Effect of systemic vascular resistance on the agreement between stroke volume by non-invasive pulse wave analysis and Doppler ultrasound in healthy volunteers.

BACKGROUND: Stroke volume can be estimated beat-to-beat and non-invasively by pulse wave analysis (PWA). However, its reliability has been questioned during marked alterations in systemic vascular resistance (SVR). We studied the effect of SVR on the agreement between stroke volume by PWA and Doppler ultrasound during reductions in stroke volume in healthy volunteers. METHODS: In a previous study we simultaneously measured stroke volume by PWA (SVPWA) and suprasternal Doppler ultrasound (SVUS). We exposed 16 healthy volunteers to lower body negative pressure (LBNP) to reduce stroke volume in combination with isometric hand grip to elevate SVR. LBNP was increased by 20 mmHg every 6 minutes from 0 to 80 mmHg, or until hemodynamic decompensation. The agreement between SVPWA and SVUS was examined using Bland-Altman analysis with mixed regression. Within-subject limits of agreement (LOA) was calculated from the residual standard deviation. SVRUS was calculated from SVUS. We allowed for a sloped bias line by introducing the mean of the methods and SVRUS as explanatory variables to examine whether the agreement was dependent on the magnitude of stroke volume and SVRUS. RESULTS: Bias ± limits of agreement (LOA) was 27.0 ± 30.1 mL. The within-subject LOA was ±11.1 mL. The within-subject percentage error was 14.6%. The difference between methods decreased with higher means of the methods (-0.15 mL/mL, confidence interval (CI): -0.19 to -0.11, P<0.001). The difference between methods increased with higher SVRUS (0.60 mL/mmHg × min × L-1, 95% CI: 0.48 to 0.72, P<0.001). CONCLUSION: PWA overestimated stroke volume compared to Doppler ultrasound during reductions in stroke volume and elevated SVR in healthy volunteers. The agreement between SVPWA and SVUS decreased during increases in SVR. This is relevant in settings where a high level of reliability is required.

Hemodynamic effects of supplemental oxygen versus air in simulated blood loss in healthy volunteers: a randomized, controlled, double-blind, crossover trial.

BACKGROUND: Trauma patients frequently receive supplemental oxygen, but its hemodynamic effects in blood loss are poorly understood. We studied the effects of oxygen on the hemodynamic response and tolerance to simulated blood loss in healthy volunteers. METHODS: Fifteen healthy volunteers were exposed to simulated blood loss by lower body negative pressure (LBNP) on two separate visits at least 24 h apart. They were randomized to inhale 100% oxygen or medical air on visit 1, while inhaling the other on visit 2. To simulate progressive blood loss LBNP was increased every 3 min in levels of 10 mmHg from 0 to 80 mmHg or until hemodynamic decompensation. Oxygen and air were delivered on a reservoired face mask at 15 L/min. The effect of oxygen compared to air on the changes in cardiac output, stroke volume and middle cerebral artery blood velocity (MCAV) was examined with mixed regression to account for repeated measurements within subjects. The effect of oxygen compared to air on the tolerance to blood loss was measured as the time to hemodynamic decompensation in a shared frailty model. Cardiac output was the primary outcome variable. RESULTS: Oxygen had no statistically significant effect on the changes in cardiac output (0.031 L/min/LBNP level, 95% confidence interval (CI): - 0.015 to 0.077, P = 0.188), stroke volume (0.39 mL/LBNP level, 95% CI: - 0.39 to 1.2, P = 0.383), or MCAV (0.25 cm/s/LBNP level, 95% CI: - 0.11 to 0.61, P = 0.176). Four subjects exhibited hemodynamic decompensation when inhaling oxygen compared to 10 when inhaling air (proportional hazard ratio 0.24, 95% CI: 0.065 to 0.85, P = 0.027). CONCLUSIONS: We found no effect of oxygen compared to air on the changes in cardiac output, stroke volume or MCAV during simulated blood loss in healthy volunteers. However, oxygen had a favorable effect on the tolerance to simulated blood loss with fewer hemodynamic decompensations. Our findings suggest that supplemental oxygen does not adversely affect the hemodynamic response to simulated blood loss. Trial registration This trial was registered in ClinicalTrials.gov (NCT05150418) December 9, 2021.

