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.

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.

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.

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.

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.

Terapia de presión negativa con instilación para el tratamiento de heridas infectadas: recomendaciones de utilización basadas en la evidencia / Negative pressure therapy with instillation for the treatment of infected wounds: recommendations of utilization based on evidence

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

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

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 of fluid loading as a countermeasure to the hemodynamic and hormonal changes of 28-h head-down bed rest.

After exposure to microgravity, or head-down bed rest (HDBR), fluid loading is often used with the intent of increasing plasma volume and maintaining mean arterial pressure during orthostatic stress. Nine men (aged 18-32 years) underwent three randomized trials with lower body negative pressure (LBNP) before and after: (1) 4-h of sitting with fluid loading (1 g sodium chloride/125 mL of water starting 2.5-h before LBNP), (2) 28-h of 6-degree HDBR without fluid loading, and (3) 28-h of 6-degree HDBR with fluid loading. LBNP was progressive from 0 to -40 mmHg. After 28-h HDBR, fluid loading did not protect against the loss of plasma volume (-280 ± 64 mL without fluid loading, -207 ± 86 with fluid loading, P = 0.472) nor did it protect against a drop of mean arterial pressure (P = 0.017) during LBNP (Post-28 h HDBR response from 0 to -40 mmHg LBNP: 88 ± 4 to 85 ± 4 mmHg without fluid loading and 93 ± 4 to 88 ± 5 mmHg with fluid loading, P = 0.557 between trials). However, fluid loading did protect against the loss of stroke volume index and central venous pressure observed after 28-h HDBR. Fluid loading also attenuated the increase of angiotensin II seen after 28-h HDBR and throughout the LBNP protocol (Post-28 h HDBR response from 0 to -40 mmHg LBNP: 16.6 ± 3.4 to 23.7 ± 5.0 pg/mL without fluid loading and 6.1 ± 0.8 to 12.2 ± 2.3 pg/mL with fluid loading, P < 0.001 between trials). Our results indicate that fluid loading did not protect against plasma volume loss due to HDBR or change blood pressure responses to LBNP. However, changes in central venous pressure, stroke volume and fluid regulatory hormones could potentially influence longer duration studies and those with more severe orthostatic stress.

Effect of acute hypoxemia on cerebral blood flow velocity control during lower body negative pressure.

The ability to maintain adequate cerebral blood flow and oxygenation determines tolerance to central hypovolemia. We tested the hypothesis that acute hypoxemia during simulated blood loss in humans would cause impairments in cerebral blood flow control. Ten healthy subjects (32 ± 6 years, BMI 27 ± 2 kg·m-2 ) were exposed to stepwise lower body negative pressure (LBNP, 5 min at 0, -15, -30, and -45 mmHg) during both normoxia and hypoxia (Fi O2  = 0.12-0.15 O2 titrated to an SaO2 of ~85%). Physiological responses during both protocols were expressed as absolute changes from baseline, one subject was excluded from analysis due to presyncope during the first stage of LBNP during hypoxia. LBNP induced greater reductions in mean arterial pressure during hypoxia versus normoxia (MAP, at -45 mmHg: -20 ± 3 vs. -5 ± 3 mmHg, P < 0.01). Despite differences in MAP, middle cerebral artery velocity responses (MCAv) were similar between protocols (P = 0.41) due to increased cerebrovascular conductance index (CVCi) during hypoxia (main effect, P = 0.04). Low frequency MAP (at -45 mmHg: 17 ± 5 vs. 0 ± 5 mmHg2 , P = 0.01) and MCAv (at -45 mmHg: 4 ± 2 vs. -1 ± 1 cm·s-2 , P = 0.04) spectral power density, as well as low frequency MAP-mean MCAv transfer function gain (at -30 mmHg: 0.09 ± 0.06 vs. -0.07 ± 0.06 cm·s-1 ·mmHg-1 , P = 0.04) increased more during hypoxia versus normoxia. Contrary to our hypothesis, these findings support the notion that cerebral blood flow control is not impaired during exposure to acute hypoxia and progressive central hypovolemia despite lower MAP as a result of compensated increases in cerebral conductance and flow variability.

Intracranial and Intraocular Pressure During Various Degrees of Head-Down Tilt.

