Compare Between Two Doses of Palonosetron on the Prevention of Postoperative Nausea and Vomiting in Obese Patients
Condition: Postoperative Nausea and Vomiting
MeSH terms: Nausea; Vomiting; Postoperative Nausea and Vomiting
Study type: Interventional
Phase: Phase 4

Summary: 
      BACKGROUND: Palonosetron is a second generation serotonin antagonist usually used in a ﬁxed
      dose of 75 mcg for the prophylaxis of postoperative nausea and vomiting. Although there are a
      few trials evaluating bodyweight-adjusted doses of palonosetron, the ideal dose for obese
      patients has not yet been investigated. The aim of this study is to evaluate if the use of
      bodyweight-adjusted doses of palonosetron (1mcg / kg) is more effective than a fixed dose
      (75mcg) on preventing postoperative nausea and vomiting in female patients with a body mass
      index equal to or above 30 kg /m2 whom have undergone breast surgery METHODS: A prospective,
      randomized double-blind trial will be conducted at the National Cancer Institute (INCA -
      HCIII), in Rio de Janeiro, Brazil. Eligible patients are female aged between 18-70 years of
      age with an ASA physical status of one to three, with body mass index equal to or greater
      than 30 kg / m2, scheduled to undergo elective breast surgery. Forty patients will be
      randomized to receive a fix dose of 75 μg of palonosetron (group I - GI) and 40 patients will
      receive a bodyweight-adjusted dose of 1mcg/kg of palonosetron (group II - GII). Patients will
      be assessed over 3 time periods: 0-6 h, 6-26 h and 24-48 h after surgery. After discharge,
      all patients will be contacted by telephone at regular intervals to record the episodes of
      nausea and vomiting as well as analgesic and antiemetic requirements. The primary outcome
      measure will include the number of emetic episodes, the incidence of nausea, the need for
      rescue antiemetics and the analgesic requirement over 48h. The secondary outcome will be to
      evaluate the frequency of polymorphism of the 5-HT3 receptors and their correlation with the
      antiemetic effect and adverse effects.
    

Detailed description: 
      Prevention of nausea and vomiting after surgery is a routine throughout anesthetic-surgical
      procedure, since the discomfort and morbidity associated with this anesthetic complication
      are widely known. The serotonin antagonists are largely used for this purpose because they
      exhibit superior prophylactic efficacy when compared with other antiemetic drugs. Its
      mechanism of action is the inhibition of calcium influx caused by stimulation of serotonin
      5-hydroxytryptamine type 3 receptor (5-HT3).

      Palonosetron is a second generation serotonin antagonist with high affinity binding to the
      5-HT3 receptor. It has a unique chemical structure and longer half-life than older 5-HT3
      antagonists. It was initially approved for use in the prevention of chemotherapy induced
      nausea and vomiting but also proved effective in the prophylaxis of postoperative nausea and
      vomiting. Palonosetron is usually used in a ﬁxed dose of 75 mcg for the prophylaxis of
      postoperative nausea and vomiting. Although there are a few trials evaluating
      bodyweight-adjusted doses of palonosetron, the ideal dose of obese patient has not yet been
      investigated.

      Aims & Objectives: The hypothesis for this study is that the use of bodyweight-adjusted doses
      of palonosetron (1mcg / kg) is more effective than a fixed dose (75mcg) for preventing
      postoperative nausea and vomiting in female patients with a body mass index equal to or above
      30 kg / m2 whom have undergone breast surgery.

      Methods: A prospective, randomized double-blind trial will be conducted at the National
      Cancer Institute (INCA - HCIII), in Rio de Janeiro, Brazil. All patients will be provided
      with written informed consent form prior to study enrolment.

      Using computer-generated random numbers, the patients will be assigned into one of the two
      treatment groups on the morning of surgery. Forty patients will be randomized to receive a
      fix dose of 75 μg of palonosetron (group I - fix dose group) and another forty patients will
      receive a bodyweight-adjusted dose of 1mcg/kg of palonosetron (group II - bodyweight-adjusted
      group). Each study drug will be mixed with saline to a total volume of 10 ml in an unlabelled
      syringe and will be intravenously administered just prior to induction of anesthesia. All
      patients, surgeons, anesthesiologists involved in the study will be blinded to group
      allocation to maintain the double-blind conditions.

