Audiovisual Feedback Devices for Chest Compression Quality during CPR

During cardiopulmonary resuscitation (CPR), chest compression quality is the key for patient survival. However, several studies have shown that both professionals and laypeople often apply CPR at improper rates and depths. The use of real-time feedback devices increases adherence to CPR quality guidelines. This chapter explores new alternatives to provide feedback on the quality of chest compressions during CPR. First, we describe and evaluate three methods to compute chest compression depth and rate using exclusively the chest acceleration. To evaluate the accuracy of the methods, we used episodes of simulated cardiac arrest acquired in a manikin model. One of the methods, based on the spectral analysis of the acceleration, was particularly accurate in a wide range of conditions. Then, we assessed the feasibility of using the transthoracic impedance (TI) signal acquired through defibrillation pads to provide feedback on chest compression depth and rate. For that purpose, we retrospectively analyzed three databases of out-of-hospital cardiac arrest episodes. When a wide variety of patients and rescuers were included, TI could not be used to reliably estimate the compression depth. However, compression rate could be accurately estimated. Development of simpler methods to provide feedback on CPR quality could contribute to the widespread of these devices

Waveform Capnography for Monitoring Ventilation during Cardiopulmonary Resuscitation: The Problem of Chest Compression Artifact

Sudden cardiac arrest (SCA) is the sudden cessation of the heart’s effective pumping function, confirmed by the absence of pulse and breathing. Without appropriate treatment, it leads to sudden cardiac death, considered responsible for half of the global cardiac disease deaths. Cardiopulmonary resuscitation (CPR) is a key intervention during SCA. Current resuscitation guidelines emphasize the use of waveform capnography during CPR in order to enhance CPR quality and improve patient outcomes. Capnography represents the concentration of the partial pressure of carbon dioxide (CO2) in respiratory gases and reflects ventilation and perfusion of the patient. Waveform capnography should be used for confirming the correct placement of the tracheal tube and monitoring ventilation. Other potential uses of capnography in resuscitation involve monitoring CPR quality, early identification of restoration of spontaneous circulation (ROSC), and determination of patient prognosis. An important role of waveform capnography is ventilation rate monitoring to prevent overventilation. However, some studies have reported the appearance of high-frequency oscillations synchronized with chest compressions superimposed on the capnogram. This chapter explores the incidence of chest compression artifact in out-of-hospital capnograms, assesses its negative influence in the automated detection of ventilations, and proposes several methods to enhance ventilation detection and capnography waveform

Modeling the impact of ventilations on the capnogram in out-of-hospital cardiac arrest

Aim Current resuscitation guidelines recommend waveform capnography as an indirect indicator of perfusion during cardiopulmonary resuscitation (CPR). Chest compressions (CCs) and ventilations during CPR have opposing effects on the exhaled carbon dioxide (CO2) concentration, which need to be better characterized. The purpose of this study was to model the impact of ventilations in the exhaled CO2 measured from capnograms collected during out-of-hospital cardiac arrest (OHCA) resuscitation. Methods We retrospectively analyzed OHCA monitor-defibrillator files with concurrent capnogram, compression depth, transthoracic impedance and ECG signals. Segments with CC pauses, two or more ventilations, and with no pulse-generating rhythm were selected. Thus, only ventilations should have caused the decrease in CO2 concentration. The variation in the exhaled CO2 concentration with each ventilation was modeled with an exponential decay function using non-linear-least-squares curve fitting. Results Out of the original 1002 OHCA dataset (one per patient), 377 episodes had the required signals, and 196 segments from 96 patients met the inclusion criteria. Airway type was endotracheal tube in 64.8% of the segments, supraglottic King LT-D (TM) in 30.1%, and unknown in 5.1%. Median (IQR) decay factor of the exhaled CO2 concentration was 10.0% (7.8 - 12.9) with R-2 = 0.98(0.95 - 0.99). Differences in decay factor with airway type were not statistically significant (p = 0.17). From these results, we propose a model for estimating the contribution of CCs to the end-tidal CO2 level between consecutive ventilations and for estimating the end-tidal CO2 variation as a function of ventilation rate. Conclusion We have modeled the decrease in exhaled CO2 concentration with ventilations during chest compression pauses in CPR. This finding allowed us to hypothesize a mathematical model for explaining the effect of chest compressions on ETCO2 compensating for the influence of ventilation rate during CPR. However, further work is required to confirm the validity of this model during ongoing chest compressions.The Basque Government provided support in the form of a grant for research groups (IT1087-16) for authors Jose Julio Gutierrez, Jesus Maria Ruiz, Sofia Ruiz de Gauna, and Mikel Leturiondo; and in the form of a predoctoral grant (PRE-2017-2-0201) for author Mikel Leturiondo (https://www.euskadi.eus).The Spanish Ministry of Economy, Industry and Competitiveness provided support in the form of a grant for research projects (RTI2018-094396-B-I00) for authors Jose Julio Gutierrez, Jesus Maria Ruiz, Sofia Ruiz de Gauna, and Mikel Leturiondo; and in the form of the program Torres Quevedo (PTQ-16-08201) for author Digna Maria Gonzalez-Otero (http://www.ciencia.gob.es/).Bexen Cardio, a Spanish medical device manufacturer, provided support in the form of a salary for author Digna Mari ' a Gonza ' lez-Otero. None of the above funders had any additional role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific role of each author is articulated in the "author contributions" section. Authors James Knox Russell, Carlos Corcuera, Juan Francisco Urtusagasti, and Mohamud Ramzan Daya received no funding for this work

