Anaesthetic Management Guided by COMET Measurements (AIMED COMET)

Anaesthetic Management Guided by Cellular Oxygen Metabolism Measurements in Abdominal Surgery: a Randomised Controlled Trial

Surgical site infection (SSI) is a significant cause of morbidity and mortality, prolonged hospital stays and healthcare costs. Perioperative low tissue oxygen tension is associated with a high risk of SSI. Standard anaesthetic management guided by continuous monitoring of oxygen delivery with a non-invasive method of measuring mitochondrial oxygenation tension (mitoPO2) using the Cellular Oxygen METabolism (COMET) monitor may benefit the intraoperative oxygenation on the tissue level. This randomised, controlled, single-centre, parallel-arm, patient-blinded trial aims to investigate if standard anaesthetic management guided by mitoPO2 monitoring results in higher tissue oxygen tension including patients undergoing elective abdominal surgery. Anaesthetists in the intervention group strive to a minimum mitoPO2 of 66 mmHg. Patients in the control group receive standard care. The primary outcome is the difference in means of the mean mitoPO2 during surgery.

mitochondria, mitochondrial oxygenation, tissue oxygenation, microcirculation, surgical site infection, wound infection, abdominal surgery

The mitoPO2 in the control group is covered and made invisible to the anaesthetists. During the procedure, the outcome assessor is present to troubleshoot the device when needed and is also not blinded. Patients, surgeons and healthcare professionals during the postoperative period are blinded to the treatment allocation.

Anaesthetists for patients allocated to the intervention group were asked to strive and maintain the intraoperative mitoPO2 to the individualised preoperative baseline mitoPO2 with a minimum of 66 mmHg

Patients allocated to the control group were treated as per anaesthetist preference and followed our institution's conventional care

Exploration analysis of the correlation coefficients between the intraoperative mitoPO2 and the intraoperative monitoring measurement values

Calculation of the correlation coefficients between the intraoperative mitoPO2 values and the intraoperative values of each monitoring measurement. The measurement pairs are defined as measurements performed within the same time interval. The mean value is used if multiple measurements of the same type have been performed in that time interval. The outcomes are the pooled correlation coefficients of the correlation between the mitoPO2 and each monitoring measure. We going to examine the following monitoring measurements: non-invasive or arterial blood pressure in mmHg, plethysmographic variability index, heart rate, peripheral oxygen saturation, temperature in Celsius, end-tidal oxygen in mmHg, end-tidal carbon dioxide in mmHg and amplitude frequency effect (pulse pressure and heart rate)).

The respective effect per intervention in mitoPO2 after notification in which mitoPO2 aids decision making on anaesthetic management

The potential effects of the anaesthetic interventions on the mitoPO2 values is assessed amongst patients from the intervention group. The anaesthetic interventions of interest are only those given to increase the mitoPO2 values. For all these interventions, we look for the difference between aggregated mitoPO2 values over a period before administering the anaesthetic intervention and aggregated mitoPO2 values over a period when the treatment is active. The lengths of the intervals, the time between intervals, and the type of aggregation are based on the observable patterns in the data. The time between intervals is at least the average time for the anaesthetic intervention to reach maximum plasma concentration; this duration may be longer because the effect could be delayed. If possible, we summarise the effect of the anaesthetic interventions by type and dose.

Effect when using the COMET in sequentially treated patients in mitoPO2 assessed with a mixed effects model

The relationship between the intervention number of patients from the interventions group sequentially treated by one anaesthetist and the mean intraoperative mitoPO2 value. The effect is defined as the average increase in mean intraoperative mitoPO2 when an anaesthetist treats a new patient from the intervention group.

Similair as the primary outcome, but exploring the effect in patients with or without epidural anaesthesia [2].

Similair as the primary outcome, but exploring the effect in patients with open versus laparoscopic surgical procedure [3].

Inclusion Criteria: Patients are at least 18 years old Patients undergo elective open or laparoscopic abdominal surgery with an expected minimal total incision size of 5 cm Patients are able and willing to give written informed consent Exclusion Criteria: Known photodermatoses of varying pathology and frequency Mitochondrial disease Porphyria Skin lesions on the upper arm which impede measurements Hypersensitivity to the active substance or the 5-ALA medicated plaster material Emergency surgery Reoperation for complications from recent surgery (within last three months) Participation in another study with interference with this study Pregnancy or breastfeeding

Kabon B, Fleischmann E, Treschan T, Taguchi A, Kapral S, Kurz A. Thoracic epidural anesthesia increases tissue oxygenation during major abdominal surgery. Anesth Analg. 2003 Dec;97(6):1812-1817. doi: 10.1213/01.ANE.0000087040.48267.54.

Fleischmann E, Kugener A, Kabon B, Kimberger O, Herbst F, Kurz A. Laparoscopic surgery impairs tissue oxygen tension more than open surgery. Br J Surg. 2007 Mar;94(3):362-8. doi: 10.1002/bjs.5569.

Reference 4. de Wijs C, et al. MITOCHONDRIAL OXYGENATION DURING CARDIOPULMONARY BYPASS: A PILOT STUDY [abstract]. Virtual: In: EACTAIC-ICCVA Joint Congress / Journal of Cardiothoracic and Vascular Anesthesia 35 (2021) S1-S21, 2021

http://esicmlives40.process.y-congress.com/ScientificProcess/schedule/?sessionGuid=0e0f17ea-3753-4e89-b3a5-d13e124a6e7b

Reference 5. Hilderink B, et al. Mitochondrial oxygen tension in patients after cardiac surgery: preliminary results [abstract]. Madrid, Spain: In: European society of intensive medicine LIVES 40, 2022