Haemodynamic effects of methoxyflurane versus fentanyl and placebo in hypovolaemia: a randomised, double-blind crossover study in healthy volunteers.

Background: Methoxyflurane is approved for relief of moderate to severe pain in conscious adult trauma patients: it may be self-administrated and is well suited for use in austere environments. Trauma patients may sustain injuries causing occult haemorrhage compromising haemodynamic stability, and it is therefore important to elucidate whether methoxyflurane may adversely affect the haemodynamic response to hypovolaemia. Methods: In this randomised, double-blinded, placebo-controlled, three-period crossover study, inhaled methoxyflurane 3 ml, i.v. fentanyl 25 µg, and placebo were administered to 15 healthy volunteers exposed to experimental hypovolaemia in the lower body negative pressure model. The primary endpoint was the effect of treatment on changes in cardiac output, while secondary endpoints were changes in stroke volume and mean arterial pressure and time to haemodynamic decompensation during lower body negative pressure. Results: There were no statistically significant effects of treatment on the changes in cardiac output, stroke volume, or mean arterial pressure during lower body negative pressure. The time to decompensation was longer for methoxyflurane compared with fentanyl (hazard ratio 1.9; 95% confidence interval 0.4-3.4; P=0.010), whereas there was no significant difference to placebo (hazard ratio -1.3; 95% confidence interval -2.8 to 0.23; P=0.117). Conclusions: The present study does not indicate that methoxyflurane has significant adverse haemodynamic effects in conscious adults experiencing hypovolaemia. Clinical trial registration: ClinicalTrials.gov (NCT04641949) and EudraCT (2019-004144-29) https://www.clinicaltrialsregister.eu/ctr-search/trial/2019-004144-29/NO.

Effects of experimental hypovolemia and pain on pre-ejection period and pulse transit time in healthy volunteers.

Trauma patients may suffer significant blood loss, and noninvasive methods to diagnose hypovolemia in these patients are needed. Physiologic effects of hypovolemia, aiming to maintain blood pressure, are largely mediated by increased sympathetic nervous activity. Trauma patients may however experience pain, which also increases sympathetic nervous activity, potentially confounding measures of hypovolemia. Elucidating the common and separate effects of the two stimuli on diagnostic methods is therefore important. Lower body negative pressure (LBNP) and cold pressor test (CPT) are experimental models of central hypovolemia and pain, respectively. In the present analysis, we explored the effects of LBNP and CPT on pre-ejection period and pulse transit time, aiming to further elucidate the potential use of these variables in diagnosing hypovolemia in trauma patients. We exposed healthy volunteers to four experimental sequences with hypovolemia (LBNP 60 mmHg) or normovolemia (LBNP 0 mmHg) and pain (CPT) or no pain (sham) in a 2 × 2 fashion. We calculated pre-ejection period and pulse transit time from ECG and ascending aortic blood velocity (suprasternal Doppler) and continuous noninvasive arterial pressure waveform (volume-clamp method). Fourteen subjects were available for the current analyses. This experimental study found that pre-ejection period increased with hypovolemia and remained unaltered with pain. Pulse transit time was reduced by pain and increased with hypovolemia. Thus, the direction of change in pulse transit time has the potential to distinguish hypovolemia and pain.

Effects of supplemental oxygen on systemic and cerebral hemodynamics in experimental hypovolemia: Protocol for a randomized, double blinded crossover study.

