Fluctuations in Serum Sodium Level Are Associated With an Increased Risk of Death in Surgical ICU Patients

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Yasser Sakr, MD, PhD1; Steffen Rother, MD 1; Alberto Mendonca Pires Ferreira, MD1; Christian Ewald, MD2; Pedro Dünisch, MD2; Niels Riedemmann, MD1; Konrad Reinhart, MD1

Objective: Dysnatremia may have an impact on outcomes in critically ill patients, but this has not been widely investigated in surgical ICU patients. We investigated the epidemiology of dysnatremia in a large cohort of surgical ICU patients and evaluated the possible influence of the time of acquisition of dysnatremia and fluctuations in serum sodium concentrations on hospital mortality in these ­ patients. Design: Retrospective analysis. Setting: Fifty-bed surgical ICU. Patients: All patients admitted to the ICU between January 2004 and January 2009. Measurements and Main Results: Hyponatremia was defined as a serum sodium concentration <135 mmol/L and hypernatremia as a serum sodium concentration >145 mmol/L. Of the 10,923 surgical ICU patients included in the study, 1,215 (11.2%) had hyponatremia and 277 (2.5%) had hypernatremia at admission to the ICU. Among patients with normonatremia at admission to the ICU (n = 9431), the prevalence of ICU–acquired dysnatremia was 31.3%. Dysnatremia present at ­ I CU admission (odds ratio 2.53; 95% confidence interval 2.06–3.12; p < .001) and ICU–acquired dysnatremia (odds ratio 2.06; 95% confidence

interval 1.71–2.48; p < 0.001) were independently associated with an increased risk of in-hospital death compared to normonatremia. Dysnatremia at ICU admission (odds ratio 1.23; 95% confidence interval 1.01–1.50) was associated with a higher risk of in-hospital death, compared with ICU–acquired dysnatremia. Fluctuation in serum sodium concentration was also independently associated with an increased risk of in-hospital mortality, in patients who remained normonatremic (>6 mmol/L/ ICU stay) and in those with dysnatremia (>12 mmol/L/24 hrs or >12 mmol/L/ICU stay). Conclusions: Dysnatremia was common in surgical ICU patients and was independently associated with an increased risk of in-hospital death in these patients. Dysnatremia at ICU admission was associated with a higher risk of death compared with ICU– acquired dysnatremia. Fluctuations in serum sodium concentrations were independently associated with an increased risk of in-hospital death, even in patients who remained normonatremic during the ICU stay.  (Crit Care Med 2013; 41:133–142) Key Words: electrolyte disturbances; postoperative; prognosis; sodium

*See also p. 351. 1 Departments of Anesthesiology and Intensive Care, Friedrich-SchillerUniver­ sity Hospital, Jena, Germany. 2 Department of Neurosurgery, Friedrich-Schiller-University Hospital, Jena, Germany. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s Web site (http://journals.lww.com/ ccmjournal). The study was supported, in part, by institutional funds. The authors have not disclosed any potential conflicts of interest. For information regarding this article, E-mail: yasser.sakr@med.uni-jena.de Copyright © 2013 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins DOI: 10.1097/CCM.0b013e318265f576

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odium is the main extracellular cation and the most osmotically active solute in the human body (1). Under normal conditions, serum sodium is preserved within a physiologic range despite large variations in daily sodium and water intake. Sodium metabolism is tightly regulated by the kidney through ­ the interaction of numerous neurohormonal mechanisms, including the renin–angiotesin–aldosterone system, the sympathetic nervous system, and the presence of atrial natriuretic and brain natriuretic peptides (2). Disorders of sodium homeostasis are the most common electrolyte disturbances in clinical medicine (3). The prevalence of dysnatremia in the ICU ranges between 25% and 45% and varies according to the time of onset, the threshold for diagnosis, and the population being assessed (4–6). Dysnatremia imposes a considerable burden on healthcare resources because of its impact on morbidity and mortality (7). Even mild hyponatrewww.ccmjournal.org

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Whether the time of onset of dysnatremia can influence outcomes after major surgical interventions is still unknown. hyperoncotic intravenous solutions were not used for volume resuscitation in the ICU.org . The maximum fluctuation in sodium concentration during ICU stay was also computed. However. Bad Homburg. to investigate the epidemiology of dysnatremia in a large cohort of surgical ICU patients and to evaluate the possible influence of the time of acquisition of dysnatremia and of fluctuations in serum sodium concentrations on hospital mortality in these patients. Definitions Hyponatremia was defined as a serum sodium concentration <135 mmol/L and hypernatremia as a serum sodium concentration >145 mmol/L. January 2013 • Volume 41 • Number 1 MATERIALS AND METHODS The study was approved by the ethics committee of Friedrich Schiller University hospital (Bachstrasse 8. and those acquiring dysnatremia thereafter. During the study period. 