The Effect of Prophylactic Antiemetic Dexamethasone on Plasma Cortisol Levels

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2013 by McGill University Health Center
Sponsor:
Information provided by (Responsible Party):
William Li Pi Shan, McGill University Health Center
ClinicalTrials.gov Identifier:
NCT01524731
First received: January 24, 2012
Last updated: November 12, 2013
Last verified: November 2013
  Purpose

Dexamethasone is a synthetic corticosteroid that has been proven to be effective and relatively safe for the prophylaxis of the postoperative nausea and vomiting (PONV).

However, little is known about its effect on the hypothalamic-pituitary-adrenal (HPA) axis after surgery. The investigators hypothesize that it will inhibit the normal physiologic HPA surge and reduce cortisol levels post-operatively ia a dose-dependant fashion. To answer this question, the investigators will conduct a randomized, double-blinded placebo-controlled trial with two different doses of dexamethasone in women undergoing elective gynecologic laparotomy.


Condition Intervention
Postoperative Nausea and Vomiting
Drug: Saline
Drug: Dexamethasone

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: The Effect of Prophylactic Antiemetic Dexamethasone on Plasma Cortisol Levels After Gynecologic Laparotomy

Resource links provided by NLM:


Further study details as provided by McGill University Health Center:

Primary Outcome Measures:
  • Post operative cortisol level [ Time Frame: 24h post-operation ] [ Designated as safety issue: Yes ]
    The primary outcome is the plasma cortisol level at 24h post-operation.


Secondary Outcome Measures:
  • plasma cortisol [ Time Frame: 72 hours post-operatively ] [ Designated as safety issue: Yes ]
    Plasma cortisol levels at 6, 48 and 72 hours

  • Post operative nausea and vomiting scale [ Time Frame: 72 hours post-operatively ] [ Designated as safety issue: No ]
    Post operative nausea and vomiting at 6, 24, 48 and 72 hours

  • Post operative pain score [ Time Frame: 72 hours post operatively ] [ Designated as safety issue: No ]
    postoperative pain scores at 6, 24, 48 and 72 hours

  • Blood glucose level [ Time Frame: 72 hours post-operatively ] [ Designated as safety issue: Yes ]
    blood glucose levels at 6, 24, 48 and 72 hours


Estimated Enrollment: 63
Study Start Date: May 2012
Estimated Study Completion Date: February 2014
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo
Placebo group
Drug: Saline
Normal Saline
Other Name: Normal Saline
Active Comparator: 4 mg dexamethasone
4 mg dexamethasone group
Drug: Dexamethasone
4 mg
Other Name: 4 mg dexamethasone
Active Comparator: Dexamethasone 8 mg
Dexamethasone 8 mg group
Drug: Dexamethasone
8 mg
Other Name: 8 mg dexamethasone

Detailed Description:

Hypothesis:

The investigators hypothesize that preoperative administration of intravenous dexamethasone in non-cancer gynecologic laparotomy will decrease postoperative cortisol levels in a dose-dependent fashion.

Objectives:

To compare the post-operative plasma cortisol and glucose level in patients receiving various single doses of dexamethasone versus placebo at the start of gynecologic laparotomy.

To assess the dose-dependent effect of dexamethasone on postoperative pain, nausea and vomiting in this particular context.

To assess the dose-dependent effect of dexamethasone on length of hospital stay.

Methods:

This will be a prospective, randomised, double-blinded trial with two intervention arms and a placebo-control arm conducted at the Royal Victoria Hospital of the McGill University Health Center, Montreal, Canada.

Patients eligible to participate in the study based on inclusion and exclusion criteria will be approached in the preoperative anesthesia clinic (at least one week before the scheduled operation) and some patients will be recruited on the day of surgery hours before in the waiting room by a study personnel who will not be involved in the patient care the day of the surgery. After addressing the patient's questions and concerns, informed consent will be obtained. The patient, the investigators and the anesthesiologist in charge of the patient will be blinded to group allocation until completion of the study.

