Skip to main content
Top
Published in: Critical Care 1/2015

Open Access 01-12-2015 | Research

Influence of a strict glucose protocol on serum potassium and glucose concentrations and their association with mortality in intensive care patients

Authors: Esther V. Uijtendaal, Jeannette E.F. Zwart-van Rijkom, Dylan W. de Lange, Arief Lalmohamed, Wouter W. van Solinge, Toine C.G. Egberts

Published in: Critical Care | Issue 1/2015

Login to get access

Abstract

Introduction

Tight glucose control therapy (TGC) has been implemented to control hyperglycemia in ICU patients. TGC may also influence serum potassium concentrations. We therefore investigated the influence of TGC on both serum glucose and serum potassium concentrations and associated mortality.

Method

We performed a retrospective analysis including all patients admitted to the ICU of a tertiary hospital for 24 hours or more and with at least three serum glucose and serum potassium concentrations between 1999–2001 (conventional period), 2002–2006 (implementation period) or 2007–2009 (TGC period). Segmented regression analysis was used to estimate changes in outcomes that occurred after the intervention controlling for pre-intervention trends. Means and standard deviations (SDs) of serum glucose and serum potassium concentrations, and rate of severe hypoglycemia (≤2.2 mmol/L) and hypokalemia (≤3 mmol/L), were compared between the TGC and conventional period.

Results

Although mean serum glucose concentrations dropped 2.1 mmol/L (95 % CI =−1.8 to −2.3 mmol/L, p<0.002), mean serum potassium concentrations did not change (absolute increase 0.02 mmol/L; 95 % CI = −0.06 to 0.09 mmol/L, p=0.64). The rate of severe hypoglycemia increased with 5.9 % (95 % CI=−3.0 to −8.9, p<0.002), but the rate of hypokalemia remained equal (absolute reduction 4.8 %; 95 % CI = −11.1 % to 1.5 %, p=0.13). The SD of serum glucose concentrations within a patient did not change, while the SD of serum potassium concentrations even decreased 0.04 mmol/L (95 % CI = −0.01 to −0.07, p=0.01). ICU mortality decreased but this decrease was not significant (absolute difference −3.63 %; 95 % CI = −9.33 to 2.09, p=0.20).
Mean serum glucose concentrations, mean serum potassium concentrations and SDs of both serum glucose and serum potassium concentrations were all independently associated with ICU mortality. Highest mortality rates were seen at both the lowest and highest mean values (U/J-shaped association) and mortality rates increased with increasing variability (SDs) for both serum glucose and serum potassium concentrations.

