Nasal cannula and face mask gas flow rates when connecting to the Y-piece of the anesthesia circuit.

STUDY OBJECTIVE: To determine the relationship between the delivered gas flows via nasal cannulas and face masks and the set gas flow and the breathing circuit pressure when connecting to the Y-adapter of the anesthesia breathing circuit and using the oxygen blender on the anesthesia machine, relevant to surgery when there is concern for causing a fire. The flow rates that are delivered at various flow rates and circuit pressures have not been previously studied. DESIGN: Laboratory investigation. SETTING: Academic medical center. PATIENTS: None. INTERVENTIONS: The gas flows from each of 3 anesthesia machines from the same manufacturer were systematically increased from 1 to 15 L/min with changes to the adjustable pressure limiting valve to maintain 0-40 cm water pressure in the breathing circuit for nasal cannula testing and at 20-30 cm water circuit pressure for face masks. MEASUREMENTS: The delivered gas flows to the cannula were determined using a float-ball flowmeter for combinations of set gas flows and circuit pressures after connecting the cannula tubing to the Y-piece of the anesthesia circuit via a tracheal tube adapter. Decreasing the supply tubing length on the delivered flow rates was evaluated. MAIN RESULTS: There was a highly linear relationship between the anesthesia circuit pressure and the delivered nasal cannula flow rates, with 0 flow observed when the APL valve was fully open (i.e., 0 cm water). However, even under maximum conditions (40 cm water and 15 L/min), the delivered nasal cannula flow rate was 3.5 L/min. Shortening the 6.5-ft cannula tubing increased the flow at 20 and 30 cm water by approximately 0.12 L/min/ft. The estimated FiO2 assuming a minute ventilation of 5 L/min and 30% FiO2 ranged from 21.7% to 27.0% at nasal cannula flow rates of 0.5 to 4.0 L/min. When using a face mask and the APL fully closed, delivered flow rates were 0.25 L/min less than the set flow rate between 1 and 3 L/min and equal to the set flow rate between 4 and 8 L/min. CONCLUSIONS: When using a nasal cannula adapted to the Y-piece of the anesthesia circuit, the delivery system is linearly dependent on the pressure in the circuit and uninfluenced by the flow rate set on the anesthesia machine. However, only modest flow rates (≤ 3.5 L/min) and a limited increase in the inspired FiO2 are possible when using this delivery method. When using a face mask and the anesthesia circuit, flow rates close to the set flow rate are possible with the APL valve fully closed. Patients scheduled for sedation for head and neck procedures with increased fire risk who require more than a marginal increase in the FiO2 to maintain an acceptable pulse oximetry saturation may need general anesthesia with tracheal intubation.

Infusiones controladas por objetivo y sistemas de circuito cerrado. Límites en expansión / Target-controlled infusions and closed-loop systems: expansion limits

Introducción: La administración manual en bolo ha evolucionado desde la infusión volumétrica basada en regímenes farmacológicos estandarizados, hasta los sistemas de infusión controlada por objetivo y los más sofisticados sistemas de circuito cerrado. Objetivo: Describir los principios tecnológicos y aplicaciones clínicas extendidas de la infusión controlada por objetivo y los sistemas de circuito cerrado. Métodos: Se realizó una revisión no sistemática de la literatura, en bases de datos científicas como Cochrane Database of Systematic Reviews, Pubmed/Medline, EMBASE, Scopus, Web of Science, EBSCOhost, Science Direct, OVID y el buscador académico Google Scholar, en el mes de septiembre del año 2020. Desarrollo: La disponibilidad y portabilidad de dispositivos electrónicos con capacidad de procesamiento avanzado a precios relativamente accesibles, el perfeccionamiento del aprendizaje automático e inteligencia artificial aplicado a las decisiones médicas, y las iteraciones tecnológicas complejas incorporadas en los sistemas de circuito abierto y cerrado, desarrollados originalmente en el campo de la Anestesiología, han posibilitado su expansión a otras especialidades y entornos clínicos tan disímiles como el tratamiento de la diabetes mellitus, administración de fármacos antineoplásicos, ventilación mecánica, control de las variables hemodinámicas y la terapia antimicrobiana en pacientes críticos. Conclusiones: La infusión controlada por objetivo y los sistemas de circuito cerrado se han convertido en tecnologías maduras, seguras y viables, aplicadas clínicamente en múltiples naciones y escenarios, con un desempeño superior a los sistemas manuales tradicionales(AU)

