Hyponatremia as a predictor of cognitive deterioration in hospitalized post-stroke patients.

PURPOSE: Evidence is scarce regarding the association between hyponatremia and alterations in cognitive function among hospitalized older patients. We aimed to investigate the associations between hyponatremia and the baseline cognitive status, as well as the improvement in cognitive function, in hospitalized post-stroke patients. METHODS: This retrospective cohort study included consecutive 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 < 135 mEq/L. The main outcomes included admission and discharge scores for cognitive levels, assessed through the cognitive domain of the Functional Independence Measure (FIM-cognition), as well as the score changes observed during the hospitalization period. 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 included in the analysis. The median baseline blood sodium level was 139 [137, 141], and 84 patients (8.8 %) exhibited hyponatremia. After full adjustment for confounders, the baseline hyponatremia was significantly and negatively associated with FIM-cognition values at admission (ß = -0.009, p = 0.016), discharge (ß = -0.038, p = 0.043), and the gain during hospital stay (ß = -0.040, p = 0.011). CONCLUSION: Baseline hyponatremia has demonstrated a correlation with decline in cognitive level over the course of rehabilitation in individuals after stroke. Assessing hyponatremia at the outset proves to be a pivotal prognostic indicator.

Dysnatremia in a changing climate: A global systematic review of the association between serum sodium and ambient temperature.

OBJECTIVE: Both hyponatremia and hypernatremia have been reported to occur more frequently with higher ambient temperatures, although the underlying mechanisms are not well understood. Global temperatures are rising due to climate change, which may impact the incidence of dysnatremia worldwide. We aimed to identify, collate and critically appraise studies analyzing the relationship between climate measures (outdoor temperature, humidity) and serum sodium concentrations. DESIGN: Systematic review, reported in accordance with PRISMA guidelines. METHODS: MEDLINE and Embase were searched with relevant key terms. Studies assessing the effect on serum sodium measurement of elevated temperature or humidity versus a comparator were included. RESULTS: Of 1466 potentially relevant studies, 34 met inclusion criteria, originating from 23 countries spanning all inhabited continents. The majority (30 of 34, 88%) reported a significant association between outdoor temperature and dysnatremia, predominantly lower serum sodium with increased ambient temperature. Humidity had a less consistent effect. Individuals aged above 65 years, children, those taking diuretics and antidepressants, those with chronic renal impairment or those undertaking physical exertion had increased vulnerability to heat-associated dysnatremia. The risk of bias was assessed to be high in all but four studies. CONCLUSIONS: Higher ambient temperature is consistently associated with an increased incidence of hyponatremia. We infer that hyponatremia presentations are likely to rise with increasing global temperatures and the frequency of extreme heat events secondary to climate change. Evidence-based public health messages, clinician education and reduction in fossil fuel consumption are necessary to reduce the expected burden on healthcare services worldwide.

A machine learning approach for predicting treatment response of hyponatremia.

Hyponatremia leads to severe central nervous system disorders and requires immediate treatment in some cases. However, a rapid increase in serum sodium (s-Na) concentration could cause osmotic demyelination syndrome. To achieve a safety hyponatremia treatment, we develop a prediction model of s-Na concentration using a machine learning. Among the 341 and 47 patients admitted to two tertiary hospitals for hyponatremia treatment (s-Na <130 mEq/L), those who were admitted to the general unit with urine sodium <20 mEq/L or treated with desmopressin were excluded. Ultimately, 74 and 15 patients (342 and 146 6-hourly datasets) were included in the learning and validation data, respectively. We trained the prediction model using three regression algorithms for shallow machine learning to predict s-Na every 6 h during treatment with the data of patients with hyponatremia (median s-Na: 112.5 mEq/L; range: 110.0-116.8 mEq/L) from one hospital. The model was validated externally using the data of patients with hyponatremia (median s-Na: 117.0 mEq/L; range: 112.9-120.0 mEq/L) from another hospital. Using 5-7 predictors (water intake, sodium intake, potassium intake, urine volume, s-Na concentration, serum potassium concentration, serum chloride concentration), the support vector regression model showed the best performance overall (root mean square error = 0.05396; R2 = 0.92), followed by the linear regression and regression tree models. The predicted s-Na levels, using explainable machine learning algorithms and clinically accessible parameters, correlated well with the actual levels. Thus, our model could be applied to the treatment of hyponatremia in clinical practice.

