Associations between Baseline Hyponatremia and Activities of Daily                    Living and Muscle Health in Convalescent Stroke Patients

Yoshihiro Yoshimura; Hidetaka Wakabayashi; Fumihiko Nagano; Ayaka Matsumoto; Sayuri Shimazu; Ai Shiraishi; Yoshifumi Kido; Takahiro Bise; Aomi Kuzuhara; Kota Hori; Takenori Hamada; Kouki Yoneda; Kenichiro Maekawa

doi:10.2490/prm.20240019

ABSTRACT

Objectives: Evidence is scarce regarding the association between hyponatremia and functional outcomes among older hospitalized patients. We aimed to evaluate the associations between baseline hyponatremia and improvement in activities of daily living (ADL) and muscle health in hospitalized post-stroke patients.

Methods: This retrospective cohort study included hospitalized post-stroke patients. Serum sodium concentrations were extracted from medical records based on blood tests performed within 24 h of admission, with hyponatremia defined as a serum sodium concentration below135 mEq/L. Primary outcome was the discharge ADL as assessed by the motor domain of the Functional Independence Measure (FIM-motor) and its corresponding gain during hospitalization. Other outcomes encompassed the discharge scores for skeletal muscle mass (SMI) and handgrip strength (HGS). Multivariate linear regression analyses were used to determine the association between hyponatremia and outcomes of interest, adjusted for potential confounders.

Results: Data from 955 patients (mean age 73.2 years; 53.6% men) were analyzed. The median baseline blood sodium level was 139 [interquartile range: 137, 141] mEq/L, and 84 patients (8.8%) exhibited hyponatremia. After full adjustment for confounders, baseline hyponatremia was significantly and negatively associated with FIM-motor at discharge (β=−0.036, P=0.033) and its gain during hospital stay (β=−0.051, P=0.033). Baseline hyponatremia exhibited an independent and negative association with discharge HGS (β=−0.031, P=0.027), whereas no significant association was found between baseline hyponatremia and discharge SMI (β=−0.015, P=0.244).

Conclusions: Baseline hyponatremia demonstrated a correlation with compromised ADL and muscle health in individuals undergoing rehabilitation after stroke.

INTRODUCTION

Hyponatremia stands as the most prevalent electrolyte disorder encountered in hospital settings. Numerous studies have delved into the epidemiological aspects of hospital-associated hyponatremia, revealing its negative impact on outcomes.¹^,²^,³⁾ The prevalence of hyponatremia varies widely, ranging from (5.5% to 38%), but much of this variation can be attributed to different hyponatremia cutoff values in various studies.¹^,³^,⁴^,⁵⁾ In addition, several investigations have underscored the association between hyponatremia and adverse clinical outcomes, including heightened mortality, extended hospital stay, increased readmission rates, and elevated healthcare costs.¹^,²^,⁶^,⁷^,⁸⁾ Although risk factors for hyponatremia development encompass a spectrum of medical conditions, medications, and lifestyle habits, many of these factors are preventable or treatable. Hence, hyponatremia is commonplace in hospitals and stands as a substantial risk factor for adverse outcomes, necessitating attention to mitigate its impact on patient health.

Currently, there is insufficient evidence regarding the association between hyponatremia and functional outcomes in post-stroke patients. Only a few studies have evaluated the impact of hyponatremia on clinical outcomes other than mortality and short-term complications.⁹^,¹⁰^,¹¹⁾ To our knowledge, no studies have examined the potential impact of hyponatremia on rehabilitation outcomes. Functional recovery after stroke is important, because it is closely correlated with subsequent activities of daily living (ADL) and quality of life. Nonetheless, post-stroke patients are likely to have various contributing factors to hyponatremia, including diuretics, antiepileptic drugs, chronic heart failure, and inadequate energy intake.

It is clinically imperative to elucidate the association between hyponatremia and functional prognosis in post-stroke patients. Therefore, we conducted a retrospective cohort study to examine the associations between hyponatremia and ADL as well as muscle function (muscle mass and strength) in patients undergoing convalescent rehabilitation after stroke.

MATERIALS AND METHODS

Participants and Setting

We conducted a single-center retrospective cohort study in a post-acute care hospital with 135 convalescent rehabilitation beds. All stroke patients consecutively admitted and discharged between 2016 and 2022 were included. Patients were excluded from the study if they refused consent to participate, had incomplete data, or had altered consciousness at the time of admission. Patients were followed until discharge.

