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[5-羟色胺3受体拮抗剂、类固醇、抗组胺药、抗胆碱能药、生长抑素拮抗剂、苯二氮卓类药物和大麻素类药物用于姑息治疗患者恶心呕吐的治疗:一项系统评价]

[Treatment of nausea and vomiting with 5HT3 receptor antagonists, steroids, antihistamines, anticholinergics, somatostatinantagonists, benzodiazepines and cannabinoids in palliative care patients : a systematic review].

作者信息

Benze G, Geyer A, Alt-Epping B, Nauck F

机构信息

Abteilung Palliativmedizin, Zentrum Anaesthesiologie, Rettungs- und Intensivmedizin, Georg-August-Universität Göttingen, Robert-Koch-Str. 40, 37075, Göttingen, Deutschland.

出版信息

Schmerz. 2012 Sep;26(5):481-99. doi: 10.1007/s00482-012-1235-4.

Abstract

BACKGROUND

Various recommendations exist for the treatment of nausea and vomiting in palliative care but only few studies and even less systematic reviews look into antiemetic therapy for patients receiving palliative care.

OBJECTIVES

This systematic review aims to analyze the current evidence for antiemetic treatment with 5HT3 receptor antagonists, steroids, antihistamines, anticholinergics, somatostatin analogs, benzodiazepines and cannabinoids in palliative care patients with far advanced cancer not receiving chemotherapy or radiotherapy, acquired immune deficiency syndrome (AIDS), chronic obstructive pulmonary disease (COPD), progressive heart failure, amyotrophic lateral sclerosis (ALS) or multiple sclerosis (MS). Results regarding evidence of treatment with prokinetic and neuroleptic agents will be published separately.

METHODS

The electronic databases PubMed and EmBase were systematically searched for studies (published 1966-2011) dealing with antiemetic therapy in palliative care and electronic retrieval was completed by manual searching. Studies with patients undergoing chemotherapy or radiotherapy, pediatric studies and studies published in languages other than English or German were excluded. Studies addressing therapy with 5HT3 receptor antagonists, steroids, antihistamines, anticholinergics, somatostatin analogs, benzodiazepines or cannabinoids were identified and selected for this systematic review.

RESULTS

In the general search 75 relevant studies were found. Of those 36 addressed 5HT3 receptor antagonists, steroids, antihistamines, anticholinergics, somatostatin analogs, benzodiazepines and cannabinoids, 13 considered 5HT3 receptor antagonists, 10 somatostatin antagonists, 9 steroids, 5 cannabinoids, 4 anticholinergics, 1 antihistamines and none benzodiazepines. Furthermore six systematic reviews exist. Evidence for any drug used as an antiemetic is low. Concerning 5HT3 receptor antagonists data are insufficient for recommendations on the treatment of patients with AIDS and MS due to the small size of included patient groups. For patients with cancer contradictory results were published: the larger studies showed a positive effect of 5HT3 receptor antagonists and better efficacy, as compared to metoclopramide, dexamethasone and neuroleptics. Heterogeneous results were found for steroids, with a positive trend for patients with cancer. Data are insufficient for antihistamines. Studies prove effectiveness of butylscopolammonium in the treatment of nausea and vomiting caused by malignant gastrointestinal obstruction, whereas octreotide is superior to butylscopolammonium. Regarding benzodiazepines for symptom control of nausea and vomiting in palliative care patients no studies were detected. Cannabinoids were found to relieve nausea and vomiting in patients with cancer and AIDS but with notable side effects. Furthermore, the studies compared cannabinoids to less recent antiemetic drugs but not, for example to 5HT3 receptor antagonists. Regarding symptom control of nausea and vomiting in patients with COPD, progressive heart failure and ALS no studies were undertaken in patients receiving palliative care.