Retrospective analysis of patients diagnosed with severe hyponatraemia in the emergency department.

Background . We investigated the demographic, aetiological and clinical characteristics of patients who presented to the emergency department and had severe hyponatraemia. Methods . We retrospectively evaluated 1171 patients who presented to the emergency department and were diagnosed with severe hyponatraemia. Results . Over half the patients studied were women (53.5%). The mean age of women was higher (p<0.0001). The most common complaint was dyspnoea (16.8%) and 42.5% of the patients had an oral intake disorder. In addition, 22.3% of the patients were on loop diuretics. About 76.3% of patients were conscious, and the mean sodium level of these patients was higher than the mean sodium level of those who responded to verbal and painful stimuli (p<0.001). Severe isolated hyponatraemia was observed in 61.8% of the patients. The mortality rate was 12.8%. There was no difference between the mean sodium levels of the deceased and discharged patients (p=1.0). The mortality rate was higher in patients who had a history of cirrhosis and cancer, but was lower in patients with a history of coronary artery disease (p=0.0002, p<0.0001 and p=0.04, respectively). Conclusion . Severe hyponatraemia was more prevalent in women, serum sodium levels were higher in conscious patients, and the mortality rate was higher in patients who had a history of cirrhosis and cancer. We found that the mean serum sodium levels did not help in distinguishing between the deceased and discharged patients.

Renin, antidiuretic hormone (ADH), and ADH receptor levels in cerebral salt wasting associated with tuberculous meningitis.

BACKGROUND: To evaluate serum antidiuretic hormone (ADH), its receptors, and renin levels in cerebral salt wasting (CSW) in tuberculous meningitis (TBM). METHODS: Patients diagnosed with definite (n = 30) or probable TBM (n = 47) who developed hyponatremia (CSW, SIADH, or miscellaneous causes) were included. Sequential measurement of serum ADH, ADH-R, and renin activity by enzyme-linked immunosorbent assay was done and correlated with serum sodium level, urinary output, and fluid balance. RESULTS: Out of 79 TBM patients, CSW was observed in 36, SIADH in four, and miscellaneous hyponatremia in eight patients. CSW patients had a longer hospital stay (P < 0.001), lower GCS score (P < 0.007), higher MRC grade (P < 0.007), and a lower serum Na (P < 0.001) compared to non-CSW TBM patients. In severe CSW patients, serum ADH and ADH-R were correlated with hyponatremia and returned to baseline on correction; however, serum renin levels remained elevated. Serum ADH was related to hyponatremia but ADH-R and renin were not. ADH-R and renin levels did not significantly differ in CSW and SIADH. CONCLUSION: CSW is the commonest cause of hyponatremia in TBM and correlates with disease severity. ADH is related to hyponatremia, but ADH receptor and renin are not.

Impact of Sodium Levels on Functional Outcomes in Patients With Stroke - A Swiss Stroke Registry Analysis.

