Anesthetic Method and Cerebral Outcomes: A Prospective Randomized Controlled Trial.
Sponsor:
Rabin Medical Center
Collaborators:
Information provided by (Responsible Party):
Leonid Eidelman，Rabin Medical Center
| Tracking Information | |||
|---|---|---|---|
| First Submitted Date ICMJE | October 3, 2018 | ||
| First Posted Date ICMJE | October 5, 2018 | ||
| Last Update Posted Date | October 5, 2018 | ||
| Actual Study Start Date ICMJE | November 1, 2018 | ||
| Estimated Primary Completion Date | November 1, 2019 (Final data collection date for primary outcome measure) | ||
| Current Primary Outcome Measures ICMJE |
NSE serum level in PACU[ Time Frame: 1 hour after surgery completion ] |
||
| Original Primary Outcome Measures ICMJE | Same as current | ||
| Current Secondary Outcome Measures ICMJE |
|
||
| Descriptive Information | |||
| Brief Title ICMJE | Anesthetic Method and Cerebral Outcomes: A Prospective Randomized Controlled Trial. |
||
| Official Title ICMJE | Rabin Medical Center |
||
| Brief Summary | Research regarding the effects of anesthesia on the central nervous system remain controversial with some studies suggesting a neurotoxic effect and others indicating a neuroprotective effect. In recent years numerous neuronal proteins have been found to be useful tools for diagnosis and prognosis of cerebral tissue damage. Among these neuronal proteins are the following markers: Neuron Specific Enolase (NSE), Tau protein, Glial Fibrillary Acidic Protein (GFAP), Ubiquitin Carboxy-Hydrolase L1 (UCH-L1). BIS is a non-invasive brain monitoring technology which monitors the depth of anesthesia. In this randomized clinical trial, we aim to examine the effect of anesthetic method (General anesthesia and neuroaxial anesthesia) on neuronal damage as measured by NSE serum levels. One hundred and forty patients aged 18 and above undergoing Transurethral resection of the prostate, Trans Urethral Resection of the Bladder Tumor, Tension Free Vaginal Tap , Trans Obturator Tension Free Vaginal Tap and pelvic floor repair surgeries will be enrolled in the study. Patients will randomly be assigned to undergo the study either under general anesthesia or with neuroaxial anesthesia. Participants will be monitored using the BIS monitor, to measure the depth of anesthesia. Additionally, 9 cc of venous blood be collected from each participant in the surgery room prior to anesthesia induction, throughout anesthesia and one hour following surgery in the PACU in order to assess NSE levels. |
||
| Detailed Description | Introduction: Since the first use of Anesthesia for surgery in 1846, the general assumption has been that it is a reversible temporary procedure, with no long-lasting damage to the central nervous system (CNS) (1). Since then numerous beliefs have evolved. To date, debate remains ongoing regarding the effect of anesthetic agents on the CNS, with a wide range of proposed theories varying from a neuroprotective effect to a neurotoxic effect (2). In recent years, numerous neuronal proteins, which can be found in human plasma have been shown to directly correlate to cerebral tissue damage. These biochemical tests have become usual tools for diagnosis and prognosis of cerebral tissue damage, analogous to the increase in troponin in response to acute myocardial ischemia (1, 3) . These biomarkers have been found to be predictive of traumatic brain injury and stroke. Among these neuronal proteins are the following markers: Neuron Specific Enolase (NSE), Tau protein, Glial Fibrillary Acidic Protein (GFAP), Ubiquitin Carboxy-Hydrolase L1 (UCH-L1). NSE a brain injury biomarker, is an intracytoplasmic glycolytic enzyme enolase (4, 5). The enzyme is expressed in neurons and neuroendocrine tissue (5). Increased levels of NSE are released into the blood circulation in accordance to the death rate of those cells (5). NSE has been found to correlate to the level of severity and prognosis after brain trauma, stroke and resuscitation. An increase in this enzyme level may indicate a subclinical injury (2) . Evered et al found a correlation between increased blood levels of NSE and postoperative cognitive declines after general anesthesia (GA) (1). To the best of our knowledge, there has been no study, to date, comparing the effect of different anesthetic methods on the level of neuronal injury biomarkers in the plasma. GFAP is an intermediate filament protein which is distributed in the astrocytes of the central nervous system. This protein has high specificity for the brain tissue and is predictive of different clinical outcomes (6, 7). High serum levels of this indicator, were found in patients who had tumors with intracranial pressure greater than 25 mmHg. In a recent study, GFAP levels were shown to be closely related to the occurrence of post-operative delirium (POD) and post-operative cognitive dysfunction (POCD) (6, 7). Tau is a microtubule protein, found in the brain and spinal cord. This protein stabilizes the axonal microtubules. Phosphorylation of the Tau protein correlates with neural death rate and has become the hallmark of neurodegenerative disorder. Elevated levels of this protein were found in patients suffering from POCD. Furthermore, elevated plasma levels of this protein were correlated with the severity of brain injury in patients who underwent non cardiac surgery, and this protein may be useful as a predictive marker for neurological outcome (2). UCH-L1 is specific neuronal protein which is consolidated in the perikarya, in the grey matter of the brain. Its role is to remove misfolded or oxidized proteins in the central nervous system (2, 8). Elevated levels of the tau protein were found in human serum one hour after traumatic brain injury. In addition, serum levels of this protein were correlated with grading on the Glasgow scale, clinical implications of cerebral CT imaging findings, and the need for surgical intervention (1). Transurethral resection of the prostate (TURB) and Trans Urethral Resection of the Bladder Tumor (TURBT) are commonly performed surgeries. TURB is a gold standard treatment for benign prostatic hyperplasia (BPH)(9) . In this surgical technique the prostatectomy is performed through the urethra (10). TURBT is usually recommended for treatment of bladder tumors. Treatment protocols can include chemotherapy treatment in addition to surgery, or intravesicular washing the bladder with biological agents. Tension Free Vaginal Tap (TVT), Trans Obturator Tension Free Vaginal Tap (TVT-O) and pelvic floor repair surgeries are performed for urinary incontinence treatment in women (11). Both general and neuroaxial anesthesia are feasible anesthetic methods for these surgeries. BIS brain monitoring technology uses innovative technology to link patient-specific EEG information to the individual clinical state of each patient and monitors the depth of GA. BIS level less than 60 is defined as GA. Research has shown that BIS values between 40 and 60 in patients undergoing major surgeries can prevent POD and POCD. Deviations from those values was correlated to increases of serum cerebral biomarkers (12). While research suggests that anesthetics agents themselves can be neurotoxic, to date, it remains unclear which anesthetic method (NA vs GA) causes greater neuronal damage. In this study, we would like to examine the correlation between anesthetic method (GA vs NA) and elevation in neuronal damage biomarker as measured by NSE. Specific Aim: Primary Endpoint Our primary endpoint is to compare the effect of anesthetic method (GA vs. NA) on plasma level of neuronal damage biomarker NSE. Study Design: This is a prospective, single center, randomized controlled trial that try to assess the effect of anesthetic method on neuronal damage biomarker level. The study will be conducted at the Rabin Medical Center (Beilinson Campus), Petach Tikva, Israel, a tertiary university hospital. One hundred and forty patients aged 18 and above, undergoing elective TURB, TURBT, (TVT-O) and pelvic floor repair surgeries, will be enrolled in the study following providing their consent for participation. Subject inclusion Criteria: The study will conducted in Beilinson Hospital . All patients above 18 presenting for primary TURP, TURBT, TVT, TVT-O and pelvic floor repair surgeries. All patients who are able to comply with the study requirements and gave a written informed consents. Index procedure: After consenting to participation patients will be randomly assigned to one of the following study groups: 1. Patients undergoing surgery under GA 2. Patients undergoing surgery with NA. Anesthetic regime will be subject to standard clinical guidelines and to clinical judgement of the attending