Supplemental oxygen is widely administered in trauma patients, often leading to hyperoxia. However, the clinical evidence for providing supplemental oxygen in all trauma patients is scarce, and hyperoxia has been found to increase mortality in some patient populations. Hypovolemia is a common finding in trauma patients, which affects many hemodynamic parameters, but little is known about how supplemental oxygen affects systemic and cerebral hemodynamics during hypovolemia. We therefore plan to conduct an experimental, randomized, double blinded crossover study to investigate the effect of 100% oxygen compared to room air delivered by a face mask with reservoir on systemic and cerebral hemodynamics during simulated hypovolemia in the lower body negative pressure model in 15 healthy volunteers. We will measure cardiac output, stroke volume, blood pressure, middle cerebral artery velocity and tolerance to hypovolemia continuously in all subjects at two visits to investigate whether oxygen affects the cardiovascular response to simulated hypovolemia. The effect of oxygen on the outcome variables will be analyzed with mixed linear regression. Trial registration: The study is registered in the European Union Drug Regulating Authorities Clinical Trials Database (EudraCT, registration number 2021-003238-35).

Core Temperature during Cold-Water Triathlon Swimming.

Triathlon and other endurance races have grown in popularity. Although participants are generally fit and presumably healthy, there is measurable morbidity and mortality associated with participation. In triathlon, most deaths occur during the swim leg, and more insight into risk factors, such as hypothermia, is warranted. In this study, we measured the core temperature of 51 participants who ingested temperature sensor capsules before the swim leg of a full-distance triathlon. The water temperature was 14.4-16.4 °C, and the subjects wore wetsuits. One subject with a low body mass index and a long swim time experienced hypothermia (<35 °C). Among the remaining subjects, we found no association between core temperature and swim time, body mass index, or sex. To conclude, the present study indicates that during the swim leg of a full-distance triathlon in water temperatures ≈ 15-16 °C, subjects with a low body mass index and long swim times may be at risk of hypothermia even when wearing wetsuits.

Effects of intermittent negative pressure treatment on circulating vascular biomarkers in patients with intermittent claudication.

The aim of this study was to investigate the effects of lower extremity intermittent negative pressure (INP) treatment for 1 hour twice daily for 12 weeks, on circulating vascular biomarkers in patients with intermittent claudication. Patients were randomized to treatment with -40 mmHg INP (treatment group), or -10 mmHg INP (sham control group). Venous blood samples were collected at baseline and after 12 weeks, and concentrations of vascular adhesion molecule-1 (VCAM-1), intracellular adhesion molecule-1 (ICAM-1), E-selectin, P-selectin, von Willebrand factor (vWF), l-arginine, asymmetric dimethylarginine (ADMA), and symmetric dimethylarginine (SDMA) were analyzed. A larger proportion of the patients in the treatment group (25/31) had a reduction in vWF levels after 12 weeks, compared to the sham control group (17/30) (p = 0.043). Within the treatment group there was a significant mean (SEM) reduction in the concentration of vWF of -11% (4) (p = 0.019), whereas there was no significant change in the levels of vWF in the sham control group (1% (6); p = 0.85). There were no significant differences in the change of any of the biomarker levels between the groups after 12 weeks of treatment. In conclusion, there were no differences in the change of the circulating levels of the measured biomarkers between the treatment group and the sham control group after 12 weeks of INP treatment. However, the observed changes in vWF might indicate a beneficial effect of INP treatment on endothelial activation and endothelial injury. Clinicaltrials.gov Identifier: NCT03640676.

Cerebral blood flow velocity during simultaneous changes in mean arterial pressure and cardiac output in healthy volunteers.