CONTEXT: Correction of hyponatremia might represent an additional treatment for improving stroke patients' clinical outcomes. OBJECTIVE: Admission hyponatremia is associated with worse clinical outcome in stroke patients, but whether normalization of hyponatremia improves outcome is unknown. We investigated whether normalization of hyponatremia affects patients' disability, mortality, and stroke recurrence within 3 months; length of hospitalization; and discharge destination. DESIGN: This was a registry-based analysis of data collected between January 2016 and December 2018. We linked data from Swiss Stroke Registry (SSR) with electronic patients' records for extracting sodium values. SETTING: We analyzed data of hospitalized patients treated at University Hospital of Basel. PATIENTS: Stroke patients whose data and informed consent were available. MAIN OUTCOME MEASURE: Modified Rankin Scale (mRS) score at 3 months. The tested hypothesis was formulated after SSR data collection but before linkage with electronic patients' records. RESULTS: Of 1995 patients, 144 (7.2%) had hyponatremia on admission; 102 (70.8%) reached normonatremia, and 42 (29.2%) remained hyponatremic at discharge. An increase of initial sodium was associated with better functional outcome at 3 months (odds ratio [OR] 0.94; 95% CI, 0.90-0.99, for a shift to higher mRS per 1 mmol/L sodium increase). Compared with normonatremic patients, patients who remained hyponatremic at discharge had a worse functional outcome at 3 months (odds ratio 2.46; 95% CI, 1.20-5.03, for a shift to higher mRS). No effect was found on mortality, recurrence, or length of hospitalization. CONCLUSIONS: In hospitalized acute stroke patients, persistent hyponatremia is associated with worse functional outcome. Whether active correction of hyponatremia improves outcome remains to be determined in prospective studies.

Increased cytokines/chemokines and hyponatremia as a possible cause of clinically mild encephalitis/encephalopathy with a reversible splenial lesion associated with acute focal bacterial nephritis.

OBJECTIVE: Clinically mild encephalitis/encephalopathy with a reversible splenial lesion (MERS), the second most common encephalopathy syndrome in Japan, is most often associated with viral infection. Bacterial MERS has been rarely reported but is mostly associated with acute focal bacterial nephritis (AFBN) for an unknown reason. We examined cytokines and chemokines in four MERS patients with AFBN to determine if they play an important role in the pathogenesis. METHODS: We examined the clinical charts and MRI results in four MERS patients with AFBN, and measured 10 cytokines and chemokines in serum and cerebrospinal fluid in the acute phase. These were analyzed using the Mann-Whitney U test, compared with the control group (cases with a non-inflammatory neurological disease). Longitudinal changes in the serum cytokine and chemokine levels were evaluated in two patients. RESULTS: Hyponatremia was observed in all four patients with MERS associated with AFBN (128-134 mEq/L). CSF analysis revealed increased cytokines/chemokines associated with Th1 (CXCL10, TNF-α, IFN-γ), T reg (IL-10), Th17 (IL-6), and neutrophil (IL-8 and CXCL1). In serum, upregulation was observed in those associated with Th1 (CXCL10, TNF-α, IFN-γ), Th17 (IL-6), and inflammasome (IL-1ß). The increased serum cytokines/chemokines in the acute stage normalized within 2 weeks in patients 1 and 2, so examined, in accordance with their clinical improvement. CONCLUSION: Increased cytokines/chemokines and hyponatremia may be factors that explain why AFBN is likely to cause MERS.

Clinical factors within a week of birth influencing sodium level difference between an arterial blood gas analyzer and an autoanalyzer in VLBWIs: A retrospective study.

ABSTRACT: Neonatologists often experience sodium ion level difference between an arterial blood gas analyzer (direct method) and an autoanalyzer (indirect method) in critically ill neonates. We hypothesize that clinical factors besides albumin and protein in the blood that cause laboratory errors might be associated with sodium ion level difference between the 2 methods in very-low-birth-weight infants during early life after birth. Among very-low-birth-weight infants who were admitted to Jeonbuk National Hospital Neonatal Intensive Care Units from October 2013 to December 2016, 106 neonates were included in this study. Arterial blood sample was collected within an hour after birth. Blood gas analyzer and biochemistry autoanalyzer were performed simultaneously. Seventy-six (71.7%) were found to have sodium ion difference exceeding 4 mmol/L between 2 methods. The mean difference of sodium ion level was 5.9 ±â€Š6.1 mmol/L, exceeding 4 mmol/L. Based on sodium ion level difference, patients were divided into >4 and ≤4 mmol/L groups. The sodium level difference >4 mmol/L group showed significantly (P < .05) higher sodium level by biochemistry autoanalyzer, lower albumin, lower protein, and higher maximum percent of physiological weight than the sodium level difference ≤4 mmol/L group. After adjusting for factors showing significant difference between the 2 groups, protein at birth (odds ratio: 0.835, 95% confidence interval: 0.760-0.918, P < .001) and percent of maximum weight loss (odds ratio: 1.137, 95% confidence interval: 1.021-1.265, P = .019) were factor showing significant associations with sodium level difference >4 mmol/L between 2 methods. Thus, difference in sodium level between blood gas analyzer and biochemistry autoanalyzer in early stages of life could reflect maximum physiology weight loss. Based on this study, if the study to predict the body's composition of extracellular and intracellular fluid is proceeded, it will help neonatologist make clinical decisions at early life of preterm infants.

