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Background: Previously, the authors found "liberal" fluid administration (approximately 3 l Ringer's lactate [RL]) to improve early rehabilitation after laparoscopic cholecystectomy, suggesting functional hypovolemia to be present in patients receiving "restrictive" fluid administration (approximately 1 l RL). Because volume kinetic analysis after a volume load may distinguish between hypovolemic versus normovolemic states, the authors applied volume kinetic analysis after laparoscopic cholecystectomy to explain the difference in outcome between 3 and 1 l RL.Methods: In a prospective, nonrandomized trial, the authors studied 20 patients undergoing laparoscopic cholecystectomy. Ten patients received 15 ml/kg RL (group 1) and 10 patients received 40 ml/kg RL (group 2) intraoperatively. All other aspects of perioperative management were standardized. A 12.5-ml/kg RL volume load was infused preoperatively and 4 h postoperatively. The distribution and elimination of the fluid load was estimated using volume kinetic analysis.Results: Patient baseline demographics and intraoperative data did not differ between groups, except for intraoperative RL, having a median of 1,118 ml (range, 900-1,400 ml) in group 1 compared with a median of 2,960 ml (range, 2,000-3,960 ml) in group 2 (P<0.01). There were no significant preoperative versus postoperative differences in the size of the body fluid space expanded by infused fluid (V), whereas the clearance constant kr was higher postoperatively versus preoperatively (P=0.03). The preoperative versus postoperative changes in volume kinetics including V were not different between the two groups.Conclusions: Elimination of an intravenous fluid load was increased after laparoscopic cholecystectomy per se but not influenced by the amount of intraoperative fluid administration. [ABSTRACT FROM AUTHOR]

Group A beta-hemolytic streptococcal pharyngitis, scarlet fever, and rarely asymptomatic carrier states are associated with a number of poststreptococcal suppurative and nonsuppurative complications. As in streptococcal pharyngitis, acute rheumatic fever, pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection, and poststreptococcal glomerulonephritis most often occur in children. The hallmarks of rheumatic fever include arthritis, carditis, cutaneous disease, chorea, and subsequent acquired valvular disease. Pediatric autoimmune neuropsychiatric disorders encompass a subgroup of illnesses involving the basal ganglia in children with obsessive-compulsive disorders, tic disorders, dystonia, chorea encephalitis, and dystonic choreoathetosis. Poststreptococcal glomerulonephritis is most frequently encountered in children between two and six years of age with a recent history of pharyngitis and a rash in the setting of poor personal hygiene during the winter months. The clinical examination of a patient with possible poststreptococcal complications should begin with an evaluation for signs of inflammation (i.e., complete blood count, erythrocyte sedimentation rate, C-reactive protein) and evidence of a preceding streptococcal infection. Antistreptolysin O titers should be obtained to confirm a recent invasive streptococcal infection. Other important antibody markers include antihyaluronidase, antideoxyribonuclease B, and antistreptokinase antibodies. [ABSTRACT FROM AUTHOR]

