Enzymatic Evaluation of General Anesthetic Induced Neurotoxicity in Patients With Aneurysmal Subarachnoid Haemorrhage
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 32
- 试验地点
- 1
- 主要终点
- Estimation of changes in caspase 3 levels as a marker of neurotoxicity in patients with aneurysmal SAH following exposure to general anaesthetics.
研究概览
简要总结
General anesthetic induced neurotoxicity has received considerable attention in the past decade from various pre-clinical studies in rodents and non-human primates. Which demonstrated that exposure to general anesthetic agents for a longer duration can induce neuronal cell death that can lead to adverse neurodevelopmental outcomes.
The neuroapoptosis and impairment of neurodevelopmental processes has been postulated as the underlying mechanism, but the molecular mechanisms was not completely understood. Various hypothesis has been proposed they are- Antagonistic effect on N-methyl-D-aspartate receptors and agonistic effect on gamma-aminobutyric acid type A receptors; mitochondrial perturbations and activation of reactive oxygen species and dysregulation of intracellular calcium homeostasis. They trigger neuroapoptosis and cell death through the activation of caspases.3 Caspases, a group of cysteine proteases, plays an important role in regulation and execution of apoptosis. Caspase-3 is most important since it is activated by many cell death signals and cleaves a variety of important cellular proteins.4 Various anesthetic agents like isoflurane, halothane, sevoflurane, nitrous oxide and propofol causes neurotoxicity by activation of caspase-3. Which has been proven from various animal studies western blot analysis, immunohistochemical analysis and flow cytometric analysis.3, 5-9 Though it is documented that exposure to general anesthetics causes neurotoxicity during active brain growth in animals, there is no evidence of such effects in adult humans.10 and it is difficult to separate the effects of anesthetics from surgical impact and other factors associated with diseases.11 The patients with aneurysmal subarachnoid hemorrhage (SAH) have variable degree of neurological insults and it is possible, based on the evidence from animal models that administration of general anesthetics could add to the neuronal insults.
详细描述
Sixteen patients will be included for the study under each intervention (surgery or endovascular coiling). Total thirty two patients who meet the inclusion criteria will be recruited to the study. The patients will be randomized into four groups to receive Propofol (Group P), Isoflurane (Group I), Sevoflurane (Group S) or Desflurane (Group D) using a computer generated algorithm for the maintenance of anesthesia.
The surgery or endovascular coiling will be conducted by an experienced neurosurgeon or radiologist who will be blinded to the anesthetic agent used for maintenance of anesthesia. Pre-anesthetic checkup will be conducted prior to the intervention. Patient will be thoroughly examined and all the investigations will be reviewed. Written informed consent will be obtained from the patient's next of kin.
ANESTHESIA PROTOCOL:
Routine non-invasive monitors will be attached to the patients. It will include noninvasive blood pressure (NIBP), heart rate (HR), electrocardiography (ECG), pulse oximetry (SpO2), end tidal carbon dioxide (EtCO2), state entropy (SE) and urine output. All patients will be preloaded with 10-15 ml/kg of normal saline Fentanyl will be administered intravenously in dose of 2µg/kg prior to induction followed by 0.5-2 µg/kg/hr as infusion. Patients in all 4 groups will be induced with propofol 1 to 2 mg/kg, titrated to loss of verbal response. Vecuronium 0.1 mg/kg will be given to facilitate tracheal intubation. Lignocaine 1.5mg/kg will be given 120 seconds prior to laryngoscopy. For beat to beat monitoring of blood pressure and blood gas analysis an arterial catheter will be placed after induction of anesthesia. Patients will be maintained according to the group allocation along with 50/50% Oxygen/Air. BIS monitoring will be used to maintain comparable depth of anesthesia in all the groups and will be titrated to keep SE in range of 40 to 60. Vecuronium will be given intermittently to maintain less than two twitches on neurostimulation. Body temperature will be maintained using forced air warming blanket.
Normal Saline will be used as the intraoperative fluid. PaCO2 will be maintained around 32-36 mmHg. Neuromuscular blockade will be reversed with a combination of neostigmine 50 µg /kg and glycopyrrolate 10 µg /kg. Subsequently trachea will be extubated.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
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 with aneurysmal SAH who are scheduled for surgical or endovascular intervention.
- •Age between 18 to 65 yrs.
- •WFNS grade 1 or 2
- •Fischer grade 1 or 2
- •ASA grade 1 or 2.
排除标准
- •Patients with giant aneurysms of the internal carotid artery that require external carotid-internal carotid bypass or intra operative ligation of internal carotid artery.
- •Patients with known psychiatric disease.
- •Patients with any other neurological or neuro degenerative disorders.
- •History of drug abuse.
- •Patients with any history of carcinoma or any immune deficiency diseases.
- •Intra-operative surgical complications like massive blood loss, prolonged clipping time (>20 minutes), severe intra-operative brain swelling requiring extended craniotomy or lobectomy or precluding replacement of bone flap.
研究组 & 干预措施
SUPRA ORBITAL KEYHOLE CLIPPING/ COILING
Aneurysms should be either clipped or coiled to prevent re rupture general anesthesia is required to carry out these procedures.various anesthetic agents are used as an maintenance agents.
干预措施: Anesthetic Agents (Drug)
结局指标
主要结局
Estimation of changes in caspase 3 levels as a marker of neurotoxicity in patients with aneurysmal SAH following exposure to general anaesthetics.
时间窗: baseline( pre- induction), one hour after the exposure to anesthetic agents and after extubation
enzyme Caspase-3 is used as a marker of apoptosis and will be used as an indirect marker for neurotoxicity caused by general anesthetic agents
次要结局
未报告次要终点
研究者
Mukilan Balu
principal investigator-resident in the department of neuroanesthesia
Post Graduate Institute of Medical Education and Research, Chandigarh