Resumption of Cardiac Activity after Withdrawal of Life-Sustaining Measures.

BACKGROUND: The minimum duration of pulselessness required before organ donation after circulatory determination of death has not been well studied. METHODS: We conducted a prospective observational study of the incidence and timing of resumption of cardiac electrical and pulsatile activity in adults who died after planned withdrawal of life-sustaining measures in 20 intensive care units in three countries. Patients were intended to be monitored for 30 minutes after determination of death. Clinicians at the bedside reported resumption of cardiac activity prospectively. Continuous blood-pressure and electrocardiographic (ECG) waveforms were recorded and reviewed retrospectively to confirm bedside observations and to determine whether there were additional instances of resumption of cardiac activity. RESULTS: A total of 1999 patients were screened, and 631 were included in the study. Clinically reported resumption of cardiac activity, respiratory movement, or both that was confirmed by waveform analysis occurred in 5 patients (1%). Retrospective analysis of ECG and blood-pressure waveforms from 480 patients identified 67 instances (14%) with resumption of cardiac activity after a period of pulselessness, including the 5 reported by bedside clinicians. The longest duration after pulselessness before resumption of cardiac activity was 4 minutes 20 seconds. The last QRS complex coincided with the last arterial pulse in 19% of the patients. CONCLUSIONS: After withdrawal of life-sustaining measures, transient resumption of at least one cycle of cardiac activity after pulselessness occurred in 14% of patients according to retrospective analysis of waveforms; only 1% of such resumptions were identified at the bedside. These events occurred within 4 minutes 20 seconds after a period of pulselessness. (Funded by the Canadian Institutes for Health Research and others.).

The impact of age, type 2 diabetes and hypertension on heart rate variability during rest and exercise at increasing levels of heat stress.

PURPOSE: In older adults with type 2 diabetes (T2D) and hypertension (HTN), cardiac autonomic modulation is markedly attenuated during exercise-heat stress. However, the extent to which this impairment is evident under increasing levels of heat stress remains unknown. METHODS: We examined heart rate variability (HRV), a surrogate of cardiac autonomic modulation, during incremental exercise-heat stress exposures in young (20-30 years) and middle-aged-to-older individuals (50-70 years) without and with T2D and HTN. Thirteen young and healthy (Young, n = 13) and 37 older men without (Older, n = 14) and with HTN (n = 13) or T2D (n = 10) performed 180-min treadmill walking at a fixed metabolic rate (~ 200 W/m2; ~ 3.5 METs) in a differing wet-bulb globe temperature (WBGT; 16 °C, 24 °C, 28 °C, and 32 °C). Electrocardiogram (ECG) and core temperature measurements were recorded throughout. Data were analysed using 5-min averaged epochs following 60-min exercise, which represented the last common timepoint across groups and conditions. RESULTS: Ageing did not significantly reduce HRV during increasing exercise-heat stress (all p > 0.050). However, T2D and HTN modified HRV during exercise-heat stress such that Detrended Fluctuation Analysis (DFA) α1 (p = 0.012) and the cardiac sympathetic index (p = 0.037) were decreased compared to Older in all except the warmest WBGT condition (32 °C). CONCLUSION: Our unique observations indicate that, relative to their younger counterparts, HRV in healthy older individuals is not perturbed during exercise heat-stress. However, relative to their age-matched healthy counterparts, HRV is reduced during exercise-heat stress in individuals with age-associated chronic conditions, indicative of cardiac autonomic dysfunction.

Economic feasibility of a novel tool to assist extubation decision-making: an early health economic modeling.

