Safety and Efficacy of Neostigmine Infusion as Adjuvant Therapy in Sepsis and Septic Shock
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 50
- 试验地点
- 1
- 主要终点
- Sequential organ failure assessment (SOFA score)
研究概览
简要总结
The inflammatory response represents an important, central component of sepsis. Therefore, it is believed that blunting inflammation will decrease mortality. In vivo test series with mice that had undergone cecal ligation and puncture (recognized sepsis model), physostigmine salicylate significantly inhibited the release of various cytokines (tumor necrosis factor α, interleukin1β, and interleukin 6). These results were similar to those obtained by vagus nerve stimulation.
In animal sepsis model using physostigmine not only decreased inflammation but also, diminished the decrease in blood pressure following infection.
Animals treated with the peripheral choline esterase inhibitor neostigmine showed no difference compared with physostigmine-treated animals. Therefore, this study aims to investigate the efficacy of choline esterase inhibitors as adjuvant therapy in patients with sepsis or septic shock. Outcome measures include: percentage reduction in procalcitonin blood level, percentage of patients achieving significant reduction in procalcitonin levels, Mean Sequential Organ Failure Assessment score, percentage decrease in lactate dehydrogenase blood level, length of stay in hospital intensive care unit, and in hospital mortality.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Participant)
入排标准
- 年龄范围
- 18 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 18-85 years.
- •Patients diagnosed with sepsis or septic shock according to Third International Consensus Definitions for Sepsis and Septic Shock mentioned above.
- •Patients who have ≥ 2 of the following four criteria plus documented infection:
- •Fever ≥ 38 °C or hypothermia ≤ 36 °C.
- •Tachycardia ≥ 100/min.
- •Tachypnea ≥ 20/min or hyperventilation.
- •Leukocytosis ≥ 12000/mm3 or leukopenia ≤ 4000/mm3 or ≥ 10% immature neutrophils in the differential count.
- •Exclusion criteria:
- •Known hypersensitivity to choline esterase inhibitors.
- •Known absolute contra-indications against choline esterase inhibitors such as, myotonic dystrophy; depolarization block by depolarizing muscle relaxants; intoxication by irreversibly acting cholinesterase inhibitors; closed craniocerebral trauma; obstruction in the gastrointestinal tract (mechanical constipation); obstruction in the urinary tract (mechanical urinary retention)
- •Known relative contraindications against choline esterase inhibitors: bronchial asthma; bradycardia; AV-conduction disturbances.
- •Having undergone solid organ transplantation.
- •Pregnant and lactating women.
- •Participation in another clinical trial.
- •Presence of primary or concomitant illness, impending death.
排除标准
- 未提供
研究组 & 干预措施
Neostigmine group
This arm will receive -in addition to standard therapy for sepsis and septic shock-Neostigmine methylsulfate ampoule diluted in normal saline, and administered as continuous infusion for five days. The rate of infusion is 0.2 mg/hr.
干预措施: Neostigmine (Drug)
Standard group
This arm will receive the standard therapy for sepsis and septic shock only and followed for five days.
干预措施: Standard therapy (Drug)
结局指标
主要结局
Sequential organ failure assessment (SOFA score)
时间窗: Change from baseline SOFA score at five days
Increase in SOFA score is associated with worse outcome.
次要结局
未报告次要终点
研究者
Mona Mohammed El-Tamalawy
Assistant lecturer
Mansoura University