Effect of Target Intraoperative Blood Pressure on the Incidence of Post-operative Cognitive Dysfunction in Patients Aged 75 and Older Undergoing General Anesthesia for Non-cardiac Surgery: an International Multicenter Randomized Controlled Trial
试验速览
- 阶段
- 2 期
- 状态
- 暂停
- 入组人数
- 1,812
- 试验地点
- 1
- 主要终点
- Post-operative cognitive dysfunction (POCD) at 3 months
研究概览
简要总结
BACKGROUND: Post-operative cognitive dysfunction (POCD) is a potentially irreversible loss of brain functions observed in elderly patients after surgical operations under general anaesthesia. POCD at 3 post-operative months is observed in up to 15% of patients aged 70 years and more, and the only recognized risk factor for this condition is increasing age. Importantly, the incidence of POCD at 3 months has been associated to an increased disability and mortality.
OBJECTIVES: The present study will evaluate in patients aged 75 years and older undergoing general anaesthesia for non-cardiac surgery, whether an hemodynamic strategy, aiming at maintaining intra-operative arterial blood pressure close to patient's preoperative blood pressure, i.e., to avoid hypotensive episodes, reduces the incidence of POCD at three months.
METHODS: Around 1800 consecutive patients scheduled to undergo general anaesthesia for elective non-cardiac surgery will be enrolled. Each patient's cognitive function will be evaluated preoperatively and at 3 months and 1 year postoperatively, together with the occurrence of hearing loss and vestibular function impairment. Furthermore, the incidence of postoperative delirium and cardiovascular, respiratory and infectious complications will be evaluated.
EXPECTED RESULTS: The primary outcome is a 25% relative reduction in the incidence of POCD at 3 postoperative months. Secondary outcomes are the reduction of POCD incidence at 1 postoperative year, a reduction in postoperative hearing loss and vestibular impairment at 3 months, a reduction in the incidence of delirium. Hospital length of stay and 90 day mortality will also be assessed. This present study could have a high socio-economic impact, reduce healthcare costs and patient morbidity and mortality with a simple not expensive intraoperative intervention.
详细描述
BACKGROUND Post-operative cognitive dysfunction (POCD) is defined as a spectrum of postoperative central nervous system dysfunctions both acute and persistent, including subtle neurologic signs and neuropsychological impairment. The incidence of POCD is clearly associated with the age of patients, with older patients being more susceptible to neurologic impairment following anesthesia and surgery. Due to the increasing life expectances and ameliorated surgical and anesthesiologic techniques, more and more elderly people are undergoing surgical procedures. In this respect, POCD is a complication that needs to be taken into account in the perioperative course of elderly patients, especially in those with reduced neurological functional reserve capacity and high prevalence of comorbidities. It is worth underlining that the occurrence of POCD brings a very important subjective burden on the quality of life of the patient and also and outstanding social impact.
Several observational studies have shown that POCD occurs in 25% of patients 1 week after the surgical procedure (early POCD) and in approximately 15% of patients at 3 months (late POCD). Importantly, the incidence of POCD at 3 months has been associated to an increased disability and mortality.
Post-operative cognitive dysfunction is probably a multifactorial syndrome, nevertheless 3 principal pathophysiological hypothesis, that certainly could co-exist, have been formulated:
- Pharmacological hypothesis: drugs employed during anesthesia can produce alterations in the neuronal network, principally through alterations of the cholinergic transduction signal;
- Toxic hypothesis: the neuronal damage is a direct consequence of the drugs employed during anesthesia and of the inflammatory mediators associated to the surgical procedure;
- Hemodynamic hypothesis: hemodynamic changes induced by general anesthesia cause alterations in cerebral blood flow, potentially resulting in ischemic neuronal damage.
The present study focuses on the third hypothesis and aims to evaluate the influence of a target of intraoperative arterial blood pressure based on preoperative values on the development of POCD at 3 months after elective non-cardiac surgery under general anesthesia in patients aged 75 years and older.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Double (Participant, Outcomes Assessor)
入排标准
- 年龄范围
- 75 Years 至 —（Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •any patient aged 75 years and more scheduled for elective non-cardiac surgery under general anesthesia.
