondansetron, Orally Disintegrating Tablets Versus Intravenous Injection for Prevention of Intrathecal Morphine-Induced Nausea, Vomiting, and Pruritus in Young Males
Anesth. Analg., November 1, 2005; 101(5): 1330 - 1336.
[Abstract] [Full Text] [PDF]

Home page
 Anesth. Analg.Home page
C. A. Iatrou, C. K. Dragoumanis, T. D. Vogiatzaki, G. I. Vretzakis, C. E. Simopoulos, and V. K. Dimitriou
Prophylactic Intravenous Ondansetron and Dolasetron in Intrathecal Morphine-Induced Pruritus: A Randomized, Double-Blinded, Placebo-Controlled Study
Anesth. Analg., November 1, 2005; 101(5): 1516 - 1520.
[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 ISI 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
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via ISI Web of Science (7)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Szarvas, S.
Right arrow Articles by Shorten, G. D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Szarvas, S.
Right arrow Articles by Shorten, G. D.
Related Collections
Right arrow Postanesthetic Care Unit
Right arrow Regional Anesthesia
Right arrow Pharmacology

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