Immune-mediatory Response of Intravenous Ketamine Versus Propofol for Major Abdominal Surgeries: a Prospective Randomized Study
试验速览
- 阶段
- 不适用
- 入组人数
- 36
- 主要终点
- Serum level of interleukin 6 (IL-6)
研究概览
简要总结
Host systemic responses to vigorous stimuli as trauma, surgical tissue injury, anesthesia and post-operative pain, leads to release a variety of pro-inflammatory cytokines including interleukin-1 (IL-1) and interleukin-6 (IL-6) mainly from monocytes and macrophages Thus, the rise of IL-6 is regarded as an early marker of tissue damage and its rise proportional to the degree of tissue damage .
It has been demonstrated that systemic responses to stress may be modified by the anesthetic technique used . Total intravenous anesthesia (TIVA) especially propofol based greatly suppresses the stress response induced by surgery when compared to inhalation by lowering cortisol levels.
Ketamine has the ability to modulate (modify) inflammation . Even the sub-anesthetic doses of ketamine in animal models were even provided to have an effect on the inflammatory response system in the central nervous system
详细描述
The release a variety of pro-inflammatory cytokines including tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1) and interleukin-6 (IL-6) mainly from monocytes and macrophages due to surgical trauma or anesthesia .
IL-6 is constantly found in the peripheral blood and rapidly within few minutes unlike other pro inflammatory mediators. Thus, the rise of IL-6 is regarded as an early marker of tissue damage and IL-6 levels are proportional to the degree of tissue damage . The two major actions of IL-6 are having a key role in regulating stress responses by activating the hypothalamic-pituitary- adrenal (HPA) axis and synthesizing fibrinogen (which is necessary for the acute-phase response) serving as a growth factor for activated B-cells .
While appropriate inflammatory reactions are advantageous and essential for wound healing and host defense against microorganisms, excessive immune responses can be detrimental. The released mediators prompt systemic endocrine, immunological and metabolic responses result in increased pain sensitivity, altered metabolism, hyperthermia and greater secretion of liver acute phase proteins and stress hormones, so yields unstable patient's hemodynamic status
Propofol was documented to have an advantage in terms of inflammatory and immunomodulatory effects through significant effect on TNF-α, IL-6 and IL-10 release .
Ketamine has the ability to modulate (modify) inflammation and this is why it is recommended in patients with sepsis undergoing surgery . This may be possibly related with the variations in TNF-α and nuclear factor-κB expression . Even the sub-anesthetic doses of ketamine in animal models were even provided to have an effect on the inflammatory response system in the central nervous system which is involved in its therapeutic effect on depression (Yang-2 et al., 2013).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Supportive Care
- 盲法
- Double (Participant, Care Provider)
盲法说明
Double -blinded ( masking of both participant and care provider)
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Elective major abdominal surgeries with median incision with right or left extension.
- •ASA -physical status I -II
- •aged from 18 till 70 years
排除标准
- •body mass index more than 35 kg/m2,
- •Patients having severe cardiovascular, respiratory, hepatic, renal, Endocrinol disorders, malignant
- •Patients having chronic inflammatory diseases
- •Patients received suppressant drugs in the 6 weeks before surgery.
- •Any known allergy or any contraindications to anesthetic drugs;
- •patient refusal,
- •The usage of anti- emetic drug 24 hours before operation
研究组 & 干预措施
Propofol group (P)
The maintenance of anesthesia , patient will receive sevoflurane 1%-2.5% with intravenous infusion of propofol 17 mcg /kg/min and 0.5 mg/kg fentanyl will be given if the heart rate or mean blood pressure increased by 30 % or more from the basal readings
干预措施: Propofol (Drug)
Ketamine group ((K)
The maintenance of anesthesia , patient will receive sevoflurane 1%-2.5% with intravenous infusion of ketamine 5 mcg /kg/min and 0.5 mg/kg fentanyl will be given if the heart rate or mean blood pressure increased by 30 % or more from the basal readings
干预措施: Ketamine (Drug)
结局指标
主要结局
Serum level of interleukin 6 (IL-6)
时间窗: The time frame extend from 10 minutes before the induction of anesthesia till the first 24 hours postoperative
picogram/milliliter using ELISA techniques .Five measurement points : before the induction of general anesthesia, 30 min after beginning infusion of the anesthetic agent , then 2h, 8h and 24 hours postoperative.
Serum level of interleukin IL-1β (IL-1β)
时间窗: The time frame extend from 10 minutes before induction of anesthesia till the first 24 hours postoperative
picogram/milliliter using ELSA techniques .Five measurement points : before the induction of general anesthesia, 30 min after beginning infusion of the anesthetic agent , then 2h, 8h and 24 hours postoperative.
次要结局
- Absolute neutrophil count(The time frame extend from 10 minutes before induction of anesthesia till the first 24 hours postoperative)
- Total leukocyte count(The time frame extend from 10 minutes before induction of anesthesia till the first 24 hours postoperative)
- Neutrophil-lymphocyte ratio (N/L ratio)(The time frame extend from 10 minutes before induction of anesthesia till the first 24 hours postoperative)
- C-reactive protein serum level(The time frame extend from 10 minutes before induction of anesthesia till the first 24 hours postoperative)
- Serum Cortisol level(The time frame extend from 10 minutes before induction of anesthesia till the first 24 hours postoperative)
研究者
Abdelraouf Elsharkawy
Lecturer of anesthesia and surgical intensive care
Mansoura University Hospital