Conclusion

Our study shows that a TGC was not associated with an increased risk of serum potassium related events. Low and high mean values and high variability of both serum glucose and serum potassium concentrations are predictors for high ICU mortality.
Appendix
Available only for authorised users
Literature
1.
go back to reference Lepper PM, Ott S, Nüesch E, Von Eynatten M, Schumann C, Pletz MW, et al. Serum glucose levels for predicting death in patients admitted to hospital for community acquired pneumonia: prospective cohort study. BMJ. 2012;344:e3397.CrossRefPubMedPubMedCentral Lepper PM, Ott S, Nüesch E, Von Eynatten M, Schumann C, Pletz MW, et al. Serum glucose levels for predicting death in patients admitted to hospital for community acquired pneumonia: prospective cohort study. BMJ. 2012;344:e3397.CrossRefPubMedPubMedCentral
2.
go back to reference Brownlee M. Biochemistry and molecular cell biology of diabetic complications. Nature. 2001;414:813–20.CrossRefPubMed Brownlee M. Biochemistry and molecular cell biology of diabetic complications. Nature. 2001;414:813–20.CrossRefPubMed
3.
go back to reference Weekers F, Giulietti AP, Michalaki M, Coopmans W, Van Herck E, Mathieu C, et al. Metabolic, endocrine and immune effects of stress hyperglycemia in a rabbit model of prolonged critical illness. Endocrinology. 2003;144:5329–38.CrossRefPubMed Weekers F, Giulietti AP, Michalaki M, Coopmans W, Van Herck E, Mathieu C, et al. Metabolic, endocrine and immune effects of stress hyperglycemia in a rabbit model of prolonged critical illness. Endocrinology. 2003;144:5329–38.CrossRefPubMed
4.
go back to reference Mizock BA. Alterations in carbohydrate metabolism during stress: A review of the literature. Am J Med. 1995;98:75–84.CrossRefPubMed Mizock BA. Alterations in carbohydrate metabolism during stress: A review of the literature. Am J Med. 1995;98:75–84.CrossRefPubMed
5.
go back to reference Van Cromphaut SJ. Hyperglycaemia as part of the stress response: the underlying mechanisms. Best Pract Res Clin Anaesthesiol. 2009;23:375–86.CrossRefPubMed Van Cromphaut SJ. Hyperglycaemia as part of the stress response: the underlying mechanisms. Best Pract Res Clin Anaesthesiol. 2009;23:375–86.CrossRefPubMed
8.
go back to reference Van den Berghe G, Wouters P, Weekers F, Verwaest C, Bruyninckx F, Schetz M, et al. Intensive insulin therapy in critically ill patients. N Engl J Med. 2001;345:1359–67.CrossRefPubMed Van den Berghe G, Wouters P, Weekers F, Verwaest C, Bruyninckx F, Schetz M, et al. Intensive insulin therapy in critically ill patients. N Engl J Med. 2001;345:1359–67.CrossRefPubMed
9.
go back to reference Van den Berghe G, Wilmer A, Hermans G, Meersseman W, Wouters PJ, Milants I, et al. Intensive insulin therapy in the medical ICU. N Engl J Med. 2006;354:449–61.CrossRefPubMed Van den Berghe G, Wilmer A, Hermans G, Meersseman W, Wouters PJ, Milants I, et al. Intensive insulin therapy in the medical ICU. N Engl J Med. 2006;354:449–61.CrossRefPubMed
10.
go back to reference De La Rosa GDC, Donado JH, Restrepo AH, Quintero AM, González LG, Saldarriaga NE, et al. Strict glycaemic control in patients hospitalised in a mixed medical and surgical intensive care unit: a randomised clinical trial. Crit Care. 2008;12:R120.CrossRef De La Rosa GDC, Donado JH, Restrepo AH, Quintero AM, González LG, Saldarriaga NE, et al. Strict glycaemic control in patients hospitalised in a mixed medical and surgical intensive care unit: a randomised clinical trial. Crit Care. 2008;12:R120.CrossRef
11.
go back to reference Arabi YM, Dabbagh OC, Tamim HM, Al-Shimemeri AA, Memish ZA, Haddad SH, et al. Intensive versus conventional insulin therapy: a randomized controlled trial in medical and surgical critically ill patients. Crit Care Med. 2008;36:3190–7.CrossRefPubMed Arabi YM, Dabbagh OC, Tamim HM, Al-Shimemeri AA, Memish ZA, Haddad SH, et al. Intensive versus conventional insulin therapy: a randomized controlled trial in medical and surgical critically ill patients. Crit Care Med. 2008;36:3190–7.CrossRefPubMed
12.