Introduction: Manual bolus administration has evolved from volumetric infusion based on standardized pharmacological regimens to target-controlled infusion systems and the most sophisticated closed-loop systems. Objective: To describe the technological principles and extended clinical applications of target-controlled infusion and closed-loop systems. Methods: A nonsystematic review of the literature was carried out, during September 2020, in scientific databases such as Cochrane Database of Systematic Reviews, Pubmed/Medline, EMBASE, Scopus, Web of Science, EBSCOhost, Science Direct, OVID and the academic search engine Google Scholar. Development: The availability and portability of electronic devices with advanced processing capacity at relatively affordable prices, the refinement of machine learning and artificial intelligence applied to medical decisions, as well as the complex technological iterations incorporated into open and closed-loop systems, originally developed in the field of anesthesiology, have enabled their expansion to other specialties and clinical settings so diverse as treatment of diabetes mellitus, administration of antineoplastic drugs, mechanical ventilation, control of hemodynamic variables and antimicrobial therapy in critical patients. Conclusions: Target-controlled infusion and closed-loop systems have become mature, safe and viable technologies, applied clinically in multiple nations and settings, with superior performance compared to traditional manual systems(AU)

Estimating the Impact of Carbon Dioxide Absorbent Performance Differences on Absorbent Cost During Low-Flow Anesthesia.

BACKGROUND: Reducing fresh gas flow when using a circle anesthesia circuit is the most effective strategy for reducing both inhaled anesthetic vapor cost and waste. As fresh gas flow is reduced, the amount of exhaled gas rebreathed increases, but the utilization of carbon dioxide absorbent increases as well. Reducing fresh gas flow may not make economic sense if the increased cost of absorbent utilization exceeds the reduced cost of anesthetic vapor. The primary objective of this study was to determine the minimum fresh gas flow at which absorbent costs do not exceed vapor savings. Another objective is to provide a qualitative insight into the factors that influence absorbent performance as fresh gas flow is reduced. METHODS: A mathematical model was developed to compare the vapor savings with the cost of carbon dioxide absorbent as a function of fresh gas flow. Parameters of the model include patient size, unit cost of vapor and carbon dioxide absorbent, and absorbent capacity and efficiency. Boundaries for fresh gas flow were based on oxygen consumption or a closed-circuit condition at the low end and minute ventilation to approximate an open-circuit condition at the high end. Carbon dioxide production was estimated from oxygen consumption assuming a respiratory quotient of 0.8. RESULTS: For desflurane, the cost of carbon dioxide absorbent did not exceed vapor savings until fresh gas flow was almost equal to closed-circuit conditions. For sevoflurane, as fresh gas flow is reduced, absorbent costs increase more slowly than vapor costs decrease so that total costs are still minimized for a closed circuit. Due to the low cost of isoflurane, even with the most effective absorbent, the rate of absorbent costs increase more rapidly than vapor savings as fresh gas flow is reduced, so that an open circuit is least expensive. The total cost of vapor and absorbent is still lowest for isoflurane when compared with the other agents. CONCLUSIONS: The relative costs of anesthetic vapor and carbon dioxide absorbent as fresh gas flow is reduced are dependent on choice of anesthetic vapor and performance of the carbon dioxide absorbent. Absorbent performance is determined by the product selected and strategy for replacement. Clinicians can maximize the performance of absorbents by replacing them based on the appearance of inspired carbon dioxide rather than the indicator. Even though absorbent costs exceed vapor savings as fresh gas flow is reduced, isoflurane is still the lowest cost choice for the environmentally sound practice of closed-circuit anesthesia.

Influence of Remifentanil on the Control Performance of the Bispectral Index Controlled Bayesian-Based Closed-Loop System for Propofol Administration.

