How Different Sedatives Affect Hip Fracture Patient's Postoperative Delirium

Influence on Incidence of Postoperative Delirium by Various Sedatives in Elderly Patients With Hip Fracture Under Lumbar Anesthesia: A Randomized, Control and Multi-center Trial

the hypothesis is that Dexmedetomidine seems to decrease incidence of post-operative delirium . one possible mechanism is that Dex have a minor influence on cognition, since it has no effect on GABA receptor，another is that Dex could induce a sleep similar to natural sleep, thereby decreasing sleep deprivation and circadian rhythm disorder in post-operative patients.

In this study , investigators devise the two different sedatives(Dexmedetomidine and Propofol)'influence on postoperative delirium in hip fracture elderly participants under spinal anesthesia

Study Overview

• Status: Unknown
• Conditions: Delirium in Old Age
• Intervention / Treatment: Drug: Dexmedetomidine Hydrochloride; Drug: Propofol

Detailed Description

With a complex etiology, delirium is usually caused by various peri-operative stimuli on basis of predisposing factors, including senility, hypoxia and hypotension, pain, drug (such as pethidine, benzodiazepine, anticholinergic, and drug withdrawal), complications prior to surgery, post-operative sleep disorder. As for the mechanism of delirium, the commonly accepted hypothesis includes the decreased central cholinergic neurons function and the inflammation of central nervous system. Most of the hip fracture patients are senile, suffering generally from many complications with exposure to many drugs, and poor in nutritional status with decreased cognitive function even before the surgery in some of them, all of which are risk factors for post-operative delirium. Systematic review suggests that incidence of POD in patients undergoing elective hip arthroplasty is up to 4-53.3%. It is of great importance, therefore, to explore the effective approaches to lower POD incidence in senile patients with operation on hip fracture.

Dexmedetomidine Hydrochloride is a novel highly-selective α2 adrenergic receptor agonist, and its selectivity to α2 receptor is 8 times of that of clonidine. It has multiple functions including sedation, anti-anxiety, hypnosis, analgesia and sympathetic blockade, with a wide application prospect for peri-operative patients. Researches suggest that Dex applied peri-operatively may stabilize blood pressure and heart rate, control intra-operative stress, and decrease post-operative side reactions such as nausea, vomiting, restlessness, delirium and chills. Moreover, advantages of Dex also include analgesia and reduction of opioid usage. Clinical pharmacological characteristics of Dex suggest its possible function to decrease post-operative delirium. Meanwhile, Dex seems to have a minor influence on cognition, since it has no effect on GABA receptor.

Another important feature of it is that Dex induces a sleep similar to natural sleep, thereby decreasing sleep deprivation and circadian rhythm disorder in post-operative patients, and decreasing incidence of post-operative delirium. Researches evaluating the capability of Dex to decrease delirium incidence are focused on ICU sedation post to operation. Riker et al compared the sedative effect between Dex and midazolam in patients with severe mechanical ventilation, revealing a lower delirium incidence in Dex than in midazolam (54.0% vs 76.6%) in patients maintained with the same depth of sedation. Systematic review concludes that Dex in effective to prevent and treat post-operative delirium in ICU patients.

In this study ,the investigators devise the two different sedatives (Dexmedetomidine and Propofol)'influence on postoperative delirium in hip fracture elderly participants under spinal anesthesia

• Study Type: Interventional
• Enrollment (Anticipated): 1000
• Phase: Phase 4

Contacts and Locations

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years to 90 years (Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Acquisition of informed consent,
2. Patients with hip fracture surgery under lumbar anesthesia,
3. Grade II to III based on American Society of Anesthesiologists ASA classification,
4. Age ≥65 and ≤90 years old.

Exclusion Criteria:

