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1154 www.anesthesia-analgesia.org June 2014 Volume 118 Number 6

Copyright 2014 International Anesthesia Research Society

DOI: 10.1213/ANE.0000000000000223

The routine use of dexamethasone for the prophylaxisof postoperative nausea and vomiting (PONV) has

been controversial and debated among anesthesiolo-gists and anesthesia providers for many years. Why is this?There are clear data to support that dexamethasone, withits relative low cost and high efficacy, is a preferred anti-emetic for the prevention of PONV, as recommended by thePONV Consensus Guidelines.1 Compared with ondanse-tron, a 5-HT-3 receptor antagonist, which is likely the mostcommonly used antiemetic to prevent and treat PONV, thenumber needed-to-treat to prevent PONV for dexametha-sone is 4, compared with 6 to 7 for ondansetron.2,3The idealprophylactic dosage appears to be 4 mg IV at induction ofanesthesia;4however, 8 mg IV may provide the additional

benefit of pain relief because of opioid-sparing effects5 aswell as shorten recovery time.6

The reason for this controversy, of course, is that dexa-methasone is a glucocorticoid with many feared side effectswhen used in the perioperative patient population. There

have been concerns regarding the risk of wound infections,wound healing, perioperative bleeding, cortisol suppres-sion, neuromuscular weakness, high blood glucose levels,and even cancer recurrence.710 In this issue of Anesthesia& Analgesia, 2 concerns of dexamethasone, the associationwith steroids and the recurrence of cancer, as well as theconcern for the induction of perioperative hyperglycemia,are examined.

Glucocorticoids and their use in cancer patients have longbeen a topic of concern in the perioperative setting. Surgicalexcision is the primary definitive treatment for many formsof cancer, with tumor recurrence and metastatic disease

being the most important cause of mortality in surgical can-

cer patients. The suppression of host defenses in the periop-erative period, as well as the role of anesthetic techniques

and drug choices, are becoming increasingly scrutinizedregarding their effect on host immunity.11 Dexamethasonehas been shown to suppress T cell function as well as natu-ral killer cell development,12,13both of which are known toparticipate in antitumor immune responses.14Despite thesefindings, there are few data at this point regarding cortico-steroid use and cancer recurrence.

In this issue, De Oliveira et al.15present a retrospectiveobservational study that analyzes the effect of perioperativesystemic dexamethasone (410 mg) for PONV prophylaxisin women who underwent primary ovarian cytoreductivesurgery for ovarian cancer and the risk of ovarian cancerrecurrence. The primary aim was to determine the overallincrease in the risk of ovarian cancer recurrence in thesepatients by determining tumor recurrence in women givenperioperative dexamethasone versus those who did notreceive the medication. Of 260 women included in the study,178 had cancer recurrence; 102 of these patients receiveddexamethasone. The study ultimately found no significant

association between perioperative dexamethasone use andovarian cancer recurrence after primary surgical treatmentand therefore does not support the avoidance of single-dosedexamethasone for PONV prophylaxis. There are someacknowledged weaknesses to the study, such as a smallsample size and a lack of standardization of intraoperativeand postoperative analgesic management. This is particu-larly important in that several studies have suggested thatthe use of opioids in the perioperative setting may havean effect on angiogenesis and cancer outcomes. Opioidshave been found to regulate the growth of neoplastic cellsthrough the modulation of cell proliferation and apopto-sis; they cause immunosuppression, as well as modulate

angiogenesis, aiding tumor metastasis and growth throughactivation of vascular growth cell receptors such as vascularendothelial growth factor and platelet derived growth fac-tor.16 Another study presented evidence that opioids mayhave a direct effect on lung cancer progression throughinteraction with the -opioid receptor.17 In cancer recur-rence from single-dose dexamethasone, there is no clini-cal evidence in the literature to refute the above findings.In fact, Egberts et al.18created an animal model in whichdexamethasone had utility in preventing the recurrence andmetastasis of pancreatic cancer. A study by Munstedt et al.19found that dexamethasone used along with chemotherapydid not affect ovarian cancer outcomes but may have pro-

tective effects on bone marrow.

Cancer Recurrence and Hyperglycemia with

Dexamethasone for Postoperative Nausea andVomiting Prophylaxis: More Moot Points?