Intravenous volume loading is a common treatment when hypovolemia is a potential cause of oliguria. We studied whether the effectiveness of Ringer's solution and 20% albumin in inducing diuresis differs depending on the mean arterial pressure (MAP). For this purpose, volume kinetic analysis was performed based on urine output and hemoglobin-derived plasma dilution obtained during and after 136 infusions of Ringer and 85 infusions of 20% albumin. Covariance analysis quantified the diuretic response at different arterial pressures. The results show that the diuretic response to a known plasma volume expansion was greater for Ringer's solution above a MAP of 70 mmHg, while 20% albumin was significantly more effective at lower pressures (p < 0.03). Simulations of the urinary output in response to infusion of a predefined fluid volume yielded superior efficacy for 20% albumin when the MAP was low, while Ringer's was similarly effective when the MAP averaged 100 mmHg. In conclusion, urine output in response to plasma volume expansion with 20% albumin was similar to, or even stronger, than that of Ringer's solution when the MAP was below 70 mmHg., (© 2024 The Author(s). Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Background and Aims: The National Institute for Health and Care Excellence's (NICE) Guideline for Maintenance Fluid Therapy in Adults in Hospital is widely used, but the recommendations have not been evaluated properly. In this study, we investigated whether the recommendation of providing 25-30 mL/kg/day of fluid and 1 mmol/kg each of sodium and potassium is sufficient for human needs., Methods: First, we calculated the distribution of fluid between the extracellular fluid volume (ECV) and intracellular fluid volume (ICV) during a cross-over infusion experiment where 12 volunteers received 25 mL/kg/day of either a high-sodium (154 mmol/L) or low-sodium (54 mmol/L) solution over 48 h. Second, urine samples from 719 volunteers and clinical patients were used to quantify their renal water conservation and excretion of sodium and potassium. Third, retrospective analysis of a diet study was used to extrapolate how large the fluid intake and the electrolyte excretion likely had been in the 719 volunteers and hospital patients who delivered urine., Results: The high-sodium fluid maintained the ECV but the ICV had decreased by 1.3 L after 48 h. The low-sodium fluid resulted in a volume deficit of 1.7 L that equally affected the ECV and the ICV. Regression equations based on the diet study suggested that the daily intake of water in the 719 subjects averaged 2.6 L and that 2 mmol/kg of sodium and 1 mmol/kg of potassium was excreted., Conclusion: The NICE guideline recommends too little water and sodium for a human to adequately maintain the ECV and ICV., Clinical Trial Registrations: EudraCT 2016-001846-24 and ISRCTN 12215472., Competing Interests: Declaration of competing interest RGH has received a research grant from Grifols for studies of 20% albumin (2019–2021) and is Member of Baxter's European IV Fluid Therapy Management Advisory Board. NVR has received speaker's fees and resided in a medical advisory board organized by Baxter Healthcare, USA. NVR is co-chairman of the International Fluid Academy (www.fluidacademy.org), a non-profit organization promoting education in fluid management and hemodynamic monitoring that received sponsoring from the industry., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The distribution and elimination of infused crystalloid fluid is known to be affected by general anesthesia, but it is unclear whether changes differ depending on whether the patient is operated in the flat recumbent position, the Trendelenburg ("legs up") position, or the reverse Trendelenburg ("head up") position., Methods: Retrospective data on hemodilution and urine output obtained during and after infusion of 1-2 L of Ringer's solution over 30-60 min were collected from 61 patients undergoing surgery under general anesthesia and 106 volunteers matched with respect to the infusion volume and infusion time. Parameters describing fluid distribution in the anesthetized and awake subjects were compared by population volume kinetic analysis., Results: General anesthesia decreased the rate constant for urine output by 79% (flat recumbent), 91% (legs up) and 91% (head up), suggesting that laparoscopic surgery per se intensified the already strong anesthesia-induced fluid retention. General anesthesia also decreased the rate constant governing the return of the distributed fluid to the plasma by 32%, 15%, and 70%, respectively. These results agree with laboratory data showing a depressive effect of anesthetic drugs on lymphatic pumping, and further suggest that the "legs up" position facilitates lymphatic flow, whereas the "head up" position slows this flow. Both Trendelenburg positions increased swelling of the "third fluid space"., Conclusions: General anesthesia caused retention of infused fluid with preferential distribution to the extravascular space. Both Trendelenburg positions had a modifying influence on the kinetic adaptations that agreed with the gravitational forces inflicted by tilting to body., (© 2024 The Author(s). Acta Anaesthesiologica Scandinavica published by John Wiley & Sons Ltd on behalf of Acta Anaesthesiologica Scandinavica Foundation.)

Introduction: The interstitial space harbours two fluid compartments linked serially to the plasma. This study explores conditions that lead to fluid accumulation in the most secluded compartment, termed the "third space"., Methods: Retrospective data was collected from 326 experiments in which intravenous crystalloid fluid was administered to conscious volunteers as well as a small group of anaesthetized patients. The urinary excretion and plasma dilution derived from haemoglobin served as input variables in nine population volume kinetic analyses representing subtly different settings., Results: An infusion of 250-500 mL of Ringer's solution expanded only the central fluid space (plasma), whereas the infusion of 500-1,000 mL extended into a rapidly exchanging interstitial fluid space. When more than 1 L was infused over 30 min, it was distributed across plasma and both interstitial fluid compartments. The remote space, characterized by slow turnover, abruptly accommodated fluid upon accumulation of 700-800 mL in the rapidly exchanging space, equivalent to an 11%-13% volume increase. However, larger expansion was necessary to trigger this event in a perioperative setting. The plasma half-life of crystalloid fluid was 25 times longer when 2,000-2,700 mL expanded all three fluid compartments compared to when only 250-500 mL expanded the central space (14 h versus 30 min)., Conclusion: As the volume of crystalloid fluid increases, it apparently occupies a larger proportion of the interstitial space. When more than 1 L is administered at a high rate, there is expansion of a remote "third space", which considerably extends the intravascular half-life., Competing Interests: The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Hahn.)

