Previous article Table of Contents  Next article

REVIEW ARTICLE
Year : 2019  |  Volume : 13  |  Issue : 3  |  Page : 231-236

Extended release granisetron: Review of pharmacologic considerations and clinical role in the perioperative setting


1 Beth Israel Deaconess Medical Center, Department of Anesthesia, Critical Care, and Pain Medicine, Harvard Medical School, Boston, MA, USA
2 University of Pennsylvania, Philadelphia, PA, USA
3 Valley Anesthesiology and Pain Consultants, Phoenix, AZ; University of Arizona College of Medicine-Phoenix, Department of Anesthesiology, Phoenix, AZ; Creighton University School of Medicine, Department of Anesthesiology, Omaha, NE, USA
4 Brigham and Women's Hospital, Department of Anesthesiology, Perioperative, and Pain Medicine, Harvard Medical School, Boston, MA, USA

Correspondence Address:
Dr. Ivan Urits
Department of Anesthesia, Critical Care, and Pain Medicine, 330 Brookline Ave, Boston, MA - 02215
USA
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/sja.SJA_817_18

Rights and Permissions
Date of Web Publication26-Jun-2019
 

  Abstract 


In this review, we evaluate recent literature on use of ER granisetron in clinical practice as compared with current antiemetics and describe its potential uses for perioperative PONV prophylaxis and treatment. Recent literature was evaluated on ER granisetron use compared with currently used antiemetic agents ondansetron, droperidol, metoclopramide, promethazine, and dexamethasone with a focus on procedural anti-emesis. Though promising great effect, application of extended release granisetron to clinical use may be limited by it's increased relative cost.

Keywords: 5-HT3 antagonists; anti-emetics; pharmacotherapy; post-operative nausea and vomiting


How to cite this article:
Ngo AL, Orhurhu V, Urits I, Delfin EO, Sharma M, Jones MR, Viswanath O, Urman RD. Extended release granisetron: Review of pharmacologic considerations and clinical role in the perioperative setting. Saudi J Anaesth 2019;13:231-6

How to cite this URL:
Ngo AL, Orhurhu V, Urits I, Delfin EO, Sharma M, Jones MR, Viswanath O, Urman RD. Extended release granisetron: Review of pharmacologic considerations and clinical role in the perioperative setting. Saudi J Anaesth [serial online] 2019 [cited 2019 Aug 18];13:231-6. Available from: http://www.saudija.org/text.asp?2019/13/3/231/260817




  Introduction Top


Antiemetics ondansetron, metoclopramide, droperidol, promethazine, and dexamethasone are commonly used in anesthesia. Relatively safe and effective in managing postoperative nausea and vomiting (PONV), each has drawbacks and restrictions in clinical practice. Extended-release (ER) granisetron (Sustol®), a novel 5-hydroxytryptamine (5-HT3) receptor antagonist through soft drug development received recent U.S. Drug and Food Administration approval for prevention of acute and delayed nausea and vomiting in cancer patients. Because controversy surrounding data reliability on short-acting granisetron has resolved, it has been useful in treatment of PONV.[1],[2],[3],[4],[5],[6] In this review, we evaluate recent literature on use of ER granisetron in clinical practice as compared with current antiemetics and describe its potential uses for perioperative PONV prophylaxis and treatment. We performed a literature search of the Medline database (2013 - March 2017). Additional references were identified from review of literature citations, manufacturer reports, and professional meeting abstracts. Premarket studies that involved ER granisetron as the primary study drug were evaluated. Literature describing the pharmacokinetics and pharmacodynamics of the short acting granisetron (Kytril®), ondansetron, metoclopramide, droperidol, promethazine, and dexamethasone was also included. Phase I, II, and III studies in the United States have shown ER granisetron to be safe and effective for the prevention of nausea and vomiting in cancer patients, which may be applicable to post-surgical patients. Economic analyses of costs versus benefits will need to be examined.


  Materials and Methods Top


Recent literature was evaluated on ER granisetron use compared with currently used antiemetic agents ondansetron, droperidol, metoclopramide, promethazine, and dexamethasone with a focus on procedural anti-emesis. Medline database search was performed using the term, “extended release granisetron.”Additional references were identified from a review of manufacturer reports, literature citations, and abstracts from professional meetings. All premarket studies involving granisetron as the primary study drug were evaluated. Literature describing the pharmacokinetics and pharmacodynamics of granisetron, ondansetron, droperidol, metoclopramide, promethazine, and dexamethasone were included.