The Role of Chest Compressions on Ventilation during Advanced Cardiopulmonary Resuscitation

There is growing interest in the quality of manual ventilation during cardiopulmonary resuscitation (CPR), but accurate assessment of ventilation parameters remains a challenge. Waveform capnography is currently the reference for monitoring ventilation rate in intubated patients, but fails to provide information on tidal volumes and inspiration–expiration timing. Moreover, the capnogram is often distorted when chest compressions (CCs) are performed during ventilation compromising its reliability during CPR. Our main purpose was to characterize manual ventilation during CPR and to assess how CCs may impact on ventilation quality. Methods: Retrospective analysis were performed of CPR recordings fromtwo databases of adult patients in cardiac arrest including capnogram, compression depth, and airway flow, pressure and volume signals. Using automated signal processing techniques followed by manual revision, individual ventilations were identified and ventilation parameters were measured. Oscillations on the capnogram plateau during CCs were characterized, and its correlation with compression depth and airway volume was assessed. Finally, we identified events of reversed airflow caused by CCs and their effect on volume and capnogram waveform. Results: Ventilation rates were higher than the recommended 10 breaths/min in 66.7% of the cases. Variability in ventilation rates correlated with the variability in tidal volumes and other ventilatory parameters. Oscillations caused by CCs on capnograms were of high amplitude (median above 74%) and were associated with low pseudo-volumes (median 26 mL). Correlation between the amplitude of those oscillations with either the CCs depth or the generated passive volumes was low, with correlation coefficients of −0.24 and 0.40, respectively. During inspiration and expiration, reversed airflow events caused opposed movement of gases in 80% of ventilations. Conclusions: Our study confirmed lack of adherence between measured ventilation rates and the guideline recommendations, and a substantial dispersion in manual ventilation parameters during CPR. Oscillations on the capnogram plateau caused by CCs did not correlate with compression depth or associated small tidal volumes. CCs caused reversed flow during inspiration, expiration and in the interval between ventilations, sufficient to generate volume changes and causing oscillations on capnogram. Further research is warranted to assess the impact of these findings on ventilation quality during CPR.This research was funded by the grant PID2021-126021OB-I00 by MCIN/AEI/10.13039/501100011033 and by ERDF A way of making Europe, and by the grant IT1590-22 by the Basque Government. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Cholangiocarcinoma progression depends on the uptake and metabolization of extracellular lipids

