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British Journal of Anaesthesia Jul 2023Postoperative nausea and vomiting (PONV) has been identified as a big (very frequently encountered) little (not linked to life-threatening outcomes) problem. Traditional...
Postoperative nausea and vomiting (PONV) has been identified as a big (very frequently encountered) little (not linked to life-threatening outcomes) problem. Traditional drugs (dexamethasone, droperidol or similar drugs, serotonin receptor antagonists) each have significant but limited effect, leading to an increasing use of combination therapies. High-risk patients, often identified through use of risk scoring systems, remain with a significant residual risk despite combining up to three traditional drugs. A recent correspondence in this Journal proposes the use of up to five anti-emetic drugs to further minimise the risk. This disruptive strategy was supported by favourable initial results, absence of side-effects and lower acquisition costs of the added new drugs (aprepitant and palonosetron) because of their recent loss of patent protection. These results are provocative and hypothesis generating, but need confirmation and do not warrant immediate changes in clinical practice. The next steps will also necessitate wider implementation of protocols protecting patients from PONV and a search for additional drugs and techniques aimed at treating established PONV.
Topics: Humans; Postoperative Nausea and Vomiting; Antiemetics; Droperidol; Serotonin Antagonists; Risk Factors; Vomiting; Dexamethasone; Drug Therapy, Combination
PubMed: 37179157
DOI: 10.1016/j.bja.2023.04.004 -
Journal of Ethnopharmacology Jan 2024Xiaobanxia Decoction (XBXD), a traditional antiemetic formula, is effective in preventing chemotherapy-induced nausea and vomiting (CINV), but its underlying mechanism...
ETHNOPHARMACOLOGICAL RELEVANCE
Xiaobanxia Decoction (XBXD), a traditional antiemetic formula, is effective in preventing chemotherapy-induced nausea and vomiting (CINV), but its underlying mechanism has not been fully clarified.
AIM OF THE STUDY
To investigate whether the antiemetic mechanisms of XBXD against CINV is associated with the reduction of GSDME-mediated pyroptosis and the alleviation of gastrointestinal inflammation induced by cisplatin.
MATERIALS AND METHODS
We established the in vivo pica rat model and the in vitro small intestinal epithelial cell (IEC-6 cell) injury model by cisplatin challenge. The levels of ROS, IL-1β, IL-18, HMGB1 were measured by ELISA. The histopathological changes of gastrointestinal (GI) tissues were examined by HE staining. The expression and localization of GSDME in GI tissues were determined by IHC. The GSDME mRNA expression in GI tissues was determined by RT-PCR. The IEC-6 cell viability was detected by CCK-8. The morphology of IEC-6 cells was observed by optical microscope and scanning electron microscopy. Pyroptosis was examined using Hoechst33342/PI staining. The intracellular ROS levels were measured with the fluorescent probe DCFH-DA. The expression levels of JNK, p-JNK, Bax, Bcl-2, caspase-9, caspase-3 and GSDME in GI tissues and IEC-6 cells were determined by WB.
RESULTS
We found that the cumulative kaolin intake (pica behavior, analogous to emesis) significantly increased in cisplatin-treated rats, accompanied by significant inflammatory pathological changes of GI tissues. XBXD decreased the cumulative kaolin intake and alleviated GI inflammation in cisplatin-treated rats by inhibiting the activation of the ROS/JNK/Bax signaling pathway and by reducing GSDME-mediated pyroptosis. Additionally, cisplatin damaged IEC-6 cells by activating GSDME-dependent pyroptosis. XBXD reduced GSDME-mediated IEC-6 cell pyroptotic death by regulating the ROS/JNK/Bax signaling pathway.
CONCLUSIONS
This study suggested that GSDME-mediated pyroptosis greatly contributes to the occurrence of CINV, and suppressing GSDME-mediated pyroptosis is the important antiemetic mechanism of XBXD.