BACKGROUND: This study investigated the clinical performance of a model-based, patient-individualized closed-loop (CL) control system for propofol administration using the bispectral index (BIS) as a controlled variable during the induction and maintenance of anesthesia with propofol and remifentanil and studied the influence of the targeted effect-site concentration of remifentanil (CeREMI) on its clinical performance. METHODS: In 163 patients, propofol was administered using a CL system (BIS target [BISTARGET] between 40 and 50). Initial CeREMI targets between 2 and 7.5 ng/mL were selected as deemed clinically required. Performance parameters during induction were the time required to initially cross the target BIS, the time required to reach the maximal drug effect after induction (TPEAK, BIS) and the corresponding BIS at this moment, and the time required to regain the target BIS at the end of induction. Performance during maintenance was defined as the percentage of case time with target BIS ± 10 from target and the amount of performance error (PE) between the observed and target BIS values and its derived median PE (MDPE) as a measure of control bias, median absolute PE (MDAPE) as a measure of control inaccuracy, divergence as a measure of the time-related trend of the measured BIS values relative to the target BIS values, and wobble as a measure of intrasubject variability in prediction error. The secondary end point was the hemodynamic stability of the patient during CL control. RESULTS: The applied CL system induced and maintained anesthesia within clinically accepted ranges. The percentage of case time [mean (standard deviation [SD]) across all study participants] with BIS ± 10 from the target was 82% (14%). The mean (SD) population MDPE and MDAPE were -6.6% (5.5%) and 11.2% (5.5%), respectively. A negative divergence [-0.001 (0.004)] and acceptable wobble [9.7% (4.0%)] were found. The correlation between the system PE and CeREMI was low and only influenced by a CeREMI <2.8 ng/mL. Hemodynamic stability stayed within the clinically acceptable range. CONCLUSIONS: The applied CL system for propofol administration has an acceptable performance in the CeREMI range of 2.8-7.5 ng/mL during the induction and maintenance of anesthesia. There was no evidence of a strong association between CeREM and the CL performance. This study also shows that when the CeREMI is <2.8 ng/mL, it might be more challenging to prevent arousal during propofol anesthesia.

Behavior of a dual closed-loop controller of propofol and remifentanil guided by the bispectral index for postoperative sedation of adult cardiac surgery patients: a preliminary open study.

A dual-loop controller permits the automated titration of propofol and remifentanil during anesthesia; it has never been used in intensive care after cardiac surgery. The goal of this preliminary study was to determine the efficacy of this controller to provide postoperative sedation in 19 adult cardiac surgery patients with a Bispectral Index target of 50. Results are presented as numbers (percentages) or medians [25th-75th percentiles]. The sedation period lasted 139 min [89-205] during which the Richmond Agitation Sedation Scale was at - 5 and the Behavioral Pain Scale score at three points for all patients and observation times but one (82 out of 83 assessments). Sedation time in the range 40-60 for the Bispectral Index was 87% [57-95]; one patient had a period of electrical silence defined as Suppression Ratio at least > 10% for more than 60 s. The time between the end of infusions and tracheal extubation was 84 min [63-129]. The Richmond Agitation Sedation Scale was 0 [0-0], 0 [- 1 to 0], and 0 [0-0] respectively during the 3 h following extubation while the verbal numerical pain scores were 6 [4.5-7], 5 [4-6], and 2 [0-5]. Mean arterial pressure decreased during sedation requiring therapeutic interventions, mainly vascular filling in 15 (79%) patients. Automated sedation device was discontinued in two patients for hemodynamic instability. No patient had awareness of the postoperative sedation period. Dual closed-loop can provide postoperative sedation after cardiac surgery but the choice of the depth of sedation should take into account the risk of hypotension.

Hemodynamic stability of closed-loop anesthesia systems: a systematic review.

INTRODUCTION: This systematic review investigates the effect of closed-loop anesthesia delivery on the maintenance of cardiovascular parameters. The specific challenges arise from the fact that many physiological variables used for the control of anesthetic delivery and maintenance of hemodynamic stability are regulated by the autonomic nervous system, which is subject to high inter-individual variability. EVIDENCE ACQUISITION: A systematic database search (MEDLINE, EMBASE and Web of Science) was conducted following the PRISMA guidelines and the principles of the Cochrane Handbook for Systematic Reviews of Interventions. Identified articles were screened and studies that fulfilled the eligibility criteria using the PICO approach (Patient, Intervention, Comparison, Outcome) were included in a random effects model to calculate weighted mean and 95% confidence intervals. EVIDENCE SYNTHESIS: Twenty studies (1402 subjects: 706 intervention and 696 control) were included in this review. Meta-analysis showed that closed-loop systems achieved longer duration of heart rate and MAP control, at 90.9% (95% CI: 90.0-91.8%) and 88.2% (95% CI: 87.4-89.0%) respectively, compared to the respective manual control group at 86.6% (95% CI: 85.1-88.0%) and 85.1% (95% CI: 84.3-86.0%). Subgroup analysis demonstrated better performance and faster recovery compared to the control group. CONCLUSIONS: The findings support the use of closed-loop systems for anesthetic delivery. Interpretation should take into account limitations, such as the large variations in the selected studies in the type of parameters used to measure outcomes. In summary, this review provides evidence supporting the importance of considering cardiovascular variables in the design of automated anesthetic delivery systems.

