Comparative Study Between High and Low Dose Methylene Blue Infusion in Septic Cancer Patients. A Randomized Blinded Controlled Study
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 90
- 试验地点
- 1
- 主要终点
- Discontinuation of vasopressor
研究概览
简要总结
The main aim of this study is to examine the various effects of continuous methylene blue infusion in septic cancer patients and to compare it with the traditional infusion of noradrenaline in such patients .
详细描述
Exaggerated host response to infection, may result in sepsis, which is life-threatening organ dysfunction . Though considered the number one cause of in-hospital deaths , it can be treatable with early prompt interventions.
The 2021 SSC Guidelines use the Third International Consensus definitions, also known as Sepsis-3. Where sepsis is defined as "life-threatening organ dysfunction caused by a dysregulated host response to infection." Organ dysfunction is evidenced by an increased score of 2 or more in the Quick Sequential [Sepsis-related] Organ Failure Assessment (QSOFA), and septic shock is considered as "a subset of sepsis in which particularly profound circulatory, cellular, and metabolic abnormalities are associated with a greater risk of mortality than with sepsis alone." To diagnose septic shock, an euvolemic patient must require vasopressor support to achieve a mean arterial pressure of at least 65 mm Hg and have a lactate level above 2 mmol/L.
The triad of intravenous fluid, vasopressors and antibiotics in the first hour is the mainstay of septic shock management. Aim of management is to maintain patient hemodynamically stable until antibiotics kick in and fight infection. In case of non-responders, low dose corticosteroids are prescribed. Other drugs need to be studied to also help in cases of non-responders and to improve outcome in general. Methylene blue (MB) is a nitric oxide inhibitor that can counteract the vasodilatation in early septic shock.
Nitric oxide (NO) activates soluble guanylyl cyclase (sGC) which activates cyclic guanosine monophosphate (cGMP)-dependent protein kinases (PKGs) that cause vasodilatation. Methylene blue selectively blocks sGC and inhibits iNOS. Therefore, it selectively acts on the microcirculation.
Onset of action of intravenous MB is 30-60 min. Peak concentration at 30 min. It is excreted through bile and fecal routes plus through the kidneys. Due to the short Plasma half-life of 5-6 hours, some studies used continuous infusion of 0.25-2 mg/kg/h, for up to 3 days following the initial bolus dose
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
- Double (Participant, Care Provider)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients aged ≥ 18 years and ≤ 65 with septic shock as defined by Sepsis-3 criteria (confirmed infection, requiring vasopressor to maintain a mean arterial blood pressure (MAP) ≥ 65 mmHg, and serum lactate > 2 mmol/L after adequate fluid resuscitation), and requiring mechanical ventilation.
排除标准
- •myocardial infarction or cerebrovascular accident within the last 3 months.
- •severe lung , liver or kidney disease (creatinine >3.5 mg/dL).
- •pregnancy.
- •glucose 6-phosphate-dehydrogenase deficiency.
- •known allergy to MB or food dyes and the use of nitrates within the last 3 days.
- •more than 24 hrs since initiation of norepinephrine.
- •other causes of shock than sepsis .
- •recent intake (4-weeks) of selective serotonin re-uptake inhibitors or MAOi.
- •refusal of the patient guardian to participate.
研究组 & 干预措施
Normal saline
30 patients will receive placebo of 100ml 0.9% Nacl over 20 minutes followed by continuous infusion of Nacl for 72 hours.
干预措施: Methylene Blue low dose (Drug)
Normal saline
30 patients will receive placebo of 100ml 0.9% Nacl over 20 minutes followed by continuous infusion of Nacl for 72 hours.
干预措施: Methylene Blue high dose (Drug)
methylene blue low dose
30 patients will receive a bolus of MB 1mg/kg in 100ml 0.9% Nacl over 20 minutes followed by continuous infusion of 0.25mg/kg/hour for 72 hours.
干预措施: Normal saline (Drug)
methylene blue low dose
30 patients will receive a bolus of MB 1mg/kg in 100ml 0.9% Nacl over 20 minutes followed by continuous infusion of 0.25mg/kg/hour for 72 hours.
干预措施: Methylene Blue high dose (Drug)
methylene blue high dose
30 patients will receive a bolus of MB 4mg/kg in 100ml 0.9% Nacl over 20 minutes followed by continuous infusion of 0.25mg/kg/hour for 72 hours.
干预措施: Normal saline (Drug)
methylene blue high dose
30 patients will receive a bolus of MB 4mg/kg in 100ml 0.9% Nacl over 20 minutes followed by continuous infusion of 0.25mg/kg/hour for 72 hours.
干预措施: Methylene Blue low dose (Drug)
结局指标
主要结局
Discontinuation of vasopressor
时间窗: 7 days
Time for noradrenaline discontinuation
次要结局
- Mortality(28 days)
研究者
Ehab Hanafy Shaker
Associate Professor of Anesthesia, ICU and Pain management
National Cancer Institute, Egypt