OBJECTIVES: To estimate the minimum percent change in failed extubation to make a tool designed to reduce extubation failure (Extubation Advisor [EA]) economically viable. METHODS: We conducted an early return on investment (ROI) analysis using data from intubated intensive care unit (ICU) patients at a large Canadian tertiary care hospital. We obtained input parameters from the hospital database and published literature. We ran generalized linear models to estimate the attributable length of stay, total hospital cost, and time to subsequent extubation attempt following failure. We developed a Markov model to estimate the expected ROI and performed probabilistic sensitivity analyses to assess the robustness of findings. Costs were presented in 2020 Canadian dollars (C$). RESULTS: The model estimated a 1 percent reduction in failed extubation could save the hospital C$289 per intubated patient (95 percent CI: 197, 459). A large center seeing 2,500 intubated ICU patients per year could save C$723,124/year/percent reduction in failed extubation. At the current annual price of C$164,221, the EA tool must reduce extubation failure by at least 0.24 percent (95 percent CI: .14, .41) to make the tool cost-effective at our site. CONCLUSIONS: Clinical decision-support tools like the EA may play an important role in reducing healthcare costs by reducing the rate of extubation failure, a costly event in the ICU.

Variability Predictors of Vasospasm in Subarachnoid Hemorrhage: A Feasibility Study.

BACKGROUND: Mean cerebral blood flow velocity (mean-CBFV) obtained from Transcranial Doppler (TCD) poorly predicts cerebral vasospasm in patients with aneurysmal subarachnoid hemorrhage (aSAH). Variability descriptors of mean-CBFV obtained during extended TCD recordings may improve this prediction. We assessed the feasibility of generating reliable linear and non-linear descriptors of mean-CBFV variability using extended recordings in aSAH patients and in healthy controls. We also explored which of those metrics might have the ability to discriminate between aSAH patients and healthy controls, and among patients who would go on to develop vasospasm and those who would not. METHODS: Bilateral mean-CBFV, blood pressure, and heart rate were continuously recorded for 40 minutes in aSAH patients (n = 8) within the first 5 days after ictus, in age-matched healthy controls (n = 8) and in additional young controls (n = 8). We obtained linear [standard deviation, coefficient of variations, and the very-low (0.003-0.040 Hz), low (0.040-0.150 Hz), and high-frequency (0.15-0.4 Hz) power spectra] and non-linear (Fractality, deterministic Chaos analyses) variability metrics. RESULTS: We successfully obtained TCD recordings from patients and healthy controls and calculated the desired metrics of mean-CBFV variability. Differences were appreciable between aSAH patients and healthy controls, as well as between aSAH patients who later developed vasospasm and those who did not. CONCLUSIONS: A 40-minute TCD recording provides reliable variability metrics in aSAH patients and healthy controls. Future studies are required to determine if mean-CBFV variability metrics remain stable over time, and whether they may serve to identify patients who are at greatest risk of developing cerebral vasospasm after aSAH.

First evidence that intrinsic fetal heart rate variability exists and is affected by hypoxic pregnancy.

KEY POINTS: We introduce a technique to test whether intrinsic fetal heart rate variability (iFHRV) exists and we show the utility of the technique by testing the hypothesis that iFHRV is affected by chronic fetal hypoxia, one of the most common adverse outcomes of human pregnancy complicated by fetal growth restriction. Using an established late gestation ovine model of fetal development under chronic hypoxic conditions, we identify iFHRV in isolated fetal hearts and show that it is markedly affected by hypoxic pregnancy. Therefore, the isolated fetal heart has intrinsic variability and carries a memory of adverse intrauterine conditions experienced during the last third of pregnancy. ABSTRACT: Fetal heart rate variability (FHRV) emerges from influences of the autonomic nervous system, fetal body and breathing movements, and from baroreflex and circadian processes. We tested whether intrinsic heart rate variability (iHRV), devoid of any external influences, exists in the fetal period and whether it is affected by chronic fetal hypoxia. Chronically catheterized ewes carrying male singleton fetuses were exposed to normoxia (n = 6) or hypoxia (10% inspired O2 , n = 9) for the last third of gestation (105-138 days of gestation (dG); term ∼145 dG) in isobaric chambers. At 138 dG, isolated hearts were studied using a Langendorff preparation. We calculated basal intrinsic FHRV (iFHRV) indices reflecting iFHRV's variability, predictability, temporal symmetry, fractality and chaotic behaviour, from the systolic peaks within 15 min segments in each heart. Significance was assumed at P < 0.05. Hearts of fetuses isolated from hypoxic pregnancy showed approximately 4-fold increases in the Grid transformation as well as the AND similarity index (sgridAND) and a 4-fold reduction in the scale-dependent Lyapunov exponent slope. We also detected a 2-fold reduction in the Recurrence quantification analysis, percentage of laminarity (pL) and recurrences, maximum and average diagonal line (dlmax, dlmean) and the Multiscale time irreversibility asymmetry index. The iHRV measures dlmax, dlmean, pL and sgridAND correlated with left ventricular end-diastolic pressure across both groups (average R2  = 0.38 ± 0.03). This is the first evidence that iHRV originates in fetal life and that chronic fetal hypoxia significantly alters it. Isolated fetal hearts from hypoxic pregnancy exhibit a time scale-dependent higher complexity in iFHRV.

