Most cases of serotonin toxicity are provoked by therapeutic doses of a combination of two or more serotonergic drugs, defined as drugs affecting the serotonin neurotransmitter system. Common serotonergic drugs include many antidepressants, antipsychotics, and opioid analgesics, particularly fentanyl, tramadol, meperidine (pethidine), and methadone, but rarely morphine and other related phenanthrenes. Symptoms of serotonin toxicity are attributable to an effect on monoaminergic transmission caused by an increased synaptic concentration of serotonin. The serotonin transporter (SERT) maintains low serotonin concentrations and is important for the reuptake of the neurotransmitter into the presynaptic nerve terminals. Some opioids inhibit the reuptake of serotonin by inhibiting SERT, thus increasing the plasma and synaptic cleft serotonin concentrations that activate the serotonin receptors. Opioids that are good inhibitors of SERT (tramadol, dextromethorphan, methadone, and meperidine) are most frequently associated with serotonin toxicity. Tramadol also has a direct serotonin-releasing action. Fentanyl produces an efflux of serotonin, and binds to 5-hydroxytryptamine (5-HT)1A and 5-HT2A receptors, whilst methadone, meperidine, and more weakly tapentadol, bind to 5-HT2A but not 5-HT1A receptors. The perioperative period is a time where opioids and other serotonergic drugs are frequently administered in rapid succession, sometimes to patients with other serotonergic drugs in their system. This makes the perioperative period a relatively risky time for serotonin toxicity to occur. The intraoperative recognition of serotonin toxicity is challenging as it can mimic other serious syndromes, such as malignant hyperthermia, sepsis, thyroid storm, and neuroleptic malignant syndrome. Anaesthetists must maintain a heightened awareness of its possible occurrence and a readiness to engage in early treatment to avoid poor outcomes.

中文翻译：

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麻醉药，阿片类镇痛药和5-羟色胺毒性：机理和临床综述。

5-羟色胺毒性的大多数情况是由两种或多种5-羟色胺能药物（定义为影响5-羟色胺神经递质系统的药物）的治疗剂量引起的。常见的血清素能药物包括许多抗抑郁药，抗精神病药和阿片类镇痛药，尤其是芬太尼，曲马多，哌替啶（哌替啶）和美沙酮，但很少含有吗啡和其他相关的菲。5-羟色胺毒性的症状归因于5-羟色胺的突触浓度增加引起的对单胺能传递的影响。血清素转运蛋白（SERT）维持较低的血清素浓度，对于将神经递质重新摄取到突触前神经末梢很重要。一些阿片类药物通过抑制SERT抑制5-羟色胺的再摄取，因此增加了激活5-羟色胺受体的血浆和突触裂隙5-羟色胺的浓度。作为SERT良好抑制剂的阿片类药物（曲马多，右美沙芬，美沙酮和甲哌丁啶）最常与5-羟色胺毒性相关。曲马多还具有直接的5-羟色胺释放作用。芬太尼产生5-羟色胺外排，并与5-羟色胺（5-HT）1A和5-HT2A受体结合，而美沙酮，哌替啶和更弱的他喷他多与5-HT2A受体结合，但与5-HT1A受体结合。围手术期是阿片类药物和其他5-羟色胺能药物频繁连续给药的时期，有时是系统中使用其他5-羟色胺能药物的患者。这使围手术期成为发生5-羟色胺毒性的相对危险的时间。术中对5-羟色胺毒性的识别具有挑战性，因为它可以模仿其他严重的综合症，例如恶性高热，败血症，甲状腺风暴和抗精神病药物恶性综合症。麻醉师必须对可能发生的情况保持高度警惕，并准备好进行早期治疗以避免不良后果。