酒精戒断

苯二氮䓬类药物是酒精戒断症状以及酒精戒断相关性癫痫发作的一线治疗药物。[12]Dixit D, Endicott J, Burry L, et al. Management of acute alcohol withdrawal syndrome in critically ill patients. Pharmacotherapy. 2016;36:797-822.http://onlinelibrary.wiley.com/doi/10.1002/phar.1770/fullhttp://www.ncbi.nlm.nih.gov/pubmed/27196747?tool=bestpractice.com[73]Long D, Long B, Koyfman A. The emergency medicine management of severe alcohol withdrawal. Am J Emerg Med. 2017 Feb 4. [Epub ahead of print]http://www.ncbi.nlm.nih.gov/pubmed/28188055?tool=bestpractice.com[74]Ebell MH. Benzodiazepines for alcohol withdrawal. Am Fam Physician. 2006;73:1191.http://www.aafp.org/afp/2006/0401/p1191.htmlhttp://www.ncbi.nlm.nih.gov/pubmed/16623205?tool=bestpractice.com[75]Bråthen G, Ben-Menachem E, Brodtkorb E, et al. Chapter 29: alcohol-related seizures. EFNS guidelines of alcohol-related seizures. In: Gilhus NE, Barnes MP, Brainin M, eds. European handbook of neurological management. 2nd ed, v1. Oxford, UK: Blackwell publishing; 2011:429-436.http://www.efns.org/fileadmin/user_upload/guidline_papers/EFNS_guideline_2011_Alcohol-related_seizures.pdf[76]Amato L, Minozzi S, Davoli M. Efficacy and safety of pharmacological interventions for the treatment of the alcohol withdrawal syndrome. Cochrane Database Syst Rev. 2011;(6):CD008537.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD008537.pub2/fullhttp://www.ncbi.nlm.nih.gov/pubmed/21678378?tool=bestpractice.com[77]Amato L, Minozzi S, Vecchi S, et al. Benzodiazepines for alcohol withdrawal. Cochrane Database Syst Rev. 2010;(3):CD005063.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD005063.pub3/fullhttp://www.ncbi.nlm.nih.gov/pubmed/20238336?tool=bestpractice.com[86]Schmidt KJ, Doshi MR, Holzhausen JM, et al. Treatment of severe alcohol withdrawal. Ann Pharmacother. 2016;50:389-401.http://www.ncbi.nlm.nih.gov/pubmed/26861990?tool=bestpractice.com欧洲神经学会联盟关于酒精相关性癫痫发作的指南以及其他一些资料推荐将劳拉西泮和地西泮作为首选药物。[73]Long D, Long B, Koyfman A. The emergency medicine management of severe alcohol withdrawal. Am J Emerg Med. 2017 Feb 4. [Epub ahead of print]http://www.ncbi.nlm.nih.gov/pubmed/28188055?tool=bestpractice.com[75]Bråthen G, Ben-Menachem E, Brodtkorb E, et al. Chapter 29: alcohol-related seizures. EFNS guidelines of alcohol-related seizures. In: Gilhus NE, Barnes MP, Brainin M, eds. European handbook of neurological management. 2nd ed, v1. Oxford, UK: Blackwell publishing; 2011:429-436.http://www.efns.org/fileadmin/user_upload/guidline_papers/EFNS_guideline_2011_Alcohol-related_seizures.pdf

对于酒精戒断性癫痫发作患者，使用苯二氮䓬类药物比使用安慰剂更有效。[77]Amato L, Minozzi S, Vecchi S, et al. Benzodiazepines for alcohol withdrawal. Cochrane Database Syst Rev. 2010;(3):CD005063.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD005063.pub3/fullhttp://www.ncbi.nlm.nih.gov/pubmed/20238336?tool=bestpractice.com没有哪一种苯二氮䓬类药物优于另一种，但有一些（无统计学意义）数据提示，氯氮卓（在英国、美国和其他一些国家，只有口服制剂）可能比其他药物更有效。[77]Amato L, Minozzi S, Vecchi S, et al. Benzodiazepines for alcohol withdrawal. Cochrane Database Syst Rev. 2010;(3):CD005063.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD005063.pub3/fullhttp://www.ncbi.nlm.nih.gov/pubmed/20238336?tool=bestpractice.com口服药物适合用于有轻度戒断症状的患者，但对于中至重度 AWS，首选苯二氮䓬类药物静脉给药。在建立静脉通路前，劳拉西泮肌内注射给药可能是合适的。对肝衰竭的患者，劳拉西泮比氯氮卓在避免过度镇静方面要好一些，