Age differences in cardiac autonomic regulation during intermittent exercise in the heat.

PURPOSE: This study aimed to detect potential differences in heart-rate variability (HRV) during a moderate-intensity intermittent exercise in the heat among physically active young (25.8 ± 1.9 years), middle-aged (43.5 ± 2.8 years), and older (62.9 ± 3.7 years) men. METHODS: Thirty-three participants (11/group) performed four successive bouts of 15-min cycling at a moderate fixed rate of metabolic heat production of ~ 400 W; each separated by a 15-min recovery with 1 h of final recovery in a hot and dry environment (35 °C, 20% relative humidity). Twelve HRV indices were computed that have been commonly described in the literature, and characterized various domains of the variability and complexity of heart rate. RESULTS: Cardiac autonomic regulation during intermittent exercise in the heat, as well as during pre-exercise rest and recovery was significantly affected by age, as changes were observed among the three different aged groups in five indices (p ≤ 0.05). Similarly, time influenced cardiac autonomic regulation as three indices showed changes across time (p ≤ 0.05) during intermittent exercise, whilst five indices displayed significant changes (p ≤ 0.05) during rest and recovery in the heat. CONCLUSIONS: This study supports that moderate-intensity intermittent exercise in the heat is associated with significant cardiac autonomic dysregulation in older men, as compared to young and middle-aged men, yet it highlights the importance of developing preventative health strategies for heat-related illness in aged individuals.

Heart rate variability in older workers during work under the Threshold Limit Values for heat exposure.

BACKGROUND: The Threshold Limit Values (TLV) of the American Conference of Governmental and Industrial Hygienists indicate the levels of heat stress that all workers may be repeatedly exposed to without adverse health effects. In this study, we evaluated heart rate variability (HRV) during moderate-to-heavy work performed continuously or according to different TLV work-rest (WR) allocations in healthy physically active older workers. METHODS: Nine healthy older (58 ± 5 years) males performed three different 120-minute conditions in accordance with TLV guidelines for moderate-to-heavy intensity work (360 W fixed rate of heat production) in different wet-bulb globe temperatures (WBGT): continuous cycling at 28°C WBGT (CON), as well as intermitted work performed at WR of 3:1 in 29°C WBGT (WR3:1), and at WR of 1:1 at 30°C (WR1:1). Rectal temperature and HRV (3-lead electrocardiogram [ECG]) were assessed throughout. RESULTS: Coefficient of Variation, Poincaré SD2, and Shannon Entropy were decreased during the CON compared with the WR3:1 when core temperature exceeded 38°C and after 1 hour of continuous work (P < .05). Also, 4 of the 12 HRV indices studied were reduced at CON compared with WR1:1 after 2 hours of accumulated work time (P < .05). Participants worked longer before core temperature reached 38°C during the WR1:1 and the WR3:1, compared with CON (P < .05). CONCLUSIONS: Incorporating breaks during moderate-to-heavy work in the heat for older adults can reduce autonomic stress and prolong the work performed at safe core temperature levels. The TLV WR1:1 provides increased cardiac protection for older workers, as compared with the CON and the WR3:1.

Heart rate variability in older men on the day following prolonged work in the heat.

