NMTSimulator

The Testbench platform tool is designed to show its validity in the definition of the performance of an NMT (NeuroMuscular Transmission)  control algorithm. Once developed, a considerable number of test cases is carried out in order to prove its validity, first in the Patient´s model behaviour and then the control algorithm. There is on going work in the definition of the algorithm, but the objectives of VALU3S in the development of this tool have been fully achieved. PATIENT SIMULATOR TESTS The Testbench platform tool has been successfully tested and shows its validity in the definition of the performance of a control algorithm. It has been carried out a considerable number of test cases in order to prove its validity, first in the Patient´s model behaviour and then the control algorithm. For this purpose, the best control algorithm can be identified and tested. There will be on going work in the ultimate definition of the algorithm,outside VALU3S project, but the objectives of VALU3S in the development of this tool have been fully achieved.
Improved
Includes a Simulator of a human patient's neuromuscular transmission. The tools is used for experiments with various anesthesia strategies.

In order to verify the correct behavior of the simulator, the simulator can be run with different patient configurations. In these tests, an initial dose of relaxant has been applied to the patient and has been allowed to evolve (without applying additional doses) until complete recovery.

The tests have been carried out in series where a single parameter of the simulation is varied, in order to verify that the effects of said parameter are consistent with clinical experience.

The modules within the simulation infrastructure are the following:

  • Test Case Manager (TCM)
  • NMT Controller (CNT)
  • Patient Model (PATMOD)
  • Infusion pumps (PUMP)
  • and TOF/PTC Sensors (SENSOR)

 

These modules have been provided by different partners, so it was decided to interoperate between the modules using a protocol constructed on designated platform REDIS. REDIS database provides data storage capability as well as message broadcasting.

The experimental testbench was intended to work in two main regimes:

  • fully simulated - all participants are simulated, including CNT.
  • hardware in the loop - CNT is real, Pumps&Sensors are optionally real or simulated.

TCM is supposed to implement:

  • maintain library of defined test cases
  • perform automated testing, i.e. run simulation experiments)
Development of a new distributed simulator environment for integration of patient model, anesthesia controller, infusion pumps and TOF/PTC measurement sensor.
Test Bench PLatform for NMT best performance Controller algorithm
NMT Infusion Controller

Some 

PATIENT SIMULATIONS

In order to verify the correct behavior of the simulator, the simulator has been run with different patient configurations. In these tests, an initial dose of relaxant has been applied to the patient and has been allowed to evolve (without applying additional doses) until complete recovery.

The tests have been carried out in series where a single parameter of the simulation is varied, in order to verify that the effects of said parameter are consistent with clinical experience.

Volume of Distribution (Vd)

When the drug is injected into the patient, it is dispersed in a volume known as the “volume of distribution” and is expressed in ml/kg.

In the following graphs we see how both the concentration of the drug in plasma (CP) and the neuromuscular transmission (NMT) evolve depending on the different Vd of the patient.

We can see how as Vd increases the concentration of the drug in the plasma decreases. Logically, its concentration is lower as the volume where the drug is distributed is greater.

The behavior of the NMT recovery is also logical. As Vd increases (and therefore Cp decreases) the time over which the drug takes effect decreases.

Plasma Concentration Cp50

Cp50 is the plasma concentration which would, at steady state, produce 50% depression of NMT response. This means that the lower the Cp50, the more sensitive the patient is to the drug.

In the following graph we see how neuromuscular transmission (NMT) evolves depending on the different Cp50 of the patient.

In the graph, it can be seen that the recovery time increases with a lower Cp50. This is consistent with the actual behavior of patients, since the patient who is more sensitive to the drug (<Cp50) needs less drug plasma concentration to have the same effect on NMT and therefore takes longer to recover the NMT.

Initial Dose

In the following graphs we see how both the plasma drug concentration (CP) and the neuromuscular transmission (NMT) evolve as a function of different initial drug doses.

The higher the dose, the higher the concentration in plasma and therefore the longer the drug remains in the patient, prolonging his recovery.

NMT CONTROL (STRATEGY CONTROL ALGORITHM 1

Once the correct operation of the patient simulator has been verified, we will apply it to evaluate Dr. Biro's NMT control strategy.

In order to assess the effectiveness of the strategy, several controls are performed by varying the patient's parameters of Vd and Cp50. The following graphs show the results obtained.

 

Tabla 1.  Control data with control algorithm 1

 

Target PTC

Media PTC

(sd)

PTC Above (%)

PTC Below (%)

PTC Target (%)

Vd = 20 ml/kg

4

3.94

1.4

31

48

21

Vd = 38 ml/kg (*)

4

4.5

1.05

45

25

30

Vd = 70 ml/kg

4

5.53

1.46

71

3

26

Cp50 = 0.6 µg/mL

4

4.22

1.56

41

42

17

Cp50 = 0.8 µg/mL (*)

4

4.5

1.05

45

25

30

Cp50 = 1.3 µg/mL

4

5.25

1.15

67

8

25

(*) Are the same control.

With this control algorithm, the control strategy is best achieved when the patient's configuration matches standard values ​​(Vd = 38 mL/kg, Cp50 = 0.8 µg/mL). In this case, the standard deviation is the lowest (1.05) and the time spent on target is also the highest (30%).

When the patient's configuration is not very sensitive to the drug (high Vd or high Cp50), then the dose applied by this strategy is insufficient and the NMT value remains above the target for a long time (71% and 67%).

When the patient's configuration is very sensitive to the drug (low Cp50) then the dose applied by this strategy causes large variations in the NMT value (its standard deviation is very large 1.56).




Simulation of NMT Infusion Control.bmp

The NMT control algorithm has been embedded in our VISION AIR monitor, and is capable of performing the simulated tests in near to real conditions, but yet under laboratory regime. 

  • Conference paper accepted for publication. "Simulation setup for a closed-loop regulation of neuro-muscular blockade", https://eurocast2022.fulp.ulpgc.es/
Relationships with other web-repo artefacts
Improvement Classification
Simulation environment functionality, Simulation-level system robustness, Simulation environment quality
Coverage of test set, Number of test cases
Open source - Goals
Yes
Safety, Functional Requirements
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