在获得实验室检查结果之前就应开始给疑似苯丙胺中毒的患者进行治疗。 主要是支持治疗,旨在降低核心体温、补液、镇静(需要时)以及心电监护。[8]Hall AP, Henry JA. Acute toxic effects of 'Ecstasy' (MDMA) and related compounds: overview of pathophysiology and clinical management. Br J Anaesth. 2006;96:678-685.http://bja.oxfordjournals.org/cgi/content/full/96/6/678http://www.ncbi.nlm.nih.gov/pubmed/16595612?tool=bestpractice.com[15]Courtney KE, Ray LA. Methamphetamine: an update on epidemiology, pharmacology, clinical phenomenology, and treatment literature. Drug Alcohol Depend. 2014;143:11-21.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4164186/http://www.ncbi.nlm.nih.gov/pubmed/25176528?tool=bestpractice.com[21]Schep LJ, Slaughter RJ, Beasley DM. The clinical toxicology of metamfetamine. Clin Toxicol (Phila). 2010;48:675-694.http://www.ncbi.nlm.nih.gov/pubmed/20849327?tool=bestpractice.com[36]Glasner-Edwards S, Mooney LJ. Methamphetamine psychosis: epidemiology and management. CNS Drugs. 2014;28:1115-1126.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5027896/http://www.ncbi.nlm.nih.gov/pubmed/25373627?tool=bestpractice.com[37]Richards JR, Albertson TE, Derlet RW, et al. Treatment of toxicity from amphetamines, related derivatives, and analogues: a systematic clinical review. Drug Alcohol Depend. 2015;150:1-13.http://www.ncbi.nlm.nih.gov/pubmed/25724076?tool=bestpractice.com[59]Richards JR, Derlet RW, Albertson TE, et al. Methamphetamine, "bath salts," and other amphetamine-related derivatives: progressive treatment update. August 2014. http://www.enlivenarchive.org/ (last accessed 24 May 2017).http://www.enlivenarchive.org/articles/methamphetamine-bath-salts-and-other-amphetaminerelated-derivatives-progressive-treatment-update.pdf[60]Radfar SR, Rawson RA. Current research on methamphetamine: epidemiology, medical and psychiatric effects, treatment, and harm reduction efforts. Addict Health. 2014;6:146-154.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4354220/http://www.ncbi.nlm.nih.gov/pubmed/25984282?tool=bestpractice.com 频繁监测生命体征,因为患者病情可能会迅速变化。严重病例可能需要在重症监护室(ICU)内治疗,ICU要具备多脏器支持,远程心电监护,机械通气以及紧密一对一观察的能力。
初始治疗
如果患者配合且其服药时间在1h以内,可给予口服活性炭治疗。 如果是轻度中毒,将患者置于安静环境中进行观察和监测可能是最好的处理,必要时给予支持措施(静脉输液、降温)。
伴有激惹
如果出现激惹状态,需先是确定患者的配合程度,迅速控制任何行为障碍。[37]Richards JR, Albertson TE, Derlet RW, et al. Treatment of toxicity from amphetamines, related derivatives, and analogues: a systematic clinical review. Drug Alcohol Depend. 2015;150:1-13.http://www.ncbi.nlm.nih.gov/pubmed/25724076?tool=bestpractice.com[57]Shoptaw, SJ, Kao U, Ling W. Treatment for amphetamine psychosis. Cochrane Database Syst Rev. 2009;(1):CD003026.http://www.ncbi.nlm.nih.gov/pubmed/19160215?tool=bestpractice.com[59]Richards JR, Derlet RW, Albertson TE, et al. Methamphetamine, "bath salts," and other amphetamine-related derivatives: progressive treatment update. August 2014. http://www.enlivenarchive.org/ (last accessed 24 May 2017).http://www.enlivenarchive.org/articles/methamphetamine-bath-salts-and-other-amphetaminerelated-derivatives-progressive-treatment-update.pdf 目的是确保不理智的行为或攻击行为不妨碍及时的病情评估和管理,以及确保患者、医务工作者和其他人员的安全。非药物治疗措施可有助于平息患者和削弱治疗难度。包括向患者(及其家人或朋友)承诺保密,安静倾听患者诉说,使用平静和开放式问句以及非威胁性词句、平缓的语气,使用他/她的姓名,允许患者有更多的空间,同时避免太多的眼神接触(如果患者对你感到敌意或是偏执状态,患者可能感觉受到威胁)。
