Background With increasing altitude, the partial pressure of oxygen and oxygen saturation (SpO2) decrease, reducing physical performance. This study investigates whether the nutritional supplement Sanopal® (5-hydroxymethyl-2-furfural and α-ketoglutaric acid) increases hemoglobin-oxygen affinity and SpO₂ during exercise at moderate altitude.Methods Nineteen healthy young sports students (12 females, 7 males) participated in a single-blinded, placebo-controlled crossover study investigating the effects of Sanopal® at low (590 m) and moderate altitude (2900 m). Participants received Sanopal® or placebo in a randomized order, with measurements of SpO₂, heart rate, and blood parameters taken before and after ingestion, as well as before and after exercise at altitude.Results Under resting and acute hypoxia conditions, Sanopal® did not increase hemoglobin-oxygen affinity or SpO₂. At altitude and post-exercise, Hb-O₂ affinity decreased by approximately 5% in the PL trial but increased by approximately 2% in the SA session (interaction effect: p = 0.030). There were no significant differences in SpO₂ or heart rate between the Sanopal® and placebo groups.Conclusions Sanopal® did not alter hemoglobin-oxygen affinity or SpO₂ under resting conditions in normoxia or acute hypoxia. After exercise at altitude, it slightly increased Hb-O₂ affinity without significantly affecting SpO₂ or other measured blood parameters. The modest increase in Hb-O2 affinity following exercise may have limited the exercise-induced decrease in Hb-O2 affinity. However, this increase was likely too small to significantly raise SpO₂ in this cohort at a relatively low altitude.

Background: The urea-to-creatinine ratio (UCR) is used as a biomarker of protein catabolism in critical illness. However, the impact of acute kidney injury (AKI) severity on UCR dynamics remains poorly understood.Methods: This retrospective study analyzed 1567 consecutive ICU (intensive care unit) patients at two different ICUs at the university hospital of Innsbruck. Patients were categorized by AKI stage (KDIGO criteria). Temporal trajectories of UCR, urea generation rate and creatinine clearance were modeled using generalized additive models. Risk factors for an elevated UCR (>75 mg/dl:mg/dl) were identified via multivariate logistic regression.Results: Peak urea levels occurred consistently around days 6–7 across all groups. In contrast, creatinine peaked earlier (day 2 in stage 0; days 4–5 in stages I–III). The delay between urea and creatinine in achieving peak levels led to a decrease in UCR in dependence of AKI severity. Urea generation rate remained fairly comparable between groups. Multivariate analysis revealed that higher urea generation rate, protein intake, SAPS III, and older age independently predicted elevated UCR on day 4. However, the presence of AKI and male sex significantly reduced the risk of an elevated UCR.Conclusions: UCR dynamics are strongly influenced by asynchronous trajectories of creatinine and urea across different stages of acute kidney injury. In severe AKI, the earlier peak in creatinine relative to urea transiently lowers the UCR, potentially masking catabolic signals and limiting its reliability as a standalone marker of catabolism.

Bei septischen Patient:innen ist die Sauerstoffversorgung häufig beeinträchtigt, doch der spezifische Einfluss von Inflammation auf die Sauerstofftransporteigenschaften der Erythrozyten ist weitgehend unerforscht. Diese Studie untersuchte die direkten Effekte von Endotoxin-induzierter Inflammation auf die Sauerstoffbindungskurve (ODC). Akute Lipopolysaccharid(LPS)-induzierte Inflammation veränderte die Hämoglobin-Sauerstoffbindung nicht signifikant. Interessanterweise induzierte Dexamethason jedoch eine signifikante Rechtsverschiebung der ODC, was die Sauerstoffabgabe an das Gewebe erleichtern und klinische Implikationen für die Steroidtherapie bei septischen Patient:innen haben könnte.

