Neurokinin-1 receptor antagonists for postoperative nausea and vomiting: a systematic review and meta-analysis

Murakami, Chiaki; Kakuta, Nami; Satomi, Shiho; Nakamura, Ryuji; Miyoshi, Hirotsugu; Morio, Atsushi; Saeki, Noboru; Kato, Takahiro; Ohshita, Naohiro; Tanaka, Katsuya; Tsutsumi, Yasuo M.

doi:10.1016/j.bjane.2020.06.015

Cited by 6 publications

(5 citation statements)

References 33 publications

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“…As research on NK1R has intensified, several NK1Rspecific inhibitors have been developed. To make it easier to translate our findings for clinical application, in this study, we chose Aprepitant which is the first NK1R-specific antagonist approved by FDA for the treatment of chemotherapyinduced nausea and vomiting [59]. Aprepitant can cross the blood-brain barrier and competitively bind to NK1R receptors in the brain antagonizing the effects of the natural ligand SP [60].…”

Section: Discussionmentioning

confidence: 99%

Neurokinin Receptor 1 (NK1R) Antagonist Aprepitant Enhances Hematoma Clearance by Regulating Microglial Polarization via PKC/p38MAPK/NFκB Pathway After Experimental Intracerebral Hemorrhage in Mice

et al. 2021

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Hematoma clearance is an important therapeutic target to improve outcome following intracerebral hemorrhage (ICH). Recent studies showed that Neurokinin receptor-1 (NK1R) inhibition exerts protective effects in various neurological disease models, but its role in ICH has not been explored. The objective of this study was to investigate the role of NK1R and its relation to hematoma clearance after ICH using an autologous blood injection mouse model. A total of 332 adult male CD1 mice were used. We found that the expression levels of NK1R and its endogenous ligand, substance P (SP), were significantly upregulated after ICH. Intraperitoneal administration of the NK1R selective antagonist, Aprepitant, significantly improved neurobehavior, reduced hematoma volume and hemoglobin levels after ICH, and promoted microglia polarization towards M2 phenotype. Aprepitant decreased phosphorylated PKC, p38MAPK, and NFκB p65, and downregulated M1 markers while upregulating M2 markers after ICH. Intracerebroventricular administration of the NK1R agonist, GR73632 or PKC agonist, phorbol 12-myristate 13-acetate (PMA) reversed the effects of Aprepitant. To demonstrate the upstream mediator of NK1R activation, we performed thrombin injection and found that it increased SP. Inhibiting thrombin suppressed SP and decreased M1 markers while increasing M2 microglia polarization. Thus, NK1R inhibition promoted hematoma clearance after ICH by increasing M2 microglial polarization via downregulating PKC/p38MAPK/NFκB signaling pathway, and thrombin may be a key upstream mediator of NK1R activation. Therapeutic interventions inhibiting NK1R signaling may be a new target for the treatment of ICH.

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Section: Discussionmentioning

confidence: 99%

Neurokinin Receptor 1 (NK1R) Antagonist Aprepitant Enhances Hematoma Clearance by Regulating Microglial Polarization via PKC/p38MAPK/NFκB Pathway After Experimental Intracerebral Hemorrhage in Mice

et al. 2021

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“…Moreover, metoclopramide being a D2 receptor acting as a central dopaminergic antagonist increases gastric emptying. Looking into the mechanisms of action of the different drugs used for the same purpose, it is seen that for the treatment of postoperative nausea and vomiting, dexamethasone was found to be superior in the control of nausea and vomiting [ 5 ]. However, the results of the statistical calculation obtained from the study weightage the theories about the efficiency of dexamethasone against vomiting and nausea [ 14 - 16 ].…”