Background: Physiological studies suggest that the interstitial space contains 2 fluid compartments, but no analysis has been performed to quantify their sizes and turnover rates., Methods: Retrospective data were retrieved from 270 experiments where Ringer's solution of between 238 and 2750 mL (mean, 1487 mL) had been administered by intravenous infusion to awake and anesthetized humans (mean age 39 years, 47% females). Urinary excretion and hemoglobin-derived plasma dilution served as input variables in a volume kinetic analysis using mixed-models software., Results: The kinetic analysis successfully separated 2 interstitial fluid compartments. One equilibrated rapidly with the plasma and the other equilibrated slowly. General anesthesia doubled the rate constants for fluid entering these 2 compartments (from 0.072 to 0.155 and from 0.026 to 0.080 min -1 , respectively). The return flows to the plasma were impeded by intensive fluid therapy; the rate constant for the fast-exchange compartment decreased from 0.251 to 0.050 when the infusion time increased from 15 to 60 minutes, and the rate constant for the slow-exchange compartment decreased from 0.019 to 0.005 when the infused volume increased from 500 to 1500 mL. The slow-exchange compartment became disproportionately expanded when larger fluid volumes were infused and even attained an unphysiologically large size when general anesthesia was added, suggesting that the flow of fluid was restrained and not solely determined by hydrostatic and oncotic forces. The dependence of the slow-exchange compartment on general anesthesia, crystalloid infusion rate, and infusion volume all suggest a causal physiological process., Conclusions: Kinetic analysis supported that Ringer's solution distributes in 2 interstitial compartments with different turnover times. The slow compartment became dominant when large amounts of fluid were infused and during general anesthesia. These findings may explain why fluid accumulates in peripheral tissues during surgery and why infused fluid can remain in the body for several days after general anesthesia., Competing Interests: Conflicts of Interest: See Disclosures at the end of the article., (Copyright © 2024 International Anesthesia Research Society.)

General anesthetics adversely alters the distribution of infused fluid between the plasma compartment and the extravascular space. This maldistribution occurs largely from the effects of anesthetic agents on lymphatic pumping, which can be demonstrated by macroscopic fluid kinetics studies in awake versus anesthetized patients. The magnitude of this effect can be appreciated as follows: a 30% reduction in lymph flow may result in a fivefold increase of fluid-induced volume expansion of the interstitial space relative to plasma volume. Anesthesia-induced lymphatic dysfunction is a key factor why anesthetized patients require greater than expected fluid administration than can be accounted for by blood loss, urine output, and insensible losses. Anesthesia also blunts the transvascular refill response to bleeding, an important compensatory mechanism during hemorrhagic hypovolemia, in part through lymphatic inhibition. Last, this study addresses how catecholamines and hypertonic and hyperoncotic fluids may mobilize interstitial fluid to mitigate anesthesia-induced lymphatic dysfunction., (Copyright © 2024 American Society of Anesthesiologists. All Rights Reserved.)

Background: Kinetic analysis of crystalloid fluid yields a central distribution volume (V c ) of the same size as the expected plasma volume (approximately 3 L) except during general anesthesia during which V c might be only half as large. The present study examined whether this difference is due to influence of the intravascular albumin balance., Methods: A population volume kinetic analysis according to a three-compartment model was performed based on retrospective data from 160 infusion experiments during which 1-2.5 L of crystalloid fluid had been infused intravenously over 20-30 min. The plasma dilution based on blood hemoglobin (Hb) and plasma albumin (Alb) was measured on 2,408 occasions and the urine output on 454 occasions. One-third of the infusions were performed on anesthetized patients while two-thirds were given to awake healthy volunteers., Results: The Hb-Alb dilution difference was four times greater during general anesthesia than in the awake state (+ 0.024 ± 0.060 versus - 0.008 ± 0.050; mean ± SD; P < 0.001) which shows that more albumin entered the plasma than was lost by capillary leakage. The Hb-Alb dilution difference correlated strongly and positively with the kinetic parameters governing the rate of fluid transfer through the fast-exchange interstitial fluid compartment (k 12 and k 21 ) and inversely with the size of V c . Simulations suggest that approximately 200 mL of fluid might be translocated from the interstitial space to the plasma despite ongoing fluid administration., Conclusions: Pronounced plasma volume expansion early during general anesthesia is associated with a positive intravascular albumin balance that is due to accelerated lymphatic flow. This phenomenon probably represents adjustment of the body fluid volumes to anesthesia-induced vasodilatation., (© 2024. The Author(s).)

