Validation of simplified postoperative nausea and vomiting intensity scale in Taiwan.

This study determined whether the Simplified Postoperative Nausea and Vomiting Impact Scale (SPONVIS), could be used to predict clinically important PONV in Taiwanese. In this prospective, observational study, SPONVIS, simplified Apfel PONV Risk Scores, post-operative anti-emetic drug use, total PONV score, and 3-month recall score for PONV were recorded from Taiwanese patients who had undergone general anesthesia and surgery. With antiemetic use and 3-month recall score as validations of clinical significance, we determined whether the elements and cut-off points used in the original SPONVIS study could be used in Taiwanese patients. A total of 378 patients were included in the analysis. One hundred forty (37.1%) patients had PONV. Forty-eight patients (12.7%) had clinically important PONV (SPONVIS score ≥ 5). The odds ratios were 14.26 (CI 6.91-29.43; P < 0.001) and 4.95 (CI 2.42 to 10.11; P < 0.001), respectively, for prediction of anti-emetic drug use and 3-month recall. The SPONVIS and its construct elements were significantly related to anti-emetic drug use, 3-month recall score for PONV, total PONV score, and Apfel risk score (all P ≤ 0.005), results similar to those reported in the original Australian PONV impact score study. The SPONVIS cut-off points 3 and 5 were statistically significant predictors of anti-emetic drug use. However, a cut-off point of 3 had a higher OR (24.08) than a cut-off of 5 (14.26) for prediction of anti-emetic drug use. SPONVIS and both construct elements (the nausea and vomiting impact scores) are useful predictors of clinically important PONV in Taiwanese.

Sevoflurane-induced pica in female rats.

We examined the effects of volatile anesthetics on pica, which can be used to assess nausea and vomiting in rats. We found that inhalation anesthesia with sevoflurane significantly induced pica in female but not male rats. Among the female rats, young rats (8 weeks old) were more susceptible to its induction than adult rats (20 weeks old) with ovariectomy or sham-surgery. Anti-emetic drugs that are used to prevent postoperative nausea and vomiting (PONV) inhibited the pica. These results suggest that sevoflurane-induced pica in young female rats has the potential to be an animal model of PONV in humans.

Efficacy and safety of antiemetic regimens for highly emetogenic chemotherapy-induced nausea and vomiting: A systematic review and network meta-analysis.

BACKGROUND: Several regimens have been introduced in clinical practice in the last twenty years to treat chemotherapy-induced nausea and vomiting (CINV). However, direct comparative data remain insufficient, as many new regimes lack head-to-head comparisons. In this study, through an indirect comparison, we overcome this limit by providing the most up-to-date estimate of the efficacy and safety of all combinations used for HEC-induced nausea and vomiting. PATIENTS AND METHODS: We retrieved randomized controlled trials (RCTs) published in Pubmed, Embase, and Cochrane Library until June, 30th 2022. We included phase II-III RCTs, including adults with any cancer receiving HEC, and compared different antiemetic regimes to prevent CINV. The primary outcome was the overall complete response (defined as the absence of vomiting and of the use of rescue drugs from 0 to 120 hrs since chemotherapy); secondary outcomes were acute (absence of vomiting and use of rescue medicine 0-24 hrs after chemotherapy) and delayed (24-120 hrs) response and adverse events. RESULTS: A total of 53 RCTs enrolling 22 228 patients were included. We classified the different antiemetic regimes into 21 different groups. Overall, 3- or 4-drug regimens containing a combination of dexamethasone, 5HT3 antagonists, mirtazapine or olanzapine with or without NK antagonists, yielded the highest probability to be the most effective regimen in terms of complete response. Regimens containing a combination of dexamethasone and 5-HT3 antagonist have the lowest probability of being the most effective regimen in terms of complete, acute, and delayed response. CONCLUSION: In our network meta-analysis, 4-drug regimens with olanzapine displayed the highest probability of efficacy in terms of complete response. A 3-drug regimen with olanzapine represents a valid option in a limited resource context.

The effect of anti-emetic drugs on rat embryonic heart activity.