During rapid exposure to hypobaric hypoxia (HH), arterial oxygen tension and haemoglobin oxygen saturation decrease. The oxygen dissociation curve (ODC) describes the relationship of oxygen tension and haemoglobin oxygen saturation. Previous methods for ODC determination are mostly limited to standard conditions (40 mmHg PCO2, 37 °C), and measurements of 2,3-bisphosphoglycerate (2,3-BPG) and adenosine triphosphate (ATP) are omitted. This study aimed to investigate hypoxia-induced changes on the ODC in a strictly controlled hypobaric chamber setting utilising a novel method for ODC determination, incorporating innovative 2,3-BPG and ATP measurements. In a randomised crossover design, ten healthy males completed two 4-day sojourns, one in HH (3,500 m) and one in normoxia (NX, 262 m). ODCs were determined from venous blood at 96 h using a highly customisable high-throughput microplate reader method. Haemoglobin half saturation pressure (P50) was measured for a standardised CO2 tension of 40 mmHg (P50st) and individual end-tidal CO2 tensions (PetCO2) (P50act). 2,3-BPG and ATP were determined by liquid chromatography–tandem mass spectrometry. P50st were increased in HH compared to NX but missed statistical significance (28.3 ± 2.0 mmHg vs. 26.8 ± 1.9 mmHg; p = 0.054), whilst P50act was similar in HH and NX (26.4 ± 1.6 mmHg vs. 26.1 ± 2.7 mmHg; p = 0.360) despite reduced PetCO2 (31.0 ± 2.1 mmHg vs. 38.4 ± 2.5 mmHg; p < 0.001). 2,3-BPG and pH were significantly increased in HH compared to NX (16.8 ± 1.6 µmol/gHb and 20.5 ± 1.1 µmol/gHb, p < 0.001; 7.36 ± 0.01 versus 7.39 ± 0.02, p < 0.001). The 2,3-BPG increase after 96 h in HH compensates the effect of hypoxia-induced decrease in PetCO2/increase in pH on the ODC.

In septic patients, oxygen delivery is often impaired, yet the specific impact of inflammation on erythrocyte oxygen transport characteristics remains largely unexplored. This study examined the direct effects of endotoxin-induced inflammation on the oxygen dissociation curve (ODC) and evaluated dexamethasone and noradrenaline as potential pharmacological interventions to modulate hemoglobin oxygen-binding properties during inflammation. Blood samples from ten healthy male volunteers were allocated to four groups: control, lipopolysaccharide (LPS), LPS with dexamethasone, and LPS with noradrenaline. Samples were incubated at 37 °C for two hours. ODCs were determined, providing p50 values and Hill coefficients. Blood gas analysis, 2,3-bisphosphoglycerate levels, and interleukin-6 (IL-6) levels were measured to assess metabolic parameters and inflammatory response. p50 values and Hill coefficients showed no significant differences between LPS-stimulated samples and controls. LPS effectively induced inflammatory activation with significantly elevated IL-6 levels (1416 (1226–1778) vs. 3 [2–4] ng/l, p = 0.002). Dexamethasone co-treatment significantly increased p50 values compared to LPS alone (29.2 (28.1–29.7) vs. 26.9 (25.7–27.9) mmHg, p = 0.030) and altered Hill coefficients (2.47 (2.32–2.56) vs. 2.65 (2.57–2.86), p = 0.002), indicating a rightward shift of the ODC. Noradrenaline demonstrated anti-inflammatory effects with reduced IL-6 levels (1212 (1068–1427) vs. 1416 (1226–1778) ng/l, p = 0.013) but did not significantly alter oxygen-binding properties. Acute inflammation does not directly alter hemoglobin oxygen-binding properties. The novel dexamethasone-induced rightward shift of the ODC may facilitate oxygen release to tissues and could have important clinical implications for steroid therapy in septic patients.