Systemic lupus erythematosus presenting as hyponatremia-associated rhabdomyolysis: A case report.

RATIONALE: Systemic lupus erythematosus (SLE) is an autoimmune disease that involves multiple organs and causes various clinical manifestations. Cases of rhabdomyolysis as the initial presentation of SLE are rare, and there are no reported cases of SLE presenting hyponatremia-associated rhabdomyolysis as the first manifestation. Herein, we report a case of SLE with lupus nephritis in a patient with acute hyponatremia-associated rhabdomyolysis. PATIENT CONCERNS: A 44-year-old woman was admitted with complaints of altered consciousness, myalgia, and red-brownish urine that first appeared three days prior. Peripheral blood tests revealed elevated creatine kinase (19,013 IU/L) and myoglobin (5099 U/L) levels and severe hyponatremia (111 mEq/L) with no azotemia. Urinalysis showed nephritic sediments. DIAGNOSIS: Whole-body bone scintigraphy showed increased uptake of radiotracer in the both upper and lower extremities. Serological evaluation revealed the presence of anti-nuclear (speckled pattern, 1:640), anti-double stranded DNA, and anti-Smith antibodies and absence of anti-Jo-1 antibody. A kidney biopsy demonstrated mesangial proliferative (class II) lupus nephritis. INTERVENTIONS: Fluid therapy, including intravenous administration of 3% NaCl, was initiated. After three consecutive days of intravenous methylprednisolone (1 g/d), oral prednisolone (1 mg/kg/d), mycophenolate mofetil, and hydroxychloroquine were administered. OUTCOMES: On day 28, the patient was discharged with marked resolution of SLE-associated symptoms and laboratory findings. Lupus reactivation was not present during the subsequent six-month follow-up. LESSONS: Hyponatremia-associated rhabdomyolysis can be the first manifestation of SLE. Moreover, prompt fluid therapy and timely administration of immunosuppressive agents in SLE patients presenting with hyponatremia and rhabdomyolysis can significantly help alleviate disease activity and improve clinical outcomes.

Pregnancy outcomes in women with hyponatraemia and preeclampsia: Case series and literature review.

OBJECTIVES: To determine the prevalence, clinical course, complications and management of preeclampsia complicated by hyponatraemia. STUDY DESIGN: A ten year retrospective audit of women delivering at a tertiary referral hospital with preeclampsia complicated by hyponatraemia (defined as serum sodium < 130 mmol/L). MAIN OUTCOME MEASURES: The prevalence, time to delivery, complications, treatment and time to recovery of hyponatraemia in women with preeclampsia associated with hyponatraemia. RESULTS: There were 129 cases of preeclampsia associated with hyponatraemia, representing 9% of women with preeclampsia, and 0.27% of deliveries overall. Hyponatraemia was associated with a significant rate of complications of preeclampsia; acute kidney injury in 34.1%, HELLP syndrome in 17.1%, fetal growth restriction in 36.4%, stillbirth in 2.3%, the use of magnesium sulphate in 44.2%, and postpartum maternal admission to an intensive care unit in 28.7%. Moderate/severe hyponatraemia was associated with greater risk of acute kidney injury, fetal growth restriction and post-partum maternal admission to an intensive care unit than mild hyponatraemia. Urgent delivery was required in 71% of women for either obstetric or fetal indications within 24 h of diagnosis of moderate/severe hyponatraemia. In almost all cases, hyponatraemia rapidly resolved postpartum without requirement for fluid restriction or intravenous saline. CONCLUSIONS: Hyponatraemia should be regarded as a marker of severity in the setting of preeclampsia, and in the absence of an alternative cause may be an indication for expedited delivery. Hyponatraemia typically recovers rapidly following delivery without the need for specific therapy.

