Intermittent Occlusion of the Superior Vena Cava to Improve Hemodynamics in Patients With Acutely Decompensated Heart Failure: The VENUS-HF Early Feasibility Study

Background: Reducing congestion remains a primary target of therapy for acutely decompensated heart failure. The VENUS-HF EFS (VENUS-Heart Failure Early Feasibility Study) is the first clinical trial testing intermittent occlusion of the superior vena cava with the preCARDIA system, a catheter mounted balloon and pump console, to improve decongestion in acutely decompensated heart failure. Methods: In a multicenter, prospective, single-arm exploratory safety and feasibility trial, 30 patients with acutely decompensated heart failure were assigned to preCARDIA therapy for 12 or 24 hours. The primary safety outcome was a composite of major adverse cardiovascular and cerebrovascular events through 30 days. Secondary end points included technical success defined as successful preCARDIA placement, treatment, and removal and reduction in right atrial and pulmonary capillary wedge pressure. Other efficacy measures included urine output and patient-reported symptoms. Results: Thirty patients were enrolled and assigned to receive the preCARDIA system. Freedom from device- or procedure-related major adverse events was observed in 100% (n=30/30) of patients. The system was successfully placed, activated and removed after 12 (n=6) or 24 hours (n=23) in 97% (n=29/30) of patients. Compared with baseline values, right atrial pressure decreased by 34% (17±4 versus 11±5 mm Hg, P <0.001) and pulmonary capillary wedge pressure decreased by 27% (31±8 versus 22±9 mm Hg, P <0.001). Compared with pretreatment values, urine output and net fluid balance increased by 130% and 156%, respectively, with up to 24 hours of treatment ( P <0.01). Conclusions: We report the first-in-human experience of intermittent superior vena cava occlusion using the preCARDIA system to reduce congestion in acutely decompensated heart failure. PreCARDIA treatment for up to 24 hours was well tolerated without device- or procedure-related serious or major adverse events and associated with reduced filling pressures and increased urine output. These results support future studies characterizing the clinical utility of the preCARDIA system. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03836079.

Renal Dysfunction Criteria in Critically Ill Children: The PODIUM Consensus Conference

CONTEXT Renal dysfunction is associated with poor outcomes in critically ill children. OBJECTIVE To evaluate the current evidence for criteria defining renal dysfunction in critically ill children and association with adverse outcomes. To develop contemporary consensus criteria for renal dysfunction in critically ill children. DATA SOURCES PubMed and Embase were searched from January 1992 to January 2020. STUDY SELECTION Included studies evaluated critically ill children with renal dysfunction, performance characteristics of assessment tools for renal dysfunction, and outcomes related to mortality, functional status, or organ-specific or other patient-centered outcomes. Studies with adults or premature infants (≤36 weeks' gestational age), animal studies, reviews, case series, and studies not published in English with inability to determine eligibility criteria were excluded. DATA EXTRACTION Data were extracted from included studies into a standard data extraction form by task force members. RESULTS The systematic review supported the following criteria for renal dysfunction: (1) urine output &lt;0.5 mL/kg per hour for ≥6 hours and serum creatinine increase of 1.5 to 1.9 times baseline or ≥0.3 mg/dL, or (2) urine output &lt;0.5 mL/kg per hour for ≥12 hours, or (3) serum creatinine increase ≥2 times baseline, or (4) estimated glomerular filtration rate &lt;35 mL/minute/1.73 m2, or (5) initiation of renal replacement therapy, or (6) fluid overload ≥20%. Data also support criteria for persistent renal dysfunction and for high risk of renal dysfunction. LIMITATIONS All included studies were observational and many were retrospective. CONCLUSIONS We present consensus criteria for renal dysfunction in critically ill children.

EXTRACORPOREAL DETOXIFICATION METHODS IN THE PATHOGENETIC THERAPY OF OBSTETRIC SEPSIS

Раннее включение НВВГФ в комплексном лечении сепсиса и септического шока приводит к снижению клинических признаков эндотоксикоза, стабилизации гемодинамики в более ранние сроки, что связано с быстрой элиминацией цитокинов, коррекцией осмотического равновесия, увеличением диуреза, благодаря более раннему протезированию гомеостатической функции почек. Early inclusion of NVHF in the complex treatment of sepsis and septic shock leads to a decrease in clinical signs of endotoxicosis, stabilization of hemodynamics at an earlier time, which is associated with rapid elimination of cytokines, correction of osmotic balance, increased urine output due to earlier prosthetics of homeostatic renal function.

Evaluation of Diuretic activity of Fractional Extracts of Ajuga remota Benth (Lamiaceae) in Albino mice

The present study was evaluated the in vivo diuretic activity of fractional extracts of A. remota in albino mice. The dried aqueous crude extracts were subjected to soxhlet extraction by n-butanol, methanol and water solvents. The mice were randomly divided into eleven groups with 8 mice in each. All fractions were administered orally at doses of 250, 500 and 1000 mg/kg to adult male mice, and the positive and negative controls were treated with furosemide (10 mg/kg, p.o) and the vehicle distilled water (2 ml/100 gm of body weight) respectively. The diuretic effect of the extracts was evaluated by measuring urine volume, urinary electrolytes and urinary pH. The result indicates that aqueous and methanolic fractions at 1000 mg/kg dose produced significant (p<0.001) increase in urine output and electrolyte excretion (p<0.001) when compared to control. Additionally, potassium sparing activity (27%, p<0.05) and high natriuretic index (2.7-3.03) were produced by the n-butanol fraction relatively even if it showed minimal effect on urine output. Therefore, from the present study it may be concluded that the compounds present in methanolic and aqueous fraction are responsible for diuretic activity. This finding together with previous results on the aqueous crude extracts provides a quantitative basis for developing a new diuretic medicine from A. remota plant.

Nalfurafine, a G-Protein–Biased KOR (Kappa Opioid Receptor) Agonist, Enhances the Diuretic Response and Limits Electrolyte Losses to Standard-of-Care Diuretics

Nalfurafine is a G-protein–biased KOR (kappa opioid receptor) agonist that produces analgesia and lacks CNS adverse effects. Here, we examined the cardiovascular and renal responses to intravenous and oral nalfurafine alone and in combination with furosemide, hydrochlorothiazide, or amiloride. We hypothesized that nalfurafine, given its distinct mechanism of vasopressin inhibition, would increase urine output to these diuretics and limit electrolyte loss. Following catheterization, conscious Sprague-Dawley rats received an isotonic saline infusion and were then administered an intravenous bolus of nalfurafine, a diuretic, or a combination. Mean arterial pressure, heart rate, and urine output were recorded for 90 minutes. In another study, rats were placed in metabolic cages and administered drug in an oral volume load. Hourly urine samples were then collected for 5 hours. Intravenous and oral nalfurafine produced a marked diuresis, antinatriuresis, antikaliuresis, and a decrease in mean arterial pressure. Compared with diuretic treatment alone, intravenous coadministration with nalfurafine significantly increased urine output to furosemide and hydrochlorothiazide and decreased sodium and potassium excretion. Notably, mean arterial pressure was reduced with nalfurafine/diuretic combination therapy compared to diuretics alone. Similarly, oral coadministration of nalfurafine significantly increased urine output to hydrochlorothiazide and decreased sodium and potassium excretion, whereas combination with furosemide only limited the amount of sodium excreted. Further, both intravenous and oral coadministration of nalfurafine enhanced the diuresis to amiloride and decreased sodium excretion. Together, these findings demonstrate that nalfurafine enhances the diuresis to standard-of-care diuretics without causing an excessive loss of electrolytes, offering a new approach to treat several cardiovascular conditions.