Clinical trial NCT02213380: Effect of Anesthesia on Post-operative Delirium in Elderly Patients Undergoing Hip Fracture Surgery
Official title: Effect of Regional Anaesthesia and General Anaesthesia on Postoperative Delirium in Elderly Patients Undergoing Hip Fracture Surgery: a Multicenter Randomized Controlled Trial.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Post Operative Delirium
Keywords: delirium
general anesthesia
regional anesthesia
elderly patient
hip fracture
Lead sponsor: Wenzhou Medical University
Sponsor class: OTHER
Collaborators: name: National Research Institute for Family Planning, China
First posted: 2014-08-11
Enrollment: 950
Sex: ALL
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The purpose of this study is evaluate postoperative delirium after general anesthesia and regional anesthesia in elderly patients undergoing hip fracture surgery. Our research hypotheses are: (1) regional anesthesia may contribute to decrease the incidence of postoperative delirium. (2) Regional anesthesia may improve the outcome of elderly patient and reduce healthcare costs associated with postoperative delirium. (3) Postoperative delirium may result in poor long-term functional outcomes.

Detailed description: Postoperative delirium (POD) is an acute confusional state associated with changes in consciousness, arousal level and cognitive status. Elderly patients with hip fractures have the high incidence of delirium. The high risk factor of delirium include: Age 65 years or older, cognitive impairment/dementia, current hip fracture, severe illness and so on. Many previous studies predict that the majority of general anesthetic and sedative agents can favour postoperative delirium. However, none of studies have investigated the effect of general anesthesia and the effect of regional anesthesia and general anesthesia on the postoperative delirium in elderly patients undergoing hip fracture surgery in China. This multicentre, prospective, randomized controlled clinical trial is designed to evaluate postoperative delirium after general anesthesia and regional anesthesia in elderly patients undergoing hip fracture surgery. Our research hypotheses are: (1) regional anesthesia may contribute to decrease the incidence of postoperative delirium. (2) Regional anesthesia may improve the outcome of elderly patient and reduce healthcare costs associated with postoperative delirium. (3) Postoperative delirium may result in poor long-term functional outcomes.

This trial has the following nine investigational centers: Department of Anesthesiology, The Second Affiliated Hospital \& Yuying Children hospital of Wenzhou Medical University, Wenzhou, China; Department of Anesthesiology, Tongji Hospital, Tongji Medical college, Huazhong University of Science \& Technology, Wuhan, China; Department of Anesthesiology, West China Hospital of Sichuan University, Chengdu, China; Department of Anesthesiology, Southwest Hospital, Chongqing, China; Department of Anesthesiology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China; Department of Anesthesiology, Beijing Jishuitan Hospital, Beijing, China; Department of Anesthesiology, The First Affiliated Hospital of Nanchang University, Nanchang, China; Department of Anesthesiology, The Second Hospital of Anhui Medical University, Anhui, China; The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China;

Eligible patients will be assigned into two study groups (group RA: regional anesthesia will be used, group GA: General anesthesia will be used) by centre-minimization randomization (web or telephone). There are 3 stratification factors: age (65-79,≥80), presence of delirium(yes, no), dementia(yes, no). There will be two teams of investigators involved in trial procedure and the patient's follow-up. Investigator A (experienced anesthetist), who are competent in caring for patients undergoing hip fracture surgery, will perform following works, which includes informed consent, randomization, anesthesia and recovery parameters. Investigator B will visit patient the day before surgery and 7days after surgery or until discharge to assess patient for presence, type and severity of delirium, collect other data during in hospital stay and follow up patients at 6 and 12 months. Investigator B will receive uniform training of using of CAM, Delirium Rating Scale-Revised-98 (DRS-R-98), MMSE and other test used in this trial) and will be not clear about protocol.

Within 24 h before surgery, cognitive function of each patient will be assessed with the MMSE, the presence of delirium will be diagnosed with the CAM, the type and severity of delirium will be assessed with DRS-R-98 and the pain will be assessed with a 100-mm visual analog scale (VAS). Routine monitoring (NBP, continuous ECG, and pulse oximetry) was initiated on all patients. Premedication for anesthesia will be avoided before surgery. Any medication impairing cognitive function will not be recommended, if administered, must be recorded it in detail.

Investigator A will allocated the patient into group GA or group RA according the centre-randomization with a unique registration number for each eligible patient. Treatment protocols for both groups will also stipulate no sedative be administrated during operation. Routine monitoring was initiated on all patients. Hypotension (Systolic Blood Pressure\<90mmHg or drop of Mean Arterial Pressure\>30%) should be treated with vasoactive agents or fluid boluses as deemed appropriate by anesthetists.

Postoperative analgesia will be administered according to the local procedures of each clinical trial site, aiming to maintain a VAS pain score ≤ 30 mm. Both groups will receive routine postoperative care on orthopedic ward.

