Can Changes in the Plasma Sodium Concentration Be Predicted Based on the Mass Balance of Sodium, Potassium, and Water in the Face of Osmotically Inactive Sodium Storage?

<b><i>Context:</i></b> Alterations in the plasma sodium concentration ([Na⁺]_p) is predicted based on changes in the mass balance of Na⁺, K⁺, and H₂O. However, it is well appreciated that Na⁺ retention results in both osmotically active and osmotically inactive Na⁺ storage and that only osmotically active Na⁺ contributes to the modulation of the [Na⁺]_p^. <b><i>Subject of Review:</i></b> Recent clinical studies suggested that prediction of changes in the [Na⁺]_p based on the mass balance of Na⁺, K⁺, and H₂O is inaccurate since the osmotically inactive Na⁺ storage pool is dynamically regulated. In contrast, animal studies demonstrated that changes in the [Na⁺]_p can be predicted if the total body Na⁺, K⁺, and H₂O were to be accurately accounted for. <b><i>Second Opinion:</i></b> Our analysis demonstrated that alterations in the [Na⁺]_p are predictable at the total body level if all sources of input and output of Na⁺, K⁺, and H₂O can be accurately accounted for despite the paradoxical finding that there are changes in the osmotically inactive Na⁺ storage pool at the tissue level. However, future prospective clinical studies are needed to corroborate the findings in the animal studies. We proposed that the fundamental question as to whether changes in the [Na⁺]_p can be predicted in the face of osmotically inactive sodium storage is best addressed by serial measurements of total body exchangeable Na⁺ and K⁺ and total body water by isotope dilution at different time intervals.

COVID-19 and dysnatremia: A comparison between COVID-19 and non-COVID-19 respiratory illness

Objective: To investigate the occurrence of disorders of water and sodium balance in COVID-19 in our clinic. Methods: In this retrospective chart review, patients were included if a polymerase chain test result for SARS-CoV-2 was obtained and if at least one plasma sodium concentration measurement was obtained during the period from March to June 2020. The occurrences of hyponatremia and hypernatremia were compared between 193 SARS-CoV-2-positive and 138 SARS-CoV-2-negative patients. A χ² test was used to determine statistical significance, and the corresponding p-values were calculated. Results: Hypernatremia was significantly more frequently observed in COVID-19 patients, in 38% (74 of 193), versus only 8% in SARS-CoV-2-negative patients (11 of 138) ( p < 0.01). Hyponatremia was observed in 34% of the included COVID-19 patients (65 of 193) versus 24% of SARS-CoV-2-negative patients (33 of 138). In 12% of all COVID-19 patients (23 of 193), both hyponatremia and hypernatremia were observed at some point during their admission. Among the non-COVID-19 patients, only 4% showed these plasma sodium concentration fluctuations (5 of 138). The mortality rate among the hospitalized COVID-19 patients was 23% (45 of 193). Correcting for double-counting, more than 71% (32 of 45) of the deceased COVID-19 patients developed dysnatremia (hyponatremia, hypernatremia or both) versus 57% (84 out of 148) of the surviving COVID-19 patients. Conclusion: Disorders of water and sodium balance—and especially hypernatremia—seem to be a common occurrence in COVID-19 patients. This has important implications for the treatment of COVID-19 patients.

Fluid Restriction Therapy for Chronic SIAD; Results of a Prospective Randomized Controlled Trial

Context Fluid restriction (FR) is the recommended first-line treatment for syndrome of inappropriate antidiuresis (SIAD), despite the lack of prospective data to support its efficacy. Design A prospective nonblinded randomized controlled trial of FR versus no treatment in chronic SIAD. Interventions and Outcome A total of 46 patients with chronic asymptomatic SIAD were randomized to either FR (1 liter/day) or no specific hyponatremia treatment (NoTx) for 1 month. The primary endpoints were change in plasma sodium concentration (pNa) at days 4 and 30. Results Median baseline pNa was similar in the 2 groups [127 mmol/L (interquartile range [IQR] 126-129) FR and 128 mmol/L (IQR 126–129) NoTx, P = 0.36]. PNa rose by 3 mmol/L (IQR 2-4) after 3 days FR, compared with 1 mmol/L (IQR 0-3) NoTx, P = 0.005. There was minimal additional rise in pNa by day 30; median pNa increased from baseline by 4 mmol/L (IQR 2-6) in FR, compared with 1 mmol/L (IQR 0-1) NoTx, P = 0.04. After 3 days, 17% of FR had a rise in pNa of ≥5 mmol/L, compared with 4% NoTx, RR 4.0 (95% CI 0.66-25.69), P = 0.35. After 3 days, 61% of FR corrected pNa to ≥130 mmol/L, compared with 39% of NoTx, RR 1.56 (95% CI 0.87-2.94), P = 0.24. Conclusion FR induces a modest early rise in pNa in patients with chronic SIAD, with minimal additional rise thereafter, and it is well-tolerated. More than one-third of patients fail to reach a pNa ≥130 mmol/L after 3 days of FR, emphasizing the clinical need for additional therapies for SIAD in some patients.