Background: The f-cell ratio of 0.91 is a conversion factor between the hematocrit measured in peripheral blood and the hematocrit obtained by separate measurements of the red blood cell mass and plasma volume. The physiological background of the f-cell ratio is unclear., Methods: Data were retrieved from 155 intravenous infusion experiments where 15-25 mL/kg of crystalloid fluid diluted the blood hemoglobin and plasma albumin concentrations. The hemodilution was converted to plasma dilution using the peripheral hematocrit, and the volume of distribution of exogenous albumin was calculated in 41 volunteers who received 20 % or 5 % albumin by intravenous infusion. Finally, the kinetics of plasma albumin was studied during 98 infusion experiments with 20 % albumin., Results: Plasma dilution based on hemoglobin and albumin showed a median difference of -0.001 and a mean difference of 0.000 (N = 2184), which demonstrates that these biomarkers indicate the same expandable vascular space. In contrast, exogenous albumin occupied a volume that was 10 % larger than the plasma volume indicated by the anthropometric equations of Nadler et al. and Retzlaff et al. The kinetic analysis identified a secondary compartment that was 450 mL in size and rapidly exchanged albumin with the circulating plasma., Conclusions: The results suggest that the f-cell ratio is due to rapid exchange of albumin between the plasma and a non-expandable compartment located outside the circulating blood (possibly the liver sinusoids). This means that the hematocrit measured in peripheral blood correctly represents the ratio between the red cell volume and the circulating plasma volume., Competing Interests: Declaration of competing interest RGH is member of Baxter's IV Fluid Therapy Management Advisory Board., (Copyright © 2023. Published by Elsevier Inc.)

Background: Volume replacement with crystalloid fluid is the conventional treatment of hemorrhage. We challenged whether a standardized amount of 5% or 20% albumin could be a viable option to maintain the blood volume during surgery associated with major hemorrhage. Therefore, the aim of this study was to quantify and compare the plasma volume expansion properties of 5% albumin, 20% albumin, and Ringer-lactate, when infused during major surgery., Methods: In this single-center randomized controlled trial, fluid replacement therapy to combat hypovolemia during the hemorrhagic phase of cystectomy was randomly allocated in 42 patients to receive either 5% albumin (12 mL/kg) or 20% albumin (3 mL/kg) over 30 min at the beginning of the hemorrhagic phase, both completed by a Ringer-lactate replacing blood loss in a 1:1 ratio, or Ringer-lactate alone to replace blood loss in a 3:1 ratio. Measurements of blood hemoglobin over 5 h were used to estimate the effectiveness of each fluid to expand the blood volume using the following regression equation: blood loss plus blood volume expansion = factor + volume of infused albumin + volume of infused Ringer-lactate., Results: The median hemorrhage was 848 mL [IQR: 615-1145]. The regression equation showed that the Ringer-lactate solution expanded the plasma volume by 0.18 times the infused volume while the corresponding power of 5% and 20% albumin was 0.74 and 2.09, respectively. The Ringer-lactate only fluid program resulted in slight hypovolemia (mean, - 313 mL). The 5% and 20% albumin programs were more effective in filling the vascular system; this was evidenced by blood volume changes of only + 63 mL and - 44 mL, respectively, by long-lasting plasma volume expansion with median half time of 5.5 h and 4.8 h, respectively, and by an increase in the central venous pressure., Conclusion: The power to expand the plasma volume was 4 and almost 12 times greater for 5% albumin and 20% albumin than for Ringer-lactate, and the effect was sustained over 5 h. The clinical efficacy of albumin during major hemorrhage was quite similar to previous studies with no hemorrhage., Trial Registration: ClinicalTrials.gov NCT05391607, date of registration May 26, 2022., (© 2024. The Author(s).)