Serum Sodium Concentration and Hyponatremia

Data on serum sodium (Na) level (mEq/L) were extracted from medical records on blood draws performed within 24 h of admission and prior to discharge, which are part of routine clinical procedure. In this study, hyponatremia was defined as a serum sodium concentration below 135 mEq/L.¹²⁾ According to the serum sodium level on admission, patients were classified as hyponatremic or non-hyponatremic.

Data Collection

Patients’ demographic and clinical characteristics such as age, sex, stroke type, severity of lower limb hemiplegia as indicated by the Brunnstrom Recovery Stage (BRS-lower extremity), stroke history, and other laboratory data (serum levels of albumin, hemoglobin, C-reactive protein, and electrolytes) were recorded upon admission. Pre-stroke ADL and severity of comorbidities were assessed by physicians using the modified Rankin Scale (mRS)¹³⁾ and the Charlson Comorbidity Index (CCI),¹⁴⁾ respectively. Comorbidities associated with susceptibility to hyponatremia, such as chronic heart failure, stage IV and V chronic kidney disease, diabetes mellitus, and liver cirrhosis, were investigated.²⁾ Functional Independence Measure motor (FIM-motor) and cognition (FIM-cognition) domains were used to assess ADL and cognitive level, respectively.¹⁵⁾ FIM assessments were performed by suitably trained physical and occupational therapists. Body composition data, including skeletal muscle mass (SMI), were recorded by bioimpedance analysis (BIA) within 78 h of admission. Handgrip strength (HGS) was measured by physical or occupational therapists upon admission. If the patient had difficulty measuring grip strength because of cognitive decline or other reasons, it was recorded as 0.0 kg. The energy and protein intake were calculated by nurses or nutritionists by visually evaluating the ratio of intake to the amount provided to the patient, and the average of the intake for 1 week was taken as the daily intake at baseline: the nutrient intake was calculated by dividing each intake by the actual body weight. The total number of units of rehabilitation therapy received during hospitalization was calculated based on the national health insurance standard (1 unit=20 min of therapy). The number of regularly prescribed oral medications at the time of admission and the length of hospital stay were also recorded.

Outcomes

The primary outcome was the FIM-motor as a measure of ADL. In this study, we assessed FIM-motor at discharge and its gain as study outcomes: FIM-motor gain was defined as the change in FIM-motor from admission to discharge. The FIM is an 18-item assessment tool used to evaluate an individual’s functional capability in various areas, including self-care, continence, mobility, transfers, communication, and cognition. Each of the 18 items are graded on a scale of 1–7 to give a possible FIM range of 18–126. The motor component ranges between 13 and 91, whereas the cognitive component ranges between 5 and 35. The reliability and validity of the FIM instrument are generally reported to be good, with very good inter-rater reliability for the total score, motor score, and cognitive score.¹⁵⁾

The secondary outcomes were gains (changes) in SMI and HGS during hospitalization. The study used the SMI of all limbs derived from BIA. A multifrequency, validated BIA device (InBody S10; InBody, Tokyo, Japan) was used to measure skeletal muscle mass. SMI was calculated from the measured skeletal muscle mass divided by squared height (meters). SMI was measured within 3 days of admission and within 3 days before discharge, and SMI gain (changes) were evaluated by subtracting the SMI at admission from that at discharge. Other outcomes of interest included changes in HGS (HGS gain) during hospitalization. HGS of the non-dominant hand (or the non-paralyzed hand in case of hemiparesis) was measured three times using a Smedley hand-dynamometer (TTM, Tokyo, Japan); the highest value of the three measurements was recorded. For patients who could not perform this test, HGS was recorded as 0.0 kg.¹⁶⁾ To reduce biases, the rehabilitation therapists and nurses who evaluated the FIM and HGS were independent from those involved in the collection, evaluation, and analysis of the data and the conclusions of the study.

