The Effect of Prophylactic Antiemetic Dexamethasone on Plasma Cortisol Levels
Condition: Postoperative Nausea and Vomiting
MeSH terms: Vomiting; Postoperative Nausea and Vomiting
Study type: Interventional

Summary: 
      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.
    

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.
    

Intervention name(s): Saline; Dexamethasone; Dexamethasone
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Normal Saline; 4 mg; 8 mg
Other intervention name(s): Normal Saline; 4 mg dexamethasone; 8 mg dexamethasone
Intervention MeSH terms: Dexamethasone; Dexamethasone acetate; BB 1101
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment