Clinical trial NCT05511610: MAAS Method (Minimal-flow Auto-control Anesthesia System) for the Administration of Desflurane and Sevoflurane
Official title: Accuracy of the MAAS Method (Minimal-flow Auto-control Anesthesia System) for the Administration of Desflurane and Sevoflurane in the Anesthetic Maintenance Phase. Prospective and Paired Observational Study.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Anesthesia
Sevoflurane
Desflurane
Low Flow Anesthesia
Keywords: Sevoflurane
Desflurane
Anesthesia, Closed-Circuit
Lead sponsor: Fundación Pública Andaluza para la gestión de la Investigación en Sevilla
Sponsor class: OTHER
First posted: 2022-08-23
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: In the present work the investigators will study the accuracy of the MAAS (Minimal-flow Autocontrol Anesthesia System) method to estimate the percentage of halogenated anesthetic (HA) to be supplied to the anesthetic circuit based on the estimation of HA uptake during the maintenance phase. The investigators will evaluate the accuracy of sevoflurane and desflurane vaporizers to guarantee the administration of that amount of estimated HA, thus guaranteeing the maintenance of the target concentration of HA at the end of expiration: end-tidal target HA% (ettHA%). To do this, the investigators will quantify the number of adjustments that need to be made to each vaporizer to maintain ettHA%. As secondary objectives, the investigators will analyze the time to reach the target concentration of HA, the deviations that occur from that concentration despite the correct application of the method, and the consumption of HA during the procedure.

Through the entire procedure, all participants will be ventilated under a tailored open lung approach (tOLA) strategy.

Detailed description: Halogenated anesthetics (HAs) are the gaseous drugs commonly used in inhalation anesthesia to ensure, among other effects, loss of consciousness or induction of "anesthetic sleep". They are administered in their gaseous state through the anesthesia vaporizers inserted in the anesthesia workstations. Like other gaseous hydrocarbons, HAs contribute to global warming, with the particularity that their global warming potential (GWP) is hundreds of times higher than that of the reference molecule, CO2, especially in the case of desflurane. For this reason, professionals and administrations must be especially sensitive when handling this type of drugs. Indeed, the investigators consider that its use should be questioned in the absence of administration devices capable of minimizing atmospheric emissions, provided that there are adequate therapeutic alternatives.

Currently, there are "universally" available tools that guarantee that these minimum contamination principles can be met in daily practice. The fundamental tool would be the anesthesia circle breathing circuit. Circle circuits are conceived as artificial breathing systems that allow the rebreathing of exhaled gases. Rebreathing exhaled gases, once the CO2 has been removed by means of gas neutralization systems incorporated in anesthesia stations (CO2 absorbers), is safe and effective, and today this mode of administration of the inhalation anesthesia has become the gold standard. The usefulness and efficiency of circle circuits is anesthesiologist-dependent, since the reuse of exhaled gases will depend on the amount of "new" (fresh) medicinal gases that the anesthesiologist allows to enter the anesthesia workstation every minute, by means of the regulation of the fresh gas flow (FGF): the higher FGF, the less reuse of exhaled gases and at the greater surplus of "waste" gases to be evacuated and expelled into the atmosphere. On the contrary, the fewer new gases the anesthesiologist allows to enter the anesthesia workstation, the greater the reuse of exhaled gases, and the smaller the volume of gases expelled into the atmosphere. The administration of inhalation anesthesia through the use of low FGF, known as low flow anesthesia (LFA) techniques, would therefore constitute one of the main contributors to the reduction of HA emissions into the atmosphere.

The majority of anesthesia workstations used in daily practice allow anesthesiologists to work with FGF lower than 500 milliliters per minute (ml/min) or reaching to the closed-circuit anesthesia mode, that modality of inhalation anesthesia in which it is supplied to the system (anesthesia workstation and patient) the amount of gases (ml/min) that are transferred ("lost") from the central compartment (blood and highly perfused organs- HPO) to other compartments due to the principle of partial pressures equilibrium between different compartments (uptake phenomenon by muscle and fat), or metabolic consumption in the case of O2.

Different techniques for administering LFA have been described. The MAAS method (Minimal-flow Autocontrol Anesthesia System) proposes a didactic and easy way to estimate the needs for HA supplementation during the anesthetic maintenance phase, and includes a feasible formulation when adjusting the supply of HA to the system. The maintenance phase would comprise from the moment in which the target concentration of HA in the central compartment is reached, until the moment in which HA stops being administered to the system. During this period, HA keeps on being transferred towards muscle and fat from the central compartment (highly perfused organs (HPO) compartment) following the principle of partial pressures equilibrium. The estimation of HA uptake (HAup) by muscle and fat once the equilibrium state between the anesthesia workstation (respiratory circuit) and the HPO is reached, is based on the calculation HAup (ml/min) =HAfi-HAfe\*MV(ml/min), where HAfi and HAfe state for inspired and expired fraction of HA, respectively; and MV for volume minute.

The estimate of the ml of HA to be supplied to the anesthetic circuit through the FGF, would be done following the formula HAdel (from HA delivered)= HAup (ml/min )\*100% /FGF(ml).

The main objective of this work will be to compare the accuracy of sevoflurane and desflurane vaporizers to guarantee the ettHA% based on the MAAS method, which will be quantified based on the number of adjustments that must be made in each vaporizer to maintain the predefined ettHA% As secondary objectives, the investigators will analyze the time to reach the ettHA%, the deviations that occur from that ettHA% despite the correct application of the method, and the consumption of HA (ml of HA in its liquid phase) during the procedure

METHODS Prospective, paired, observational study with consecutive recruitment of participants to be carried out in a tertiary care teaching hospital (Hospital Universitario Virgen del Rocío, Sevilla). Approval for this study will be sought from the local ethics committee (Ethics Committee of the Hospital Universitario Virgen del Rocío y Virgen Macarena, Seville), and the study will be registered in Clinical Trials prior to the start of recruitment (http://www.clinicaltrials .gov.) Study design Those adult subjects (≥ 18 years) scheduled for robotic urological, coloproctological or gynecological surgery in the investigators´ institution will be included after obtaining the corresponding written informed consent. The participants will be recruited consecutively depending on the availability of the researchers until the estimated sample is completed. Exclusion criteria are detailed in the "Eligibility" section of this document.

Study protocol On the day of surgery, standard monitoring will begin upon arrival in the operating room, including electrocardiography, pulse oximetry, and non-invasive blood pressure monitoring. After conscious sedation with intravenous (IV) midazolam 1 to 2 mg and remifentanil infused 0.03-0.05 µg/kg/min, participants will be pre-oxygenated through a face mask for 5 min under spontaneous ventilation with an inspired fraction of oxygen (FIO2) of 0.8 and a FGF of 6 L/min. General anesthesia will be induced with propofol (1-1.5 mg/kg of predicted body weight \[PBW\]), administer 0.8 mg/kg rocuronium PBW, and proceed with orotracheal intubation (OTI). Patients will be ventilated through a Primus anesthesia workstation (Drager, Telford, PA, USA) using a tidal volume (TV) of 7 mg\*kg-1 PBW. The ventilatory mode used will be volume control, using a tailored open lung approach (tOLA) protective pulmonary ventilation strategy (see below) that will include an inspiration:expiration ratio of 1:2 and a respiratory rate of 12-15 breaths/min to maintain an end-tidal CO2 (etCO2) between 35 and 40 mmHg and an initial PEEP of 5 cmH2O (10 cmH2O in the case of BMI \> 30). A 30% inspiratory pause will be scheduled for all participants. A FGF corresponding with the 10% of minute volume with an inspired FIO2 of 0.5 will be used throughout the procedure. Anesthesia will be maintained with remifentanil 0.03 to 0.05 µg/kg/min and sevoflurane or desflurane, depending on the phase of the study.

Initially sevoflurane will be used, with a minimum alveolar concentration (MAC) ranging from 0.7 to 0.8 adjusted to the patient's age (predefined MAC), to guarantee a Bispectral Index (BIS Quatro; Covidien Ilc, Mansfield, MA, USA) between 40-60. The investigators will establish as an objective for anesthetic maintenance an ettHA% that will correspond to the predefined MAC and will be the parameter used as a reference throughout the study. Rocuronium will be administered to ensure deep neuromuscular blockade during the procedure, and will be monitored by train of four neuromuscular relaxation (TOF-watch®, Organon Ltd., Swords, Co. Dublin, Ireland). Other drugs that will be systematically used enclose dexamethasone 8 mg IV after induction, paracetamol 1 g after induction and 1 g at the end of the procedure (in surgeries lasting \> 2 h); dexketoprofen 50 mg at the end of surgery. Ondansetron 8 mg prior to eduction; and local anesthesia with 0.25% bupivacaine on the access ports. All ventilation parameters will remain stable throughout the study except PEEP, which will be adapted according to tOLA ventilation principles.

