BACKGROUND: The prior trials investigating triple-H therapy for preventing delayed cerebral ischemia (DCI) enrolled patients with aneurysmal subarachnoid hemorrhage (aSAH) who underwent early aneurysm therapy within 3 days. However, surgical clipping might be performed during 4-7 days that high incidence cerebral vasospasm is likely. We examined effects of hypervolemia-augmented blood pressure (HV-ABP) protocol on DCI prevention when clipping was delayed.
METHODS: The study enrolled aSAH patients hospitalized during 2013-2019 who underwent clipping 4-7 days after rupture in a university hospital in Thailand. DCI and secondary outcomes were compared among patients who achieved the HV-ABP protocol (3-5 L/day fluid intake and 140-180 mmHg systolic blood pressure maintained for 72 hours postoperatively) and those who did not. The intervention-outcome associations were estimated using logistic regression for the whole group and a patient subgroup with similar propensity scores (PS) for protocol achievement.
RESULTS: One hundred seventy-seven aSAH patients were clipped 4-7 days after rupture; 97 patients (54.8%) achieved the HV-ABP protocol, while 80 patients (45.2%) did not. One hundred twenty-two patients with one-to-one PS matching reduced the originally unequal patient characteristics. The observed DCI was lower in patients with protocol-achieved (8.3%) than in their nonachieved counterparts (22.5%). This resulted in an association with the HV-ABP intervention with adjusted odds ratios of 0.201 (95% confidence interval, 0.066-0.613) in the whole sample and 0.228 (0.065-0.794) in the PS-matched subsample. No statistically significant differences in the secondary outcomes were found.
CONCLUSIONS: Achieving the targets recommended in the HV-ABP protocol was associated with reducing the DCI incidence in patients with aSAH who underwent delayed clipping.

BACKGROUND: Early fluid management in patients with advanced chronic kidney disease (CKD) and sepsis-induced hypotension is challenging with limited evidence to support treatment recommendations. We aimed to compare an early restrictive versus liberal fluid management for sepsis-induced hypotension in patients with advanced CKD.
METHODS: This post-hoc analysis included patients with advanced CKD (eGFR of less than 30 mL/min/1.73 m2 or history of end-stage renal disease on chronic dialysis) from the crystalloid liberal or vasopressor early resuscitation in sepsis (CLOVERS) trial. The primary endpoint was death from any cause before discharge home by day 90.
RESULTS: Of 1563 participants enrolled in the CLOVERS trial, 196 participants had advanced CKD (45% on chronic dialysis), with 92 participants randomly assigned to the restrictive treatment group and 104 assigned to the liberal fluid group. Death from any cause before discharge home by day 90 occurred significantly less often in the restrictive fluid group compared with the liberal fluid group (20 [21.7%] vs. 41 [39.4%], HR 0.5, 95% CI 0.29-0.85). Participants in the restrictive fluid group had more vasopressor-free days (19.7 ± 10.4 days vs. 15.4 ± 12.6 days; mean difference 4.3 days, 95% CI, 1.0-7.5) and ventilator-free days by day 28 (21.0 ± 11.8 vs. 16.5 ± 13.6 days; mean difference 4.5 days, 95% CI, 0.9-8.1).
CONCLUSIONS: In patients with advanced CKD and sepsis-induced hypotension, an early restrictive fluid strategy, prioritizing vasopressor use, was associated with a lower risk of death from any cause before discharge home by day 90 as compared with an early liberal fluid strategy.
BACKGROUND: NCT03434028 (2018-02-09), BioLINCC 14149.

Fluid overload in hemodialysis patients (HD) has been proven to be associated with inflammation. Elevated levels of the pro-inflammatory cytokine interleukin-6 (IL-6) appear to be inadequately counterbalanced by the anti-inflammatory cytokine interleukin-10 (IL-10). We initiated a cross-sectional study enrolling 40 HD patients who were categorized by a bioimpedance measurement in normovolemic (N; 23) and hypervolemic (H; 17) groups to test whether IL-10- and IL-6-related signal transduction pathways (signal transducer of transcript 3: STAT3) and/or a post-transcriptional regulating mechanism (miR-142) are impaired by hypervolemia. IL-10/IL-6 transcript and protein production by PBMCs (peripheral blood mononuclear cells) were determined. Phospho-flow cytometry was used to detect the phosphorylated forms of STAT3 (pY705 and pS727). miR-142-3p/5p levels were detected by qPCR. Hypervolemic patients were older, more frequently had diabetes, and showed higher CRP levels. IL-10 transcripts were elevated in H patients but not IL-10 protein levels. In spite of the elevated mRNA expression of the suppressor of cytokine expression 3 (SOCS3), IL-6 mRNA and protein expression were increased in immune cells of H patients. The percentage of cells staining positive for STAT3 (pY705) were comparable in both groups; in STAT3 (pS727), however, the signal needed for full transactivation was decreased in H patients. miR-142-3p, a proven target of IL-10 and IL-6, was significantly elevated in H patients. Insufficient phosphorylation of STAT3 may impair inflammatory and anti-inflammatory cytokine signaling. How far degradative mechanisms induced by elevated miR-142-3p levels contribute to an inefficient anti-inflammatory IL-10 signaling remains elusive.