Convalescent Rehabilitation Program during Hospitalization

The convalescent rehabilitation program (up to 3 h/day) was implemented through multiple rehabilitation disciplines according to patient functional abilities and disabilities. Rehabilitation included aspects of physical, occupational, speech, and hearing therapy and management of nutrition,¹⁷⁾ oral hygiene,¹⁸⁾ and medication.¹⁹⁾ Physical therapy included the facilitation of paralyzed limbs, range-of-motion exercises, and basic movement, gait, resistance, and ADL training.²⁰⁾

Sample Size Calculation

The sample size was calculated using data from our previous study,²¹⁾ the results of which showed that the FIM-motor of patients admitted to the hospital was normally distributed with a standard deviation (SD) of 26.0. Based on clinical expertise, we estimated the proportion of patients with hyponatremia to be one-fifth or less of the healthy population. Assuming a true mean difference of 17 between the hyponatremic and normonatremic groups,²²⁾ to reject the null hypothesis with 80% power at an α level of 0.05, a sample size of at least 23 participants in the hyponatremic group and 112 participants in the normonatremic group was required. Therefore, to obtain this sample size, we retrospectively collected data over a period exceeding 1 year.

Statistical Analysis

Parametric data were reported as mean (±SD), whereas non-parametric and categorical data were reported as median [interquartile range; IQR] and number (percentage), respectively. In bivariate analysis, patients were stratified as hyponatremic or non-hyponatremic. Between-group comparisons were performed using the t-test, Mann–Whitney U test, or chi-square test, depending on the variables.

Multiple linear regression analysis was used to evaluate the relationships between baseline hyponatremia and discharge FIM-Motor, SMI, and HGS, as well as the gains observed during hospitalization. From a clinical and academic perspective, confounding factors for the study outcomes (FIM-motor, SMI, and HGS) were extracted and incorporated into the adjustment factors for the multivariate analysis. Potential confounders including age, sex, baseline values of outcomes (FIM-motor, SMI, and HGS), stroke type, pre-stroke mRS, CCI, BRS-lower extremity, FIM-cognition, number of medications, protein intake, rehabilitation, and length of hospital stay were extracted through multi-investigator discussion and prior research review.²³^,²⁴^,²⁵^,²⁶^,²⁷^,²⁸⁾ Multicollinearity was assessed using the variance inflation factor (VIF): a VIF value of 1–10 indicated absence of multicollinearity. P values <0.05 were considered statistically significant. All analyses were performed using IBM SPSS version 21 (Armonk, NY, USA).

Ethics

This study was approved by the Institutional Review Board of Kumamoto Rehabilitation Hospital (approval ID: 190–220315). We were unable to obtain written informed consent because of the retrospective nature of the study. Participants were granted the right to withdraw from this study at any time using an opt-out procedure. The study was conducted in accordance with the 1964 Declaration of Helsinki and its subsequent amendments and the Ethical Guidelines for Medical and Health Research Involving Human Subjects (Provisional Translation as of March 2015).

RESULTS

During the study period, a total of 1012 stroke patients were newly admitted to the hospital. Patients with missing data (n=46) and altered consciousness (n=11) were excluded. Data from 955 patients were included in the analysis (Fig. 1).

Fig. 1.

Flowchart of participant screening, exclusion criteria, and follow-up.

Patients’ baseline characteristics are presented in Table 1. The mean age was 73.2 (±13.3) years. Fifty-three percent of the included patients were male. Recorded stroke types included cerebral infarction (63.0%), cerebral hemorrhage (29.9%), and subarachnoid hemorrhage (7.1%). The median baseline blood sodium level was 139 [137, 141] mEq/L, and 84 patients (8.8%) exhibited hyponatremia. The median values for the baseline study outcomes, namely FIM-motor, SMI, and HGS, were 45 [19, 67], 6.3 [5.3, 7.3] kg/m², and 18.7 [9.8, 27.5] kg, respectively. There were significant differences between the two groups in variables such as age, BRS-lower extremity, pre-stroke mRS, CCI, FIM, SMI, HGS, drug count, and electrolytes other than sodium (potassium and chloride).