10. including results of blood gases. Germany) or 4% gelatin solutions (Gelafusal. Only validated results were included in our analysis. Colloid solutions were 134 www. 07743 Jena. Bernburg. Fresenius Kabi GmbH.g. Germany). were transmitted automatically to the patients’ electronic charts and validated regularly for plausibility by the attending physician using an electronic signature.ccmjournal.4. Data Collection Data were collected from vital sign monitors. Additional samples were obtained. Germany). the possible impact on outcome of fluctuations in serum sodium concentrations during the ICU stay has not been adequately investigated. 8–13). although a strong association between the rate of correction of hypernatremia and outcome has been reported (16. Daily fluctuations in serum sodium concentrations were calculated as the difference between the maximum and the minimum values obtained within 24 hrs. Patients admitted to the ICU for medical reasons and those in whom serum sodium concentrations were not determined within 2 hrs of admission to the ICU were excluded from the analysis. Samples were obtained from arterial lines at least six hourly for determination of arterial blood gases and electrolytes. Glucose 5%. including serum electrolytes. we corrected the measured serum sodium levels in hyponatremic patients using the following formula: corrected sodium = measured sodium + 0. 15). Germany). and calcium. additionally used in some patients according to clinical indication in the form of 6% hydroxyethyl starches (130/0. gender.Sakr et al mia and hypernatremia have been reported to be associated with significantly higher mortality and a longer duration of hospitalization (8). primary and secondary admission diagnoses. Bernburg. therefore. Bad Homburg. 17). ventilators. and intravenous medications were diluted using sodium-free solutions. Radiometer. according to our local standard operative procedures. patients received basic infusions using balanced full-electrolyte infusions (E153. Data recorded routinely at admission also included age. and mortality rates were compared between groups. e. 14) or during the ICU stay (9. whenever required. Denmark). Serumwerk Bernburg AG. medication).4 (blood sugar– 5.. half-electrolyte infusions (Jonosteril HD 5.g. Laboratory parameters. In addition. ­ 8. Sasbachwalden. referring facility. potassium. order entry (e. Repeated determination of arterial blood gases (more than four times per day). The aim of our study was. using an automated blood gas analyzer (ABL700. and infusion pumps and automatically recorded in a patient data management system (Copra System. Germany) were used. Intravenous Fluid Administration During the study period. Measurement of Serum Sodium Level Serum sodium levels were routinely checked in a venous blood sample at admission to the ICU and at least once per day at 6:00 AM during ICU stay. The Simplified Acute Physiology Score II (19) and Sequential Organ Failure Assessment score (20) were calculated by the attending physician who was in charge of the patient. In patients with hypernatremia. these studies were mostly performed in mixed medical and surgical ICU populations (6. was performed commonly in unstable cardiorespiratory patients and in those with abnormal blood sugar levels. All consecutive surgical adult patients (older than 18 yrs) admitted to our 50-bed ICU between January 2004 and January 2009 were included. and informed consent was not required because of the anonymous and observational nature of the study. and surgical procedures preceding admission.. Voluven. and direct access to laboratory results. Patients were classified according to the onset of dysnatremia into those who had abnormal sodium concentrations in the initial blood sample. 10–12) and evaluated sodium levels either at admission to the ICU (6. Germany). according to the judgment of the attending physician (available 24 hrs/day). Comorbidities were identified on the basis of routinely recorded codes from the International Statistical Classification of Diseases and Related Health Problems. Mixed dysnatremia was defined as the occurrence of both hyponatremia and hypernatremia during ICU stay in the same patient. and electronic patient charts. tenth revision (18). which includes complete electronic documentation of clinical progress performed by the attending physicians. Fresenius-Kabi. including sodium. Patients were reclassified according to the corrected sodium. Copenhagen. Several studies have investigated the epidemiology of dysnatremia and its possible impact on adverse outcomes in critically ill patients (5. Serumwerk Bernburg AG. To assess the possible influence of blood sugar level on the epidemiology of and outcome from hyponatremia. analyzed within 2 hrs of admission to the ICU. 6.5 mmol/L) (21) Calculations were performed using the blood sugar values measured concomitantly with serum sodium from the same arterial blood sample.

