Clinical trial NCT03346226: How Different Sedatives Affect Hip Fracture Patient's Postoperative Delirium
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Delirium in Old Age
Keywords: Delirium Dexmedetomidine elderly
Lead sponsor: Shanghai Zhongshan Hospital
Sponsor class: OTHER
Collaborators: name: First Affiliated Hospital of Guangxi Medical University
name: The Second Affiliated Hospital of Harbin Medical University
name: The First Affiliated Hospital of Nanchang University
name: Qianfoshan Hospital
name: Shanghai 6th People's Hospital
name: Tang-Du Hospital
name: Second Hospital of Shanxi Medical University
name: The First Affiliated Hospital of Soochow University
name: Shanghai Changzheng Hospital
name: The Fuzhou No 2 Hospital
name: Foshan Hospital of Traditional Chinese Medicine
name: Beijing Jishuitan Hospital
First posted: 2017-11-17
Enrollment: 1000
Sex: ALL
Minimum age (years): 65
Maximum age (years): 90
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Dexmedetomidine group：dexmedetomidine is given to patients under spinal anesthesia until the end of surgery propofol group:Propofol is given to patients uunder spinal anesthesia until the end of surgery
Primary purpose: PREVENTION

Brief summary: 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

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

Eligibility criteria: 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.

Primary outcomes:
measure: occurrence of postoperative delirium in postoperative 72 hours
timeFrame: 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 outcomes:
measure: Consumption of analgesic
timeFrame: record the data of comsumption of analgeisic at 48 hours after operation
measure: Times of intra-operative occurrence of hypotension, bradycardia, hypertension and tachycardia that need treatment.
timeFrame: during the operation
measure: Score of quality of post-operative sleeping
timeFrame: quality of sleeping will be assessed at 9Am during post-operative day 1-3
measure: Hospital stay
timeFrame: record the days of hospital stay at the 30 days after surgery
measure: Post-operative complications besides delirium
timeFrame: observe and evaluate complications at the 30 days after surgery
measure: Mortality up to day 30 post to operation
timeFrame: the data will be collected after 30 days of operation
measure: pain score
timeFrame: Pain score will be evaluated at time point of operation, 1，6，24, 48 hours after operation, using NRS score
Other outcomes:
Locations:
Study officials:
affiliation: Anesthesiology Department of Shanghai Zhongshan Hospital
name: Xue ZhangGang, doctor
role: PRINCIPAL_INVESTIGATOR
References: