Effect of Dexamethasone in Postoperative Symptoms After Mastectomy for Breast Cancer
Condition: Postoperative Pain; Postoperative Nausea; Postoperative Vomiting
MeSH terms: Pain, Postoperative; Nausea; Vomiting; Postoperative Nausea and Vomiting
Study type: Interventional
Phase: Phase 3

Summary: 
      Postoperative pain, nausea and vomiting (PONV) are the most common complications after
      anesthesia and surgery. Women undergoing mastectomy with axillary dissection are at a
      particularly high risk for the development of PONV and an incidence of 60-80% in patients
      receiving no antiemetic has been reported. Emetic episodes predispose to aspiration of
      gastric contents, wound dehiscence, psychological distress, and delayed recovery and
      discharge times. These justify the use of prophylactic antiemetics in women scheduled for
      mastectomy. Most of the currently used antiemetics, including antihistamines, butyrophenones
      and dopamine receptor antagonists have been reported to cause occasional undesirable adverse
      effects, such as excessive sedation, hypotension, dry mouth, dysphoria, hallucinations and
      extrapyramidal signs. Antiserotonins (e.g., ondansetron) are available for the prevention and
      treatment of PONV in patients undergoing various types of surgery [4]. However, the use of
      prophylactic antiemetic therapy with antiserotonins has been criticized for being too
      expensive.

      Dexamethasone was first reported to be an effective antiemetic regimen in patients receiving
      cancer chemotherapy.

      The purpose of this study was to evaluate the efficacy of dexamethasone treatment for
      reducing pain and PONV as well as analgesic and antiemetic requirements in women undergoing
      general anesthesia for mastectomy with axillary lymph node dissection.
    

Detailed description: 
      Breast cancer is the most frequent malignant neoplasm worldwide. In emerging countries such
      as Mexico, there has been an increase in its frequency and mortality [1, 2] and it is the
      second most frequent neoplasm after cervical carcinoma. Between 25,000 and 30,000 new cases
      are diagnosed annually. Unfortunately, only a few women have regular mammography screening so
      the proportion of patients with locally advanced disease at diagnosis is high. In 2003, only
      5-10% of newly diagnosed cases in Mexico were clinical stages 0 or I [2]. Surgical resection
      with axillary lymph node dissection constitutes the treatment of choice associated with
      neoadjuvant therapy and postoperative chemotherapy and/or radiation therapy.

      Postoperative pain, nausea and vomiting (PONV) are the most common complications after
      anesthesia and surgery. Women undergoing mastectomy with axillary dissection are at a
      particularly high risk for the development of PONV and an incidence of 60-80% in patients
      receiving no antiemetic has been reported. Emetic episodes predispose to aspiration of
      gastric contents, wound dehiscence, psychological distress, and delayed recovery and
      discharge times. These justify the use of prophylactic antiemetics in women scheduled for
      mastectomy. Most of the currently used antiemetics, including antihistamines, butyrophenones
      and dopamine receptor antagonists have been reported to cause occasional undesirable adverse
      effects, such as excessive sedation, hypotension, dry mouth, dysphoria, hallucinations and
      extrapyramidal signs. Antiserotonins (e.g., ondansetron) are available for the prevention and
      treatment of PONV in patients undergoing various types of surgery. However, the use of
      prophylactic antiemetic therapy with antiserotonins has been criticized for being too
      expensive.

      Dexamethasone was first reported to be an effective antiemetic regimen in patients receiving
      cancer chemotherapy. Some authors have reviewed the available randomized trials (1996-2001)
      regarding perioperative single-dose steroid administration and found that dexamethasone had
      antiemetic and analgesic effects in various types of operations. One ot this studies
      demostrated that intravenous dexamethasone at 4 mg was effective for the prevention of PONV
      following breast surgery but they could not demonstrate any difference in postoperative pain.

      The purpose of this study was to evaluate the efficacy of dexamethasone treatment for
      reducing pain and PONV as well as analgesic and antiemetic requirements in women undergoing
      general anesthesia for mastectomy with axillary node dissection.