Background: An elevated urea–creatinine ratio (UCR) is used as a surrogate for catabolism and elevated protein metabolism in critically ill patients. This study investigated the effect of continuous renal replacement therapy (CRRT) on UCR. Methods: In this retrospective single-centre study, ICU patients from 2011 to 2022 with an ICU stay >2 days before CRRT and a CRRT duration of ≥4 days were included. Patients were grouped by UCR at CRRT initiation into high (UCR ≥ 75 mg/dL:mg/dL) and low groups and compared to matched controls not requiring CRRT. Propensity score matching considered age, sex, bodyweight, SAPS3, SOFA score, and UCR values on baseline and pre-baseline days. Results: In the high UCR group, UCR significantly decreased after CRRT initiation, reaching a significant difference from controls on day 2 (85.0 [IQR: 69.5–96.4] vs. 94.4 [IQR: 83.0–115.2]; p = 0.036) and falling below the threshold of 75 by day 3. In the low group, UCR increased post-CRRT initiation, but was less pronounced than in controls, with significant differences on day 1 (44.0 [IQR: 34.2–59.8] vs. 40.6 [IQR: 32.1–52.5]; p = 0.024). Conclusions: CRRT significantly affects UCR in critically ill patients, showing a marked decrease when compared to matched controls.

BACKGROUND:Companion rescue using avalanche transceivers can lead to a disproportionate increase in mental stress and arousal, which can negatively affect performance. The aim of this mixed-methods field study was to assess the effects of automated verbal commands on mental stress and affective responses. METHODS:Participants performed two search trials using avalanche transceivers with either verbal commands (VOICE) or without verbal commands (NO VOICE) in simulated avalanche rescue scenarios. The study assessed perceived mental stress with a visual analogue scale (VAS 1-10 points) and used the Self-Assessment-Manikin with 9-point Likert scales to measure affective response (valence, arousal, and dominance). Semistructured interviews were performed to assess the specific effects of verbal commands. RESULTS:Participants reported higher levels of mental stress after the trials than before the trials (-1.2 ± 2.3 points; p ≤ 0.001). A smaller increase (59.0 ± 8.2 s vs. larger increase [81.0 ± 11.5 s]) in mental stress, as detected in participants using VOICE navigation, resulted in shorter coarse search times. VOICE (Δ -1.2 ± 3.2 vs. Δ -0.6 ± 2.7 points; p = 0.041) showed a greater reduction in arousal, resulting in faster coarse search. In the qualitative interviews, the majority described VOICE navigation to be helpful. In the individual semistructured interviews, those subjects reporting a stress reduction through VOICE (38.5 ± 4.7 s vs. no stress reduction [107.4 ± 24.3 s]; p = 0.001) had a significantly faster coarse search time, and those who indicated VOICE to be helpful were faster in the coarse search (p = 0.013). CONCLUSIONS:The study demonstrated that even a simulated avalanche rescue scenario results in increased mental stress levels. VOICE navigation may be an interesting option for companion avalanche rescue since it helps to reduce mental stress and arousal, thereby leading to shorter search times. The most significant limitation of the study was the setting of an experimentally created avalanche scenario, which cannot fully replicate all the environmental and psychological factors of a veritable burial situation.

Background:The aim of this study was to analyse the influence of voice navigation in a new generation of transceivers on the time and success rate of transceiver search in a simulated avalanche rescue scenario. Methods:Fifty participants performed two randomized test runs, using two different transmitters with and without voice navigation. Primary outcome was success rate, total transceiver search and total location time, secondary outcome parameters comprised predefined time intervals (coarse search time, fine search time, probing time) and deviations from the recommended standard search procedure. Results:The study shows comparable results in success rate, total transceiver search time (111.1 s ± SD84.3 s) and total location time (134.4 s ± SD 112.6 s) for trials with and without voice navigation. Wrong initial search direction was corrected earlier in trials with voice (49.6 ± 6.9 s versus 93.7 ± 18.4 s p = 0.011). Participants were significantly faster in the second search trial (first 203.0 s versus 143.2 s; p = 0.002), a learning effect, more pronounced with voice navigation (voice 119.8 s vs. no-voice 164.8 s; p = 0.014). Deviations from the recommended standard search procedure were common (55 % of trials), without any difference between voice and no-voice navigation. Conclusions:This study demonstrated a wide inter-individual variation in total transceiver search times and total location time in participants without experience. Voice navigation did not result in a significant reduction of transceiver search times but led to a faster correction of a wrong initial search direction and improved the learning effect significantly in second trials. Voice navigation could possibly optimize performance in participants without prior experience in stressful situations.

