Detection of a Stroke Volume Decrease by Machine-Learning Algorithms Based on Thoracic Bioimpedance in Experimental Hypovolaemia.

Compensated shock and hypovolaemia are frequent conditions that remain clinically undetected and can quickly cause deterioration of perioperative and critically ill patients. Automated, accurate and non-invasive detection methods are needed to avoid such critical situations. In this experimental study, we aimed to create a prediction model for stroke volume index (SVI) decrease based on electrical cardiometry (EC) measurements. Transthoracic echo served as reference for SVI assessment (SVI-TTE). In 30 healthy male volunteers, central hypovolaemia was simulated using a lower body negative pressure (LBNP) chamber. A machine-learning algorithm based on variables of EC was designed. During LBNP, SVI-TTE declined consecutively, whereas the vital signs (arterial pressures and heart rate) remained within normal ranges. Compared to heart rate (AUC: 0.83 (95% CI: 0.73-0.87)) and systolic arterial pressure (AUC: 0.82 (95% CI: 0.74-0.85)), a model integrating EC variables (AUC: 0.91 (0.83-0.94)) showed a superior ability to predict a decrease in SVI-TTE ≥ 20% (p = 0.013 compared to heart rate, and p = 0.002 compared to systolic blood pressure). Simulated central hypovolaemia was related to a substantial decline in SVI-TTE but only minor changes in vital signs. A model of EC variables based on machine-learning algorithms showed high predictive power to detect a relevant decrease in SVI and may provide an automated, non-invasive method to indicate hypovolaemia and compensated shock.

A randomized controlled trial of treatment with intermittent negative pressure for intermittent claudication.

OBJECTIVE: We investigated the effects of lower extremity intermittent negative pressure (INP) treatment for 1 hour two times daily for 12 weeks on the walking distance of patients with intermittent claudication (IC). METHODS: Patients with IC were randomized to treatment with -40 mm Hg INP (treatment group) or -10 mm Hg INP (sham control group). Pain-free walking distance (PWD) and maximal walking distance (MWD) on a treadmill, resting and postexercise ankle-brachial index, resting and postischemic blood flow (plethysmography), and quality of life (EQ-5D-5L and Vascuqol-6) were measured at baseline and after 12 weeks of treatment. RESULTS: A total of 72 patients were randomized, and 63 had data available for the intention-to-treat analyses. The between-group comparisons showed a significant change in the PWD, favoring the treatment group over the sham control group (estimated treatment effect, 50 m; 95% confidence interval [CI], 11-89; P = .014). The PWD had increased by 68 m (P < .001) in the treatment group and 18 m (P = .064) in the sham control group. No significant difference was found in the change in the MWD between the two groups (estimated treatment effect, 42 m; 95% CI, -14 to 97; P = .139). The MWD had increased by 62 m (P = .006) in the treatment group and 20 m (P = .265) in the sham control group. For patients with a baseline PWD of <200 m (n = 56), significant changes had occurred in both PWD and MWD between the two groups, favoring the treatment group (estimated treatment effect, 42 m; 95% CI, 2-83; P = .042; and estimated treatment effect, 62 m; 95% CI, 5-118; P = .032; respectively). Both overall and for the group of patients with a PWD <200 m, no significant differences were found in the changes in the resting and postexercise ankle-brachial index, resting and postischemic blood flow, or quality of life parameters between the two groups. CONCLUSIONS: Treatment with -40 mm Hg INP increased the PWD compared with sham treatment in patients with IC. For the patients with a baseline PWD of <200 m, an increase was found in both PWD and MWD compared with sham treatment.

Lower Extremity Intermittent Negative Pressure for Intermittent Claudication. Follow-Up after 24 Weeks of Treatment.