Feasibility of Fully Automated Hypnosis, Analgesia, and Fluid Management Using 2 Independent Closed-Loop Systems During Major Vascular Surgery: A Pilot Study.

Automated titration of intravenous anesthesia and analgesia using processed electroencephalography monitoring is no longer a novel concept. Closed-loop control of fluid administration to provide goal-directed fluid therapy has also been increasingly described. However, simultaneously combining 2 independent closed-loop systems together in patients undergoing major vascular surgery has not been previously detailed. The aim of this pilot study was to evaluate the clinical performance of fully automated hypnosis, analgesia, and fluid management using 2 independent closed-loop controllers in patients undergoing major vascular surgery before implementation within a larger study evaluating true patient outcomes.

Perioperative Considerations for Evolving Artificial Pancreas Devices.

Type 1 diabetes mellitus is a lifelong condition. It requires intensive patient involvement including frequent glucose measurements and subcutaneous insulin dosing to provide optimal glycemic control to decrease short- and long-term complications of diabetes mellitus without causing hypoglycemia. Variations in insulin pharmacokinetics and responsiveness over time in addition to illness, stress, and a myriad of other factors make ideal glucose control a challenge. Control-to-range and control-to-target artificial pancreas devices (closed-loop artificial pancreas devices [C-APDs]) consist of a continuous glucose monitor, response algorithm, and insulin delivery device that work together to automate much of the glycemic management for an individual while continually adjusting insulin dosing toward a glycemic target. In this way, a C-APD can improve glycemic control and decrease the rate of hypoglycemia. The MiniMed 670G (Medtronic, Fridley, MN) system is currently the only Food and Drug Administration-cleared C-APD in the United States. In this system, insulin delivery is continually adjusted to a glucose concentration, and the patient inputs meal-time information to modify insulin delivery as needed. Data thus far suggest improved glycemic control and decreased hypoglycemic events using the system, with decreased need for patient self-management. Thus, the anticipated use of these devices is likely to increase dramatically over time. There are limited case reports of safe intraoperative use of C-APDs, but the Food and Drug Administration has not cleared any device for such use. Nonetheless, C-APDs may offer an opportunity to improve patient safety and outcomes through enhanced intraoperative glycemic control. Anesthesiologists should become familiar with C-APD technology to help develop safe and effective protocols for their intraoperative use. We provide an overview of C-APDs and propose an introductory strategy for intraoperative study of these devices.

Regulatory Considerations for Physiological Closed-Loop Controlled Medical Devices Used for Automated Critical Care: Food and Drug Administration Workshop Discussion Topics.

Part of the mission of the Center for Devices and Radiological Health (CDRH) at the US Food and Drug Administration is to facilitate medical device innovation. Therefore, CDRH plays an important role in helping its stakeholders such as manufacturers, health care professionals, patients, patient advocates, academia, and other government agencies navigate the regulatory landscape for medical devices. This is particularly important for innovative physiological closed-loop controlled (PCLC) devices used in critical care environments, such as intensive care units, emergency settings, and battlefield environments. CDRH's current working definition of a PCLC medical device is a medical device that incorporates physiological sensor(s) for automatic manipulation of a physiological variable through actuation of therapy that is conventionally made by a clinician. These emerging devices enable automatic therapy delivery and may have the potential to revolutionize the standard of care by ensuring adequate and timely therapy delivery with improved performance in high workload and high-stress environments. For emergency response and military applications, automatic PCLC devices may play an important role in reducing cognitive overload, minimizing human error, and enhancing medical care during surge scenarios (ie, events that exceed the capability of the normal medical infrastructure). CDRH held an open public workshop on October 13 and 14, 2015 with the aim of fostering an open discussion on design, implementation, and evaluation considerations associated with PCLC devices used in critical care environments. CDRH is currently developing regulatory recommendations and guidelines that will facilitate innovation for PCLC devices. This article highlights the contents of the white paper that was central to the workshop and focuses on the ensuing discussions regarding the engineering, clinical, and human factors considerations.