[Background and Aims] Cholangiocarcinoma (CCA) includes a heterogeneous group of biliary cancers with a dismal prognosis. We investigated if lipid metabolism is disrupted in CCA and its role in tumor proliferation.[Approach and Results] The in vitro and in vivo tumorigenic capacity of five human CCA cell lines was analyzed. Proteome, lipid content, and metabolic fluxes were evaluated in CCA cells and compared with normal human cholangiocytes (NHC). The Akt1/NOTCH1 intracellular cytoplasmic domain (Nicd1)-driven CCA mouse model was also evaluated. The proteome of CCA cells was enriched in pathways involved in lipid and lipoprotein metabolism. The EGI1 CCA cell line presented the highest tumorigenic capacity. Metabolic studies in high (EGI1) versus low (HUCCT1) proliferative CCA cells in vitro showed that both EGI1 and HUCCT1 incorporated more fatty acids (FA) than NHC, leading to increased triglyceride storage, also observed in Akt1/Nicd1-driven CCA mouse model. The highly proliferative EGI1 CCA cells showed greater uptake of very-low-density and HDLs than NHC and HUCCT1 CCA cells and increased cholesteryl ester content. The FA oxidation (FAO) and related proteome enrichment were specifically up-regulated in EGI1, and consequently, pharmacological blockade of FAO induced more pronounced inhibition of their tumorigenic capacity compared with HUCCT1. The expression of acyl-CoA dehydrogenase ACADM, the first enzyme involved in FAO, was increased in human CCA tissues and correlated with the proliferation marker PCNA.[Conclusions] Highly proliferative human CCA cells rely on lipid and lipoprotein uptake to fuel FA catabolism, suggesting that inhibition of FAO and/or lipid uptake could represent a therapeutic strategy for this CCA subclass.This work was supported by “Ayudas para apoyar grupos de investigación del sistema Universitario Vasco” (IT971‐16 to PA), MCIU/AEI/FEDER, UE (2018‐095134‐B‐100 to PA and by the University of Basque Country COLAB20/01 to PA; Spanish Carlos III Health Institute (ISCIII) (FIS PI15/01132, PI18/01075, PI21/00922, and Miguel Servet Program CON14/00129 and CPII19/00008 to JMB; FIS PI14/00399, PI17/00022 and PI20/00186 to MJP; Sara Borrell [CD19/00254 to PMR]) cofinanced by “Fondo Europeo de Desarrollo Regional” (FEDER); CIBERehd (ISCIII) to JMB, MJP, PMR, PA and LB); “Diputación Foral Gipuzkoa” (DFG15/010, DFG16/004 to JMB and 2020‐CIEN‐000067‐01 to PMR), Department of Health of the Basque Country (2019111024 to MJP, 2017111010 to JMB, and 2020111077 to JMB and PA), “Euskadi RIS3” (2016222001, 2017222014, 2018222029, 2019222054, 2020333010 to JMB), BIOEF (Basque Foundation for Innovation and Health Research: EiTB Maratoia BIO15/CA/016/BD to JMB) and Department of Industry of the Basque Country (Elkartek: KK‐2020/00008 to JMB); La Caixa Scientific Foundation (HR17‐00601 to JMB). “Fundación Científica de la Asociación Española Contra el Cáncer” (AECC Scientific Foundation, to JMB). AMMF‐The Cholangiocarcinoma Charity (EU/2019/AMMFt/001, to JMB and PMR). MRDG was funded by “Fundación Científica de la Asociación Española Contra el Cáncer” (AECC de Bizkaia), MJP was funded by the Spanish Ministry of Economy and Competitiveness (MINECO: “Ramón y Cajal” Program RYC‐2015‐17755), IL, AL and FG‐R by the Basque Government (PRE_2016_1_0152, PRE_2018_2_0195 and PRE 2020 2 02500, respectively), AN‐Z and BG‐S by the UPV/EHU, AB‐V by “Programa de especialización de Personal Investigador Doctor” at the UPV/EHU (2019‐2020) and MA by the MCIU/AEI/FEDER

Methionine adenosyltransferase 1a antisense oligonucleotides activate the liver-brown adipose tissue axis preventing obesity and associated hepatosteatosis

Altered methionine metabolism is associated with weight gain in obesity. The methionine adenosyltransferase (MAT), catalyzing the first reaction of the methionine cycle, plays an important role regulating lipid metabolism. However, its role in obesity, when a plethora of metabolic diseases occurs, is still unknown. By using antisense oligonucleotides (ASO) and genetic depletion of Mat1a, here, we demonstrate that Mat1a deficiency in diet-induce obese or genetically obese mice prevented and reversed obesity and obesity-associated insulin resistance and hepatosteatosis by increasing energy expenditure in a hepatocyte FGF21 dependent fashion. The increased NRF2-mediated FGF21 secretion induced by targeting Mat1a, mobilized plasma lipids towards the BAT to be catabolized, induced thermogenesis and reduced body weight, inhibiting hepatic de novo lipogenesis. The beneficial effects of Mat1a ASO were abolished following FGF21 depletion in hepatocytes. Thus, targeting Mat1a activates the liver-BAT axis by increasing NRF2-mediated FGF21 secretion, which prevents obesity, insulin resistance and hepatosteatosis. High methionine and S-adenosylmethionine serum levels are related with obesity. Here the authors show that knockdown of methionine adenosyltransferase by using antisense oligonucleotides provides beneficial effects in obesity and comorbidities.This work was supported by Ayudas para apoyar grupos de investigacion del sistema Universitario Vasco (IT971-16) and MCIU/AEI/FEDER, UE (RTI2018-095134-B-100) (to P.A.), (RTI2018-099413-B-I00 and RED2018-102379-T) (to R.N.), PID2020119486RB-100 (to M.V.R.) and (RTI2018-096759-A-100) (to T.C.D). EFSD/Lilly European Diabetes Research Program, MICIU (PID2019-104399RB-I00), Fundacion AECC PROYE19047SABI, and Comunidad de Madrid IMMUNOTHERCAN-CM B2017/BMD-3733 (to G.S.). La CAIXA Foundation LCF/PR/HP17/52190004, MINECO-FEDER SAF2017-87301-R, AYUDAS FUNDACION BBVA A EQUIPOS DE INVESTIGACION CIENTIFICA UMBRELLA 2018 and AECC Scientific Foundation, grant name: Rare Cancers 2017 (to M.L.M.-C.). AECC Scientific Foundation (to T.C.D.). Xunta de Galicia 2020-PG015 (to R.N.) Gilead Sciences International Research Scholars Program in Liver Disease (to M.V.R.). Personal fellows: E.P.F. was awarded with Juan de la Cierva-Formacion, FJC2018-035449-I. C.F. was awarded with Sara Borrell (CD19/00078). CIC bioGUNE thanks MCIU for the Severo Ochoa Excellence Accreditation (SEV-2016-0644). The authors thank Dr. Manuel Lafitas laboratory (Getxo, Bizkaia, Spain) for his valuable help in the analysis of biochemical parameters