BACKGROUND: Treatment with lower extremity intermittent negative pressure (INP) of -40 mm Hg for one hour twice daily for 12 weeks, increases walking capacity in patients with intermittent claudication (IC). However, the effects of INP treatment beyond 12 weeks have not been elucidated. The aim of the present study was to investigate the clinical effects of INP treatment after 24 weeks in patients with IC. METHODS: This was a follow-up study after a randomized sham-controlled trial, where patients randomized to the active treatment group were offered to continue treatment for 12 additional weeks (24 weeks in total). Treatment with -40 mm Hg INP was applied in a pressure chamber sealed around the lower leg, and the patients were instructed to treat themselves at home one hour in the morning and one hour in the evening. Pain free walking distance (PWD), maximal walking distance (MWD), resting ankle-brachial index (ABI) and post exercise ABI were measured at baseline, after 12 and 24 weeks. RESULTS: Ten out of 32 patients (31%) from the active treatment group in the initial trial were included in this follow-up study. At baseline, PWD was (mean ±SD) 151 ± 91 m and MWD was 362 ±159 m. There was a significant increase in both PWD and MWD after 24 weeks of treatment, compared to baseline (ANOVA; P= 0.006 and P= 0.012, respectively). Post hoc tests revealed that PWD increased significantly from baseline to 12 weeks (mean 81 m; 95% CI [6, 156]; P = 0.032), and that MWD increased significantly from 12 to 24 weeks (mean 145 m; 95% CI [22, 268]; P = 0.018). There were no significant changes in resting ABI or post exercise ABI during the 24-week treatment period (ANOVA; P= 0.157 and P= 0.450, respectively). CONCLUSION: Both PWD and MWD improved after treatment with - 40 mm Hg INP for one hour twice daily for 24 weeks, compared to baseline. The main improvement in PWD occurred during the first 12 weeks of treatment, whereas the main improvement in MWD occurred between 12 and 24 weeks of treatment.

The effect of hypercapnia on regional cerebral blood flow regulation during progressive lower-body negative pressure.

PURPOSE: Previous work indicates that dynamic cerebral blood flow (CBF) regulation is impaired during hypercapnia; however, less is known about the impact of resting hypercapnia on regional CBF regulation during hypovolemia. Furthermore, there is disparity within the literature on whether differences between anterior and posterior CBF regulation exist during physiological stressors. We hypothesized: (a) lower-body negative pressure (LBNP)-induced reductions in cerebral blood velocity (surrogate for CBF) would be more pronounced during hypercapnia, indicating impaired CBF regulation; and (b) the anterior and posterior cerebral circulations will exhibit similar responses to LBNP. METHODS: In 12 healthy participants (6 females), heart rate (electrocardiogram), mean arterial pressure (MAP; finger photoplethosmography), partial pressure of end-tidal carbon dioxide (PETCO2), middle cerebral artery blood velocity (MCAv) and posterior cerebral artery blood velocity (PCAv; transcranial Doppler ultrasound) were measured. Cerebrovascular conductance (CVC) was calculated as MCAv or PCAv indexed to MAP. Two randomized incremental LBNP protocols were conducted (- 20, - 40, - 60 and - 80 mmHg; three-minute stages), during coached normocapnia (i.e., room air), and inspired 5% hypercapnia (~ + 7 mmHg PETCO2 in normoxia). RESULTS: The main findings were: (a) static CBF regulation in the MCA and PCA was similar during normocapnic and hypercapnic LBNP trials, (b) MCA and PCA CBV and CVC responded similarly to LBNP during normocapnia, but (c) PCAv and PCA CVC were reduced to a greater extent at - 60 mmHg LBNP (P = 0.029; P < 0.001) during hypercapnia. CONCLUSION: CBF regulation during hypovolemia was preserved in hypercapnia, and regional differences in cerebrovascular control may exist during superimposed hypovolemia and hypercapnia.

Neurovascular coupling is not influenced by lower body negative pressure in humans.