Extended release granisetron

Developed as APF530 by A.P. Pharma (now Heron Therapeutics), ER granisetron received regluatory approval in August 2016 under trade name Sustol® for treatment in acute and delayed phase of chemotherapy induced nausea and vomiting (CINV).[7] It has experienced successful adoption as a delayed-release antiemetic.[8] With increased durability of effect, ER granisetron has potential for future use in PONV.

Mechanism, pharmacokinetics, pharmacodynamics, and efficacy

Granisetron selectively binds and antagonizes 5-HT3 receptors to prevent serotonin mediated emetogenic stimuli. ER granisetron demonstrates favorable bio-parameters, including slow hydrolysis with plasma detection for 7 days with maximum plasma concentration at 24 h following single dose. Dosing frequency is maximized at once per week.[9] Composed of 2% granisetron and a bioerodible tri (ethylene glycol) poly (orthoester) polymer, drug delivery is sustained release with a terminal elimination half-life of 24 h and predominantly cleared through hepatic metabolism.[10]

ER granisetron appears to be superior to ondansetron. In phase 3 studies, ER granisetron treated group experienced a greater complete response (CR) rate (65%) compared to IV ondansetron (56%; P = 0.014) in the delayed phase onset phase of CINV (24-120 h post HEC) with better secondary endpoints including delayed complete control (CC), overall CR, overall CC, and overall no emesis. In addition, ER granisetron showed a comparable safety and tolerability profile compared to ondansetron.[11] As an antiemetic, the increasing durability of therapeutic efficacy from granisetron and a competitive safety and tolerability against commonly used antiemetics make it well-suited for potential use beyond chemotherapy. The findings of clinical trials assessing safety and efficacy of ER granisetron are summarized in [Table 1].
Table 1: Summary of extended release granisetron trial data

Click here to view


Use in procedures as a prophylactic and therapeutic antiemetic

ER granisetron can be useful in clinical anesthesia. In procedures for patients with known severe nausea and vomiting, it can decrease morbidity and mortality in medical conditions where PONV would exacerbate complications.

One potential area for use of ER granisetron is pregnancy, especially in patients with hyperemesis gravidarum and cesarean delivery patients under general or neuraxial anesthesia. In a double blinded randomized controlled trial (RCT), short-acting granisetron showed a reduced PONV incidence of 25% in the granisetron group versus 62.5% in placebo.[12] Compared to ondansetron, which is commonly used in pregnant patients, granisetron presents with similar efficacy, but potency and duration are far superior. Hyperemesis gravidarum has been traditionally treated with promethazine and ondansetron.[13] Limited safety data exist for 5-HT3 receptor antagonists in pregnancy, given the popular use of ondansetron. In a double blind randomized RCT assessing efficacy and incidence of adverse reactions for managing hyperemesis gravidarum, granisetron was superior to promethazine with patients receiving granisetron experiencing fewer vomiting episodes at 48 h, shorter hospital stays, lower rates of rehospitalization, and no reported adverse drug reactions.[14] An ER formulation could benefit this patient population with less frequent dosing, especially in those with a known history of nausea and vomiting.

ER granisetron can be used in surgical patients with a high incidence of PONV such as abdominal, gynecologic, laparoscopic, breast, and ENT surgery. Granisetron has been shown to be effective as prophylactic anti-emetic therapy in these populations. One study showed granisetron was more efficacious than droperidol in preventing PONV during the first 24 h following surgery (incidence of PONV 22% vs. 42%).[15] Overall, surgical patients with high risk for prolonged PONV or known history, may find ER granisetron to be effective and better tolerated, reducing post-operative recovery, and unexpected medical visits.

Further development and potential for clinical use

Since FDA approval, ER granisetron has been used in patients undergoing cytotoxic chemotherapeutic therapy. However recently, granisetron has been described as a treatment for pain given serotonin's role in pain pathways. In a double blind RCT, patients treated with repeated intramuscular tender-point injections with granisetron for pain of temporomandibular regions demonstrated a 40% decrease in pain versus control at 1 month and 55% decrease at 6 months.[16] Further studies may elucidate a role for granisetron in many generalized pain syndromes, where ER granisetron may help in pain control with infrequent outpatient dosing.

Safety concerns

A major safety concern exists for 5-HT3 antagonists, namely QTc interval prolongation causing serious arrhythmias and subsequently death. The FDA has issued a warning for this drug class regarding these potential cardiac effects. Granisetron has not been found to have any significant effects on QTc interval in clinical trials.[15],[17],[18] However, limited information is available in regard to ER granisetron, and more studies are needed to address potential safety concerns.