Closed-loop regulation of arterial pressure after acute brain death.

The purpose of this concept study was to investigate the possibility of automatic mean arterial pressure (MAP) regulation in a porcine heart-beating brain death (BD) model. Hemodynamic stability of BD donors is necessary for maintaining acceptable quality of donated organs for transplantation. Manual stabilization is challenging, due to the lack of vasomotor function in BD donors. Closed-loop stabilization therefore has the potential of increasing availability of acceptable donor organs, and serves to indicate feasibility within less demanding patient groups. A dynamic model of nitroglycerine pharmacology, suitable for controller synthesis, was identified from an experiment involving an anesthetized pig, using a gradient-based output error method. The model was used to synthesize a robust PID controller for hypertension prevention, evaluated in a second experiment, on a second, brain dead, pig. Hypotension was simultaneously prevented using closed-loop controlled infusion of noradrenaline, by means of a previously published controller. A linear model of low order, with variable (uncertain) gain, was sufficient to describe the dynamics to be controlled. The robustly tuned PID controller utilized in the second experiment kept the MAP within a user-defined range. The system was able to prevent hypertension, exceeding a reference of 100 mmHg by more than 10%, during 98% of a 12 h experiment. This early work demonstrates feasibility of the investigated modelling and control synthesis approach, for the purpose of maintaining normotension in a porcine BD model. There remains a need to characterize individual variability, in order to ensure robust performance over the expected population.

Pressure-flow characteristics of breathing systems and their components for pediatric and adult patients.

BACKGROUND: Breathing circuits connect the ventilator to the patients' respiratory system. Breathing tubes, connectors, and sensors contribute to artificial airway resistance to a varying extent. We hypothesized that the flow-dependent resistance is higher in pediatric breathing systems and their components compared to respective types for adults. AIMS: We aimed to characterize the resistance of representative breathing systems and their components used in pediatric patients (including devices for adults) by their nonlinear pressure-flow relationship. METHODS: We used a physical model to measure the flow-dependent pressure gradient (∆P) across breathing tubes, breathing tube extensions, 90°- and Y-connectors, flow- and carbon dioxide sensors, water traps and reusable, disposable and coaxial breathing systems for pediatric and for adult patients. ∆P was analyzed for usual flow ranges and statistically compared at a representative flow rate of 300 mL∙s-1 (∆P300 ). RESULTS: ∆P across pediatric devices always exceeded ∆P across the corresponding devices for adult patients (all P < .001 [no 95% CI includes 0]). ∆P300 across breathing system components for adults was always below 0.2 cmH2 O but reached up to 4.6 cmH2 O in a flow sensor for pediatric patients. ∆P300 was considerably higher across the reusable compared to the disposable pediatric breathing systems (1.9 vs 0.3 cmH2 O, P < .001, [95% CI -1.59 to -1.56]). CONCLUSION: The resistances of pediatric breathing systems and their components result in pressure gradients exceeding those for adults several fold. Considering the resistance of individual components is crucial for composing a breathing system matching the patient's needs. Compensation of the additional resistance should be considered if a large composed resistance is unavoidable.

Closed-Loop Control of Total Intravenous Anesthesia During Significant Intraoperative Blood Loss: A Case Report.

Closed-loop control of anesthesia based on continuous feedback from processed electroencephalography adjusts drug dosing to target a desired depth of hypnosis during dynamic clinical circumstances, freeing the anesthesiologist to focus on more complex tasks. We describe a case of closed-loop control of total intravenous anesthesia in which a sudden loss of blood required immediate intervention. This case illustrates that closed-loop control of drug delivery maintained an appropriate depth of hypnosis during a rapidly changing surgical situation, and that processed electroencephalography may be a useful adjunct indicator for cerebral hypoperfusion.