Relationship between Hyponatremia and Peripheral Neuropathy in Patients with Diabetes.

OBJECTIVES: Hyponatremia is a common complication of diabetes. However, the relationship between serum sodium level and diabetic peripheral neuropathy (DPN) is unknown. This study was aimed at investigating the relationship between low serum sodium level and DPN in Chinese patients with type 2 diabetes mellitus. METHODS: A retrospective study was performed on 1928 patients with type 2 diabetes between 2010 and 2018. The multivariate test was used to analyze the relationship between the serum sodium level and the nerve conduction function. A restricted cubic spline was used to flexibly model and visualize the relationship between the serum sodium level and DPN, followed by logistic regression with adjustment. RESULTS: As the serum sodium level increased, the prevalence of DPN had a reverse J-curve distribution with the serum sodium levels (69.6%, 53.7%, 49.6%, 43.9%, and 49.7%; P = 0.001). Significant differences existed between the serum sodium level and the motor nerve conduction velocity, sensory nerve conduction velocity, part of compound muscle action potential, and sensory nerve action potential of the participants. Compared with hyponatremia, the higher serum sodium level was a relative lower risk factor for DPN after adjusting for several potential confounders (OR = 0.430, 95%CI = 0.220-0.841; OR = 0.386, 95%CI = 0.198-0.755; OR = 0.297, 95%CI = 0.152-0.580; OR = 0.376, 95%CI = 0.190-0.743; all P < 0.05). Compared with low-normal serum sodium groups, the high-normal serum sodium level was also a risk factor for DPN (OR = 0.690, 95%CI = 0.526-0.905, P = 0.007). This relationship was particularly apparent in male participants, those aged <65 years, those with a duration of diabetes of <10 years, and those with a urinary albumin - to - creatinine ratio (UACR) < 30 mg/g. CONCLUSIONS: Low serum sodium levels were independently associated with DPN, even within the normal range of the serum sodium. We should pay more attention to avoid the low serum sodium level in patients with type 2 diabetes mellitus.

Hyponatremia and Renal Venous Congestion in Heart Failure Patients.

OBJECTIVE: The interrelationship between the heart and kidneys has a great importance in the homeostasis of the cardiovascular system. Heart failure patients present intrarenal arterial hypoperfusion and intrarenal venous congestion due to reduced left ventricle ejection fraction, which triggers numerous neurohormonal factors. The aim of this study was to investigate intrarenal vascularization (arterial and venous), as well as the links between it and systemic congestion and, on the other side, with the mortality in patients with heart failure. Material and Methods. This cross-sectional study was performed on a group of 44 patients with heart failure in different stages of evolution and 44 healthy subjects, matched for age and gender, as controls. Serum natremia, NT-proBNP, and creatinine analyses were performed in all patients and controls. Renal and cardiac ultrasonography was done in all patients and controls, recording intrarenal arterial resistive index (RRI), intrarenal venous flow (IRVF) pattern, renal venous stasis index (RVSI), and left ventricular ejection fraction (LVEF). Data are recorded and presented as mean ± standard deviation. Statistical analyses were performed using the Student t-test, ANOVA test, and the Pearson correlation. Differences were considered statistically significant at the value of p < 0.05. RESULTS: Hyponatremia was identified in 47.72% of the HF patients. This study revealed correlations between serum natremia and LVEF, NT-proBNP, serum creatinine, interlobar venous RVSI (p < 0.00001), and interlobar artery RRI (p ≤ 0.002). Hyponatremia and renal venous congestion represent negative prognostic factors in HF patients. CONCLUSION: In HF patients, hyponatremia was correlated with cardiac dysfunction and intrarenal venous congestion. Hyponatremia and renal venous congestion represented negative prognostic factors in HF patients.