Table 1. Baseline characteristics of patients post stroke

Variable	Total n=955	Patients without hyponatremia n=871	Patients with hyponatremia n=84	P value
Age, years	73.2 (±13.3)	72.8 (±13.4)	77.8 (±10.6)	0.001
Sex, male	511 (53.6)	466 (53.5)	45 (54.2)	0.909
Stroke type
Cerebral infarction	601 (63.0)	557 (63.9)	44 (53.0)	0.057
Cerebral hemorrhage	285 (29.9)	251 (28.8)	34 (41.0)	0.024
SAH	68 (7.1)	64 (7.3)	4 (4.8)	0.506
BRS
Upper extremity	5 [3, 6]	5 [3, 6]	4 [2, 5]	<0.001
Finger	5 [3, 6]	5 [3, 6]	4 [2, 5]	<0.001
Lower extremity	5 [3, 6]	5 [3, 6]	4 [1, 6]	<0.001
Stroke history	223 (23.4)	193 (22.2)	30 (36.1)	0.006
Pre-stroke mRS	0 [0, 2]	0 [0, 2]	1 [0, 3]	<0.001
Comorbidity
CCI	3 [2, 4]	3 [2, 4]	4 [3, 4]	<0.001
CHF	163 (17.1)	152 (17.0)	15 (17.9)	0.102
CKD (stage IV or V)	549 (57.4)	499 (57.3)	48 (57.2)	0.269
DM	171 (17.9)	155 (17.8)	16 (19.0)	0.131
Liver cirrhosis	5 (5.1)	5 (5.6)	0 (0.0)	0.910
FIM
Total	64 [33, 92]	68 [37, 93]	26 [19, 49]	<0.001
Motor	45 [19, 67]	48 [22, 68]	14 [13, 34]	<0.001
Cognition	20 [12, 27]	21 [13, 27]	10 [6, 19]	<0.001
Muscle-related variables
SMI, kg/m²	6.3 [5.3, 7.3]	6.3 [5.3, 7.3]	5.7 [4.8, 6.7]	0.002
HGS, kg	18.7 [9.8, 27.5]	19.3 [10.8, 27.7]	8.4 [5.0, 20.1]	<0.001
Nutrition intake
Energy, kcal/kg per day	27.3 [23.2, 31.8]	27.5 [23.3, 32.1]	25.9 [22.6, 30.5]	0.037
Protein, g/kg per day	1.0 [0.9, 1.2]	1.0 [0.9, 1.2]	1.0 [0.9, 1.2]	0.225
Rehabilitation units ^a	8.2 [7.3, 8.6]	8.2 [7.4, 8.5]	7.9 [6.3, 8.3]	0.004
LOS, days	89 [55, 136]	87 [53, 134]	109 [74, 141]	0.011
Medication
Diuretics	128 (13.5)	113 (13.0)	15 (17.8)	0.093
Antiepileptics	1 (0.1)	1 (0.1)	0 (0.0)	0.999
Antidepressants	6 (0.6)	5 (0.6)	1 (1.2)	0.422
Antipsychotics	77 (8.1)	71 (8.1)	7 (8.3)	0.861
PPI	527 (55.2)	473 (54.3)	54 (65.1)	0.151
Total number	5 [3, 7]	5 [3, 7]	7 [5, 8]	<0.001
Laboratory data
Albumin, g/dL	3.6 [3.2, 4.0]	3.7 [3.3, 4.0]	3.5 [3.1, 3.8]	0.101
Hemoglobin, g/dL	13.3 [11.9, 14.5]	13.4 [12.0, 14.6]	12.9 [11.9, 13.9]	0.115
CRP, mg/dL	0.2 [0.1, 0.8]	0.2 [0.1, 0.8]	0.4 [0.1, 1.3]	0.061
Sodium, mEq/L	139 [137, 141]	140 [138, 141]	132 [130, 133]	-
Hyponatremia	84 (8.8)	-	-	-
Potassium, mEq/L	4.2 [3.9, 4.5]	4.1 [3.9, 4.4]	4.4 [4.1, 4.7]	<0.001
Chloride, mEq/L	104 [102, 106]	105 [103, 106]	98 [96, 100]	<0.001

Data given as mean (±SD), median [IQR], or number (percentage).

^a Rehabilitation therapy (including physical, occupational, and speech and swallowing therapy) performed during hospitalization (1 unit=20 min).

CHF, chronic heart failure; CKD, chronic kidney disease; CRP, C-reactive protein; DM, diabetes mellitus; LOS, length of hospital stay; PPI, proton pump inhibitor; SAH, subarachnoid hemorrhage.