Cerebral blood flow is tightly coupled with local neuronal activation and metabolism, i.e., neurovascular coupling (NVC). Studies suggest a role of sympathetic nervous system in the regulation of cerebral blood flow. However, this is controversial, and the sympathetic regulation of NVC in humans remains unclear. Since impaired NVC has been identified in several chronic diseases associated with a heightened sympathetic activity, we aimed to determine whether reflex-mediated sympathetic activation via lower body negative pressure (LBNP) attenuates NVC in humans. NVC was assessed using a visual stimulation protocol (5 cycles of 30 s eyes closed and 30 s of reading) in 11 healthy participants (aged 24 ± 3 yr). NVC assessments were made under control conditions and during LBNP at -20 and -40 mmHg. Posterior (PCA) and middle (MCA) cerebral artery mean blood velocity (Vmean) and vertebral artery blood flow (VAflow) were simultaneously determined with cardiorespiratory variables. Under control conditions, the visual stimulation evoked a robust increase in PCAVmean (∆18.0 ± 4.5%), a moderate rise in VAflow (∆9.6 ± 4.3%), and a modest increase in MCAVmean (∆3.0 ± 1.9%). The magnitude of NVC response was not affected by mild-to-moderate LBNP (all P > 0.05 for repeated-measures ANOVA). Given the small change that occurred in partial pressure of end-tidal CO2 during LBNP, this hypocapnia condition was matched via voluntary hyperventilation in absence of LBNP in a subgroup of participants (n = 8). The mild hypocapnia during LBNP did not exert a confounding influence on the NVC response. These findings indicate that the NVC is not influenced by LBNP or mild hypocapnia in humans.NEW & NOTEWORTHY Visual stimulation evoked a robust increase in posterior cerebral artery velocity and a modest increase in vertebral artery blood flow, i.e., neurovascular coupling (NVC), which was unaffected by lower body negative pressure (LBNP) in humans. In addition, although LBNP induced a mild hypocapnia, this degree of hypocapnia in the absence of LBNP failed to modify the NVC response.

Cardiac power parameters during hypovolemia, induced by the lower body negative pressure technique, in healthy volunteers.

BACKGROUND: Changes in cardiac power parameters incorporate changes in both aortic flow and blood pressure. We hypothesized that dynamic and non-dynamic cardiac power parameters would track hypovolemia better than equivalent flow- and pressure parameters, both during spontaneous breathing and non-invasive positive pressure ventilation (NPPV). METHODS: Fourteen healthy volunteers underwent lower body negative pressure (LBNP) of 0, -20, -40, -60 and -80 mmHg to simulate hypovolemia, both during spontaneous breathing and during NPPV. We recorded aortic flow using suprasternal ultrasound Doppler and blood pressure using Finometer, and calculated dynamic and non-dynamic parameters of cardiac power, flow and blood pressure. These were assessed on their association with LBNP-levels. RESULTS: Respiratory variation in peak aortic flow was the dynamic parameter most affected during spontaneous breathing increasing 103 % (p < 0.001) from baseline to LBNP -80 mmHg. Respiratory variation in pulse pressure was the most affected dynamic parameter during NPPV, increasing 119 % (p < 0.001) from baseline to LBNP -80 mmHg. The cardiac power integral was the most affected non-dynamic parameter falling 59 % (p < 0.001) from baseline to LBNP -80 mmHg during spontaneous breathing, and 68 % (p < 0.001) during NPPV. CONCLUSIONS: Dynamic cardiac power parameters were not better than dynamic flow- and pressure parameters at tracking hypovolemia, seemingly due to previously unknown variation in peripheral vascular resistance matching respiratory changes in hemodynamics. Of non-dynamic parameters, the power parameters track hypovolemia slightly better than equivalent flow parameters, and far better than equivalent pressure parameters.

Beneficial effects of elevating cardiac preload on left-ventricular diastolic function and volume during heat stress: implications toward tolerance during a hemorrhagic insult.

Volume loading normalizes tolerance to a simulated hemorrhagic challenge in heat-stressed individuals, relative to when these individuals are thermoneutral. The mechanism(s) by which this occurs is unknown. This project tested two unique hypotheses; that is, the elevation of central blood volume via volume loading while heat stressed would 1) increase indices of left ventricular diastolic function, and 2) preserve left ventricular end-diastolic volume (LVEDV) during a subsequent simulated hemorrhagic challenge induced by lower-body negative pressure (LBNP). Indices of left ventricular diastolic function were evaluated in nine subjects during the following conditions: thermoneutral, heat stress, and heat stress after acute volume loading sufficient to return ventricular filling pressures toward thermoneutral levels. LVEDV was also measured in these subjects during the aforementioned conditions prior to and during a simulated hemorrhagic challenge. Heat stress did not change indices of diastolic function. Subsequent volume infusion elevated indices of diastolic function, specifically early diastolic mitral annular tissue velocity (E') and early diastolic propagation velocity (E) relative to both thermoneutral and heat stress conditions (P < 0.05 for both). Heat stress reduced LVEDV (P < 0.05), while volume infusion returned LVEDV to thermoneutral levels. The reduction in LVEDV to LBNP was similar between thermoneutral and heat stress conditions, whereas the reduction after volume infusion was attenuated relative to both conditions (P < 0.05). Absolute LVEDV during LBNP after volume loading was appreciably greater relative to the same level of LBNP during heat stress alone. Thus, rapid volume infusion during heat stress increased indices of left ventricular diastolic function and attenuated the reduction in LVEDV during LBNP, both of which may serve as mechanisms by which volume loading improves tolerance to a combined hyperthermic and hemorrhagic challenge.