Background/Objectives: The urea-to-creatinine ratio (UCR) serves as a biochemical marker for catabolism in the intensive care unit (ICU). UCR increases mainly due to an elevated urea generation from increased protein metabolism. This study aimed to evaluate the impact of protein intake on UCR progression in ICU patients. Methods: The inclusion criteria of this retrospective, single-center analysis required an ICU stay of at least 14 days without requirement of renal replacement therapy (n = 346 patients). Patients were grouped based on daily mean protein intake per kilogram between days 5 and 14: low (≤0.8 g/kg/d, n = 120), medium (0.9–1.2 g/kg/d, n = 132), and high (≥1.3 g/kg/d, n = 94). Data on daily protein and calorie intake, calorie deficit, urea generation rate, serum creatinine, urea, UCR and creatinine clearances were analysed. Risk factors for developing a high UCR were determined via logistic regression analysis adjusted for sex, age, bodyweight, disease severity (SAPS III admission score) as well as mean protein intake and calorie deficit during day 5 and 14 on ICU. Results: Higher protein intake was associated with increased calorie intake, lower calorie deficit, and led to an elevated urea generation rate and higher UCR. Renal function and serum urea trends were comparable between all groups, while creatinine was significantly lower in the high-protein group. Risk factors for developing an elevated UCR included older age, female sex and higher protein intake. Conclusions: An elevated UCR in the early ICU phase may indicate an increased protein metabolism, not only deriving from catabolism but also from a high protein feed.

Recently, chronic intermittent inhalation of low-dose carbon monoxide (CO) has been postulated as a practice to increase total hemoglobin mass with potential beneficial effects on endurance performance. In this perspective article, we discuss the potential performance enhancing capabilities as well as the safety concerns, which include individual variability in CO response, and acute and chronic health effects. It is also important to note that according to the World-Anti-Doping-Agency (WADA), CO inhalation could fall under “M1. Manipulation of Blood and Blood Components“ and therefore could be considered a prohibited method if used as a non-diagnostic tool.

The shape and position of the hemoglobin-oxygen dissociation curve (ODC) is of critical importance in medicine, as it determines the uptake of O2 in the lungs and the delivery of O2 to the tissues. Numerous reports have identified affinity-modulating effects of drugs in humans. Such effects may be relevant to conditions such as pulmonary diffusion disorders, peripheral vascular disease, or coronary artery disease. The aim of this scoping review was to assess and summarize the current evidence on these effects. The review was based on the PRISMA-ScR guidelines. We searched PubMed and the Cochrane Library and only included papers with free full-text access. The search covers all papers published before September 2024 and used the following keywords: “Oxygen affinity” or “oxygen dissociation curve” in combination with > 100 substance classes that should cover most drugs in clinical use. The search returned 2447 hits of which 80 were selected for further full text review. In terms of discipline, cardiology accounted for the largest proportion, and in terms of effect quality, a right-ward shift resulting in improved tissue oxygenation was most common. For example, quantitative data show an increase in P50 of 6.1–12.4