PURPOSE: Cerebral blood flow (CBF) needs to be precisely controlled to maintain brain functions. While previously believed to be autoregulated and near constant over a wide blood pressure range, CBF is now understood as more pressure passive. However, there are still questions regarding the integrated nature of CBF regulation and more specifically the role of cardiac output. Our aim was, therefore, to explore the effects of MAP and cardiac output on CBF in a combined model of reduced preload and increased afterload. METHOD: 16 healthy volunteers were exposed to combinations of different levels of simultaneous lower body negative pressure and isometric hand grip. We measured blood velocity in the middle cerebral artery (MCAV) and internal carotid artery (ICAV) by Doppler ultrasound, and cerebral oxygen saturation (ScO2) by near-infrared spectroscopy, as surrogates for CBF. The effect of changes in MAP and cardiac output on CBF was estimated with mixed multiple regression. RESULT: Both MAP and cardiac output had independent effects on MCAV, ICAV and ScO2. For ICAV and ScO2 there was also a statistically significant interaction effect between MAP and cardiac output. The estimated effect of a change of 10 mmHg in MAP on MCAV was 3.11 cm/s (95% CI 2.51-3.71, P < 0.001), and the effect of a change of 1 L/min in cardiac output was 3.41 cm/s (95% CI 2.82-4.00, P < 0.001). CONCLUSION: The present study indicates that during reductions in cardiac output, both MAP and cardiac output have independent effects on CBF.

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.

Oculometric Feature Changes During Acute Hypoxia in a Simulated High-Altitude Airdrop Scenario.

BACKGROUND: Severe acute hypoxia results in a rapid deterioration of cognitive functioning and thus poses a risk for human operations in high altitude environments. This study aimed at investigating the effects of oxygen system failure during a high-altitude high-opening (HAHO) parachute jump scenario from 30,000 ft (9144 m) on human physiology and cognitive performance using a noncontact eye-tracking task.METHODS: Nine healthy male volunteers (ages 27-48) were recruited from the Norwegian Special Operations Commandos. Eye-tracking data were collected to derive information on cognitive performance in the context of rapid dynamic changes in pressure altitude while performing a modified King-Devick test. The baseline data was collected at 8000 ft (2438 m) while breathing 100% oxygen during decompression. For every test, the corresponding arterial blood gas analysis was performed.RESULTS: The study subjects endured severe hypoxia, which resulted in significant prolongations of fixation time (range: 284.1-245.6 ms) until 23,397 ft (131 m) and fixation size (range: 34.6-32.4 mm) until 25,389 ft (7739 m) as compared to the baseline (217.6 ± 17.8 ms and 27.2 ± 4.5 mm, respectively). The increase in the saccadic movement and decrease in the saccadic velocity was observed until 28,998 ft and 27,360 ft (8839 and 8339 m), respectively.DISCUSSION: This is the first study to investigate cognitive performance from measured oculometric variables during severe hypobaric hypoxia in a simulated high-altitude airdrop mission scenario. The measurement of altered oculometric variables under hypoxic conditions represents a potential avenue to study altered cognitive performance using noncontact sensors that can derive information and serve to provide the individual with a warning from impending incapacitation.Pradhan GN, Ottestad W, Meland A, Kåsin JI, Høiseth LØ, Cevette MJ, Stepanek J. Oculometric feature changes during acute hypoxia in a simulated high-altitude airdrop scenario. Aerosp Med Hum Perform. 2021; 92(12):928-936.

Factors mediating the pressor response to isometric muscle contraction: An experimental study in healthy volunteers during lower body negative pressure.

Whilst both cardiac output (CO) and total peripheral resistance (TPR) determine mean arterial blood pressure (MAP), their relative importance in the pressor response to isometric exercise remains unclear. This study aimed to elucidate the relative importance of these two different factors by examining pressor responses during cardiopulmonary unloading leading to step-wise reductions in CO. Hemodynamics were investigated in 11 healthy individuals before, during and after two-minute isometric exercise during lower body negative pressure (LBNP; -20mmHg and -40mmHg). The blood pressure response to isometric exercise was similar during normal and reduced preload, despite a step-wise reduction in CO during LBNP (-20mmHg and -40mmHg). During -20mmHg LBNP, the decreased stroke volume, and consequently CO, was counteracted by an increased TPR, while heart rate (HR) was unaffected. HR was increased during -40 mmHg LBNP, although insufficient to maintain CO; the drop in CO was perfectly compensated by an increased TPR to maintain MAP. Likewise, transient application of LBNP (-20mmHg and -40mmHg) resulted in a short transient drop in MAP, caused by a decrease in CO, which was compensated by an increase in TPR. This study suggests that, in case of reductions of CO, changes in TPR are primarily responsible for maintaining the pressor response during isometric exercise. This highlights the relative importance of TPR compared to CO in mediating the pressor response during isometric exercise.