Aortic distensibility is reduced during intense lower body negative pressure and is related to low frequency power of systolic blood pressure.

As sympathetic activity approximately doubles during intense lower body negative pressure (LBNP) of -60 mmHg or greater, we examined the relationship between surrogate markers of sympathetic activation and central arterial distensibility during severe LBNP. Eight participants were exposed to progressive 8-min stages of LBNP of increasing intensity (-20, -40, -60, and -80 mmHg), while recording carotid-femoral pulse wave velocity (cPWV), stroke volume (SV), heart rate, and beat-by-beat blood pressure. The spectral power of low frequency oscillations in SBP (SBP(LF)) was used as a surrogate indicator of sympathetically modulated vasomotor modulation. Total arterial compliance (C) was calculated as C = SV/pulse pressure. Both cPWV and C were compared between baseline, 50 % of the maximally tolerated LBNP stage (LBNP(50)), and the maximum fully tolerated stage of LBNP (LBNP(max)). No change in mean arterial pressure (MAP) occurred over LBNP. An increase in cPWV (6.5 ± 2.2; 7.2 ± 1.4; 9.0 ± 2.5 m/s; P = 0.004) occurred during LBNP(max). Over progressive LBNP, SBP(LF) increased (8.5 ± 4.6; 9.3 ± 5.8; 16.1 ± 12.9 mmHg(2); P = 0.04) and C decreased significantly (18.3 ± 6.8; 14.3 ± 4.1; 11.6 ± 4.8 ml/mmHg × 10; P = 0.03). The mean correlation (r) between cPWV and SBP(LF) was 0.9 ± 0.03 (95 % CI 0.79-0.99). Severe LBNP increased central stiffness and reduced total arterial compliance. It appears that increased sympathetic vasomotor tone during LBNP is associated with reduced aortic distensibility in the absence of changes in MAP.

Short-term variability of blood pressure: effects of lower-body negative pressure and long-duration bed rest.

Mild lower-body negative pressure (LBNP) has been utilized to selectively unload cardiopulmonary baroreceptors, but there is evidence that arterial baroreceptors can be transiently unloaded after the onset of mild LBNP. In this paper, a black box mathematical model for the prediction of diastolic blood pressure (DBP) variability from multiple inputs (systolic blood pressure, R-R interval duration, and central venous pressure) was applied to interpret the dynamics of blood pressure maintenance under the challenge of LBNP and in long-duration, head-down bed rest (HDBR). Hemodynamic recordings from seven participants in the WISE (Women's International Space Simulation for Exploration) Study collected during an experiment of incremental LBNP (-10 mmHg, -20 mmHg, -30 mmHg) were analyzed before and on day 50 of a 60-day-long HDBR campaign. Autoregressive spectral analysis focused on low-frequency (LF, ~0.1 Hz) oscillations of DBP, which are related to fluctuations in vascular resistance due to sympathetic and baroreflex regulation of vasomotor tone. The arterial baroreflex-related component explained 49 ± 13% of LF variability of DBP in spontaneous conditions, and 89 ± 9% (P < 0.05) on day 50 of HDBR, while the cardiopulmonary baroreflex component explained 17 ± 9% and 12 ± 4%, respectively. The arterial baroreflex-related variability was significantly increased in bed rest also for LBNP equal to -20 and -30 mmHg. The proposed technique provided a model interpretation of the proportional effect of arterial baroreflex vs. cardiopulmonary baroreflex-mediated components of blood pressure control and showed that arterial baroreflex was the main player in the mediation of DBP variability. Data during bed rest suggested that cardiopulmonary baroreflex-related effects are blunted and that blood pressure maintenance in the presence of an orthostatic stimulus relies mostly on arterial control.

Feature Importance Analysis for Compensatory Reserve to Predict Hemorrhagic Shock.