Background: Hypovolemia and peripheral edema are frequent components of preeclampsia. The level of the dysregulation of the body fluid distribution is unclear, which complicates the choice of infusion fluid during surgery. The present fluid kinetic study challenges whether the maldistribution of fluid is due to increased capillary leakage or to poor return of already distributed fluid, which occurs via lymphatic pathways., Methods: Ringeŕs solution was infused in 10 awake non-pregnant women, eight healthy pregnant women, and in eight women with mild-to-moderately severe preeclampsia. Distribution and redistribution of the infused fluid was calculated with mixed models kinetics based on the excreted urine volumes and 675 measurements of hemodilution. Differences in fluid kinetics between the three groups were studied with covariance analysis., Results: The return flow of fluid volume to the plasma after distribution (rate parameter k 21 ) was almost zero in women with preeclampsia, while the rate was normal in the other two groups (P< 0.001). By contrast, the capillary leakage rate of fluid in response to the infusion (k 12 ) was normal. The urinary excretion (k 10 ) was moderately accelerated., Conclusion: Decreased flow of extravascular fluid to the plasma was the key disturbance in women with preeclampsia. Such decreased flow alone promotes hypovolemia, peripheral edema, and hypoalbuminemia, and may be explained by inhibition of lymphatic pumping and/or a decreased interstitial hydrostatic pressure due to the presence of vasoactive and inflammatory signal molecules. The moderately accelerated urine flow may be due to "pressure diuresis" in response to hypertension., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Urine output < 1 L per 24 h is a clinical warning sign that requires attention from hospital staff, who should determine whether the low flow is due to low habitual intake of water or disease-induced dehydration. The incidence of this condition is unclear., Methods: A cohort of 20 healthy volunteers (mean age 42 years, range 23-62 years) recorded their food and water intakes daily for 8 days. They also collected and measured all urine and delivered first morning urine samples for analysis of osmolality and creatinine. Optimal cutoffs for these biomarkers to indicate urine output of < 1 L or 15 mL/kg during the preceding 24 h were applied with and without correction for age to cross-sectional data from 1,316 subjects in various clinical settings, including healthy volunteers, preoperative patients, patients seeking acute care at a hospital, and patients receiving institutional geriatric care., Results: The urine output amounted to < 1 L during 22 of the 159 evaluable study days and was indicated by urine osmolality > 760 mosmol/kg or urine creatinine > 13 mmol/L, which had sensitivity and specificity of approximately 80%. Days with urine output < 1 L were associated with significantly less intake of both water (-41%) and calories (-22%) compared to other days. Application of age-corrected biomarker cutoffs to the 1,316 subjects showed a stronger dependency of low urine output on age than the clinical setting, occurring in 44% of the 72 participants aged 15-30 years and 18% of the 62 patients aged 90-104 years., Conclusion: Biomarkers measured in morning urine of young and middle-aged volunteers indicated urine output of < 1 L with good precision, but the cutoffs should be validated in older age groups to yield reliable results., Trial Registrations: ISRCTN12215472 at http://www.isrctn.com ; NCT01458678 at ClinicalTrials.gov, and ChiCTR-TNRC-14,004,479 at the chictr.org/en., (© 2024. The Author(s).)

Background: Kinetic analysis of fluid volume shifts can identify two interstitial fluid compartments with different turnover rates, but how they are connected to the bloodstream is unknown., Methods: Retrospective data were retrieved from 217 experiments where 1.5 L of Ringer's solution (mean) had been administered by intravenous infusion over 30 min to awake and anesthetized humans (mean age 40 years). Urinary excretion and hemoglobin-derived plasma dilution served as input variables in a volume kinetic analysis using mixed models software. Possible modes of connection between the two interstitial fluid compartments and the bloodstream were judged by covariance analysis between kinetic rate constants, physiological variables, and time factors., Results: The return flow of already distributed fluid to the plasma via a fast-exchange interstitial compartment was inhibited ongoing infusion of fluid (-38 %), which was probably due to increase of the venous pressure during volume loading. Ongoing infusion also greatly retarded the entrance of fluid to the slow-exchange compartment (-85 %), which suggests that infused Ringer's first had to enter the fast-exchange compartment. A high mean arterial pressure markedly increased the urine output and, to a lesser degree, also the rate of entrance of fluid to the fast-exchange compartment. Moreover, a high blood hemoglobin concentration retarded the rate of entrance of fluid to the fast-exchange compartment., Conclusions: The fast-exchange but not the slow-exchange interstitial fluid compartment was affected by intravascular events, which suggests that only the fast-exchange compartment is directly connected to the circulating blood., Competing Interests: Declaration of competing interest RGH is Member of Baxter's IV Fluid Therapy Management Advisory Board., (Copyright © 2023 The Author. Published by Elsevier Inc. All rights reserved.)

Introduction: Oscillations are frequently observed on plasma dilution curves during intravenous fluid therapy. This study aimed to examine how common these oscillations are and what they represent., Methods: Fourier transforms were used to analyze the residuals obtained during fitting of a volume kinetic model to 269 plasma dilution curves. Oscillating patterns were identified in two-thirds of the fluid infusion experiments., Results: The wave frequency usually had a dominating frequency of 1 h or multiples thereof. The wave amplitudes varied between 1% and 4% of the plasma volume. The "peak-to-peak" amplitudes were then twice as large, which corresponded to blood volume changes of 60-240 mL. A population kinetic analysis of the distribution of infused fluid between body fluid compartments was then applied to search for clues that could explain the oscillations. This analysis showed that amplitudes &gt;1.5% were associated with doubled turnover of fluid in a fast-exchange interstitial fluid compartment and, together with data on plasma albumin, suggested that oscillations might represent bursts of efferent lymph., Conclusions: Oscillations with very low frequency were often observed on plasma dilution-time curves obtained during fluid therapy. They were associated with fast turnover of interstitial fluid and can possibly have resulted from accelerated lymphatic flow., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Background: Endothelial glycocalyx (EG) plays a crucial role in maintaining the plasma proteins within the intravascular space., Objective: We studied whether exogenous albumin protects the EG in an experimental model of EG enzymatic damage in rats., Methods: Rats were divided into three groups of 10 animals that received (1) Evans blue (2) Evans blue + hyaluronidase, or (3) Evans blue + hyaluronidase + 20% human albumin via the tail vein. Spectrophotometric analysis was performed 2 h later to quantify the leakage of Evans blue-labeled albumin into the heart, lungs, brain, kidneys, liver, small intestine, spleen, and skeletal muscle., Results: Administration of hyaluronidase numerically increased the capillary leakage of Evans blue in all examined tissues. Co-administration of albumin decreased the leakage of albumin in all tissues except the heart. In the lungs, the ratio between the absorbance and dry organ weight decreased from 5.3 ± 2.4 to 1.7 ± 0.5 (mean ± SD) (P < 0.002), and in the liver, the absorbance decreased from 2.2 ± 0.7 to 1.5 ± 0.4 (P < 0.011)., Conclusion: Exogenous albumin decreased the capillary leakage of albumin which was interpreted as a sign of maintained EG integrity.