After patient recruitment, an intravenous line will be placed inside the operating room. Blood will simultaneously be drawn for a baseline plasma cortisol levels. The patients will receive a single IV bolus dose of dexamethasone 4mg, 8mg or an IV normal saline placebo (based on group allocation by randomization) immediately after induction of anesthesia 8. Anesthetic premedication will comprise of 1mg of midazolam. Induction will be performed using 2-3 mg/kg propofol, 2-3 mcg/kg fentanyl, 0.5-1.0 mg/kg rocuronium. Anesthetic maintenance will be performed through an endotracheal tube using desflurane at a minimum of 1 MAC in an equal air/oxygen mixture. Endtidal carbon dioxide tension will be maintained at 40 mmHg using the appropriate ventilator adjustments. Fluid management consists of crystalloid boluses of 20 mg/kg to replace fasting losses, colloid and blood products as necessary according to the surgical losses. Neostigmine and glycopyrrolate reversal will be used if no train of four twitch exists. Ondansetron 4 mg will be given to all patients prior to tracheal extubation.

In the postoperative anesthesia care unit, dimenhydrinate 25-50 mg, prochlorperazine 10 mg will be used should nausea, vomiting, or retching occur. Pain will be controlled by rectal acetaminophen 325mg-1.3 g. Patient controlled analgesia fentanyl will be administered to all patients at a lockout interval of 7 minutes. In the gynaecological ward, dimenhydrinate will be used to control nausea and vomiting.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Women between 18 and 80 years-old scheduled for non-oncologic gynecologic laparotomy, including fibroid myomectomy, hysterectomy and endometrioma resection

Exclusion Criteria:

  • Communication barrier rendering informed consent inadequate
  • Pregnancy
  • Diabetes mellitus
  • Chronic or acute renal failure
  • Chronic or acute hepatic failure
  • History of chronic opioid use
  • History of corticosteroid use more than 3 weeks in the last 6 months (inhaled, oral or intravenous)
  • History of disorders of the hypothalamus, pituitary gland and/or adrenal glands
  • History of depression and/or bipolar disorder
  • History of allergy or sensitivity to dexamethasone or any medication used in the standardised anesthetic care
  • American Society of Anesthesiologists Physical Status class of 3 and above.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01524731

Contacts
Contact: Aly Elbahrawy, MD 5149033772 aly.elbahrawy@mail.mcgill.ca

Locations
Canada, Quebec
Royal Victoria Hospital Recruiting
Montreal, Quebec, Canada, H3A 1A1
Contact: William K. Li Pi Shan, MD       william.li_pi_shan@mcgill.ca   
Contact: Roupen Hatzakorzian, MD, M.Sc       roupenhatz@hotmail.com   
Principal Investigator: William Li Pi Shan, MD         
McGill University Health Centre-Royal Victoria Hospital Recruiting
Montreal, Quebec, Canada, H3A 1A1
Contact: William K Li Pi Shan, MD       william.li_pi_shan@mcgill.ca   
Sponsors and Collaborators
William Li Pi Shan
Investigators
Principal Investigator: William K. Li Pi Shan, MD McGill University
  More Information

No publications provided

Responsible Party: William Li Pi Shan, Assistant Professor, McGill University Health Center
ClinicalTrials.gov Identifier: NCT01524731     History of Changes
Other Study ID Numbers: 11-149-SDR
Study First Received: January 24, 2012
Last Updated: November 12, 2013
Health Authority: Canada: Ethics Review Committee
United States: Food and Drug Administration

Additional relevant MeSH terms:
Vomiting
Postoperative Nausea and Vomiting
Signs and Symptoms, Digestive
Signs and Symptoms
Postoperative Complications
Pathologic Processes
Nausea
Antiemetics
Dexamethasone
Dexamethasone acetate
Hydrocortisone
Dexamethasone 21-phosphate
BB 1101
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Gastrointestinal Agents
Anti-Inflammatory Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 24, 2014