BACKGROUND: More than half of astronauts develop ophthalmic changes during long-duration spaceflight consistent with an abnormal intraocular and intracranial pressure (IOP, ICP) difference. The aim of our study was to assess IOP and ICP during head-down tilt (HDT) and the additive or attenuating effects of 1% CO2 and lower body negative pressure (LBNP). METHODS: In Experiment I, IOP and ICP were measured in nine healthy subjects after 3.5 h HDT in five conditions: -6°, -12°, and -18° HDT, -12° with 1% CO2, and -12° with -20 mmHg LBNP. In Experiment II, IOP was measured in 16 healthy subjects after 5 min tilt at +12°, 0°, -6°, -12°, -18°, and -24°, with and without -40 mmHg LBNP. RESULTS: ICP was only found to increase from supine baseline during -18° HDT (9.2 ± 0.9 and 14.4 ± 1 mmHg, respectively), whereas IOP increased from 15.7 ± 0.3 mmHg at 0° to 17.9 ± 0.4 mmHg during -12° HDT and from 15.3 ± 0.4 mmHg at 0° to 18.7 ± 0.4 mmHg during -18° HDT. The addition of -20 mmHg LBNP or 1% CO2 had no further effects on ICP or IOP. However, the use of -40 mmHg LBNP during HDT lowered IOP back to baseline values, except at -24° HDT. DISCUSSION: A small, posterior intraocular-intracranial pressure difference (IOP > ICP) is maintained during HDT, and a sustained or further decreased difference may lead to structural changes in the eye in real and simulated microgravity.Marshall-Goebel K, Mulder E, Bershad E, Laing C, Eklund A, Malm J, Stern C, Rittweger J. Intracranial and intraocular pressure during various degrees of head-down tilt. Aerosp Med Hum Perform. 2017; 88(1):10-16.

Internal carotid artery blood flow in healthy awake subjects is reduced by simulated hypovolemia and noninvasive mechanical ventilation.

Intact cerebral blood flow (CBF) is essential for cerebral metabolism and function, whereas hypoperfusion in relation to hypovolemia and hypocapnia can lead to severe cerebral damage. This study was designed to assess internal carotid artery blood flow (ICA-BF) during simulated hypovolemia and noninvasive positive pressure ventilation (PPV) in young healthy humans. Beat-by-beat blood velocity (ICA and aorta) were measured by Doppler ultrasound during normovolemia and simulated hypovolemia (lower body negative pressure), with or without PPV in 15 awake subjects. Heart rate, plethysmographic finger arterial pressure, respiratory frequency, and end-tidal CO2 (ETCO2) were also recorded. Cardiac index (CI) and ICA-BF were calculated beat-by-beat. Medians and 95% confidence intervals and Wilcoxon signed rank test for paired samples were used to test the difference between conditions. Effects on ICA-BF were modeled by linear mixed-effects regression analysis. During spontaneous breathing, ICA-BF was reduced from normovolemia (247, 202-284 mL/min) to hypovolemia (218, 194-271 mL/min). During combined PPV and hypovolemia, ICA-BF decreased by 15% (200, 152-231 mL/min, P = 0.001). Regression analysis attributed this fall to concurrent reductions in CI (ß: 43.2, SE: 17.1, P = 0.013) and ETCO2 (ß: 32.8, SE: 9.3, P = 0.001). Mean arterial pressure was maintained and did not contribute to ICA-BF variance. In healthy awake subjects, ICA-BF was significantly reduced during simulated hypovolemia combined with noninvasive PPV Reductions in CI and ETCO2 had additive effects on ICA-BF reduction. In hypovolemic patients, even low-pressure noninvasive ventilation may cause clinically relevant reductions in CBF, despite maintained arterial blood pressure.

The effects of superimposed tilt and lower body negative pressure on anterior and posterior cerebral circulations.

Steady-state tilt has no effect on cerebrovascular reactivity to increases in the partial pressure of end-tidal carbon dioxide (PETCO2). However, the anterior and posterior cerebral circulations may respond differently to a variety of stimuli that alter central blood volume, including lower body negative pressure (LBNP). Little is known about the superimposed effects of head-up tilt (HUT; decreased central blood volume and intracranial pressure) and head-down tilt (HDT; increased central blood volume and intracranial pressure), and LBNP on cerebral blood flow (CBF) responses. We hypothesized that (a) cerebral blood velocity (CBV; an index of CBF) responses during LBNP would not change with HUT and HDT, and (b) CBV in the anterior cerebral circulation would decrease to a greater extent compared to posterior CBV during LBNP when controlling PETCO2 In 13 male participants, we measured CBV in the anterior (middle cerebral artery, MCAv) and posterior (posterior cerebral artery, PCAv) cerebral circulations using transcranial Doppler ultrasound during LBNP stress (-50 mmHg) in three body positions (45°HUT, supine, 45°HDT). PETCO2 was measured continuously and maintained at constant levels during LBNP through coached breathing. Our main findings were that (a) steady-state tilt had no effect on CBV responses during LBNP in both the MCA (P = 0.077) and PCA (P = 0.583), and (b) despite controlling for PETCO2, both the MCAv and PCAv decreased by the same magnitude during LBNP in HUT (P = 0.348), supine (P = 0.694), and HDT (P = 0.407). Here, we demonstrate that there are no differences in anterior and posterior circulations in response to LBNP in different body positions.