Although effective and appropriate fluid management is a critical aspect of quality care during hospitalization, the widespread adoption of consistent policies that ensure adequate fluid stewardship has been slow and heterogenous. Despite evidence-based guidelines on fluid management being available, clinical opinions continue to diverge on important aspects of care in this setting, and the consistency of guideline implementation is far from ideal. A multidisciplinary panel of leading practitioners and experts convened to discuss best practices for ongoing staff education, intravenous fluid therapy, new training technologies, and strategies to track the success of institutional fluid stewardship efforts. Fluid leads should be identified in every hospital to ensure consistency in fluid administration and monitoring. In this article, strategies to communicate the importance of effective fluid stewardship for the purposes of education, training, institutional support, and improvement of patient outcomes are reviewed and recommendations are summarized., (© 2023. La Société de Réanimation de Langue Francaise = The French Society of Intensive Care (SRLF).)

Perioperative fluid management, a critical aspect of major surgeries, is characterized by pronounced stress responses, altered capillary permeability, and significant fluid shifts. Recognized as a cornerstone of enhanced recovery protocols, effective perioperative fluid management is crucial for optimizing patient recovery and preventing postoperative complications, especially in high-risk patients. The scientific literature has extensively investigated various fluid infusion regimens, but recent publications indicate that not only the volume but also the type of fluid infused significantly influences surgical outcomes. Adequate fluid therapy prescription requires a thorough understanding of the physiological and biochemical principles that govern the body's internal environment and the potential perioperative alterations that may arise. Recently published clinical trials have questioned the safety of synthetic colloids, widely used in the surgical field. A new clinical scenario has arisen in which crystalloids could play a pivotal role in perioperative fluid therapy. This review aims to offer evidence-based clinical principles for prescribing fluid therapy tailored to the patient's physiology during the perioperative period. The approach combines these principles with current recommendations for enhanced recovery programs for surgical patients, grounded in physiological and biochemical principles.

Background: Fluid therapy during major surgery can be managed by providing repeated bolus infusions until stroke volume no longer increases by ≥ 10%. However, the final bolus in an optimization round increases stroke volume by < 10% and is not necessary. We studied how different cut-off values for the hemodynamic indications given by esophagus Doppler monitoring, as well as augmentation by pulse oximetry, are associated with a higher or smaller chance that stroke volume increases by ≥ 10% (fluid responsiveness) before fluid is infused., Methods: An esophagus Doppler and a pulse oximeter that displayed the pleth variability index were used to monitor the effects of a bolus infusion in 108 patients undergoing goal-directed fluid therapy during major open abdominal surgery., Results: The analyzed data set comprised 266 bolus infusions. The overall incidence of fluid responsiveness was 44%, but this varied greatly depending on pre-infusion hemodynamics. The likelihood of being fluid-responsive was 30%-38% in the presence of stroke volume > 80 mL, corrected flow time > 360 ms, or pleth variability index < 10%. The likelihood was 21% if stroke volume had decreased by <8% since the previous optimization, which decreased to 0% if combined with stroke volume > 100 mL. By contrast, the likelihood of fluid responsiveness increased to 50%-55% when stroke volume ≤ 50 mL, corrected flow time ≤ 360 ms, or pleth variability index ≥ 10. A decrease in stroke volume by > 8% since the previous optimization was followed by a 58% likelihood of fluid responsiveness that, in combination with any of the other hemodynamic variables, increased to 66%-76%., Conclusions: Single or combined hemodynamic variables provided by esophagus Doppler monitoring and pulse oximetry derived pleth variability index could help clinicians avoid unnecessary fluid bolus infusions., (© 2023 The Authors. Acta Anaesthesiologica Scandinavica published by John Wiley & Sons Ltd on behalf of Acta Anaesthesiologica Scandinavica Foundation.)

