Dexmedetomidine and Long-term Outcomes in Elderly Patients After Cardiac Surgery

Sponsor

Peking University First Hospital (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT03289325

Collaborator

Chinese Academy of Medical Sciences, Fuwai Hospital (Other)

285

Enrollment

Location

Arms

Anticipated Duration (Months)

4.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

A retrospective study showed that intraoperative dexmedetomidine administration was associated with decreased risk of 1-year mortality after cardiac surgery. In a previous randomized controlled trial, 285 elderly patients undergoing cardiac surgery were randomized to receive either perioperative dexmedetomidine or placebo (normal saline) administration. The purpose of this 6-year follow-up study is to investigate whether perioperative dexmedetomidine can improve long-term outcomes in those recruited elderly patients after cardiac surgery.

Condition or Disease	Intervention/Treatment	Phase
Cardiac Surgery Dexmedetomidine Long-term Outcome Mortality Quality of Life	Drug: dexmedetomidine hydrochloride for injection Drug: 0.9% sodium chloride for injection	N/A

Detailed Description

Dexmedetomidine is a highly selective alpha 2-adrenergic receptor agonist that provides anti-anxiety, sedation, and modest analgesic effects. In a retrospective cohort study of patients undergoing cardiac surgery, perioperative dexmedetomidine administration was associated with decreased risk of 1-year mortality. Theoretically, perioperative dexmedetomidine may exert the following favorable for cardiac surgery patients: (1) reduces perioperative opioid consumption and thereby mitigates opioid-induced immunosuppression, (2) dampens hyper-inflammatory response induced by surgery, and (3) improves postoperative sleep quality. However, prospective studies investigating the long-term effects of perioperative dexmedetomidine in cardiac surgery patients are still lacking.

In a previous randomized controlled trial, 285 patients of 60 years or older who were scheduled to undergo coronary artery bypass graft surgery and/or valve replacement surgery were randomized to receive either perioperative dexmedetomidine administration (0.6 microgram/kg in 10 minutes before anesthesia induction, followed by a continuous infusion at a rate of 0.4 microgram/kg/h until the end of surgery, then a continuous infusion at a rate of 0.1 microgram/kg/h until the end of mechanical ventilation) or placebo (normal saline, administered in the same rate or volume for the same duration as in the dexmedetomidine group). The results showed that perioperative dexmedetomidine reduced the incidence of pulmonary complications and shortened the duration of mechanical ventilation after surgery.

The purpose of this 6-year follow-up study is to investigate the effects of perioperative dexmedetomidine on the long-term outcomes in elderly patients after cardiac surgery.

Study Design

Study Type:

Interventional

Actual Enrollment :

285 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Prevention

Official Title:

Impact of Perioperative Dexmedetomidine on Long-term Outcomes in Elderly Patients After Cardiac Surgery: 6-year Follow-up of a Randomized Controlled Trial

Actual Study Start Date :

Dec 1, 2016

Anticipated Primary Completion Date :

Apr 1, 2022

Anticipated Study Completion Date :

May 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: DEX group The active drug (dexmedetomidine hydrochloride for injection) will be administered during a period from before anesthesia induction until the end of mechanical ventilation after surgery.	Drug: dexmedetomidine hydrochloride for injection Before anesthesia, dexmedetomidine hydrochloride for injection (200 ug/2 ml) will be diluted with normal saline to 50 ml (final dexmedetomidine concentration 4 ug/ml). Before anesthesia induction, a loading dose will be administered by intravenous infusion at a rate of [0.9kg] ml/h for 10 minutes (i.e., dexmedetomidine 0.6 ug/kg in 10 minutes), followed by continuous infusion at a rate of [0.1kg] ml/h (i.e., dexmedetomidine at a rate of 0.4 ug/kg/h) until the end of surgery. After surgery, the infusion rate will be decreased to [0.025*kg] ml/h (i.e., dexmedetomidine at a rate of 0.1 ug/kg/h) and continued until the end of mechanical ventilation. Other Names: Aibeining (trade name)
Placebo Comparator: CTRL group The placebo drug (normal saline, or 0.9% sodium chloride for injection) will be administered in the same rate and volume for a same duration as that in the DEX group.	Drug: 0.9% sodium chloride for injection Before anesthesia, 0.9% sodium chloride for injection 50 ml will be prepared. Before anesthesia induction, a loading dose will be administered by intravenous infusion at a rate of [0.9kg] ml/h for 10 minutes, followed by continuous infusion at a rate of [0.1kg] ml/h until the end of surgery. After surgery, the infusion rate will be decreased to [0.025*kg] ml/h and continued until the end of mechanical ventilation. Other Names: Normal saline

