Effect of High vs. Low MAP Levels on Clinical Outcomes in Elderly Patients During Noncardiothoracic Surgery

Not Applicable

• Conditions: Surgery; Postoperative Delirium; Anesthesia; Blood Loss, Surgical; Aging; Blood Pressure
• Interventions: Drug: Urapidil; Drug: Phenylephrine; Procedure: Low-level MAP; Procedure: High-level MAP

• Registration Number: NCT02857153
• Lead Sponsor: Hu Anmin

Brief Summary

This will be a multicentre, randomised, controlled and prospective clinical trial. All participants provided their written informed consent to participate in a randomized trial that examined the effects of low-level MAP (60-70 mmHg) vs. high-level MAP (90-100 mmHg) in elderly patients (65 or more years of age) during noncardiothoracic surgery under general anesthesia. The investigators hypothesise high-level blood presure of the intervention for reducing the incidence of post-operative complications.

Detailed Description

This will be a multicentre, randomised, controlled and prospective clinical trial. Elderly patients will be included from seven centers, including Shenzhen People's Hospital affiliated to Jinan University, West China Hospital affiliated to Sichuan University, Taihe Hospital affiliated to Hubei University of Medicine, The Third Affiliated Hospital of Kunming Medical University, Sichuan Provincial People's Hospital, Guizhou Provincial People's Hospital and Henan Provincial People's Hospital. This research protocol was approved by the Institutional Review Board of Jinan University (2016001).

On the day of surgery, patients come to the operating room and are provided with standard monitoring. General anesthesia is given using midazolam and propofol, opioids, muscle relaxants and maintained with sevoflurane with inhaled concentrations of 1.5% sevoflurane in oxygen. Supplemental dosing of 1 μg/kg of fentanyl is used every hour from induction up to approximately 1 hour prior to the end of surgery. A tramadol bolus of 2 mg/kg is given 15 to 30 mins before the end of surgery. Propofol infusion is stopped 5 to 10 mins prior to the end of surgery, whereas at the end of skin closure, remifentanil was discontinued.

According to grouping, MAP is regulated to the goal level (60-70 mmHg or 95-100 mmHg) during general anesthesia. If necessary, intravenous antihypertensives (urapidil or phenylephrine when mean arterial pressure exceeded 10 mmHg of the target value), rather than more anesthesia, may be used in situations wherein sympathetic stimulation was high; yet a sufficient amount of anesthesia was being administered and bispectral index showed an adequate depth of hypnosis. Sedation was provided by a propofol infusion targeted to a BIS number of approximately 50 during general anesthesia. Atropine and esmolol would be used at the time of heart rate \<50 beats/min and \>110 beats/min, respectively.

Lactated Ringer's solution was given to bring the maintenance fluids to 10 ml/kg/h. Blood loss could be corrected for in a 1:1 ratio using gelofusine. Hospital transfusion guidelines were used to determine whether blood products were necessary (haemoglobin level less than 10 g/dl in patients with cardiac comorbidities, and below 7 g.dl-1 in those without cardiac disease). For later starting cases, an additional bolus of Ringer's solution of 1.5 ml/kg/fasted hour from 8 AM was given to bring the total 2 ml/kg/fasted hour. If urine output decreased to \<0.5 mL/kg/h for 1 hour, fursemide 0.3 mg/kg was given.

Mechanical ventilation patterns are adjusted to obtain an end-tidal carbon dioxide value of 35-45 mmHg, at 5-10 min after induction of anesthesia.

For patients with endotracheal tubes, intravenous sedatives including propofol or midazolam were administrated continuously and titrated by bedside nurses to a target sedation level. Daily awakening is used for those who were not extubated in the morning.

All patients receive patient controlled intravenous analgesia during postoperative days 1 to 3.

Study Timeline

• Study Start: 2016-07
• Study First Submitted: 2016-07-15
• Status Verified: 2016-08
• Study First Submitted QC: 2016-08-02
• Study First Posted: 2016-08-05
• Last Update Submitted: 2016-08-15
• Last Update Posted: 2016-08-16
• Primary Completion: 2017-07
• Study Completion: 2017-10

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 322

Inclusion Criteria

• male and females, American Society of Anesthesiologists I-II-III, 65 or more years of age, scheduled to undergo noncardiothoracic surgery with general anesthesia are enrolled.

Exclusion Criteria

• the patient suffered from Cardiovascular Disease and Metabolic Diseases, such as hypertension, cardiac disease, diabetes;
• the patient has severe liver, kidney or blood disease;
• the patient is accompanied severe cognitive impairment (Mini-Mental State Examination (MMSE) score < 15);
• preoperative history of schizophrenia, epilepsy, parkinsonism, use of cholinesterase inhibitor, or levodopa treatment;
• use of haloperidol or other neuroleptics during or after anesthesia;
• neurosurgery;
• individuals unlikely to survive for >24 hrs; previous participation in this study.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Low-level MAP	Low-level MAP	According to grouping, MAP is regulated to the goal level (60-70 mmHg) during general anesthesia.
High-level MAP	High-level MAP	According to grouping, MAP is regulated to the goal level (90-100 mmHg) during general anesthesia.
Low-level MAP	Urapidil	According to grouping, MAP is regulated to the goal level (60-70 mmHg) during general anesthesia.
High-level MAP	Urapidil	According to grouping, MAP is regulated to the goal level (90-100 mmHg) during general anesthesia.
Low-level MAP	Phenylephrine	According to grouping, MAP is regulated to the goal level (60-70 mmHg) during general anesthesia.
High-level MAP	Phenylephrine	According to grouping, MAP is regulated to the goal level (90-100 mmHg) during general anesthesia.

Primary Outcome Measures

Name	Time	Method
Incidence of delirium	Within the first 7 days after surgery

Secondary Outcome Measures

Name	Time	Method
Intra-operative blood loss	Intra-operative	Estimate of blood loss occurring during the surgical procedure as determined by anesthesia staff and documented by anesthesia, nursing and surgical staff as per hospital protocol.
Intraoperative urine volume.	Intra-operative
All-cause 28-day mortality.	The investigators would observe it within the 28-day period after surgery.	Outcome assessment will be performed by independent researchers.
Delirium duration days (Postoperative delirium defined by the confusion assessment method for the ICU (CAM-ICU))	Within the first 7 days after surgery

Trial Locations

Locations (7)

West China Hospital affiliated to Sichuan University; 🇨🇳 Chengdu, Sichuan, China

The Third Affiliated Hospital of Kunming Medical University; 🇨🇳 Kunming, Yunnan, China

Shenzhen People's Hospital; 🇨🇳 Shenzhen, Guangdong, China

The affiliated Hospital of Guizhou Medical University; 🇨🇳 Guiyang, Guizhou, China

Henan Provincial People's Hospital; 🇨🇳 Zhengzhou, Henan, China

Taihe Hospital affiliated to Hubei University of Medicine; 🇨🇳 Shiyan, Hubei, China

Sichuan Provincial People's Hospital; 🇨🇳 Chengdu, Sichuan, China