Perioperative Evolution of Sodium Levels in Cirrhotic Patients Undergoing Liver Transplantation: An Observational, Prospective Study

Background & Aims: Hyponatremia is an important predictor of early death among cirrhotic patients in the orthotopic liver transplantation (OLT) waiting list. Evidence exists that prioritizing OLT waiting list according to the MELD score combined with plasma sodium concentration might prevent pretransplantation death. However, the evolution of plasma sodium concentrations during the perioperative period of OLT is not well known. We aimed to describe the evolution of perioperative sodium concentration during OLT and its relation to perioperative neurohormonal responses.Methods: Twenty-seven consecutive cirrhotic patients who underwent OLT were prospectively included in the study over a period of 27 months. We studied the evolution of plasma sodium levels, the hemodynamics, the neurohormonal response and other biological markers during the perioperative period of OLT.Results: All patients with a hyponatremia before OLT were in the Child C group. None of the patients had acute or chronic renal impairment. Interestingly, in patients with hyponatremia, plasmatic sodium reached normal levels as soon as the injured livers were removed during surgery and the plasma sodium concentration remained within normal ranges 1 day, 7 days, as well as 6 months after surgery.Conclusions: Further investigation of rapid correction and stabilization of sodium levels after OLT, as observed in our study, would be of interest in order to fully understand the mecanisms involved in cirrhosis related hyponatremia, its prognostic value and clinical implications.

Elevated cerebrospinal fluid sodium in hypertensive human subjects with a family history of Alzheimer’s disease

High salt (sodium) intake leads to the development of hypertension despite the fact that plasma sodium concentration ([Na+]) is usually normal in hypertensive human patients. Increased cerebrospinal fluid (CSF) sodium contributes to elevated sympathetic activity and high blood pressure (BP) in rodent models of hypertension. However, whether there is an increased accumulation of sodium in the CSF of humans with chronic hypertension is not well defined. Here, we investigated CSF [Na+] from hypertensive and normotensive human subjects with family histories of Alzheimer’s disease in samples collected in a clinical trial, as spinal tap is not a routine clinical procedure for hypertensive patients. The [Na+] and osmolality in plasma and CSF were measured by flame photometry. Daytime ambulatory BP was monitored while individuals were awake. Participants were deidentified and data were analyzed in conjunction with a retrospective analysis of patient history and diagnosis. We found that CSF [Na+] was significantly higher in participants with high BP compared with normotensive participants; there was no difference in plasma [Na+], or plasma and CSF osmolality between groups. Subsequent multiple linear regression analyses controlling for age, sex, race, and body mass index revealed a significant positive correlation between CSF [Na+] and BP but showed no correlation between plasma [Na+] and BP. In sum, CSF [Na+] was higher in chronic hypertensive individuals and may play a key role in the pathogenesis of human hypertension. Collectively, our findings provide evidence for the clinical significance of CSF [Na+] in chronic hypertension in humans.

Sodium-Based Osmotherapy in Continuous Renal Replacement Therapy: a Mathematical Approach

Cerebral edema, in a variety of circumstances, may be accompanied by states of hyponatremia. The threat of brain injury from hypotonic stress-induced astrocyte demyelination is more common when vulnerable patients with hyponatremia who have end stage liver disease, traumatic brain injury, heart failure, or other conditions undergo overly rapid correction of hyponatremia. These scenarios, in the context of declining urinary output from CKD and/or AKI, may require controlled elevations of plasma tonicity vis-à-vis increases of the plasma sodium concentration. We offer a strategic solution to this problem via sodium-based osmotherapy applied through a conventional continuous RRT modality: predilution continuous venovenous hemofiltration.

Evaluation of intradialytic sodium shifts during sodium controlled hemodialysis

Plasma sodium shifts during hemodialysis treatments can be minimized by application of a sodium control algorithm. The present randomized cross-over trial was designed to apply this option on a large patient cohort and to observe the time course of plasma sodium over the treatment. In one study phase, patients received post-dilution online hemodiafiltration treatments with sodium control over the entire treatment. In the other study phase, patients received isolated ultrafiltration during the first 90 min followed by post-dilution online hemodiafiltration with sodium control for the remainder of the session, with the purpose to follow a possible initial equilibration process without the influence of a diffusive solute transfer. Each phase included six treatments and was delivered in randomized order. Eighty-one patients were enrolled, 77 patients could be analyzed as intention-to-treat population. The difference of the mean plasma sodium concentration between start and end of the treatment was −0.60 mmol/L (confidence interval −0.88 to −0.32) and −0.15 mmol/L (confidence interval −0.43 to 0.13), for sodium control and isolated ultrafiltration during the first 90 min followed by post-dilution online hemodiafiltration with sodium control, respectively. The functionality of the sodium control option could be confirmed and further reproduced in a bigger population of dialysis patients, providing the basis to investigate the clinical benefit of individually adjusting dialysate sodium in further clinical studies.