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Hyponatraemia at hospital admission is a predictor of overall mortality L. Balling,1 F. Gustafsson,1 J. P. Goetze,2 M. Dalsgaard,3 H. Nielsen,4 S. Boesgaard,1 M. Bay,5 V. Kirk,6 O. W. Nielsen,4 L. Køber1 and K. Iversen3 1
Departments of Cardiology, and 2Clinical Biochemistry, Rigshospitalet, University Hospital of Copenhagen, 4Department of Cardiology, Bispebjerg Hospital, Copenhagen, 5Department of Cardiology, Frederiksberg Hospital, Frederiksberg, 6Department of Oncology, Herlev Hospital, Herlev and 3
Department of Cardiology and Endocrinology, Hillerød Hospital, Hillerød, Denmark
Key words hyponatraemia, all-cause mortality, electrolyte disturbance. Correspondence Louise Balling, Department of Cardiology, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, Copenhagen, Denmark. Email: [email protected] Received 6 August 2014; accepted 22 October 2014. doi:10.1111/imj.12623
Abstract Background: Hyponatraemia is a prognostic marker of increased mortality and morbidity in selected groups of hospitalised patients. The aim of the present study was to examine the prevalence and prognostic significance of hyponatraemia at hospital admission in an unselected population with a broad spectrum of medical and surgical diagnoses. Methods: Consecutive patients >40 years of age admitted to a general district hospital in Greater Copenhagen between 1 April 1998 and 31 March 1999. Median follow-up time was 5.16 years (range 0–4372 days). Plasma sodium measurements were available in 2960 patients, and hyponatraemia defined as P-Na+ 0.05 for all interaction analyses). Conclusion: Hyponatraemia is associated with increased all-cause mortality and longer admission length independently of diagnosis and clinical variables.
Introduction Hyponatraemia is the most common electrolyte disturbance in hospitalised and ambulatory patients.1,2 The presence of hyponatraemia is a prognostic marker for increased morbidity and mortality in patients with specific diagnoses, such as heart failure,3 myocardial infarction,4 liver cirrhosis,5 renal insufficiency,6 endocrine disease,7 stroke8 as well as in patients with bone fractures.9–14 Increased neurohormonal activity has been associated with the development of hyponatraemia.15,16 Funding: The CHHF study was supported by grants from the Arvid Nilssons Foundation and from the Joint Proof-of-Concept Fund, the Ministry of Science, Technology and Innovation, Denmark. The present analysis was funded by Otsuka Pharma Scandinavia AB. Conflict of interest: None
The pathology is multifactorial, and the complete mechanisms of development of hyponatraemia remain incompletely understood. Symptoms as a consequence of hyponatraemia vary from asymptomatic or subtle to severe neurologic symptoms with a need for prompt medical treatment. Mild hyponatraemia is often unnoticed by the physician, but is associated with an increased risk of fall and bone fractures as well as attention deficits in the elderly population.2,17 Hence, specific attention towards both mild and severe hyponatraemia remains important in the daily clinical practice. The prognostic importance of hyponatraemia in a general population admitted to hospital has not been examined previously. Also, it is unclear whether the prognostic importance of hyponatraemia differs between medical and surgical diagnoses. The aim of the present study was to examine if baseline hyponatraemia
© 2014 Royal Australasian College of Physicians
195
Balling et al.
measured at hospital admission predicts increased mortality and morbidity in an unselected population above 40 years of age admitted to a general hospital with a broad spectrum of medical and surgical conditions. A secondary aim was to investigate whether there was interaction between baseline hyponatraemia and admission diagnosis on overall mortality.