Topics: Rats; Animals; Pyroptosis; Cisplatin; Antiemetics; bcl-2-Associated X Protein; Reactive Oxygen Species; Kaolin; Pica; Antineoplastic Agents; Vomiting; Nausea; Inflammation; Caspase 3
PubMed: 37516392
DOI: 10.1016/j.jep.2023.116970 -
The Journal of Pharmacology and... Sep 2020Attenuating emesis elicited by both disease and medical treatments of disease remains a critical public health challenge. Although cannabinergic medications have been...
Attenuating emesis elicited by both disease and medical treatments of disease remains a critical public health challenge. Although cannabinergic medications have been used in certain treatment-resistant populations, Food and Drug Administration-approved cannabinoid antiemetics are associated with undesirable side effects, including cognitive disruption, that limit their prescription. Previous studies have shown that a metabolically stable analog of the endocannabinoid anandamide, methanandamide (mAEA), may produce lesser cognitive disruption than that associated with the primary psychoactive constituent in cannabis, Δ-tetrahydrocannabinol (Δ-THC), raising the possibility that endocannabinoids may offer a therapeutic advantage over currently used medications. The present studies were conducted to evaluate this possibility by comparing the antiemetic effects of Δ-THC (0.032-0.1 mg/kg) and mAEA (3.2-10.0 mg/kg) against nicotine- and lithium chloride (LiCl)-induced emesis and prodromal hypersalivation in squirrel monkeys. Pretreatment with 0.1 mg/kg Δ-THC blocked nicotine-induced emesis and reduced hypersalivation in all subjects and blocked LiCl-induced emesis and reduced hypersalivation in three of four subjects. Pretreatment with 10 mg/kg mAEA blocked nicotine-induced emesis in three of four subjects and LiCl-induced emesis in one of four subjects and reduced both nicotine- and LiCl-induced hypersalivation. Antiemetic effects of Δ-THC and mAEA were reversed by rimonabant pretreatment, providing verification of cannabinoid receptor type 1 mediation. These studies systematically demonstrate for the first time the antiemetic effects of cannabinoid agonists in nonhuman primates. Importantly, although Δ-THC produced superior antiemetic effects, the milder cognitive effects of mAEA demonstrated in previous studies suggest that it may provide a favorable treatment option under clinical circumstances in which antiemetic efficacy must be balanced against side effect liability. SIGNIFICANCE STATEMENT: Emesis has significant evolutionary value as a defense mechanism against ingested toxins; however, it is also one of the most common adverse symptoms associated with both disease and medical treatments of disease. The development of improved antiemetic pharmacotherapies has been impeded by a paucity of animal models. The present studies systematically demonstrate for the first time the antiemetic effects of the phytocannabinoid Δ-tetrahydrocannabinol and endocannabinoid analog methanandamide in nonhuman primates.
Topics: Animals; Antiemetics; Arachidonic Acids; Cannabinoid Receptor Agonists; Dronabinol; Drug Interactions; Male; Receptor, Cannabinoid, CB1; Saimiri; Salivation; Vomiting
PubMed: 32561684
DOI: 10.1124/jpet.120.265710 -
Journal of Pediatric Gastroenterology... Apr 2019Vomiting is not only unpleasant for both children and families, but can lead to frequent hospital admission. The persistent vomiting hampers oral intake and increases... (Review)
Review
Vomiting is not only unpleasant for both children and families, but can lead to frequent hospital admission. The persistent vomiting hampers oral intake and increases the risk of dehydration, so the proper use of antiemetic drugs can be useful. The pharmacological treatment of vomiting in children remains a challenge for the pediatrician because several antiemetics are prescribed as "off-label," outside their authorized drug label. Domperidone and ondansetron are the most commonly known antiemetic drugs. A single oral dose of ondansetron has been shown to reduce the risk of recurrent vomiting, the need for intravenous fluids, and hospital admissions in children with acute gastroenteritis. There is enough evidence to support ondansetron administration in children, so the clinical use can be defined as "off-label/on evidence." This review aims to provide an overview of therapeutic use, safety, and main pharmacological properties of antiemetic drugs in children. A comprehensive search of published literature using the PubMed MEDLINE database was carried out to identify all articles published in English from 1998 to February 2018. At present time, the "off-label/on-evidence" use of some antiemetics could improve the success rate of oral rehydration therapy in pediatric emergency settings and to change the management of vomiting with the prevention of the complications.
