The TI.VA Algorithm: A First-in-Humans Test. (TIVAly)

The TI.VA Algorithm: Vector Analysis Applied to a Decision-Making Matrix to Model the Reactive Control Strategy During General Anesthesia: a First-in-Humans Test.

The TI.VA algorithm is a new method to titrate the anesthetic drug concentrations whenever the planned level of anesthesia results to be not appropriate to blunt the patient's reaction to surgical stimulation.

TI.VA is a multiple inputs/multiple outputs algorithm. The control variables are the bispectral index (BIS) and the mean arterial pressure (MAP) combined in a decision-making matrix. The optimal range for the two control variables (BIS: 540-60 and MAP: 65-75 mmHg) identified the Optimal Anesthesia Zone (OAZ) at the center of the matrix. Any time one or both control variables escape from the PAZ, the algorithm proposes an intervention on the hypnotic and/or opioid levels (algorithm outputs).

A First-in-Humans study was designed to capture preliminary data on the safety and performance of the TI.VA algorithm.

Study Overview

• Status: Completed
• Conditions: Anesthesia
• Intervention / Treatment: Other: TI.VA algorithm: decision support system

Detailed Description

The TI.VA algorithm is a new method to titrate the anesthetic drug concentrations whenever the planned level of anesthesia results to be not appropriate to blunt the patient's reaction to surgical stimulation.

TI.VA is a multiple inputs/multiple outputs algorithm. The control variables are the bispectral index (BIS) and the mean arterial pressure (MAP) combined in a decision-making matrix (DMM). The optimal range for the two control variables (BIS: 540-60 and MAP: 65-75 mmHg) identified the Optimal Anesthesia Zone (OAZ) at the center of the matrix. Any time one or both control variables escape from the OAZ, the algorithm quantifies the inadequacy of anesthesia level through a vector connecting the patient's current position on the DMM to the central point identified by the coordinates BIS= 50 and MAP = 75mmHg. Thereafter, the analysis of the vector main components allows the generation of two coefficients that are used to set out a balanced intervention on the hypnotic and opioid levels (algorithm outputs).

A First-in-Humans study was designed to capture preliminary data on the safety and performance of the TI.VA algorithm This is a prospective study involving a single cohort of patients without major comorbidity and candidate for minor superficial surgery. All patients received Propofol and Remifentanil administered by TCI systems as part of Total Intravenous Anaesthesia.

The algorithm was tested during maintenance of anesthesia defined as the period between skin incision and completion of surgical resection. In this step of the procedure, the titration strategy for anesthetic drug concentrations was suggested by TI.VA algorithm.

Data was collected automatically using dedicated software.

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Italy
  • Milano, Italy, 20133
    • Fondazione IRCCS Istituto Nazionale dei Tumori

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

The inclusion criteria were: :

• age 18-65 years at the time of recruitment.
• candidates for curative surgery for breast cancer.
• American Society of Anaesthesiologists (ASA) status I/II.

The exclusion criteria were:

• ASA status > II.
• counter-indications for use of the drugs employed in this protocol.
• pregnancy or lactation.
• incapacity to understand the study explanation and sign the informed consent form.

These criteria were selected according to the risk mitigation strategy described in the protocol.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: OTHER
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: TI.VA group; The titration of Propofol and Remifentanil levels will be guided by TI.VA algorithm in the time between skin incision and completion of surgical resection.	Other: TI.VA algorithm: decision support system; TI.VA algorithm uses BIS and MAP values as control variables to suggest the intervention on propofol and remifentanil levels.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Events	An adverse event is defined as any untoward medical occurrence in the study period. Intra-operative adverse events were reported using the institutional incident reporting system. Data was collected in the time between skin incision and the completion of surgical resection.	during the surgical procedure intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Stability of the Control Variables	To characterize the patient's repose to surgery, the TI.VA algorithm uses a Decision-Making Matrix drawn by crossing BIS (Min-max: 0-100, optimal range 40-60 ) and Mean Arterial Pressure (Min-max: 0-150mmHg. Optimal range 65-75mmHg). The Optimal anesthesia zone is defined as the area of the Decision-Making Matrix identify by the optimal range for the two control variables (BIS and MAP). The stability of the control variables during anesthesia was quantified by the percentage of monitoring points registered in the Optimal Anaesthesia Zone during anesthesia. A monitoring point is understood as a value of BIS and MAP recorded at the same time. The system records a monitoring point every 5 seconds. Data was collected in the time between skin incision and the completion of surgical resection.	during the surgical procedure intervention
Performance Error analysis	The performance of the algorithm was assessed using the performance error (PE), median PE (MDPE), median absolute PE (MDAPE), and wobble according to the method of Performance Error. Data was collected in the time between skin incision and the completion of surgical resection.	during the surgical procedure intervention

Collaborators and Investigators

• Sponsor: Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
• Investigators: Principal Investigator: Emiliano Tognoli, MD, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

Publications and helpful links

General Publications

• Brown EN, Lydic R, Schiff ND. General anesthesia, sleep, and coma. N Engl J Med. 2010 Dec 30;363(27):2638-50. doi: 10.1056/NEJMra0808281. No abstract available.
• A.R. Absalom, MMRF Struys. Overview on Target Controlled Infusion and Total Intravenous Anaesthesia. 2Ed. Gent, Academia Press 2019.
• Absalom AR, De Keyser R, Struys MM. Closed loop anesthesia: are we getting close to finding the holy grail? Anesth Analg. 2011 Mar;112(3):516-8. doi: 10.1213/ANE.0b013e318203f5ad. No abstract available.
• Varvel JR, Donoho DL, Shafer SL. Measuring the predictive performance of computer-controlled infusion pumps. J Pharmacokinet Biopharm. 1992 Feb;20(1):63-94. doi: 10.1007/BF01143186.

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 1, 2020
• Primary Completion (ACTUAL): January 31, 2021
• Study Completion (ACTUAL): January 31, 2021

Study Registration Dates

• First Submitted: October 21, 2021
• First Submitted That Met QC Criteria: January 19, 2022
• First Posted (ACTUAL): January 20, 2022

Study Record Updates

• Last Update Posted (ACTUAL): February 3, 2022
• Last Update Submitted That Met QC Criteria: January 19, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Keywords: open feedback control system; Balanced Anaesthesia; Total Intravenous Anaesthesia
• Other Study ID Numbers: INT150/20

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: all IPD that underlie results in a publication
• IPD Sharing Time Frame: Nov 2021
• IPD Sharing Access Criteria: free
• IPD Sharing Supporting Information Type: CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No