In unadjusted two-group comparisons, patients with hyponatremia showed significantly lower scores for FIM-motor at discharge (44 [15, 78] vs. 81 [55, 89], P<0.001) and its gain during hospitalization (15 [2, 35] vs. 21 [10, 34], P=0.044). Moreover, although SMI at discharge was not significantly different between the two groups, HGS at discharge was significantly lower in patients with hyponatremia compared to those without hyponatremia (17.6 [12.7, 23.9] kg vs. 21.5 [13.9, 30.2] kg, P<0.001) (Table 2).

Table 2. Two-group comparison of study outcomes between post-stroke patients with and without hyponatremia

Parameter	Patients without hyponatremia n=871	Patients with hyponatremia n=84	P value
FIM-motor at discharge	81 [55, 89]	44 [15, 78]	<0.001
FIM-motor gain	21 [10, 34]	15 [2, 35]	0.044
SMI at discharge	6.4 [5.5, 7.4]	6.1 [4.9, 6.9]	0.070
HGS at discharge	21.5 [13.9, 30.2]	14.9 [0.5, 22.9]	<0.001

Data presented as median [IQR].

The serum sodium level and frequency of hyponatremia at discharge and the results of the two-group comparison of FIM-motor and its gain at discharge according to the presence of hyponatremia at discharge are shown in Tables 3 and 4, respectively. The frequency of hyponatremia at discharge was 11.1% (106 patients), and patients with hyponatremia at discharge had significantly higher FIM-motor gains than those without hyponatremia.

Table 3. Serum sodium levels and hyponatremia at admission and discharge in post-stroke hospitalized patients

	On admission	On discharge
Sodium, mEq/L	139 [137, 141]	141 [139, 142]
Hyponatremia	84 (8.8)	106 (11.1)

Data shown as median [IQR] or number (percentage) based on total number of patients (n=955).

Table 4. Two-group comparison of study outcomes between patients with and without hyponatremia at discharge

	No hyponatremia at discharge n=849	Hyponatremia at discharge n=106	P value
FIM-motor at discharge	79 [49, 88]	84 [51, 89]	0.247
FIM-motor gain	21 [10, 35]	14 [5, 24]	<0.001

Data shown as median [IQR].

Table 5 shows the results of multiple linear analyses of baseline hyponatremia for FIM-motor at discharge and its gain in patients post stroke. Two multivariate analyses included the same covariates for adjustments to reduce bias, and there was no multicollinearity between the variables. After fully adjusting for confounding factors, the baseline hyponatremia was significantly and negatively associated with FIM-motor at discharge (β=−0.036, P=0.033) and its gain during hospital stay (β=−0.051, P=0.033).

Table 5. Multiple linear analysis of baseline hyponatremia for FIM-motor at discharge and its gain in patients post stroke

Parameter	FIM-motor at discharge			FIM-motor gain
Parameter	B (95% CI)	β	P value	B (95% CI)	β	P value
Age	−0.085 (−0.188, 0.019)	−0.045	0.109	−0.085 (−0.188, 0.019)	−0.062	0.109
Sex, male	−5.232 (−7.975, −2.489)	−0.105	0.001	−5.232 (−7.975, −2.489)	−0.146	0.001
Ischemic stroke	3.276 (−1.023, 7.574)	0.063	0.135	3.276 (−1.023, 7.574)	0.088	0.135
Hemorrhagic stroke	5.087 (0.617, 9.557)	0.093	0.026	5.087 (0.617, 9.557)	0.130	0.026
Pre-stroke mRS	−2.750 (−3.715, −1.784)	−0.142	<0.001	−2.750 (−3.715, −1.784)	−0.197	<0.001
CCI	−0.246 (−0.839, 0.248)	−0.009	0.281	−0.146 (−0.839, 0.548)	−0.013	0.680
FIM-motor	0.326 (0.238, 0.413)	0.329	<0.001	−0.674 (−0.762, −0.587)	−0.948	<0.001
FIM-cognition	0.498 (0.319, 0.677)	0.177	<0.001	0.498 (0.319, 0.677)	0.246	<0.001
BRS-lower extremity	3.008 (2.151, 3.865)	0.220	<0.001	3.008 (2.151, 3.865)	0.307	<0.001
HGS	0.504 (0.360, 0.648)	0.242	<0.001	0.504 (0.360, 0.648)	0.337	<0.001
SMI	1.432 (0.321, 2.543)	0.078	0.012	1.432 (0.321, 2.543)	0.109	0.012
Number of medications	−0.279 (−0.460, 0.002)	−0.019	0.082	−0.279 (−0.460, 0.003)	−0.013	0.082
Rehabilitation units ^a	0.239 (−0.265, 0.743)	0.020	0.352	0.239 (−0.265, 0.743)	0.028	0.352
LOS	0.060 (0.030, 0.090)	0.114	<0.001	0.060 (0.030, 0.090)	0.158	<0.001
Hyponatremia	−3.277 (−6.447, −0.093)	−0.036	0.033	−3.287 (−6.449, −0.089)	−0.051	0.033
	R²=0.701			R²=0.725