or hypernatremia at admission to the ICU had higher severity scores at ICU admission and a higher prevalence of chronic renal failure than those with normonatremia. respectively (Fig.8) 954 (8. We performed a logistic regression multivariate analysis with hospital outcome as the dependent factor to investigate the possible influence of dysnatremia on hospital outcome.4%) mortality rates (both p < 0. n (%)   Elective surgery   Emergency surgery Mortality rates. we performed logistic regression analyses as detailed above with hospital outcome as the dependent variable in patients with normonatremia throughout ICU stay and in those who had dysnatremia at any time during ICU stay.7) 525 (4. n (%)   Diabetes mellitus   Arterial hypertension  Cancer   Heart failure   Renal failure  Cirrhosis   Hematologic cancer Type of surgery at admission day. 4. Dysnatremia at ICU Admission The prevalences of hyponatremia and hypernatremia at ICU admission were 11.0) 456 (4.215) and 2. n (%)   ICU mortality   Hospital mortality ICU length of stay.1% (n = 1. Simplified Acute Physiology Score II and ­ Sequential O ­ rgan Failure Assessment scores on admission. n (%) Severity scores.001 www. obstetric/gynecologic.2) 5153 (47. To further assess the impact of fluctuations in s ­erum ­ sodium levels on outcome. Patients with hypernatremia were younger. Overall ICU mortality was 4. Fluctuations in serum sodium levels were introduced as categorical variables in the multivariate models.9 ± 18. mean ± SD at Admission to the ICU of the Study Group n = 10.Laboratory Investigation Statistical Analysis Data were analyzed using SPSS 17. and hospital mortality was 8.6) 2247 (20.05 was considered significant. Another multivariate model was performed in patients with normonatremia at admission to the ICU to assess the impact of ICU-acquired dysnatremia on hospital outcome. Chicago.org 135 .0%) and hospital (18.7%.2) 2650 (24.6) 1543 (14. respectively). and maxillofacial surgery. Patients with hypo.923 63 ± 14 6905 (63.2) 38.4) 8113 (74. yrs. Patients with hypernatremia or hyponatremia at ICU admission had higher ICU (13. n (%)  Cardiothoracic  Gastrointestinal  Neurosurgery  Trauma  Other a Type of intervention.2) 128 (1. the site of surgery. two models were constructed: model #1 including dysnatremia at admission to the ICU and model #2 classifying dysnatremia according to the time of acquisition in the ICU and including ICU length of stay (LOS) as a covariate. A Bonferroni correction was done for multiple comparisons. and neurosurgery were the most common types of ­ surgical intervention (47. mean ± SD Male.8%. or the Cochran–Armitage trend test.3) 2810 (25.923 consecutively admitted surgical ICU patients were included in the cohort. Discrete variables are expressed as counts (percentage) and continuous variables as means ± SD or median and interquartile range (IQR) unless stated otherwise. Patients with hyponatremia were older.8% and 16. Categorical data were compared using the chi-square test with Yates’ correction. had fewer comorbid conditions.0%. digestive. as appropriate. using the same covariates mentioned above.7% and 8.3 ± 3. and whether surgery was emergency or electively performed. 7.2) 913 (8.0 for Windows (SPSS. and neurosurgery compared to patients with hyponatremia. The Kolmogorov–Smirnov test was used to verify the normality of distribution of continuous variables. and were more likely to be admitted to the ICU after emergency.2%. 24. The median ICU LOS was 1 (IQR 1–3) day.7) 1 (1–3)   Simplified Acute Physiology Score II   Sequential Organ Failure Assessment Score Comorbidities. Fisher’s exact test.9) 352 (3. Patients with hypernatremia had higher Sequential Organ Failure Assessment scores and were more commonly referred to the ICU after emergency. RESULTS A total of 10. A p value < 0.  Characteristics Characteristic Age.7 5899 (54. TABLE 1. and neurosurgery Critical Care Medicine than patients with normonatremia. Cardiothoracic. trauma. trauma. and had a higher prevalence of comorbidities than patients with normonatremia (Table 2).3 6. days. Variables considered for the multivariate modeling included demographic data.3%. median (interquartile range) a Otorhinolaryngologic. The baseline characteristics of the study population are summarized in Table 1. IL). In the whole cohort.3) 1751 (16. 1).9% vs. oral. Continuous variables conforming to a normal distribution were compared using analysis of variance and Student’s t test. and 16. comorbidities. and odds ratios (ORs) (95% confidence interval [CI]) were computed. All variables included in the model were tested for colinearity. otherwise the Kruskal–Wallis and Mann–Whitney U test were applied.0) 2582 (23.5% vs.ccmjournal. A Hosmer and Lemeshow goodness-of-fit test was performed.5% (n = 277).1) 859 (7.