Topics: Antiemetics; Child; Humans; Ondansetron; Vomiting
PubMed: 30540713
DOI: 10.1097/MPG.0000000000002225 -
Anesthesia and Analgesia Mar 2016Research has shown that high-risk surgical patients benefit from a multimodal therapeutic approach to prevent postoperative nausea and vomiting (PONV). Our group sought... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Research has shown that high-risk surgical patients benefit from a multimodal therapeutic approach to prevent postoperative nausea and vomiting (PONV). Our group sought to investigate the effect of administering IV midazolam on PONV.
METHODS
This meta-analysis included 12 randomized controlled trials (n = 841) of adults undergoing a variety of surgical procedures that investigated the effect of both preoperative and intraoperative IV midazolam on PONV in patients undergoing general anesthesia.
RESULTS
Administration of IV midazolam was associated with significantly reduced PONV (risk ratio [RR] = 0.55; 95% confidence interval [CI], 0.43-0.70), nausea (RR = 0.62; 95% CI, 0.40-0.94), vomiting (RR = 0.61; 95% CI, 0.45-0.82), and rescue antiemetic administration (RR = 0.49; 95% CI, 0.37-0.65) within 24 hours. Individual subgroup analyses of trials excluding the use of thiopental for induction, trials of either female sex or high-risk surgery, trials involving nitrous oxide maintenance, and trials using midazolam in combination with known antiemetics all yielded similar reductions in PONV end points within 24 hours of surgery.
CONCLUSIONS
Administration of preoperative or intraoperative IV midazolam is associated with a significant decrease in overall PONV, nausea, vomiting, and rescue antiemetic use. Providers may consider the administration of IV midazolam as part of a multimodal approach in preventing PONV.
Topics: Antiemetics; Humans; Injections, Intravenous; Midazolam; Postoperative Nausea and Vomiting; Randomized Controlled Trials as Topic
PubMed: 26332858
DOI: 10.1213/ANE.0000000000000941 -
Pharmacotherapy Sep 2023Despite the availability of several classes of antiemetics, postoperative nausea and vomiting (PONV) remains a substantial burden for patients following surgery,... (Review)
Review
Despite the availability of several classes of antiemetics, postoperative nausea and vomiting (PONV) remains a substantial burden for patients following surgery, resulting in patient dissatisfaction and prolonged stays in post-anesthesia care units and ultimately increasing the cost of care. Enhanced recovery protocols and PONV management guidelines are now centered on the assessment of the individual patient's risk for developing PONV, as well as multimodal prophylaxis using antiemetics targeting different mechanisms of action. Over the last two decades, the neurokinin-1 receptor (NK1R) has emerged as a therapeutic target for the management of PONV. This review of the literature explains the role of the NK1R and its ligand-substance P-in vomiting, describes the pharmacologic and pharmacokinetic properties of NK1R antagonists (NK1RAs) and summarizes the clinical evidence supporting NK1RAs for PONV prophylaxis in patients undergoing surgery. In particular, we discuss the therapeutic application of NK1RA in PONV prophylaxis protocols owing to their advantages over other antiemetic classes in efficacy, duration of efficacy, safety, pharmacology, and ease of administration. Future studies will be aimed at further investigating the efficacy and safety of NK1RA-based multimodal combinations, particularly among vulnerable populations (e.g., children and elderly).