Contribution of chest compressions to end-tidal carbon dioxide levels generated during out-of-hospital cardiopulmonary resuscitation

Aim Characterise how changes in chest compression depth and rate affect variations in end-tidal CO2 (ETCO2) during manual cardiopulmonary resuscitation (CPR) in out-of-hospital cardiac arrest (OHCA). Methods Retrospective analysis of adult OHCA monitor-defibrillator recordings having concurrent capnogram, compression depth, transthoracic impedance and ECG, and with atleast 1,000 compressions. Within each patient, during no spontaneous circulation, nearby segments with changes in chest compression depth and rate were identified. Average ETCO2 within each segment was standardised to compensate for ventilation rate variability. Contributions of relative variations in depth and rate to relative variations in standardised ETCO2 were characterised using linear and non-linear models. Normalisation between paired segments removed intra and inter-patient variation and made coefficients of the model independent of the scale of measurement and therefore directly comparable. Results A total of 394 pairs of segments from 221 patients were analysed (33% female, median (IQR) age 66 (55–74) years). Chest compression depth and rate were 50.4 (43.2–57.0) mm and 111.1 (106.5–116.1) compressions per minute. ETCO2 before and after standardization was 32.1 (23.0–41.4) mmHg and 28.5 (19.4–38.7) mmHg. Linear model coefficient of determination was 0.89. Variation in compression depth mainly explained ETCO2 variation (coefficient 0.95, 95% confidence interval (CI): 0.93–0.98) while changes in compression rate did not (coefficient 0.04, 95% CI: 0.01–0.07). Non-linear trend analysis confirmed the results. Conclusion This study quantified the relative importance of chest compression characteristics in terms of their impact on CO2 production during CPR. With ventilation rate standardised, variation in chest compression depth explained variations in ETCO2 better than variation in chest compression rateThis study was funded by the grant RTI2018-094396-B-I00 by MCIN/AEI/10.13039/501100011033 and by ERDF A way of making Europe. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Assessment of the evolution of end-tidal carbon dioxide within chest compression pauses to detect restoration of spontaneous circulation.

BackgroundMeasurement of end-tidal CO2 (ETCO2) can help to monitor circulation during cardiopulmonary resuscitation (CPR). However, early detection of restoration of spontaneous circulation (ROSC) during CPR using waveform capnography remains a challenge. The aim of the study was to investigate if the assessment of ETCO2 variation during chest compression pauses could allow for ROSC detection. We hypothesized that a decay in ETCO2 during a compression pause indicates no ROSC while a constant or increasing ETCO2 indicates ROSC.MethodsWe conducted a retrospective analysis of adult out-of-hospital cardiac arrest (OHCA) episodes treated by the advanced life support (ALS). Continuous chest compressions and ventilations were provided manually. Segments of capnography signal during pauses in chest compressions were selected, including at least three ventilations and with durations less than 20 s. Segments were classified as ROSC or non-ROSC according to case chart annotation and examination of the ECG and transthoracic impedance signals. The percentage variation of ETCO2 between consecutive ventilations was computed and its average value, ΔETavg, was used as a single feature to discriminate between ROSC and non-ROSC segments.ResultsA total of 384 segments (130 ROSC, 254 non-ROSC) from 205 OHCA patients (30.7% female, median age 66) were analyzed. Median (IQR) duration was 16.3 (12.9,18.1) s. ΔETavg was 0.0 (-0.7, 0.9)% for ROSC segments and -11.0 (-14.1, -8.0)% for non-ROSC segments (p ConclusionAverage percent variation of ETCO2 during pauses in chest compressions allowed for ROSC discrimination. This metric could help confirm ROSC during compression pauses in ALS settings