02– 1.80. hypernatremia (OR 2. i.25–2. Patients who experienced 136 www. 95% CI 1. the maximum daily fluctuation was reached within 4 days of admission to the ICU (89. lww. ICU admission hyponatremia (OR 1. p < 0.4%) had blood sugar–corrected sodium levels within the normal range. The prevalence of ICU-acquired hyponatremia was 13.com/CCM/A594). 95% CI 2. fluctuations in serum sodium concentrations >12 mmol/L per day or during the ICU stay were i ­ndependently associated with an increased risk of in-hospital death (Table S4.001) were independently associated with in-hospital mortality (Table S2. http:// links. and mixed dysnatremia had higher severity scores at admission to the ICU.72.6% of patients who stayed in the ICU for >14 days remained normonatremic during ICU stay. on the second day of ICU admission in 8. 9.036).1% (n = 995).ccmjournal.59.32.70.2%).lww. p = 0.lww.038).075 patients (92. more frequently had chronic renal failure and diabetes mellitus.215 patients with hyponatremia at admission to the ICU. Supplemental Digital Content 1. In 10. and were more commonly admitted to the ICU after emergency surgery than the other groups (Table 3).04–2.033.6% (n = 1. in patients with dysnatremia present at admission to the ICU or acquired during ICU stay. had higher severity scores. p = 0. 95% CI 1. Fluctuations in Serum Sodium Concentrations The median fluctuations in serum sodium concentrations within 24 hrs and during ICU stay were 4 (IQR 2–7. Likewise. Patients with ICU-acquired hyponatremia. p < 0.483) and of hypernatremia.. ICU-Acquired Dysnatremia Dysnatremia did not occur during ICU stay in 59. Supplemental Digital Content 1.01–1.5% on the second day following admission to the ICU).70–3.e. after multivariable adjustment in the whole cohort.98. 3 and 4).lww.3%).76. The magnitude of the deviation in serum sodium levels from normal values (serum sodium levels ≥135 mmol/L and ≤145 mmol/L) was positively correlated to the ICU and hospital mortality rates (Fig. The maximum fluctuation in serum sodium levels during ICU stay was reached within the first week following admission to the ICU in 10. translational hyponatremia. hypernatremia.  Schematic representation of the study population according to the presence of dysnatremia at admission to the ICU and the development of dysnatremia during ICU stay. In a multivariable logistic regression analysis.Sakr et al Figure 1. 95% CI 1. 102 (8.com/CCM/A594). p = 0.396 patients (95. each p < 0. 3 and 4). p = 0. Patients with all forms of ICU-acquired dysnatremia had higher ICU and hospital mortality rates and longer ICU LOS compared to those who were normonatremic throughout their ICU stay (Table 4).3%) experienced at least one episode of hyponatremia and of hypernatremia (mixed dysnatremia) during their ICU stay.com/CCM/A594). However.40–2. Patients who acquired hypernatremia in the ICU were older. and were more likely to be admitted after emergency interventions compared to those with ICU-acquired hyponatremia. Only 2.001) were independently associated with a greater risk of in-hospital death (Table S1.23. Reaching the maximum fluctuation in serum sodium levels within 24 hrs was associated with a higher mortality rate than reaching a maximum fluctuation during ICU stay (Figs. 1 [IQR 1–3]. 95% CI 1. http://links.483) of the whole cohort.36–3. Supplemental Digital Content 1. 95% CI 1. Maximum fluctuations in serum sodium were positively correlated to ICU and hospital mortality (Figs.50. The Impact of Blood Sugar Level on the Epidemiology of and Outcome From Hyponatremia Among the 1.org . compared with ICU-acquired dysnatremia (OR 1. Supplemental Digital Content 1.001) and hypernatremia (OR 1.049 patients (73. dysnatremia at ICU admission was associated with an increased risk of in-hospital death. Patients who developed hypernatremia alone or in combination with hyponatremia had higher ICU and hospital mortality rates than those with ICU-acquired hyponatremia (Table 3). range: 0–41) mmol/L/day and 5 (IQR 3–8.55. range: 0–53) mmol/L/ICU stay. The measured sodium levels in patients with translational hyponatremia at admission to the ICU ranged from 130 to 134 January 2013 • Volume 41 • Number 1 pair­ wise and longer ICU LOS 3 [IQR 1–14] and 1 [IQR 1–4] vs.com/CCM/A594).01.7%). fluctuation in serum sodium concentrations >6 mmol/L during ICU stay was independently associated with an increased risk of in-hospital death (OR 1. In a multivariable logistic regression analysis. http://links. respectively. had the highest severity scores and prevalence of chronic renal failure. 2).4% (n = 6. Four hundred seventy patients (4. http://links.001). ICU-acquired hyponatremia (OR 1.001 pairwise) compared to patients with normonatremia.31. ICU and hospital mortality rates were higher in patients with hypernatremia compared to those with hyponatremia (Table 2). The prevalence of ICU-acquired dysnatremia increased in patients with longer ICU LOS. p < 0.46. a higher prevalence of cirrhosis and chronic renal failure at admission. mixed dysnatremia during ICU stay. and mixed dysnatremia (OR 2.42. Table S3. In patients who remained normonatremic during ICU stay. and were more commonly admitted to the ICU after emergency surgical procedures compared to patients with normonatremia (Table 3). 95% CI 1.

