RELIEF II Pilot: Low-dose Noradrenaline in Major Surgery

INTERVENTION: Low‐dose intravenous continuous noradrenaline infusion (10mcg/ml) in patients undergoing major surgery, titrated to a target systolic BP (120mmHg or within 10% of the patient’s lowest preoperative systolic BP value, whichever is lower) with a maximum rate of 0.1mcg/kg/min. The study drug infusion will commence on induction and continue for up to 4 hours postoperatively for patients going to the ward via PACU, and up to 24 hours postoperatively for patients being admitted to HDU/ICU. CONDITION: Anaesthesiology ‐ Anaesthetics Blood Pressure during and after surgery; ; Blood Pressure during and after surgery Cardiovascular ‐ Normal development and function of the cardiovascular system PRIMARY OUTCOME: ‐ Inadvertent unblinding[At the end of the case, the anaesthesiologist will be asked which group they think their patient has been allocated to: Noradrenaline, placebo, or uncertain.] ‐ Successful study drug administration [Proportion of patients who have completed the study and without interruption (not according to protocol) of the study drug infusion intraoperatively. If the study drug infusion is interrupted for greater than 5 minutes (not according to protocol), or the infusion is discontinued prior to the end of surgery, reasons for these occurrences will be recorded.] 1. Feasibility endpoints, as defined by:; ‐ Number of eligible patients per week at each centre ; ‐ Consent rate; [Number of eligible patients per week at each centre: Total number of patients consented and randomised to receive study treatment, per week, for each site; ; Consent rate: Number of patients who are approached for consent and choose to participate (and are eligible), divided by the total number of patients who are approached for consent ] SECONDARY OUTCOME: ‐ Adjunctive vasopressor or inotrope therapy ; [Intraoperative and postoperative record of any additional vasopressor or inotropes administered, including total dosages, until cessation of the study drug (up to 4 hours post‐op for PACU, 24 hours for HDU/ICU admission).] ‐ Any drug errors including other drugs being administered via the dedicated arm of the TIVA 3 way giving set through which the study drug is being administered[The anaesthesiologist will document whether any other drug was administered through the dedicated arm of the TIVA 3 way giving set] ‐ Drop‐out rate and reason for drop‐out[If the study drug infusion is ceased prior to the end of surgery or target completion time postoperatively (4 hours for PACU, 24 hours for HDU/ICU admission), this event will be recorded, including the time the study drug was ceased, and the associated reasons ] ‐ Intraoperative urine output ; [Intraoperative total urinary volume (ml) measured via In‐dwelling catheter (IDC), excluding first bladder urinary volume] ‐ Postoperative renal function, as measured by delta‐creatinine ; [Difference between preoperative creatinine and highest postoperative creatinine value within 48 hours (mmol/L) and also at discharge, as measured by pathology blood results.] ‐ Study drug average and peak infusion rate, duration and total volume ; [Intraoperative average study drug infusion rate (ml/min), minimum infusion rate (ml/min), maximum infusion rate (ml/min), total volume of intraoperative infusion delivered (ml), total duration of intraoperative and postoperative study drug infusion (minutes)] ‐ Total intraoperative IV fluid volume ; [Total volume of intraoperative fluid administration (ml), as documented by the anaesthesiologist administering the fluid.] 2. Efficacy endpoints, as defined by: ; ‐ Mean and systolic BP during and after surgery until cessation of study drug infusion ; ‐ Local and systemic complications from study drug administration ; [Intraoperative and postoperative side effects will be monitored: ; [BP measurements Intraoperatively and postoperatively until cessation of study drug infusion, via invasive arterial line: Highest SBP (persisting > 5 minutes), lowest SBP (persisting > 5 minutes), average SBP (mmHg), maximum MAP (persisting > 5 minutes), minimum MAP (persisting > 5 minutes), average MAP (mmHg)] 3. Safety endpoints, as defined by: ; Local ‐ in the absence of a central line, the skin surrounding the peripheral cannula used for study drug administration will be assessed postoperatively on days 0, 1, and 2 or 3 for skin injury, using a scoring system 0‐4, where 0 is none, 1 is minor, 2 is moderate, 3 is moderately severe and 4 is severe or evidence of skin necrosis. ; Systemic ‐ haemodynamic, including severe tachyarrhythmias, bradycardia, hypotension or hypertension, and metabolic, including severe derangements of blood sugar or lactate ; ] INCLUSION CRITERIA: Adults requiring general anaesthesia for non‐cardiac elective surgery, of at least 2 hour duration, and expected hospital stay of at least three days. In addition, patients should be at increased risk of postoperative complications, such as increased age, ASA score 3‐4, history of cardiac disease, or extremes of weight.