苯丙胺中毒的诊断主要根据临床症状。 患者通常表现为交感神经系统过度兴奋,并且近期有合法药品或违禁药品使用史。
最初表现
苯丙胺中毒患者往往会出现激越、不理智、躁动和攻击行为,并可能表现出过度警觉、偏执以及精神病的体征。[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 在确诊以及治疗之前,必须控制行为。[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 在患者本人或其他记录中不能反应病史的情况下,任何具有此类描述症状的患者都应该被高度怀疑是精神兴奋剂中毒。[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
另一种提示苯丙胺滥用的指征是近期参与了狂欢派对(有电子舞蹈音乐的青年聚会)和/或疯狂的俱乐部舞会。俱乐部吸毒者更有可能使用多种违禁药物,这可能会妨碍对临床情况的清晰理解。[38]Armenian P, Mamantov TM, Tsutaoka BT, et al. Multiple MDMA (Ecstasy) overdoses at a rave event: a case series. J Intensive Care Med. 2013;28:252-258.http://www.ncbi.nlm.nih.gov/pubmed/22640978?tool=bestpractice.com[39]Yacoubian GS Jr, Peters RJ. An exploration of recent club drug use among rave attendees. J Drug Educ. 2007;37:145-161.http://www.ncbi.nlm.nih.gov/pubmed/17977238?tool=bestpractice.com[40]Fendrich M, Wislar JS, Johnson TP, et al. A contextual profile of club drug use among adults in Chicago. Addiction. 2003;98:1693-1703.http://www.ncbi.nlm.nih.gov/pubmed/14651501?tool=bestpractice.com 狂欢派对参加者更可能报告频繁使用 3,4-二亚甲基双氧苯丙胺。[40]Fendrich M, Wislar JS, Johnson TP, et al. A contextual profile of club drug use among adults in Chicago. Addiction. 2003;98:1693-1703.http://www.ncbi.nlm.nih.gov/pubmed/14651501?tool=bestpractice.com 齿列不良(“冰毒嘴”)也可能提示潜在的苯丙胺滥用。[41]De-Carolis C, Boyd GA, Mancinelli L, et al. Methamphetamine abuse and "meth mouth" in Europe. Med Oral Patol Oral Cir Bucal. 2015;20:e205-e210.http://www.medicinaoral.com/pubmed/medoralv20_i2_p205.pdfhttp://www.ncbi.nlm.nih.gov/pubmed/25662544?tool=bestpractice.com[42]Richards JR, Brofeldt BT. Patterns of tooth wear associated with methamphetamine use. J Periodontol. 2000;71:1371-1374.http://www.ncbi.nlm.nih.gov/pubmed/10972655?tool=bestpractice.com
病史
引起苯丙胺过量的已知风险因素包括:暴露于高温下、运动、出汗以及容量不足、出席舞会或狂欢派对、多种药物和酒精混用、焦虑、抑郁、行为偏差或犯罪行为,以及注意缺陷多动障碍疾病等。[29]Russell K, Dryden DM, Liang Y, et al. Risk factors for methamphetamine use in youth: a systematic review. BMC Pediatr. 2008;8:48.http://www.biomedcentral.com/1471-2431/8/48http://www.ncbi.nlm.nih.gov/pubmed/18957076?tool=bestpractice.com[31]Cumming C, Troeung L, Young JT, et al. Barriers to accessing methamphetamine treatment: a systematic review and meta-analysis. Drug Alcohol Depend. 2016;168:263-273.http://www.ncbi.nlm.nih.gov/pubmed/27736680?tool=bestpractice.com
如果患者配合,或是从家人或朋友处获得详细的用药史,可能会发现既存药物滥用,苯丙胺过量的已知高危因素。 应询问目前以及过去使用过的药物类型、过程、数量、时间以及效力(如作用时间长度和强度)。 常见多药联用(如酒精、大麻、可卡因、海洛因等),可能会混淆并使临床表现复杂化。[25]Schifano F, Corkery J, Naidoo V, et al. Overview of amphetamine-type stimulant mortality data - UK, 1997-2007. Neuropsychobiology. 2010;61:122-130.http://www.ncbi.nlm.nih.gov/pubmed/20110737?tool=bestpractice.com[43]Degenhardt L, Coffey C, Carlin JB, et al. Who are the new amphetamine users? A 10-year prospective study of young Australians. Addiction. 2007;102:1269-1279.http://www.ncbi.nlm.nih.gov/pubmed/17624977?tool=bestpractice.com[44]Sterk CE, Theall KP, Elifson KW. Getting into ecstasy: comparing moderate and heavy young adult users. J Psychoactive Drugs. 