g 80 (28.e 2 (0.g 163 (58. only 44 (3%) had blood sugar–corrected sodium levels within the normal range throughout ICU stay.2) 259 (2. p = 0.8)d 3 (1–14)d.01–0.5) 4432 (47. 6.001 compared to normonatremia.5)d 194 (16.8)d.g 30 (10.4)d 108 (8.4) 1 (1–3) 433 (35.4) 667 (7.5)d 1 (1–4)d 145 (52.1 ± 4.1 ± 20. p = 0.5)d. d p < 0.7%. mean ± SD Male.7%.g 132 (47.8) 79 (6.1%.g 63 (22.9 ± 18 6.6) 108 (8.01 compared to normonatremia. 14.6)c 265 (21. ICU (5.9)d 35 (12. days. Of 1.e 52 (18.2) 99 (1. 8.org 137 .2d 7. n (%)   ICU mortality   Hospital mortality ICU length of stay. and maxillofacial surgery.3) 37.3d.f 104 (37.1) 33 (11.7)d.9% vs.3 ± 18.8) 46. DISCUSSION In this large cohort of surgical ICU patients.8)d.g 52 (18.6)d 782 (64.3)d. dysnatremia occurred in >40% of patients at some point during ICU stay. p = 0.g 22 (7.0) 44 (3.795) were similar in patients with translational hyponatremia at admission to the ICU and hyponatremic patients within the same category of measured sodium levels.05–0.9)d.7)d.168) and hospital mortality rates (6.0) 2307 (24.g 63 ± 14 5966 (63. f p = 0.4) 360 (3.01 compared to hyponatremia.7)d.2) 122 (10.3 ± 3.6)d 24 (8.6) 27 (2. e p = 0.001 compared to hyponatremia.5%.0) 1549 (16.3) 658 (54.8% vs.3) 379 (4. 3. yrs. p = 0. n (%)   Emergency surgery   Elective surgery Mortality rates.05–0.9)d. p = 0.2)d 283 (23.  Characteristics and Outcome of the Study Cohort According to the Serum Sodium Level at Admission to the ICU Normonatremia n = 9431 Age.7d 712 (58. almost 97.7) 7199 (76.01–0.3) 2232 (23.0) 701 (7.Laboratory Investigation TABLE 2.9) 2287 (24. oral. median (interquartile range) Otorhinolaryngologic. mean ± SD   Simplified Acute Physiology Score II   Sequential Organ Failure Assessment score Comorbidities. a c b Hyponatremia n = 1215 65 ± 13d 776 (63. n (%)   Diabetes mellitus   Arterial hypertension  Cirrhosis  Cancer   Renal failure   Heart failure   Hematologic cancer Type of surgery at admission day.001 compared to normonatremia.001 compared to hyponatremia.7) 60 (21. obstetric/gynecologic.7% vs.9)d 177 (14. n (%) Severity scores. Critical Care Medicine p = 0.0)d 157 (12.9) Hypernatremia n = 277 56 ± 19d.369) and hospital mortality rates (13.g 14 (5.483 patients with secondary hyponatremia.5% of patients requiring >14 days of treatment in the www.9)d 201 (16.7 5083 (53.9) 45.8) 783 (8. The ICU (6.ccmjournal. n (%)  Gastrointestinal  Cardiothoracic  Neurosurgery  Trauma  Othera Type of intervention.7)d.g mmol/L.8% vs.1) 1342 (14.g 38 (13.984) were similar in patients with translational hyponatremia during ICU stay and in other patients with ICU-acquired hyponatremia.7) 2020 (21.0d 8.1 ± 3.7)b. g p < 0.