  Discussion Top


The effective management of PONV is important in perioperative care. In some studies, PONV is often rated as worse than postoperative pain by patients.[19] PONV can affect patient satisfaction, impact traditional outcome variables, including hospital length of stay and readmission rates, and results in complications such as dehydration, aspiration, wound dehiscence, and secondary complications such as esophageal rupture or pneumothorax.[20] PONV is common-without prophylaxis, it is reported to occur in 30% to 80% of patients.[21] Serotonin (5-HT3) receptor antagonists are the current standard for PONV and are relatively safe and efficacious.[22] They lack sedative side effects, as compared to the other PONV drugs that act as antagonists for dopamine D2 receptors in the chemoreceptor trigger zone in the area postrema of the medulla.[23] This is an important advantage postoperatively, which is why some clinicians reserve these drugs for post-anesthesia care. ER granisetron, another 5-HT3 receptor antagonist, was FDA-approved in 2016 for acute and delayed nausea and vomiting in cancer patients.[24] This is a high-risk group, and given its efficacy for CINV, it may prove useful in PONV.

In current regimen, 10 mg of ER granisetron injected subcutaneously versus intravenous administration with other antiemetics has important implications in nursing resource utilization.[9] Its slow release over 7 days with a peak concentration in plasma 24 h after injection makes it a viable candidate to treat PONV, while at the same time, addressing drawbacks of regular-release granisetron (Kytril®), which is short-acting, has a half-life of 6 h, and possesses a narrow therapeutic index.[9] The ability of extended release granisetron to maintain therapeutic drug levels for 5 days with a single subcutaneous injection provides a high convenience factor for staffing and costs reduction.[25] However, this benefit addresses not only acute phase postoperatively but also has potential impact on readmission rates, which is particularly important in surgeries associated with high PONV predictive scores. Many surgeries, such as laparoscopic cholecystectomy, gynecologic surgeries, and tympanoplasty, are increasingly performed in the same day surgery centers or on in-patients with rapid discharge planning, where most benefit can be achieved.

Granisetron, as an antiemetic drug, demonstrates favorable efficacy and fewer side effects. As a selective 5-HT3 antagonist, antiemetic effects are achieved by blocking vagus nerve 5-HT receptors without affinity for other 5-HT receptors. Although major antiemetics used in PONV are more effective than placebo, 5-HT3 antagonists were more effective in meta-analysis in children compared to metoclopramide and droperidol.[26],[27] Furthermore, 5-HT3 antagonists were far less likely to cause extrapyramidal side effects (metoclopramide), sedation (phenothiazines, butyrophenones - droperidol), or QTc prolongation (droperidol).[28],[29] This makes using granisetron easier when considering patients with polypharmacy who may be taking other drugs known to prolong the QTc interval (anti-depressants, anti-psychotics, antihistamines, and some antibiotics such as the macrolides and quinolones). Although prokinetic effects of metoclopramide are effective in pregnancy, extrapyramidal side effects are deleterious in higher doses.[30] In addition, combination therapy for high-risk patients with PONV is more effective than monotherapy, and in this scenario, using extended release granisetron as the 5-HT3 antagonist with phenothiazine may allow coverage beyond the early postoperative phase while avoiding delayed sedation.[29] Further, subcutaneous ER granisetron use will avoid severe tissue injury associated with accidental promethazine extravasation. Although dexamethasone was found to be as effective as others therapies, including tropisetron and ramosetron, consideration must be made of the risk and benefits in diabetics, pregnant patients, and those prone to anxiety and gastric ulceration.[31]

ER granisetron may play a role in enhancing efficiency and better care in organizations. Institutional policies consider safety, efficacy, ease of ordering, administration, and patient satisfaction when generating standards of care and algorithms in care pathways. When ER granisetron was compared to gold standard antiemetics, specifically ondansetron, it had similar if not better safety and tolerability profiles. The added advantage of delayed release antiemetic effect (avoiding the narrow therapeutic index of granisetron) and durability of effect makes it very attractive when considering early discharge and avoiding readmission.[32] Most organizations have algorithms for prophylaxis of PONV, a reportable quality measure to CMS with possible punitive consequences for Medicare reimbursement. Droperidol, promethazine, and metoclopramide have side effects including headache, sedation, drowsiness, fatigue, and extrapyramidal symptoms. In addition, droperidol, as mentioned above, had an FDA-issued warning about arrhythmias and deaths from QTc interval prolongation. Promethazine also cannot be given to patients with neurological, cardiac, or respiratory depression, and the FDA issued a black box warning for it causing gangrene or severe tissue injury if leaked into local tissues. Side effects of dexamethasone include anxiety, insomnia, psychosis, and gastric ulcers.[31] Overall, side effect profiles of 5-HT3 antagonists are less.[27]

