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/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.

Bioelectrical impedance vector analysis (BIVA) is a method used to estimate variation in body hydration. We assessed the potential of BIVA for monitoring daily body hydration fluctuations in nine healthy, normally active males under matching normoxic (NX) and hypobaric hypoxic (HH) experimental conditions. Furthermore, we aimed to investigate whether changes in BIVA may correspond with the development of acute mountain sickness (AMS). Subjects were exposed in a hypobaric chamber to both NX (corresponding to an altitude of 262 m) and HH conditions corresponding to an altitude of 3500 m during two four-day sojourns within which food, water intake and physical activity were controlled. Bioimpedance and body weight measurements were performed three times a day and medical symptoms were assessed every morning using the Lake Louise score (LLS). Total body water (TBW) was also assessed on the last day of both sojourns using the deuterium dilution technique. We detected circadian changes in vector length, indicating circadian body water variations that did not differ between NX and HH conditions (ANOVA effects: time: p = 0.018, eta² = 0.149; interaction: p = 0.214, eta² = 0.083; condition: p = 0.920, eta² = 0.001). Even though none of the subjects developed AMS, four subjects showed clinical symptoms according to the LLS during the first 24 hours of HH conditions. These subjects showed a pronounced (Cohen’s d: 1.09), yet not statistically significant (p = 0.206) decrease in phase angle 6 hours after exposure, which may indicate fluid shift from the intracellular to the extracellular compartment. At the end of each sojourn, vector length correlated with deuterium dilution TBW “gold standard” measurements (linear regression: NX: p = 0.002 and r² = 0.756, HH: p < 0.001 and r² = 0.84). BIVA can be considered a valuable method for monitoring body hydration changes at altitude. Whether such changes are related to the development of clinical symptoms associated with AMS, as indicated in the present investigation, must be confirmed in future studies.

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).

5-Hydroxymethylfurfural (5-HMF) is known to increase hemoglobin oxygen affinity (Hb–O₂ affinity) and to induce a left shift of the oxygen dissociation curve (ODC). It is under investigation as a therapeutic agent in sickle cell anemia and in conditions where pulmonary oxygen uptake is deteriorated or limited (e.g., various clinical conditions or altitude exposure). The combination of 5-HMF and α-ketoglutaric acid (αKG) is commercially available as a nutritional supplement. To further elucidate dose effects, ODCs were measured in vitro in venous whole blood samples of 20 healthy volunteers (10 female and 10 male) after the addition of three different doses of 5-HMF, αKG and the combination of both. Linear regression analysis revealed a strong dose-dependent increase in Hb–O₂ affinity for 5-HMF (R² = 0.887; p < 0.001) and the commercially available combination with αKG (R² = 0.882; p < 0.001). αKG alone increased Hb–O₂ affinity as well but to a lower extent. Both the combination (5-HMF + αKG) and 5-HMF alone exerted different P50 and Hill coefficient responses overall and between sexes, with more pronounced effects in females. With increasing Hb–O₂ affinity, the sigmoidal shape of the ODC was better preserved by the combination of 5-HMF and αKG than by 5-HMF alone. Concerning the therapeutic effects of 5-HMF, this study emphasizes the importance of adequate dosing in various physiological and clinical conditions, where a left-shifted ODC might be beneficial. By preserving the sigmoidal shape of the ODC, the combination of 5-HMF and αKG at low (both sexes) and medium (males only) doses might be able to better maintain efficient oxygen transport, particularly by mitigating potentially deteriorated oxygen unloading in the tissue. However, expanding knowledge on the interaction between 5-HMF and Hb–O₂ affinity in vitro necessitates further investigations in vivo to additionally assess pharmacokinetic mechanisms.

Inhalational prostacyclins act as strong vasodilators, potentially improving oxygenation by reducing shunt fraction and ventilation-perfusion mismatch. As prostacyclin receptors are known to be present on human erythrocytes, possible direct effects on hemoglobin oxygen transport were further explored by examining the sole in vitro influence of prostacyclins on hemoglobin oxygen (Hb-O₂) affinity. Venous blood samples from 20 healthy volunteers were exposed in vitro to supramaximal doses of epoprostenol, iloprost, and compared with control. By high-throughput measurements, hemoglobin oxygen dissociation curves (ODCs) were derived. Hb-O₂ affinity, expressed by P50 and Hill coefficient, was determined and analyzed for three subgroups: males ( n = 10), females not taking oral contraceptives ( n = 4), and females taking oral contraceptives ( n = 6). Epoprostenol significantly decreased P50 in all (males, females without contraceptives, and females taking oral contraceptives) [27.5 (26.4–28.6) mmHg (control) vs. 24.2 (22.7–25.3) mmHg; P < 0.001. median (interquartile range, IQR)] thereby increasing Hb-O₂ affinity. Inversely, iloprost only showed significant effects in females taking oral contraceptives where P50 was markedly increased and therefore Hb-O₂ affinity decreased [28.4 (27.9–28.9) mmHg (control) vs. 34.4 (32.2–36.0) mmHg; P < 0.001]. Prostacyclin-receptor stimulation and subsequent cAMP-mediated ATP release from erythrocytes are discussed as a possible underlying mechanism for the effect of epoprostenol on Hb-O₂ affinity. The reason for the sex hormone-modified iloprost effect remains unclear. Being aware of potentially differing effects on Hb-O₂ affinity might help select the right prostacyclin (epoprostenol vs. iloprost) depending on the patient and the underlying disease (e.g., acute respiratory distress syndrome vs. peripheral arterial disease).