- •Exclusion criteria:
- •Failure to obtain informed consent to the study;
- •Impossibility to perform scheduled geriatric and neuropsychological tests during the preoperative evaluation;
- •Mini-mental state examination score (corrected for age and education) ≤ 23 at the preoperative evaluation;
- •Patients scheduled to undergo intracranic neurosurgical procedures or vascular surgery;
- •Patients who have been subjected to a surgical procedure under general anesthesia in the preceding 6 months;
- •Patients with metastatic cancer; patients falling in the category of the American Society of Anaesthesiologists (ASA) physical status 4;
- •Patients already included in the study, i.e. second surgical procedure;
- •Inclusion criteria for the Control Group:
- •Subjects of 75 years and more in whom no hospitalization or surgical procedure is scheduled in the following 3 months.
- •Exclusion criteria for the Control Group:
- •Failure to obtain informed consent to the study;
- •Impossibility to perform scheduled geriatric and neuropsychological tests during the baseline evaluation;
- •Mini-mental state examination score (corrected for age and scholarity) ≤ 23 at the baseline evaluation;
- •Subjects who have undergone a surgical procedure under general anesthesia in the preceding 6 months;
- •Subjects who have undergone an unexpected surgical procedure under general anesthesia in the timeframe between baseline 3 months evaluation.
排除标准
- 未提供
研究组 & 干预措施
Treatment
The anesthesiologist will have as hemodynamic target for patients assigned to this arm the maintenance of mean arterial blood pressure within 10% of the baseline blood pressure value (recorded at the preoperative evaluation). The strategy to reach this hemodynamic target will be left to the clinical judgment of the anaesthesiologist in charge. The possible strategies include a vasoconstrictor agent (either phenylephrine, ephedrine, epinephrine, norepinephrine or dopamine), intravenous fluids, patient's positioning or reduction of depth of anesthesia.
干预措施: Hemodynamic target (Procedure)
Treatment
The anesthesiologist will have as hemodynamic target for patients assigned to this arm the maintenance of mean arterial blood pressure within 10% of the baseline blood pressure value (recorded at the preoperative evaluation). The strategy to reach this hemodynamic target will be left to the clinical judgment of the anaesthesiologist in charge. The possible strategies include a vasoconstrictor agent (either phenylephrine, ephedrine, epinephrine, norepinephrine or dopamine), intravenous fluids, patient's positioning or reduction of depth of anesthesia.
干预措施: Phenylephrine (Drug)
Treatment
The anesthesiologist will have as hemodynamic target for patients assigned to this arm the maintenance of mean arterial blood pressure within 10% of the baseline blood pressure value (recorded at the preoperative evaluation). The strategy to reach this hemodynamic target will be left to the clinical judgment of the anaesthesiologist in charge. The possible strategies include a vasoconstrictor agent (either phenylephrine, ephedrine, epinephrine, norepinephrine or dopamine), intravenous fluids, patient's positioning or reduction of depth of anesthesia.
干预措施: Intravenous fluids (Drug)
Treatment
The anesthesiologist will have as hemodynamic target for patients assigned to this arm the maintenance of mean arterial blood pressure within 10% of the baseline blood pressure value (recorded at the preoperative evaluation). The strategy to reach this hemodynamic target will be left to the clinical judgment of the anaesthesiologist in charge. The possible strategies include a vasoconstrictor agent (either phenylephrine, ephedrine, epinephrine, norepinephrine or dopamine), intravenous fluids, patient's positioning or reduction of depth of anesthesia.
干预措施: Patient's positioning (Procedure)
Treatment
The anesthesiologist will have as hemodynamic target for patients assigned to this arm the maintenance of mean arterial blood pressure within 10% of the baseline blood pressure value (recorded at the preoperative evaluation). The strategy to reach this hemodynamic target will be left to the clinical judgment of the anaesthesiologist in charge. The possible strategies include a vasoconstrictor agent (either phenylephrine, ephedrine, epinephrine, norepinephrine or dopamine), intravenous fluids, patient's positioning or reduction of depth of anesthesia.