Section: Discussionmentioning

confidence: 99%

“…Postoperative nausea and vomiting thus are the most commonly occurring after-effects of any surgical procedure and targets about 50% of the patients who have undergone craniotomy [ 3 , 4 ]. These adverse effects threaten life by dangerously elevating the arterial pressure and intracranial pressure of the patients [ 5 ]. All these contrary signs make the way for hemorrhage and ultimately for deaths.…”

Section: Introductionmentioning

confidence: 99%

A Clinical Research on the Impact of Dexamethasone Versus Dexamethasone-Metoclopramide Combination in Reducing Postoperative Vomiting and Nausea After Cranial Surgery

Eryilmaz

Farooque

2021

Cureus

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IntroductionThis brief study shows the consumption of two medications that are related to those patients who have gone through the complicated procedure of craniotomy. The basic aim of these drugs is to subside the aftereffects of the procedure like postoperative nausea and vomiting in patients. Hereby, the study outlines the functional efficiency of dexamethasone along with the metoclopramide and dexamethasone alone. Materials and methodsRandomly two groups were listed of 120 patients that have undergone elective craniotomy with ASA I-II. These groups were called out as group A and group B. Group A was under the medication of combination of dexamethasone and metoclopramide 8 mg and 10 mg, respectively, induced separately while group B was induced with 8 mg of dexamethasone along with 2 ml of normal saline. These drugs were induced right before anesthesia. The procedure from here on gets the same for both groups. After the surgical approach, a verbal evaluation was taken from the members of each group to collect specific data accordingly within the first 24 hours. As the method is double-blinded thus the patients were unaware of the ongoing research study. In any case of a mishap, rescue antiemetic drugs were also considered for the patients who would have experienced uncontrolled nausea and vomiting in the timeframe. ResultsThe results show that only 16.7% of the patients from group A showed signs of nausea and only 5% showed vomiting while 31.7% of the patients from group B showed signs of nausea and 11.7% showed vomiting. It clearly showed that the patients tend to have either no sign of nausea and vomiting or showed little controllable nausea and vomiting when induced with dexamethasone and metoclopramide compared to those who were induced with the dexamethasone alone. ConclusionsPostoperative nausea and vomiting are studied in terms of those who had undergone craniotomy. This study shows the prophylaxis of adverse effects of postoperative nausea and vomiting between the two groups under the influence of altered drugs. Thus, the results were noticeably in the favor of the combination treatment of dexamethasone and metoclopramide.

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“…As NVPO são respostas não somente do pós-operatório, mas de eventos anteriores a cirurgia, ou que ocorrem durante o procedimento e tem causas multifatoriais (AMIRI et al, 2020), podendo ser desencadeadas pela ativação de diversos receptores periféricos e/ou centrais e podem estar relacionados aos agentes emetogênicos, como os anestésicos inalatórios e os opióides, a técnica anestésica, uso de óxido nitroso e duração da anestesia (SCHMIDT, 2020). Há ainda fatores de risco relacionados ao paciente como ser do sexo feminino, ser não fumante e ter histórico de cinetose e/ou NVPO (MURAKAMI et al, 2020).…”

Section: Características Gerais De Náuseas E Vômitos No Pós-operatóriounclassified

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Ascari¹

2021

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Neurokinin-1 receptor antagonists for postoperative nausea and vomiting: a systematic review and meta-analysis

Cited by 6 publications

References 33 publications

Neurokinin Receptor 1 (NK1R) Antagonist Aprepitant Enhances Hematoma Clearance by Regulating Microglial Polarization via PKC/p38MAPK/NFκB Pathway After Experimental Intracerebral Hemorrhage in Mice

Neurokinin Receptor 1 (NK1R) Antagonist Aprepitant Enhances Hematoma Clearance by Regulating Microglial Polarization via PKC/p38MAPK/NFκB Pathway After Experimental Intracerebral Hemorrhage in Mice

A Clinical Research on the Impact of Dexamethasone Versus Dexamethasone-Metoclopramide Combination in Reducing Postoperative Vomiting and Nausea After Cranial Surgery

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