^a Rehabilitation therapy (including physical, occupational, and speech and swallowing therapy) performed during hospitalization (1 unit=20 min).

CI, confidence interval; SAH, subarachnoid hemorrhage; LOS, length of hospital stay.

Table 6 presents the outcomes of multiple linear regression analyses of baseline hyponatremia for SMI gain and HGS gain. No multicollinearity was observed among the variables. After fully adjusting for confounding factors, baseline hyponatremia exhibited an independent and negative association with HGS gain (β=−0.033, P=0.024), whereas no significant association was found between baseline hyponatremia and SMI gain (β=−0.017, P=0.233).

Table 6. Multiple linear analysis of baseline hyponatremia for SMI gain and HGS gain in patients post stroke

Parameter	SMI gain			HGS gain
Parameter	B (95% CI)	β	P value	B (95% CI)	β	P value
Age	−0.008 (−0.012, −0.003)	−0.072	0.003	−0.101 (−0.148, −0.051)	−0.106	<0.001
Sex, male	0.231 (0.104, 0.362)	0.087	<0.001	1.621 (0.339, 2.903)	0.065	0.013
Ischemic stroke	0.084 (−0.125, 0.296)	0.031	0.426	1.163 (−0.845, 3.172)	0.045	0.256
Hemorrhagic stroke	0.175 (−0.043, 0.394)	0.060	0.115	2.195 (0.106, 4.283)	0.081	0.039
Pre-stroke mRS	−0.009 (−0.056, 0.038)	−0.008	0.715	−0.598 (−1.049, −0.147)	−0.062	0.009
CCI	0.043 (0.009, 0.077)	0.051	0.013	−0.073 (−0.397, 0.251)	−0.010	0.357
FIM-motor	0.005 (−0.004, 0.004)	−0.002	0.963	0.045 (−0.046, −0.094)	0.091	0.031
FIM-cognition	0.002 (−0.007, 0.010)	0.010	0.726	0.069 (−0.015, 0.152)	0.049	0.107
BRS-lower extremity	0.071 (0.029, 0.113)	0.096	0.001	0.008 (−0.392, 0.408)	0.001	0.969
HGS	0.010 (0.003, 0.017)	0.090	0.004	0.728 (0.654, 0.815)	0.696	<0.001
SMI	0.768 (0.686, 0.828)	0.750	<0.001	0.829 (0.310, 1.348)	0.091	0.002
Number of medications	−0.015 (−0.114, 0.023)	−0.010	0.119	−0.227 (−0.405, −0.049)	−0.054	0.012
Rehabilitation units ^a	0.018 (−0.019, 0.054)	0.018	0.342	0.035 (−0.201, 0.270)	0.006	0.372
LOS	0.001 (−0.001, 0.002)	0.033	0.218	0.006 (−0.008, 0.020)	0.024	0.375
Hyponatremia	−0.166 (−0.704, 0.237)	−0.017	0.233	−1.163 (−3.359, −0.084)	−0.033	0.024
	R²=0.834			R²=0.736

^a Rehabilitation therapy (including physical, occupational, and speech and swallowing therapy) performed during hospitalization (1 unit=20 min).

CI, confidence interval; SAH, subarachnoid hemorrhage; LOS, length of hospital stay.

DISCUSSION

In this cohort study, we investigated the association between baseline hyponatremia and both ADL recovery and muscle function (muscle mass and strength) in patients undergoing convalescent rehabilitation after stroke. Our results unveiled two noteworthy findings concerning baseline hyponatremia in this patient cohort: first, hyponatremia was negatively associated with ADL recovery during hospitalization; and second, hyponatremia was associated with a decline in muscle strength during hospitalization, with no observed association with the loss of muscle mass.