Susceptibility to heat illness during physically demanding work in hot environments is greater on the second of two consecutive workdays. While it has been demonstrated that heat storage is exacerbated on the second compared to first workday in older workers (50-65 yr), the effects on heart rate variability (HRV), an established surrogate of cardiac autonomic modulation, remain unclear. This study evaluated HRV in older workers on the day following prolonged work in the heat. Electrocardiogram was recorded in nine older (53-64 yr) males at rest, during three 30-min bouts of semi-recumbent cycling at fixed rates of metabolic heat production (150, 200, 250 W/m2), each separated by 15-min recovery. Experiments were conducted in hot-dry conditions (40 °C, 20% relative humidity), immediately prior to (Day 1), and on the day following (Day 2), a prolonged work simulation (∼7.5 hr) involving moderate intensity intermittent exercise in hot-dry conditions (38 °C, 34% relative humidity). Core temperature, as well as time, frequency, and nonlinear HRV indices were derived for analysis during rest, the final 5-min of exercise at the highest heat production and recovery. The change in core temperature at the end of work (mean ±SD) was significantly greater on Day 2 (1.0 °C ±0.3) relative to Day 1 (0.8 °C ±0.2; p < 0.01). Heart rate, however, did not significantly differ between days 1 and 2 at rest (Day 1, 59 ±11 bpm; Day 2, 62 ±13 bpm), during exercise (Day 1, 113 ±21 bpm; Day 2, 114 ±18 bpm ) and at the end of recovery (Day 1, 75 ±16 bpm; Day 2, 76 ±12 bpm). Likewise, there were no significant differences in any HRV indices derived from time, frequency, and nonlinear domains (all p > 0.05). Prolonged work in the heat did not modulate next-day heart rhythms, as reflected by HRV, despite augmented core temperature. While HRV can reflect physiological aspects of cardiac autonomic stressors, these findings indicate it does not provide a means to identify exacerbated heat strain in older workers over consecutive work shifts in the heat.

Heart rate variability dynamics during treatment for exertional heat strain when immediate response is not possible.

NEW FINDINGS: What is the central question of this study? Does a delay in cold water immersion treatment affect the cardiac autonomic control of exertionally heat-strained individuals? What is the main finding and its importance? Cold water immersion is effective for treating exertionally heat-strained individuals even when treatment is commenced with a significant delay. However, that treatment delay leads to only partial/transient restoration of cardiac autonomic control. Therefore, we recommend that exertional heatstroke patients are continuously monitored for several hours even after core temperature has returned to normal values. ABSTRACT: Immediate cold water immersion (CWI) is the gold-standard treatment for exertional heatstroke. In the field, however, treatment is often delayed, primarily owing to a delayed paramedic response and/or inaccurate diagnosis. We examined the effect of treatment (reduction of rectal temperature to 37.5°C) delays of 5 (short), 20 (moderate) and 40 (prolonged) min on cardiac autonomic control [as assessed via heart rate variability (HRV)] in eight exertionally heat-strained (40.0°C rectal temperature) individuals. Eleven HRV indices were computed that have been described commonly in the literature and characterize almost all known domains of the variability and complexity of the cardiopulmonary system. We found that the cardiac autonomic control (as assessed via HRV) of exertionally heat-strained individuals was significantly affected by the amount of time it took for the CWI treatment to be applied. Six out of 11 HRV indices studied, from all variability domains, displayed strong (P ≤ 0.005) time × delay interaction effects. Moreover, the number of significantly (P ≤ 0.005) abnormal (i.e. different from the short delay) HRV indices more than doubled (seven versus 15) from the moderate delay to the prolonged delay. Finally, our results demonstrated that a CWI treatment applied with delays of 20 and, primarily, 40 min did not lead to a full restoration of cardiac autonomic control of exertionally heat-strained individuals. In conclusion, this study supports CWI for treating exertionally heat-strained individuals even when applied with prolonged delay, but it highlights the importance of continued cardiac monitoring of patients who have suffered exertional heatstroke for several hours after restoration of core temperature to normal.

Helpful Only When Elevated: Initial Serum Lactate in Stable Emergency Department Patients with Sepsis Is Specific, but Not Sensitive for Future Deterioration.