All randomized patients will be followed up to 7 days after surgery (or discharge from the hospital). The 7 days follow-up includes: CAM, DRS-98-R (if applicable), VAS, Analgesic use (if applicable), Sedative use (if applicable), Post-operative morbidity and laboratory results (including serum hemoglobin, hematocrit, leucocytes, aspartate aminotransferase (AST), alanine aminotransferase (ALT), albumin, serum creatinine and urea concentrations, serum sodium and potassium and serum glucose concentration). Concomitant medications, adverse events and serious adverse events are record in all study visits. Economic parameters include: time to be discharged from post operation, total cost in hospital and cost for anesthesia of patient. Investigator B will also assess patient with POD in clinic or at their residence at 6 and 12 months to assess for presence of delirium, its type and severity (CAM, DRS-98-R), cognitive function using MMSE, and quality of life using The MOS 36-item Short-Form Health Survey (SF-36) questionnaire.

The study will be monitored regularly by the clinical research associate (CRA) through visits or telephone. CRA will verify the consistency of the data recorded on the case report forms with the source documents and the management of therapeutic batches, the presence and completeness of the investigator file.

Eligibility criteria: Inclusion Criteria:

* older patient (≥65 years)
* patient with hip fracture and planned hip fracture surgery
* patient willing to complete this study.

Exclusion Criteria:

* patient with multiple trauma or multiple fractures, pathological fractures, pelvic fractures, femur fractures
* contraindication (serious illness or medical conditions) for general anesthesia
* contraindication (infection at the site of needle insertion, coagulopathy, international normalized ratio \>1.4, platelet count \<80×109 litre-1, allergy to local anaesthetics and so on) for regional anesthesia;
* patient who cannot complete the preoperative mental tests (CAM and/or Mini-Mental State Examination (MMSE)) of this clinical trial
* patient known to susceptible to malignant hyperthermia
* known allergy or hypersensitivity to any drugs administered during this clinical trial
* previous participation in this clinical trial
* participation in another clinical trial within 4 weeks prior to selection

Primary outcomes:
measure: Number of Participants With Post-operative Delirium in 7 Days Post Operation
timeFrame: in 7 days post operation
Secondary outcomes:
measure: Number of Participants With Post-operative Delirium
timeFrame: within fist 7days post operation
measure: Severity of Delirium
timeFrame: within first 7days post operation
measure: The Subtypes of Delirium Diagnosed in 7 Days Post Operation
timeFrame: within first 7 days post operation
measure: 30 Day Mortality
timeFrame: 30 days after surgery
measure: Acute Pain Score Using Visual Analogue Scale (VAS)
timeFrame: In 7days post operation
measure: Length of Hospital Stay
timeFrame: till the day of discharge from hospital, an average of 7 days
measure: Costs of Anesthetic Procedure
timeFrame: 1 day after operation
measure: Total In-hospital Costs
timeFrame: till the day of discharge
measure: 6 Months Incidence of Delirium
timeFrame: 6 months after discharge
measure: 12 Months Incidence of Delirium
timeFrame: 12 months after discharge
measure: 6 Months Quality of Life
timeFrame: 6 months after discharge
measure: 12 Months Quality of Life
timeFrame: 12months after discharge
Other outcomes:
Locations:
city: Hefei
country: China
facility: The Second Hospital of Anhui Medical University
state: Anhui
city: Wuhan
country: China
facility: Tongji Hospital, Tongji Medical college
state: Hubei
city: Nanchang
country: China
facility: The First Affiliated Hospital of Nanchang University
state: Jiangxi
city: Chengdu
country: China
facility: West China Hospital of Sichuan University
state: Sichuan
city: Hangzhou
country: China
facility: The Second Affiliated Hospital of Zhejiang University School of Medicine
state: Zhejiang
city: Lishi
country: China
facility: The People's Hospital of Lishi
state: Zhejiang
city: Lishui
country: China
facility: The Central Hospital of Lishui City
state: Zhejiang
city: Ningbo
country: China
facility: Ningbo No.2 Hospital
state: Zhejiang
city: Ningbo
country: China
facility: Ningbo No.6 Hospital
state: Zhejiang
city: Taizhou
country: China
facility: Taizhou Hospital of Zhejiang Province
state: Zhejiang
city: Wenzhou
country: China
facility: The First Affiliated Hospital of Wenzhou Medical University
state: Zhejiang
city: Beijing
country: China
facility: Beijing Jishuitan Hospital
city: Chongqing
country: China
facility: Southwest Hospital
Study officials:
affiliation: The Second Affiliated Hospital & Yuying Children hospital of Wenzhou Medical University
name: Fang Gao, M.D.
role: STUDY_CHAIR
affiliation: The Second Affiliated Hospital & Yuying Children hospital of Wenzhou Medical University
name: Qingquan Lian, M.D.
role: STUDY_CHAIR
affiliation: The Second Affiliated Hospital & Yuying Children hospital of Wenzhou Medical University
name: Jun Li, M.D.
role: STUDY_DIRECTOR
affiliation: The Second Affiliated Hospital & Yuying Children hospital of Wenzhou Medical University
name: Ting Li, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Heart of England NHS Foundation Trust
name: Joice Yeung, M.D.
role: STUDY_DIRECTOR
affiliation: Heart of England NHS Foundation Trust
name: Teresa Moledy
role: STUDY_DIRECTOR
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