The affinity of hemoglobin (Hb) to oxygen (O2) influences processes of oxygen delivery and extraction at the tissue level. Despite cannabinoids being utilized or ingested in various ways, their possible impact on Hb-O2 affinity has barely been studied. This is an experimental ex-vivo trial. Venous blood samples were drawn from 5 male and 6 female healthy volunteers and subsequently exposed to different cannabinoid types: (delta-9-tetrahydrocannabinol [Δ9-THC], delta-8-tetrahydrocannabinol [Δ8-THC], cannabidiol [CBD]) at different concentrations. Oxygen dissociation curves (ODC) were measured and blood gas analyses were performed for methemoglobin (MetHb) determination. The results revealed no MetHb formation. Besides two statistically significant changes (+1.4mmHg and -0.9mmHg) in the female cohort, following Δ9-THC and Δ8-THC exposure, no further P50 changes could be observed. The study demonstrated an in-vitro effect of selected cannabinoids and dosages on P50 values in female participants, with variations not observed at other dosages, leaving the underlying mechanisms open for debate. MetHb formation, as potential mechanism, was not detected in this study. The precise reasons why changes only occurred at specific dosages remain unclear, indicating a need for further in-vivo research to understand the interaction between cannabinoids and Hb-O2 affinity completely.

Background Hemoglobin‑oxygen (Hb-O2) affinity is an important determinant for oxygen delivery and oxygen extraction. Although cardiovascular agents such as noradrenaline, adrenaline, atropine, milrinone and levosimendan are widely used in intensive care units worldwide, nothing is known about their possible effects on Hb-O2 affinity. Methods In this experimental ex-vivo trial, venous blood samples were taken from 5 male and 6 female volunteers and incubated with the particular cardiovascular agents. Oxygen dissociation curves (ODC) were measured in-vitro with a new high-throughput method. Results Compared to the P50 in male and female controls, a significant right-shift of the ODC was found for noradrenaline and milrinone in all participants and for levosimendan in male samples only. Adrenaline decreased Hb-O2 affinity in male samples, atropine in female samples only. Discussion All investigated agents decreased Hb-O2 affinity, with marked differences between males and females. Although the underlying mechanisms remain unclear, the extent of these effects may increase oxygen extraction at the tissue level as long as pulmonary oxygen uptake is maintained.

Purpose: To further analyse causes and effects of ICU-acquired hypernatremia.Methods: This retrospective, single-centre study, analysed 994 patients regarding ICU-acquired hypernatremia. Non-hypernatremic patients (n=617) were compared to early-hypernatremic (only before ICU-day 4; n=87), prolonged-hypernatremic (before and after ICU-day 4; n=169) and late-hypernatremic patients (only after ICU- day 4; n=121). Trends in glomerular filtration rate (eGFR), urea-to-creatinine ratio (UCR), fraction of urea in total urine osmolality and urine sodium were compared. Risk factors for i) the development of hypernatremia and ii) mortality were determined.Results: Thirty-eight percent (n=377) developed ICU-acquired hypernatremia. Specifically in the prolonged- and late-group, decreased eGFRs and urine sodium but increased UCR and fractions of urea in urine osmolality were present. Decreased eGFR was a risk factor for the development of hypernatremia in all groups; disease severity and increased catabolism particularly in the prolonged- and late-hypernatremic group. Increased age, SAPS-III and signs of catabolism but not the development of hypernatremia itself was identified as significant risk fac- tor for mortality.Conclusions: Late- and prolonged-hypernatremia is highly related to an increased protein metabolism. Besides excessive catabolism, initial disease severity and a decrease in renal function must be considered when con- fronted with ICU-acquired hypernatremia.

