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      Bolus Administration of Intravenous Glucose in the Treatment of Hyperkalemia: A Randomized Controlled Trial

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          Abstract

          Background: Hyperkalemia is a common medical emergency that may result in serious cardiac arrhythmias. Standard therapy with insulin plus glucose reliably lowers the serum potassium concentration ([K<sup>+</sup>]) but carries the risk of hypoglycemia. This study examined whether an intravenous glucose-only bolus lowers serum [K<sup>+</sup>] in stable, nondiabetic, hyperkalemic patients and compared this intervention with insulin-plus-glucose therapy. Methods: A randomized, crossover study was conducted in 10 chronic hemodialysis patients who were prone to hyperkalemia. Administration of 10 units of insulin with 100 ml of 50% glucose (50 g) was compared with the administration of 100 ml of 50% glucose only. Serum [K<sup>+</sup>] was measured up to 60 min. Patients were monitored for hypoglycemia and EKG changes. Results: Baseline serum [K<sup>+</sup>] was 6.01 ± 0.87 and 6.23 ± 1.20 mmol/l in the insulin and glucose-only groups, respectively (p = 0.45). At 60 min, the glucose-only group had a fall in [K<sup>+</sup>] of 0.50 ± 0.31 mmol/l (p < 0.001). In the insulin group, there was a fall of 0.83 ± 0.53 mmol/l at 60 min (p < 0.001) and a lower serum [K<sup>+</sup>] at that time compared to the glucose-only group (5.18 ± 0.76 vs. 5.73 ± 1.12 mmol/l, respectively; p = 0.01). In the glucose-only group, the glucose area under the curve (AUC) was greater and the insulin AUC was smaller. Two patients in the insulin group developed hypoglycemia. Conclusion: Infusion of a glucose-only bolus caused a clinically significant decrease in serum [K<sup>+</sup>] without any episodes of hypoglycemia.

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          Most cited references30

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          Lactate transport in skeletal muscle - role and regulation of the monocarboxylate transporter.

          Skeletal muscle is the major producer of lactic acid in the body, but its oxidative fibres also use lactic acid as a respiratory fuel. The stereoselective transport of L-lactic acid across the plasma membrane of muscle fibres has been shown to involve a proton-linked monocarboxylate transporter (MCT) similar to that described in erythrocytes and other cells. This transporter plays an important role in the pH regulation of skeletal muscle. A family of eight MCTs has now been cloned and sequenced, and the tissue distribution of each isoform varies. Skeletal muscle contains both MCT1 (the only isoform found in erythrocytes but also present in most other cells) and MCT4. The latter is found in all fibre types, although least in more oxidative red muscles such as soleus, whereas expression of MCT1 is highest in the more oxidative muscles and very low in white muscles that are almost entirely glycolytic. The properties of MCT1 and MCT2 have been described in some detail and the latter shown to have a higher affinity for substrates. MCT4 has been less well characterized but has a lower affinity for L-lactate (i.e. a higher Km of 20 mM) than does MCT1 (Km of 5 mM). MCT1 expression is increased in response to chronic stimulation and either endurance or explosive exercise training in rats and humans, whereas denervation decreases expression of both MCT1 and MCT4. The mechanism of regulation is not established, but does not appear to be accompanied by changes in mRNA concentrations. However, in other cells MCT1 and MCT4 are intimately associated with an ancillary protein OX-47 (also known as CD147). This protein is a member of the immunoglobulin superfamily with a single transmembrane helix, whose expression is known to be increased in a range of cells when their metabolic activity is increased.
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            Ion-exchange resins for the treatment of hyperkalemia: are they safe and effective?

