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

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

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.