如果非药物性治疗手段未能安抚患者,使其镇静,就必须立即使用镇静药物。[8]Hall AP, Henry JA. Acute toxic effects of 'Ecstasy' (MDMA) and related compounds: overview of pathophysiology and clinical management. Br J Anaesth. 2006;96:678-685.http://bja.oxfordjournals.org/cgi/content/full/96/6/678http://www.ncbi.nlm.nih.gov/pubmed/16595612?tool=bestpractice.com[15]Courtney KE, Ray LA. Methamphetamine: an update on epidemiology, pharmacology, clinical phenomenology, and treatment literature. Drug Alcohol Depend. 2014;143:11-21.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4164186/http://www.ncbi.nlm.nih.gov/pubmed/25176528?tool=bestpractice.com[21]Schep LJ, Slaughter RJ, Beasley DM. The clinical toxicology of metamfetamine. Clin Toxicol (Phila). 2010;48:675-694.http://www.ncbi.nlm.nih.gov/pubmed/20849327?tool=bestpractice.com[36]Glasner-Edwards S, Mooney LJ. Methamphetamine psychosis: epidemiology and management. CNS Drugs. 2014;28:1115-1126.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5027896/http://www.ncbi.nlm.nih.gov/pubmed/25373627?tool=bestpractice.com[37]Richards JR, Albertson TE, Derlet RW, et al. Treatment of toxicity from amphetamines, related derivatives, and analogues: a systematic clinical review. Drug Alcohol Depend. 2015;150:1-13.http://www.ncbi.nlm.nih.gov/pubmed/25724076?tool=bestpractice.com[59]Richards JR, Derlet RW, Albertson TE, et al. Methamphetamine, "bath salts," and other amphetamine-related derivatives: progressive treatment update. August 2014. http://www.enlivenarchive.org/ (last accessed 24 May 2017).http://www.enlivenarchive.org/articles/methamphetamine-bath-salts-and-other-amphetaminerelated-derivatives-progressive-treatment-update.pdf[60]Radfar SR, Rawson RA. Current research on methamphetamine: epidemiology, medical and psychiatric effects, treatment, and harm reduction efforts. Addict Health. 2014;6:146-154.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4354220/http://www.ncbi.nlm.nih.gov/pubmed/25984282?tool=bestpractice.com 对于该适应证,最常使用苯二氮卓类药物进行控制。氟哌啶醇、奥氮平和氟哌利多等抗精神病药也有帮助,可与苯二氮卓类药物联合使用。[64]Canadian Agency for Drugs and Technologies in Health. Use of antipsychotics and/or benzodiazepines as rapid tranquilization in in-patients of mental facilities and emergency departments: a review of the clinical effectiveness and guidelines. October 2015. https://www.cadth.ca/ (last accessed 15 May 2017).https://www.cadth.ca/use-antipsychotics-andor-benzodiazepines-rapid-tranquilization-patients-mental-facilities-and[65]Calver L, Drinkwater V, Gupta R, et al. Droperidol v. haloperidol for sedation of aggressive behaviour in acute mental health: randomised controlled trial. Br J Psychiatry. 2015;206:223-228.http://bjp.rcpsych.org/content/206/3/223.long 在临床试验中,已经证实联合使用这些不同的镇静剂比单药治疗更有效。[66]Yap CY, Taylor DM, Knott JC, et al. Intravenous midazolam-droperidol combination, droperidol or olanzapine monotherapy for methamphetamine-related acute agitation: subgroup analysis of a randomized controlled trial. Addiction. 2017 Feb 4 [Epub ahead of print].http://www.ncbi.nlm.nih.gov/pubmed/28160494?tool=bestpractice.com[67]Taylor DM, Yap CY, Knott JC, et al. Midazolam-droperidol, droperidol, or olanzapine for acute agitation: a randomized clinical trial. Ann Emerg Med. 2017;69:318-326.http://www.ncbi.nlm.nih.gov/pubmed/27745766?tool=bestpractice.com[68]Chan EW, Taylor DM, Knott JC, et al. Intravenous droperidol or olanzapine as an adjunct to midazolam for the acutely agitated patient: a multicenter, randomized, double-blind, placebo-controlled clinical trial. Ann Emerg Med. 2013;61:72-81.http://www.ncbi.nlm.nih.gov/pubmed/22981685?tool=bestpractice.com 使用低中剂量的氟哌利多治疗激越已被证明是安全且有效的。[69]Richards JR, Schneir AB. Droperidol in the emergency department: is it safe? J Emerg Med. 2003;24:441-447.http://www.ncbi.nlm.nih.gov/pubmed/12745049?tool=bestpractice.com[70]Perkins J, Ho JD, Vilke GM, et al. American Academy of Emergency Medicine position statement: safety of droperidol use in the emergency department. J Emerg Med. 2015;49:91-97.http://www.ncbi.nlm.nih.gov/pubmed/25837231?tool=bestpractice.com 如果可能,应在给予氟哌利多或静脉使用氟哌啶醇之前,测量 QT 间期。 Richmond 躁动镇静评分量表 (RASS) 可用于指导镇静治疗。[1]Ely EW, Truman B, Shintani A, et al. Monitoring sedation status over time in ICU patients: reliability and validity of the Richmond Agitation-Sedation Scale (RASS). JAMA. 2003;289:2983-2991.http://jamanetwork.com/journals/jama/fullarticle/196696http://www.ncbi.nlm.nih.gov/pubmed/12799407?tool=bestpractice.com
(+1 至 2):如果患者轻度亢奋、踱步且易激惹,但仍能够配合并愿意讨论和交待病史,同时生命体征基本正常,则可合理给予口服苯二氮卓类药物。 如果无效,则可再次给予或给予加大剂量的口服苯二氮卓类药物,或者给予口服奥氮平。 也可给予口服氟哌啶醇。[37]Richards JR, Albertson TE, Derlet RW, et al. Treatment of toxicity from amphetamines, related derivatives, and analogues: a systematic clinical review. Drug Alcohol Depend. 2015;150:1-13.http://www.ncbi.nlm.nih.gov/pubmed/25724076?tool=bestpractice.com[57]Shoptaw, SJ, Kao U, Ling W. Treatment for amphetamine psychosis. Cochrane Database Syst Rev. 2009;(1):CD003026.http://www.ncbi.nlm.nih.gov/pubmed/19160215?tool=bestpractice.com[59]Richards JR, Derlet RW, Albertson TE, et al. Methamphetamine, "bath salts," and other amphetamine-related derivatives: progressive treatment update. August 2014. http://www.enlivenarchive.org/ (last accessed 24 May 2017).http://www.enlivenarchive.org/articles/methamphetamine-bath-salts-and-other-amphetaminerelated-derivatives-progressive-treatment-update.pdf
