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.

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.

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.

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.

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.

Intermittent negative pressure applied to the lower limb increases foot macrocirculatory and microcirculatory blood flow pulsatility in people with spinal cord injury.

STUDY DESIGN: Experimental prestudy and poststudy. OBJECTIVES: Examine the acute effects of intermittent negative pressure (INP) applied to the lower limb on foot circulation in people with spinal cord injuries (SCIs). SETTING: Vascular laboratory, Oslo University Hospital. METHODS: Twenty-four people with SCI (median age 59 years, range 29-74) were exposed to lower leg INP (-40 mm Hg) using an air-tight pressure chamber connected to an INP generator. The contralateral leg was placed outside the pressure chamber. We continuously measured arterial blood flow velocity (ultrasound Doppler), skin blood flow (laser Doppler), skin temperature of the dorsum of the foot, heart rate (ECG) and systemic blood pressure (Finometer) during 5-min baseline (atmospheric pressure), followed by 10-min INP (alternating 10 s -40 mm Hg and 7 s atmospheric pressure), and 5-min post-INP (atmospheric pressure). Skin blood flow was measured on the foot placed outside the pressure chamber. A mixed effects regression model was applied to estimate the effect of INP on blood flow. To quantify flow fluctuations, we calculated cumulative up-and-down changes in arterial blood flow velocity per minute. RESULTS: Flow fluctuations increased during INP compared to baseline [32.3 cm/s/min (95% CI 26.9 to 37.7) vs. 15.2 cm/s/min (95% CI 9.8 to 20.6), P < 0.001]. Peak blood flow velocity and skin blood flow was reached 2-3 s after the onset of negative pressure and increased 33% (95% CI 16 to 46, P < 0.001) and 11% (95% CI -4.1 to 60, P = 0.14) above baseline, respectively. CONCLUSIONS: INP induced increased foot arterial blood flow fluctuations compared to baseline. SPONSORSHIPS: The Norwegian Research Council provided funding to Otivio (grant: 241589).

Predicting fluid responsiveness in whom? A simulated example of patient spectrum influencing the receiver operating characteristics curve.

The influence of patient spectrum on the sensitivities and specificities of diagnostic methods has been termed spectrum bias or spectrum effect. Receiver operating characteristics curves are often used to assess the ability of diagnostic methods to predict fluid responsiveness. As a receiver operating characteristics curve is a presentation of sensitivity and specificity, the purpose of the present manuscript was to explore if patient spectrum could affect areas under receiver operating characteristics curves and their gray zones. Relationships between stroke volume variation and change in stroke volume in two different patient populations using simulated data. Simulated patient populations with stroke volume variation values between 5 and 15 or 3 and 25% had median (2.5th-97.5th percentiles) areas under receiver operating characteristics curves of 0.79 (0.65-0.90) and 0.93 (0.85-0.99), respectively. The gray zones indicating range of diagnostic uncertainty were also affected. The patient spectrum can affect common statistics from receiver operating characteristics curves, indicating the need for considering patient spectrum when evaluating the abilities of different methods to predict fluid responsiveness.

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.

Impact of Norepinephrine on Regional Cerebral Oxygenation During Cardiopulmonary Bypass.

OBJECTIVES: Norepinephrine is used to increase mean arterial pressure during cardiopulmonary bypass. However, it has been suggested that norepinephrine could constrict cerebral arteries, reducing cerebral blood flow. The aim of this study, therefore, was to explore whether there was an association between doses of norepinephrine to maintain mean arterial pressure at ≈80 mmHg during cardiopulmonary bypass and cerebral oxygen saturation measured using near-infrared spectroscopy. DESIGN: Observational study. SETTING: University hospital. PARTICIPANTS: Patients undergoing cardiac surgery (n = 45) using cardiopulmonary bypass. INTERVENTIONS: Norepinephrine was administered to maintain mean arterial pressure ≈80 mmHg during cardiopulmonary bypass. MEASUREMENTS AND MAIN RESULTS: From initiation of cardiopulmonary bypass to removal of the aortic cross-clamp, norepinephrine dose, mean arterial pressure, partial pressure of arterial carbon dioxide, partial pressure of arterial oxygen, hemoglobin, and pump flow values were averaged over 1 minute, giving a total of 3,460 data points entered as covariates in a linear mixed model for repeated measurements, with cerebral oxygen saturation measured using near-infrared spectroscopy as outcome. There was no statistically significant association between norepinephrine dose to maintain mean arterial pressure and cerebral oxygen saturation (p = 0.46) in this model. CONCLUSIONS: Administration of norepinephrine to maintain mean arterial pressure ≈80 mmHg during cardiopulmonary bypass was not associated with statistically significant changes in cerebral oxygen saturation. These results indicated that norepinephrine could be used to increase mean arterial pressure during cardiopulmonary bypass without reducing cerebral oxygen saturation.

Respiratory variations in the photoplethysmographic waveform amplitude depend on type of pulse oximetry device.

Respiratory variations in the photoplethysmographic waveform amplitude predict fluid responsiveness under certain conditions. Processing of the photoplethysmographic signal may vary between different devices, and may affect respiratory amplitude variations calculated by the standard formula. The aim of the present analysis was to explore agreement between respiratory amplitude variations calculated using photoplethysmographic waveforms available from two different pulse oximeters. Analysis of registrations before and after fluid loads performed before and after open-heart surgery (aortic valve replacement and/or coronary artery bypass grafting) with patients on controlled mechanical ventilation. Photoplethysmographic (Nellcor and Masimo pulse oximeters) and arterial pressure waveforms were recorded. Amplitude variations induced by ventilation were calculated and averaged over ten respiratory cycles. Agreements for absolute values are presented in scatterplots (with least median square regression through the origin, LMSO) and Bland-Altman plots. Agreement for trending presented in a four-quadrant plot. Agreement between respiratory photoplethysmographic amplitude variations from the two pulse oximeters was poor with LMSO ΔPOPNellc = 1.5 × ΔPOPMas and bias ± limits of agreement 7.4 ± 23 %. Concordance rate with a fluid load was 91 %. Agreement between respiratory variations in the photoplethysmographic waveform amplitude calculated from the available signals output by two different pulse oximeters was poor, both evaluated by LMSO and Bland-Altman plot. Respiratory amplitude variations from the available signals output by these two pulse oximeters are not interchangeable.

Agreement between stroke volume measured by oesophageal Doppler and uncalibrated pulse contour analysis during fluid loads in severe aortic stenosis.

The purpose of this analysis was to study agreement and trending of stroke volume measured by oesophageal Doppler and 3rd generation Vigileo during fluid loads in patients with severe aortic stenosis. Observational study in 32 patients (30 analyzed) scheduled for aortic valve replacement due to severe aortic stenosis. After induction of anesthesia and before start of surgery, hemodynamic registrations for 1 min were obtained before and after a fluid load. Agreement between stroke volume measured by oesophageal Doppler (SVOD) and Vigileo (SVVig) was evaluated in Bland-Altman plot and trending in four-quadrant and polar plots. Bias ± limits of agreement (LOA) between SVOD and SVVig was 24 ± 37 ml (percentage error 45%). Concordance of the two methods from before to after a fluid load was 100%. Angular bias ± LOA was 12° ± 28°. Absolute values of SVOD and SVVig agreed poorly, but changes were highly concordant during fluid loads in aortic stenosis patients. The angular agreement indicated acceptable trending. The two measurement methods are not interchangeable in patients with aortic stenosis.

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 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).

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.

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.

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.

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.