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      Treatment of hypophosphatemia in the intensive care unit: a review

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          Abstract

          Introduction

          Currently no evidence-based guideline exists for the approach to hypophosphatemia in critically ill patients.

          Methods

          We performed a narrative review of the medical literature to identify the incidence, symptoms, and treatment of hypophosphatemia in critically ill patients. Specifically, we searched for answers to the questions whether correction of hypophosphatemia is associated with improved outcome, and whether a certain treatment strategy is superior.

          Results

          Incidence: hypophosphatemia is frequently encountered in the intensive care unit; and critically ill patients are at increased risk for developing hypophosphatemia due to the presence of multiple causal factors. Symptoms: hypophosphatemia may lead to a multitude of symptoms, including cardiac and respiratory failure. Treatment: hypophosphatemia is generally corrected when it is symptomatic or severe. However, although multiple studies confirm the efficacy and safety of intravenous phosphate administration, it remains uncertain when and how to correct hypophosphatemia. Outcome: in some studies, hypophosphatemia was associated with higher mortality; a paucity of randomized controlled evidence exists for whether correction of hypophosphatemia improves the outcome in critically ill patients.

          Conclusions

          Additional studies addressing the current approach to hypophosphatemia in critically ill patients are required. Studies should focus on the association between hypophosphatemia and morbidity and/or mortality, as well as the effect of correction of this electrolyte disorder.

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          Most cited references67

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          Hypophosphatemia: an update on its etiology and treatment.

          Phosphate plays a key role in several biological processes. In recent years, new insights have been obtained into the regulation of the phosphate metabolism, including a growing amount of evidence suggesting that factors other than parathyroid hormone (PTH) and vitamin D are involved in maintaining the phosphate balance. A new class of phosphate-regulating factors, the so-called "phosphatonins," have been shown to be important in phosphate-wasting diseases. However, the role of the phosphatonins in the normal human homeostasis remains to be established. The incidence of hypophosphatemia in selected patient series can be more than 20%, with clinical sequelae ranging from mild to life threatening. Only when combined with phosphate depletion does hypophosphatemia become clinically significant. The factors that are involved in the phosphate homeostasis, the pathophysiology, the relevance in patient care, the clinical manifestations, and an appropriate management of phosphate depletion are discussed in this review.
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            Proximal tubular phosphate reabsorption: molecular mechanisms.

            Renal proximal tubular reabsorption of P(i) is a key element in overall P(i) homeostasis, and it involves a secondary active P(i) transport mechanism. Among the molecularly identified sodium-phosphate (Na/P(i)) cotransport systems a brush-border membrane type IIa Na-P(i) cotransporter is the key player in proximal tubular P(i) reabsorption. Physiological and pathophysiological alterations in renal P(i) reabsorption are related to altered brush-border membrane expression/content of the type IIa Na-P(i) cotransporter. Complex membrane retrieval/insertion mechanisms are involved in modulating transporter content in the brush-border membrane. In a tissue culture model (OK cells) expressing intrinsically the type IIa Na-P(i) cotransporter, the cellular cascades involved in "physiological/pathophysiological" control of P(i) reabsorption have been explored. As this cell model offers a "proximal tubular" environment, it is useful for characterization (in heterologous expression studies) of the cellular/molecular requirements for transport regulation. Finally, the oocyte expression system has permitted a thorough characterization of the transport characteristics and of structure/function relationships. Thus the cloning of the type IIa Na-P(i )cotransporter (in 1993) provided the tools to study renal brush-border membrane Na-P(i) cotransport function/regulation at the cellular/molecular level as well as at the organ level and led to an understanding of cellular mechanisms involved in control of proximal tubular P(i) handling and, thus, of overall P(i) homeostasis.
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              Effect of hypophosphatemia on diaphragmatic contractility in patients with acute respiratory failure.

              We studied the effects of hypophosphatemia on diaphragmatic function in eight patients with acute respiratory failure who were artificially ventilated. Their mean serum phosphorus level was 0.55 +/- 0.18 mmol per liter (normal value, 1.20 +/- 0.10). The contractile properties of the diaphragm were assessed by measuring the transdiaphragmatic pressure generated at functional residual capacity during bilateral supramaximal electrical stimulation of the phrenic nerves. Diaphragmatic function was evaluated in each patient before and after correction of hypophosphatemia, which was achieved by administration of 10 mmol of phosphorus (as KH2PO4) as a continuous infusion for four hours. After phosphate infusion, the mean serum phosphorus level increased significantly (1.33 +/- 0.21 mmol per liter, P less than 0.0001). The increase in serum phosphorus was accompanied by a marked increase in the transdiaphragmatic pressure after phrenic stimulation (17.25 +/- 6.5 cm H2O as compared with 9.75 +/- 3.8 before phosphate infusion, P less than 0.001). Changes in the serum phosphorus level and transdiaphragmatic pressure were well correlated (r = 0.73). These results strongly suggest that hypophosphatemia impairs the contractile properties of the diaphragm during acute respiratory failure, and they emphasize the importance of maintaining normal serum inorganic phosphate levels in such patients.
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                Author and article information

                Journal
                Crit Care
                Critical Care
                BioMed Central
                1364-8535
                1466-609X
                2010
                3 August 2010
                : 14
                : 4
                : R147
                Affiliations
                [1 ]Department of Intensive Care Medicine, Catharina Hospital Eindhoven, Michelangelolaan 2, Eindhoven, 5623 EJ, The Netherlands
                [2 ]Department of Intensive Care Medicine, Medical Centre Leeuwarden, PO Box 888, Leeuwarden, 8901 BR, The Netherlands
                [3 ]Department of Intensive Care Medicine, Academic Medical Center, University of Amsterdam, Meibergdreef 9, Amsterdam, 1105 AZ, The Netherlands
                [4 ]HERMES Critical Care Group, Meibergdreef 9, Amsterdam, Amsterdam, 1105 AZ, The Netherlands
                [5 ]Department of Intensive Care Medicine, Gelre Hospitals, location Lukas, PO Box 9014, Apeldoorn, 7300 DS, The Netherlands
                [6 ]Laboratory of Experimental Intensive Care and Anesthesiology (LEICA), Academic Medical Center, University of Amsterdam, Meibergdreef 9, Amsterdam, 1105 AZ, The Netherlands
                Article
                cc9215
                10.1186/cc9215
                2945130
                20682049
                345b6f4c-0e01-4ced-907a-2e103b7ffe17
                Copyright ©2010 Geerse et al.; licensee BioMed Central Ltd

                This is an open access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 28 October 2009
                : 2 June 2010
                : 3 August 2010
                Categories
                Research

                Emergency medicine & Trauma
                Emergency medicine & Trauma

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