5-羟色胺中毒的治疗包括停用 5-羟色胺能药物,评估中毒严重程度,提供支持性疗法,中度和重度中毒时,使用特定的抗 5-羟色胺能药物。[1]Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med. 2005;352:1112-1120.http://www.ncbi.nlm.nih.gov/pubmed/15784664?tool=bestpractice.com[2]Buckley NA, Dawson AH, Isbister GK. Serotonin syndrome. BMJ. 2014;348:g1626http://www.ncbi.nlm.nih.gov/pubmed/24554467?tool=bestpractice.com重度 5-羟色胺中毒是一种医疗急症,通常需要急诊处理。[1]Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med. 2005;352:1112-1120.http://www.ncbi.nlm.nih.gov/pubmed/15784664?tool=bestpractice.com[2]Buckley NA, Dawson AH, Isbister GK. Serotonin syndrome. BMJ. 2014;348:g1626http://www.ncbi.nlm.nih.gov/pubmed/24554467?tool=bestpractice.com[3]Isbister GK, Buckley NA. The pathophysiology of serotonin toxicity in animals and humans: implications for diagnosis and treatment. Clin Neuropharmacol. 2005;28:205-214.http://www.ncbi.nlm.nih.gov/pubmed/16239759?tool=bestpractice.com
严重程度评估
根据所需医疗干预,可将 5-羟色胺毒性反应划分为 3 种严重程度。[2]Buckley NA, Dawson AH, Isbister GK. Serotonin syndrome. BMJ. 2014;348:g1626http://www.ncbi.nlm.nih.gov/pubmed/24554467?tool=bestpractice.com[4]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应及早评估严重程度,以尽早进行适当治疗。
轻度毒性
5-羟色胺能特征可能与患者有关,也可能无关。此类特征包括反射亢进(在服用处方类选择性 5-羟色胺再摄取抑制剂的患者中普遍存在)、可诱发的阵挛、震颤、肌阵挛性抽搐和发汗,有时还会出现更多非特异性症状,例如头痛或出汗。
这些患者不符合 Hunter 5-羟色胺毒性标准 (HSTC)。[4]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
中度毒性
出现明显的烦躁不安,需要治疗,但没有生命危险。
临床表现为焦虑和激越。心动过速也很常见。
患者符合 HSTC,但未出现高热(体温 > 38.5℃ [> 101.3°F] 或快速上升)和张力过高。[4]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
重度毒性
可视为医疗急症,如不及时治疗,会发展为多器官衰竭。几乎始终与通过不同药理学作用机制发挥药效的 5-羟色胺能药物联用有关。
患者符合 HSTC,并存在高热和张力过高症状。[4]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
重度 5-羟色胺中毒
必须停用所有 5-羟色胺能药物。这是医疗急症,患者需在重症监护室接受治疗。应对气道、呼吸和循环进行初步评估。应用快速降温法治疗高热。[2]Buckley NA, Dawson AH, Isbister GK. Serotonin syndrome. BMJ. 2014;348:g1626http://www.ncbi.nlm.nih.gov/pubmed/24554467?tool=bestpractice.com[3]Isbister GK, Buckley NA. The pathophysiology of serotonin toxicity in animals and humans: implications for diagnosis and treatment. Clin Neuropharmacol. 2005;28:205-214.http://www.ncbi.nlm.nih.gov/pubmed/16239759?tool=bestpractice.com对大多数患者来说,最好及早进行镇静、插管和通气,包括诱发肌肉麻痹以治疗自发阵挛和高热。可用吗啡和咪达唑仑或异丙酚进行镇静。与吗啡和咪达唑仑相比,患者使用异丙酚后能够迅速苏醒。目的是为了预防主要并发症,包括横纹肌溶解症、多器官衰竭和死亡。[25]Neuvonen PJ, Pohjola-Sintonen S, Tacke U, et al. Five fatal cases of serotonin syndrome after moclobemide-citalopram or moclobemide-clomipramine overdoses. Lancet. 1993;342:1419.http://www.ncbi.nlm.nih.gov/pubmed/7901695?tool=bestpractice.com及早治疗可防止这些并发症。患横纹肌溶解症的患者,应采用肌肉麻痹和降温治疗。[25]Neuvonen PJ, Pohjola-Sintonen S, Tacke U, et al. Five fatal cases of serotonin syndrome after moclobemide-citalopram or moclobemide-clomipramine overdoses. Lancet. 1993;342:1419.http://www.ncbi.nlm.nih.gov/pubmed/7901695?tool=bestpractice.com[26]Graham PM. Successful treatment of the toxic serotonin syndrome with chlorpromazine. Med J Aust. 1997;166:166-167.http://www.ncbi.nlm.nih.gov/pubmed/9059446?tool=bestpractice.com[27]Power BM, Pinder M, Hackett LP, et al. Fatal serotonin syndrome following a combined overdose of moclobemide, clomipramine and fluoxetine. Anaesth Intensive Care. 1995;23:499-502.http://www.ncbi.nlm.nih.gov/pubmed/7485947?tool=bestpractice.com
若重度 5-羟色胺中毒是因过量用药导致,且发生在 1 小时内,则可考虑单次给予活性炭进行净化。
尽管使用特异性 5-HT 拮抗剂进行治疗的依据有限,但坊间传闻认为静脉注射氯丙嗪是有效的。[26]Graham PM. Successful treatment of the toxic serotonin syndrome with chlorpromazine. Med J Aust. 1997;166:166-167.http://www.ncbi.nlm.nih.gov/pubmed/9059446?tool=bestpractice.com[28]Gillman PK. The serotonin syndrome and its treatment. J Psychopharmacol. 1999;13:100-109.http://www.ncbi.nlm.nih.gov/pubmed/10221364?tool=bestpractice.com 可以重复给药,还可单次给药用于镇静患者,而不是用苯二氮卓类药物。必须通过在给药前进行静脉输液,避免周围神经 α 拮抗作用导致的血压过低。
中度 5-羟色胺中毒
必须停用所有 5-羟色胺能药物。患者应留院观察至少 6 小时,尽管不太可能加重或危及生命。早期重度 5-羟色胺中毒偶尔可表现为中度中毒,例如使用万拉法新缓释剂时。[10]Isbister GK, Hackett LP, Dawson AH, et al. Moclobemide poisoning: toxicokinetics and occurrence of serotonin toxicity. Br J Clin Pharm. 2003;56:441-450.http://onlinelibrary.wiley.com/doi/10.1046/j.1365-2125.2003.01895.x/fullhttp://www.ncbi.nlm.nih.gov/pubmed/12968990?tool=bestpractice.com如果毒性危及生命,患者应按重度毒性指导原则进行治疗。
治疗着重于缓解患者焦虑、激越和神经肌肉兴奋作用导致的烦躁不安症状。除了病例报告,没有依据支持最佳疗法。[1]Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med. 2005;352:1112-1120.http://www.ncbi.nlm.nih.gov/pubmed/15784664?tool=bestpractice.com[2]Buckley NA, Dawson AH, Isbister GK. Serotonin syndrome. BMJ. 2014;348:g1626http://www.ncbi.nlm.nih.gov/pubmed/24554467?tool=bestpractice.com[3]Isbister GK, Buckley NA. The pathophysiology of serotonin toxicity in animals and humans: implications for diagnosis and treatment. Clin Neuropharmacol. 2005;28:205-214.http://www.ncbi.nlm.nih.gov/pubmed/16239759?tool=bestpractice.com苯二氮卓类药物可用于治疗焦虑,还有镇静作用。对于神经肌肉兴奋和表现为激越或情绪不佳的激动症状患者,可以使用赛庚啶(一种非特异性 5-HT2 拮抗剂和抗组胺剂)。[28]Gillman PK. The serotonin syndrome and its treatment. J Psychopharmacol. 1999;13:100-109.http://www.ncbi.nlm.nih.gov/pubmed/10221364?tool=bestpractice.com[29]Boddy R, Dowsett RP, Jeganathan D. Sublingual olanzapine for the treatment of serotonin syndrome (abstract). Clin Toxicol. 2006;44:426.[30]Graudins A, Stearman A, Chan B. Treatment of the serotonin syndrome with cyproheptadine. J Emerg Med. 1998;16:615-619.http://www.ncbi.nlm.nih.gov/pubmed/9696181?tool=bestpractice.com[31]Chan BS, Graudins A, Whyte IM, et al. Serotonin syndrome resulting from drug interactions. Med J Aust. 1998;169:523-525.http://www.ncbi.nlm.nih.gov/pubmed/9861909?tool=bestpractice.com 它还具有有效的镇静作用。
轻度 5-羟色胺中毒
此类患者无需治疗,可能只需在适当情况下停用致病药物或降低药物剂量即可。[4]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通常情况下,简单鉴别 5-羟色胺症状即可,然后可以根据患者对症状的耐受性和治疗获益决定是否继续服用药物。
重新开始治疗
根据导致 5-羟色胺中毒的原因(例如剂量增加、过量、药物间相互作用),可在恢复后以较低的剂量重新使用单一的 5-羟色胺能药物,同时对患者进行密切监测。