Hyponatremia was negatively associated with ADL recovery during hospitalization. To our knowledge, this study may represent the first attempt to assess such an association in this particular setting. The potential mechanisms contributing to this association are likely multifactorial. Hyponatremia can manifest neurological symptoms ranging from mild to severe, including cognitive impairment, potentially impeding a patient’s ADL.²⁹^,³⁰^,³¹⁾ In addition, hyponatremia often accompanies underlying medical conditions such as heart failure, kidney failure, and liver cirrhosis, further compromising a patient’s functional status.²⁹^,³²⁾ Furthermore, the management of hyponatremia itself can impact ADL recovery. Treatment strategies like fluid restriction and medication adjustments may impact a patient’s physical and cognitive function, potentially influencing their ability to perform ADL.³⁰^,³³⁾ These findings underscore the significance of prompt diagnosis and effective management of hyponatremia in rehabilitation patients to optimize their functional recovery.

Hyponatremia exhibited a correlation with a decline in muscle strength during the hospital stay, with no observed association with the loss of muscle mass. These findings shed light on the potential impact of hyponatremia on muscle health, particularly in older individuals. Although previous research has linked hyponatremia to various adverse clinical outcomes, the specific correlation between hyponatremia and a decline in muscle strength, independent of muscle mass, appears to be a new finding.³⁴⁾ Several factors may contribute to this result. Hyponatremia can affect neurological function, causing cognitive dysfunction and muscle weakness.³⁵⁾ It is also associated with peripheral nervous system dysfunction,³⁶^,³⁷⁾ cellular swelling affecting muscle cells,³⁶⁾ and cardiovascular changes affecting grip strength because of effects on blood flow and microcirculation.³⁸⁾ Further research is required to comprehend these mechanisms and move toward targeted treatment strategies, noting that hospital-associated sarcopenia is closely associated with adverse clinical outcomes, including physical function and ADL.³⁹⁾

Addressing electrolyte abnormalities and implementing the triad of rehabilitation, nutrition, and oral management is crucial for enhancing functional prognosis. Although this study does not provide specific guidance on rehabilitation approaches based on these findings, our results suggest that patients with hyponatremia may be at risk of suboptimal improvement in ADL. Therefore, in addition to correcting electrolyte imbalances, a multidisciplinary rehabilitative approach aimed at facilitating ADL recovery and musculoskeletal health may be warranted for this patient population.³⁰^,³³^,⁴⁰⁾ Such an approach would need to be validated in future interventional studies. There is a need to scrutinize the cause of hyponatremia and, if treatable, to adjust the therapy as required. Given that electrolyte abnormalities, malnutrition, and sarcopenia are frequently found in older patients undergoing post-stroke rehabilitation,⁴¹^,⁴²⁾ it may be necessary to implement the triad of rehabilitation, nutrition, and oral management.⁴³^,⁴⁴^,⁴⁵⁾ This multifaceted approach aims to enhance nutritional status, oral health, and overall functional recovery, highlighting the significance of integrated patient care through perspectives such as rehabilitation nutrition⁴⁶^,⁴⁷^,⁴⁸⁾ and rehabilitation pharmacotherapy.¹⁹^,⁴⁹^,⁵⁰⁾

This study had limitations. First, this was a single-center study in a rehabilitation hospital in Japan, which may limit the generalizability of our findings. Future multicenter studies are needed to replicate the present results in different populations. Second, given the retrospective nature of the study, we could not fully adjust for the effect of confounding factors, and we were unable to determine causality. Future high-quality prospective intervention studies that adjust for these confounders are needed.

CONCLUSION

Baseline hyponatremia demonstrated a correlation with compromised ADL and muscle health in individuals undergoing rehabilitation after stroke. Evaluating hyponatremia at the outset serves as a crucial prognostic indicator. Future investigations should explore the potential enhancement of functional recovery in this population through targeted treatment of hyponatremia.

ACKNOWLEDGMENTS

This research did not receive any funding from agencies in the public, commercial, or not-for-profit sectors.

CONFLICTS OF INTEREST

The authors declare no conflict of interest.

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