Dexamethasone Improves Postoperative Symptoms After Laparoscopic Cholecystectomy
Condition: Postoperative Nausea and Vomiting; Postoperative Pain; Postoperative Fatigue
MeSH terms: Vomiting; Postoperative Nausea and Vomiting
Study type: Interventional
Phase: Phase 3

Summary: 
      Dexamethasone has been reported to reduce postoperative nausea and vomiting (PONV) after
      laparoscopic cholecystectomy (LC). However, its effects on other surgical outcomes such as
      pain and fatigue have been unclear. We evaluated the efficacy of preoperative dexamethasone
      in ameliorating postoperative symptoms after LC.

      Methods: Prospective, double-blind, placebo-controlled study, 210 patients scheduled for
      elective LC were analyzed after randomization to intravenous dexamethasone (8 mg) or to a
      placebo. All patients underwent standardized procedures for general anesthesia and surgery.
      Episodes of PONV and pain and fatigue scores were recorded on a visual analogue scale.
      Analgesic and antiemetic requirements were also recorded.
    

Detailed description: 
      Patients and methods

      Patients Between January 2007 and August 2008, 210 patients undergoing LC were studied in
      accordance with a prospective, randomized, double-blind clinical trial. Patients were
      randomized to receive intravenous dexamethasone (8 mg) or homologated placebo 60 minutes
      before skin incisions, using an equal number of blind envelopes. Patients of American Society
      of Anesthesiologists (ASA) classes III and IV were excluded. Further exclusion criteria were
      age more than 80 years; pregnancy; treatment with steroids; severe diabetes mellitus (HbA1c >
      8%); use of opioids, sedatives or any kind of analgesics less than one week before LC; a
      history of alcohol or drug abuse; preoperative diagnosis of acute cholecystitis, acute
      pancreatitis, choledocolithiasis, gallbladder carcinoma and/or conversion of the LC to an
      open procedure. All patients were followed from hospital admission until 30 days after the
      surgical procedure.

      Anesthesia and surgery All patients underwent a standardized general anesthesia procedure.
      Induction used intravenous midazolam (1.5 mg) and fentanyl (3-5 mcg/kg of body weight) and
      propofol (2 mg/kg body weight). Anesthesia was maintained with 2 to 3% sevoflurane and 100%
      oxygen concentration. Neuromuscular blocking was maintained with intravenous vecuronium (0.1
      mg/kg body weight). All patients were monitored with indirect determinations of arterial
      pressure and heart rate using the standard technique as well as expired CO2 content and
      oxygen blood saturation. A nasogastric tube was placed in all patients during the operation
      and taken out at the end of the surgical procedure. Afterwards, all patients were extubated
      and transferred to the immediate postsurgical care unit with cardiovascular and oxygen
      monitoring.

      All patients received preoperative intravenous antibiotics (1 g of intravenous
      first-generation cephalosporin). LC was performed using a 2-handed, 4-trocar technique with 2
      10-mm ports and 2 5-mm ports. A 10-mm subumbilical port was introduced by the open method,
      subsequently creating a pneumoperitoneum, maintained at 12 to 14 mmHg of intra-abdominal
      pressure. All of the laparoscopic treatments were performed by expert surgeons, each having
      sufficient experience of laparoscopic surgery (more than 150 LCs per year). The skin was
      closed with single nonabsorbable sutures. Closed suction drains were placed in the inferior
      surface of the liver, using a 5-mm lateral port in some patients according to each surgeon's
      preference. The drains were removed during the following 12-24 h.

      Analgesia and antiemetics Pain and fatigue were assessed preoperatively and 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/fatigue to 10 = most severe pain/fatigue) [7,15,16].
      Analgesia was given as intravenous sodium ketorolac (30 mg every 8 h). Intramuscular
      buprenorphine (0.15-0.30 mcg) 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 four-point ordinal scale (0 = none, 1 = nausea, 2 = nausea with request
      for antiemetic, 3 = vomiting). 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. Data collected
      also included patient age, sex, body mass index (BMI), ASA score, history of previous
      abdominal surgery, anesthesia and operation time and frequency of use of analgesic and
      antiemetic drugs. These parameters were summed and compared between the dexamethasone and
      placebo groups. The study endpoints were degree of postoperative nausea, vomiting, pain and
      fatigue and additional analgesic and antiemetic drugs.

      The sample size was predetermined. We expected a 20% difference in the incidence of nausea
      and vomiting between groups. The error alpha error was set at 0.05 and beta error at 0.20; n
      = 103 patients for each group was considered adequate, according to a power analysis. Results
      were expressed as percentages and as the mean ± standard deviation (SD). Student's t test and
      the chi squared 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 Regional Hospital # 110 of the Mexican Institute for Social Security in Jalisco, Mexico
      approved all protocols. Full, written informed consent was obtained from all patients before
      their inclusion in the study.
    

Intervention name(s): Dexamethasone; placebo
Intervention type(s): Drug; Drug
Intervention description(s): intravenous dexamethasone 8 mgr before laparoscopic cholecystectomy or intravenous placebo before laparoscopic cholecystectomy; One hundred five patients were randomized to receive intravenous placebo before laparoscopic cholecystectomy
Intervention MeSH terms: Dexamethasone
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: Laparoscopic cholecystectomy,postoperative symptoms