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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
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 \<60-70 mm Hg will be required in both groups. Individual baseline MAP value will be defined as resting blood pressure obtained in at least two measurements at the surgery ward on the day before surgery. Noradrenaline will be administered peripherally in all patients who do not have a central venous catheter in place.
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 practice regarding the choice and timing of vasopressors and fluids to be administered during and after surgery, therefore, hypotension treatment will not be further protocolized to increase the feasibility and generalizability of the trial.
Uniwersyteckie Centrum Kliniczne im. Prof. Kornela Gibińskiego Śląski Uniwersytet Medyczny
Katowice, Poland
RECRUITING5 Wojskowy Szpital Kliniczny z Polikliniką Samodzielny Publiczny Zakład Opieki Zdrowotnej w Krakowie
Krakow, Poland
RECRUITINGWojewódzki Szpital Specjalistyczny w Olsztynie
Olsztyn, Poland
Perioperative hypotension
Number of episodes of perioperative hypotension defined as any mean arterial pressure (MAP) reading ≤55 mm Hg in the setting of a continuous blood pressure measurement.
Time frame: During and up to 4 hours after surgery
Myocardial Injury after Non-cardiac Surgery (MINS)
Number of patients who experience MINS defined as any myocardial infarction and any acutely elevated postoperative cardiac troponin judged as resulting from myocardial ischemia using Roche's fifth generation Elecsys hsTnT, with an established cut-off of 20 ng/L combined with an absolute change of 5 ng/L or more (judged as due to ischemia)
Time frame: During hospitalization and up to 30 days after surgery
Acute kidney injury fulfilling Kidney Disease Improving Global Outcomes (KDIGO) criteria
Number of patients who experience an acute kidney injury (fulfilling KDIGO criteria)
Time frame: During hospitalization and up to 30 days after surgery
Stroke
Number of patients who experience a stroke is defined as a new focal neurological deficit thought to be vascular in origin with signs or symptoms lasting more than 24 hours or leading to death. Stroke will be sub-classified into hemorrhagic and non-hemorrhagic stroke.
Time frame: During hospitalization and up to 30 days after surgery
Non-fatal cardiac arrest
Number of patients who experience non-fatal cardiac arrest defined as successful resuscitation from either documented or presumed ventricular fibrillation, sustained ventricular tachycardia, asystole, or pulseless electrical activity (PEA) requiring cardiopulmonary resuscitation, pharmacological therapy, or cardiac defibrillation
Time frame: During hospitalization and up to 30 days after surgery
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Uniwersytecki Szpital Kliniczny w Opolu
Opole, Poland
RECRUITINGSamodzielny Publiczny Szpital Kliniczny Nr 1 im. Prof. Stanisława Szyszko Śląskiego Uniwersytetu Medycznego w Katowicach
Zabrze, Poland
RECRUITINGSepsis
Number of patients who experience sepsis is defined as an increase in SOFA score of 2 or more, with evidence of infection. This outcome includes septic shock defined as sepsis with shock (vasopressor requirement to maintain a mean arterial pressure of 65 mm Hg or greater and serum lactate level greater than 2 mM \[above18 mg/dL\] in the absence of hypovolemia). Infection is defined as a pathologic process caused by the invasion of normally sterile tissue or fluid or body cavity by pathogenic or potentially pathogenic organisms.
Time frame: During hospitalization and up to 30 days after surgery
Death
Number of patients who die of any cause
Time frame: During hospitalization and up to 30 days after surgery
Infusion-related reactions
The number of patients who experience infusion-related reactions, defined as disorders such as flushing, rash, fever, rigors, chills, dyspnoea, bronchospasms, cardiac dysfunction, and anaphylaxis. Grades of infusion site extravasation are defined according to the Common Terminology Criteria for Adverse Events.
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
Number of days when a patient is alive and out of hospital
Time frame: 30 days after surgery
Clinically important atrial fibrillation
Number of patients who experience clinically important atrial fibrillation, defined as new-onset atrial fibrillation or atrial flutter of any duration on an ECG or rhythm strip, which results in angina, congestive heart failure, symptomatic hypotension, or requires treatment with a rate-controlling drug, antiarrhythmic drug, or electrical cardioversion
Time frame: During hospitalization and up to 30 days after surgery
Major bleeding
Number of patients who experience an International Society on Thrombosis and Haemostasis (ISTH) major bleeding
Time frame: During hospitalization and up to 30 days after surgery
Peripheral ischemia
Number of patients who experience peripheral ischemia defined as the fingertip necrosis of upper and lower limbs
Time frame: During hospitalization and up to 30 days after surgery