(+2 至 3):如果患者中度亢奋、躁动、激越、吵闹、不理智、有敌意且不配合,并存在心动过速和高血压,可开始使用如上口服药物治疗方案。 治疗可以从上述口服药开始,如果患者拒绝服药或药物无效,则过渡到静脉或肌肉注射。 可以静脉使用苯二氮卓类药物,必要时重复使用;可以口服或肌内注射抗精神病药。 此阶段可能需要约束患者躯体,应由多名医务人员参与,最好一人固定患者一肢,另有一人建立静脉通路,并给予镇静剂。
(+3 至 4):如果患者高度亢奋、痛苦、恐惧、高度激越、谩骂、不配合甚至有暴力倾向,则需要尽快镇静,开始时经静脉使用苯二氮卓类药物和/或抗精神病药,可重复使用,直到获得充分镇静。 如果不能建立安全有效的静脉通道,则进行肌肉注射。 如果这些措施都失败,必须对患者进行快速顺序诱导插管,以免患者和医务人员受到伤害,并有助于行进一步检查,例如 CT。
伴容量不足
大多数急性苯丙胺中毒患者表现为明显的血容量不足,需要快速静脉输液治疗(例如输注生理盐水或乳酸林格氏液)。是否使用钾取决于患者血清钾浓度。
伴有横纹肌溶解
及时适当的液体复苏对于处理横纹肌溶解至关重要。 横纹肌溶解可通过肌酸激酶确诊,其峰值水平在501-1670μkat/L(30 000到100 000U/L)。[23]Richards JR, Johnson EB, Stark RW, et al. Methamphetamine abuse and rhabdomyolysis in the ED: a 5-year study. Am J Emerg Med. 1999;17:681-685.http://www.ncbi.nlm.nih.gov/pubmed/10597089?tool=bestpractice.com[71]O'Connor AD, Padilla-Jones A, Gerkin RD, et al. Prevalence of rhabdomyolysis in sympathomimetic toxicity: a comparison of stimulants. J Med Toxicol. 2015;11:195-200.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4469713/http://www.ncbi.nlm.nih.gov/pubmed/25468315?tool=bestpractice.com 横纹肌溶解症存活者肌酸激酶峰值的最高记录是9268.5μkat/L(555 000U/L)。通过静脉输液,保证充足尿量是成功治疗此病的关键。
伴有代谢性酸中毒
高热可导致类似重症中暑的临床表现,伴有代谢性酸中毒及其他严重生理紊乱。 可能需要使用碳酸氢钠来纠正严重的代谢性酸中毒。 大量碳酸氢钠可引起高钠血症和低钾血症风险,所以要密切监测电解质。
有些专家认为,尿液碱化可能影响苯丙胺的 pH 依赖性肾脏排泄,所以不应碱化尿液。 然而,肾脏对苯丙胺的清除不会对苯丙胺过量造成较大影响。 因此,碳酸氢钠并不是禁忌;但不提倡酸化尿液,因为 pH 值低时,会出现肌红蛋白在肾小管中沉积的风险。[23]Richards JR, Johnson EB, Stark RW, et al. Methamphetamine abuse and rhabdomyolysis in the ED: a 5-year study. Am J Emerg Med. 1999;17:681-685.http://www.ncbi.nlm.nih.gov/pubmed/10597089?tool=bestpractice.com[71]O'Connor AD, Padilla-Jones A, Gerkin RD, et al. Prevalence of rhabdomyolysis in sympathomimetic toxicity: a comparison of stimulants. J Med Toxicol. 2015;11:195-200.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4469713/http://www.ncbi.nlm.nih.gov/pubmed/25468315?tool=bestpractice.com
伴有高热
肛温最接近人体核心温度。 当体温超过 38℃ (100℉) 时,通常采取积极降温。[5]Matsumoto RR, Seminerio MJ, Turner RC, et al. Methamphetamine-induced toxicity: an updated review on issues related to hyperthermia. Pharmacol Ther. 2014;144:28-40.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4700537/http://www.ncbi.nlm.nih.gov/pubmed/24836729?tool=bestpractice.com[26]Bordo DJ, Dorfman MA. Ecstasy overdose: rapid cooling leads to successful outcome. Am J Emerg Med. 2004;22:326-327.http://www.ncbi.nlm.nih.gov/pubmed/15258886?tool=bestpractice.com[72]Richards JR, Colby DK. Stimulant-induced hyperthermia and ice-water submersion: practical considerations. Clin Toxicol (Phila). 2016;54:69-70.http://www.ncbi.nlm.nih.gov/pubmed/26515112?tool=bestpractice.com 在任何情况下,为了实现快速降温,最简单的方法为使用温热喷雾,并使用风扇以传导、蒸发和对流散热。[72]Richards JR, Colby DK. Stimulant-induced hyperthermia and ice-water submersion: practical considerations. Clin Toxicol (Phila). 2016;54:69-70.http://www.ncbi.nlm.nih.gov/pubmed/26515112?tool=bestpractice.com 其他措施包括使用降温毯和冰袋。 需注意监测低钠血症的发生。 给予苯二氮卓类药物,以松弛肌肉。