Tailored Open Lung Approach strategy The base of this strategy will be: 1) TV of 7 ml/kg of ideal weight (PBW, of the English predicted body weight); 2) performing a systematic alveolar recruitment maneuver (ARM) following the model of Tusman and Ferrando; 3) the use of individualized and optimized positive end expiratory pressure (PEEP), understood as that which guarantees greater compliance of the respiratory system after ARM.

Statistical analysis Statistical analysis will be performed by the principal investigator. For data analysis, the statistical software IBM SPSS Statistics for Windows, version 24 (IBM Corp., Armonk, NY, USA) will be used. The investigators will perform an exploratory analysis of the data, using the mean ± standard deviation or the median with interquartile range for quantitative variables, and will use percentages for the analysis of qualitative variables. The investigators will check the normality of data distribution with the Kolmogorov-Smirnov test or with the Shapiro-Wilk test for variables with less than 50 records. The Student's t test for paired samples will be used to study the behavior of the quantitative variables at different times (intragroup comparisons). To compare intragroup qualitative variables, the Wilcoxon test for paired samples will be used.

Sample's size calculation To calculate the size of the sample, version 4.2 of the statistical program EPIDAT (General Directorate of Innovation and Public Health Management of the Ministry of Health of the Junta de Galicia) will be used. The minimum required sample will be determined based on the results of the study on a pilot sample of 5 paired cases (1st sevoflurane and 2nd desflurane) in which the number of precise changes in the vaporizer to guarantee the stability of the ettHA% will be determined. The sample size will be calculated to obtain a power of 80% to detect differences in the contrast of the null hypothesis h₀: μ₁ = μ₂ using a two-sided Student's t-test for two related samples, considering a level of significance of 5% and assuming the respective standard deviation in each group.

Eligibility criteria: Inclusion Criteria:

* Adult subjects (≥ 18 years) scheduled for robotic urological, coloproctological or gynecological surgery in the investigators´ institution
* Written informed consent

Exclusion Criteria:

* Participation in another interventional study
* Participants unable to understand the information contained in the informed consent
* American Society of Anesthesiologists (ASA) classification grade = IV
* Patient in dialysis
* Chronic obstructive pulmonary disease (COPD) grade Global Initiative for Chronic Obstructive Lung Disease(GOLD) \> 2
* Functional vital capacity \< 60% or \> 120% of the predicted
* Body mass index (BMI) \> 35 kg/m2
* New York Heart Association (NYHA) functional class ≥ 3
* Clinically suspected heart failure
* Diagnosis or suspicion of intracranial hypertension
* Presence of pneumothorax or giant bullae on preoperative imaging tests
* Use of Continuous Positive Airway Pressure (CPAP).

Primary outcomes:
measure: Changes made in the sevoflurane vaporizer
timeFrame: 60 minutes, starting from the end of Phase sevo 1 (once filled the HPO compartment)
measure: Changes made in the desflurane vaporizer
timeFrame: 60 minutes, starting from the end of Phase desflu 1(once filled the HPO compartment)
Secondary outcomes:
measure: Time to reach the ettSEVO%
timeFrame: Immediately after OTI and until completing the Phase sevo 1
measure: Time to reach the ettDESFLU%
timeFrame: Immediately after completing the Washout phase and until completing the Phase desflu 1.
measure: Deviations from ettSEVO% despite the correct application of the method
timeFrame: 60 minutes: starting from the end of Phase sevo 1 until the end of Phase sevo 2
measure: Deviations from ettDESFLU% despite the correct application of the method
timeFrame: 60 minutes: starting from the end of Phase desflu1 until the end of Phase desflu 2
measure: Consumption of HA (ml of HA in its liquid phase) during the procedure
timeFrame: During the procedure: starting pre-intervention and immediately after the procedure
Other outcomes:
Locations:
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocío
Study officials:
affiliation: Hospitales Universitarios Virgen del Rocío
name: Manuel de la Matta, PhD
role: PRINCIPAL_INVESTIGATOR
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