30). 22). respectively.54% to 8. 14). Acute changes in serum 138 www. 8.7% and from 0. we found that dysnatremia was indein serum sodium concentrations was independently associated pendently associated with a higher risk of in-hospital death.9%. similar results in mixed (6. 10.(9. we demonstrated that greater fluctuations than in surgical ICU patients. A rate of change in serum concentraThe prevalence of dysnatremia was. an additional impact on outcome. 31. at ICU The possible influence of fluctuation in serum sodium admission in a mixed ICU population. mild deviations from normal sodium levels were associated with higher mortality rates. lower in surgical tion of ≥12 mmol/L/day during the ICU stay was also related than in mixed or medical ICU patients (9–13. even in patients who regardless of the time of onset. may also be a marker of underlying disease severity. with an increased risk of in-hospital death. 22). supporting the hypothesis that time may be a with the results of previous studies (6.org January 2013 • Volume 41 • Number 1 . 5). In the ICU may reflect chronic derangements or may be related a large multicenter database including 151. a potentially life-threatening complication (24).4% subsequently. This variability in the occurrence of dysnatremia may be risk of in-hospital death compared with ICU-acquired dysnaexplained by the differences in case mix and the differences in tremia. In a cohort of postoperative patients admitted to the els throughout ICU stay. was independently diac function (29. died with hypernatremia. Funk et al (6) reported prevalences of 17. levels in normonatremic patients. Disturbances in serum sodium level at admission to the cutoff levels used to define dysnatremia in these studies. which natremia or the adverse effects of rapid correction of serum may be related to the inclusion in our study of neurosurgical sodium levels as previously reported (11. Stelfox et al (22) reported a lower explained either by the well-known deleterious effects of dysprevalence of dysnatremia (16%) than that in our study. 9. to the severity of the initial insult prior to ICU admission with. This observation could be useful in risk stratificaand hypernatremia at admission to the ICU ranged from tion of ICU patients. 11. In agreement during ICU stay. and impaired carless of the time of acquisition in the ICU.7% to 17.myelinolysis. ICU developed some form of dysnatremia.486 ICU patients. ICU and hospipatients who are more liable to disturbances in serum sodium tal mortality rates associated with reaching the maximum fluclevels (4. dysna. neuFigure 2. after adjustment for possible confounders. the prevalences of hypo. regard. 11. tuation in serum sodium level within 24 hrs were higher than Our data characterize patterns of comorbidities associated those associated with reaching the maximum fluctuation later with dysnatremia in a surgical ICU population. for hyponatremia and hypernatremia.and hypernatremia at acute rise in serum sodium concentrations in patients who ICU admission in our study were 11% and 2. 22. 26). Dysnatremia. coma. and rhabdomyolysis) (27.crucial factor in dysnatremia-related adverse outcomes. We also found that dysnatremia at admis13. Although this study concentrations on outcome has been poorly investigated. respectively. to the ICU. includof death compared with ICU-acquired dysnatremia. In our study. This may be with higher mortality in patients following cardiac surgery related to the expectedly higher severity of illness in medical (22). Neverdysnatremia at ICU admission was associated with a higher risk theless.Sakr et al In our cohort. Hoorn et al (11) reported a more in our study.  Bar chart representing ICU and hospital mortality rates according to sodium levels at admission rological impairment (seizures. respectively (6. and hypernatremia has been associated with aggravated peripheral insulin resistance and hyperglycemia. In a used similar cutoff levels to define dysnatremia as those used matched case-control study. 28). Disturbances in serum sodium levels associated with a greater risk of in-hospital mortality. The nature of our study does not enable us to determine the reasons underlying this effect. impaired hepatic gluconeogenesis and lactate clearance (25. however. In dysnatremic patients.7% and 6. therefore. p < 0. ours is the first study to and had a higher prevalence of chronic renal failure compared explore the possible influence of fluctuations in serum sodium to others. Several studies have reported remained normonatremic during ICU stay. intracerebral hemorrhage. sion to the ICU was independently associated with a higher 14).3% of patients who had normal sodium increased risk of in-hospital death. death. tremic patients in our study were sicker (higher severity scores) To the best of our knowledge. not only in patients with levels at admission to the ICU developed dysnatremia during dysnatremia but also in those with normal serum sodium levtheir stay. this could be ICU after cardiac surgery.5%.ccmjournal. ICU-acquired delirium. Hyponatremia can lead to cerebral edema.01 for ICU and hospital mortality among groups (Cochran–Armitage trend test). in serum sodium levels were independently associated with an In our study. Fluctuation ing severity of illness. 11–13. 12) and medical ICU patients Previous studies have reported that the prevalence of hypo. 23).