go back to reference The NICE-SUGAR Study Investigators. Intensive versus conventional glucose control in critically ill patients. N Engl J Med. 2009;360:1283–97.CrossRef The NICE-SUGAR Study Investigators. Intensive versus conventional glucose control in critically ill patients. N Engl J Med. 2009;360:1283–97.CrossRef
13.
go back to reference Van den Berghe G, Mesotten D, Vanhorebeek I. Intensive insulin therapy in the intensive care unit. CMJA. 2009;180:799–800. Van den Berghe G, Mesotten D, Vanhorebeek I. Intensive insulin therapy in the intensive care unit. CMJA. 2009;180:799–800.
14.
go back to reference Friedrich JO, Chant C, Adhikari NKJ. Does intensive insulin therapy really reduce mortality in critically ill surgical patients? A reanalysis of meta-analytic data. Crit Care. 2010;14:324–30.CrossRefPubMedPubMedCentral Friedrich JO, Chant C, Adhikari NKJ. Does intensive insulin therapy really reduce mortality in critically ill surgical patients? A reanalysis of meta-analytic data. Crit Care. 2010;14:324–30.CrossRefPubMedPubMedCentral
15.
go back to reference Wiener SR, Wiener D, Larson R. Benefits and risks of tight glucose control in critically ill adults. JAMA. 2008;300:933–44.CrossRefPubMed Wiener SR, Wiener D, Larson R. Benefits and risks of tight glucose control in critically ill adults. JAMA. 2008;300:933–44.CrossRefPubMed
16.
go back to reference Kansagara D, Fu R, Freeman M, Wolf F, Helfand M. Intensive insulin therapy in hospitalized patients: a systematic review. Ann Intern Med. 2011;154:268–82.CrossRefPubMed Kansagara D, Fu R, Freeman M, Wolf F, Helfand M. Intensive insulin therapy in hospitalized patients: a systematic review. Ann Intern Med. 2011;154:268–82.CrossRefPubMed
17.
go back to reference Bagshaw SM, Bellomo R, Jacka MJ, Egi M, Hart GK, George C. The impact of early hypoglycemia and blood glucose variability on outcome in critical illness. Crit Care. 2009;13:R91.CrossRefPubMedPubMedCentral Bagshaw SM, Bellomo R, Jacka MJ, Egi M, Hart GK, George C. The impact of early hypoglycemia and blood glucose variability on outcome in critical illness. Crit Care. 2009;13:R91.CrossRefPubMedPubMedCentral
18.
go back to reference Quagliaro L, Piconi L, Assaloni R, Martinelli L, Motz E, Ceriello A. Intermittent high glucose enhances apoptosis related to oxidative stress in human umbilical vein endothelial cells: the role of protein kinase C and NAD(P)H-oxidase activation. Diabetes. 2003;52:2795–804.CrossRefPubMed Quagliaro L, Piconi L, Assaloni R, Martinelli L, Motz E, Ceriello A. Intermittent high glucose enhances apoptosis related to oxidative stress in human umbilical vein endothelial cells: the role of protein kinase C and NAD(P)H-oxidase activation. Diabetes. 2003;52:2795–804.CrossRefPubMed
19.
go back to reference Monnier L, Mas E, Ginet C, Michel F, Villon L, Cristol JP, et al. Activation of Oxidative Stress by Acute Glucose Fluctuations Compared With Sustained Chronic Hyperglycemia in Patients With Type 2 Diabetes. JAMA. 2006;295:1681–7.CrossRefPubMed Monnier L, Mas E, Ginet C, Michel F, Villon L, Cristol JP, et al. Activation of Oxidative Stress by Acute Glucose Fluctuations Compared With Sustained Chronic Hyperglycemia in Patients With Type 2 Diabetes. JAMA. 2006;295:1681–7.CrossRefPubMed
20.
go back to reference Egi M, Bellomo R, Stachowski E, French CJ, Hart G. Variability of Blood Glucose Concentration and Short-term Mortality in Critically Ill Patients. Anesthesiology. 2006;105:244–52.CrossRefPubMed Egi M, Bellomo R, Stachowski E, French CJ, Hart G. Variability of Blood Glucose Concentration and Short-term Mortality in Critically Ill Patients. Anesthesiology. 2006;105:244–52.CrossRefPubMed
21.
go back to reference Krinsley JS. Glycemic variability: A strong independent predictor of mortality in critically ill patients. Crit Care Med. 2008;36:3008–13.CrossRefPubMed Krinsley JS. Glycemic variability: A strong independent predictor of mortality in critically ill patients. Crit Care Med. 2008;36:3008–13.CrossRefPubMed
22.
go back to reference Ali NA, O'Brien JM, Dungan K, Phillips G, Marsh CB, Lemeshow S, et al. Glucose variability and mortality in patients with sepsis. Crit Care Med. 2008;36:2316–21.CrossRefPubMedPubMedCentral Ali NA, O'Brien JM, Dungan K, Phillips G, Marsh CB, Lemeshow S, et al. Glucose variability and mortality in patients with sepsis. Crit Care Med. 2008;36:2316–21.CrossRefPubMedPubMedCentral