BACKGROUND: Early emergency department (ED) identification of septic patients at risk of deterioration is critical. Lactate is associated with 28-day mortality in admitted patients, but little evidence exists on its use in predicting short-term deterioration. OBJECTIVE: Our aim was to determine the role of initial serum lactate for prediction of short-term deterioration in stable ED patients with suspected sepsis. METHODS: We conducted a prospective cohort study of adult ED sepsis patients. Venous lactate was obtained within 2 h of ED arrival. Main outcome was subsequent deterioration (defined as any of the following: death, intensive care admission > 24 h, intubation, vasoactive medications for > 1 h, or noninvasive positive pressure ventilation for > 1 h) within 72 h. Patients meeting any endpoint within 1 h of arrival were excluded. RESULTS: Nine hundred and eighty-five patients were enrolled, of whom 84 (8.5%) met the primary outcome of deterioration. Initial lactate ≥ 4.0 mmol/L had a specificity of 97% (95% confidence interval [CI] 94-100%), but a sensitivity of 27% (95% CI 18-37%) for predicting deterioration, with positive and negative likelihood ratios of 10.7 (95% CI 6.3-18.3) and 0.8 (95% CI 0.7-0.9), respectively. A lower threshold of lactate (≥2.0 mmol/L) had a sensitivity of 67% (95% CI 55-76%) and specificity of 66% (95% CI 63-69%), with corresponding positive and negative likelihood ratios of 2.0 (95% CI 1.7-2.3) and 0.5 (95% CI 0.4-0.7). CONCLUSIONS: High ED lactate is predictive of subsequent deterioration from sepsis within 72 h, and may be useful in determining disposition, but low lactate is not effective in screening stable patients at risk of deterioration.

Use of the low-frequency/high-frequency ratio of heart rate variability to predict short-term deterioration in emergency department patients with sepsis.

OBJECTIVE: To examine the ability of the low-frequency/high-frequency (LF/HF) ratio of heart rate variability (HRV) analysis to identify patients with sepsis at risk of early deterioration. METHODS: This is a prospective observational cohort study of patients with sepsis presenting to the Montefiore Medical Center ED from December 2014 through September 2015. On presentation, a single ECG Holter recording was obtained and analysed to obtain the LF/HF ratio of HRV. Initial Sequential Organ Failure Assessment (SOFA) scores were computed. Patients were followed for 72 hours to identify those with early deterioration. RESULTS: 466 patients presenting to the ED with sepsis were analysed. Thirty-two (7%) reached at least one endpoint within 72 hours. An LF/HF ratio <1 had a sensitivity and specificity of 34% (95% CI (19% to 53%)) and 82% (95% CI (78% to 85%)), respectively, with positive and negative likelihood ratios of 1.9 (95% CI (1.1 to 3.2)) and 0.8 (95% CI (0.6 to 1.0)). An initial SOFA score ≥3 had a sensitivity and specificity of 38% (95% CI (22% to 56%)) and 92% (95% CI (89% to 95%)), with positive and negative likelihood ratios of 4.9 (95% CI (2.8 to 8.6)) and 0.7 (95% CI (0.5 to 0.9)). The composite measure of HRV+SOFA had improved sensitivity (56%, 95% CI (38% to 73%)) but at the expense of specificity (77%, 95% CI (72% to 80%)), with positive and negative likelihood ratios of 2.4 (95% CI (1.7 to 3.4)) and 0.6 (95% CI (0.4 to 0.9)). Receiver operating characteristic analysis did not identify a superior alternate threshold for the LF/HF ratio. Kaplan-Meier survival functions differed significantly (p=0.02) between low (<1) and high (≥1) LF/HF groups. CONCLUSIONS: While we found a statistically significant relationship between HRV, SOFA and HRV+SOFA, and early deterioration, none reliably functioned as a clinical predictive tool. More complex multivariable models will likely be required to construct models with clinical utility.

Heart rate variability during high heat stress: a comparison between young and older adults with and without Type 2 diabetes.