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.

Cerebral Blood Flow Velocity During Combined Lower Body Negative Pressure and Cognitive Stress.

BACKGROUND: Lower body negative pressure (LBNP) decreases middle cerebral artery blood velocity (MCAv) and can induce hypotension. Mental stress increases MCAv, but the MCAv response to combined LBNP and mental stress (COMBO) is unknown. We hypothesized that performing a stressful cognitive challenge (i.e., mental stress) concurrently with LBNP would prevent LBNP-induced reductions of MCAv. METHODS: There were 18 subjects (9 men, 9 women; ages 20.1±0.3 yr) who completed 3 randomized 3-min trials: 1) LBNP (-40 mmHg); 2) mental stress (serial subtraction); and 3) COMBO (LBNP+mental stress). All reported values are mean±SE. Mean arterial pressure (MAP), heart rate (HR), forearm blood flow (FBF), and MCAv were measured continuously. Subjects also reported perceived stress following the mental stress and COMBO trials. RESULTS: LBNP decreased MAP (Δ-1.4±0.5 mmHg), MCAv (Δ-2.6±1.1 cm s(-1)) and FBF (Δ-0.8±0.1 units), and increased HR (Δ2.7±1.2 bpm). Mental stress increased MAP (Δ10.1±1.3 mmHg), HR (Δ17.4±2.2 bpm), and FBF (Δ2.4±0.4 units), while MCAv (Δ2.8±1.3 cm s(-1)) tended to increase. COMBO increased MAP (Δ5.3±2.3 mmHg) and HR (Δ21.3±2.6 bpm), and tended to increase FBF (Δ0.5±0.3 units). However, MCAv (Δ-4.6±2.0 cm s(-1)) decreased during COMBO. Decreases in MCAv during COMBO were not statistically different from LBNP-induced decreases (Δ-4.6±2.0 vs. Δ-2.6±1.1 cm s(-1)). Subjective ratings of perceived stress (standard 0 to 4 scale) tended to be higher during COMBO than mental stress (2.9±0.1 vs. 2.5±0.1 units). CONCLUSION: Our results suggest that mental stress does not effectively preserve MCAv when combined with central hypovolemia (i.e., LBNP).

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.

Running on empty? The compensatory reserve index.

BACKGROUND: Hemorrhage is a leading cause of traumatic death. We hypothesized that state-of-the-art feature extraction and machine learning techniques could be used to discover, detect, and continuously trend beat-to-beat changes in arterial pulse waveforms associated with the progression to hemodynamic decompensation. METHODS: We exposed 184 healthy humans to progressive central hypovolemia using lower-body negative pressure to the point of hemodynamic decompensation (systolic blood pressure > 80 mm Hg with or without bradycardia). Initial models were developed using continuous noninvasive blood pressure waveform data. The resulting algorithm calculates a compensatory reserve index (CRI), where 1 represents supine normovolemia and 0 represents the circulatory volume at which hemodynamic decompensation occurs (i.e., "running on empty"). Values between 1 and 0 indicate the proportion of reserve remaining before hemodynamic decompensation-much like the fuel gauge of a car indicates the amount of fuel remaining in the tank. A CRI estimate is produced after the first 30 heart beats, followed by a new CRI estimate after each subsequent beat. RESULTS: The CRI model with a 30-beat window has an absolute difference between actual and expected time to decompensation of 0.1, with a SD of 0.09. The model distinguishes individuals with low tolerance to reduced central blood volume (i.e., those most likely to develop early shock) from those with high tolerance and are able to estimate how near or far an individual may be from hemodynamic decompensation. CONCLUSION: Machine modeling can quickly and accurately detect and trend central blood volume reduction in real time during the compensatory phase of hemorrhage as well as estimate when an individual is "running on empty" and will decompensate (CRI, 0), well in advance of meaningful changes in traditional vital signs.