Hyponatremia is a Prognostic Factor in Patients Receiving Nutrition Support.

BACKGROUND: Hyponatremia, the most common electrolyte disorder, has been reported to be related to increased mortality. However, the association between hyponatremia and prognoses remains unclear in patients with nutrition support team (NST) intervention. This study aimed to determine the prevalence of abnormal serum sodium levels, its relation to patient data, and the impact of hyponatremia on prognosis. METHODS: Patients who received nutrition support at Tokushima University Hospital for the first time and whose serum sodium levels were measured at the start of NST intervention were enrolled. Patients were classified into three groups according to their serum Na levels at the start of NST intervention: hyponatremia group, normonatremia group, and hypernatremia group. RESULTS: In the hyponatremia group compared to the normonatremia group, body weight and body mass index were significantly lower. C-reactive protein levels and urea nitrogen/creatinine ratios were significantly higher. Meanwhile, there was no significant difference in the estimated glomerular filtration rate among the groups. The prevalence of malnutrition and anemia were the highest in the hyponatremia group. The 3-year survival rate was approximately 45% in the hyponatremia group, which was the lowest of all three groups. The mortality risk ratio of the hyponatremia group to the normonatremia group was 2.29. CONCLUSIONS: Hyponatremia in NST intervention patients is an independent prognostic predictor. Therefore, adding an assessment of serum sodium at the beginning of NST intervention can identify patients at high risk at an early stage and may improve the quality of NST activity.

Incidence and Possible Predictors of Sodium Disturbance After Craniopharyngioma Resection Based on QST Classification.

OBJECTIVE: Serum sodium abnormalities are one of the most common manifestations after radical craniopharyngioma (CP) excision. The aim of this study was to report the incidence and possible predictors of serum sodium disturbance and explore features of sodium destabilization manifestation among QST classification results after CP resection. METHODS: A retrospective analysis was performed of clinical, biochemical, radiologic, and operative data for 134 successive patients who underwent primary CP removal between September 2016 and March 2018. Univariate and multivariate analyses were conducted to determine predictors. RESULTS: Sixty patients (44.8%) experienced hyponatremia and 67 patients (50%) hypernatremia; the median time of onset was 6 days and the first day after surgery, respectively. The incidence, onset, severity, and type of sodium disturbance among different types of CP differed significantly based on statistical tests (P < 0.05). Sodium disturbance was more common and severe in patients with type T tumors (P < 0.05). Age, tumor type, and preoperative diabetes insipidus were independent prognostic factors for obvious disorders of serum sodium. CONCLUSIONS: Hyponatremia/hypernatremia is common after primary CP resection. The site of tumor origin has a direct effect on the growth pattern of CP, which may serve as a useful index for anticipating sodium perturbation after surgery. The level of sodium in children and patients with type T tumors, preoperative diabetes insipidus should be monitored closely throughout hospitalization.

Evaluation of Desmopressin in Critically Ill Patients with Hyponatremia Requiring 3% Hypertonic Saline.

BACKGROUND: Desmopressin (DDAVP) is often used for hyponatremia management but has been associated with increases in hospital length of stay and duration of hypertonic saline use. The purpose of this study was to evaluate hyponatremia management strategies and their effect on sodium correction in critically ill patients requiring 3% hypertonic saline (3HS). METHODS: This retrospective, single-center study included critically ill patients with hyponatremia (serum sodium ≤ 125 mEq/L) receiving 3HS from May 31 2015, to May 31 2019. Patients were divided into those who received 3HS for hyponatremia management (HTS) and those who received proactive or reactive DDAVP in addition to 3HS (D-HTS). Patients in either group could receive rescue DDAVP. The primary outcome was the percentage of patients achieving goal sodium correction of 5-10 mEq/L 24 h after 3HS initiation. RESULTS: Goal sodium correction was achieved in 52.5% of patients in HTS compared to 65.6% of patients in D-HTS (p = 0.21). Patients in HTS had a shorter duration of 3HS infusion (p = 0.0022) with no difference in ICU length of stay, free water intake, urine output, or serum sodium increases 12 and 24 h after receiving 3HS. Overcorrection during any 24- or 48 h period was not statistically different between groups. CONCLUSION: Patients in HTS and D-HTS had similar rates of achieving goal sodium correction at 24 h. A proactive or reactive DDAVP strategy led to an increase in 3HS duration and total amount with no significant difference in rates of overcorrection. Prospective, randomized studies assessing standardized strategies for hyponatremia management and DDAVP administration are warranted.