anesthesiologist. Intraoperative and postoperative hemodynamic monitoring will be according to standard departmental and clinical guidelines. Data will be recorded and stored electronically by Metavision system (iMDsoft company). BIS monitoring: In addition to the standard monitoring prescribed by the American society of Anesthesiologists, all study participants will be monitored with the BIS, a noninvasive monitoring device which measures the depth of anesthesia. The monitoring is performed using noninvasive electrodes placed on the forehead. Blood tests: Venous blood will be collected from each participant in the surgery room prior to anesthesia induction, throughout anesthesia and one hour following surgery in the PACU in order to assess cerebral biomarkers according to the ELISA method requirements. At each one of the assessment points 9 cc of venous of blood will be taken from each of the study participants, while routine blood tests are taken. Data Collection For each participating patient the following data will be collected and recorded through the study duration: 1. Demographic data 2. Each participant medical history including concomitant medications. 3. Hemodynamic data including heart rate, automatic non-invasive blood pressure measurements, temperature as well pulse oximetry as routine procedures will be recorded and stored by Metavision system. 4. Anesthetic data: anesthetic method, anesthetic agents given throughout surgery, anesthetic complications. 5. Opioid use in the first 24 hours after surgery. 6. Duration of stay in the PACU. 7. Duration of hospital stay 8. Functional status upon hospital release. Subject exclusion Criteria: 1. Patients with a history of a cerebrovascular accident (CVA) or Transient ischemic attack (TIA) in the year prior to surgery. 2. Patients with significant decreases in cognitive function prior to surgery. 3. Patients presenting for a secondary TURB surgery. 4. Patient with a contraindication to NA. 5. Patients who are unable to sign an informed consent form. Criteria for Patient participation removal: All patients with symptoms of neurological damage presenting within one hour from anesthesia induction will be removed from study participation. | ||
| Study Type ICMJE | Interventional | ||
| Study Phase | N/A | ||
| Study Design ICMJE | Allocation: Randomized Intervention Model: Parallel Assignment Intervention Model Description: Masking: Interventional Masking Description: Primary Purpose: Screening |
||
| Condition ICMJE | |||
| Intervention ICMJE |
|
||
| Study Arms |
|
||
| Recruitment Information | |||
| Recruitment Status ICMJE | Not yet recruiting | ||
| Estimated Enrollment ICMJE |
140 | ||
| Original Estimated Enrollment ICMJE | Same as current | ||
| Estimated Study Completion Date | November 1, 2019 | ||
| Estimated Primary Completion Date | November 1, 2019 (Final data collection date for primary outcome measure) | ||
| Eligibility Criteria ICMJE | Inclusion Criteria: The study will conducted in Beilinson Hospital . All patients above 18 presenting for primary TURP, TURBT, TVT, TVT-O and pelvic floor repair surgeries. All patients who are able to comply with the study requirements and gave a written informed consents. Exclusion Criteria: 1. Patients with a history of a cerebrovascular accident (CVA) or Transient ischemic attack (TIA) in the year prior to surgery. 2. Patients with significant decreases in cognitive function prior to surgery. 3. Patients presenting for a secondary TURB surgery. 4. Patient with a contraindication to NA. 5. Patients who are unable to sign an informed consent form. | ||
| Sex/Gender |
|
||
| Ages | 18 Years and older (Adult, Older Adult) | ||
| Accepts Healthy Volunteers | No | ||
| Listed Location Countries ICMJE | Israel | ||
| Removed Location Countries | |||
| Administrative Information | Has Data Monitoring Committee | No | |
| U.S. FDA-regulated Product |
Studies a U.S. FDA-regulated Drug Product: No Studies a U.S. FDA-regulated Device Product: No |
||
| IPD Sharing Statement |
|
||
| Responsible Party | Leonid Eidelman，Rabin Medical Center | ||
| Study Sponsor ICMJE | Rabin Medical Center | ||
| Collaborators ICMJE | |||
| Investigators ICMJE |
|
||
| PRS Account | Rabin Medical Center | ||
| Verification Date | October 2018 | ||
|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |
|||
请使用微信扫码报名
京公网安备 11010102003638号