39.5℃ (103℉) 以上的高热表明严重、可能危及生命的中毒,必须立即降温(例如,使用静脉冷液体输注、擦浴、冰袋)和镇静。 最好在重症监护治疗病房内进行,并进行肌松和机械通气。[8]Hall AP, Henry JA. Acute toxic effects of 'Ecstasy' (MDMA) and related compounds: overview of pathophysiology and clinical management. Br J Anaesth. 2006;96:678-685.http://bja.oxfordjournals.org/cgi/content/full/96/6/678http://www.ncbi.nlm.nih.gov/pubmed/16595612?tool=bestpractice.com 可能需要延长肌松时间来避免再次出现药物诱导的高热,一般通过使用泮库溴铵等作用时间适中的非去极化神经肌肉阻滞剂来实现。 在肌松药应用之前必须行气管插管。
伴有心律失常
已有报道表明,在有潜在缺血性心脏病和传导缺陷的苯丙胺过量患者中,已出现心律失常导致死亡的情况。[47]Turnipseed SD, Richards JR, Kirk JD, et al. Frequency of acute coronary syndrome in patients presenting to the emergency department with chest pain after methamphetamine use. J Emerg Med. 2003;24:369-373.http://www.ncbi.nlm.nih.gov/pubmed/12745036?tool=bestpractice.com[73]Li J, Li J, Chen Y, et al. Methamphetamine use associated with monomorphic ventricular tachycardia. J Addict Med. 2014;8:470-473.http://www.ncbi.nlm.nih.gov/pubmed/25230370?tool=bestpractice.com[74]Haning W, Goebert D. Electrocardiographic abnormalities in methamphetamine abusers. Addiction. 2007;102(suppl 1):70-75.http://www.ncbi.nlm.nih.gov/pubmed/17493055?tool=bestpractice.com 对于所有存在胸痛或心律失常的苯丙胺中毒患者,进行心电图检查和心电监护是明智的。大部分心动过速起源于窦房结,可以在几小时内自行缓解。不过,治疗是有益的,因为长时间心动过速会使患者因心肌耗氧量增大而有心肌缺血的风险。[59]Richards JR, Derlet RW, Albertson TE, et al. Methamphetamine, "bath salts," and other amphetamine-related derivatives: progressive treatment update. August 2014. http://www.enlivenarchive.org/ (last accessed 24 May 2017).http://www.enlivenarchive.org/articles/methamphetamine-bath-salts-and-other-amphetaminerelated-derivatives-progressive-treatment-update.pdf
苯二氮卓类药物是一线治疗药物,但可能无法可靠地控制苯丙胺引起的窦性心动过速。 对于同时存在心动过速和高血压的患者,或者担心无法对抗 α 受体兴奋效应时,使用 α/β 受体阻滞剂拉贝洛尔已被证明是安全且有效的。[37]Richards JR, Albertson TE, Derlet RW, et al. Treatment of toxicity from amphetamines, related derivatives, and analogues: a systematic clinical review. Drug Alcohol Depend. 2015;150:1-13.http://www.ncbi.nlm.nih.gov/pubmed/25724076?tool=bestpractice.com 在血压正常的患者中,可以考虑使用 β 受体阻滞剂美托洛尔治疗窦性心动过速。[37]Richards JR, Albertson TE, Derlet RW, et al. Treatment of toxicity from amphetamines, related derivatives, and analogues: a systematic clinical review. Drug Alcohol Depend. 2015;150:1-13.http://www.ncbi.nlm.nih.gov/pubmed/25724076?tool=bestpractice.com
伴有血流动力学稳定的室上性心动过速最好通过短效β-受体阻断剂处理(如:静注艾司洛尔)。[8]Hall AP, Henry JA. Acute toxic effects of 'Ecstasy' (MDMA) and related compounds: overview of pathophysiology and clinical management. Br J Anaesth. 2006;96:678-685.http://bja.oxfordjournals.org/cgi/content/full/96/6/678http://www.ncbi.nlm.nih.gov/pubmed/16595612?tool=bestpractice.com[54]Jones AL, Dargan PI. Churchill's textbook of toxicology. Edinburgh, UK: Churchill-Livingstone; 2001.