01. c p < 0.6) 1 (1–1) 755 (50.  Characteristics and Outcome of Patients With ICU–Acquired Dysnatremia and Those Who Remained Normonatremic During the ICU Normonatremia n = 6483 Age.g 209 (21.0)d.4) 73 (1.1) 45 (4. n (%)   Diabetes mellitus   Arterial hypertension  Cirrhosis  Cancer   Renal failure   Heart failure   Hematologic cancer Type of surgery at admission day.g.001.g 93 (19.05–0.7 ± 15.5d 6.g 597 (60.4)c 73 (4.2) 91 (1. oral.h 53.8)d.org 139 .5d Hypernatremia n = 995 66 ± 14d.g.01.8) 302 (4.7)d.0) 2882 (44.4) 299 (4.01.8 ± 3.j 79 (16.7) 34. p = 0.7)c.0)df.5) 971 (15.8)d.j 107 (22. g p < 0.6) 68 (14. Hypernatremia: serum sodium levels >145 mmol/L. i p < 0.j 70 (14. yrs.4 3493 (53.001 compared to hypernatremia.g 17 (8–27)d.1) 248 (52. n (%)  Gastrointestinal  Cardiothoracic  Neurosurgery  Trauma  Other a Hyponatremia n = 1483 62 ± 14c 1042 (70.f Type of intervention.2)d.1) 13 (0.g Otorhinolaryngologic.0) 24 (5.3)h 103 (21.9) d 594 (59.2)d 100 (6.1 ± 16.1d.g 178 (17. mean ± SD   Simplified Acute Physiology Score II   Sequential Organ Failure Assessment score Comorbidities.j 239 (16.g 266 (26.01–0.7) 840 (56.01–0.g.3 ± 3.1)d.8)d.001.3)d 39.g.g 558 (56.j 9.4)d. days.05–0.1)d 112 (7. j p < 0.0) 143 (30.001 compared to hyponatremia.6) 581 (9.01–0.001.j 63 ± 14 4067 (62.4d.Laboratory Investigation TABLE 3.6)e. mean ± SD Male. obstetric/gynecologic.7) 38 (3. even though within the normal range. and maxillofacial surgery.3)d 1048 (70.9) 247 (16.9) 51 (3.6d.9) 1511 (23.9 5.2)d 146 (14.g.8 ± 3. f p < 0.05–0.9) 3 (0.0) 236 (3.9 ± 17.7)c 1 (1–4)d 141 (14.ccmjournal.6)d 224 (15. Normonatremia: serum sodium levels ≥135 mmol/L and ≤145 mmol/L. n (%)   ICU mortality   Hospital mortality ICU length of stay. Especially in the postoperative setting. Hyponatremia: serum sodium levels <135 mmol/L.j 299 (63.2)d.7)d 48 (3.001 compared to normonatremia. e p = 0.4) 80 (5.9)d 10 (1.8) d 241 (51.9) 407 (27.4) 435 (29.j 222 (47.0)d.8)d.7 ± 3.7) 870 (13.3) 128 (2.f d. sodium level.5) 207 (44.g.6) 170 (17.9) 20 (4.5) 98 (9.f d.4) 28 (6.0)d. n (%) Severity scores. median (­interquartile range) a b 398 (40.6) 265 (17.g.g 50.4 ± 16.g 4 (2–10)d.9d.8) d. d p < 0. Mixed dysnatremia: patients who experienced at least one episode of hyponatremia and one of hypernatremia during ICU stay.0) 1151 (17.f d.1) 1813 (28.8) 5332 (82.g 161 (16. 503 (50. h p = 0. n (%)   Emergency surgery   Elective surgery Outcome.g 8.0) 1605 (24. may be expected to trigger rapid changes in serum osmolarity with subsequent neurohormonal and metabolic consequences Critical Care Medicine similar to acute dysnatremia. the neurological manifestations of these acute fluctuations in sodium level may be masked due to sedation www.g Mixed Dysnatremia n = 470 61 ± 16g.3)c 35 (7.0) 179 (18.

3)c.05–0.Sakr et al TABLE 4.0)b 721 (48.9)f 494 (16.9 5. c p < 0.3)d 288 (9.4)d.9)d 1081 (36.7)d 1867 (63.6) 1 (1–1) Otorhinolaryngologic.9 ± 3.9) 45.001. which can lead to coma and death (33). Our data suggest that rapid changes in January 2013 • Volume 41 • Number 1 .4) 73 (1.0)c 26 (0. p = 0.3)b 202 (13.01–0.7) 295 (19.9) 1511 (23. d p < 0. in patients with prolonged hypernatremia. yrs.5) 29 (1.0) 1.4) 299 (4.4) 45.01.605 (24. n (%) Severity scores.8) 5332 (82.9)b 343 (23.5) 971 (15.org correction rates >12 mmol/L per day.3)d 146 (9. g p < 0. n (%)  Gastrointestinal  Cardiothoracic  Neurosurgery  Trauma  Othera Type of intervention. treatment with hypotonic fluids may cause cerebral edema.2)d 202 (6.001.01–0.6)d 124 (4.6d 7. Furthermore.0) 236 (3. depending on the time of onset of hyponatremia (13). Obstetrical/gynecologic.6) 581 (9.05–0.0)d 1 (1–5) ICU-Acquired Dysnatremia n = 2948 63 ± 14 1899 (6. dysnatremia at ICU admission: serum sodium levels <135 mmol/L or >145 mmol/L in the first data set after admission. therefore. Oral. and may be aggravated by preexisting conditions.0d 7.5)b 96 (6.5 ± 3.4)d 472 (16.0) 1151 (17. this observation was based on retrospective data and has not been confirmed in prospective randomized trials. ICU-acquired dysnatremia: initially normal serum sodium levels and abnormal levels at some point during ICU stay.6)d 578 (19. such as hypoxia and low cardiac output (31).8)d 402 (13.2) 91 (1.4 3493 (53.4)b 130 (8.f 131 (4.f 3 (1–11) Age.9)d 201 (13. a serious complication of rapid correction of hyponatremia.3) 128 (2. mean ± SD   Simplified Acute Physiology Score II   Sequential Organ Failure Assessment score Comorbidities.2)d 192 (12.e 415 (14.4 ± 16. n (%)   ICU mortality   Hospital mortality ICU length of stay.ccmjournal.7) 870 (13. median (interquartile range) a b 63 ± 14 4067 (62.2)d 227 (15.7)d 914 (61.01. n (%)   Emergency surgery   Elective surgery Outcome.5 ± 18. and maxillofacial surgery. Although correction rates of hyponatremia up to 12 mmol/L per day have been recommended (32).8)d 1550 (52. It may not be surprising. has been reported at 140 www. Central pontine myelinolysis.8)c 93 (6.8d 816 (54.0) 2882 (44. e p = 0.6)d.8) 302 (4. that acute severe fluctuations in serum sodium levels within the normal range may adversely influence outcome.6d. mean ± SD Male.  