干预措施: Reduction of depth of anesthesia (Procedure)
Treatment
The anesthesiologist will have as hemodynamic target for patients assigned to this arm the maintenance of mean arterial blood pressure within 10% of the baseline blood pressure value (recorded at the preoperative evaluation). The strategy to reach this hemodynamic target will be left to the clinical judgment of the anaesthesiologist in charge. The possible strategies include a vasoconstrictor agent (either phenylephrine, ephedrine, epinephrine, norepinephrine or dopamine), intravenous fluids, patient's positioning or reduction of depth of anesthesia.
干预措施: Ephedrine (Drug)
Treatment
The anesthesiologist will have as hemodynamic target for patients assigned to this arm the maintenance of mean arterial blood pressure within 10% of the baseline blood pressure value (recorded at the preoperative evaluation). The strategy to reach this hemodynamic target will be left to the clinical judgment of the anaesthesiologist in charge. The possible strategies include a vasoconstrictor agent (either phenylephrine, ephedrine, epinephrine, norepinephrine or dopamine), intravenous fluids, patient's positioning or reduction of depth of anesthesia.
干预措施: Epinephrine (Drug)
Treatment
The anesthesiologist will have as hemodynamic target for patients assigned to this arm the maintenance of mean arterial blood pressure within 10% of the baseline blood pressure value (recorded at the preoperative evaluation). The strategy to reach this hemodynamic target will be left to the clinical judgment of the anaesthesiologist in charge. The possible strategies include a vasoconstrictor agent (either phenylephrine, ephedrine, epinephrine, norepinephrine or dopamine), intravenous fluids, patient's positioning or reduction of depth of anesthesia.
干预措施: Norepinephrine (Drug)
Treatment
The anesthesiologist will have as hemodynamic target for patients assigned to this arm the maintenance of mean arterial blood pressure within 10% of the baseline blood pressure value (recorded at the preoperative evaluation). The strategy to reach this hemodynamic target will be left to the clinical judgment of the anaesthesiologist in charge. The possible strategies include a vasoconstrictor agent (either phenylephrine, ephedrine, epinephrine, norepinephrine or dopamine), intravenous fluids, patient's positioning or reduction of depth of anesthesia.
干预措施: Dopamine (Drug)
结局指标
主要结局
Post-operative cognitive dysfunction (POCD) at 3 months
时间窗: 3 months after surgical operation
For each of the neuropsychological tests a Z-score will be calculated. The Z score represents the magnitude of the deviation (in number of standard deviations) in the test results from the reference (Control Group). The Z-score is calculated as the difference between the baseline and the 3 months test result for a patient, corrected for the expected difference (the mean difference for that test observed in the Control Group), divided by the standard deviation of the mean difference for that test observed in the Control Group. From the Z-scores of the single tests a combined Z-score can be calculated. Patients in whom the difference (worsening) in the score at 3 months to the score at baseline in at least 2 tests will be greater than 2 standard deviations from the expected difference (i.e. Z-score ≥ 2 in at least 2 tests), will be diagnosed with POCD. Also patients in which the combined Z-score will be equal or greater than 2 will be diagnosed with POCD.
次要结局
- Mortality(90 days)
- Vestibular dysfunction at 3 months(3 months after surgical operation)
- Hearing loss at 1 year(1 year after surgical operation)
- Post-operative delirium(Within 7 days after surgical operation)
- Vestibular dysfunction at 1 year(1 year after surgical operation)
- Post-operative cognitive dysfunction (POCD) at 1 year(1 year after surgical operation)
- Hearing loss at 3 months(3 months after surgical operation)
- Hospital length of stay(Up to 30 days after surgical operation)
- Number of patients with at least one post-operative complication(Within 7 days after surgical operation)