Periodic Fluctuation of Tidal Volumes Further Improves Variable Ventilation in Experimental Acute Respiratory Distress Syndrome

In experimental acute respiratory distress syndrome (ARDS), random variation of tidal volumes (VT ) during volume controlled ventilation improves gas exchange and respiratory system mechanics (so-called stochastic resonance hypothesis). It is unknown whether those positive effects may be further enhanced by periodic VT fluctuation at distinct frequencies, also known as deterministic frequency resonance.We hypothesized that the positive effects of variable ventilation on lung functionmay be further amplified by periodic VT fluctuation at specific frequencies. In anesthetized and mechanically ventilated pigs, severe ARDS was induced by saline lung lavage and injurious VT (double-hit model). Animals were then randomly assigned to 6 h of protective ventilation with one of four VT patterns: (1) random variation of VT (WN); (2) P04, main VT frequency of 0.13Hz; (3) P10, main VT frequency of 0.05Hz; (4) VCV, conventional non-variable volume controlled ventilation. In groups with variable VT , the coefficient of variation was identical (30%). We assessed lung mechanics and gas exchange, and determined lung histology and inflammation. Compared to VCV, WN, P04, and P10 resulted in lower respiratory system elastance (63 ± 13 cm H2O/L vs. 50 ± 14 cm H2O/L, 48.4 ± 21 cm H2O/L, and 45.1 ± 5.9 cm H2O/L respectively, P < 0.05 all), but only P10 improved PaO2/FIO2 after 6 h of ventilation (318 ± 96 vs. 445 ± 110mm Hg, P < 0.05). Cycle-by-cycle analysis of lung mechanics suggested intertidal recruitment/de-recruitment in P10. Lung histologic damage and inflammation did not differ among groups. In this experimental model of severe ARDS, periodic VT fluctuation at a frequency of 0.05Hz improved oxygenation during variable ventilation, suggesting that deterministic resonance adds further benefit to variable ventilation

Methods for determination of individual PEEP for intraoperative mechanical ventilation using a decremental PEEP trial

(1) Background: Individual PEEP settings (PEEP(IND)) may improve intraoperative oxygenation and optimize lung mechanics. However, there is uncertainty concerning the optimal procedure to determine PEEP(IND). In this secondary analysis of a randomized controlled clinical trial, we compared different methods for PEEP(IND) determination. (2) Methods: Offline analysis of decremental PEEP trials was performed and PEEP(IND) was retrospectively determined according to five different methods (EIT-based: RVD(I) method, Global Inhomogeneity Index [GI], distribution of tidal ventilation [EIT VT]; global dynamic and quasi-static compliance). (3) Results: In the 45 obese and non-obese patients included, PEEP(IND) using the RVD(I) method (PEEP(RVD)) was 16.3 ± 4.5 cm H(2)O. Determination of PEEP(IND) using the GI and EIT VT resulted in a mean difference of −2.4 cm H(2)O (95%CI: −1.2;−3.6 cm H(2)O, p = 0.01) and −2.3 cm H(2)O (95% CI: −0.9;3.7 cm H(2)O, p = 0.01) to PEEP(RVD), respectively. PEEP(IND) selection according to quasi-static compliance showed the highest agreement with PEEP(RVD) (p = 0.67), with deviations > 4 cm H(2)O in 3/42 patients. PEEP(RVD) and PEEP(IND) according to dynamic compliance also showed a high level of agreement, with deviations > 4 cm H(2)O in 5/42 patients (p = 0.57). (4) Conclusions: High agreement of PEEP(IND) determined by the RVD(I) method and compliance-based methods suggests that, for routine clinical practice, PEEP selection based on best quasi-static or dynamic compliance is favorable