We examined whether older individuals with and without Type 2 diabetes (T2D) experience differences in heart rate variability (HRV) during a 3-h exposure to high heat stress compared with young adults. Young (Young; n = 22; 23 ± 3 yr) and older individuals with (T2D; n = 11; 59 ± 9 yr) and without (Older; n = 25; 63 ± 5 yr) T2D were exposed to heat stress (44°C, 30% relative humidity) for 3 h. Fifty-five HRV measures were assessed for 15 min at baseline and at minutes 82.5-97.5 (Mid) and minutes 165-180 (End) during heat stress. When compared with Young, a similar number of HRV indices were significantly different (P < 0.05) in Older (Baseline: 35; Mid: 29; End: 32) and T2D (Baseline: 31; Mid: 30; End: 27). In contrast, the number of HRV indices significantly different (P < 0.05) between Older and T2D were far fewer (Baseline: 13, Mid: 1, End: 3). Within-group analyses demonstrated a greater change in the Young group's HRV during heat stress compared with Older and T2D; the number of significantly different (P < 0.05) HRV indices between baseline and End were 42, 29, and 20, for Young, Older, and T2D, respectively. Analysis of specific HRV domains suggest that the Young group experienced greater sympathetic activity during heat stress compared with Older and T2D. In conclusion, when compared with young, older individuals with and without T2D demonstrate low HRV at baseline and less change in HRV (including an attenuated sympathetic response) during 3 h high heat stress, potentially contributing to impaired thermoregulatory function.

Can Monitoring Fetal Intestinal Inflammation Using Heart Rate Variability Analysis Signal Incipient Necrotizing Enterocolitis of the Neonate?

OBJECTIVE: Necrotizing enterocolitis of the neonate is an acute inflammatory intestinal disease that can cause necrosis and sepsis. Chorioamnionitis is a risk factor of necrotizing enterocolitis. The gut represents the biggest vagus-innervated organ. Vagal activity can be measured via fetal heart rate variability. We hypothesized that fetal heart rate variability can detect fetuses with incipient gut inflammation. DESIGN: Prospective animal study. SETTING: University research laboratory. SUBJECTS: Chronically instrumented near-term fetal sheep (n = 21). MEASUREMENTS AND MAIN RESULTS: Animals were surgically instrumented with vascular catheters and electrocardiogram to allow manipulation and recording from nonanesthetized animals. In 14 fetal sheep, inflammation was induced with lipopolysaccharide (IV) to mimic chorioamnionitis. Fetal arterial blood samples were drawn at selected time points over 54 hours post lipopolysaccharide for blood gas and cytokines (interleukin-6 and tumor necrosis factor-α enzymelinked immunosorbent assay). Fetal heart rateV was quantified throughout the experiment. The time-matched fetal heart rate variability measures were correlated to the levels of interleukin-6 and tumor necrosis factor-α. Upon necropsy, ionized calcium binding adaptor molecule 1+ (Iba1+), CD11c+ (M1), CD206+ (M2 macrophages), and occludin (leakiness marker) immunofluorescence in the terminal ileum was quantified along with regional Iba1+ signal in the brain (microglia). Interleukin-6 peaked at 3 hours post lipopolysaccharide accompanied by mild cardiovascular signs of sepsis. At 54 hours, we identified an increase in Iba1+ and, specifically, M1 macrophages in the ileum accompanied by increased leakiness, with no change in Iba1 signal in the brain. Preceding this change on tissue level, at 24 hours, a subset of nine fetal heart rate variability measures correlated exclusively to the Iba+ markers of ileal, but not brain, inflammation. An additional fetal heart rate variability measure, mean of the differences of R-R intervals, correlated uniquely to M1 ileum macrophages increasing due to lipopolysaccharide. CONCLUSIONS: We identified a unique subset of fetal heart rate variability measures reflecting 1.5 days ahead of time the levels of macrophage activation and increased leakiness in terminal ileum. We propose that such subset of fetal heart rate variability measures reflects brain-gut communication via the vagus nerve. Detecting such noninvasively obtainable organ-specific fetal heart rate variability signature of inflammation would alarm neonatologists about neonates at risk of developing necrotizing enterocolitis and sepsis. Clinical validation studies are required.

Heart rate variability in relation to stress in the Asian elephant (Elephas maximus).

This study describes a safe, reliable, and accessible means to measure heart rate (HR) and HR variability (HRV) and evaluates the use of HRV as a physiological correlate of stress in the Asian elephant. A probabilistic model indicates that HRV measurements may adequately distinguish between stressed and non-stressed elephants.

