Noradrenaline Versus Standard Blood Pressure Management for Perioperative Hypotension in Non-cardiac Surgery (HYP-NOR)

Jagiellonian University

Status and phase: Enrolling; Phase 3

Conditions: Intraoperative Hypotension; Non-cardiac Surgery; Blood Pressure Management

Treatments: Combination Product: standard blood pressure management; Drug: noradrenaline infusion for management blood pressure

Study type: Interventional

Funder types: Other

Identifiers

NCT06885268

HYP-NOR

2023-508255-39-00 (EU Trial (CTIS) Number)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 750 estimated patients

Sex: All

Ages: 45+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

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

Exclusion criteria

1. 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
2. Persistent difference in recorded SBP between right and left upper limb >10 mm Hg
3. Persistent atrial fibrillation
4. Have a documented history of dementia
5. Have language, vision, or hearing impairments that may compromise cognitive assessments
6. Have a condition that precludes routine blood pressure management such as surgeon request for relative hypotension
7. Receiving irreversible nonselective monoamine oxidase inhibitors (e.g. tranylcypromine, phenelzine) within 2 weeks preceding study enrolment
8. The use of tricyclic antidepressants
9. Have Prinzmetal angina
10. Have contraindications to noradrenaline per clinician judgement
11. Noradrenaline infusion started before surgery or plan to use continuous noradrenaline infusion throughout the procedure
12. Treating physician (surgeon/anaesthetist) decides on the necessity of extended continuous hemodynamic monitoring during or after surgery
13. Severe kidney disease (MDRD creatinine clearance <15 mL/min/1.73m2) or renal replacement therapy
14. End-stage heart failure: defined as NYHA Class IV - severe limitations in daily activity. Patients experience symptoms even while at rest. Mostly bedbound patients.
15. 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).
16. Emergency and urgent surgery defined as performed within 24 hours of sudden illness/unplanned admission to hospital
17. Have previously participated in the trial: patient already took a part in the HYP-NOR trial in the past
18. Pregnant or breastfeeding women.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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750 participants in 2 patient groups

Intervention group

Active Comparator group

Description:

In the intervention group, a standardized noradrenaline infusion at a concentration of 10 µg/mL will be initiated 15 to 60 seconds before induction of anaesthesia. The infusion will be titrated and maintained during surgery and postoperatively for up to 4 hours, with a minimum duration of 2 hours, until haemodynamic stability is achieved. Haemodynamic stability is defined as stable blood pressure requiring minimal noradrenaline support of 0.01 µg/kg/min or less for at least 1 hour. We will mandate avoidance of mean arterial pressure decreasing below 60 to 70 mm Hg. Once haemodynamic stability is achieved during the postoperative observation period, noradrenaline infusion may be discontinued. Safety criteria for discontinuation include systolic blood pressure above 180 mm Hg, in which case the infusion will be stopped. If systolic blood pressure is between 140 and 170 mm Hg, dose reduction or continuation at a very low noradrenaline infusion of 0.005 µg/kg/min, approximately 1 mL per h

Treatment:

Drug: noradrenaline infusion for management blood pressure

Control group

Active Comparator group

Description:

Standard blood pressure management reactive to blood pressure values. According to the 2022 ESA/ESC guidelines, patients in the control group will be treated to avoid a mean arterial pressure below 60 to 70 mm Hg. Ephedrine boluses (5 mg per bolus, up to a total intravenous dose of 25 mg) are recommended as first line treatment for hypotension. If hypotension persists, peripheral noradrenaline may be administered. Due to variability in clinical practice regarding the choice and timing of vasopressors and fluid therapy during and after surgery, further protocolization of hypotension management will not be mandated in order to enhance feasibility and generalizability of the trial.

Treatment:

Combination Product: standard blood pressure management