      Patients and Methods Patients Between June and August 2009, 70 patients undergoing mastectomy
      with axillary dissection were studied in a prospective, randomized, double-blind clinical
      trial. Patients were randomized to receive intravenous dexamethasone (8 mg) or homologated
      placebo 60 minutes before skin incision, using an equal number of blinded envelopes. Patients
      of American Society of Anesthesiologists classes III and IV were excluded. Further exclusion
      criteria were age more than 80 years; pregnancy; active menstruation; treatment with
      steroids; severe diabetes mellitus (serum HbA1c > 8%); use of opioids, sedatives or any kind
      of analgesics less than one week before mastectomy, or a history of alcohol or drug abuse.
      Patients with any history of motion sickness and ⁄or previous PONV after any surgical
      procedure were excluded. All patients were admitted to the hospital one day before the
      operation and were followed from hospital admission until 30 days after the surgical
      procedure to detect any medical or surgical morbidity.

      Anesthesia and surgery All patients underwent a standardized general anesthesia procedure and
      none of them received any preanesthetic medication. Induction used intravenous propofol (2
      mg/kg body weight) and fentanyl (3-5 mcg/kg). Vecuronium bromide (0.1 mg/kg) was used to
      facilitate tracheal intubation. Anesthesia was maintained with 2-3% sevoflurane and 66%
      nitrous oxide in oxygen. Ventilation was controlled mechanically and maintained constant
      throughout surgery using an anesthetic and respiratory gas analyzer for monitoring.

      All patients were monitored with indirect determinations of arterial pressure and heart rate
      using standard techniques, as well as the expired CO2 content and oxygen blood saturation.
      Afterwards, all patients were extubated and transferred to the immediate postsurgical care
      unit with cardiovascular and oxygen monitoring.

      Surgical procedures All patients were treated according to the preoperative clinical stage
      with radical mastectomy or breast conservative surgery with lymph node axillary dissection by
      the same surgical team. In all patients, closed suction drains were placed in the region
      subjected to surgery and were removed during the following days. Chemotherapy and/or
      radiotherapy were administered 3-4 weeks after uncomplicated surgical resections.

      Analgesia and antiemetic therapies Pain was assessed immediately on return to the recovery
      room and at 6, 12 and 24 h after the operation using a visual analogue scale (VAS; 0 = no
      pain to 10 = most severe pain). Analgesia was given as intravenous sodium ketorolac (30 mg
      every 8 hours) and intravenous tramadol infusion (50 mg) was used as a backup analgesic
      medication. The incidence of PONV was recorded immediately on return to the recovery room and
      at 6, 12 and 24 h after the operation, using a three point ordinal scale (0 = none, 1 =
      nausea, 2 = retching, 3 = vomiting). Nausea was defined as a subjectively unpleasant
      sensation associated with awareness of the urge to vomit, retching was defined as the
      labored, spasmodic, rhythmic contraction of the respiratory muscles without the expulsion of
      gastric contents, and vomiting was defined as the forceful expulsion of gastric contents from
      the mouth. Intravenous ondansetron (4-8 mg) was given for antiemetic treatment on demand.

      Data collection and statistical analysis Postoperative complications were recorded during
      hospitalization and the patients were followed up to 30 days after discharge. Additional data
      collected included patient age, body mass index (BMI), any history of smoking and neoadjuvant
      chemotherapy, anesthesia and operation time and the frequency of use of analgesic and
      antiemetic drugs. These parameters were summed and compared between the dexamethasone and
      placebo groups.The study endpoints were postoperative nausea and vomiting, and pain measured
      by the VAS and the need for additional analgesic and antiemetic drugs.

      The sample size was predetermined. We expected a 35% difference in the incidence of nausea
      and vomiting between groups. The alpha error was set at 0.05 and beta error at 0.20; n = 35
      patients for each group was considered adequate, according to a power analysis. Results are
      expressed as percentages and as the mean ± standard deviation (SD). Student's t test, the
      Chi-squared test or Fisher's Exact Test were used for the analysis of quantitative and
      qualitative data, respectively. Differences were considered statistically significant at p <
      0.05.

      Ethical considerations The study was conducted according to the principles of the Declaration
      of Helsinki of 1989 and the Mexican Health Guidelines. The Ethical and Research Committees of
      the Oncologic Institute, approved all protocols. Full, written informed consent was obtained
      from all patients before their inclusion in the study.
    

Intervention name(s): intravenous dexamethasone; Homologated placebo.
Intervention type(s): Drug; Drug
Intervention description(s): One dose of intravenous dexamethasone (8 mg) 60 minutes before skin incision.; Patients of the control group received homologated placebo 60 minutes before skin incision
Other intervention name(s): no other intervention; no other intervention
Intervention MeSH terms: Dexamethasone
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: Mastectomy; Breast cancer; Postoperative pain; Postoperative nausea and vomiting