1. History of psychiatric disease or a disease needing long-term exposure to psychotropic drugs (dementia, schizophrenia), or history of alcoholic abuse.
2. More than 8 errors in preoperative Simplified Psychology and Mental Status Questionnaire (SPMSQ) , and diagnosed as severe cognitive impairment.
3. CAM positive diagnosed preoperatively.
4. Any cerebrovascular accident occurring within 3 months, such as cerebral stroke or transient ischemic attack (TIA).
5. Systolic pressure < 90mmHg and diastolic pressure < 60mm Hg at the preoperative follow up or HR< 50/minute.
6. History of heat failure or EF<30% as shown by ultrasound cardiogram; degree 2 type 2 and degree 3 atrioventricular block. History of active heart disease (such as acute cardiac infarction, unstable angina pectoris)
7. Severe abnormality in hepatic or renal function (severe abnormality in liver function: more than 2-times increase than upper normal limit in any one of the markers including ALT,, conjugated bilirubin, AST, ALP, total bilirubin; severe abnormality in renal function; Cr clearance<30ml/min), Scr>443μmol/L.
8. Diabetes patients with severe complications of diabetes (Diabetic ketoacidosis, hyperosmolar coma, various infections, macrovascular diseases, and diabetic nephropathy)
9. Patients with severe infection.
10. Postoperative PaO2<60mmHg or SpO2<92%.
11. Participation in clinical trials of other drugs within past 30 days.
12. Disturbed verbal communication, and unable to accomplish the test on cognition.
13. Patients with prosthesis fracture or restoration; hip fracture but complicated with severe trauma in other sites.
14. Being allergic to investigational drug or having contradiction of lumbar anesthesia.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dexmedetomidine Hydrochloride; Dex Group: 0.5 μg/kg of Dex is given 10 minutes before operation through injection pump during 15 minutes. After the operation starts, the initial pumping ratio of Dex is 0.5ug/kg/h and adjusted under BIS surveillance to keep BIS between 70-80 until 30 minutes before the end of surgery. Meanwhile, OAA/S grade is evaluated every 15 minutes to maintain OAA/S at grade 4. If discrepancy occurs, OAA/S prevails.	Drug: Dexmedetomidine Hydrochloride; Dexmedetomidine is given to patients during spinal anesthesia at the dose of 0.5 μg/kg，adjusted the dose to keep BIS between 70-80 until 30 minutes before the end of surgery; Other Names: brand name ：YiSi
Active Comparator: Propofol; Prop Group: Propofol is given with an initial ratio of 2-10mg/kg/h, when the operation starts. Under BIS surveillance, dripping rate is adjusted to keep BIS between 70-80 until 5 minutes before the end of surgery. Meanwhile, OAA/S grade is evaluated every 15 minutes to maintain OAA/S at grade 4. If discrepancy occurs, OAA/S prevails.	Drug: Propofol; Propofol is given with an initial ratio of 2-10mg/kg/h, when the operation starts，adjust the propofol's dose to keep BIS between 70-80 before the end of surgery; Other Names: Brand name：Diprivan or other brands of propofol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
occurrence of postoperative delirium in postoperative 72 hours	Evaluation of delirium is performed by trained investigational assistant who does not know the randomization of patients. Follow up is carried out before operation and at 9Am and 3Pm during post-operative day 1-3 (POD1-3). During follow up, RASS (Richmond Agitation-Sedation Scale, RASS) is used firstly to evaluate sedation of the patients, and for those with ARSS >-4 (-3～+4), the Confusion Assessment Method (CAM) is adopted for evaluation. A case consistent with delirium standard at any time point during follow up is determined to be delirium positive. Diagnosis should be confirmed for a CAM-positive patient by a psychological expert based on DSM-V standard	patient enrolled will be evaluated at 9Am and 3Pm during post-operative day 1-3 (POD1-3).At any time point above，delirium is detected，then the patient will be diagnosed as postoperative delirium. All patients enrolled is Non-delirium before surgery。

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Consumption of analgesic	the patients will receive patient-controlled intravenous analgesia，record the consumption of intravenous analgesia in the 48 postoperative hours	record the data of comsumption of analgeisic at 48 hours after operation
Times of intra-operative occurrence of hypotension, bradycardia, hypertension and tachycardia that need treatment.	assess the adverse effect of anaesthetic	during the operation
Score of quality of post-operative sleeping	Score of sleeping quality is evaluated based on the some questions during follow up	quality of sleeping will be assessed at 9Am during post-operative day 1-3
Hospital stay	the duration from the day of operation to the date meeting discharge criteria as determined by doctor in charge	record the days of hospital stay at the 30 days after surgery
Post-operative complications besides delirium	complications besides delirium ，such as vomiting，nausea，hypotention，hypertention，bradycardia	observe and evaluate complications at the 30 days after surgery
Mortality up to day 30 post to operation	Data for 30-day survival is collected through telephone follow up by the assistant.	the data will be collected after 30 days of operation
pain score	describe severity of the pain the patient feel using Numerical Rating Scale （NRS）	Pain score will be evaluated at time point of operation, 1，6，24, 48 hours after operation, using NRS score

Collaborators and Investigators

• Sponsor: Shanghai Zhongshan Hospital
• Collaborators: The First Affiliated Hospital of Nanchang University; The First Affiliated Hospital of Soochow University; Qianfoshan Hospital; Tang-Du Hospital; The Second Affiliated Hospital of Harbin Medical University; Shanghai Changzheng Hospital; Beijing Jishuitan Hospital; Second Hospital of Shanxi Medical University; Shanghai 6th People's Hospital; First Affiliated Hospital of Guangxi Medical University; Foshan Hospital of Traditional Chinese Medicine; The Fuzhou No 2 Hospital
• Investigators: Principal Investigator: Xue ZhangGang, doctor, Anesthesiology Department of Shanghai Zhongshan Hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): January 1, 2018
• Primary Completion (Anticipated): December 30, 2018
• Study Completion (Anticipated): June 30, 2019

Study Registration Dates

• First Submitted: September 14, 2017
• First Submitted That Met QC Criteria: November 14, 2017
• First Posted (Actual): November 17, 2017

Study Record Updates

• Last Update Posted (Actual): December 13, 2017
• Last Update Submitted That Met QC Criteria: December 11, 2017
• Last Verified: December 1, 2017

More Information

Terms related to this study

• Keywords: Delirium Dexmedetomidine elderly
• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Neurologic Manifestations; Fractures, Bone; Wounds and Injuries; Confusion; Neurobehavioral Manifestations; Neurocognitive Disorders; Leg Injuries; Femoral Fractures; Hip Injuries; Delirium; Hip Fractures; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Analgesics, Non-Narcotic; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Hypnotics and Sedatives; Propofol; Dexmedetomidine
• Other Study ID Numbers: Postoperative Delirium

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No