Methods The Copenhagen Hospital Heart Failure Study (CHHF) included all patients above the age of 40 years admitted to a general city hospital in Copenhagen between 1 April 1998 and 31 March 1999 to either a medical (internal medicine and cardiology) or a surgical (gastrointestinal or orthopaedic) department. The primary aim of CHHF was to investigate if N-Terminal pro-brain natriuretic peptide (NT-proBNP) could be used as a biomarker to predict a low left ventricular ejection fraction or clinical signs of HF in an unselected group of patients admitted to a general hospital. A thorough medical interview as well as a comprehensive medical examination, echocardiography and blood analyses were performed within the first 24 h after admission. A detailed description of the CHHF study has previously been published.18–20 Discharge diagnosis and events during hospitalisation were collected from patient files. Outcome information regarding death and re-hospitalisations was collected from the Danish National Patient Registry, which records all information regarding mortality and discharge diagnoses according to an individual civil registration number.21 The validity of end points obtained from the Danish National Patient Registry has previously been obtained.21 Patients were divided into one of eight possible admission diagnoses (i) cardiovascular, (ii) orthopaedic, (iii) gastrointestinal, (iv) haematological/oncological, (v) pulmonary, (vi) neurologic, (vii) infectious and (viii) other diagnoses (endocrinological, nephrological, rheumatological and nonspecific diagnoses, such as dehydration, social causes and drug abuse). Complete follow up was possible for all except nine patients (0.6 %). Patients were lost to follow up because of emigration and were censored at the time of emigration.
Blood sample analyses Blood samples were obtained within the first 24 h of hospital admission in the time period between 8 am and 10 am as part of the CHHF study. Sodium, potassium, C-reactive protein as well as creatinine levels were analysed according to the local standard method of the
hospital laboratory. The glomerular filtration rate (eGFR) was estimated using the modification of diet in renal disease formula.22 NT-proBNP was measured consecutively during the later 10 months of the study with an enzyme-linked immunosorbent assay (a two step sandwich assay, Roche, Basel, Switzerland).
Ethics All patients gave informed consent prior to study inclusion. The study complied with the Helsinki Declaration and was approved by the local ethics committee of Copenhagen.
Statistical analyses Patients were divided into two groups according to the plasma sodium level. Normonatraemia was defined as a plasma sodium concentration ≥137 mmol/L and hyponatraemia as a plasma sodium concentration
Hyponatraemia at hospital admission is a predictor of overall mortality L. Balling,1 F. Gustafsson,1 J. P. Goetze,2 M. Dalsgaard,3 H. Nielsen,4 S. Boesgaard,1 M. Bay,5 V. Kirk,6 O. W. Nielsen,4 L. Køber1 and K. Iversen3 1
Departments of Cardiology, and 2Clinical Biochemistry, Rigshospitalet, University Hospital of Copenhagen, 4Department of Cardiology, Bispebjerg Hospital, Copenhagen, 5Department of Cardiology, Frederiksberg Hospital, Frederiksberg, 6Department of Oncology, Herlev Hospital, Herlev and 3
Department of Cardiology and Endocrinology, Hillerød Hospital, Hillerød, Denmark
Key words hyponatraemia, all-cause mortality, electrolyte disturbance. Correspondence Louise Balling, Department of Cardiology, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, Copenhagen, Denmark. Email: [email protected] Received 6 August 2014; accepted 22 October 2014. doi:10.1111/imj.12623
Abstract Background: Hyponatraemia is a prognostic marker of increased mortality and morbidity in selected groups of hospitalised patients. The aim of the present study was to examine the prevalence and prognostic significance of hyponatraemia at hospital admission in an unselected population with a broad spectrum of medical and surgical diagnoses. Methods: Consecutive patients >40 years of age admitted to a general district hospital in Greater Copenhagen between 1 April 1998 and 31 March 1999. Median follow-up time was 5.16 years (range 0–4372 days). Plasma sodium measurements were available in 2960 patients, and hyponatraemia defined as P-Na+ 0.05 for all interaction analyses). Conclusion: Hyponatraemia is associated with increased all-cause mortality and longer admission length independently of diagnosis and clinical variables.
