Intravenous ketamine for treatment of super-refractory convulsive status epilepticus with septic shock: A report of two cases

Refractory and super-refractory status epilepticus is a life-threatening neurological emergency, associated with high morbidity and mortality. Treatment should be aimed to stop seizure and to avoid cerebral damage and another morbidity. Published data about effectiveness, safety and outcome of various therapies and treatment approaches are sparse and are mainly based on small case series and retrospective data. Here we report successful management of two cases of super-refractory status epilepticus refractory to anesthetic therapy with midazolam and complicated by septic shock, managed successfully with ketamine infusion.     

氯胺酮肌肉注射与面罩下吸入七氟醚两种麻醉方式在小儿麻醉手术中的临床效果及安全性比较

目的 将面罩下吸入七氟醚应用于小儿麻醉手术的临床效果及安全性与氯胺酮肌肉注射相比较,探讨其有效性、安全性.方法 选择2013年1-12月该院收治的择期手术的患儿228例,ASAⅠ～Ⅱ级,将所有患儿随机分成二组,其中氯胺酮组100例,给予氯胺酮5mg/kg肌肉注射麻醉,七氟醚组128例,给予4L/min纯氧吸入,经面罩吸入七氟醚,吸入浓度从3％逐渐增加至8％.在手术前后对患儿心率(HR)、平均动脉压(MAP)、动脉血氧 饱和度(SPQ)进行监测,采用数字分级法(NRS)对麻醉效果进行评价,观察二组患儿麻醉诱导时间、苏醒时间、手术时间、麻醉费用及不良反应发生情况.结果二组患儿麻醉效果、手术时间、麻醉费用差异无统计学意义(t=0.38、0.77、0.31,P＞0.05),七氟醚组麻醉诱导时间、苏醒时间显著短于氯胺酮组,二组差异有统计学意义(t=55.43、30.42,P＜0.05);二组患儿在插管前后HR、MAP、SPQ平稳,二组差异无统计学意义(P＞0.05);二组不良反应差异有统计学意义(P＜0.05).结论面罩下吸入七氟醚应用于小儿麻醉手术较氯胺酮肌肉注射效果显著,其具有起效快、苏醒时间短、患儿易于接受、不良反应小等优点,为小儿麻醉诱导的理想药物.     

Kétamine,psilocybine, et antidépresseurs d'action rapide : de nouvelles promesses pour la psychiatrie?

The hypothesis of monoaminergic deficiency has long dominated the conceptual framework for the development of new antidepressant strategies, but the limits of conventional antidepressant treatments targeting monoaminergic signaling have motivated the search for new antidepressant pathways. The success of ketamine in the management of depressive disorders has provoked a renewed interest in hallucinogenic substances such as psilocybin targeting the serotonergic signaling 5HT^2A and neurosteroid allosteric modulator of γ-aminobutyric acid (GABAA) receptors such as brexanolone. Unlike conventional treatments, these modulators of glutamatergic, serotonergic and GABAergic systems exert a rapid antidepressant effect ranging from 24 hours to a week. Apart from their clinical interest and the fantasized search for a “miracle” molecule that jointly meets the expectations of patients and clinicians, these new targets could lead to the identification of potential new biomarkers for the development of rapid-acting antidepressants and redefine therapeutic strategies in mood disorders.     

Perspectives of Ketamine Use in COVID-19 Patients

Hospitalized coronavirus disease 2019 (COVID-19)-infected patients suffer from both physical impairments and mental stress. Respiratory insufficiency and cardiovascular disturbances require most of the intensive care interventions, but they are also accompanied by depressive conditions, sadness and fear of dying. Sedatives are mostly respiratory and cardiovascular depressants and do not provide resistance to the pro-inflammatory burst induced by the virus. Ketamine is a unique and safe drug that enables well-controlled sedation and anesthesia, attenuates depression and mitigates suicidal thoughts, without depressing respiratory or cardiovascular mechanics. This brief communication highlights the benefits potentially provided by ketamine to patients hospitalized for COVID-19 infection.     

Rapid and long-lasting antidepressant-like effects of ketamine and their relationship with the expression of brain enzymes,BDNF, and astrocytes

Ketamine (KET) is an N-methyl-D-aspartate (NMDA) antagonist with rapid and long-lasting antidepressant effects, but how the drug shows its sustained effects is still a matter of controversy. The objectives were to evaluate the mechanisms for KET rapid (30 min) and long-lasting (15 and 30 days after) antidepressant effects in mice. A single dose of KET (2, 5, or 10 mg/kg, po) was administered to male Swiss mice and the forced swim test (FST) was performed 30 min, 15, or 30 days later. Imipramine (IMI, 30 mg/kg, ip), a tricyclic antidepressant drug, was used as reference. The mice were euthanized, separated into two time-point groups (D1, first day after KET injection; D30, 30 days later), and brain sections were processed for glycogen synthase kinase-3 (GSK-3), histone deacetylase (HDAC), brain-derived neurotrophic factor (BDNF), and glial fibrillary acidic protein (GFAP) immunohistochemical assays. KET (5 and 10 mg/kg) presented rapid and long-lasting antidepressant-like effects. As expected, the immunoreactivities for brain GSK-3 and HDAC decreased compared to control groups in all areas (striatum, DG, CA1, CA3, and mainly pre-frontal cortex, PFC) after KET injection. Increases in BDNF immunostaining were demonstrated in the PFC, DG, CA1, and CA3 areas at D1 and D30 time-points. GFAP immunoreactivity was also increased in the PFC and striatum at both time-points. In conclusion, KET changed brain BDNF and GFAP expressions 30 days after a single administration. Although neuroplasticity could be involved in the observed effects of KET, more studies are needed to explain the mechanisms for the drug’s sustained antidepressant-like effects.     