23.
go back to reference Eslami S, Taherzadeh Z, Schultz M, Abu-Hanna A. Glucose variability measures and their effect on mortality: a systematic review. Int Care Med. 2011;37:583–93.CrossRef Eslami S, Taherzadeh Z, Schultz M, Abu-Hanna A. Glucose variability measures and their effect on mortality: a systematic review. Int Care Med. 2011;37:583–93.CrossRef
24.
go back to reference Van den Berghe G, Schetz M, Vlasselaers D, Hermans G, Wilmer A, Bouillon R, et al. Intensive insulin therapy in critically ill patients: NICE-SUGAR or Leuven blood glucose target? J Clin Endocrin Metab. 2009;94:3163–70.CrossRef Van den Berghe G, Schetz M, Vlasselaers D, Hermans G, Wilmer A, Bouillon R, et al. Intensive insulin therapy in critically ill patients: NICE-SUGAR or Leuven blood glucose target? J Clin Endocrin Metab. 2009;94:3163–70.CrossRef
26.
go back to reference The NICE-SUGAR Study Investigators. Hypoglycemia and risk of death in critically ill patients. N Engl J Med. 2012;367:1108–18.CrossRef The NICE-SUGAR Study Investigators. Hypoglycemia and risk of death in critically ill patients. N Engl J Med. 2012;367:1108–18.CrossRef
27.
go back to reference Onyenweni AJ, Winterstein AG. Rates of hypokalaemia after implementation of aggressive insulin dosing in critical care patients. Pharmacoepidemiol Drug Saf. 2007;16:S011. Onyenweni AJ, Winterstein AG. Rates of hypokalaemia after implementation of aggressive insulin dosing in critical care patients. Pharmacoepidemiol Drug Saf. 2007;16:S011.
28.
go back to reference Ten Berg MJ, Huisman A, Van den Bemt PM, Schobben AF, Egberts AC, Van Solinge WW. Linking laboratory and medication data: new opportunities for pharmacoepidemiological research. Clin Chem Lab Med. 2007;45:13–9.PubMed Ten Berg MJ, Huisman A, Van den Bemt PM, Schobben AF, Egberts AC, Van Solinge WW. Linking laboratory and medication data: new opportunities for pharmacoepidemiological research. Clin Chem Lab Med. 2007;45:13–9.PubMed
29.
go back to reference Wagner AK, Soumerai SB, Zhang F, Ross-Degnan D. Segmented regression analysis of interrupted time series studies in medical use research. J Clin Pharm Therapeut. 2002;27:299–309.CrossRef Wagner AK, Soumerai SB, Zhang F, Ross-Degnan D. Segmented regression analysis of interrupted time series studies in medical use research. J Clin Pharm Therapeut. 2002;27:299–309.CrossRef
30.
go back to reference Hermanides J, Bosman RJ, Vriesendorp TM, Dotsch R, Rosendaal FR, Zandstra DF, et al. Hypoglycemia is associated with intensive care unit mortality. Crit Care Med. 2010;38:1430–4.CrossRefPubMed Hermanides J, Bosman RJ, Vriesendorp TM, Dotsch R, Rosendaal FR, Zandstra DF, et al. Hypoglycemia is associated with intensive care unit mortality. Crit Care Med. 2010;38:1430–4.CrossRefPubMed
31.
go back to reference Kosiborod M, Inzucchi SE, Goyal A, Krumholz HM, Masoudi FA, Xiao L, et al. Relationship between spontaneous and iatrogenic hypoglycemia and mortality in patients hospitalized with acute myocardial infarction. JAMA. 2009;301:1556–64.CrossRefPubMed Kosiborod M, Inzucchi SE, Goyal A, Krumholz HM, Masoudi FA, Xiao L, et al. Relationship between spontaneous and iatrogenic hypoglycemia and mortality in patients hospitalized with acute myocardial infarction. JAMA. 2009;301:1556–64.CrossRefPubMed
32.
go back to reference Vlasselaers D, Milants I, Desmet L, Wouters PJ, Vanhorebeek I, van den Heuvel I, et al. Intensive insulin therapy for patients in paediatric intensive care: a prospective, randomised controlled study. Lancet. 2009;373:547–56.CrossRefPubMed Vlasselaers D, Milants I, Desmet L, Wouters PJ, Vanhorebeek I, van den Heuvel I, et al. Intensive insulin therapy for patients in paediatric intensive care: a prospective, randomised controlled study. Lancet. 2009;373:547–56.CrossRefPubMed
33.
go back to reference Paltiel O, Salakhov E, Ronen I, Berg D, Israeli A. Management of severe hypokalaemia in hospitalized patients. Arch Int Med. 2001;161:108995.CrossRef Paltiel O, Salakhov E, Ronen I, Berg D, Israeli A. Management of severe hypokalaemia in hospitalized patients. Arch Int Med. 2001;161:108995.CrossRef