Safety and effectiveness concerns of lopinavir/ritonavir in COVID-19 affected patients: a retrospective series.

CONTEXT: Originally developed for treatment of human immunodeficiency virus (HIV), the antiviral combination lopinavir/ritonavir (LPV/r) is being repurposed for treating the novel coronavirus disease (COVID-19) despite minimal experience in this markedly different population and an in-vitro derived EC50 against SARS-CoV-2 several hundred-fold greater than for HIV. We present a case series including a case of severe hyponatremia and a 32-fold overdose raising safety and effectiveness concerns in COVID-19 patients. METHODS: We measured LPV trough concentrations in 12 patients and reviewed their clinical charts for side effects known to occur in HIV patients. FINDINGS: Compared to established LPV trough concentrations in HIV patients, concentrations in COVID-19 patients were 3-fold greater (19.37 ± 10.12 mcg/mL versus 6.25 mcg/mL). In addition, cholestasis and dyslipidemia toxicity thresholds were exceeded in 12/12 and 11/12 patients respectively. No patients achieved the presumed therapeutic concentration. Side effects included gastrointestinal symptoms (5/12), electrolyte imbalances (4/12), liver enzyme disturbances (5/12) and triglyceride elevations (2/12). CONCLUSION: No patients reached presumed therapeutic LPV concentrations despite experiencing side effects and exceeding cholestasis and dyslipidemia toxicity thresholds. This raises concerns for the safety and effectiveness of LPV/r. Clinicians should consider closely monitoring for side effects and not necessarily attribute them to COVID-19.

Treatment of symptomatic hyponatremia with hypertonic saline: a real-life observational study.

OBJECTIVE: Treatment of symptomatic hyponatremia is not well established. The European guidelines recommend bolus-wise administration of 150 mL of 3% hypertonic saline. This recommendation is, however, based on low level of evidence. DESIGN: Observational study. METHODS: Sixty-two consecutive hyponatremic patients admitted to the emergency department or intensive care unit of the University Hospital Wuerzburg were divided in subgroups according to treatment (150 mL bolus of 3% hypertonic saline or conventional treatment) and symptom severity. Treatment target was defined as an increase in serum sodium by 5-10 mEq/L within first 24 h and maximum 8 mEq/L during subsequent 24 h. RESULTS: Thirty-three out of sixty-two patients (53%) were presented with moderate symptoms and 29/62 (47%) with severe symptoms. Thirty-six were treated with hypertonic saline and 26 conventionally. In the hypertonic saline group, serum sodium increased from 116 ± 7 to 123 ± 6 (24 h) and 127 ± 6 mEq/L (48 h) and from 121 ± 6 to 126 ± 5 and 129 ± 4 mEq/L in the conventional group, respectively. Overcorrection at 24 h occurred more frequent in patients with severe symptoms than with moderate symptoms (38% vs 6%, P < 0.05). Diuresis correlated positively with the degree of sodium overcorrection at 24 h (r = 0.6, P < 0.01). Conventional therapies exposed patients to higher degrees of sodium fluctuations and an increased risk for insufficient sodium correction at 24 h compared to hypertonic saline (RR: 2.8, 95% CI: 1.4-5.5). CONCLUSION: Sodium increase was more constant with hypertonic saline, but overcorrection rate was high, especially in severely symptomatic patients. Reducing bolus-volume and reevaluation before repeating bolus infusion might prevent overcorrection. Symptoms caused by hypovolemia can be misinterpreted as severely symptomatic hyponatremia and diuresis should be monitored.