Arm

Intervention/Treatment

Experimental: DEX group

The active drug (dexmedetomidine hydrochloride for injection) will be administered during a period from before anesthesia induction until the end of mechanical ventilation after surgery.

Drug: dexmedetomidine hydrochloride for injection

Before anesthesia, dexmedetomidine hydrochloride for injection (200 ug/2 ml) will be diluted with normal saline to 50 ml (final dexmedetomidine concentration 4 ug/ml). Before anesthesia induction, a loading dose will be administered by intravenous infusion at a rate of [0.9*kg] ml/h for 10 minutes (i.e., dexmedetomidine 0.6 ug/kg in 10 minutes), followed by continuous infusion at a rate of [0.1*kg] ml/h (i.e., dexmedetomidine at a rate of 0.4 ug/kg/h) until the end of surgery. After surgery, the infusion rate will be decreased to [0.025*kg] ml/h (i.e., dexmedetomidine at a rate of 0.1 ug/kg/h) and continued until the end of mechanical ventilation.

Other Names:

Aibeining (trade name)

Placebo Comparator: CTRL group

The placebo drug (normal saline, or 0.9% sodium chloride for injection) will be administered in the same rate and volume for a same duration as that in the DEX group.

Drug: 0.9% sodium chloride for injection

Before anesthesia, 0.9% sodium chloride for injection 50 ml will be prepared. Before anesthesia induction, a loading dose will be administered by intravenous infusion at a rate of [0.9*kg] ml/h for 10 minutes, followed by continuous infusion at a rate of [0.1*kg] ml/h until the end of surgery. After surgery, the infusion rate will be decreased to [0.025*kg] ml/h and continued until the end of mechanical ventilation.

Other Names:

Normal saline

Outcome Measures

Primary Outcome Measures

Overall survival after surgery [Up to 6 years after surgery]
Overall survival after surgery

Secondary Outcome Measures

Major adverse cardiovascular events-free survival after surgery [Up to 6 years after surgery]
Major adverse cardiovascular events include cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, and myocardial revascularization.
Hospital-free survival after surgery [Up to 6 years after surgery]
Event indicates any medical condition that lead to hospitalization after surgery.
Cognitive function in 6-year survivors after surgery [At the 6th year after surgery]
Cognitive function is assessed with Telephone Interview for Cognitive Status-Modified (TICS-M; scores range from 0 to 50, with higher score indicating better cognitive function).
Health related quality of life in 6-year survivors after surgery [At the 6th year after surgery]
Health related quality of life is assessed with the short-form 36-item health survey questionnaire (SF-36). The SF-36 scale measures eight aspects of health status, i.e., physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional, and mental health. It also measures changes of subjective healthy status during the last year (reported health transition). The scores of the above 9 items are calculated separately with scores range from 0 to 100, with higher score indicating better quality.

Eligibility Criteria

Criteria

Ages Eligible for Study:

60 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age of 60 years or older;
Scheduled to undergo cardiac surgery (coronary artery bypass graft and/or valve replacement surgery);
Provide written informed consents.

Exclusion Criteria: Patients who meet any of the following criteria will be excluded.

Preoperative history of schizophrenia, epilepsia, Parkinson syndrome, or severe dementia;
Inability to communicate in the preoperative period because of severe visual/auditory dysfunction or language barrier;
History of brain injury or neurosurgery;
Preoperative sick sinus syndrome, severe bradycardia (HR < 50 bpm), second-degree or above atrioventricular block without pacemaker;
Severe hepatic dysfunction (Child-Pugh class C);
Severe renal dysfunction (requirement of renal replacement therapy);
Other conditions that are considered unsuitable for participation.