Yamanaka Daiki, Kawano Takashi, Tateiwa Hiroki, Iwata Hideki, Locatelli Fabricio M, Yokoyama Masataka
Department of Anesthesiology and Intensive Care Medicine, Kochi Medical School, Kohasu, Oko-cho, Nankoku, Kochi 783-8505 Japan.
Springerplus. 2016 Aug 22;5(1):1380. doi: 10.1186/s40064-016-3079-3. eCollection 2016.
Anti-N-methyl-d-aspartate receptor (NMDA-R) encephalitis is a recently identified but increasingly recognized autoimmune paraneoplastic disease. Because these patients present complex neuropsychiatric symptoms due to NMDA-R dysfunction, the optimal methods of sedation/anesthesia remain controversial. Here, we present animal experiment data, along with a related case report, implying the safe and effective use of dexmedetomidine in patients with anti-NMDA-R encephalitis.
(1) Animal experiment: in order to investigate whether dexmedetomidine may interfere with NMDA-R activity, an NMDA antagonist (MK-801) model in rats was used to simulate anti-NMDA-R encephalitis. Administration of MK-801 produced well-characterized schizophrenia-like behaviors, i.e. hyperlocomotion and stereotyped sniffing. Ketamine, an NMDA receptor-dependent anesthetic, exaggerated both behaviors, even at sub-anesthetic doses. On the other hand, dexmedetomidine did not show any exacerbation, suggesting that dexmedetomidine has no clinically relevant interaction with the NMDA-R in vivo. (2) CASE REPORT: our patient, a 27-year-old female, was diagnosed with anti-NMDA-R encephalitis secondary to ovarian teratoma. She underwent laparoscopic ovariectomy under general anesthesia using thiopental, sevoflurane, and remifentanil, which were well tolerated. After transfer to the intensive care unit, she became increasingly agitated despite repeated boluses of intravenous fentanyl. Infusion of dexmedetomidine (0.5-1.0 μg/kg/h) was started, and an adequate level of sedation was achieved uneventfully. After discontinuation of dexmedetomidine, recovery from sedation was smooth and quick without any deterioration of neurological or psychological symptoms.
Our experimental findings and the presented case suggest that dexmedetomidine may be safely used in patients with anti-NMDA-R encephalitis. Further clinical evaluation is warranted to validate this finding.
抗N-甲基-D-天冬氨酸受体（NMDA-R）脑炎是一种最近才被发现但越来越受到认可的自身免疫性副肿瘤疾病。由于这些患者因NMDA-R功能障碍而出现复杂的神经精神症状，镇静/麻醉的最佳方法仍存在争议。在此，我们展示动物实验数据以及一份相关病例报告，提示右美托咪定在抗NMDA-R脑炎患者中使用安全有效。
（1）动物实验：为研究右美托咪定是否会干扰NMDA-R活性，采用大鼠NMDA拮抗剂（MK-801）模型模拟抗NMDA-R脑炎。给予MK-801会产生典型的精神分裂症样行为，即活动亢进和刻板嗅探。氯胺酮是一种依赖NMDA受体发挥作用的麻醉剂，即使在亚麻醉剂量下也会加剧这两种行为。另一方面，右美托咪定未显示出任何加剧作用，表明右美托咪定在体内与NMDA-R无临床相关相互作用。（2）病例报告：我们的患者是一名27岁女性，被诊断为继发于卵巢畸胎瘤的抗NMDA-R脑炎。她在全身麻醉下接受了腹腔镜卵巢切除术，使用硫喷妥钠、七氟醚和瑞芬太尼，耐受性良好。转入重症监护病房后，尽管多次静脉注射芬太尼，她仍变得越来越烦躁。开始输注右美托咪定（0.5 - 1.0μg/kg/h），并顺利达到了适当的镇静水平。停用右美托咪定后，镇静恢复顺利且迅速，神经或心理症状未出现任何恶化。
我们的实验结果和所展示的病例表明，右美托咪定可安全用于抗NMDA-R脑炎患者。需要进一步的临床评估来验证这一发现。