Variabilité de la fréquence cardiaque en relation avec le stress chez un éléphant d'Asie(Elephas maximus). Cette étude décrit un moyen sûr, fiable et accessible de mesurer la fréquence cardiaque (FC) et la variabilité de la FC (VFC) et évalue l'utilisation de la VFC comme corrélat physiologique du stress chez l'éléphant d'Asie. Un modèle probabiliste indique que les mesures de la VFC peuvent adéquatement distinguer entre des éléphants stressés et non stressés.(Traduit par Isabelle Vallières).

Do heart and respiratory rate variability improve prediction of extubation outcomes in critically ill patients?

INTRODUCTION: Prolonged ventilation and failed extubation are associated with increased harm and cost. The added value of heart and respiratory rate variability (HRV and RRV) during spontaneous breathing trials (SBTs) to predict extubation failure remains unknown. METHODS: We enrolled 721 patients in a multicenter (12 sites), prospective, observational study, evaluating clinical estimates of risk of extubation failure, physiologic measures recorded during SBTs, HRV and RRV recorded before and during the last SBT prior to extubation, and extubation outcomes. We excluded 287 patients because of protocol or technical violations, or poor data quality. Measures of variability (97 HRV, 82 RRV) were calculated from electrocardiogram and capnography waveforms followed by automated cleaning and variability analysis using Continuous Individualized Multiorgan Variability Analysis (CIMVA™) software. Repeated randomized subsampling with training, validation, and testing were used to derive and compare predictive models. RESULTS: Of 434 patients with high-quality data, 51 (12%) failed extubation. Two HRV and eight RRV measures showed statistically significant association with extubation failure (P <0.0041, 5% false discovery rate). An ensemble average of five univariate logistic regression models using RRV during SBT, yielding a probability of extubation failure (called WAVE score), demonstrated optimal predictive capacity. With repeated random subsampling and testing, the model showed mean receiver operating characteristic area under the curve (ROC AUC) of 0.69, higher than heart rate (0.51), rapid shallow breathing index (RBSI; 0.61) and respiratory rate (0.63). After deriving a WAVE model based on all data, training-set performance demonstrated that the model increased its predictive power when applied to patients conventionally considered high risk: a WAVE score >0.5 in patients with RSBI >105 and perceived high risk of failure yielded a fold increase in risk of extubation failure of 3.0 (95% confidence interval (CI) 1.2 to 5.2) and 3.5 (95% CI 1.9 to 5.4), respectively. CONCLUSIONS: Altered HRV and RRV (during the SBT prior to extubation) are significantly associated with extubation failure. A predictive model using RRV during the last SBT provided optimal accuracy of prediction in all patients, with improved accuracy when combined with clinical impression or RSBI. This model requires a validation cohort to evaluate accuracy and generalizability. TRIAL REGISTRATION: ClinicalTrials.gov NCT01237886. Registered 13 October 2010.

Changes in heart rate variability during the induction and decay of heat acclimation.

PURPOSE: We evaluated the changes in core temperature, heart rate, and heart rate variability (HRV) during the induction and decay of heat acclimation. METHODS: Ten males (23 ± 3 years; 79.5 ± 3.5 kg; 15.2 ± 4.5 percent body fat; 51.13 ± 4.61 mLO(2)∙kg(-1)∙min(-1) peak oxygen uptake) underwent a 14-day heat acclimation protocol comprising of 90-min cycling at ~50 % peak oxygen uptake at 40 °C and ~20 % relative humidity. Core temperature, heart rate, and 102 HRV measures were recorded during a heat tolerance test conducted at baseline (day 0) and at the end of the induction (day 14) and decay (day 28) phases. RESULTS: Heat acclimation resulted in significantly reduced core temperature [rectal (χ (2) = 1298.14, p < 0.001); esophageal (χ (2) = 1069.88, p < 0.001)] and heart rate (χ (2) = 1230.17, p < 0.001). Following the decay phase, 26, 40, and 60 % of the heat acclimation-induced reductions in rectal temperature, esophageal temperature, and heart rate, respectively, were lost. Heat acclimation was accompanied by profound and broad changes in HRV: at the end of the induction phase, 75 of the 102 variability measures computed were significantly different (p < 0.001), compared to only 47 of the 102 at the end of the decay phase. CONCLUSIONS: Heat acclimation is accompanied by reduced core temperature, significant bradycardia, and marked alterations in HRV, which we interpret as being related to vagal dominance. The observed changes in core temperature persist for at least 2 weeks of non-exposure to heat, while the changes in heart rate and HRV decay faster and are only partly evident after 2 weeks of non-exposure to heat.