CONCLUSIONS

In palliative care patients with nausea and vomiting 5HT3 receptor antagonists can be used if treatment with other antiemetics, such as metoclopramide and neuroleptics is not sufficient. There is a trend that steroids in combination with other antiemetics improve symptom relief. Cannabinoids rather have a status as a second line antiemetic. In cases of nausea and vomiting caused by malignant gastrointestinal obstruction octreotide showed the best and butylscopolammonium bromide the second best results. Concerning antihistamines and benzodiazepines insufficient data was found. Recommendations in the literature are mainly based on studies in patients with cancer. The overall strength of evidence is low. More well designed studies in palliative care patients are needed in order to provide evidence-based therapy. The English full text version of this article will be available in SpringerLink as of November 2012 (under "Supplemental").

摘要

背景

姑息治疗中针对恶心和呕吐的治疗有多种建议,但仅有少数研究,系统评价更是少之又少,探讨接受姑息治疗患者的止吐疗法。

目的

本系统评价旨在分析5-羟色胺3(5HT3)受体拮抗剂、类固醇、抗组胺药、抗胆碱能药、生长抑素类似物、苯二氮䓬类药物和大麻素类药物用于未接受化疗或放疗的晚期癌症、获得性免疫缺陷综合征(AIDS)、慢性阻塞性肺疾病(COPD)、进行性心力衰竭、肌萎缩侧索硬化症(ALS)或多发性硬化症(MS)姑息治疗患者止吐治疗的现有证据。关于促动力药和抗精神病药治疗证据的结果将另行发表。

方法

系统检索电子数据库PubMed和EmBase中有关姑息治疗中使用止吐疗法的研究(发表时间为1966 - 2011年),并通过手工检索完成电子检索。排除接受化疗或放疗患者的研究、儿科研究以及非英语或德语发表的研究。确定并选择涉及5HT3受体拮抗剂、类固醇、抗组胺药、抗胆碱能药、生长抑素类似物、苯二氮䓬类药物或大麻素类药物治疗的研究进行本系统评价。

结果

在全面检索中发现75项相关研究。其中36项涉及5HT3受体拮抗剂、类固醇、抗组胺药、抗胆碱能药、生长抑素类似物、苯二氮䓬类药物和大麻素类药物,13项考虑了5HT3受体拮抗剂,10项考虑了生长抑素拮抗剂,9项考虑了类固醇,5项考虑了大麻素,4项考虑了抗胆碱能药,1项考虑了抗组胺药,未发现涉及苯二氮䓬类药物的研究。此外,存在6篇系统评价。用作止吐药的任何药物的证据都很薄弱。关于5HT3受体拮抗剂,由于纳入患者组规模较小,因此缺乏足够数据为AIDS和MS患者的治疗提供推荐。关于癌症患者,发表了相互矛盾的结果:规模较大的研究表明5HT3受体拮抗剂有积极作用,且与甲氧氯普胺、地塞米松和抗精神病药相比疗效更佳。类固醇的结果存在异质性,癌症患者有积极趋势。抗组胺药的数据不足。研究证明丁溴东莨菪碱对治疗恶性胃肠道梗阻引起的恶心和呕吐有效,而奥曲肽优于丁溴东莨菪碱。关于苯二氮䓬类药物用于姑息治疗患者恶心和呕吐症状控制的研究未被发现。大麻素类药物可缓解癌症和AIDS患者的恶心和呕吐,但有明显副作用。此外,这些研究将大麻素类药物与较早期的止吐药进行了比较,但未与例如5HT3受体拮抗剂等进行比较。关于COPD、进行性心力衰竭和ALS患者恶心和呕吐症状控制,未对接受姑息治疗的患者进行研究。

结论

在有恶心和呕吐症状的姑息治疗患者中,如果使用其他止吐药(如甲氧氯普胺和抗精神病药)治疗不足,可使用5HT3受体拮抗剂。有趋势表明类固醇与其他止吐药联合使用可改善症状缓解。大麻素类药物更适合作为二线止吐药。在恶性胃肠道梗阻引起的恶心和呕吐病例中,奥曲肽显示出最佳效果,丁溴东莨菪碱次之。关于抗组胺药和苯二氮䓬类药物,发现的数据不足。文献中的推荐主要基于对癌症患者的研究。证据的总体强度较低。需要对姑息治疗患者进行更多设计良好的研究,以提供循证治疗。本文的英文全文版本将于2012年11月在SpringerLink上提供(在“补充材料”下)。

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