酒精戒断性癫痫发作通常是自限性的；对于癫痫反复发作或癫痫持续状态，应使用苯二氮䓬类药物治疗，但还应立即检查癫痫发作的其他原因。对于酒精所致癫痫持续状态的初始治疗，静脉注射劳拉西泮是安全有效的。[73]Long D, Long B, Koyfman A. The emergency medicine management of severe alcohol withdrawal. Am J Emerg Med. 2017 Feb 4. [Epub ahead of print]http://www.ncbi.nlm.nih.gov/pubmed/28188055?tool=bestpractice.com[75]Bråthen G, Ben-Menachem E, Brodtkorb E, et al. Chapter 29: alcohol-related seizures. EFNS guidelines of alcohol-related seizures. In: Gilhus NE, Barnes MP, Brainin M, eds. European handbook of neurological management. 2nd ed, v1. Oxford, UK: Blackwell publishing; 2011:429-436.http://www.efns.org/fileadmin/user_upload/guidline_papers/EFNS_guideline_2011_Alcohol-related_seizures.pdf静脉使用地西泮是一种很好的替代选择。[73]Long D, Long B, Koyfman A. The emergency medicine management of severe alcohol withdrawal. Am J Emerg Med. 2017 Feb 4. [Epub ahead of print]http://www.ncbi.nlm.nih.gov/pubmed/28188055?tool=bestpractice.com[75]Bråthen G, Ben-Menachem E, Brodtkorb E, et al. Chapter 29: alcohol-related seizures. EFNS guidelines of alcohol-related seizures. In: Gilhus NE, Barnes MP, Brainin M, eds. European handbook of neurological management. 2nd ed, v1. Oxford, UK: Blackwell publishing; 2011:429-436.http://www.efns.org/fileadmin/user_upload/guidline_papers/EFNS_guideline_2011_Alcohol-related_seizures.pdf

苯二氮䓬类药物治疗的并发症包括过度镇静以及较少见的呼吸抑制。因而需要频繁评估。首选长效苯二氮䓬类药物，但对于肝病患者，应使用短效苯二氮䓬类药物，以防止过度镇静。

应用苯二氮䓬类药物治疗有两种方法：[78]Skinner RT. Symptom-triggered vs. fixed-dosing management of alcohol withdrawal syndrome. Medsurg Nurs. 2014;23:307-315, 329.http://www.ncbi.nlm.nih.gov/pubmed/26292436?tool=bestpractice.com(1) 症状导向方案，是指在修订版临床机构酒精戒断评估量表 (CIWA-Ar) 评分超过 8 分时使用药物治疗；(2) 固定剂量方案，按照一定的时间间隔给药，并根据症状需要，可以给予额外的剂量。门诊治疗通常采用固定给药法。

治疗失败的门诊患者，可能需要更高剂量的苯二氮䓬类药物，并且他们可能需要住院接受进一步治疗。

氯美噻唑是除了苯二氮卓类药物以外的一个选择。这个药物使用时要谨慎，只用于住院患者，按照处方使用。[71]National Institute for Health and Care Excellence. Alcohol-use disorders: diagnosis and clinical management of alcohol-related physical complications. April 2017. https://www.nice.org.uk/ (last accessed 20 May 2017).https://www.nice.org.uk/guidance/cg100

治疗的主要目的是减少戒断症状、帮助远期戒酒、发现和治疗并发的躯体或精神疾病。[67]Alcohol withdrawal syndrome: how to predict, prevent, diagnose and treat it. Prescrire Int. 2007;16:24-31.http://www.ncbi.nlm.nih.gov/pubmed/17323538?tool=bestpractice.com