Brian Colin, MD, and Tong J. Gan, MD, MHS, FRCA

From the Anesthesiology Department, Duke University Medical Center,Durham, North Carolina.

Accepted for publication February 7, 2014.

Funding: None.

Conflicts of Interest: See Disclosures at the end of the article.

Reprints will not be available from the authors.

Address correspondence to Tong J. Gan, MD, MHS, FRCA, Department ofAnesthesiology, Duke University Medical Center, Durham, NC 27710. Ad-dress e-mail totjgan@duke.edu.

EDITORIALE

mailto:tjgan@duke.edumailto:tjgan@duke.edu

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Cancer Recurrence and Hyperglycemia with Dexamethasone

June 2014 Volume 118 Number 6 www.anesthesia-analgesia.org 1155

Another often-touted risk of dexamethasone use is

the concern for intraoperative and postoperative hyper-

glycemia, with several previous studies demonstrating a

transient rise in glucose levels with the use of glucocorti-

coids.20,21Glucocorticoids are known to increase hepatic

glucose production, while increasing insulin resistance

and decreasing glucose oxidation and uptake.22 These

hyperglycemic effects may be associated with adverse

outcomes in the critically ill and postsurgical patients,

such as suppression of immune function, increase in

proinflammatory cytokines, increased systemic vascular

resistance, osmotic diuresis, and electrolyte as well as

acidbase imbalances.23

Murphy et al.24address this concern in this issue with a

randomized, placebo-controlled trial to address the effect of

dexamethasone on blood glucose concentration in the peri-

operative environment for gynecologic surgical patients. The

primary outcome was to determine the effect of a single low-

dose dexamethasone therapy (4 and 8 mg) on blood glucose

concentrations during the first 24 hours following adminis-

tration and to record the incidence of hyperglycemic events(blood glucose level >180 mg/dL). Patients presenting for

elective hysterectomies were randomized to receive saline,

dexamethasone 4 mg, or dexamethasone 8 mg, with blood

glucose measurements at specified times for each group

within a 24-hour perioperative period. The study found that

while blood glucose concentrations increased significantly

in all control and dexamethasone groups, they did not differ

significantly between the dexamethasone and saline control

groups at any time within the 24-hour perioperative period.

Therefore, the results suggest that low-dose dexamethasone

used for PONV prophylaxis should not be avoided because of

concerns for hyperglycemic events. This finding is supported

by other evidence in the literature. One study by Abdelmalaket al.25showed that while patients undergoing major noncar-

diac surgery had higher blood glucose levels after receiving

dexamethasone 8 mg versus placebo, the effect was very lim-

ited in both diabetic and nondiabetic patients. A similar study

by Nazar et al.26investigated a group of 40 nondiabetic and

30 type-2 diabetic patients undergoing laparoscopic cholecys-

tectomy. Patients were randomized to receive either saline or

dexamethasone 8 mg, and the results showed that there was

no higher susceptibility in the type-2 diabetic patients than

the nondiabetic patients to develop perioperative hypergly-

cemia following PONV doses of dexamethasone.

Our group recently wrote an editorial in this journalwith the title: Wound complications with dexamethasone for

postoperative nausea and vomiting prophylaxis: a moot point?27

We concluded that the current literature does not sup-

port the concern that single-dose use of intraoperative

dexamethasone contributes to a statistically significant

increase in the incidence of wound complications or time

to complete wound healing.27This, along with the above

evaluations of the concerns of the use of single-dose dexa-

methasone for PONV and the recurrence of cancer or

intraoperative hyperglycemia, suggest again that anesthe-

siologists can safely use dexamethasone 4 to 8 mg doses

for PONV prophylaxis.E

DISCLOSURES

Name:Brian Colin, MD.Contribution:The author helped write the manuscript.Conflicts of Interest:The author has no conflicts of interest todeclare.Name:Tong J. Gan, MD, MHS, FRCA.Contribution:The author helped write the manuscript.Conflicts of Interest:Research Support from: Pacira, Covidien,

Fresenius, Merck, Purdue, AcelRx, Acacia. Honoraria receivedfrom: Merck, Cadence, Edwards, Covidien.This manuscript was handled by:Sorin J. Brull, MD, FCARCSI(Hon).

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