Currently, ondansetron is the standard. However, ER granisetron, being in the same class, has a similar efficacy, but is more potent, has a longer duration, and is possibly better in safety because of greater selective 5-HT3 antagonism.[15] In addition, potential side effects of ondansetron include headache, malaise, constipation, and diarrhea with the most harmful being cardiac arrhythmias and death. ER granisetron, however, has shown not to cause electrocardiogram (ECG) changes, only yielding side effects of constipation, diarrhea, dyspepsia, abdominal pain, and headache.[33] Ondansetron is useful as prophylaxis, but granisetron is more potent, longer-acting, making it potentially more useful in those patients with a known PONV history or refractory PONV.[4]

When compared with dexamethasone, ER granisetron presents strong merits for use. Dexamethasone, used for PONV prophylaxis, is effective in immediate as well as initial postoperative period.[34] However, dexamethasone may cause glycemic disturbances in diabetics, anxiety/insomnia in elderly, and impact those on psychiatric medications, making ER granisetron more attractive in patients with multiple comorbidities.[31] The single injection model of ER granisetron could ensure better compliance and safety in cognitively impaired elderly. In the “early discharge” paradigms, ER granisetron may have advantages over phenothiazines and dexamethasone, given less sedation and perturbation of glycemic control, respectively.[28]

ER granisetron presents usability in multiple clinical settings. In ICU, ER granisetron may have advantages in avoiding QTc prolongation with polypharmacy, especially with other drugs that may be contraindicated in cardiac patients.[33] It can be used in outpatient settings, such as clinics or for elderly nursing homes because ER granisetron is subcutaneously injected rather than intravenously given. Results have shown that ER granisetron to be safe and efficacious in certain patients such as pregnant women.[14] Its potency and efficacy needs to be compared to newer generation 5-HT3 antagonists such as palonosetron, also approved for CINV, but is more expensive than ER granisetron (granisetron costs $23.36 per 3 mg, whereas palonosetron costs $118 for 0.75 mg).[25] However, ER granisetron may have unknown effects such as desensitization or rebound phenomena because of its prolonged nature.[4] Further safety and efficacy studies are needed to investigate potential long-term effects.

The relatively good safety profile and selectivity of granisetron as a 5-HT3 antagonist may make it appealing for other clinical indications. Most promising is chronic pain management through local injection in pain areas.


  Conclusion Top


ER granisetron is a recent anti-emetic agent to arise out of soft drug development. It has a potential as a valuable adjunctive anti-emetic agent. It has received FDA approval for market in 2016 as an antiemetic for CINV with the potential to be used in the perioperative setting. More studies must be conducted to compare the efficacy of ER granisetron on reducing nausea and vomiting in relation to commonly used drugs today. Although promising great effect, application to clinical use may be limited by increased relative cost.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Kranke P, Apfel CC, Roewer N, Fujii Y. Reported data on granisetron and postoperative nausea and vomiting by Fujii,et al. Are incredibly nice! Anesth Analg 2000;90:1004-7.  Back to cited text no. 1
    
2.
Tramèr MR. The Fujii story. Eur J Anaesthesiol 2013;30:195-8.  Back to cited text no. 2
    
3.
Saito M, Aogi K, Sekine I, Yoshizawa H, Yanagita Y, Sakai H,et al. Palonosetron plus dexamethasone versus granisetron plus dexamethasone for prevention of nausea and vomiting during chemotherapy: Adouble-blind, double-dummy, randomised, comparative phase III trial. Lancet Oncol 2009;10:115-24.  Back to cited text no. 3
    
4.
Savant K, Khandeparker RVS, Berwal V, Khandeparker PV, Jain H. Comparison of ondansetron and granisetron for antiemetic prophylaxis in maxillofacial surgery patients receiving general anesthesia: Aprospective, randomised, and double blind study. J Korean Assoc Oral Maxillofac Surg 2016;42:84-9.  Back to cited text no. 4
    
