Original contributionTiming of administration of dolasetron affects dose necessary to prevent postoperative nausea and vomiting
Introduction
The dramatic evolution toward minimally invasive surgery and from inpatient to outpatient surgical care over the past decade has directed scrutiny of anesthetic complications, among the most common being postoperative nausea and vomiting (PONV). The incidence of PONV following balanced general anesthesia is estimated to be 25% to 30%.1, 2 Surgical providers, hospital utilization review committees, and health insurance companies have little patience for these idiosyncratic reactions to general anesthesia, resulting in unhappy patients and families, delayed discharge, or unexpected, costly hospitalization after ambulatory surgery.3
Efforts to prevent and treat PONV begin by identifying risk factors. Many variables within the history and physical examination—female gender, younger age, nonsmoking status, history of motion sickness or PONV—have been quite predictive.4, 5, 6 Factors related to anesthesia and specific operative sites can also adversely affect the incidence of PONV. For instance, postoperative use of opioids,5 prolonged anesthesia/surgery,4, 6 and ophthalmologic, oral, ENT, head/neck, obstetric, gynecological, laparoscopic, and abdominal procedures7 have all been shown to increase the incidence of PONV. At-risk candidates (i.e., those with one or more risk factors) might be considered for preventive intervention, whereas those least likely to suffer this outcome are oftentimes treated expectantly.
5-Hydroxytryptamine3 (5-HT3) receptor antagonists (e.g., ondansetron, dolasetron) have been approved for the prevention and treatment of PONV. Results of ondansetron studies suggest that efficacy is significantly improved when administered at the end rather than before induction of anesthesia,8, 9 raising the hypothesis that timing of administration may also affect the efficacy of dolasetron.
We evaluated the clinical efficacy of dolasetron mesylate (Anzemet®, Hoechst Marion Roussel, Kansas City, MO) in preventing or treating established PONV following balanced general anesthesia. This evaluation was accomplished by compiling data from eight prospective, randomized, double-blinded, placebo-controlled clinical trials with similar enrollment criteria (ASA physical status classification) in which balanced general anesthesia was utilized. In selecting relevant studies, we were mindful of the recommendations of Apfel et al.10 concerning the proper design, conduct, and presentation of trials to study PONV. The recommendations included use of placebo, proper randomization, blinding, selection of primary and secondary endpoints, and pertinent statistical treatment of the data. Our attention was focused on route of administration (oral, parenteral), dosage, and timing of delivery with regard to surgery and anesthesia. Efficacy was quantitatively measured with complete response (no vomiting/retching and no rescue medications) and qualitatively rated with nausea visual analog scale (VAS) assessment. We wanted to answer a clinically important question: Does timing of dolasetron administration affect dose necessary to PONV?
Section snippets
Patients
Adult patients between 18 and 65 years of age (70 in one study) with ASA physical status of I, II, or III, who were scheduled for a surgical procedure with balanced general anesthesia, were eligible to participate in the studies. Those with significant cardiac or hepatic disease, those who vomited or received any drug with antiemetic activity within 24 hours of surgery, or who were scheduled for gastric suctioning during or after surgery were excluded from enrollment. Four of the six trials
Results
A total of 4,587 patients were treated in the pooled dataset, including 4,124 females (94%) undergoing primarily gynecologic procedures and 463 males (6%) undergoing various surgical procedures (i.e., thyroidectomy or orthopedic, ophthalmologic, urologic, ENT, or laparoscopic surgery). Patients enrolled in the pooled studies were similar based on baseline demographic and clinical characteristics (Table 2 11, 12, 13, 14, 15, 16, 17, 18), as would be expected based on common inclusion criteria.
Discussion
The primary purpose of this study was to determine if timing of administration affects the dose of dolasetron necessary to prevent PONV. Data from studies with similar protocols (study design, conduct, efficacy measurements) were pooled to provide a large (>4,500), homogeneous patient population in which a comparison of dolasetron doses could be conducted. The limited number of published studies with optimal (double-blind, randomized, placebo-controlled) and comparable study designs prompted
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Cited by (9)
Update on the Management of Postoperative Nausea and Vomiting and Postdischarge Nausea and Vomiting in Ambulatory Surgery
2010, Anesthesiology ClinicsCitation Excerpt :However, the differing chemical structures of each drug may explain slight differences in receptor binding affinity, dose response, and duration of action.23 Most available data suggest that 5-HT3 RAs are most effective when administered at the end of surgery,48–50 but at least one study has suggested that dolasetron may be administered around the time of induction of anesthesia, with little effect on efficacy.51 All of the 5-HT3 RAs are equally effective for the treatment of PONV.52
Postoperative nausea and vomiting after surgery for prognathism: Not only a question of patients' comfort. A placebo-controlled comparison of dolasetron and droperidol
2008, Journal of Cranio-Maxillofacial SurgeryCitation Excerpt :Most of the currently used antiemetics including butyrophenones, phenothiazines, dopamine receptor antagonists, anticholinergics and antihistamines have undesirable side effects such as sedation and extrapyramidal symptoms (Wachta and White, 1992; Freymond et al., 2002; Piper et al., 2002b). The availability of 5-hydroxytryptamine type 3 (5-HT3) antagonists has offered a new option in the prevention of PONV without sedative and with negligible centrally acting side effects (Harter, 2000; Korttila and Jokinen, 2004; Kontrimaviciute et al., 2005). So far there are no controlled studies evaluating the efficacy of preventing PONV using 5-HT3 antagonists in patients undergoing surgery for prognathism.
Drugs for preventing postoperative nausea and vomiting in adults after general anaesthesia: a network meta-analysis
2020, Cochrane Database of Systematic ReviewsThe management of postoperative nausea and vomiting: Current thoughts and protocols
2013, Aesthetic Plastic Surgery
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Vice President, Biostatistics, Cinetic Consulting