2007;39:103-113.http://www.ncbi.nlm.nih.gov/pubmed/17703705?tool=bestpractice.com 对包括处方药在内的所有滥用药物进行调查。[38]Armenian P, Mamantov TM, Tsutaoka BT, et al. Multiple MDMA (Ecstasy) overdoses at a rave event: a case series. J Intensive Care Med. 2013;28:252-258.http://www.ncbi.nlm.nih.gov/pubmed/22640978?tool=bestpractice.com[39]Yacoubian GS Jr, Peters RJ. An exploration of recent club drug use among rave attendees. J Drug Educ. 2007;37:145-161.http://www.ncbi.nlm.nih.gov/pubmed/17977238?tool=bestpractice.com[40]Fendrich M, Wislar JS, Johnson TP, et al. A contextual profile of club drug use among adults in Chicago. Addiction. 2003;98:1693-1703.http://www.ncbi.nlm.nih.gov/pubmed/14651501?tool=bestpractice.com 确定患者所使用的药物,这一点非常重要。这些药物有可能与苯丙胺相互作用而产生血清素毒性(如血清素再摄取抑制剂、甲氧氯普胺、舒马普坦、锂剂、右美沙芬等)。[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
发生如心悸、胸痛等症状需接受特别仔细的检查。 苯丙胺过量可能会使心肌耗氧量增大(因心率提高及收缩性和心室壁张力增大所致),导致急性心肌梗死、心肌缺血和心律失常的风险增大。[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[46]Suarez RV, Riemersma R. "Ecstasy" and sudden cardiac death. Am J Forensic Med Pathol. 1988;9:339-341.http://www.ncbi.nlm.nih.gov/pubmed/3239555?tool=bestpractice.com[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 腹痛可能提示肠系膜缺血或者大块药物吞入引起的胃肠道梗阻。[48]Johnson TD, Berenson MM. Methamphetamine-induced ischemic colitis. J Clin Gastroenterol. 1991;13:687-689.http://www.ncbi.nlm.nih.gov/pubmed/1761842?tool=bestpractice.com 而头痛则可能是蛛网膜下腔出血或是脑出血的最初症状。 医疗史的相关发现包括乙型肝炎、丙型肝炎或艾滋病毒的暴露(间接指标或高危生活方式);创伤性的身体伤害,这也是常见的药物滥用的原因;以及潜在(可能未经治疗)的精神性疾病(如焦虑、抑郁等)。
查体
如果患者不合作或者不承认使用了精神兴奋剂,或是无法获知确凿的用药史,体征可能就是判断苯丙胺过量的唯一线索。 苯丙胺中毒的体征包括:[9]Carvalho M, Carmo H, Costa VM, et al. Toxicity of amphetamines: an update. Arch Toxicol. 2012;86:1167-1231.http://www.ncbi.nlm.nih.gov/pubmed/22392347?tool=bestpractice.com[10]Harro J. Neuropsychiatric adverse effects of amphetamine and methamphetamine. Int Rev Neurobiol. 2015;120:179-204.http://www.ncbi.nlm.nih.gov/pubmed/26070758?tool=bestpractice.com[14]Fleckenstein AE, Volz TJ, Riddle EL, et al. New insights into the mechanism of action of amphetamines. Annu Rev Pharmacol Toxicol. 2007;47:681-698.http://www.ncbi.nlm.nih.gov/pubmed/17209801?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
早期查体可发现面部皮肤因发热而通红,支持苯丙胺中毒诊断。 容量不足是典型的跳舞活动或在高温、拥挤的社交环境下体力消耗的表现。 但兴奋剂可能会掩盖干渴感,从而减少了饮水,因此加剧了容量不足的程度。[49]Baggott MJ. Preventing problems in Ecstasy users: reduce use to reduce harm. J Psychoactive Drugs. 2002;34:145-162.http://www.ncbi.nlm.nih.gov/pubmed/12691205?tool=bestpractice.com
行为和精神障碍可能是潜在的精神疾病或交感神经系统亢进的表现。 癫痫发作可能伴随着血液稀释和低钠血症引起的脑水肿,也可能会出现头痛。 呼吸系统症状(如呼吸急促)可能发生在心血管损害或是出现急性呼吸窘迫综合征的情况下。 急性呼吸窘迫综合征常继发于高热,同热休克症状类似(高体温、代谢性酸中毒、肾功能衰竭等)。 伴或不伴有心律失常的心动过速加重心脏负荷,可能导致心力衰竭。[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[50]Jafari Giv M. Exposure to amphetamines leads to development of amphetamine type stimulants associated cardiomyopathy (ATSAC). Cardiovasc Toxicol. 2017;17:13-24.http://www.ncbi.nlm.nih.gov/pubmed/27663745?tool=bestpractice.com[51]Sliman S, Waalen J, Shaw D. Methamphetamine-associated congestive heart failure: increasing prevalence and relationship of clinical outcomes to continued use or abstinence. Cardiovasc Toxicol. 