Elevations of plasma creatinine are common after major surgery, but their pathophysiology is poorly understood. To identify possible contributing mechanisms, we pooled data from eight prospective studies performed in four different countries to study circumstances during which elevation of plasma creatinine occurs. We included 642 patients undergoing mixed major surgeries, mostly open gastrointestinal. Plasma and urinary creatinine and a composite index for renal fluid conservation (Fluid Retention Index, FRI) were measured just before surgery and on the first postoperative morning. Urine flow was measured during the surgery. The results show that patients with a postoperative increase in plasma creatinine by >25% had a high urinary creatinine concentration (11.0±5.9 vs. 8.3±5.6 mmol/L; P< 0001) and higher FRI value (3.2±1.0 vs. 2.9±1.1; P< 0.04) already before surgery was initiated. Progressive increase of plasma creatinine was associated with a gradually lower urine flow and larger blood loss during the surgery (Kruskal-Wallis test, P< 0.001). The patients with an elevation > 25% also showed higher creatinine and a higher FRI value on the first postoperative morning (P< 0.001). Elevations to > 50% of baseline were associated with slightly lower mean arterial pressure (73 ± 10 vs. 80 ± 12 mmHg; P< 0.005). We conclude that elevation of plasma creatinine in the perioperative period was associated with low urine flow and greater blood loss during surgery and with concentrated urine both before and after the surgery. Renal water conservation-related mechanisms seem to contribute to the development of increased plasma creatinine after surgery., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Hahn et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Intravenous infusion of hyper-oncotic 20 % albumin expands the plasma volume by approximately twice the infused volume. We investigated whether the recruited fluid stems from accelerated flow of efferent lymph, which would add protein to the plasma, or from reversed transcapillary solvent filtration, where the solvent is expected to be low in protein., Methods: We analyzed data from 27 intravenous infusions of 20 % albumin (3 mL/kg; approximately 200 mL) over 30 min given to 27 volunteers and patients. Twelve of the volunteers were also given a 5 % solution and served as controls. The pattern of blood hemoglobin, colloid osmotic pressure, and the plasma concentrations of two immunoglobulins (IgG and IgM) were studied over 5 h., Results: A decrease of the difference between the plasma colloid osmotic pressure and plasma albumin occurred during the infusions and was almost four times greater for 5 % albumin than for 20 % albumin at 40 min (P < 0.0036), which indicates that non-albumin protein enriched the plasma when 20 % was infused. Moreover, the difference between the infusion-derived dilution of the blood plasma based on hemoglobin and the two immunoglobulins amounted to -1.9 % (-6 to +0.2) for 20 % albumin and to -4.4 % (25th-75th percentile range - 8.5 to +0.2) during experiments with 5 % albumin (P < 0.001). This supports that the plasma was enriched by immunoglobulins, probably via the lymph, when 20 % was infused., Conclusions: Between half and two-thirds of the extravascular fluid that was recruited during infusion of 20 % albumin in humans consisted of protein-containing fluid consistent with efferent lymph., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Robert G. Hahn has received a research grant from Grifols for studies of 20 % albumin and is Member of Baxter's IV Fluid Therapy Management Advisory Board. The other authors declare that they have no conflicts of interest to report., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

The pharmacokinetics (PK) of ethanol are important in pharmacology and therapeutics because of potential drug-alcohol interactions as well as in forensic science when alcohol-related crimes are investigated. The PK of ethanol have been extensively studied since the 1930s, although some issues remain unresolved, such as the significance of first-pass metabolism, whether zero-order kinetics apply, and the effects of food on bioavailability. We took advantage of nonlinear mixed-effects modeling to describe blood-alcohol concentration (BAC) profiles derived from 3 published clinical studies involving oral, intraduodenal, and intravenous administration of ethanol with and without food. The overall data set included 1510 BACs derived from 72 healthy subjects (60 men, 12 women) aged between 20 and 60 years. Two-compartment models with first-order absorption and Michaelis-Menten elimination kinetics adequately described the BAC profiles. Food intake had 2 separate effects: It reduced the absorption rate constant and accelerated the maximum elimination rate. Estimates of the maximum elimination rate (fasted) and the food effect (as a factor) were 6.31 g/h (95%CI, 6.04-6.59 g/h) and 1.39-fold (95%CI, 1.33-1.46-fold), respectively. Simulations showed that the area under the BAC-time curve (AUC) was smaller with lower input rate of ethanol, irrespective of any first-pass metabolism. The AUC from time 0 to 10 hours for a 75-kg subject was 2.34 g • h/L (fed) and 3.83 g • h/L (fasted) after an oral dose of 45 g ethanol. This difference was mainly attributable to the food effect on ethanol elimination and depended less on the absorption rate. Our new approach to explain the complex human PK of ethanol may help when BAC predictions are made in clinical pharmacology and forensic medicine., (© 2023 The Authors. The Journal of Clinical Pharmacology published by Wiley Periodicals LLC on behalf of American College of Clinical Pharmacology.)