Cardiac autonomic modulation in individuals with controlled and uncomplicated hypertension during exercise-heat stress.

TAKE-HOME MESSAGE: During short bouts of light-to-vigorous exercise in the heat, controlled and uncomplicated hypertension did not significantly modulate HRV in physically active individuals. These findings can be used to refine guidance on use of exercise for hypertension management in the heat.

Effects of sex and wet-bulb globe temperature on heart rate variability during prolonged moderate-intensity exercise: a secondary analysis.

Sex differences in heart rate (HR) and heart rate variability (HRV), a surrogate of cardiac autonomic modulation, are evident during rest and exercise in young healthy individuals. However, it remains unclear whether sex impacts HRV during prolonged exercise at differing levels of environmental heat stress. Therefore, we completed a secondary analysis upon the effects of sex and wet-bulb globe temperature (WBGT) on HR and HRV during prolonged exercise. To achieve this, HR and HRV were assessed in non-endurance-trained and non-heat-acclimatised healthy men (n = 19) and women (n = 15) aged 18-45 years during 180 min of treadmill walking at a moderate metabolic rate (200 W/m2: equivalent to ∼35% peak aerobic power) in 16, 24, 28, and 32 °C WBGT. In the final 5 min prior to exercise termination, HR was observed to be higher in women relative to men in all but the 32 °C WBGT. Although no sex differences were observed for the HRV metric of root-mean-square of successive differences, high-frequency power was higher in women relative to men across WBGT conditions. These findings indicate that, in healthy non-heat-acclimatised individuals, women respond to prolonged exercise-heat stress with a greater increase in HR despite cardiac vagal autonomic modulation remaining equal or increasing compared to men. Novelty: Prior to exercise termination, females respond with a greater increase in HR under all WBGTs except the hottest (32 °C). Sex influenced  HRV metrics during all WBGTs, but results were mixed. Further characterisation of HRV sex differences remains an important area of research.

Predicting Time to Death After Withdrawal of Life-Sustaining Measures Using Vital Sign Variability: Derivation and Validation.

To develop a predictive model using vital sign (heart rate and arterial blood pressure) variability to predict time to death after withdrawal of life-supporting measures. DESIGN: Retrospective analysis of observational data prospectively collected as part of the Death Prediction and Physiology after Removal of Therapy study between May 1, 2014, and May 1, 2018. SETTING: Adult ICU. PATIENTS: Adult patients in the ICU with a planned withdrawal of life-supporting measures and an expectation of imminent death. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Vital sign waveforms and clinical data were prospectively collected from 429 patients enrolled from 20 ICUs across Canada, the Czech Republic, and the Netherlands. Vital sign variability metrics were calculated during the hour prior to withdrawal. Patients were randomly assigned to the derivation cohort (288 patients) or the validation cohort (141 patients), of which 103 and 54, respectively, were eligible for organ donation after circulatory death. Random survival forest models were developed to predict the probability of death within 30, 60, and 120 minutes following withdrawal using variability metrics, features from existing clinical models, and/or the physician's prediction of rapid death. A model employing variability metrics alone performed similarly to a model employing clinical features, whereas the combination of variability, clinical features, and physician's prediction achieved the highest area under the receiver operating characteristics curve of all models at 0.78 (0.7-0.86), 0.79 (0.71-0.87), and 0.8 (0.72-0.88) for 30-, 60- and 120-minute predictions, respectively. CONCLUSIONS: Machine learning models of vital sign variability data before withdrawal of life-sustaining measures, combined with clinical features and the physician's prediction, are useful to predict time to death. The impact of providing this information for decision support for organ donation merits further investigation.