Characteristics and Outcome According to Time of Onset of Dysnatremia Normonatremia n = 6483 Dysnatremia at ICU Admission n = 1492 63 ± 15 939 (62.3 ± 3.1) 1813 (28.001 compared to dysnatremia at ICU admission.8)d 253 (17.g 1590 (53.7)b 578 (38. n (%)   Diabetes mellitus   Arterial hypertension  Cirrhosis  Cancer   Renal failure   Heart failure   Hematologic cancer Type of surgery on admission day.1)d 365 (12.001 compared to normonatremia.4 ± 18. f p < 0. Normonatremia: serum sodium levels ≥135 mmol/L and ≤145 mmol/L.9) 776 (26.7) 34. days.

serum sodium levels within the normal range should be however. 14). In our study. repeated measures of serum sodium natremia. the severity of illness was considered a decrease in the serum sodium without any alteration in the in the multivariate analysis. a phenomenon called translational hypo.org 141 . such as trend test). although a cause–effect relationship dysfunction/failure as assessed by the Sequential Organ Failure cannot be determined from these data. the results of our study cannot be extrapolated to other poor outcome when associated with hyperglycemia. Nevertheless. marked elevation of lipids and proteins in plasma leads to an artifactual decrease in serum sodium concentration because a larger relative proportion of plasma is occupied by excess lipid or proteins (35).rected for this factor.are routinely checked for plausibility by the attending physimia occurred in 47% of hyponatremic patients. translational hyponatremia was observed in 8. This is. Assessment scores.001 for ICU and hospital mortality among groups not necessary in terms of prognos(Cochran–Armitage trend test). because of the retrospective nature of the study. First. els may have been more commonly detected in more severely ill Hyperglycemia results in the movement of free water patients. These possible confounding factors were not measured routinely in our patients and may have influenced our results. Data on the epidemiology and prognostic value of levels may have increased the probability of erroneous results translational hyponatremia. However. especially in the postoperative because of technical issues related to handling of samples and settings.  Bar chart representing ICU and hospital mortality rates according to the maximum daily fluctuation in serum sodium concentration. and only validated values were considered in our analysis. patients with translational hyponatremia had similar outcomes to other hyponatremic patients.  Bar chart representing ICU and hospital mortality rates according to the maximum fluctuation in serum sodium concentrations during ICU stay. be useful in risk stratification of ICU patients. surgioutcome or not should be investigated in properly designed cal interventions. 12.001 for ICU and hospital mortality among groups (Cochran–Armitage or on relevant therapeutics. Therefore. Nevertheless. should be adapted to avoid such fluc­ tuations. the severity of illness. 10. Second. The authors cian. Fifth. we adjusted for several facreplacement. abnormalities in serum sodium levnevertheless. and the degree of organ prospective studies. Our study has some limitations. especially volume subject (6. In 331 patients with acute heart failure.ccmjournal. However. such as comorbidities. laboratory values in our ICU Milo-Cotter et al (34) reported that translational hyponatre. tors in the multivariate analysis that may reflect the underlying Whether active correction of these fluctuations could improve pathophysiology of dysnatremia. this information may. a common limitation of the previous studies on the recognized early and therapeutic approaches. fluid regimen. The nonsurgical ICU patients. Third. in whom repeated measures were performed during from the intracellular to the extracellular space resulting in the ICU stay. however. are scanty. which should therefore have cortotal body water. p < 0. although correction of measured sodium levels may have a therapeutic implication in hyponatremic patients with hyperglycemia.4% of patients with hyponatremia at admission to the ICU and in 3% of patients with secondary hyponatremia. measurement errors. Fourth.Laboratory Investigation study was limited. Critical Care Medicine www. Again. tication in these patients. (34) found that the hyponatremia was not associated with Finally. this correction is Figure 3. 8. the multivariable approach is limited by the variables included in the analysis and a possible influence of unmeasured variables on the results cannot be excluded. by the small number of patients. we did not elaborate on the causes of dysnatremia Figure 4. p < 0.

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