Division of Medical Toxicology, Department of Emergency Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA.
Department of Pharmacy and Therapeutics, University of Pittsburgh School of Pharmacy, Pittsburgh, PA.
Crit Care Med. 2018 Aug;46(8):e768-e771. doi: 10.1097/CCM.0000000000003204.
Ketamine offers a plausible mechanism with favorable kinetics in treatment of severe ethanol withdrawal. The purpose of this study is to determine if a treatment guideline using an adjunctive ketamine infusion improves outcomes in patients suffering from severe ethanol withdrawal.
Retrospective observational cohort study.
Academic tertiary care hospital.
Patients admitted to the ICU and diagnosed with delirium tremens by Diagnostic and Statistical Manual of Mental Disorders V criteria.
Pre and post guideline, all patients were treated in a symptom-triggered fashion with benzodiazepines and/or phenobarbital. Postguideline, standard symptom-triggered dosing continued as preguideline, plus, the patient was initiated on an IV ketamine infusion at 0.15-0.3 mg/kg/hr continuously until delirium resolved. Based upon withdrawal severity and degree of agitation, a ketamine bolus (0.3 mg/kg) was provided prior to continuous infusion in some patients.
A total of 63 patients were included (29 preguideline; 34 postguideline). Patients treated with ketamine were less likely to be intubated (odds ratio, 0.14; p < 0.01; 95% CI, 0.04-0.49) and had a decreased ICU stay by 2.83 days (95% CI, -5.58 to -0.089; p = 0.043). For ICU days outcome, correlation coefficients were significant for alcohol level and total benzodiazepine dosing. For hospital days outcome, correlation coefficients were significant for patient age, aspartate aminotransferase, and alanine aminotransferase level. Regression revealed the use of ketamine was associated with a nonsignificant decrease in hospital stay by 3.66 days (95% CI, -8.40 to 1.08; p = 0.13).
Mechanistically, adjunctive therapy with ketamine may attenuate the demonstrated neuroexcitatory contribution of N-methyl-D-aspartate receptor stimulation in severe ethanol withdrawal, reduce the need for excessive gamma-aminobutyric acid agonist mediated-sedation, and limit associated morbidity. A ketamine infusion in patients with delirium tremens was associated with reduced gamma-aminobutyric acid agonist requirements, shorter ICU length of stay, lower likelihood of intubation, and a trend toward a shorter hospitalization.
氯胺酮在治疗严重乙醇戒断方面提供了一种合理的机制，具有有利的动力学。本研究的目的是确定是否使用辅助氯胺酮输注的治疗指南可以改善患有严重乙醇戒断的患者的结局。
回顾性观察队列研究。
学术三级护理医院。
入住 ICU 并根据《精神障碍诊断与统计手册》第 5 版标准诊断为震颤谵妄的患者。
在指南前后，所有患者均以苯二氮䓬类药物和/或苯巴比妥的症状触发方式进行治疗。在指南之后，标准的症状触发剂量继续作为指南之前，另外，患者开始以 0.15-0.3mg/kg/hr 的速度静脉输注氯胺酮，持续到谵妄消退。根据戒断严重程度和激越程度，一些患者在连续输注前给予氯胺酮推注（0.3mg/kg）。
共纳入 63 例患者（29 例为指南前，34 例为指南后）。接受氯胺酮治疗的患者插管的可能性较低（比值比，0.14；p < 0.01；95%置信区间，0.04-0.49），并且 ICU 住院时间缩短了 2.83 天（95%置信区间，-5.58 至 -0.089；p = 0.043）。对于 ICU 天数的结果，酒精水平和总苯二氮䓬类药物剂量的相关系数具有显著性。对于住院天数的结果，患者年龄、天门冬氨酸氨基转移酶和丙氨酸氨基转移酶水平的相关系数具有显著性。回归显示，氯胺酮的使用与住院时间的非显著减少相关，减少了 3.66 天（95%置信区间，-8.40 至 1.08；p = 0.13）。
从机制上讲，辅助治疗氯胺酮可能会减轻严重乙醇戒断中 NMDA 受体刺激的神经兴奋作用，减少对过度 GABA 激动剂介导的镇静的需求，并限制相关发病率。在震颤谵妄患者中输注氯胺酮可减少 GABA 激动剂的需求，缩短 ICU 住院时间，降低插管的可能性，并缩短住院时间。
