Vergleich von Effektivität und Nebenwirkungen einer kombinierten medikamentösen Prophylaxe von postoperativer Übelkeit und Erbrechen (PONV) mit Dexamethason und Granisetron vs. Dexamethason und Ondansetron

Postoperative nausea and vomiting (PONV) is a relevant problem for many patients in the postoperative period. Incidence reports for PONV vary in the literature from 30% to 80% in high-risk patients. The most important prophylactic measure to reduce the risk of PONV is the administration of antiemetics. Here, it has become standard practice to use two or more antiemetics from different drug classes for PONV prophylaxis. However, there is no uniform recommendation as to exactly which drugs should be used. This varies from clinic to clinic. The aim of this work was to compare the efficacy of combined PONV prophylaxis of dexamethasone and 5-HT3-antagonists. For this purpose, the combinations "dexamethasone + granisetron" and "dexamethasone + ondansetron" were studied and the occurrence of PONV was compared between the two groups. In addition, the combinations were to be analysed regarding the occurrence of side effects, drug costs, and patient satisfaction postoperatively using the PPP33 questionnaire. For the analysis, 2344 complete patient data from the P6NV study were available. This study is a randomized, double-blind, multicentre study analysing the prophylaxis of nausea and vomiting in the postoperative period in patients receiving routine pharmacologic prophylaxis. 1026 patients received the drugs dexamethasone and granisetron, while 374 patients received the combination of dexamethasone and ondansetron. Granisetron was mostly given at a dosage of 1 mg and ondansetron at a dosage of 4 mg. PONV incidence was measured using the Simplified PONV Impact Scale (SPIS) according to Myles & Wengritzky after two hours in the recovery room and after 24 hours in the peripheral ward. Comparison of PONV incidence in the two groups revealed that the "dexamethasone + granisetron" group had a statistically significant lower 24h-SPIS score, less frequently reported nausea/vomiting of any intensity at 24 hours, and less frequently required antiemetics for PONV therapy in the recovery room and peripheral ward than the "dexamethasone + ondansetron" group. There was no difference between the groups in terms of PONV incidence after two hours in the AWR and the occurrence of clinically relevant PONV (SPIS ≥ 5 or SPIS ≥ 3). The "dexamethasone + granisetron" group suffered statistically significantly more frequently from the side effect constipation. This – as well as the less frequent occurrence of nausea/vomiting – was also reported significantly more frequently by patients in the "dexamethasone + granisetron" group when answering the PPP33 questionnaire. Pharmacoeconomic cost analysis showed different maximum markups for granisetron – depending on PONV incidence and PONV-associated costs – above which granisetron use was no longer price worthwhile. These differences between drug costs turned out to be relatively high. Using the P6NV study, it was shown that the 5-HT3-antagonist granisetron should be used preferentially in combination with dexamethasone for PONV prophylaxis and is superior to ondansetron in reducing PONV incidence at 24 hours. This can be explained by the longer half-life of granisetron compared with ondansetron. After two hours, no difference was seen between the drugs in terms of PONV incidence. The cost analysis was able to show that granisetron was also more likely to be worthwhile in terms of price than ondansetron and would have to cost significantly more to be inferior. As a caveat, it should be added that when clinically relevant PONV (SPIS ≥ 5 or SPIS ≥ 3) was considered, there was no significant difference between the groups. This was probably due to the low incidence of clinically relevant PONV in the P6NV study. In addition, the groups differed with respect to their baseline PONV risk – as measured by the Koivuranta- and Apfel-scores. Because the power of the risk assessment models is limited, an impact on the outcome of the study cannot be conclusively assessed. In conclusion, granisetron should be preferred over ondansetron for PONV prophylaxis because it is more effective in reducing PONV incidence and reduces PONV-associated costs.