The acute effects of different levels of intermittent negative pressure on peripheral circulation in patients with peripheral artery disease.

Intermittent negative pressure (INP) applied to the lower leg induces acute increase in arterial and skin blood flow. The aim of this study was to identify the optimal level of INP to increase blood flow in patients with lower extremity peripheral artery disease (PAD). We investigated the acute effects of different levels of INP in 16 subjects (7 women and 9 men, mean (SD) age 71(8) years) diagnosed with PAD. During application of INP in a pressure chamber sealed below the knee, arterial blood flow was continuously recorded in the dorsalis pedis artery or tibialis posterior artery (ultrasound Doppler), and skin blood flow was continuously recorded at the pulp of the first toe (laser Doppler). Different pressure levels (0, -10, -20, -40, and -60 mmHg) were tested in randomized order. Maximal arterial blood flow relative to baseline (median [25th, 75th percentiles]) was: 0 mmHg; 1.08 (1.02, 1.13), -10 mmHg; 1.11 (1.07, 1.17), -20 mmHg; 1.18 (1.11, 1.32), -40 mmHg; 1.39 (1.27, 1.91) and -60 mmHg; 1.48 (1.37, 1.78). Maximal laser Doppler flux (LDF) relative to baseline was: 0 mmHg; 1.06 (1.02, 1.12), -10 mmHg; 1.08 (1.05, 1.16) -20 mmHg; 1.12 (1.06, 1.27), -40 mmHg; 1.24 (1.14, 1.50) and -60 mmHg; 1.35 (1.10, 1.70). There were significantly higher maximal arterial blood flow and maximal LDF at -40 mmHg compared with -10 mmHg (P = 0.001 and P = 0.025, respectively). There were no significant differences in maximal arterial blood flow and maximal LDF between 0 and -10 mmHg (both P = 1.0), or between -40 and -60 mmHg (both P = 1.0). INP of -40 mmHg was the lowest negative pressure level that increased blood flow.

Respiratory variations in pulse pressure and photoplethysmographic waveform amplitude during positive expiratory pressure and continuous positive airway pressure in a model of progressive hypovolemia.

PURPOSE: Respiratory variations in pulse pressure (dPP) and photoplethysmographic waveform amplitude (dPOP) are used for evaluation of volume status in mechanically ventilated patients. Amplification of intrathoracic pressure changes may enable their use also during spontaneous breathing. We investigated the association between the degree of hypovolemia and dPP and dPOP at different levels of two commonly applied clinical interventions; positive expiratory pressure (PEP) and continuous positive airway pressure (CPAP). METHODS: 20 healthy volunteers were exposed to progressive hypovolemia by lower body negative pressure (LBNP). PEP of 0 (baseline), 5 and 10 cmH2O was applied by an expiratory resistor and CPAP of 0 (baseline), 5 and 10 cmH2O by a facemask. dPP was obtained non-invasively with the volume clamp method and dPOP from a pulse oximeter. Central venous pressure was measured in 10 subjects. Associations between changes were examined using linear mixed-effects regression models. RESULTS: dPP increased with progressive LBNP at all levels of PEP and CPAP. The LBNP-induced increase in dPP was amplified by PEP 10 cmH20. dPOP increased with progressive LBNP during PEP 5 and PEP 10, and during all levels of CPAP. There was no additional effect of the level of PEP or CPAP on dPOP. Progressive hypovolemia and increasing levels of PEP were reflected by increasing respiratory variations in CVP. CONCLUSION: dPP and dPOP reflected progressive hypovolemia in spontaneously breathing healthy volunteers during PEP and CPAP. An increase in PEP from baseline to 10 cmH2O augmented the increase in dPP, but not in dPOP.

