Strategies for reducing the risk of PDNV

Successful strategies for reducing the risk of PDNV take into account both the pharmacokinetics of the antiemetic agent as well as the principle of multimodal prophylaxis, utilizing agents of different pharmacologic classes. Ondansetron, the most commonly used 5-HT₃ antagonist, has little efficacy in preventing PDNV because of its short half-life of approximately 3 h[79]. Palonosetron, a second-generation 5-HT₃ antagonist with a half-life of 40 h, has been shown to reduce the risk of PONV for up to 72 h compared with placebo[80], with no effect on the QTc interval[81]. The use of propofol as part of TIVA compared with volatile anesthetics, reduces immediate postoperative nausea/vomiting; however, that benefit is likely lost in the late postoperative period, due to the short half-life of propofol[82]. When compared with the 5-HT₃ antagonists, dexamethasone appears to significantly reduce PDNV[79]. Dexamethasone has a biological half-life of 36–72 h[27], giving it a potential advantage for the prevention of PDNV.

The NK₁ receptor antagonist, aprepitant, has a relatively long half-life of between 9 and 12 h compared to ondansetron. When compared with ondansetron, aprepitant has been shown to be superior for the prevention of vomiting and reducing nausea severity over the first 48 h, likely related to a combination of superior antivomiting efficacy, as well as its significantly longer half-life[53,55]. The combination of greater antivomiting efficacy and longer half-life make aprepitant an ideal prophylactic agent for use in preventing PDNV. Rolapitant, an NK₁ receptor antagonist with an extremely long half-life of 180 h and a lack of enzyme inhibition, has been shown to be equally efficacious as ondansetron for the prevention of PONV during the first 24 h, with a decreased risk of emesis at 72 and 120 h postoperatively[83].

Although the benefits of TDS for the prevention of PDNV, between 24 and 48 h postoperatively, have not been demonstrated in a large meta-analysis[39], its long duration of action, up to 72 h, would appear to make it an ideal agent for the prevention of PDNV. More studies are needed to better evaluate the efficacy of TDS for the prevention of PDNV. However, adverse effects of TDS, specifically visual disturbances, might limit its use during this time period[39].

Strategies for managing established PONV

The successful management of established PONV must take into account both the pharmacokinetics and the pharmacodynamics of our antiemetic agents. Several of our highly effective agents for PONV prevention have poor utility for the treatment of established PONV. Dexamethasone exerts in pharmacologic activity for the prevention of PONV via its anti-inflammatory effects and prostaglandin inhibition, making it a poor choice for PONV treatment. Transdermal scopolamine is an equally poor choice because of its relatively long onset time, 2–4 h. When PONV prophylaxis fails, consideration should be given to using medications from other pharmacologic classes for treatment[2,84,85]. The 5-HT₃ antagonists have been well studied for the treatment of established PONV and are very effective for the treatment of POV, less so for the treatment of postoperative nausea[86]. There does not appear to be dose responsiveness of ondansetron for the treatment of established PONV, a dose of 1 mg IV should be considered to minimize the risk of adverse effects, specifically headache[86]. If prophylaxis with a 5-HT₃ antagonist fails, there is little evidence to support re-administering a second dose[85]. In patients who have failed prophylaxis with either ondansetron or droperidol, promethazine (6.25–25 mg IV) and dimenhydrinate (25–50 mg IV) have been shown to be significantly more effective for treatment than either of the two prophylactic agents[84].

Although its use for the treatment of established PONV has not been rigorously studied, IM ephedrine might be an ideal medication for a specific subset of patients undergoing ambulatory surgery. Its unique mechanism of action compared to first-line prophylactic agents, efficacy for the prevention of PONV and its tendency towards less sedation and shorter recovery times might make it a useful adjunct for PONV treatment[60].