Materials and methods
postoperative pain, stroke, aortic regurgitation, infection, mean, systolic and diastolic arterial pressure, hypotension, hypertension, hypotensive
CARDIAC ARRHYTHMIAS, COAGULATION DISORDERS, LOCAL INFILTRATION, STROKE, EVENT, PERMANENT ATRIAL FIBRILLATION, AORTIC REGURGITATION, COMPLICATIONS, INFECTION, SECONDARY, EVENTS, HYPERTENSION, HYPOTENSIVE, EDWARDS
This study was a single-centre RCT registered at ClinicalTrials.gov (identifier NCT04547491) and conducted at the IRCCS Policlinico Universitario Agostino Gemelli Foundation (Rome, Italy) in accordance with Good Clinical Practice guidelines and the principles of the Declaration of Helsinki. The study was approved by the Institutional Ethics Committee (ID 3672, protocol N. 0049955/20) and registered in ClinicalTrials.gov (identifier NCT04547491). The full protocol and datasets are available at lucfras75@hotmail.com on a collaborative basis.The inclusion criteria were patients ≥ 18 years old with American Society of Anesthesiologists (ASA) physical status II-IV, scheduled to major gynaecologic oncologic surgery with expected duration > 2 h under GA and planned continuous invasive blood pressure monitoring. Exclusion criteria were significant cardiac arrhythmias, such as permanent atrial fibrillation, aortic regurgitation, coagulation disorders, emergency surgery, preoperative infection, the requirement of dialysis, contraindication to radial artery cannulation and patient’s refusal of the treatment of personal data.Eligibility of consecutive patients scheduled to major gynaecologic oncologic surgery fulfilling the inclusion criteria was assessed by an investigator involved in the trial based on preoperative medical records. Written informed consent was obtained from the enrolled patients the day prior to surgery by a study staff member and enrolment ceased when the target sample size was obtained.Randomization codes to the HPI group or to the GDT group (Control group) were generated, in a 1:1 ratio, by an independent research team member, using a reproducible web-based system that uses the pseudo-random number generator of Wichmann and Hill as modified by McLeod (On arrival at the operating room, a large-bore venous catheter was inserted in a forearm vein. Standard monitoring (Life Scope TR, Nihon Kohden Co, Tokyo, Japan) included a 5-lead electrocardiogram, pulse oximetry and a non-invasive blood pressure cuff placed on the left arm. In all study participants, after mild sedation with midazolam and local infiltration with Lidocaine 2%, an arterial catheter was placed in the right radial artery before induction.Patients in the HPI group received invasive blood pressure monitoring with the Acumen IQ sensor transducer connected to the HemoSphere platform (Edwards Lifesciences, Irvine, CA). Patients in the Control group had a Flotrac sensor transducer connected to the EV1000 platform (Edwards Lifesciences). In both groups, the arterial pressure waveform was measured continuously with a sampling rate of 100 Hz. The HemoSphere and the EV1000 monitors displayed hemodynamic parameters calculated from the waveform every 20 s, including the HPI (that was detected only by the HemoSphere used in the HPI group). The signal quality of the arterial waveform was carefully checked with a fast flush test when starting the monitoring. Hemodynamic parameters displayed on both dedicated monitors (HemoSphere for HPI-group and EV1000 for Control-group) included mean, systolic and diastolic arterial pressure (MAP, SBP, DBP), heart rate (HR), stroke volume (SV), stroke volume index (SVI), stroke volume variation (SVV), pulse pressure variation (PPV), CO and cardiac index (CI).All patients were offered central neuraxial anesthesia for postoperative pain management, either intrathecal morphine 100 μg for expected laparoscopic surgery or T12-L1 epidural catheter placement for expected laparotomic surgery.Induction of GA was performed with propofol 2–3 mg·kgAll physicians involved in the study were trained on the use of the HPI and were informed about the study protocol. In the HPI group, the HPI parameter was displayed on the HemoSphere screen in addition to other hemodynamic parameters. Intraoperatively, a researcher was dedicated to recording any details related to the surgery or anesthesia. When the HPI reached the value of 85 or more, the number blinked red, and an audible alarm alerted the anaesthesiologist to the risk of hypotension. In this eventuality, the HemoSphere monitor with the Acumen software displayed a secondary screen with the following additional variables: SVV (already present in the basic screen), the peak rate of arterial pressure (dP/dtTreatment algorithm for the two groups. In HPI group (Panel In the Control group the anaesthesiologists applied perioperative GDT according to the institutional optimization protocol (Fig. The primary outcome measure was the time-weighted average (TWA) MAP under 65 mmHg during surgery. The TWA combines the number, duration, and severity of hypotensive events, corrected for the total time of measurement (“amount of hypotension”) [In order to evaluate the potential risk of overtreatment in the HPI group, we included the incidence of hypertension (defined as MAP > 110 mmHg) and severe hypertension (MAP > 130 mmHg) as the TWA-MAP above the thresholds of 110 and 130 mmHg during the entire monitoring time [Treatment choice (vasopressor, inotrope, fluids, erythrocyte transfusion) and cumulative administered dose in response to an alarm in the HPI group and to hypotension in the Control group was also evaluated and compared, as well as time from alarm to start of an intervention in the HPI group and from the onset of hypotension to start of treatment in the Control group. An alarm was deemed present when the HPI prediction value reached 85 or higher for at least 1 min and ended when the value normalized (< 85) for at least 1 min. Time to first intervention was used in case of multiple treatments to an alarm or hypotensive event; all alarms or hypotensive events per patient were considered for this analysis. All alarms or hypotensive events per patient were used for the analysis.Intraoperative exploratory outcomes included the amount of crystalloid and colloid infusion, and cumulative dose of vasoactive drugs. Postoperative exploratory outcomes included the occurrence of major complications before hospital discharge, and mortality at 30 days.