Palonosetron vs Combination of Granisetron and Dexamethasone in Preventing PONV in Laparoscopic Cholecystectomy.
Condition: Postoperative Nausea and Vomiting
MeSH terms: Nausea; Vomiting; Postoperative Nausea and Vomiting
Study type: Interventional
Phase: Phase 4

Summary: 
      This is a prospective, randomized, double-blinded study comparing the post-operative nausea
      vomiting (PONV) profile following administration of intraoperative palonosetron alone and the
      combination of granisetron and dexamethasone in moderate to high-risk patients undergoing
      elective laparoscopic cholecystectomy.

      Patients aged 18-65 years with American Society of Anesthesiologists physical status I or II
      were randomized into two groups. Group A received 1 ml of intravenous (IV) 0.9% saline after
      intubation and IV palonosetron 0.075 mg at the end of operation. Group B received IV
      dexamethasone 4 mg after intubation and IV granisetron 1 mg at the end of surgery. The
      occurrence of PONV and the need for rescue antiemetics were assessed at 30 minutes, 4, 24 and
      48 hours post-anesthesia. A complete response towards the study drugs was considered when
      patients did not experience PONV and did not require rescue antiemetics. The side effects of
      the study drugs were evaluated. Patient satisfaction with the anti-emetics administered was
      assessed.

      These parameters were compared between Group A and Group B: the occurrence of PONV, the need
      of rescue antiemetics, the side effects of the study drugs and patient satisfaction with the
      anti-emetics administered.
    

Detailed description: 
      This prospective double-blinded, randomized controlled study was conducted at Hospital
      Canselor Tuanku Muhriz, Universiti Kebangsaan Malaysia, Malaysia after obtaining approval
      from the Institutional Ethics Committee of Universiti Kebangsaan Malaysia (UKM).

      Patients aged 18 to 65 years old, American Society of Anesthesiologists (ASA) physical status
      I or II, scheduled for elective laparoscopic cholecystectomy under general anesthesia were
      recruited using convenient sampling. Patients with heart diseases, prolonged QT syndrome, a
      family history of sudden death, known allergies, or contraindications to the study drugs were
      excluded. No premedication was administered to the patients, and an intravenous (IV) drip was
      not started preoperatively.

      After obtaining written informed consent, patients were randomized to one of two groups using
      computer-generated random numbers. Group A received IV palonosetron 0.075 mg, and Group B
      received IV granisetron 1 mg and IV dexamethasone 4 mg as antiemetics.

      Patients were fasted for at least 6 hours prior to surgery. In the operating room, standard
      monitoring was applied to every patient, including continuous electrocardiography (ECG),
      non-invasive blood pressure monitoring (NIBP), pulse oximetry, capnography with multi-gas
      analyzer including minimum alveolar concentration (MAC), and monitoring of all gas levels.

      Patients were pre-oxygenated with oxygen. Induction of anesthesia was conducted using IV
      fentanyl 2 mcg/kg and IV propofol 2 mg/kg. Upon loss of consciousness, IV rocuronium 0.6
      mg/kg was administered to facilitate endotracheal intubation, following which patients were
      mechanically ventilated with a mixture of oxygen and air. Anesthesia was maintained with
      sevoflurane at MAC of 1.0 to 1.2. Ventilation parameters were adjusted to maintain
      normocapnia (end-tidal carbon dioxide of 35-40 mmHg) and saturation of oxygen above 96%.

      Group A patients received 1 ml of IV 0.9% saline while Group B patients received IV
      dexamethasone 4 mg after intubation. The amount of IV morphine given to the patients
      intraoperatively was recorded and did not exceed 0.1 mg/kg. Rescue analgesia with IV fentanyl
      was administered if needed, not exceeding 100 mcg. The surgeon infiltrated 10 ml of
      levobupivacaine 0.5% into the incisions at the end of surgery. Patients were kept adequately
      hydrated throughout the surgery with an IV drip of 2 ml/kg/h as maintenance, any fluid
      deficit was replaced. Pneumoperitoneum in laparoscopic procedure was achieved by carbon
      dioxide insufflation with intra-abdominal pressure of less than 14 mmHg.

      Thirty minutes prior to the end of the surgery, Group A received a slow bolus of IV
      palonosetron 0.075 mg, while Group B received a slow bolus of IV granisetron 1 mg.
      Intravenous neostigmine 0.05 mg/kg and IV atropine 0.02 mg/kg were administered as a reversal
      agent. The pneumoperitoneum was evacuated by the surgeon, and the nasogastric tube was
      suctioned and removed before extubation. The patients were transferred to the recovery bay
      after extubation. Rescue analgesia with IV fentanyl was administered in the recovery bay if
      needed, not exceeding 50 mcg.

      Patients were monitored by blinded anesthetists for nausea and vomiting in four time periods:
      30 minutes, 4 hours, 24 hours, and 48 hours post-anesthesia. Nausea was defined as an
      unpleasant sensation associated with the urge to vomit and its severity was rated by patients
      on a scale of 0 (no nausea) to 10 (worst possible nausea). Vomiting was defined as the
      forceful expulsion of gastric contents from the mouth, and the frequency of vomiting was
      recorded. If a patient experienced severe nausea (nausea score of 4 and more) and vomiting,
      rescue antiemetic of IV metoclopramide 10 mg was administered. Regular IV metoclopramide was
      administered if the patient experienced a second episode of vomiting or more. A complete
      response (free from emesis) was defined as no nausea, no vomiting and no need for any rescue
      medication. Side effects of the study drugs (palonosetron, granisetron, and dexamethasone)
      such as headache, constipation, dizziness, bloatedness, and palpitation were recorded. At the
      end of the study, patients were asked if they were satisfied with the antiemetics given to
      them. Patient satisfaction was assessed by using a Likert scale, which included a five-point
      scale; very satisfied, satisfied, neutral, dissatisfied, and very dissatisfied. Surgeries
      that lasted more than four hours, required conversion to open cholecystectomy or other
      procedures, and severe PONV that did not resolve with rescue anti-emetics were considered
      dropouts in this study.
    

Intervention name(s): Dexamethasone, granisetron & palonosetron
Intervention type(s): Drug
Intervention description(s): . Group A received 1 ml of intravenous (IV) 0.9% saline after intubation and IV palonosetron 0.075 mg at the end of operation. Group B received IV dexamethasone 4 mg after intubation and IV granisetron 1 mg at the end of surgery
Intervention MeSH terms: Dexamethasone; Palonosetron; Granisetron
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Care Provider)
Primary purpose: Prevention