Associations between mild hyponatremia and geriatric syndromes in outpatient settings.

PURPOSE: The impact of mild hyponatremia on geriatric syndromes is not clear. Our aim was to determine associations between mild hyponatremia and results of comprehensive geriatric assessment tools in outpatient settings. METHODS: We reviewed medical records of 1255 consecutive outpatient elderly subjects and compared results of comprehensive geriatric assessment measures among patients with mild hyponatremia (serum Na+ 130-135 mEq/L) versus normonatremia (serum Na+ 136-145 mEq/L). The comprehensive geriatric assessment measures included the Basic and Instrumental Activities of Daily Living, Mini Mental State Examination, Geriatric Depression Score, Tinetti Mobility Test, the Timed Up&Go Test, the Mini Nutritional Assessment, the handgrip test, the Insomnia Severity Index, polypharmacy, recurrent falls, urinary incontinence, orthostatic hypotension, and nocturia. RESULTS: Of the 1255 patients, 855 were female (68.1%), and the mean age was 73.7 ± 8.3 years. Mild hyponatremia was detected in 108 patients (8.6%). The median serum sodium was 140.5 [interquartile range (IQR) 138.4-141.8] versus 133.8 [IQR, 132.3-134.2] in normonatremia and mild hyponatremia groups, respectively (p < 0.001). The only significant difference for comorbidities between normonatremia and mild hyponatremia groups was the frequency of hypertension (66.9% versus 76.7%, respectively (p = 0.041). None of the comprehensive geriatric assessment tools conferred a significant association with mild hyponatremia. Of the 1061 subjects with available survival data, 96 (9.0%) deceased within 3-4 years of follow-up (p = 0.742). Hyponatremia as an independent variable did not have a significant effect on mortality in univariate logistic regression analysis (OR 1.13, 95% CI 0.55-2.33, p = 0.742). CONCLUSION: Mild hyponatremia does not apparently affect results of geriatric assessments significantly. Whether particular causes of hyponatremia may have different impacts should be tested in further studies.

Symptomatology of carbamazepine- and oxcarbazepine-induced hyponatremia in people with epilepsy.

OBJECTIVE: To ascertain whether adverse effects experienced by people taking carbamazepine or oxcarbazepine could be attributed to carbamazepine- or oxcarbazepine-induced hyponatremia (COIH). METHODS: We performed an observational study, collecting data between 2017 and 2019 on serum sodium levels and adverse effects retrospectively in people with epilepsy while receiving treatment with either carbamazepine (CBZ) or oxcarbazepine (OXC). We defined hyponatremia as sodium level ≤134 mEq/L and severe hyponatremia as sodium level ≤128 mEq/L. Adverse effects experienced were compared between groups of individuals with and without hyponatremia. RESULTS: A total of 1370 people using CBZ or OXC were identified, of whom 410 had at least one episode of hyponatremia. We checked for symptoms related to the use of CBZ and OXC in 710 people (410 with and 300 without hyponatremia) and found relevant information in 688. Adverse effects occurred in 65% of people with hyponatremia compared to 21% with normal sodium levels (odds ratio [OR] 7.5, P ≤ .001) and in 83% of people with severe hyponatremia compared to 55% in those with mild hyponatremia (P ≤ .001). Significant predictors of adverse effects were the drug (OXC vs CBZ), and the number of concomitant anti-seizure medications. Dizziness (28% vs 6%), tiredness (22% vs 7%), instability (19% vs 3%), and diplopia (16% vs 4%) were reported more often in the hyponatremia group than in patients with normal levels. SIGNIFICANCE: People with COIH had a 7-fold increased risk of developing adverse effects during treatment. Clinicians should consider ascertainment of sodium levels in patients taking CBZ and OXC and act upon findings.