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Post operative nausea and vomiting (PONV) occurs in as many as 70%-80% of high risk surgical patients. The latest prophylactic treatment recommended in the Society of Ambulatory Anesthesia Guidelines for the management of Postoperative Nausea and Vomiting for high risk patients is a combination of 2 or more interventions (multimodal therapy). A combination of a 5-HT3 receptor antagonist with dexamethasone and/or droperidol, or a 5-HT3 receptor antagonist with droperidol alone, or dexamethasone with droperidol, have been the pharmacologic combination therapies suggested in these guidelines. Palonosetron is a fairly new 5-HT3 receptor antagonist recently approved by the FDA for PONV prophylaxis. The use of this novel drug in a triple therapy combination with Dexamethasone and/ or Droperidol could be an effective treatment for the prevention of PONV. However, since the FDA issued a warning stating that droperidol may cause life – threatening arrhythmias as well as a prolongation of the QTc interval, the need to discover new combination therapies for PONV prevention in high risk patients is still in demand. Therefore, we hypothesize that the use of this novel drug Palonosetron in a triple therapy combination with Dexamethasone and Promethazine will be an effective treatment for the prevention of PONV in patients at a high risk for developing PONV during the first 120 hours after neurosurgery.