Hemorrhage is the leading cause of preventable death from trauma. Traditionally, vital signs have been used to detect blood loss and possible hemorrhagic shock. However, vital signs are not sensitive for early detection because of physiological mechanisms that compensate for blood loss. As an alternative, machine learning algorithms that operate on an arterial blood pressure (ABP) waveform acquired via photoplethysmography have been shown to provide an effective early indicator. However, these machine learning approaches lack physiological interpretability. In this paper, we evaluate the importance of nine ABP-derived features that provide physiological insight, using a database of 40 human subjects from a lower-body negative pressure model of progressive central hypovolemia. One feature was found to be considerably more important than any other. That feature, the half-rise to dicrotic notch (HRDN), measures an approximate time delay between the ABP ejected and reflected wave components. This delay is an indication of compensatory mechanisms such as reduced arterial compliance and vasoconstriction. For a scale of 0% to 100%, with 100% representing normovolemia and 0% representing decompensation, linear regression of the HRDN feature results in root-mean-squared error of 16.9%, R2 of 0.72, and an area under the receiver operating curve for detecting decompensation of 0.88. These results are comparable to previously reported results from the more complex black box machine learning models. Clinical Relevance- A single physiologically interpretable feature measured from an arterial blood pressure waveform is shown to be effective in monitoring for blood loss and impending hemorrhagic shock based on data from a human lower-body negative pressure model of progressive central hypolemia.

End-tidal carbon dioxide tension reflects arterial carbon dioxide tension in the heat-stressed human with and without simulated hemorrhage.

End-tidal carbon dioxide tension (Pet(CO(2))) is reduced during an orthostatic challenge, during heat stress, and during a combination of these two conditions. The importance of these changes is dependent on Pet(CO(2)) being an accurate surrogate for arterial carbon dioxide tension (Pa(CO(2))), the latter being the physiologically relevant variable. This study tested the hypothesis that Pet(CO(2)) provides an accurate assessment of Pa(CO(2)) during the aforementioned conditions. Comparisons between these measures were made: 1) after two levels of heat stress (N = 11); 2) during combined heat stress and simulated hemorrhage [via lower-body negative pressure (LBNP), N = 8]; and 3) during an end-tidal clamping protocol to attenuate heat stress-induced reductions in Pet(CO(2)) (N = 7). Pet(CO(2)) and Pa(CO(2)) decreased during heat stress (P < 0.001); however, there was no group difference between Pa(CO(2)) and Pet(CO(2)) (P = 0.36) nor was there a significant interaction between thermal condition and measurement technique (P = 0.06). To verify that this nonsignificant trend for the interaction was not due to a type II error, Pet(CO(2)) and Pa(CO(2)) at three distinct thermal conditions were also compared using paired t-tests, revealing no difference between Pa(CO(2)) and Pet(CO(2)) while normothermic (P = 0.14) and following a 1.0 ± 0.2°C (P = 0.21) and 1.4 ± 0.2°C (P = 0.28) increase in internal temperature. During LBNP while heat stressed, measures of Pet(CO(2)) and Pa(CO(2)) were similar (P = 0.61). Likewise, during the end-tidal carbon dioxide clamping protocol, the increases in Pet(CO(2)) (7.5 ± 2.8 mmHg) and Pa(CO(2)) (6.6 ± 3.4 mmHg) were similar (P = 0.31). These data indicate that mean Pet(CO(2)) reflects mean Pa(CO(2)) during the evaluated conditions.

Effects of oral contraceptives on sympathetic nerve activity during orthostatic stress in young, healthy women.

Recent studies report that the menstrual cycle alters sympathetic neural responses to orthostatic stress in young, eumenorrheic women. The purpose of the present study was to determine whether oral contraceptives (OC) influence sympathetic neural activation during an orthostatic challenge. Based on evidence that sympathetic baroreflex sensitivity (BRS) is increased during the "low hormone" (LH) phase (i.e., placebo pills) in women taking OC, we hypothesized an augmented muscle sympathetic nerve activity (MSNA) response to orthostatic stress during the LH phase. MSNA, mean arterial pressure (MAP), and heart rate (HR) were recorded during progressive lower body negative pressure (LBNP; -5, -10, -15, -20, -30, -40 mmHg; 3 min/stage) in 12 healthy women taking OC (age 22 +/- 1 years). Sympathetic BRS was assessed by examining relations between spontaneous fluctuations of diastolic arterial pressure and MSNA. Subjects were examined twice: once during LH phase and once approximately 3 wk after LH during the "high hormone" phase (randomized order). Resting MSNA (10 +/- 2 vs. 13 +/- 2 bursts/min), MAP (85 +/- 3 vs. 84 +/- 3 mmHg), and HR (62 +/- 2 vs. 65 +/- 3 beats/min) were not different between phases. MSNA and HR increased during progressive LBNP (P < 0.001), and these increases were similar between phases. Progressive LBNP did not change MAP during either phase. Sympathetic BRS increased during progressive LBNP, but these responses were not different between LH and high hormone phases. In conclusion, our results demonstrate that OCs do not alter cardiovascular and sympathetic neural responses to an orthostatic challenge in young, healthy women.