2016;16:381-389.http://www.ncbi.nlm.nih.gov/pubmed/26661075?tool=bestpractice.com[52]Won S, Hong RA, Shohet RV, et al. Methamphetamine-associated cardiomyopathy. Clin Cardiol. 2013;36:737-742.http://onlinelibrary.wiley.com/doi/10.1002/clc.22195/fullhttp://www.ncbi.nlm.nih.gov/pubmed/24037954?tool=bestpractice.com[53]Akhgari M, Mobaraki H, Etemadi-Aleagha A. Histopathological study of cardiac lesions in methamphetamine poisoning-related deaths. Daru. 2017;25:5.https://darujps.biomedcentral.com/articles/10.1186/s40199-017-0170-4http://www.ncbi.nlm.nih.gov/pubmed/28212679?tool=bestpractice.com
其他体征可能包括:
牙关紧闭
肌肉僵直
震颤或重复动作
语速急促
踱步
发汗
幻觉或错觉
瞳孔散大,对光反射迟钝。
可以通过明显营养不良体征和四肢注射针眼或是血栓性静脉炎判断存在长期固定的规律用药。 还有一个药物中毒的常见体征是外伤性损伤。 蛛网膜下腔出血较罕见但却是苯丙胺过量的表现,所以要仔细进行眼底评估检查是否有视乳头水肿以及检测神经系统定位体征。
血清素中毒体征
血清素中毒的临床特征如下:[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
激越
发汗
发热超过38°C(100°F)
震颤
深反射亢进
张力过高
自发性或诱导性眼阵挛
刺激中枢神经系统可能诱发激惹和震颤。 阵挛和双侧巴宾斯基征阳性也是血清素中毒的特征性表现,神经肌肉的表现通常在下肢更加明显。
实验室检查
立即行床旁手指末梢血糖水平检测以排除低血糖。 正式实验室检查可能包括:
血清电解质、葡萄糖、尿素、肌酐、肝功能检查、凝血酶原时间 (prothrombin time, PT)、部分凝血活酶时间 (partial thromboplastin time, PTT)、国际标准化比值 (international normalized ratio, INR)、肌酸激酶、脑钠肽 (brain natriuretic peptide, BNP) 和肌钙蛋白[54]Jones AL, Dargan PI. Churchill's textbook of toxicology. Edinburgh, UK: Churchill-Livingstone; 2001.
尿检(横纹肌溶解的试纸结果可能与血液呈交叉反应阳性)[54]Jones AL, Dargan PI. Churchill's textbook of toxicology. Edinburgh, UK: Churchill-Livingstone; 2001.
尿样毒品筛查(检测过去数天的药物使用情况)[55]Clinical Guidelines on Drug Misuse and Dependence Update 2017 Independent Expert Working Group (2017) Drug misuse and dependence: UK guidelines on clinical management. London: Department of Healthhttps://www.gov.uk/government/publications/drug-misuse-and-dependence-uk-guidelines-on-clinical-management
酒精呼气测试或血清酒精浓度
影像学检查
根据不同的临床表现和结果,适当选择以下影像学检查:
如果患者出现胸痛或是呼吸困难,行胸部平片检查
腹部X线检查(可能提示藏在或填充在体内的毒品包裹)[56]College of Emergency Medicine. Caring for adult patients suspected of having concealed illicit drugs. June 2014. https://www.rcem.ac.uk/ (last accessed 24 May 2017).https://www.rcem.ac.uk/docs/College%20Guidelines/5z1.%20Caring%20for%20adult%20patients%20suspected%20of%20having%20concealed%20illicit%20drugs%20(June%202014).pdf
头部CT或MRI(患者有剧烈头痛、意识状态改变、癫痫发作或者由血清素中毒引起的无法解释的神经系统体征);尽管MRI可以更好的识别脑部灰质-白质区域的图像,但行MRI更困难且耗时,特别是当苯丙胺过量的情况需要紧急处理时。所以CT仍是较常用的初次脑部成像的检查方式。
非创伤性脑出血且年龄小于40岁的患者给予脑血管造影检查。因为去甲肾上腺素的增加,会对心血管系统产生影响,特别是高血压,以及中枢神经系统出血和卒中的风险增加。[2]Moon K, Albuquerque FC, Mitkov M, et al. Methamphetamine use is an independent predictor of poor outcome after aneurysmal subarachnoid hemorrhage. J Neurointerv Surg. 2015;7:346-350.http://www.ncbi.nlm.nih.gov/pubmed/24780822?tool=bestpractice.com
其他
对于所有患者常规行心电图检查。 对于有胸痛、心动过速或心律失常的患者也需要行连续性心电监护。[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[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[46]Suarez RV, Riemersma R. "Ecstasy" and sudden cardiac death. Am J Forensic Med Pathol. 1988;9:339-341.http://www.ncbi.nlm.nih.gov/pubmed/3239555?tool=bestpractice.com[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