The Effect of a Combination Treatment Using Palonosetron, Promethazine, and Dexamethasone on the Prophylaxis of Postoperative Nausea and Vomiting and QTc Interval Duration in Patients Undergoing Craniotomy under General Anesthesia: A Pilot Study

Abstract

IntroductionPostoperative nausea and vomiting (PONV) is a displeasing experience that distresses surgical patients during the first 24 h after a surgical procedure. The incidence of postoperative nausea occurs in about 50%, the incidence of postoperative vomiting is about 30%, and in high-risk patients, the PONV rate could be as high as 80%. Therefore, the study design of this single arm, non-randomized, pilot study assessed the efficacy and safety profile of a triple therapy combination with palonosetron, dexamethasone, and promethazine to prevent PONV in patients undergoing craniotomies under general anesthesia.MethodsThe research protocol was approved by the institutional review board and 40 subjects were provided written informed consent. At induction of anesthesia, a triple therapy of palonosetron 0.075 mg IV, dexamethasone 10 mg IV, and promethazine 25 mg IV was given as PONV prophylaxis. After surgery, subjects were transferred to the surgical intensive care unit or post anesthesia care unit as clinically indicated. Ondansetron 4 mg IV was administered as primary rescue medication to subjects with PONV symptoms. PONV was assessed and collected every 24 h for 5 days via direct interview and/or medical charts review.ResultsThe overall incidence of PONV during the first 24 h after surgery was 30% (n = 12). The incidence of nausea and emesis 24 h after surgery was 30% (n = 12) and 7.5% (n = 3), respectively. The mean time to first emetic episode, first rescue, and first significant nausea was 31.3 (±33.6), 15.1 (±25.8), and 21.1 (±25.4) hours, respectively. The overall incidence of nausea and vomiting after 24–120 h period after surgery was 30% (n = 12). The percentage of subjects without emesis episodes over 24–120 h postoperatively was 70% (n = 28). No subjects presented a prolonged QTc interval ≥500 ms before and/or after surgery.ConclusionOur data demonstrated that this triple therapy regimen may be an adequate alternative regimen for the treatment of PONV in patients undergoing neurological surgery under general anesthesia. More studies with a control group should be performed to demonstrate the efficacy of this regimen and that palonosetron is a low risk for QTc prolongation.ClinicalTrials.gov IdentifierNCT02635828 ().

Postoperative Nausea and Vomiting After Craniotomy: An Evidence-based Review of General Considerations, Risk Factors, and Management

“… 26 The use of promethazine in the craniotomy population should also be considered cautiously when immediate postoperative neurological evaluation is required because of its potential sedating effect. 1 , 25 The results of the aforementioned trials using triple therapy are consistent in reporting significantly lower rates of PONV following craniotomy when compared with previously published data. 7 – 15 , 17 – 21 , 25 , 26 …”

“… 1 , 22 , 62 Furthermore, in a single-arm study using a triple therapy of palonosetron (0.075 mg), dexamethasone (10 mg), and promethazine (25 mg) we reported a 30% incidence of PON and 7.5% incidence of PONV after craniotomy, without evidence of QT interval prolongation, a common adverse effect associated with palonosetron use. 25 Last, an RCT conducted by our group found that the combination of intravenous promethazine (25 mg) and dexamethasone (10 mg) with oral aprepitant (40 mg) had similar efficacy in the prevention of PONV to intravenous promethazine (25 mg), dexamethasone (10 mg) and ondansetron (4 mg) (PONV rates of 31% and 36.2%, respectively). 26 The use of promethazine in the craniotomy population should also be considered cautiously when immediate postoperative neurological evaluation is required because of its potential sedating effect.…”

“… 5 Three clinical trials conducted by our group demonstrated an acceptable incidence of PONV following craniotomies when a novel triple therapy regimen was implemented. 22 , 25 , 26 This multimodal regimen, which includes transdermal scopolamine (1.5 mg) administration before surgery and the combination of ondansetron (4 mg) and dexamethasone (10 mg) at anesthesia induction, has proven to be effective in PONV prevention (with an incidence of 33%) during the first 24 hours postcraniotomy. 22 When discussing the potential benefits of transdermal scopolamine in reducing PONV incidence, we should consider the risk:benefit ratio of its use in craniotomy patients due to the potential for side effects (mydriasis and sedation) which could limit postoperative neurological evaluation and differential diagnosis of intracranial hypertension.…”

Protein Interactions of the Mechanosensory Proteins Wsc2 and Wsc3 for Stress Resistance in Saccharomyces cerevisiae

“…Similarly, fungal infections with Aspergillus fumigatus and Cryptococcus neoformans can be acquired from non–endogenous host surroundings ( Badiee and Hashemizadeh 2014 ). Infections in patients with severe immunological impairment can have fatal consequences due to the development of resistance by these fungi to the limited number of therapeutic antifungal drugs currently available ( Roemer and Krysan 2014 ; Sanglard 2016 ). Therefore, there is an urgent need for new therapeutic strategies to address drug resistance in fungal infections.…”

A Comparison of Ondansetron, Palonosetron and Granisetron for Prevention of Post-Operative Nausea and Vomiting after Laparoscopic Surgeries

“…1,2 Post-operative nausea and vomiting can be classified as either early PONV (0-2 hours) or delayed PONV (2-24 hours). 3 PONV has a complex and multifactorial aetiology, but there are a number of recognised contributing factors. These include patient, anaesthetic, surgical and postoperative conditions.…”