LBNP tolerance analyzed retrospectively using a structural equation model.

UNLABELLED: It would be useful to be able to predict tolerance to lower body negative pressure (LBNP) because of the association of low LBNP tolerance to low orthostatic tolerance. PURPOSE: To determine how well tolerance to LBNP can be modeled using laboratory variables assessed noninvasively. METHODS: There were 125 male and female college age and older (> 60 yr) subjects who underwent graded LBNP to presyncope. Tolerance was quantified by the LBNP tolerance index (LTI). Noninvasive variables assessed at rest and at presyncope were used to predict LTI via structural equation modeling (SEM). SEM can better address the correlation and variable interaction effects inherent in assessing orthostatic tolerance, e.g., multicollinearity, compared to traditional regression techniques. RESULTS: With SEM, the manifest variables of gender, % body fat, maximal change in heart rate from rest to presyncope (delta HR), and resting total peripheral conductance (TPC) explained 40% of the variance in LTI. All the variables had direct significant influences on LTI; in addition, % body fat mediated the influence of gender and age while AHR mediated the effects of TPC. An exaggerated HR response to LBNP was associated with an increased LBNP tolerance (beta = -0.396). CONCLUSION: About 40% of the variability in LBNP tolerance can be predicted using easily measured variables. Male gender, a potentiated HR response to LBNP, higher resting TPC, older age, and lower body fat are associated with an increased LBNP tolerance.

[Some of the aspects of comparative analysis of the hemodynamic reactions to LBNP in cosmonauts of different age groups].

This was the first study of age-related differences of the cardiovascular system functioning and reactions to the LBNP test in career cosmonauts. Results of 174 LBNP tests performed within the standard medical monitoring program using Gamma-01 (orbital station Mir) and Gamma-lM (ISS) were subjected to comparative analysis. Thirty eight cosmonauts--members of 25 long-duration Mir and ISS missions were divided into two age groups, i.e. 30-39 y.o. (mean 36 & 0.7, 39% of all subjects) and 40-55 y.o. (mean 46 & 0.8, 61% of all subjects). The testing was performed before launch and in flight (typically on FD-120). Age-specifc changes in the hemodynamic status were recorded in resting cosmonauts pre-flight and in spaceflight microgravity; relative dynamics of the CV parameters in response to standing posture imitation was on one and the same patterns and yet demonstrated unequal intensity before and in flight. Test results implicate that analysis and interpretation of cosmonauts' medical monitoring data should take into account individual age, which is of particular practical importance when dealing with the LBNP test data obtained in different periods of space flight.

Similar hemostatic responses to hypovolemia induced by hemorrhage and lower body negative pressure reveal a hyperfibrinolytic subset of non-human primates.