Introduction Hyponatraemia is the most common electrolyte disturbance in hospitalised and ambulatory patients.1,2 The presence of hyponatraemia is a prognostic marker for increased morbidity and mortality in patients with specific diagnoses, such as heart failure,3 myocardial infarction,4 liver cirrhosis,5 renal insufficiency,6 endocrine disease,7 stroke8 as well as in patients with bone fractures.9–14 Increased neurohormonal activity has been associated with the development of hyponatraemia.15,16 Funding: The CHHF study was supported by grants from the Arvid Nilssons Foundation and from the Joint Proof-of-Concept Fund, the Ministry of Science, Technology and Innovation, Denmark. The present analysis was funded by Otsuka Pharma Scandinavia AB. Conflict of interest: None
The pathology is multifactorial, and the complete mechanisms of development of hyponatraemia remain incompletely understood. Symptoms as a consequence of hyponatraemia vary from asymptomatic or subtle to severe neurologic symptoms with a need for prompt medical treatment. Mild hyponatraemia is often unnoticed by the physician, but is associated with an increased risk of fall and bone fractures as well as attention deficits in the elderly population.2,17 Hence, specific attention towards both mild and severe hyponatraemia remains important in the daily clinical practice. The prognostic importance of hyponatraemia in a general population admitted to hospital has not been examined previously. Also, it is unclear whether the prognostic importance of hyponatraemia differs between medical and surgical diagnoses. The aim of the present study was to examine if baseline hyponatraemia
© 2014 Royal Australasian College of Physicians
195
Balling et al.
measured at hospital admission predicts increased mortality and morbidity in an unselected population above 40 years of age admitted to a general hospital with a broad spectrum of medical and surgical conditions. A secondary aim was to investigate whether there was interaction between baseline hyponatraemia and admission diagnosis on overall mortality.
Methods The Copenhagen Hospital Heart Failure Study (CHHF) included all patients above the age of 40 years admitted to a general city hospital in Copenhagen between 1 April 1998 and 31 March 1999 to either a medical (internal medicine and cardiology) or a surgical (gastrointestinal or orthopaedic) department. The primary aim of CHHF was to investigate if N-Terminal pro-brain natriuretic peptide (NT-proBNP) could be used as a biomarker to predict a low left ventricular ejection fraction or clinical signs of HF in an unselected group of patients admitted to a general hospital. A thorough medical interview as well as a comprehensive medical examination, echocardiography and blood analyses were performed within the first 24 h after admission. A detailed description of the CHHF study has previously been published.18–20 Discharge diagnosis and events during hospitalisation were collected from patient files. Outcome information regarding death and re-hospitalisations was collected from the Danish National Patient Registry, which records all information regarding mortality and discharge diagnoses according to an individual civil registration number.21 The validity of end points obtained from the Danish National Patient Registry has previously been obtained.21 Patients were divided into one of eight possible admission diagnoses (i) cardiovascular, (ii) orthopaedic, (iii) gastrointestinal, (iv) haematological/oncological, (v) pulmonary, (vi) neurologic, (vii) infectious and (viii) other diagnoses (endocrinological, nephrological, rheumatological and nonspecific diagnoses, such as dehydration, social causes and drug abuse). Complete follow up was possible for all except nine patients (0.6 %). Patients were lost to follow up because of emigration and were censored at the time of emigration.
Blood sample analyses Blood samples were obtained within the first 24 h of hospital admission in the time period between 8 am and 10 am as part of the CHHF study. Sodium, potassium, C-reactive protein as well as creatinine levels were analysed according to the local standard method of the
hospital laboratory. The glomerular filtration rate (eGFR) was estimated using the modification of diet in renal disease formula.22 NT-proBNP was measured consecutively during the later 10 months of the study with an enzyme-linked immunosorbent assay (a two step sandwich assay, Roche, Basel, Switzerland).
Ethics All patients gave informed consent prior to study inclusion. The study complied with the Helsinki Declaration and was approved by the local ethics committee of Copenhagen.
Statistical analyses Patients were divided into two groups according to the plasma sodium level. Normonatraemia was defined as a plasma sodium concentration ≥137 mmol/L and hyponatraemia as a plasma sodium concentration