Metrics of impulsiveness of manual chest compressions for out-of-hospital cardiopulmonary resuscitation

Aim Propose new metrics of impulsiveness of manual chest compressions (CCs) that account for shape and duration, separate the characteristics of the compressive part of the CC cycle from those of the recoil part, and are uncorrelated to CC depth and rate. Methods We conducted a retrospective analysis of adult out-of-hospital cardiac arrest monitor-defibrillator recordings having CPR data. Specifically, episodes of adult patients with ≥ 1000 compressions free of leaning were examined. CCs were obtained from the depth signal of the valid episodes, and we calculated the novel metrics: compression area index (CAI), recoil area index (RAI), compression impulsiveness index (CII) and recoil impulsiveness index (RII). Generalized linear mixed-effects models and Jonckheere-Terpstra trend analyses were employed to measure differences between populations and trends, and the absolute value of Pearson's correlation coefficient was used to report dependence between variables. Statistics are reported as median and interquartile range. Results We analyzed 982,340 CCs corresponding to 453 episodes, for which we calculated their CAI, RAI and duty cycle (DC). We analyzed the metrics for various populations: age, sex, any ROSC achieved and disposition, and found that CAI was significantly different according to patient disposition and RAI relative to age and sex ( ). None of the metrics was correlated strongly to depth or rate ( values of 0.22 or smaller), and all of them varied for CC series corresponding to the same rescuer over the course of resuscitation ( ). However, we observed that the metrics are not balanced, in that for any value of DC, CAI and RAI span almost their entire ranges. Conclusion The proposed metrics correctly and completely describe manual CC waveforms, improve upon the DC, since they depend on the signal waveform, and provide additional information to current indicators of quality CPR, depth and rate. Furthermore, they allow to differentiate the compressive and recoil parts of the CC cycle, reflecting influence of the rescuer (via CAI or CII) and of the biomechanics of the patient's chest (via RAI or RII). Thus, they have the potential to contribute to better understanding CPR dynamics and, eventually, to enhanced quality of CPR practice as additional indicators of proper manual CC technique.This study was funded by the grant PID2021-126021OB-I00 by MCIN/AEI/10.13039/501100011033 and ERDF A way of making Europe; and by the Basque Government through the IT1590-22 grant. The financing entities had no implication in the study or the manuscript

Monitoring chest compression quality during cardiopulmonary resuscitation: Proof-of-concept of a single accelerometer-based feedback algorithm

<div><p>Background</p><p>The use of real-time feedback systems to guide rescuers during cardiopulmonary resuscitation (CPR) significantly contributes to improve adherence to published resuscitation guidelines. Recently, we designed a novel method for computing depth and rate of chest compressions relying solely on the spectral analysis of chest acceleration. That method was extensively tested in a simulated manikin scenario. The purpose of this study is to report the results of this method as tested in human out-of-hospital cardiac arrest (OHCA) cases.</p><p>Materials and methods</p><p>The algorithm was evaluated retrospectively with seventy five OHCA episodes recorded by monitor-defibrillators equipped with a CPR feedback device. The acceleration signal and the compression signal computed by the CPR feedback device were stored in each episode. The algorithm was continuously applied to the acceleration signals. The depth and rate values estimated every 2-s from the acceleration data were compared to the reference values obtained from the compression signal. The performance of the algorithm was assesed in terms of the sensitivity and positive predictive value (PPV) for detecting compressions and in terms of its accuracy through the analysis of measurement error.</p><p>Results</p><p>The algorithm reported a global sensitivity and PPV of 99.98% and 99.79%, respectively. The median (P₇₅) unsigned error in depth and rate was 0.9 (1.7) mm and 1.0 (1.7) cpm, respectively. In 95% of the analyzed 2-s windows the error was below 3.5 mm and 3.1 cpm, respectively.</p><p>Conclusions</p><p>The CPR feedback algorithm proved to be reliable and accurate when tested retrospectively with human OHCA episodes. A new CPR feedback device based on this algorithm could be helpful in the resuscitation field.</p></div