不同剂量氯胺酮对兔严重烧伤早期全身炎症反应的影响

目的：比较不同剂量氯胺酮对严重烧伤兔早期炎性细胞因子的影响,初步探讨其对创伤应激早期炎症反应的调节作用。方法选择健康雄性新西兰兔40只,按随机数字表法分正常对照组、烫伤模型组、氯胺酮镇痛组和氯胺酮麻醉组。烫伤前用戊巴比妥钠麻醉后分别经颈内静脉和颈内动脉置管备用,24 h后制备兔背部和臀部30%Ⅲ度烫伤模型,氯胺酮镇痛组于伤后0.5 h静脉注射（静注）氯胺酮负荷量0.5 mg/kg,然后持续静脉泵注氯胺酮9μg·kg-1·min-1共24 h;氯胺酮麻醉组伤后0.5 h静注氯胺酮1.5 mg/kg,然后持续静脉泵注氯胺酮45μg·kg-1·min-1共4 h维持全身麻醉;正常对照组和模型组仅给予静脉输液处理。记录各组补液量及氯胺酮镇痛组和麻醉组的氯胺酮总用量。分别于烫伤前和烫伤后0.5、6、12、24 h进行动脉血气分析,并检测血清白细胞介素（IL-1、IL-6）及肿瘤坏死因子-α（TNF-α）水平。结果4组血气分析指标虽然有所变化,但均在正常范围,说明呼吸功能在正常范围,间接反映循环功能也在正常范围,排除了呼吸和循环功能因素的影响对细胞因子的评判。4组烫伤前IL-1、IL-6及TNF-α水平比较差异均无统计学意义（均P＞0.05）。伤后0.5 h起,烫伤模型组IL-1（ng/L：30.27±0.93比13.79±1.11）、IL-6（ng/L：47.22±1.49比46.31±4.12）及TNF-α（ng/L：243.39±20.85比190.95±14.97）水平即均显著高于正常对照组（均P＜0.05）,并持续到伤后24 h;伤后6 h起氯胺酮镇痛组和麻醉组上述指标均较烫伤模型组明显降低,于伤后12 h起氯胺酮镇痛组上述指标的降低程度较氯胺酮麻醉组更显著〔IL-1（ng/L）：19.28±2.51比40.12±10.31,IL-6（ng/L）：52.10±4.23比72.20±10.11, TNF-α（ng/L）：246.03±20.74比313.71±27.34,均P＜0.05〕。结论小剂量氯胺酮镇痛和氯胺酮麻醉对兔严重烧伤后早期炎性细胞因子的表达和释放有一定抑制作用,且长时间小剂量氯胺酮镇痛效果更明显。     

Does Intravenous Ketamine Enhance Analgesia after Arthroscopic Shoulder Surgery with Ultrasound Guided Single-Injection Interscalene Block?: A Randomized,Prospective, Double-Blind Trial

Ketamine has anti-inflammatory, analgesic and antihyperalgesic effect and prevents pain associated with wind-up. We investigated whether low doses of ketamine infusion during general anesthesia combined with single-shot interscalene nerve block (SSISB) would potentiate analgesic effect of SSISB. Forty adult patients scheduled for elective arthroscopic shoulder surgery were enrolled and randomized to either the control group or the ketamine group. All patients underwent SSISB and followed by general anesthesia. During an operation, intravenous ketamine was infused to the patients of ketamine group continuously. In control group, patients received normal saline in volumes equivalent to ketamine infusions. Pain score by numeric rating scale was similar between groups at 1, 6, 12, 24, 36, and 48 hr following surgery, which was maintained lower than 3 in both groups. The time to first analgesic request after admission on post-anesthesia care unit was also not significantly different between groups. Intraoperative low dose ketamine did not decrease acute postoperative pain after arthroscopic shoulder surgery with a preincisional ultrasound guided SSISB. The preventive analgesic effect of ketamine could be mitigated by SSISB, which remains one of the most effective methods of pain relief after arthroscopic shoulder surgery.

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小儿颞下颌关节强直手术的麻醉处理

目的: 探讨小儿颞下颌关节强直手术的麻醉和困难气道管理。方法: 回顾性分析43例小儿颞下颌关节强直开口受限,困难气道病例资料,在保留自主呼吸的情况下,分为氯胺酮组（K1组）和氯胺酮复合右美托咪定组（K2组）。K1组和K2组均静脉给予氯胺酮1~2 mg/kg,K2组则追加静注右美托咪定1 μg/kg。患者意识消失后,辅以气管内和咽喉区表面麻醉。采用纤维支气管镜经鼻腔气管插管。插管过程中,根据患者反应小剂量滴定氯胺酮,维持麻醉深度。采用GraphPad Prism 6.0软件对数据进行统计学分析。结果: 所有患儿均在纤维支气管镜下经鼻腔成功气管插管。插管过程中,氧饱和度<95%发生率K2组略低于K1组,差异无统计学意义（P>0.05）。插管过程中追加氯胺酮次数和氯胺酮总剂量K2组显著低于K1组（P<0.05）,插管时心率变化和插管用时K2组显著低于K1组（P<0.05）。结论: 氯胺酮麻醉辅以良好的气管内和咽喉区表面麻醉,可完成小儿颞下颌关节强直开口受限的困难气道纤维支气管镜插管,氯胺酮复合右美托咪定可使小儿困难气道的插管过程更短、更平稳。