Pain detection with bioimpedance methodology from 3-dimensional exploration of nociception in a postoperative observational trial

Although the measurement of dielectric properties of the skin is a long-known tool for assessing the changes caused by nociception, the frequency modulated response has not been considered yet. However, for a rigorous characterization of the biological tissue during noxious stimulation, the bioimpedance needs to be analyzed over time as well as over frequency. The 3-dimensional analysis of nociception, including bioimpedance, time, and frequency changes, is provided by ANSPEC-PRO device. The objective of this observational trial is the validation of the new pain monitor, named as ANSPEC-PRO. After ethics committee approval and informed consent, 26 patients were monitored during the postoperative recovery period: 13 patients with the in-house developed prototype ANSPEC-PRO and 13 with the commercial device MEDSTORM. At every 7 min, the pain intensity was measured using the index of Anspec-pro or Medstorm and the 0-10 numeric rating scale (NRS), pre-surgery for 14 min and post-anesthesia for 140 min. Non-significant differences were reported for specificity-sensitivity analysis between ANSPEC-PRO (AUC = 0.49) and MEDSTORM (AUC = 0.52) measured indexes. A statistically significant positive linear relationship was observed between Anspec-pro index and NRS (r(2) = 0.15, p < 0.01). Hence, we have obtained a validation of the prototype Anspec-pro which performs equally well as the commercial device under similar conditions

Closed-loop control of anesthesia : survey on actual trends, challenges and perspectives

Automation empowers self-sustainable adaptive processes and personalized services in many industries. The implementation of the integrated healthcare paradigm built on Health 4.0 is expected to transform any area in medicine due to the lightning-speed advances in control, robotics, artificial intelligence, sensors etc. The two objectives of this article, as addressed to different entities, are: i) to raise awareness throughout the anesthesiologists about the usefulness of integrating automation and data exchange in their clinical practice for providing increased attention to alarming situations, ii) to provide the actualized insights of drug-delivery research in order to create an opening horizon towards precision medicine with significantly improved human outcomes. This article presents a concise overview on the recent evolution of closed-loop anesthesia delivery control systems by means of control strategies, depth of anesthesia monitors, patient modelling, safety systems, and validation in clinical trials. For decades, anesthesia control has been in the midst of transformative changes, going from simple controllers to integrative strategies of two or more components, but not achieving yet the breakthrough of an integrated system. However, the scientific advances that happen at high speed need a modern review to identify the current technological gaps, societal implications, and implementation barriers. This article provides a good basis for control research in clinical anesthesia to endorse new challenges for intelligent systems towards individualized patient care. At this connection point of clinical and engineering frameworks through (semi-) automation, the following can be granted: patient safety, economical efficiency, and clinicians' efficacy

An open source patient simulator for design and evaluation of computer based multiple drug dosing control for anesthetic and hemodynamic variables

We are witnessing a notable rise in the translational use of information technology and control systems engineering tools in clinical practice. This paper empowers the computer based drug dosing optimization of general anesthesia management by means of multiple variables for patient state stabilization. The patient simulator platform is designed through an interdisciplinary combination of medical, clinical practice and systems engineering expertise gathered in the last decades by our team. The result is an open source patient simulator in Matlab/Simulink from Mathworks(R). Simulator features include complex synergic and antagonistic interaction aspects between general anesthesia and hemodynamic stabilization variables. The anesthetic system includes the hypnosis, analgesia and neuromuscular blockade states, while the hemodynamic system includes the cardiac output and mean arterial pressure. Nociceptor stimulation is also described and acts as a disturbance together with predefined surgery profiles from a translation into signal form of most commonly encountered events in clinical practice. A broad population set of pharmacokinetic and pharmacodynamic (PKPD) variables are available for the user to describe both intra- and inter-patient variability. This simulator has some unique features, such as: i) additional bolus administration from anesthesiologist, ii) variable time-delays introduced by data window averaging when poor signal quality is detected, iii) drug trapping from heterogeneous tissue diffusion in high body mass index patients. We successfully reproduced the clinical expected effects of various drugs interacting among the anesthetic and hemodynamic states. Our work is uniquely defined in current state of the art and first of its kind for this application of dose management problem in anesthesia. This simulator provides the research community with accessible tools to allow a systematic design, evaluation and comparison of various control algorithms for multi-drug dosing optimization objectives in anesthesia

Bioimpedance sensor and methodology for acute pain monitoring

The paper aims to revive the interest in bioimpedance analysis for pain studies in communicating and non-communicating (anesthetized) individuals for monitoring purpose. The plea for exploitation of full potential offered by the complex (bio)impedance measurement is emphasized through theoretical and experimental analysis. A non-invasive, low-cost reliable sensor to measure skin impedance is designed with off-the-shelf components. This is a second generation prototype for pain detection, quantification, and modeling, with the objective to be used in fully anesthetized patients undergoing surgery. The 2D and 3D time-frequency, multi-frequency evaluation of impedance data is based on broadly available signal processing tools. Furthermore, fractional-order impedance models are implied to provide an indication of change in tissue dynamics correlated with absence/presence of nociceptor stimulation. The unique features of the proposed sensor enhancements are described and illustrated here based on mechanical and thermal tests and further reinforced with previous studies from our first generation prototype

Automated drug delivery in anesthesia

Automated drug administration by closed-loop systems has been proposed to optimize drug administration during anesthesia and sedation. Closed-loop systems are able to make decision on their own and try to reach and maintain a preset target. This review describes the milestones and recent development in automated drug delivery systems applicable during sedation, anesthesia and post-operative pain relief

Anesthesia regulation : towards completing the picture

This paper introduces for the first time in literature the complete picture of depth of anesthesia regulatory paradigm. The simulation model proposes to include not only the three anesthesia features: hypnosis, analgesia and neuromuscular blockade, but also to introduce the interaction with the hemodynamic system (cardio-regulatory loops). Disturbances occurring in the operation theatre origin from surgical stimulation, for which profiles are available. A novel addition is the model of nociceptor pathway, recently developed and thus available for analysis. The nociceptor pathway model makes the link between the surgical stimulation and the perception to the patient of its effect. In conclusion, this paper presents a nonlinear multiple input multiple output model for further development of control algorithms in this application field

Modeling and analysis of monitored vs. self-reported postsurgical acute pain in a clinical trial

This work aims to study postsurgical trauma modeling to characterize the physiological process in postoperative pain assessment in an observational trial. The skin impedance data is proposed to be fitted by derived-Cole models, i.e., single and double dispersion models and a distributed model with an inductive term related to sweat glands. These models are motivated by the biological characteristics of the skin, its physiological stratification and the current intra-and extra-cellular pathways. The correlation between the identified parameters with the patient's pain reported using the numerical rating scale (NRS) is analyzed for one patient for all three models. Following the trial, a statistically significant positive linear relationship was observed between the Anspec-Pro index and NRS (r(2) = 0.16, p=0.00), driving the further study of the relationship between the estimated dielectric parameters. The paper focuses to analyze the changes of the coefficients related to the particular clinical data, successfully identified using the non-linear least square procedure. The clinical significance of the results may be related to the individual model parameters for postoperative pain detection, validated on patients. Copyright (C) 2021 The Authors

Experimental measurement of pain stimulus effects in skin impedance

The work presented here validates the hypothesis that skin impedance is a suitable tool for assessing and quantifying nociceptor stimulation (i.e. mechanical and thermal pain stimulus) in awake healthy volunteers in a laboratory environment. The impedance exhibits interesting features such as constant phase, typical of fractional order systems. Additionally, for the first time in the research community we were able to detect and report the existence of pain memory in skin tissue