Intraoperative Goal-directed Blood Pressure and Dexmedetomidine on Outcomes

Study Overview
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Brief Summary
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Perioperative organ injuriy remain an important threat to patients undergoing major surgeries. Intraoperative hypotension is associated with an increase in postoperative morbidity and mortality. Whereas individualized intraoperative blood pressure management is likely to decrease the incidence of postoperative organ injury when compared with standard blood pressure management strategy. Dexmedetomidine, a highly selective alpha2 adrenergic agonist, has been shown to provide organ protective effects. This study aims to investigate the impact of intraoperative goal-directed blood pressure management and dexmedetomidine infusion on incidence of postoperative organ injury in high-risk patients undergoing major surgery.

Detailed Description
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The number of patients undergoing surgeries is increasing worldwide. However, some patients develop complications or even die after surgery. Perioperative organ injury is the leading cause of the unfavorable outcomes. Hypotension is not uncommon during major surgery and is highly responsible for the inadequate perfusion and organ injury. A recent study showed that individualized blood pressure management decreases the incidence of postoperative organ injury when compared with standard blood pressure management strategy. Dexmedetomidine is a highly selective alpha2 adrenergic agonist. Previous studies showed that dexmedetomidine provides organ protection in various conditions. In a recent meta-analysis, perioperative dexmedetomidine reduceds the occurrence of postoperative delirium. However, whether it can reduce postoperative complications remains inconclusive. This study aims to investigate the impact of intraoperative goal-directed blood pressure management and dexmedetomidine infusion on the incidence of postoperative organ injury in high-risk patients undergoing major abdominal surgery.

Official Title
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Impact of Intraoperative Goal-directed Blood Pressure Management and Dexmedetomidine on Outcomes of High-risk Patients After Major Abdominal Surgeries: a 2×2 Factorial Randomized Controlled Trial

Conditions
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Blood Pressure, Dexmedetomidine, High-risk Patients, Abdominal Surgery, Postoperative Complications

Intervention / Treatment
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* Drug: Dexmedetomidine
* Drug: Placebo
* Other: Goal-directed blood pressure management
* Other: Routine blood pressure management


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 50 years or older; Scheduled to undergo abdominal surgery under general anesthesia with an expected duration of 2 hours or longer; With a preoperative acute kidney injury risk index of class III or higher (meet 4 or more of the following factors: age ≥56 years, male sex, active congestive heart failure, ascites, hypertension, emergency surgery, intraperitoneal surgery, mild or moderate renal insuffificiency, diabetes mellitus requiring oral or insulin therapy). Exclusion Criteria: Severe uncontrolled hypertension (SBP>180 mmHg or diastolic blood pressure >110 mmHg); Acute or decompensated heart failure, acute coronary syndrome, or stroke within 1 month; Severe bradycardia (heart rate < 50 bpm), sick sinus syndrome, second-degree or higher atrioventricular block without pacemaker, atrial fibrillation, or frequent premature beats; Severe hepatic dysfunction (Child-Pugh C) or chronic kidney disease (glomerular filtration rate <30 ml/min/1.73 m2 or dependent on renal replacement therapy) ; Pregnant; Receiving dexmedetomidine or norepinephrine infusion before surgery; Do not provide written informed consent.

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Factorial Assignment
Interventional Model Description: This is a 2x2 factorial trial
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Placebo+goal-directed blood pressure management<br>Placebo (normal saline) is administered during anesthesia. Blood pressure is maintained within ±10% of baseline with noradrenaline infusion and fluid management. | Drug: Placebo<br>* Loading dose placebo administered before anesthesia induction, followed by a continuous infusion until 1 hour before the end of surgery.<br>* Other names: Normal saline;Other: Goal-directed blood pressure management<br>* Blood pressure is maintained within ±10% of baseline with noradrenaline infusion and fluid management.<br>|
| Experimental: Dexmedetomidine+goal-directed blood pressure management<br>Dexmedetomidine is administered during anesthesia (0.6 mcg/kg for 10 min, then 0.5 mcg/kg/h). Blood pressure is maintained within ±10% of baseline with noradrenaline infusion and fluid management. | Drug: Dexmedetomidine<br>* Loading dose dexmedetomidine (0.6 mcg/kg for 10 min) administered before anesthesia induction, followed by a continuous infusion (0.5 mcg/kg/h) until 1 hour before the end of surgery.<br>* Other names: Dexmedetomidine hydrochloride injection;Other: Goal-directed blood pressure management<br>* Blood pressure is maintained within ±10% of baseline with noradrenaline infusion and fluid management.<br>|
| Placebo Comparator: Placebo+routine blood pressure management<br>Placebo (normal saline) is administered during anesthesia. Blood pressure is managed according to routine practice. | Drug: Placebo<br>* Loading dose placebo administered before anesthesia induction, followed by a continuous infusion until 1 hour before the end of surgery.<br>* Other names: Normal saline;Other: Routine blood pressure management<br>* Blood pressure is maintained according to routine practice, i.e., systolic blood pressure > 90 mmHg or within ±30% of baseline within intermittent ephedrine or phenylephrine.<br>|
| Experimental: Dexmedetomidine+routine blood pressure management<br>Dexmedetomidine is administered during anesthesia (0.6 mcg/kg for 10 min, then 0.5 mcg/kg/h). Blood pressure is managed according to routine practice. | Drug: Dexmedetomidine<br>* Loading dose dexmedetomidine (0.6 mcg/kg for 10 min) administered before anesthesia induction, followed by a continuous infusion (0.5 mcg/kg/h) until 1 hour before the end of surgery.<br>* Other names: Dexmedetomidine hydrochloride injection;Other: Routine blood pressure management<br>* Blood pressure is maintained according to routine practice, i.e., systolic blood pressure > 90 mmHg or within ±30% of baseline within intermittent ephedrine or phenylephrine.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of organ injury and other complications within 30 days after surgery. | A composite endpoint including delirium, acute kidney injury, myocardial injury, and other complications after surgery. | Up to 30 days after surgery. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of organ injury and other complications within 7 days after surgery. | A composite endpoint including delirium, acute kidney injury, myocardial injury, and other complications after surgery. | Up to 7 days after surgery. | 
| Length of stay in the intensive care unit after surgery. | Length of stay in the intensive care unit after surgery. | Up to 30 days after surgery. | 
| Length of stay in hospital after surgery. | Length of stay in hospital after surgery. | Up to 30 days after surgery. | 
| 30-day all-cause mortality. | Rate of death due to any cause within 30 days after surgery. | Up to 30 days after surgery. | 
| Overall survival within 2 years after surgery. | Overall survival within 2 years after surgery. | Up to 2 years after surgery. | 
| Disease-free survival within 2 years after surgery. | Disease-free survival within 2 years after surgery. | Up to 2 years after surgery. | 
| Quality of life of 2-year survivors: WHOQOL-BREF | Quality of life is assessed with with the World Health Organization quality of life scale brief version (WHOQOL-BREF). | At the end of 2 years after surgery. | 
| Cognition function of 2-year survivors. | Cognitive function is assessed with the Telephone Interview for Cognitive Status-Modified (TICS-m). | At the end of 2 years after surgery. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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abdominal surgery, dexmedetomidine, blood pressure management, high-risk patients, postoperative organ injury