Physician-Directed Versus Computerized Closed-Loop Control of Blood Pressure Using Phenylephrine in a Swine Model.

BACKGROUND: Vasopressors provide a rapid and effective approach to correct hypotension in the perioperative setting. Our group developed a closed-loop control (CLC) system that titrates phenylephrine (PHP) based on the mean arterial pressure (MAP) during general anesthesia. As a means of evaluating system competence, we compared the performance of the automated CLC with physicians. We hypothesized that our CLC algorithm more effectively maintains blood pressure at a specified target with less blood pressure variability and reduces the dose of PHP required. METHODS: In a crossover study design, 6 swine under general anesthesia were subjected to a normovolemic hypotensive challenge induced by sodium nitroprusside. The physicians (MD) manually changed the PHP infusion rate, and the CLC system performed this task autonomously, adjusted every 3 seconds to achieve a predetermined MAP. RESULTS: The CLC maintained MAP within 5 mm Hg of the target for (mean ± standard deviation) 93.5% ± 3.9% of the time versus 72.4% ± 26.8% for the MD treatment (P = .054). The mean (standard deviation) percentage of time that the CLC and MD interventions were above target range was 2.1% ± 3.3% and 25.8% ± 27.4% (P = .06), respectively. Control statistics, performance error, median performance error, and median absolute performance error were not different between CLC and MD interventions. PHP infusion rate adjustments by the physician were performed 12 to 80 times in individual studies over a 60-minute period. The total dose of PHP used was not different between the 2 interventions. CONCLUSIONS: The CLC system performed as well as an anesthesiologist totally focused on MAP control by infusing PHP. Computerized CLC infusion of PHP provided tight blood pressure control under conditions of experimental vasodilation.

Effects of different fresh gas flows with or without a heat and moisture exchanger on inhaled gas humidity in adults undergoing general anaesthesia: A systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: The minimum inhaled gas absolute humidity level is 20 mgH2O l for short-duration use in general anaesthesia and 30 mgH2O l for long-duration use in intensive care to avoid respiratory tract dehydration. OBJECTIVE: The aim is to compare the effects of different fresh gas flows (FGFs) through a circle rebreathing system with or without a heat and moisture exchanger (HME) on inhaled gas absolute humidity in adults undergoing general anaesthesia. DESIGN: Systematic review and meta-analyses of randomised controlled trials. We defined FGF (l min) as minimal (0.25 to 0.5), low (0.6 to 1.0) or high (≥2). We extracted the inhaled gas absolute humidity data at 60 and 120 min after connection of the patient to the breathing circuit. The effect size is expressed as the mean differences and corresponding 95% confidence intervals (CI). DATA SOURCES: PubMed, EMBASE, SciELO, LILACS and CENTRAL until January 2017. RESULTS: We included 10 studies. The inhaled gas absolute humidity was higher with minimal flow compared with low flow at 120 min [mean differences 2.51 (95%CI: 0.32 to 4.70); P = 0.02] but not at 60 min [mean differences 2.95 (95%CI: -0.95 to 6.84); P = 0.14], and higher with low flow compared with high flow at 120 min [mean differences 7.19 (95%CI: 4.53 to 9.86); P < 0.001]. An inhaled gas absolute humidity minimum of 20 mgH2O l was attained with minimal flow at all times but not with low or high flows. An HME increased the inhaled gas absolute humidity: with minimal flow at 120 min [mean differences 8.49 (95%CI: 1.15 to 15.84); P = 0.02]; with low flow at 60 min [mean differences 9.87 (95%CI: 3.18 to 16.57); P = 0.04] and 120 min [mean differences 7.19 (95%CI: 3.29 to 11.10); P = 0.003]; and with high flow of 2 l min at 60 min [mean differences 6.46 (95%CI: 4.05 to 8.86); P < 0.001] and of 3 l min at 120 min [mean differences 12.18 (95%CI: 6.89 to 17.47); P < 0.001]. The inhaled gas absolute humidity data attained or were near 30 mgH2O l when an HME was used at all FGFs and times. CONCLUSION: All intubated patients should receive a HME with low or high flows. With minimal flow, a HME adds cost and is not needed to achieve an appropriate inhaled gas absolute humidity.