Nausea and vomiting of pregnancy (NVP) is the most common medical complaint during pregnancy affecting up to 70% of pregnant women worldwide. Some antiemetic medications (AEM) (droperidol, domperidone, granisetron, metoclopramide and trifluoperazine) used to treat NVP have the unwanted side effect of hERG blockade. The hERG potassium channel is essential for normal heart rhythm in both the adult human and the human and rat embryo. Animal studies show hERG blockade in the embryo causes bradycardia and arrhythmia leading to cardiovascular malformations and other birth defects. Whole rat embryo in vitro culture was used to determine the effect of the above listed AEM and meclizine on the heart rate of Gestational day 13 rat embryos. These embryos are similar in size and heart development to 5-6-week human embryo. The results showed that all of the AEMs caused a concentration-dependent bradycardia. Droperidol had the lowest margin of safety.

Effects of a histamine H4 receptor antagonist on cisplatin-induced anorexia in mice.

Cancer chemotherapy often induces gastrointestinal symptoms such as anorexia, nausea, and vomiting. Antiemetic agents are effective in inhibiting nausea and vomiting, but patients still experience anorexia. We previously reported that chemotherapeutic agent-induced anorexia is associated with an increase of inflammatory cytokines. Other studies also reported that antagonism of the histamine H4 receptor is anti-inflammatory. In this study, we investigated the involvement of the H4 receptor in the development of chemotherapy-induced anorexia in mice. Cisplatin-induced anorexia occurred within 24 h of its administration and continued for 3 days. The early phase (day 1), but not the delayed phase (days 2 and 3), of anorexia was inhibited by the daily injection of a 5-HT3 receptor antagonist (granisetron). However, a corticosteroid (dexamethasone) or selective H4 receptor antagonist (JNJ7777120) abolished the delayed phases of anorexia. Cisplatin significantly increased TNF-α mRNA expression in the hypothalamus and spleen, and the period of expression increase paralleled the onset period of anorexia. In addition, pretreatment with JNJ7777120 completely inhibited the increased expression. These results suggest that TNF-α mRNA expression via H4 receptors may contribute to the development of cisplatin-induced anorexia, and that H4 receptor antagonists are potentially useful treatments.

Induction and antagonism of pica induced by teriparatide in rats.

Intermittent subcutaneous injection of teriparatide, an active fragment of human parathyroid hormone, is clinically used for the treatment of osteoporosis. Patients suffer from nausea, which is one of the side effects teriparatide induces; however, the etiology of teriparatide-induced nausea remains unknown. We have reported pica, kaolin ingestion behavior, can be used as an assessment of nausea-related response in rats. In this study, we investigated the characteristics of teriparatide-induced pica and the abilities of anti-emetic drugs to inhibit teriparatide-induced pica. Male and female adolescent (4-week-old), young (8-week-old), and adult (30-week-old) naive rats, and ovariectomized (OVX: 17-week-old) and sham-operated (17-week-old) rats subcutaneously received teriparatide (0.4 mg/kg, n=4), and their kaolin and food intakes were monitored for 24 h after the injection. Among the tested rats, we found that OVX rats, rather than male, female, and sham-operated rats, showed marked teriparatide-induced pica (0 mg/kg: 0.17±0.07 g, 0.4 mg/kg: 6.18±0.91 g). Teriparatide-induced pica in OVX rats was inhibited by intraperitoneal pretreatment with serotonin 5-HT3 (granisetron 0.5 mg/kg), dopamine D2 (prochlorperazine 0.5 mg/kg), neurokinin NK1 (fosaprepitant 1 mg/kg), and histamine H1 (diphenhydramine 10 mg/kg) receptor antagonists to 70%, 11%, 19%, and 59% of that in vehicle-treated control, respectively. These results suggest that teriparatide-induced pica in OVX rats has the potential to reflect teriparatide-induced nausea; 5-HT3, D2, NK1, and H1 receptor activation is involved in the development of this behavior; antagonists of these receptors have the potential to be medical candidates used as treatments for teriparatide-induced nausea in human patients.