Volumetric and End-Tidal Capnography for the Detection of Cardiac Output Changes in Mechanically Ventilated Patients Early after Open Heart Surgery.

BACKGROUND: Exhaled carbon dioxide (CO2) reflects cardiac output (CO) provided stable ventilation and metabolism. Detecting CO changes may help distinguish hypovolemia or cardiac dysfunction from other causes of haemodynamic instability. We investigated whether CO2 measured as end-tidal concentration (EtCO2) and eliminated volume per breath (VtCO2) reflect sudden changes in cardiac output (CO). METHODS: We measured changes in CO, VtCO2, and EtCO2 during right ventricular pacing and passive leg raise in 33 ventilated patients after open heart surgery. CO was measured with oesophageal Doppler. RESULTS: During right ventricular pacing, CO was reduced by 21% (CI 18-24; p < 0.001), VtCO2 by 11% (CI 7.9-13; p < 0.001), and EtCO2 by 4.9% (CI 3.6-6.1; p < 0.001). During passive leg raise, CO increased by 21% (CI 17-24; p < 0.001), VtCO2 by 10% (CI 7.8-12; p < 0.001), and EtCO2 by 4.2% (CI 3.2-5.1; p < 0.001). Changes in VtCO2 were significantly larger than changes in EtCO2 (ventricular pacing: 11% vs. 4.9% (p < 0.001); passive leg raise: 10% vs. 4.2% (p < 0.001)). Relative changes in CO correlated with changes in VtCO2 (ρ=0.53; p=0.002) and EtCO2 (ρ=0.47; p=0.006) only during reductions in CO. When dichotomising CO changes at 15%, only EtCO2 detected a CO change as judged by area under the receiver operating characteristic curve. CONCLUSION: VtCO2 and EtCO2 reflected reductions in cardiac output, although correlations were modest. The changes in VtCO2 were larger than the changes in EtCO2, but only EtCO2 detected CO reduction as judged by receiver operating characteristic curves. The predictive ability of EtCO2 in this setting was fair. This trial is registered with NCT02070861.

Correction: Associations between changes in precerebral blood flow and cerebral oximetry in the lower body negative pressure model of hypovolemia in healthy volunteers.

[This corrects the article DOI: 10.1371/journal.pone.0219154.].

Associations between changes in precerebral blood flow and cerebral oximetry in the lower body negative pressure model of hypovolemia in healthy volunteers.

Reductions in cerebral oxygen saturation (ScO2) measured by near infra-red spectroscopy have been found during compensated hypovolemia in the lower body negative pressure (LBNP)-model, which may reflect reduced cerebral blood flow. However, ScO2 may also be contaminated from extracranial (scalp) tissues, mainly supplied by the external carotid artery (ECA), and it is possible that a ScO2 reduction during hypovolemia is caused by reduced scalp, and not cerebral, blood flow. The aim of the present study was to explore the associations between blood flow in precerebral arteries and ScO2 during LBNP-induced hypovolemia. Twenty healthy volunteers were exposed to LBNP 20, 40, 60 and 80 mmHg. Blood flow in the internal carotid artery (ICA), ECA and vertebral artery (VA) was measured by Doppler ultrasound. Stroke volume for calculating cardiac output was measured by suprasternal Doppler. Associations of changes within subjects were examined using linear mixed-effects regression models. LBNP reduced cardiac output, ScO2 and ICA and ECA blood flow. Changes in flow in both ICA and ECA were associated with changes in ScO2 and cardiac output. Flow in the VA did not change during LBNP and changes in VA flow were not associated with changes in ScO2 or cardiac output. During experimental compensated hypovolemia in healthy, conscious subjects, a reduced ScO2 may thus reflect a reduction in both cerebral and extracranial blood flow.

