PONV remains a challenge in recovery after total joint arthroplasty surgery, because it creates anxiety in patients, lowers their appetite, delays ambulation and even disturbs water and electrolyte balance. This increases risk of postoperative complications and prolongs hospitalization and consensus guidelines have been formulated for the management of PONV. Fifteen years have passed since the first international recommendations for the prophylaxis and treatment of PONV, and the incidence of PONV has fallen from approximately 80% to 20–30%, which is still relatively high. Our own work suggests that at least certain patient populations may show much higher incidence: we reported, for example, 48% incidence in patients who underwent total joint arthroplasty with general anesthesia [unpublished data]. Indeed, risk of PONV appears to be 11-fold higher when surgery is performed under general anesthesia than under regional anesthesia. While modification of risk factors should be taken firstly according to the recommendation of latest consensus, some risk factors such as gender or history of smoking and PONV were non-modifiable. Moreover, in our country, total joint arthroplasty is performed under general anesthesia routinely, because of the different medical system. On the other hand, spinal anesthesia is conductive to early ambulation and postoperative anticoagulation following enhanced total joint arthroplasty. These considerations highlight the need to improve PONV prophylaxis and treatment.
In our current study, we compared a new multimodal PONV prophylaxis protocol with a traditional anti-emetic protocol involving ondansetron and/or dexamethasone. The latter two drugs are the most commonly used perioperatively to prevent PONV. Our results indicate that addition of the oral prokinetic drug mosapride can lead to lower PONV incidence and severity, especially postoperative nausea, during the first 12 h postoperatively than the use of ondansetron alone or in combination with dexamethasone, although the difference of severe PONV rate between Dexa + Mosa group and Dexa Group was not statistically significant (p = 0.062). Moreover, preemptive application of oral mosapride can improve appetite, bowel function, time until ambulation and length of hospital stay.
5-HT3 receptor antagonists and corticosteroids are the anti-emetic drugs most commonly used perioperatively to prevent and treat PONV. These drugs act by antagonizing 5-HT3 receptors both peripherally on vagal afferents and centrally in the area postrema. Dexamethasone is a synthetic glucocorticoid showing higher potency, greater bioavailability, and longer acting time than the most widely used antagonist, ondansetron.[22–24] Low-dose systemic dexamethasone can show good anti-emetic efficacy,[25,26] although the mechanism remains unclear. The drug may inhibit prostaglandin synthesis and endogenous opioid release, controlling pain and reducing the need for opioid drugs, which can help prevent PONV. The half-life of dexamethasone is about 36–72 h, much longer than the 4 h of ondansetron.[22,23] Therefore, the combination of dexamethasone and ondansetron can be particularly effective at reducing PONV incidence during the first 12–48 h after surgery (Table 3 and Table 4). We found that combining dexamethasone with ondansetron led to lower incidence of PONV and higher incidence of complete response than with ondansetron alone. Similarly, previous work showed that combining dexamethasone with ramosetron further reduced postoperative emesis and pain without increasing risk of wound complications. Studies also have suggested that dexamethasone can help reduce postoperative pain and inflammatory responses,[11,12,24,27,28] which we did not examine here. Future work should explore the full range of benefits offered by dexamethasone.
Here we investigated additional clinical benefits of the anti-emetic mosapride, a selective 5-HT4 receptor agonist. Mosapride can promote the release of acetylcholine and stimulate the gastrointestinal tract to promote motility, thereby improving the gastrointestinal symptoms of patients with functional dyspepsia. Mosapride can inhibit emesis induced by selective serotonin reuptake inhibitors (SSRIs) in laboratory animals, probably by reversing the SSRI-induced delay in gastric emptying. We found in the present study that the preemptive use of oral mosapride can provide additional anti-emetic effects beyond dexamethasone and ondansetron in total joint arthroplasty patients. In fact, mosapride may antagonize the ability of 5-HT3 receptor antagonists to reduce gastrointestinal motility, which may help reduce the risk of constipation that affects many total hip and knee arthroplasty patients. Indeed, this motility-inducing effect may help explain why the patients in our Mosa+Dexa group showed better postoperative appetite and shorter times to first defecation and ambulation than patients who did not receive mosapride. Although some patients in Mosa + Dexa group experienced digestive side effects such as abdominal pain or dry mouth, we could not conclude the correlation between mosapride and these side effects because of non-significant difference.
As far as we know, our study provides comprehensive evidence supporting the potential clinical benefit of prokinetic drugs following total joint arthroplasty, although the results need to be interpreted in light of the following limitations. First, patients receiving mosapride alone were not included. Therefore, we cannot make the conclusion that mosapride alone was effective at reducing PONV incidence after total joint arthroplasty. Although our results implicated no incidence of prolonged QT syndrome, more further works are needed to confirm and extend our results, especially the safety profile of mosapride, because another 5-HT4 agonist that antagonizes 5-HT3 activity and that can rapidly relieve nausea induced by SSRIs was withdrawn for cardiotoxicity. Second, the sample number was calculated according to our primary outcome of PONV incidence. As a result, the sample may not have been adequately powered to detect inter-group differences in secondary outcomes, such as rate of severe PONV, and complication rates. Nevertheless, previous work from our group and others suggests that perioperative dexamethasone does not increase the incidence of postoperative infection in total hip and knee arthroplasty.[11,12,31] Third, all participants in our study were Chinese and most (67%) were women. Thus, our findings may not be widely generalizable, because female gender is a well-established risk factor for PONV. Fourth, our postoperative analgesic regimen included extensive multimodal pain control drugs and modalities such as preemptive analgesic medication and periarticular injection, which may have introduced heterogeneity into our sample. However, the rest VAS pain score at postoperative 24 h and 48 h and requirement of rescue treatment for pain were comparable among the three groups (Table 5). Fifth, our study did not investigate whether the choice of PONV management regimen affected postoperative inflammatory marker levels and pain control. This should be explored in future work, since our previous study has shown that low-dose dexamethasone can relieve postoperative pain and postoperative nausea, as well as provide additional inflammatory control and improve clinical outcomes. Lastly, our study excluded diabetic patients, so future work should examine whether our results can be generalized to this patient subpopulation.
BMC Anesthesiol. 2020;20(297) © 2020 BioMed Central, Ltd.