Topics: Child; Humans; Aged; Postoperative Nausea and Vomiting; Antiemetics; Neurokinin-1 Receptor Antagonists; Drug Therapy, Combination
PubMed: 37166582
DOI: 10.1002/phar.2814 -
Journal of Oncology Pharmacy Practice :... Jun 2020Chemotherapy-induced nausea and vomiting occurs in up to 80% of patients undergoing chemotherapy treatment and is associated with a deterioration in quality of life....
BACKGROUND
Chemotherapy-induced nausea and vomiting occurs in up to 80% of patients undergoing chemotherapy treatment and is associated with a deterioration in quality of life. Olanzapine is an atypical antipsychotic antagonist blocking a variety of neurotransmitters in the nausea and vomiting pathophysiology.
OBJECTIVES
The primary objective of this study is to determine whether olanzapine is associated with improved breakthrough nausea and vomiting in patients undergoing hematopoietic stem cell transplant. Secondary outcomes include number of documented emesis episodes, an evaluation of patient oral intake, and number of rescue antiemetic agents administered after olanzapine initiation.
METHODS
This is a retrospective cohort review examining the effects of olanzapine for the treatment of breakthrough nausea and vomiting following hematopoietic stem cell transplant. Patients undergoing autologous or allogeneic hematopoietic stem cell transplant between January 2014 and October 2017 were included.
RESULTS
A total of 150 patients were included in the study. Olanzapine use was associated with a complete response in 30% of patients for breakthrough chemotherapy-induced nausea and vomiting (p < 0.0001). An improvement in nausea (p < 0.0001) and vomiting (p = 0.02) was also observed in patients. Olanzapine administration was associated with lower as needed antiemetic usage (p < 0.0001) as well as fewer emesis episodes (p < 0.0001) but had no effect on oral intake (p = 0.13).
CONCLUSIONS
Olanzapine was associated with significant improvements in breakthrough nausea and vomiting control while reducing the number of emesis episodes and required antiemetic doses in the hematopoietic stem cell transplant population. Olanzapine may be beneficial in optimizing antiemetic regimens for breakthrough chemotherapy-induced nausea and vomiting control in patients undergoing hematopoietic stem cell transplant.
Topics: Adult; Aged; Antiemetics; Antineoplastic Agents; Female; Hematopoietic Stem Cell Transplantation; Humans; Male; Middle Aged; Nausea; Olanzapine; Retrospective Studies; Vomiting
PubMed: 31635549
DOI: 10.1177/1078155219879215 -
Critical Reviews in Oncology/hematology Apr 2017Olanzapine is an anti-psychotic drug that has been used for preventing and treating Chemotherapy-Induced Nausea and Vomiting (CINV). This study aimed to systematically... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Olanzapine is an anti-psychotic drug that has been used for preventing and treating Chemotherapy-Induced Nausea and Vomiting (CINV). This study aimed to systematically review and meta-analyze the efficacy and safety of olanzapine for prophylaxis and treatment of CINV.
METHODS
We conducted a systematic literature search of MEDLINE, EMBASE, SCOPUS, and the Cochrane Central Register of Controlled Trials-CENTRAL up to July 15, 2016. All observational and intervention studies were included, but only the intervention studies were pooled for meta-analysis. The efficacy outcome was the proportion of patients achieving complete response (CR) - no emesis and no rescue therapy, in the acute, delayed, and overall phases. The safety outcomes were the adverse events associated with olanzapine according to Common Terminology Criteria for Adverse Events (CTCAE).
RESULTS
Sixteen studies were eligible: 15 clinical trials and 1 observational study. Nine of the interventional studies were pooled for meta-analysis. The CR of olanzapine was superior to other anti-emetic regimens, in both the delayed and overall phases (RR=1.27, 95% CI 1.07-1.49, RR=1.32, 95% CI 1.08-1.62, respectively). However, olanzapine was not better than standard CINV prophylaxis of the nausea and emesis outcome in the acute phase. Drowsiness and constipation were the most reported adverse events. No grade 3 or 4 adverse events were reported.