Fluid normally exchanges freely between the plasma and interstitial space and is returned primarily via the lymphatic system. This balance can be disturbed by diseases and medications. In inflammatory disease states, such as sepsis, the return flow of fluid from the interstitial space to the plasma seems to be very slow, which promotes the well-known triad of hypovolemia, hypoalbuminemia, and peripheral edema. Similarly, general anesthesia, for example, even without mechanical ventilation, increases accumulation of infused crystalloid fluid in a slowly equilibrating fraction of the extravascular compartment. Herein, we have combined data from fluid kinetic trials with previously unconnected mechanisms of inflammation, interstitial fluid physiology and lymphatic pathology to synthesize a novel explanation for common and clinically relevant examples of circulatory dysregulation. Experimental studies suggest that two key mechanisms contribute to the combination of hypovolemia, hypoalbuminemia and edema; (1) acute lowering of the interstitial pressure by inflammatory mediators such as TNFα, IL-1β, and IL-6 and, (2) nitric oxide-induced inhibition of intrinsic lymphatic pumping., (© 2023. The Author(s).)

Background and Aims: The extracellular and intracellular fluid volumes (ECV and ICV) vary not only with age, gender, and body weight but also with the habitual intake of water. The present study examines whether the baseline variations in the ECV and ICV change the distribution and elimination of subsequently given infusion fluids., Material and Methods: Twenty healthy male volunteers underwent 50 infusion experiments with crystalloid fluid for which the fluid volume kinetics was calculated based on frequent measurements of the hemodilution using mixed-effects modeling software. The results were compared with the ECV and ICV measured with multifrequency bioimpedance analysis before each infusion started. The fluids were given over 30 minutes and comprised 25 mL/kg Ringer's acetate ( N = 20), Ringer's lactate, 5 mL/kg 7.5% saline, and 3 mL/kg 7.5% saline in 6% dextran 70 (these fluids, N = 10)., Results: A large ICV was associated with a small extravascular accumulation of infused fluid, which increased the plasma volume expansion and the urinary excretion. With hypertonic fluid, a large ECV greatly accelerated urinary excretion. The body weight did not serve as a covariate in the kinetic models. Albumin was recruited to the plasma during infusion of both types of fluid. The hypertonic fluids served as diuretics. The infused excess sodium and osmolality were distributed over a 35% larger space than the sum of the ECV and ICV., Conclusion: A large ICV reduced the rate of distribution of Ringer's solution, whereas a large ECV accelerated the excretion of hypertonic saline., Competing Interests: The author holds a research grant from Grifols for studies of 20% albumin., (Copyright: © 2022 Journal of Anaesthesiology Clinical Pharmacology.)

Background: In preparation of future pandemics, it is important to recognise population-level determinants associated with development of severe illness before efficient vaccines and evidence-based therapeutic measures are available. The aim of this study was to identify pre-pandemic diagnoses recorded in a middle-aged and elderly population that were associated with development of severe COVID-19 during the first pandemic year., Methods: A cohort study design was used. Severe COVID-19 was defined as a course of illness that resulted in hospital admission or death. A retrospective analysis was performed that comprised all individuals aged 39 years and older (N = 189,951) living in Jönköping County, Sweden. All diagnosed morbidity recorded in contacts with health care during the pre-pandemic year 2019 was used to identify which diagnoses that were associated with development of severe COVID-19 in the first pandemic year 2020. The analyses were performed separately for each diagnosis using binary logistic regression with adjustment for sex and age., Results: Severe COVID-19 was suffered by 0.67% (N = 1,280) of the middle-aged and elderly population in the first pandemic year. Individuals previously diagnosed with dementia, cerebral palsy, kidney failure, type 2 diabetes mellitus, hypertension, and obesity were at higher risk of developing severe COVID-19. For patients with Type 2 diabetes mellitus, the odds ratio (OR) was 2.18 (95% confidence interval, 1.92-2.48). Type 1 diabetes mellitus was not associated with increased risk., Conclusion: Diagnoses suggesting service provision at long-term healthcare facilities and co-morbidity with components of the metabolic syndrome were associated with an increased risk of developing severe COVID-19 in a middle-aged and elderly population before vaccines were available., (© 2023. The Author(s).)