Prefrontal hemodynamic after-effects caused by rebreathing may predict affective states - A multimodal functional near-infrared spectroscopy study.

Brain activity has been shown to be influenced by respiratory behavior. Here, we evaluated whether respiration-induced hypo- or hypercapnia may support differentiation between physiological versus pathological respiratory behavior. In particular, we investigated whether systemic physiological measures could predict the brain's time-frequency hemodynamics after three respiratory challenges (i.e., breath-holding, rebreathing, and hyperventilation) compared to resting-state. Prefrontal hemodynamics were assessed in healthy subjects (N = 27) using functional near-infrared spectroscopy (fNIRS). Systemic physiological measures were assessed in form of heart rate, partial end-tidal carbon dioxide, respiration rate, and saturation of peripheral oxygen. Time-frequency dynamics were quantified using the wavelet transform coherence (i.e., defined here as cortical-systemic coherence). We found that the three respiratory challenges modulated cortical-systemic coherence differently: (1) After rebreathing, cortical-systemic coherence could be predicted from the amplitude of the heart rate (strong negative correlation). (2) After breath-holding, the same observation was made (moderate negative correlation). (3) After hyperventilation, no significant effect was observed. (4) These effects were found only in the frequency range of very low-frequency oscillations. The presented findings highlight a distinct role of rebreathing in predicting cortical-systemic coupling based on heart rate changes, which may represents a measure of affective states in the brain. The applied multimodal assessment of hemodynamic and systemic physiological measures during respiratory challenges may therefore have potential applications in the differentiation between physiological and pathological respiratory behavior.

An adaptive and generalizable closed-loop system for control of medically induced coma and other states of anesthesia.

OBJECTIVE: Design of closed-loop anesthetic delivery (CLAD) systems is an important topic, particularly for medically induced coma, which needs to be maintained for long periods. Current CLADs for medically induced coma require a separate offline experiment for model parameter estimation, which causes interruption in treatment and is difficult to perform. Also, CLADs may exhibit bias due to inherent time-variation and non-stationarity, and may have large infusion rate variations at steady state. Finally, current CLADs lack theoretical performance guarantees. We develop the first adaptive CLAD for medically induced coma, which addresses these limitations. Further, we extend our adaptive system to be generalizable to other states of anesthesia. APPROACH: We designed general parametric pharmacodynamic, pharmacokinetic and neural observation models with associated guidelines, and derived a novel adaptive controller. We further penalized large steady-state drug infusion rate variations in the controller. We derived theoretical guarantees that the adaptive system has zero steady-state bias. Using simulations that resembled real time-varying and noisy environments, we tested the closed-loop system for control of two different anesthetic states, burst suppression in medically induced coma and unconsciousness in general anesthesia. MAIN RESULTS: In 1200 simulations, the adaptive system achieved precise control of both anesthetic states despite non-stationarity, time-variation, noise, and no initial parameter knowledge. In both cases, the adaptive system performed close to a baseline system that knew the parameters exactly. In contrast, a non-adaptive system resulted in large steady-state bias and error. The adaptive system also resulted in significantly smaller steady-state infusion rate variations compared to prior systems. SIGNIFICANCE: These results have significant implications for clinically viable CLAD design for a wide range of anesthetic states, with potential cost-saving and therapeutic benefits.

The Feasibility of a Completely Automated Total IV Anesthesia Drug Delivery System for Cardiac Surgery.