34.
go back to reference Mesotten D, Gielen M, Sterken C, Claessens K, Hermans G, Vlasselaers D. Neurocognitive development of children 4 years after critical illness and treatment with tight glucose control: a randomized controlled trial. JAMA. 2012;308:1641–50.CrossRefPubMed Mesotten D, Gielen M, Sterken C, Claessens K, Hermans G, Vlasselaers D. Neurocognitive development of children 4 years after critical illness and treatment with tight glucose control: a randomized controlled trial. JAMA. 2012;308:1641–50.CrossRefPubMed
35.
go back to reference Lipton JA, Barendse RJ, Van Domburg RT, Schinkel AF, Boersma H, Simoons MI, et al. Hyperglycemia at admission and during hospital stay are independent risk factors for mortality in high risk cardiac patients admitted to an intensive cardiac care unit. Eur Heart J Acute Cardiovasc Care. 2013;2:306–13.CrossRefPubMedPubMedCentral Lipton JA, Barendse RJ, Van Domburg RT, Schinkel AF, Boersma H, Simoons MI, et al. Hyperglycemia at admission and during hospital stay are independent risk factors for mortality in high risk cardiac patients admitted to an intensive cardiac care unit. Eur Heart J Acute Cardiovasc Care. 2013;2:306–13.CrossRefPubMedPubMedCentral
36.
go back to reference Hessels L, Hoekstra M, Mijzen LJ, Vogelzang M, Dieperink W, Lansink A, et al. The relationship between serum potassium, potassium variability and in-hospital mortality in critically ill patients and a before-after analysis on the impact of computer-assisted potassium control. Crit Care. 2015;19:4. Epub 21 Jan 2015. Hessels L, Hoekstra M, Mijzen LJ, Vogelzang M, Dieperink W, Lansink A, et al. The relationship between serum potassium, potassium variability and in-hospital mortality in critically ill patients and a before-after analysis on the impact of computer-assisted potassium control. Crit Care. 2015;19:4. Epub 21 Jan 2015.
37.
go back to reference Xu Q, Xu F, Fan L, Xiong L, Li H, Cao S, et al. Serum potassium levels and its variability in incident peritoneal dialysis patients: Associations with mortality. Plos one. 2014;9:e86750.CrossRefPubMedPubMedCentral Xu Q, Xu F, Fan L, Xiong L, Li H, Cao S, et al. Serum potassium levels and its variability in incident peritoneal dialysis patients: Associations with mortality. Plos one. 2014;9:e86750.CrossRefPubMedPubMedCentral
38.
go back to reference Rimmer JM, Horn JF, Gennari J. Hyperkalaemia as a complication of drug therapy. Arch Intern Med. 1987;147:867–9.CrossRefPubMed Rimmer JM, Horn JF, Gennari J. Hyperkalaemia as a complication of drug therapy. Arch Intern Med. 1987;147:867–9.CrossRefPubMed
39.
go back to reference Paice BJ, Paterson KR, Onyanga-Omara F, Donnelly T, Gray JM, Lawson DH. Record linkage study of hypokalaemia in hospitalized patients. Postgrad Med J. 1986;62:187–91.CrossRefPubMedPubMedCentral Paice BJ, Paterson KR, Onyanga-Omara F, Donnelly T, Gray JM, Lawson DH. Record linkage study of hypokalaemia in hospitalized patients. Postgrad Med J. 1986;62:187–91.CrossRefPubMedPubMedCentral
40.
go back to reference Salem CB, Fathallah N, Hmouda H, Bouraoui K. Drug-Induced Hypoglycaemia, an update. Drug Saf. 2011;34:21–45.CrossRefPubMed Salem CB, Fathallah N, Hmouda H, Bouraoui K. Drug-Induced Hypoglycaemia, an update. Drug Saf. 2011;34:21–45.CrossRefPubMed
42.
go back to reference Zanen P. Dalingen van het kaliumgehalte in het serum ten gevolge van ß2-sympathicomimetica. Ned Tijdschr Geneeskd. 1990;134:688–91. Dutch. Zanen P. Dalingen van het kaliumgehalte in het serum ten gevolge van ß2-sympathicomimetica. Ned Tijdschr Geneeskd. 1990;134:688–91. Dutch.
Metadata
Title
Influence of a strict glucose protocol on serum potassium and glucose concentrations and their association with mortality in intensive care patients
Authors
Esther V. Uijtendaal
Jeannette E.F. Zwart-van Rijkom
Dylan W. de Lange
Arief Lalmohamed
Wouter W. van Solinge
Toine C.G. Egberts
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Critical Care / Issue 1/2015
Electronic ISSN: 1364-8535
DOI
https://doi.org/10.1186/s13054-015-0959-9

Other articles of this Issue 1/2015

Critical Care 1/2015 Go to the issue