室性心动过速可常规给予抗心律失常药物(如:胺碘酮)或通过电复律处理。
伴有癫痫发作
癫痫发作时,可静脉使用苯二氮卓类药物进行初始处理,必要时重复给药。[37]Richards JR, Albertson TE, Derlet RW, et al. Treatment of toxicity from amphetamines, related derivatives, and analogues: a systematic clinical review. Drug Alcohol Depend. 2015;150:1-13.http://www.ncbi.nlm.nih.gov/pubmed/25724076?tool=bestpractice.com 如果癫痫持续状态对增加剂量的苯二氮卓类药物无反应,可以使用巴比妥类药物,可能需使用全身麻醉。
伴有蛛网膜下腔出血
蛛网膜下腔出血应常规给予尼莫地平,并快速转运至可以处理神经外科急诊的治疗中心。[75]Etminan N, Macdonald RL. Management of aneurysmal subarachnoid hemorrhage. Handb Clin Neurol. 2017;140:195-228.http://www.ncbi.nlm.nih.gov/pubmed/28187800?tool=bestpractice.com
伴有高血压
在某些苯丙胺中毒患者中,苯二氮卓类药物可能无法有效缓解高血压。 如果高血压持续存在,可以使用拉贝洛尔。[37]Richards JR, Albertson TE, Derlet RW, et al. Treatment of toxicity from amphetamines, related derivatives, and analogues: a systematic clinical review. Drug Alcohol Depend. 2015;150:1-13.http://www.ncbi.nlm.nih.gov/pubmed/25724076?tool=bestpractice.com[59]Richards JR, Derlet RW, Albertson TE, et al. Methamphetamine, "bath salts," and other amphetamine-related derivatives: progressive treatment update. August 2014. http://www.enlivenarchive.org/ (last accessed 24 May 2017).http://www.enlivenarchive.org/articles/methamphetamine-bath-salts-and-other-amphetaminerelated-derivatives-progressive-treatment-update.pdf
一氧化氮介导的血管舒张药(例如硝普盐和硝酸甘油)也对单纯性高血压治疗有益,α 受体阻滞剂酚妥拉明也具有该作用。
伴有低血压
低血压是一种晚期表现,在患者存在严重脱水或儿茶酚胺耗尽时可能出现。 可以通过调整患者头低脚高位获得暂时性的改善效果。 需要给予大量静脉输液。 这些措施通常可以有效地缓解低血压;不过,在极端情况下,可能需要使用多巴胺或去甲肾上腺素等升压药。
伴有血清素中毒
对于可疑血清素中毒患者,医院观察和支持治疗可获得最佳的治疗效果。 特异性治疗可能包括使用苯二氮卓类药物或赛庚啶(如果可用)。[27]Dobry Y, Rice T, Sher L. Ecstasy use and serotonin syndrome: a neglected danger to adolescents and young adults prescribed selective serotonin reuptake inhibitors. Int J Adolesc Med Health. 2013;25:193-199.http://www.ncbi.nlm.nih.gov/pubmed/24006318?tool=bestpractice.com[45]Dunkley EJ, Isbister GK, Sibbritt D, et al. The Hunter Serotonin Toxicity Criteria: simple and accurate diagnostic decision rules for serotonin toxicity. QJM. 2003;96:635-642.http://qjmed.oxfordjournals.org/content/96/9/635.fullhttp://www.ncbi.nlm.nih.gov/pubmed/12925718?tool=bestpractice.com 如怀疑血清素中毒,应咨询中毒中心的临床医师,此举至关重要。