治疗包括处理戒断症状和预防复发。通过咨询或药物来预防复发。

戒断症状较轻的患者可以门诊治疗，并随访预防复发。家庭环境不稳定的患者或重度 AWS 患者需要住院治疗，包括药物和支持性干预措施。

重度 AWS 及存在精神或躯体疾病的患者需要高水平护理（例如入住 ICU），并增加苯二氮䓬类药物剂量。在该患者人群中，并发症发生率和死亡率较高。据报告，重度 AWS 患者中有一部分对苯二氮䓬类药物耐药，可能需要辅助药物治疗 AWS。[68]Martin K, Katz A. The role of barbiturates for alcohol withdrawal syndrome. Psychosomatics. 2016;57:341-347.http://www.ncbi.nlm.nih.gov/pubmed/27207572?tool=bestpractice.com[69]Brotherton AL, Hamilton EP, Kloss HG, et al. Propofol for treatment of refractory alcohol withdrawal syndrome: a review of the literature. Pharmacotherapy. 2016;36:433-442.http://www.ncbi.nlm.nih.gov/pubmed/26893017?tool=bestpractice.com临床上，在治疗的第一个小时内需要静脉使用≥50 mg 地西泮的患者被认为存在苯二氮䓬类药物耐药性 AWS。[70]Hack JB, Hoffmann RS, Nelson LS. Resistant alcohol withdrawal: does an unexpectedly large sedative requirement identify these patients early? J Med Toxicol. 2006;2:55-60.http://www.ncbi.nlm.nih.gov/pubmed/18072114?tool=bestpractice.com

对于以下患者，应收住院，给予药物辅助酒精戒断：[71]National Institute for Health and Care Excellence. Alcohol-use disorders: diagnosis and clinical management of alcohol-related physical complications. April 2017. https://www.nice.org.uk/ (last accessed 20 May 2017).https://www.nice.org.uk/guidance/cg100处于急性酒精戒断期，，伴有或经评估存在发生酒精戒断性癫痫发作或震颤谵妄高风险的患者；处于急性酒精戒断期的 16 岁以下年轻人；处于急性酒精戒断期的某些易感人群（例如：身体虚弱、有认知障碍或多种共病、缺乏社会支持、存在学习困难以及年龄为 16-17 岁）。

此外，对于有失代偿性疾病、严重电解质异常、血清乙醇＜20 mg/dL 时 CIWA-Ar 量表评分大于 15 分，或者有震颤谵妄或酒精戒断性癫痫发作病史的患者，应当考虑收入院。[72]Stephens JR, Liles EA, Dancel R, et al. Who needs inpatient detox? Development and implementation of a hospitalist protocol for the evaluation of patients for alcohol detoxification. J Gen Intern Med. 2014;29:587-593.http://www.ncbi.nlm.nih.gov/pubmed/24395104?tool=bestpractice.com

有血流动力学不稳定、重度电解质异常、心脏疾病、呼吸功能不全、潜在重度感染、持续性体温过高、胃肠道病变体征、横纹肌溶解症的证据、肾功能不全、需要频繁或高剂量镇静剂给药或尽管血清乙醇浓度升高但仍有戒断症状的患者，应当入住 ICU。[73]Long D, Long B, Koyfman A. The emergency medicine management of severe alcohol withdrawal. Am J Emerg Med. 2017 Feb 4. [Epub ahead of print]http://www.ncbi.nlm.nih.gov/pubmed/28188055?tool=bestpractice.com

入院患者需要连续的心脏和脉搏血氧监护，并且可能需要 ICU 治疗。

对那些没有入院的酒依赖患者，要建议他们避免突然减少饮酒，给他们提供信息让他们知道如何联系当地对饮酒者提供支持的机构。[71]National Institute for Health and Care Excellence. Alcohol-use disorders: diagnosis and clinical management of alcohol-related physical complications. April 2017. https://www.nice.org.uk/ (last accessed 20 May 2017).https://www.nice.org.uk/guidance/cg100

针对经选择患者组全部患者的治疗推荐

对于需要增加苯二氮䓬类药物剂量以缓解重度戒断和震颤谵妄的患者，使用苯巴比妥可能有益。[79]Gold JA, Rimal B, Nolan A, et al. A strategy of escalating doses of benzodiazepines and phenobarbital administration reduces the need for mechanical ventilation in delirium tremens. Care Med. 2007;35:724-730.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3417045/http://www.ncbi.nlm.nih.gov/pubmed/17255852?tool=bestpractice.com

它可以降低对机械通气的需求以及减少 ICU 入住数。[79]Gold JA, Rimal B, Nolan A, et al. A strategy of escalating doses of benzodiazepines and phenobarbital administration reduces the need for mechanical ventilation in delirium tremens. Care Med. 2007;35:724-730.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3417045/http://www.ncbi.nlm.nih.gov/pubmed/17255852?tool=bestpractice.com[80]Rosenson J, Clements C, Simon B, et al. Phenobarbital for acute alcohol withdrawal: a prospective randomized double-blind placebo-controlled study. J Emerg Med. 2013;44:592-598.http://www.ncbi.nlm.nih.gov/pubmed/22999778?tool=bestpractice.com

