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The contribution of plasma urea to total osmolality during iatrogenic fluid reduction in critically ill patients
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.ORCID iD: 0000-0001-9995-3132
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.ORCID iD: 0000-0003-2278-7951
Program in Cardiovascular and Metabolic Disorders, Duke- NUS Medical School, Singapore, Singapore;Division of Nephrology and Hypertension, University Clinic Erlangen, Erlangen, Germany;Division of Nephrology, Duke University Medical Center, Durham, NC, USA.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
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2021 (English)In: Function, E-ISSN 2633-8823, Vol. 3, no 1Article in journal (Refereed) Published
Abstract [en]

Hyperosmolality is common in critically ill patients during body fluid volume reduction. It is unknown whether this is only a result of decreased total body water or an active osmole-producing mechanism similar to that found in aestivating animals, where muscle degradation increases urea levels to preserve water. We hypothesized that fluid volume reduction in critically ill patients contributes to a shift from ionic to organic osmolytes similar to mechanisms of aestivation. We performed a post-hoc analysis on data from a multicenter observational study in adult intensive care unit (ICU) patients in the postresuscitative phase. Fluid, electrolyte, energy and nitrogen intake, fluid loss, estimated glomerular filtration rate (eGFR), and estimated plasma osmolality (eOSM) were registered. Contributions of osmolytes Na+, K+, urea, and glucose to eOSM expressed as proportions of eOSM were calculated. A total of 241 patients were included. eOSM increased (median change 7.4 mOsm/kg [IQR−1.9–18]) during the study. Sodium's and potassium's proportions of eOSM decreased (P < .05 and P < .01, respectively), whereas urea's proportion increased (P < .001). The urea’s proportion of eOSM was higher in patients with negative vs. positive fluid balance. Urea's proportion of eOSM increased with eOSM (r = 0.63; adjusted for eGFR r = 0.80), but not nitrogen intake. In patients without furosemide and/or renal replacement therapy (n = 17), urea’s proportion of eOSM and eOSM correlated strongly (r = 0.92). Urea’s proportion of eOSM was higher in patients not surviving up to 90 d. In stabilized ICU patients, the contribution of urea to plasma osmolality increased during body water volume reduction, statistically independently of nitrogen administration and eGFR. The shift from ionic osmolytes to urea during body fluid volume reduction is similar to that seen in aestivating animals.

Place, publisher, year, edition, pages
Oxford University Press (OUP) Oxford University Press, 2021. Vol. 3, no 1
National Category
Anesthesiology and Intensive Care
Identifiers
URN: urn:nbn:se:uu:diva-460905DOI: 10.1093/function/zqab055ISI: 000769818500005PubMedID: 35330925OAI: oai:DiVA.org:uu-460905DiVA, id: diva2:1618316
Available from: 2021-12-09 Created: 2021-12-09 Last updated: 2025-03-07Bibliographically approved
In thesis
1. Physiological and psychological aspects of fluid therapy in anaesthesia and intensive care medicine
Open this publication in new window or tab >>Physiological and psychological aspects of fluid therapy in anaesthesia and intensive care medicine
2025 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Intravenous fluid administration is commonly used for critically ill and perioperative patients, but increasing attention is being given to its potential negative effects. In these cases, balancing fluid needs for hemodynamic stability with avoiding fluid overload and organ damage is crucial.

This thesis aimed to describe fluid administration practices in ICUs and postoperative care units in Sweden, focusing on how clinicians’ approach four key areas. It also sought to highlight the consequences of these practices and encourage clinicians to reconsider routine fluid prescriptions in both intensive care and perioperative settings.

In Paper I, a prospective multicentre interventional cross-over study, we investigated if limiting the availability of standard-sized fluid bags of Ringer’s acetate and replacing them with smaller-sized fluid bags would affect the total amount of fluid administered to ICU patients (n=437) and the impact on morbidity or mortality. However, data did not support our hypothesis.

Paper II is a retrospective, multicentre study examining fluid types given to ICU patients (n=241) in the post-resuscitation phase. We found that maintenance and drug fluids significantly exceeded resuscitative fluids, with patients receiving more maintenance fluids, drug diluents, and sodium than recommended.

Paper III is a post-hoc analysis of Paper II data. We found that plasma urea's share of estimated plasma osmolality increases during fluid volume reduction and with higher osmolality, independent of nitrogen administration and renal function. This shift from ionic osmolytes to urea resembles patterns seen in estivating animals.

Paper IV is a single-centre study examining the relationship between ADH levels, fluid administration, and urine output in postoperative major abdominal surgery patients (n=54). We found that elevated ADH levels did not predict urine output or oliguria, but hypotension did. Increased fluid administration did not normalize urine output after oliguria.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2025. p. 67
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 2161
Keywords
Anaesthesia, Critical Care, Perioperative Care, Fluid Therapy, Fluid Balance.
National Category
Anesthesiology and Intensive Care
Identifiers
urn:nbn:se:uu:diva-552076 (URN)978-91-513-2504-0 (ISBN)
Public defence
2025-08-21, H:son Holmdahlsalen, Akademiska sjukhuset, ing. 100, Uppsala, 09:15 (Swedish)
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Available from: 2025-05-26 Created: 2025-03-07 Last updated: 2025-05-26

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Nihlén, SandraFrithiof, RobertKawati, RafaelRylander, ChristianPikwer, AndreasCastegren, MarkusHultström, MichaelLipcsey, Miklós

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