BACKGROUND: In this pilot study, we tested a novel automatic anesthesia system for closed-loop administration of IV anesthesia drugs for cardiac surgical procedures with cardiopulmonary bypass. This anesthesia drug delivery robot integrates all 3 components of general anesthesia: hypnosis, analgesia, and muscle relaxation. METHODS: Twenty patients scheduled for elective cardiac surgery with cardiopulmonary bypass were enrolled. Propofol, remifentanil, and rocuronium were administered using closed-loop feedback control. The main objective was the feasibility of closed-loop anesthesia defined as successful automated cardiac anesthesia without manual override by the attending anesthesiologist. Secondary qualitative observations were clinical and controller performances. The clinical performance of hypnosis control was the efficacy to maintain a bispectral index (BIS) of 45. To evaluate the hypnosis performance, BIS values were stratified into 4 categories: "excellent," "good," "poor," and "inadequate" hypnosis control defined as BIS values within 10%, ranging from 11% to 20%, ranging from 21% to 30%, or >30% of the target value, respectively. The clinical performance of analgesia was the efficacy to maintain NociMap values close to 0. The analgesia performance was assessed classifying the NociMap values in 3 pain control groups: -33 to +33 representing excellent pain control, -34 to -66 and +34 to +66 representing good pain control, and -67 to -100 and +67 to +100 representing insufficient pain control. The controller performance was calculated using the Varvel parameters. RESULTS: Robotic anesthesia was successful in 16 patients, which is equivalent to 80% (97.5% confidence interval [CI], 53%-95%) of the patients undergoing cardiac surgery. Four patients were excluded from the final analysis because of technical problems with the automated anesthesia delivery system. The secondary qualitative observations revealed that the clinical performance of hypnosis allowed an excellent and good control during 70% (97.5% CI, 63%-76%) of maintenance time and an insufficient clinical performance of analgesia for only 3% (97.5% CI, 1%-6%) of maintenance time. CONCLUSIONS: The completely automated closed-loop system tested in this investigation could be used successfully and safely for cardiac surgery necessitating cardiopulmonary bypass. The results of the present trial showed satisfactory clinical performance of anesthesia control.

Potential rapid solutions to maintain ventilation in the event of anaesthesia machine failure with no access to the patient's airway.

Anaesthesia machine failure requires rapid solutions to maintain ventilation and anaesthesia. During procedures with poor access to the patient's airway, it may not be possible to use a self-inflating mechanical ventilation device (SIMVD) for emergency ventilation, and alternative solutions are needed. We evaluated five methods for rescue ventilation using a patient simulator. In Method 1, we used the inspiratory and expiratory tubes and the alternative common gas outlet (ACGO) on the anaesthesia machine to produce a Mapleson E system. In Method 2, we used the tubes, ACGO and an open-ended reservoir bag to produce a Mapleson F system, controlling the bag to achieve ventilation. In Method 3, we attached a SIMVD to the inspiratory tube, and controlled occlusion of the expiratory tube. In Method 4, we used the tubes and ACGO in a Mapleson F configuration, replacing the open-ended bag with a SIMVD to facilitate manual ventilation. In Method 5, we attached a SIMVD to the expiratory tube and left the inspiratory tube attached to its mounting. We were able to achieve ventilation, maintain inhalational anaesthesia, and prevent expired gas rebreathing in Methods 1 and 2. In Method 3 ventilation was achieved with minimal rebreathing of expiratory gas, but with no inhalational agent. Methods 4 and 5 led to rebreathing. Our findings indicate that Methods 1 or 2 are the preferred rapid solutions to maintain ventilation and inhalational anaesthesia in the event of anaesthesia machine failure where there is poor airway access.

Inhaled anaesthetics and nitrous oxide: Complexities overlooked: things may not be what they seem.

This review re-examines existing pharmacokinetic and pharmacodynamic concepts of inhaled anaesthetics. After showing where uptake is hidden in the classic FA/FI curve, it is argued that target-controlled delivery of inhaled agents warrants a different interpretation of the factors affecting this curve (cardiac output, ventilation and blood/gas partition coefficient). Blood/gas partition coefficients of modern agents may be less important clinically than generally assumed. The partial pressure cascade from delivered to inspired to end-expired is re-examined to better understand the effect of rebreathing during low-flow anaesthesia, including the possibility of developing a hypoxic inspired mixture despite existing machine standards. Inhaled agents are easy to administer because they are transferred according to partial pressure gradients. In addition, the narrow dose-response curves for the three end points of general anaesthesia (loss of response to verbal command, immobility and autonomic reflex control) allow the clinical use of MACawake, MAC and MACBAR to determine depth of anaesthesia. Opioids differentially affect these clinical effects of inhaled agents. The effect of ventilation-perfusion relationships on gas uptake is discussed, and it is shown how moving beyond Riley's useful but simplistic model allows us to better understand both the concept and the magnitude of the second gas effect of nitrous oxide. It is argued that nitrous oxide remains a clinically useful drug. We hope to bring old (but ignored) and new (but potentially overlooked) information into the educational and clinical arenas to stimulate discussion among clinicians and researchers. We should not let technology pass by our all too engrained older concepts.