Noradrenaline Versus Standard Blood Pressure Management for Perioperative Hypotension in Non-cardiac Surgery

Official title

The Effect of Noradrenaline Infusion Versus Standard Blood Pressure Management on Perioperative HYPotension in NOn-caRdiac Surgery HYP-NOR Trial

Overview

The effect of noradrenaline infusion versus standard blood pressure management on perioperative HYPotension in NOn-caRdiac surgery. The study aims to determine whether perioperative noradrenaline infusion is superior to standard blood pressure management for the occurrence of perioperative hypotension.

Detailed description

Patients will receive either noradrenaline infusion or standard blood pressure management during and up to 4 hours after surgery. Patients and health care providers will not be blinded to patients' allocation to either arm of the trial. Continuous blood pressure measurements will be secured in all patients who do not have an arterial line already in place for other indications using a non-invasive volume-clamp method. The medical team will not be aware of the continuous blood pressure monitoring and will use solely non-invasive blood pressure measurements at time intervals at least every 5 minutes in the operating room, and at least every 15 minutes in the post-anaesthesia care unit . In each group, patients will receive balanced crystalloids at 4 ml/kg per hour as maintenance fluid during surgery. In mechanical ventilation, a tidal volume of 8 mL/kg predicted body weight will be recommended. Other ventilatory settings, optimisation of volume status, depth of anaesthesia, patient positioning, as well as prompt diagnosis and treatment of reversible causes of hypotension will be prioritised in all patients in adherence with institutional protocols and current standards of practice.

The study aims to determine whether perioperative noradrenaline infusion can reduce exposure to hypotension compared to reactive treatment of hypotension, whether it is more effective in controlling hypotension during the intraoperatively and postoperatively, whether it reduces the risk of postoperative organ dysfunction, and whether it is safe and does not increase the risk of potential complications.

Interventions

• Drug noradrenaline infusion for management blood pressure
  A single concentration of noradrenaline (10 μg/ml) will be initiated 15-60 seconds prior to the induction of anaesthesia, then titrated and maintained until 4 hours after surgery to meet pre-specified mean arterial pressure (MAP) targets. The drug infusion will be started at a dose of 0.01 μg/kg/min and will be titrated to a maximum of 0.1 μg/kg/min. Anaesthesiologists will be advised to use the lowest possible dose of noradrenaline. Avoidance of MAP decreases of \>20% from baseline values or \<
• Combination product standard blood pressure management
  Patients in the control group will receive standard blood pressure management reactive to blood pressure values. In the light of the current ESA/ESC 2022 guidelines, all patients in the control group will be treated to avoid MAP \<60-70 mm Hg. Ephedrine boluses (5 mg each, up to 25 mg total intravenous dose) will be recommended as a first-line hypotension treatment. Subsequent treatment will involve administering peripheral noradrenaline. Notwithstanding, there is a variation in clinical practic

Primary outcome measures

• Perioperative hypotension [Time frame: During and up to 4 hours after surgery]

Secondary outcome measures (11)

• Myocardial Injury after Non-cardiac Surgery (MINS) [Time frame: During hospitalization and up to 30 days after surgery]
• Acute kidney injury fulfilling Kidney Disease Improving Global Outcomes (KDIGO) criteria [Time frame: During hospitalization and up to 30 days after surgery]
• Stroke [Time frame: During hospitalization and up to 30 days after surgery]
• Non-fatal cardiac arrest [Time frame: During hospitalization and up to 30 days after surgery]
• Sepsis [Time frame: During hospitalization and up to 30 days after surgery]
• Death [Time frame: During hospitalization and up to 30 days after surgery]
• Infusion-related reactions [Time frame: During the infusion of noradrenaline and up to 30 days after drug administration, with assessment occurring postoperatively.]
• Days alive and out of hospital [Time frame: 30 days after surgery]
• Clinically important atrial fibrillation [Time frame: During hospitalization and up to 30 days after surgery]
• Major bleeding [Time frame: During hospitalization and up to 30 days after surgery]
• Peripheral ischemia [Time frame: During hospitalization and up to 30 days after surgery]

Eligibility criteria

Inclusion criteria

• ≥45 years old
• Elective or accelerated\* non-cardiac surgery expected to last ≥1 hour and requiring general, neuraxial, or combined general with neuraxial anesthesia
• Expected to stay overnight in the hospital after surgery
• Written informed consent to participate in the HYP-NOR Trial provided
• American Society of Anesthesiologists (ASA) physical status class II or higher.

Exclusion criteria

• Newly diagnosed, untreated, or uncontrolled hypertension -in two measurements on the day before surgery Systolic Blood Pressure (SBP) ≥180 mm Hg or Diastolic Blood Pressure (DBP) ≥110 mm Hg
• Persistent difference in recorded SBP between right and left upper limb >10 mm Hg
• Persistent atrial fibrillation
• Have a documented history of dementia
• Have language, vision, or hearing impairments that may compromise cognitive assessments
• Have a condition that precludes routine blood pressure management such as surgeon request for relative hypotension
• Receiving irreversible nonselective monoamine oxidase inhibitors (e.g. tranylcypromine, phenelzine) within 2 weeks preceding study enrolment
• The use of tricyclic antidepressants
• Have Prinzmetal angina
• Have contraindications to noradrenaline per clinician judgement
• Noradrenaline infusion started before surgery or plan to use continuous noradrenaline infusion throughout the procedure
• Treating physician (surgeon/anaesthetist) decides on the necessity of extended continuous hemodynamic monitoring during or after surgery
• Severe kidney disease (MDRD creatinine clearance <15 mL/min/1.73m2) or renal replacement therapy
• End-stage heart failure: defined as NYHA Class IV - severe limitations in daily activity. Patients experience symptoms even while at rest. Mostly bedbound patients.
• Known severe liver disease: defined as the presence of liver cirrhosis or any of the symptoms of severe liver dysfunction: portal hypertension (esophageal varices, ascites), hepatocellular insufficiency (e.g., jaundice, hepatic encephalopathy) and coagulopathy (prolonged INR/APTT associated with known liver dysfunction).
• Emergency and urgent surgery defined as performed within 24 hours of sudden illness/unplanned admission to hospital
• Have previously participated in the trial: patient already took a part in the HYP-NOR trial in the past
• Pregnant or breastfeeding women.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Poland · 5 centers

• Uniwersyteckie Centrum Kliniczne im. Prof. Kornela Gibińskiego Śląski Uniwersytet Medyczny — Katowice
• 5 Wojskowy Szpital Kliniczny z Polikliniką Samodzielny Publiczny Zakład Opieki Zdrowotnej — Krakow
• Wojewódzki Szpital Specjalistyczny w Olsztynie — Olsztyn
• Uniwersytecki Szpital Kliniczny w Opolu — Opole
• Samodzielny Publiczny Szpital Kliniczny Nr 1 im. Prof. Stanisława Szyszko Śląskiego Uniwer — Zabrze

Identifiers

NCT: NCT06885268 · HYP-NOR · 2023-508255-39-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