BACKGROUND: To study central hypovolemia in humans, lower body negative pressure (LBNP) is a recognized alternative to blood removal (HEM). While LBNP mimics the cardiovascular responses of HEM in baboons, similarities in hemostatic responses to LBNP and HEM remain unknown in this species. METHODS: Thirteen anesthetized baboons were exposed to progressive hypovolemia by HEM and, four weeks later, by LBNP. Hemostatic activity was evaluated by plasma markers, thromboelastography (TEG), flow cytometry, and platelet aggregometry at baseline (BL), during and after hypovolemia. RESULTS: BL values were indistinguishable for most parameters although platelet count, maximal clot strength (MA), protein C, thrombin anti-thrombin complex (TAT), thrombin activatable fibrinolysis inhibitor (TAFI) activity significantly differed between HEM and LBNP. Central hypovolemia induced by either method activated coagulation; TEG R-time decreased and MA increased during and after hypovolemia compared to BL. Platelets displayed activation by flow cytometry; platelet count and functional aggregometry were unchanged. TAFI activity and protein, Factors V and VIII, vWF, Proteins C and S all demonstrated hemodilution during HEM and hemoconcentration during LBNP, whereas tissue plasminogen activator (tPA), plasmin/anti-plasmin complex, and plasminogen activator inhibitor-1 did not. Fibrinolysis (TEG LY30) was unchanged by either method; however, at BL, fibrinolysis varied greatly. Post-hoc analysis separated baboons into low-lysis (LY30 <2%) or high-lysis (LY30 >2%) whose fibrinolytic state matched at both HEM and LBNP BL. In high-lysis, BL tPA and LY30 correlated strongly (r = 0.95; P<0.001), but this was absent in low-lysis. In low-lysis, BL TAFI activity and tPA correlated (r = 0.88; P<0.050), but this was absent in high-lysis. CONCLUSIONS: Central hypovolemia induced by either LBNP or HEM resulted in activation of coagulation; thus, LBNP is an adjunct to study hemorrhage-induced pro-coagulation in baboons. Furthermore, this study revealed a subset of baboons with baseline hyperfibrinolysis, which was strongly coupled to tPA and uncoupled from TAFI activity.

Cerebral hemodynamics and brain functional activity during lower body negative pressure.

INTRODUCTION: Exposure to high +Gz acceleration forces on a centrifuge or in an aircraft can severely decrease cerebral blood perfusion and cause rapid G-induced loss of consciousness. However, milder acceleration may gradually reduce cerebral blood flow and affect cognitive function in subtler ways. This study used lower body negative pressure (LBNP) to mimic +Gz circulatory effects in order to study cerebral hemodynamics and brain function. METHODS: Subjects were 15 healthy men, 19-21 yr of age. They were exposed to LBNP at two levels for 5 min each separated by a 10-min recovery period. The conditions were low (LO), -4.00 kPa (-30 mmHg) and high (HI), -6.67 kPa (-50 mmHg).Variables measured before, during, and after LBNP included cerebral blood flow velocity (CBFV) in the middle cerebral artery, blood oxygen saturation (SaO2), heart rate (HR), blood pressure, P300 of event-related EEG potentials, reaction time, and tracking error. RESULTS: LO significantly reduced CBFV at 4 and 5 min, increased HR, and decreased the amplitude of P300, but none of the other variables changed from baseline. In contrast, HI produced significant changes in most variables: CBFV decreased at 2 min and then fell further at 4 and 5 min, HR increased, and SaO2 decreased. Significant neurocognitive changes included increased latency and reduced amplitude of P300, slower reaction time, and greater tracking error. CONCLUSION: The higher level of LBNP used here reduced cerebral perfusion sufficiently to impair neurocognitive function. This model may be useful for further studies of these and other variables under closely controlled conditions.

Negative pressure therapy with instillation for the treatment of infected wounds: recommendations of utilization based on evidence.

OBJECTIVE: To establish recommendations related to negative pressure therapy  with instillation according to effectiveness, safety, efficiency, consensus guidelines and stability data of instillation solutions. METHOD: A literature search was conducted to compare the available evidence  regarding effectiveness, safety and efficiency of negative pressure therapy with  instillation, as well as the existence of consensus guidelines for use. The articles  were classified according to the "Scale of evidence classification for therapeutic  studies" of the American Society of Plastic and Reconstructive Surgery. RESULTS: A total of 13 studies were included, of which five were comparative cohort studies (level II and III of evidence), and the rest  corresponded to case series (level IV of evidence). Two consensus guidelines  were selected with recommendations regarding the type of wound, instillation solution, solution retention time, vacuum pressure and appropriate  vacuum time. According to literature and available evidence, recommendations were proposed and established on negative pressure therapy  with instillation in our hospital, including stability data of the proposed solutions. CONCLUSIONS: This paper provides preliminary guidelines on the application of  negative pressure therapy with instillation until new evidence supports or  modifies these recommendations.