Out-of-hospital reduction of shoulder dislocations using the Campell method is recommended by the International Commission for Alpine Rescue and applied in the Bavarian Mountain Rescue Service (Bergwacht Bayern, BWB) protocols. This prospective observational study includes patients out-of-hospital with suspected shoulder dislocation and treated and evacuated by the BWB. Data were systematically collected using three questionnaires: one completed on-site by the rescuer, the second in hospital by the physician and the third within 28 (8–143) days after the accident by the patient. The suspected diagnosis of shoulder dislocation was confirmed in hospital in 37 (84%) of 44 cases. Concomitant injuries in other body regions were found in eight (16%) of 49 cases and were associated with incorrect diagnosis ( p = 0.002). Younger age ( p = 0.043) and first shoulder dislocation event ( p = 0.038) were associated with a higher success rate for reduction attempts. Out-of-hospital reduction of shoulder dislocations leads to significant pain relief and no poorer long-term outcome. Signs that are associated with successful out-of-hospital reduction (younger age and first event), but also those that are associated with incorrect diagnosis (concomitant injuries) should be considered before trying to reduce shoulder dislocation on site. The considerable rate of incorrect first diagnosis on site should give rise to an intensive discussion around teaching and training for this intervention. Trial registration : This study is registered with the German Registry for Clinical Trials (DRKS00023377).

Woyke, Simon, Anja Hutter, Christopher Rugg, Willi Troger, Bernd Wallner, Mathias Strohle, and Peter Paal. Sex differences in mountain bike accidents in Austria from 2006 to 2018: a retrospective analysis. High Alt Med Biol 00:000-000, 2023.Introduction: Mountain biking is becoming increasingly popular, and mountain bike (MTB) accidents are on the rise. The aim of this study was to assess sex differences in mountain biking accidents in the Austrian Alps.Methods: This retrospective study includes all MTB accidents in Austria from 2006 to 2018. Data were collected by Alpine Police officers and recorded in a national digital registry.Results: The accidents involved 5,095 mountain bikers (81% men and 19% women). The number of MTB accidents rose markedly from 208 in 2006 to 725 in 2018. Men wore a helmet more often than did women (95% vs. 92%; p = 0.001). The most common injury category was "wound/bleeding" for both sexes (men 40% and women 41%). Women were more frequently transported by helicopter or terrestrially (p > 0.001).Conclusion: In the Austrian Alps, the number of MTB accidents more than tripled between 2006 and 2018. Women were involved in only one fifth of all accidents. Sex differences in MTB accidents include (1) women wearing helmets less often, (2) women being less frequently injured, (3) women suffering fewer serious injuries, and (4) women being more frequently transported by helicopter or terrestrially, while men more often did not require transportation.

Desflurane, isoflurane and sevoflurane, three halogenated ethers, are commonly used inhaled anesthetics, both in the operating room and in the intensive care unit (ICU). The potency and dosage of these drugs is expressed by the MAC value (minimum alveolar concentration). Their interaction with hemoglobin and its affinity for oxygen, best described by the oxygen dissociation curve (ODC), has already been investigated, with conflicting results. Altered by many factors, the ODC can be shifted to the left or to the right, therefore increasing or decreasing hemoglobin oxygen (Hb-O2) affinity. In venous blood samples of 22 healthy participants (11 female, 11 male) ODC were measured with a high-throughput method in vitro. Blood samples were either exposed to control or to three different concentrations of desflurane, isoflurane or sevoflurane prior to and during measurements (low, medium and high corresponding to MAC 0.5, MAC 1.0 and MAC 2.0). With increasing concentrations from control to medium, desflurane and isoflurane significantly decreased Hb-O2 affinity by shifting the ODC to the right (p = 0.016 and p < 0.001) but sevoflurane showed no effects. When further increasing concentrations from medium to high, all three inhaled anesthetics shifted the ODC back to the left (p < 0.001). Comparing only controls to high concentrations, a significant increase in Hb-O2 affinity for desflurane (p = 0.005) and sevoflurane (p < 0.001) was detected. Our study shows a varying effect at different doses of inhaled anesthetics on Hb-O2 affinity. While the underlying mechanisms remain unclear, these results show an effect which needs to be further investigated to determine if patients undergoing anesthesia may potentially benefit or get disadvantage from this slightly increased (e.g. impaired pulmonary oxygen uptake), or decreased Hb-O2 affinity (e.g. arterial vascular disease).Trial registration: This study is registered with clinicaltrials.gov (NCT04612270).