Tight Perioperative Blood Pressure Management to Reduce Serious Cardiovascular, Renal, and Cognitive Complications: The GUARDIAN Pilot Trial
Trial Snapshot
- Phase
- Not Applicable
- Status
- Active, not recruiting
- Sponsor
- The Cleveland Clinic
- Enrollment
- 80
- Locations
- 1
- Primary Endpoint
- Intraoperative blood pressure management
Study Overview
Brief Summary
The treatments will be: 1) norepinephrine or phenylephrine infusion to maintain intraoperative MAP ≥85 mmHg, delayed resumption of chronic antihypertensive medications, and a target ward MAP ≥80 mmHg (tight pressure management); or, 2) routine intraoperative blood pressure management and prompt resumption of chronic antihypertensive medications (routine pressure management).
Detailed Description
Consenting patients who take either angiotensin converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), or calcium channel blockers will be asked not to take the medications on the morning of surgery, and instead bring them with them to the hospital. Qualifying patients will be randomized 1:1, with random-sized blocks.
Randomization will be implemented by clinicians in collaboration with research personnel. Arterial catheter transducers will be positioned at the level of the right atrium, and adjusted as necessary if patient position is changed.
The treatments will be: 1) norepinephrine or phenylephrine infusion to maintain intraoperative MAP ≥85 mmHg, delayed resumption of chronic antihypertensive medications, and a target ward MAP ≥80 mmHg (tight pressure management); or, 2) routine intraoperative blood pressure management and prompt resumption of chronic antihypertensive medications (routine pressure management).
Tight pressure management: In patients assigned to tight pressure management, angiotensin converting enzyme inhibitors and angiotensin receptor blockers will not be given the morning of surgery. Other chronic antihypertensives will only be given as necessary to treat hypertension. Clinicians will be encouraged to insert the required arterial catheter before anesthetic induction because much hypotension occurs shortly after anesthetic induction.
A norepinephrine or phenylephrine infusion (in the preferred local concentration) will be prepared, connected to an intravenous catheter, and activated at a low rate. Norepinephrine can be safely given through a central catheter or peripherally.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Prevention
- Masking
- Double (Participant, Outcomes Assessor)
Masking Description
Patients and assessors blinded to intraoperative management, postoperative antihypertensive management, and blood pressures.
Eligibility Criteria
- Ages
- 45 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •≥45 years old
- •Scheduled for major noncardiac surgery expected to last at least 2 hours;
- •Having general endotracheal, neuraxial anesthesia, or the combination;
- •Expected to require at least overnight hospitalization;
- •Are designated ASA physical status 2-4 (ranging from mild systemic disease through severe systemic disease that is a constant threat to life);
- •Chronically taking at least one anti-hypertensive medication;
- •Expected to have direct blood pressure monitoring with an arterial catheter;
- •Cared for by clinicians willing to follow the GUARDIAN protocol;
- •Subject to at least one of the following risk factors:
- •History of peripheral arterial surgery;
- •History of coronary artery disease;
- •History of stroke or transient ischemic attack;
- •Serum creatinine >175 µmol/L (>2.0 mg/dl);
- •Diabetes requiring medication;
- •Current smoking or 15 pack-year history of smoking tobacco;
- •Scheduled for major vascular surgery;
- •Body mass index ≥35 kg/m2;
- •Preoperative high-sensitivity troponin T >14 ng/L or troponin I equivalent;
- •B-type natriuretic protein (BNP) >80 ng/L or N-terminal B-type natriuretic protein (NT-ProBNP) >100 ng/L
Exclusion Criteria
- •Are scheduled for carotid artery surgery;
- •Are scheduled for intracranial surgery;
- •Are scheduled for partial or complete nephrectomy;
- •Are scheduled for pheochromocytoma surgery;
- •Are scheduled for liver transplantation;
- •Require preoperative intravenous vasoactive medications;
- •Have a condition that precludes routine or tight blood pressure management such as surgeon request for relative hypotension;
- •Require beach-chair positioning;
- •Have end-stage renal disease requiring dialysis or estimated glomerular filtration rate (eGFR) <30 ml/min;
- •Have a documented history of dementia;
- •Have language, vision, or hearing impairments that may compromise cognitive assessments;
- •Have contraindications to norepinephrine or phenylephrine per clinician judgement;
- •Have previously participated in this trial.
Arms & Interventions
Tight pressure management
Patients assigned to tight blood pressure control angiotensin converting enzyme inhibitors and angiotensin receptor blockers will not be given the morning of surgery. Other chronic antihypertensives will only be given as necessary to treat hypertension. Norepinephrine or phenylephrine infusion will be infused at a rate sufficient to maintain intraoperative MAP ≥ 85 mmHg.
Resumption of chronic anti-hypertensive medications will be delayed until the third postoperative day unless deemed necessary to treat hypertension or for some other clear indication.
The target for postoperative systolic arterial pressures ≥110 mmHg during the initial three postoperative days.
Intervention: Tight pressure management (Other)
Routine pressure management
ACEIs, ARBs, and/or calcium channel blockers can be given the morning of surgery if deemed appropriate by the attending anesthesiologist. Intraoperative blood pressure will be managed per clinical routine. As usual, chronic anti-hypertensive medications will be restarted shortly after surgery unless contraindicated by hypotension.
Intervention: Routine pressure management (Other)
Outcomes
Primary Outcomes
Intraoperative blood pressure management
Time Frame: Intraoperative
The fraction of time when intraoperative MAP is \<65 mmHg and ≥85 mmHg during surgery.
Postoperative blood pressure management
Time Frame: First 3 postoperative days
Time to restarting routine antihypertensive medications.
Secondary Outcomes
- Intraoperative pressure(Intraoperative)
- Postoperative pressure(Initial 3 postoperative days)