Hypervolemia is associated with inflammation in hemodialysis (HD) patients. How hypervolemia triggers inflammation is not entirely known. We initiated a cross-sectional study enrolling 40 hemodialysis patients who were categorized into normovolemic (N; 23) and hypervolemic (H; 17) groups by bioimpedance measurement. A caspase activity assay in combination with a specific caspase-4 inhibitor was used to detect caspase-4 activity in isolated peripheral blood mononuclear cells (PBMCs). Transcription factors RelA (pS529) and RelB (pS552) were analyzed by phospho-flow cytometry. Serum endotoxins were detected by an amebocyte lysate-based assay, and IL-6 (interleukin-6) and TNF-α (Tumor necrosis factor-α) gene expression were detected using the ELISA technique. Hypervolemic patients were older, more frequently had diabetes and showed increased CRP and IL-6 levels. Caspase-4 activity, which is linked to intracellular endotoxin detection, was significantly elevated in H patients. While the frequency of RelA-expressing immune cells and the expression density in these cells did not differ, the monocytic frequency of cells positively stained for RelB (pS552) was significantly decreased in H patients. Increased caspase-4 activity in H patients may indicate a cause of inflammation in H patients. The post-translational modification of RelB (pS552) is linked to downregulation of NF-kB activity and may indicate the resolution of inflammation, which is more distinct in N patients compared to H patients. Therefore, both higher inflammatory loads and lower inflammatory resolution capacities are characteristics of H patients.

BACKGROUND: Heart failure (HF) is associated with high mortality, morbidity, and frequent hospitalizations due to acute HF (AHF) and requires immediate diagnosis and individualized therapy. Some differences between acutely decompensated chronic heart failure (ADCHF) and de novo HF (dnHF) patients in terms of clinical profile, comorbidities, and outcomes have been previously identified, but the hemodynamics related to both of these clinical states are still not well recognized.
OBJECTIVE: To compare patients hospitalized with ADCHF to those with dnHF, with a special emphasis on hemodynamic profiles at admission and changes due to hospital treatment.
METHODS: This study enrolled patients who were at least 18 years old, hospitalized due to AHF (both ADCHF and dnHF), and who underwent detailed assessments at admission and at discharge. The patients\' hemodynamic profiles were assessed by impedance cardiography (ICG) and characterized in terms of heart rate (HR), blood pressure (BP), systemic vascular resistance index (SVRI), cardiac index (CI), stroke index (SI), and thoracic fluid content (TFC).
RESULTS: The study population consisted of 102 patients, most of whom were men (76.5%), with a mean left ventricle ejection fraction (LVEF) of 37.3 ± 14.1%. The dnHF patients were younger than the ADCHF group and more frequently presented with palpitations (p = 0.041) and peripheral hypoperfusion (p = 0.011). In terms of hemodynamics, dnHF was distinguished by higher HR (p = 0.029), diastolic BP (p = 0.029), SVRI (p = 0.013), and TFC (only numeric, p = 0.194) but lower SI (p = 0.043). The effect of hospital treatment on TFC was more pronounced in dnHF than in ADCHF, and this was also true of N-terminal pro-brain natriuretic peptide (NT-proBNP) and body mass. Some intergroup differences in the hemodynamic profile observed at admission persisted until discharge: higher HR (p = 0.002) and SVRI (trend, p = 0.087) but lower SI (p < 0.001) and CI (p = 0.023) in the dnHF group.
CONCLUSIONS: In comparison to ADCHF, dnHF is associated with greater tachycardia, vasoconstriction, depressed cardiac performance, and congestion. Despite more effective diuretic therapy, other unfavorable hemodynamic features may still be present in dnHF patients at discharge.