CONCLUSION
Olanzapine is effective and safe at reducing during the delayed and overall phase of the CINV prevention. Other regimens might be added, in cases of CINV during the acute phase of CINV.
Topics: Antiemetics; Antineoplastic Agents; Benzodiazepines; Humans; Nausea; Olanzapine; Vomiting
PubMed: 28325253
DOI: 10.1016/j.critrevonc.2017.02.017 -
Supportive Care in Cancer : Official... Feb 2018Chemotherapy-induced nausea and vomiting (CINV) can be prevented in most patients with use of guideline-recommended antiemetic regimens. However, studies have suggested...
PURPOSE
Chemotherapy-induced nausea and vomiting (CINV) can be prevented in most patients with use of guideline-recommended antiemetic regimens. However, studies have suggested that adherence to antiemetic guidelines is suboptimal. Oncology nurses, as part of a multidisciplinary team, can help promote appropriate antiemetic prophylaxis. Therefore, nurses were surveyed to assess antiemetic guideline awareness and practice patterns of antiemetic use, determine adherence to guideline recommendations, and query barriers to adherence.
METHODS
In September 2015, 531 US-based oncology nurses participated in an online survey administered and analyzed by ONS:Edge.
RESULTS
Nurses were most familiar with National Comprehensive Cancer Network (73%) and American Society of Clinical Oncology (48%) antiemetic guidelines. While most (77%) felt that antiemetics prescribed were consistent with guideline recommendations, practice patterns of antiemetic use revealed low adherence to those guidelines, particularly during the delayed (25-120 h) phase following highly emetogenic chemotherapy, where only 25% of nurses reported administration of guideline-recommended agents. Overutilization of phenothiazines and benzodiazepines was common. Only 17% of respondents reported that most (> 75%) of their patients have CINV optimally controlled; 39% reported between 6 and 20% of patients have an alteration in their chemotherapy due to CINV, and reports of emergency department/hospital visits due to poorly controlled CINV were high. The predominant barrier interfering guideline-recommended antiemetic prophylaxis was reported as physician preference (71%).
CONCLUSIONS
This survey revealed an opportunity to increase awareness of antiemetic guidelines and a critical need to address barriers interfering with utilization of guideline-recommended antiemetic agents in order to optimize CINV control for patients undergoing emetogenic chemotherapy.
Topics: Antiemetics; Female; Humans; Induction Chemotherapy; Male; Medication Adherence; Nausea; Nurse Clinicians; Surveys and Questionnaires; Vomiting
PubMed: 28871358
DOI: 10.1007/s00520-017-3866-6 -
Revista Brasileira de Enfermagem 2020To identify and discuss scientific evidence of the effects of ginger use on the management of chemotherapy-induced nausea and vomiting. (Review)
Review
OBJECTIVES
To identify and discuss scientific evidence of the effects of ginger use on the management of chemotherapy-induced nausea and vomiting.
METHODS
This is an integrative reviewperformed by Ganong's reference.
RESULTS
We included 24 studies, highlighting three thematic categories, namely 1) antiemetic action of ginger - nausea (13 articles; of these, nine significant) and emesis (10 studies; of these, six significant); 2) action in the control of nausea (11 articles; of these, six significant) and vomiting (8 articles; of these, three significant) in the acute phase; 3) action in the control of nausea (6 articles; of these, three significant) and vomiting (6 articles; of these, three significant) in the delayed phase. There were divergences of the methods used.
FINAL CONSIDERATIONS
This complementary therapy has low cost and easy access, but no statistical confirmation of its effectiveness in the management of nausea and vomiting in cancer patients was found.
Topics: Antiemetics; Drug Therapy; Female; Zingiber officinale; Humans; Male; Middle Aged; Nausea; Vomiting
PubMed: 32236378
DOI: 10.1590/0034-7167-2018-0903