Arterial Oxygen Saturation, Pulse Oximetry, and Cerebral and Tissue Oximetry in Hypobaric Hypoxia.

INTRODUCTION: Clinical accuracy of pulse oximeters (giving Spo2) is routinely tested down to an Sao2 of 70%, but lower oxygen saturations are often experienced during hypobaric hypoxia. Cerebral (Sco2) and peripheral tissue (Sto2) oxygen saturations can be measured using near infra-red spectroscopy. In a project simulating oxygen system failure during high altitude-high opening parachuting (HAHO), Sao2, Spo2, Sco2, and forearm Sto2 were measured. The aim of the present analysis was to explore the agreement between Sao2 and the three noninvasive measurements of hypoxemia (Spo2, Sco2, and Sto2).METHODS: Healthy volunteers from the Norwegian Special Operations Commando were studied in a hypobaric chamber as supplemental oxygen was removed at 301 hPa ambient pressure (30,000 ft) and recompressed at 25 hPa · min-1 (1000 ft · min-1) to ground level simulating a HAHO parachute flight. Sao2 was compared with Spo2, Sco2, and Sto2 in scatterplots and Bland-Altman plots, calculating bias and limits of agreement (LOA).RESULTS: The bias ± LOA were: Sao2 vs. Spo2: -5.8% ± 16, Sao2 vs. Sco2: -3.4% ± 11, and Sao2 vs. Sto2: 17% ± 30. The bias for Sao2 vs. Spo2 was dependent on the range of values, and correcting for this with a sloped bias line reduced the LOA to ± 8.2%.DISCUSSION: There were wide limits of agreement between Sao2 and Spo2. Sao2 and Sco2 agreed better, whereas Sao2 and forearm Sto2 had wide LOA. The agreement between Sao2 and Spo2 improved when correcting for the underestimation of Spo2 at low values. There is a poor agreement between Spo2 and the gold standard Sao2 during extreme hypobaric hypoxemia.Ottestad W, Kåsin JI, Høiseth LØ. Arterial oxygen saturation, pulse oximetery, and cerebral and tissue oximetry in hypobaric hypoxia. Aerospace Med Hum Perform. 2018; 89(12):1045-1049.

Intermittent mild negative pressure applied to the lower limb in patients with spinal cord injury and chronic lower limb ulcers: a crossover pilot study.

STUDY DESIGN: Randomized, assessor-blinded crossover pilot study. OBJECTIVES: To explore the use of an intermittent negative pressure (INP) device for home use in addition to standard wound care (SWC) for patients with spinal cord injury (SCI) and chronic leg and foot ulcers before conducting a superiority trial. SETTING: Patient homes and outpatient clinic. METHODS: A 16-week crossover trial on 9 SCI patients (median age: 57 years, interquartile range [IQR] 52-66), with leg ulcers for 52 of weeks (IQR: 12-82) duration. At baseline, patients were allocated to treatment with INP + SWC or SWC alone. After 8 weeks, the ulcers were evaluated. To assess protocol adherence, the patients were then crossed over to the other group and were evaluated again after another 8 weeks. Lower limb INP treatment consisted of an airtight pressure chamber connected to an INP generator (alternating 10 s -40mmHg/7 s atmospheric pressure) used 2 h/day at home. Ulcer healing was assessed using a photographic wound assessment tool (PWAT) and by measuring changes in wound surface area (WSA). RESULTS: Seven of nine recruited patients adhered to a median of 90% (IQR: 80-96) of the prescribed 8-week INP-protocol, and completed the study without side effects. PWAT improvement was observed in 4/4 patients for INP + SWC vs. 2/5 patients for SWC alone (P = 0.13). WSA improved in 3/4 patients allocated to INP + SWC vs. 3/5 patients in SWC alone (P = 0.72). CONCLUSIONS: INP can be used as a home-based treatment for patients with SCI, and its efficacy should be tested in an adequately sized, preferably multicenter randomized trial.