            Sodium polystyrene sulfonate (SPS), an ion-exchange resin designed to bind potassium in the colon, was approved in 1958 as a treatment for hyperkalemia by the US Food and Drug Administration, 4 years before drug manufacturers were required to prove the effectiveness and safety of their drugs. In September 2009, citing reports of colonic necrosis, the Food and Drug Administration issued a warning advising against concomitant administration of sorbitol, an osmotic cathartic used to prevent SPS-induced fecal impaction and to speed delivery of resin to the colon, with the powdered resin; however, a premixed suspension of SPS in sorbitol, the only preparation stocked by many hospital pharmacies, is prescribed routinely for treatment of hyperkalemia. We can find no convincing evidence that SPS increases fecal potassium losses in experimental animals or humans and no evidence that adding sorbitol to the resin increases its effectiveness as a treatment for hyperkalemia. There is growing concern, however, that suspensions of SPS in sorbitol can be harmful. It would be wise to exhaust other alternatives for managing hyperkalemia before turning to these largely unproven and potentially harmful therapies.
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              Insulin resistance in uremia.

              Tissue sensitivity to insulin was examined with the euglycemic insulin clamp technique in 17 chronically uremic and 36 control subjects. The plasma insulin concentration was raised by approximately 100 microU/ml and the plasma glucose concentration was maintained at the basal level with a variable glucose infusion. Under these steady-state conditions of euglycemia, the glucose infusion rate is a measure of the amount of glucose taken up by the entire body. In uremic subjects insulin-mediated glucose metabolism was reduced by 47% compared with controls (3.71 +/- 0.20 vs. 7.38 +/- 0.26 mg/kg . min; P less than 0.001). Basal hepatic glucose production (measured with [3H]-3-glucose) was normal in uremic subjects (2.17 +/- 0.04 mg/kg . min) and suppressed normally by 94 +/- 2% following insulin administration. In six uremic and six control subjects, net splanchnic glucose balance was also measured directly by the hepatic venous catheterization technique. In the postabsorptive state splanchnic glucose production was similar in uremics (1.57 +/- 0.03 mg/kg . min) and controls (1.79 +/- 0.20 mg/kg . min). After 90 min of sustained hyperinsulinemia, splanchnic glucose balance reverted to a net uptake which was similar in uremics (0.42 +/- 0.11 mg/kg . min) and controls (0.53 +/- 0.12 mg/kg . min). In contrast, glucose uptake by the leg was reduced by 60% in the uremic group (21 +/- 1 vs. 52 +/- 8 mumol/min . kg of leg wt; P less than 0.005) and this decrease closely paralleled the decrease in total glucose metabolism by the entire body. These results indicate that: (a) suppression of hepatic glucose production by physiologic hyperinsulinemia is not impaired by uremia, (b) insulin-mediated glucose uptake by the liver is normal in uremic subjects, and (c) tissue insensitivity to insulin is the primary cause of insulin resistance in uremia.
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                Author and article information

                Journal
                NEP
                Nephron Physiol
                10.1159/issn.1660-2137
                Nephron Physiology
                S. Karger AG
                1660-2137
                2014
                April 2014
                22 February 2014
                : 126
                : 1
                : 1-8
                Affiliations
                aDivision of Nephrology, Department of Medicine, Stellenbosch University and Tygerberg Hospital, bDivision of Chemical Pathology, National Health Laboratory Service and Stellenbosch University, and cFaculty of Health and Wellness Science, Cape Peninsula University of Technology, Cape Town, South Africa; dDivision of Nephrology, University of Toronto, and eKeenan Research Building, Li Ka Shing Knowledge Institute of St. Michaels Hospital, Toronto, Ont., Canada
                Author notes
                *Prof. M.R. Davids, Division of Nephrology, Department of Medicine, Stellenbosch University and Tygerberg Hospital, PO Box 19063, Tygerberg, Cape Town 7505 (South Africa), E-Mail mrd@sun.ac.za
                Article
                358836 Nephron Physiol 2014;126:1-8
                10.1159/000358836
                24576893
                7b153ab5-0308-4424-b0e9-445f7fd4640d
                © 2014 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                History
                : 21 October 2013
                : 17 January 2014
                Page count
                Figures: 4, Tables: 2, Pages: 8
                Categories
                Original Paper

                Cardiovascular Medicine,Nephrology
                Hyperkalemia,Insulin,Hypoglycemia,Glucose,Clinical trial
                Cardiovascular Medicine, Nephrology
                Hyperkalemia, Insulin, Hypoglycemia, Glucose, Clinical trial

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