The Effect of Prophylactic Antiemetic Dexamethasone on Plasma Cortisol Levels

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.

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 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.