5.
Mohammadi S, Jabbarzadeh S, Movafegh A. Efficacy of granisetron on prevention of shivering, nausea and vomiting during cesarean delivery under spinal anesthesia: A randomized double-blinded clinical trial. J Obstet Anaesth Crit Care 2015;5:22-6.  Back to cited text no. 5
  [Full text]  
6.
Wilson AJ, Diemunsch P, Lindeque BG, Scheinin H, Helbo-Hansen HS, Kroeks MV,et al. Single-dose i.v. granisetron in the prevention of postoperative nausea and vomiting. Br J Anaesth 1996;76:515-8.  Back to cited text no. 6
    
7.
Heron Therapeutics. Heron Therapeutics Announces U.S. FDA Approval of Sustol® (granisetron) Extended-Release Injection for the Prevention of Chemotherapy-Induced Nausea and Vomiting 2016.  Back to cited text no. 7
    
8.
Heron Therapeutics, Inc. FY17-Q3 Form 10-Q for the Period Ending September 30, 2017. SEC 2017:3.  Back to cited text no. 8
    
9.
Morrison D, Anderson A, Slama M, Guernsey B, Payne Y, Fu CH,et al. Phase I bioavailability study comparing 2 different subcutaneous routes of administration for APF530. Support Care Cancer 2015;23:S132.  Back to cited text no. 9
    
10.
Smith C, Yanagihara R, Spaczyński M, Cooper W, O'Boyle E, Smith C,et al. Pharmacokinetics, safety, and efficacy of APF530 (extended-release granisetron) in patients receiving moderately or highly emetogenic chemotherapy: Results of two Phase II trials. Cancer Manag Res 2015;7:83-92.  Back to cited text no. 10
    
11.
Schwartzberg L, Mosier M, Payne Y, Klepper M, Schnadig I. Phase 3 trial of APF530 vs. ondansetron, each with a neurokinin 1 antagonist and corticosteroid, for prevention of chemotherapy-induced nausea and vomiting in highly emetogenic chemotherapy regimens (MAGIC Trial): Outcomes in cisplatin-based regimen. Gynecol Oncol 2016;141:40.  Back to cited text no. 11
    
12.
Dasgupta M, Biswas BN, Chatterjee S, Mazumder P, Bhanja Chowdhury M. Randomized, placebo-controlled trial of granisetron for control of nausea and vomiting during cesarean delivery under spinal anesthesia. J Obstet Gynaecol India 2012;62:419-23.  Back to cited text no. 12
    
13.
Abramowitz A, Miller ES, Wisner KL. Treatment options for hyperemesis gravidarum. Arch Womens Ment Health 2017;20:363-72.  Back to cited text no. 13
    
14.
Aleyasin A, Saffarieh E, Torkamandi H, Hanafi S, Sadeghi F, Mahdavi A,et al. Comparison of efficacy of granisetron and promethazine in control of hyperemesis gravidarum. J Obstet Gynecol India 2016;66:409-14.  Back to cited text no. 14
    
15.
Janknegt R, Pinckaers JWM, Rohof MHC, Ausems MEM, Arbouw MEL, Van Der Velden RW,et al. Double-blind comparative study of droperidol, granisetron and granisetron plus dexamethasone as prophylactic anti-emetic therapy in patients undergoing abdominal, gynaecological, breast or otolaryngological surgery. Anaesthesia 1999;54:1059-68.  Back to cited text no. 15
    
16.
Christidis N, Omrani S, Fredriksson L, Gjelset M, Louca S, Hedenberg-Magnusson B,et al. Repeated tender point injections of granisetron alleviate chronic myofascial pain--a randomized, controlled, double-blinded trial. J Headache Pain 2015;16:104.  Back to cited text no. 16
    
17.
Carmichael J, Harris AL. The cardiovascular safety of high-dose intravenous granisetron in cancer patients receiving highly emetogenic chemotherapy. Cancer Chemother Pharmacol 2004;53:123-8.  Back to cited text no. 17
    
18.
Aapro M, Bourke JP. Rapid intravenous administration of granisetron prior to chemotherapy is not arythmogenic: Results of a pilot study. Eur J Cancer 2003;39:927-31.  Back to cited text no. 18
    
19.
Macario A, Weinger M, Carney S, Kim A. Which clinical anesthesia outcomes are important to avoid? The perspective of patients. Anesth Analg 1999;89:652-8.  Back to cited text no. 19
    