针对经选择患者组全部患者的治疗推荐

对于可能有维生素缺乏的酒精滥用患者，应当考虑补充维生素。

补充维生素 B1 可降低韦尼克脑病和 Korsakoff 综合征的风险。慢性饮酒会导致维生素 B1 吸收减少，因而建议静脉给药或肌内注射给药。[12]Dixit D, Endicott J, Burry L, et al. Management of acute alcohol withdrawal syndrome in critically ill patients. Pharmacotherapy. 2016;36:797-822.http://onlinelibrary.wiley.com/doi/10.1002/phar.1770/fullhttp://www.ncbi.nlm.nih.gov/pubmed/27196747?tool=bestpractice.com患者应当处于有监护的环境。如果怀疑韦尼克脑病，则给予高剂量维生素 B1。[86]Schmidt KJ, Doshi MR, Holzhausen JM, et al. Treatment of severe alcohol withdrawal. Ann Pharmacother. 2016;50:389-401.http://www.ncbi.nlm.nih.gov/pubmed/26861990?tool=bestpractice.com

在纠正慢性酒精中毒患者的低镁血症方面，尚无关于镁剂具体用药剂量的建议。在紧急情况下，重度低镁血症 (＜1 mg/dL) 和有症状的患者可能需要经静脉输注高达 2g 的硫酸镁。治疗期间要监测患者，定期检查患者深部腱反射和呼吸情况，防止出现高镁血症。低镁血症的进一步治疗需要在专家和初级保健医生的会诊下进行。[85]Ferri FF. Practical guide to the care of the medical patient. 7th ed. Philadelphia, PA: Mosby-Elsevier; 2007.

针对经选择患者组全部患者的治疗推荐

右美托咪定是一种镇静剂，在 ICU 可以用作苯二氮䓬类药物的辅助药物治疗 AWS，但证据有限。

来自一项小型随机试验的数据显示，接受右美托咪定治疗的患者可能需要减少苯二氮䓬类药物的使用剂量。[81]Mueller SW, Preslaski CR, Kiser TH, et al. A randomized, double-blind, placebo-controlled dose range study of dexmedetomidine as adjunctive therapy for alcohol withdrawal. Crit Care Med. 2014;42:1131-1139.http://www.ncbi.nlm.nih.gov/pubmed/24351375?tool=bestpractice.com病例系列研究报告了类似结果。[82]Woods AD, Giometti R, Weeks SM. The use of dexmedetomidine as an adjuvant to benzodiazepine-based therapy to decrease the severity of delirium in alcohol withdrawal in adult intensive care unit patients: a systematic review. JBI Database System Rev Implement Rep. 2015;13:224-252.http://www.ncbi.nlm.nih.gov/pubmed/26447017?tool=bestpractice.com

右美托咪定缺乏 GABA 受体活性，不能减少戒断相关性癫痫发作。因此，它仅应作为苯二氮䓬类药物的辅助药物开具。

针对经选择患者组全部患者的治疗推荐

丙泊酚是一种麻醉药物，仅用于对苯二氮䓬类药物耐药的患者或需要机械通气的患者。[83]Sohraby R, Attridge RL, Hughes DW. Use of propofol-containing versus benzodiazepine regimens for alcohol withdrawal requiring mechanical ventilation. Ann Pharmacother. 2014;48:456-461.http://www.ncbi.nlm.nih.gov/pubmed/24436457?tool=bestpractice.com

该药似乎有效，但是可显著增加临床护理，包括 ICU 入住时长和住院时长。[12]Dixit D, Endicott J, Burry L, et al. Management of acute alcohol withdrawal syndrome in critically ill patients. Pharmacotherapy. 2016;36:797-822.http://onlinelibrary.wiley.com/doi/10.1002/phar.1770/fullhttp://www.ncbi.nlm.nih.gov/pubmed/27196747?tool=bestpractice.com[84]Wong A, Benedict NJ, Lohr BR, et al. Management of benzodiazepine-resistant alcohol withdrawal across a healthcare system: benzodiazepine dose-escalation with or without propofol. Drug Alcohol Depend. 2015;154:296-299.http://www.ncbi.nlm.nih.gov/pubmed/26205315?tool=bestpractice.com

丙泊酚可以导致呼吸抑制；开始接受丙泊酚治疗的患者需要入住 ICU。