a randomized controlled study

Background Uncertainty persists regarding the optimal ventilatory strategy in trauma patients developing acute respiratory distress syndrome (ARDS). This work aims to assess the effects of two mechanical ventilation strategies with high positive end-expiratory pressure (PEEP) in experimental ARDS following blunt chest trauma. Methods Twenty-six juvenile pigs were anesthetized, tracheotomized and mechanically ventilated. A contusion was applied to the right chest using a bolt-shot device. Ninety minutes after contusion, animals were randomized to two different ventilation modes, applied for 24 h: Twelve pigs received conventional pressure-controlled ventilation with moderately low tidal volumes (VT, 8 ml/kg) and empirically chosen high external PEEP (16cmH2O) and are referred to as the HP-CMV-group. The other group (n = 14) underwent high-frequency inverse-ratio pressure-controlled ventilation (HFPPV) involving respiratory rate of 65breaths · min−1, inspiratory-to-expiratory- ratio 2:1, development of intrinsic PEEP and recruitment maneuvers, compatible with the rationale of the Open Lung Concept. Hemodynamics, gas exchange and respiratory mechanics were monitored during 24 h. Computed tomography and histology were analyzed in subgroups. Results Comparing changes which occurred from randomization (90 min after chest trauma) over the 24-h treatment period, groups differed statistically significantly (all P values for group effect <0.001, General Linear Model analysis) for the following parameters (values are mean ± SD for randomization vs. 24-h): PaO2 (100 % O2) (HFPPV 186 ± 82 vs. 450 ± 59 mmHg; HP-CMV 249 ± 73 vs. 243 ± 81 mmHg), venous admixture (HFPPV 34 ± 9.8 vs. 11.2 ± 3.7 %; HP-CMV 33.9 ± 10.5 vs. 21.8 ± 7.2 %), PaCO2 (HFPPV 46.9 ± 6.8 vs. 33.1 ± 2.4 mmHg; HP-CMV 46.3 ± 11.9 vs. 59.7 ± 18.3 mmHg) and normally aerated lung mass (HFPPV 42.8 ± 11.8 vs. 74.6 ± 10.0 %; HP-CMV 40.7 ± 8.6 vs. 53.4 ± 11.6 %). Improvements occurring after recruitment in the HFPPV- group persisted throughout the study. Peak airway pressure and VT did not differ significantly. HFPPV animals had lower atelectasis and inflammation scores in gravity-dependent lung areas. Conclusions In this model of ARDS following unilateral blunt chest trauma, HFPPV ventilation improved respiratory function and fulfilled relevant ventilation endpoints for trauma patients, i.e. restoration of oxygenation and lung aeration while avoiding hypercapnia and respiratory acidosis

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Cardiovascular and respiratory responses to psychophysiological tasks : methodological issues for assessing autonomic regulation

EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Cardiovascular and respiratory responses to pychophysiological tasks : methodological issues for assessing autonomic regulation

The current work studies the correlation between birth-weight and autonomic cardiovascular modulation in adult life, in order to investigate the physiological mechanisms underlying the fetal origins of cardiovascular disease. However, factors other than autonomic modulation may strongly influence the estimation of cardiovascular indexes. In this thesis, two such confounding factors were investigated in detail. Firstly, the between-task and inter-individual differences in respiratory patterns, especially in tasks involving speech were  found to be strongly reflected in cardiovascular indexes. Clear evidence was found that a very significant part of changes in indexes during the psychophysiological experimental protocol considered can be explained by modifications in respiration, without assuming between-tasks or inter-individual differences in autonomic activation elicited by psychological/cognitive processes. The second factor is the presence of within-task dynamics in the cardiovascular reaction to psychophysiological tasks.  The common approach in psychophysiological investigations is to estimate cardiovascular indexes as average values over the whole length of the task. However, the results found show that such an approach may obscure significant within-task changes in the indexes that might carry useful psychophysiological information.  Choosing shorter epochs within the tasks for estimating the indexes has also a notable impact in terms of assessing changes elicited by the tasks. Since these two factors are intrinsic in the reaction to psychophysiological tasks, they can have a profound impact on the indirect estimates of autonomic reaction through cardiovascular indexes. Controlling them during psychophysiological experiments may be difficult (if not impossible).  However, their effects should be minimized, for example by avoiding tasks involving speech and choosing appropriate data epochs for the analysis.</p

ARres - Matlab Tool for Computing Confidence Limits of Measures derived from Autoregressive Modeling of Time Series

<h3>In the assessment of physiological function, statistical tests are ubiquitous. Most commonly these focus on the average behaviour of a group of subjects, and assess distributions and significant changes across tasks or between groups of subjects, considering the variability between individuals as a random/confounding effect. However, in several experimental/clinical applications, the focus should be on the individual subject, to determine confidence limits of estimates and to test for significant changes as a result of experimental procedures, or other factors. To this end we introduce a method for computing confidence limits and perform statistical comparison for parameters derived from autoregressive AR models applied to a single time series, which exploits Monte Carlo or Bootstrap approaches.</h3><h3>The toolbox provides Matlab functions to compute several resampled realizations of the AR parameters (first estimated using least squares (idAR.m)) based on Monte Carlo resampling (idARres.m) or bootstrapping of the AR residuals (idARboot.m, to be used with the built-in function bootstrp.m), from which Confidence limits for AR-based indexes can be computed from individual time series. Examples of indexes to which the procedures are applied are measures of frequency and spectral power obtained from AR spectral decomposition (asd_ARMASpectDec.m), and measures of information storage or complexity obtained from information decomposition (its_CElinVAR1.m). The toolbox is demonstrated on simulations of a five-order AR process resempling spectral properties of heart rate variability time series (SimuConfLim.m).</h3><h3>The toolbox is based on the paper: </h3><h3>Beda A, Simpson DMS and Faes L, 'Estimation of Confidence Limits for Descriptive Indexes Derived from Autoregressive Analysis of Time Series: Methods and Application to Heart Rate Variability', Plos One, 2017.</h3

Flow chart of procedure proposed for the estimation of confidence limits.

<p>Flow chart of procedure proposed for the estimation of confidence limits of autoregressive indexes descriptive of time series data.</p