20.
Fortier J, Chung F, Su J. Unanticipated admission after ambulatory surgery — a prospective study. Can J Anaesth 1998;45:612-9.  Back to cited text no. 20
    
21.
Cohen MM, Duncan PG, DeBoer DP, Tweed WA. The postoperative interview: Assessing risk factors for nausea and vomiting. Anesth Analg 1994;78:7-16.  Back to cited text no. 21
    
22.
Tramèr MR, Reynolds DJ, Moore RA, McQuay HJ. Efficacy, dose-response, and safety of ondansetron in prevention of postoperative nausea and vomiting: Aquantitative systematic review of randomized placebo-controlled trials. Anesthesiology 1997;87:1277-89.  Back to cited text no. 22
    
23.
Storrar J, Hitchens M, Platt T, Dorman S. Droperidol for treatment of nausea and vomiting in palliative care patients. Cochrane Database Syst Rev 2014:CD006938. doi: 10.1002/14651858.CD006938.pub3.  Back to cited text no. 23
    
24.
A.P. Pharma Receives FDA Complete Response Letter for APF530. Drugs.com. https://www.drugs.com/nda/apf530_100319.html. Published 2010.  Back to cited text no. 24
    
25.
Matsumaru A, Tsutsumi Y, Ito S. Comparative investigation of the anti-emetic effects of granisetron and palonosetron during the treatment of acute myeloid leukemia. Mol Clin Oncol 2017;7:629-32.  Back to cited text no. 25
    
26.
Apfel CC, Korttila K, Abdalla M, Kerger H, Turan A, Vedder I, et al. A factorial trial of six interventions for the prevention of postoperative nausea and vomiting. N Engl J Med 2004;350:2441-51.  Back to cited text no. 26
    
27.
Loewen PS, Marra CA, Zed PJ. 5-HT3 receptor antagonistsvs traditional agents for the prophylaxis of postoperative nausea and vomiting. Can J Anesth Can Anesth 2000;47:1008-18.  Back to cited text no. 27
    
28.
Braude D, Soliz T, Crandall C, Hendey G, Andrews J, Weichenthal L. Antiemetics in the ED: Arandomized controlled trial comparing 3 common agents. Am J Emerg Med 2006;24:177-82.  Back to cited text no. 28
    
29.
Ruiz JR, Ensor JE, Lim JW, Van Meter A, Rahlfs TF. Phenothiazine vs 5HT3 antagonist prophylactic regimens to prevent post-anesthesia care unit rescue antiemetic: An observational study. Open J Anesthesiol 2015;5:27-32.  Back to cited text no. 29
    
30.
Jolliet P, Nion S, Allainveyrac G, Tilloy-Fenart L, Vanuxeem D, Berezowski V,et al. Evidence of lowest brain penetration of an antiemetic drug, metopimazine, compared to domperidone, metoclopramide and chlorpromazine, using an in vitro model of the blood–brain barrier. Pharmacol Res 2007;56:11-7.  Back to cited text no. 30
    
31.
Barbour SY. Corticosteroids in the treatment of chemotherapy-induced nausea and vomiting. J Natl Compr Canc Netw 2012;10:493-9.  Back to cited text no. 31
    
32.
Parra-Sanchez I, Abdallah R, You J, Fu AZ, Grady M, Cummings K 3rd,et al. A time-motion economic analysis of postoperative nausea and vomiting in ambulatory surgery. Can J Anesth Can Anesth 2012;59:366-75.  Back to cited text no. 32
    
33.
Mason J, Moon T, O'Boyle E, Dietz A. A randomized, placebo-controlled, four-period crossover, definitive QT study of the effects of APF530 exposure, high-dose intravenous granisetron, and moxifloxacin on QTc prolongation. Cancer Manag Res 2014;6:181-90.  Back to cited text no. 33
    
34.
De Oliveira GS, Castro-Alves LJS, Ahmad S, Kendall MC, McCarthy RJ. Dexamethasone to prevent postoperative nausea and vomiting. Anesth Analg 2013;116:58-74.  Back to cited text no. 34
    



 
 
    Tables

  [Table 1]



 

Top
 
Previous article    Next article
 
  Search
 
    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Access Statistics
    Email Alert *
    Add to My List *
* Registration required (free)  

 
  IN THIS Article
   Abstract
  Introduction
   Materials and Me...
  Discussion
  Conclusion
   References
   Article Tables

 Article Access Statistics
    Viewed185    
    Printed4    
    Emailed0    
    PDF Downloaded16    
    Comments [Add]    

Recommend this journal