Objetivo: Establecer recomendaciones relacionadas con la terapia de presión negativa con instilación según efectividad, seguridad, eficiencia, guías de  consenso y estabilidades contrastadas de las soluciones de instilación. Método: Se realizó una búsqueda bibliográfica para contrastar la evidencia disponible en cuanto a efectividad, seguridad y eficiencia de la terapia de presión negativa con instilación, así como la existencia de guías de consenso de utilización. Se clasificaron los artículos en función de la "Escala de clasificación de evidencia para estudios terapéuticos" según la  Sociedad Americana de Cirugía Plástica y Reconstructiva.Resultados: Se incluyeron 13 estudios, de los cuales cinco fueron estudios de  cohortes comparativos (nivel II y III de evidencia), y el resto correspondieron a  series de casos (nivel IV de evidencia). Se seleccionaron dos guías de consenso  con recomendaciones según tipo de herida, solución de instilación, tiempo de  retención de solución, presión de vacío y tiempo de vacío apropiado. Según la  literatura y la evidencia disponible, se propusieron y establecieron recomendaciones sobre la terapia de presión negativa con  instilación en nuestro hospital, incluyendo datos de estabilidad de las soluciones  propuestas.Conclusiones: Este manuscrito proporciona pautas preliminares para la aplicación de la terapia de presión negativa con instilación hasta que nuevas evidencias apoyen o modifiquen estas recomendaciones.

Efficacy and safety of active abdominal compression-decompression versus standard CPR for cardiac arrests: A systematic review and meta-analysis of 17 RCTs.

BACKGROUND & AIM: Active abdominal compression-decompression cardiopulmonary resuscitation (AACD-CPR), which applies to cardiac arrests with contraindication of standard chest compressions (SCC) CPR, has been utilized in cardiac arrest. However, the efficacy and safety of AACD-CPR still remained controversy. This analysis was designed to comprehensively compare AACD versus SCC-CPR in patients with cardiac arrest. METHODS: We searched the Cochrane Library, PubMed, EMBASE, Web of Science and CNKI up to April 22, 2019. Mean difference (MD) and risk ratio (RR) with its 95% confidence intervals (CIs) were estimated to compare outcomes of the groups. Our primary outcomes were restoration of spontaneous circulation (ROSC) and short-term survival. Two reviewers assessed trial quality and extracted data independently. All statistical analyses were performed using standard statistical procedures provided in Review Manager 5.2 and Stata 12.0. RESULTS: A total of seventeen studies (N = 1647 patients) were identified for the present analysis. Compared with standard CPR, AACD-CPR was superior in restoration of spontaneous circulation (ROSC) and short-term survival, with pooled RRs of 1.38 (95% CI 1.23-1.55; P < 0.00001) and RRs of 2.05 (95% CI 1.69-2.50; P < 0.00001) respectively. In addition, significant superiority of AACD-CPR was found in incidence of fracture, long-term survival, pressure of end-tidal carbon dioxide (PETCO2), coronary perfusion pressure (CPP) and adverse events. No significant difference was observed in incidence of vomiting. CONCLUSIONS: Generally, in this combined analysis we found a statistically significant improvement in survival and ROSC with the use of AACD-CPR as compared with the use of standard CPR. There was also significant improvement in incidence of fracture, long-term survival, PETCO2 and CPP with AACD-CPR in comparison with standard CPR; results were not statistically different between the groups regarding to vomiting rate and adverse events. The standardized, diversified and individualized methods of clinical operation of AACD-CPR need exploration and expectingly serve as a guideline for clinical application of AACD-CPR in the future.

Using 100% oxygen does not alter the cardiovascular autonomic regulation during non-invasively simulated haemorrhage in healthy volunteers.

We tested the effect of 100% oxygen on heart rate (HR), arterial blood pressure (ABP), cardiac output (CO), stroke volume (SV), total peripheral resistance (TPR), HR variability (HRV), systolic blood pressure variability (SBPV) and baroreflex sensitivity (BRS) in 20 healthy volunteers during simulated haemorrhage induced by -40 mmHg lower body negative pressure (LBNP). HRV in the high frequency region (HRV HF), BRS, ABP and TPR were significantly increased, SBPV in the low frequency region (SBPV LF), CO and SV were unchanged, and HR was significantly decreased by 100% oxygen administration during normovolaemia. HRV HF, BRS, CO and SV were significantly decreased, SBPV LF and ABP were unchanged, and HR and TPR were significantly increased by LBNP during 21% or 100% oxygen administration. There were no significant differences in cardiovascular autonomic and haemodynamic responses to LBNP during 21% or 100% oxygen administration, suggesting that 100% oxygen does not alter normal cardiovascular autonomic responses during simulated haemorrhage.