BACKGROUND: Elevated N-terminal pro B-type natriuretic peptide (NT-proBNP) is a potent predictor of adverse outcomes in hemodialysis initiation. These patients often experience intradialytic hypotension, which may partially reflect cardiac dysfunction, but the association of NT-proBNP with intradialytic hypotension is not clear.
METHODS: We performed a post hoc analysis of a randomized trial that tested mannitol versus placebo in 52 patients initiating hemodialysis (NCT01520207). NT-proBNP was measured prior to the first and third sessions (n = 87). Mixed-effects models (adjusting for randomized treatment, sex, race, age, diabetes, heart failure, catheter use, pre-dialysis systolic blood pressure, pre-dialysis weight, ultrafiltration volume, serum sodium, bicarbonate, urea nitrogen, phosphate, albumin, hemoglobin, and session length) were fit to examine the association of NT-proBNP with systolic blood pressure decline (pre-dialysis minus nadir systolic blood pressure). Additionally, mixed-effects Poisson models were fit to examine the association with intradialytic hypotension (≥20 mmHg decline in systolic blood pressure).
RESULTS: Mean age was 55 ± 16 years; 33% had baseline heart failure. The median NT-proBNP was 5498 [25th-75th percentile 2011, 14,790] pg/mL; 26 sessions (30%) were complicated by intradialytic hypotension. In adjusted models, each unit higher log-NT-proBNP was associated with 6.0 mmHg less decline in systolic blood pressure (95%CI -9.2 to -2.8). Higher pre-dialysis NT-proBNP, per log-unit, was associated with a 52% lower risk of intradialytic hypotension (IRR 0.48, 95%CI 0.23-0.97), without evidence for effect modification by randomized treatment (P-interaction = 0.17).
CONCLUSIONS: In patients initiating hemodialysis, higher NT-proBNP is associated with less decline in intradialytic systolic blood pressure and lower risk of intradialytic hypotension. Future studies should investigate if higher pre-dialysis NT-proBNP levels may identify patients who might tolerate more aggressive ultrafiltration.

To assess the efficacy and safety of urea in patients with hyponatremia and heart failure (HF).
This is a retrospective observational analytical study of patients with HF and hyponatremia (Na+ <135mmol/L). Forty-nine patients treated with urea and 47 patients who did not receive urea, all under standard treatment (according to usual clinical practice) for HF, were included and followed up at Álvaro Cunqueiro Hospital in Vigo (Spain) between January 2013 and May 2022. The study evaluated the normalization of sodium levels (Na >135mmol/L). The initial natremia at the start of oral urea treatment was 127±5.22 mmol/L, at 24h the sodium level was 128±2.47 (P<.009), and the mean on the day of normalization was 135.19±4.23mmol/L (P<.005). The average number of days to achieve sodium normalization was 5.03±2.37 days. The initial uremia at the start of urea treatment was 73±46.93mg/dL, and the mean on the day of Na+ normalization was 116.05±63.64mg/dL (P<.002). The average oral urea dose was 22.5g/day. No relevant adverse effects were observed, nor were there significant changes in creatinine levels.
Oral urea treatment, when added to standard treatment for short periods of time, is safe and effective in correcting natremia in patients with hypervolemic HF with hyponatremia.

There have been anecdotal observations of rhinorrhea as an isolated symptom indicating volume overload and impending congestive heart failure (CHF). We present a case of apparent cardiogenic rhinorrhea presaging acute systolic CHF, with hemodynamics supported by thoracic impedance data (Medtronic OptiVol 2.0).

Preventing hypertension by restricting dietary salt intake, sodium chloride, is well established in public health policy, but a pathophysiological mechanism has yet to explain the controversial clinical finding that some individuals have a greater risk of hypertension from exposure to salt intake, termed salt-sensitive hypertension. The present perspective paper synthesizes interdisciplinary findings from the research literature and offers novel insights proposing that the pathogenesis of salt-sensitive hypertension is mediated by interaction of salt-induced hypervolemia and phosphate-induced vascular calcification. Arterial stiffness and blood pressure increase as calcification in the vascular media layer reduces arterial elasticity, preventing arteries from expanding to accommodate extracellular fluid overload in hypervolemia related to salt intake. Furthermore, phosphate has been found to be a direct inducer of vascular calcification. Reduction of dietary phosphate may help reduce salt-sensitive hypertension by lowering the prevalence and progression of vascular calcification. Further research should investigate the correlation of vascular calcification with salt-sensitive hypertension, and public health recommendations to prevent hypertension should encourage reductions of both sodium-induced hypervolemia and phosphate-induced vascular calcification.

Hyponatremia affects patients in various settings. Nurse practitioners often face challenges in the evaluation and treatment of hyponatremia, due to the existence in the literature of different clinical guidelines and various schematic models. This article describes a systematic approach to diagnosing hyponatremia.