      All patients will receive premedication with midazolam. Intraoperative monitoring included
      electrocardiography, blood pressure measurement, peripheral oxygen saturation (SpO2), and
      end-tidal CO2 tension (ETco2). General anesthesia was induced using 1,5 mg/kg of propofol, 3
      μg/kg of fentanyl, 1,5 mg/kg of lidocaine and 0.3 mg/kg of rocuronium. Then the insertion of
      laryngeal mask will be performed and the pulmonary ventilation will be maintained with 6
      ml/kg of ideal-weight and maximum peak pressure 25 cmH2O. The anesthesia will be maintained
      with sevoflurane in 50% oxygen/air. Sevoflurane concentration was adjusted to ensure an equal
      depth of anesthesia during surgery as assessed by the bispectral index (BIS; BIS A-1050
      Monitor, Aspect Medical Systems, Newton, MA, USA), which will be held between 40-60.
      Remifentanil will be administered for supplemental intraoperative analgesia and its dose will
      be adjusted to maintain blood pressure and heart rate within 20% of baseline values. At the
      end of surgery, residual neuromuscular blockade will be reversed with 2mg/kg of Sugammadex
      and the laryngeal mask will be removed. Patients will stay on the postanesthetic care unit
      for at least 1 hour before going to the ward. In the postoperative recovery room, the
      haemodynamic variables along with postoperative complications such as shivering, hypotension,
      dizziness, constipation or any other adverse reaction to the drug will be recorded by a
      blinded observer. After surgery, rescue medication will be intravenous metoclopramide (10 mg)
      for more than one episodes of nausea or vomiting.

      All episodes of nausea and vomiting will be recorded for 48h. Patients will be assessed over
      3 time periods: 0-6 h, 6-26 h and 24-48 h after surgery. After discharge, all patients will
      be contacted by telephone at regular intervals to record the episodes of nausea and vomiting
      as well as analgesic and antiemetic requirements. The primary outcome measure will include
      the number of emetic episodes, the incidence of nausea, the need for rescue antiemetics and
      the analgesic requirement after 48h. Nausea is deﬁned as a subjective unpleasant sensation
      associated with the urge to vomit without expulsion of gastric content and vomiting is deﬁned
      as the forceful expulsion of gastric contents trough the mouth.

      The secondary outcome will be to evaluate the frequency of polymorphism of the 5-HT3
      receptors and their correlation with the antiemetic effect and adverse effects. The patients
      will have cell samples of the oral cavity, collected through smear. The collected material
      will be placed in a tube and then will be stored at freezer. Then, it will be analyzed in the
      laboratory of Clinical Research Unit at the Federal Fluminense University (UFF). After
      extracting the DNA from the samples using a DNA purification kit, a polymerase chain reaction
      (PCR) will be performed for analysis of single nucleotide polymorphisms. Biological samples
      will be discarded at the end of the analysis.

      Sample size was calculated with reference to the results of a study comparing weight-adjusted
      doses of palonosetron for prevention of PONV in laparoscopic gynaecological surgery in
      no-obese patients. For a P value of 0.05 and a power of 0.8, a minimum of 36 per dose group
      was required. To allow for possible dropouts, the aim was to recruit 40 patients in each
      group.

      SPSS version 13.0 (SPSS Inc, Chicago, IL,USA) will be used for statistical analysis. The
      Shapiro-Wilk test will be use to ensure that data will be normally distributed. Patient
      characteristics and intra- and post-operative variables will be analysed by two-tailed ANOVA.
      For nonparametric variables, Kruskal-Wallis test will be applied. Proportions will be
      compared using x2 square or Fisher's exact test. The dose-dependency effects of palonosetron
      will be assessed using the x2 trend test for proportions. A P value < 0.05 is considered
      statistically significant.
    

Intervention name(s): palonosetron
Intervention type(s): Drug
Intervention description(s): receive a fix dose of 75 μg of palonosetron (group I - GI) and another forty patients will receive a bodyweight-adjusted dose of 1mcg/kg of palonosetron (group II - GII).
Other intervention name(s): onicit
Intervention MeSH terms: Palonosetron
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Prevention