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Background: The Centers for Medicare and Medicaid Services (CMS) developed the Severe Sepsis and Septic Shock Performance Measure bundle (SEP-1) metric to improve sepsis care, but evidence supporting this bundle is limited and harms secondary to compliance have not been investigated., Objective: This study investigates the effect of an emergency department (ED) sepsis quality-improvement (QI) effort to improve CMS SEP-1 compliance, looking specifically at antibiotic overtreatment and harm from fluid resuscitation., Methods: This was a retrospective observational study conducted between March and July 2021 with patients for whom a sepsis order set was initiated. The primary outcomes included the number of patients treated with antibiotics who were ultimately deemed nonseptic and the number of patients who developed pulmonary edema, with or without need for positive pressure ventilation (PPV), within 48 h of receiving a 30 mL/kg fluid bolus. Data were collected via nonblinded chart reviews, with a free marginal κ-calculation indicating excellent interrater reliability., Results: The study cohort included 273 patients, 170 (62.3%) who were ultimately determined to be septic and 103 (37.7%) who were nonseptic. Of the 103 nonseptic patients, 82 (79.6%) received antibiotics in the ED. Of the 121 patients (44.3%) who received a 30 mL/kg bolus, 5 patients (4.1%) developed pulmonary edema and 0 of 121 patients required PPV within 48 h., Conclusions: The QI effort led to moderate rates of antibiotic overtreatment and very few patients developed pulmonary edema due to a 30 mL/kg fluid bolus., Competing Interests: Declaration of competing interest None., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose of the Review: Progressive intravascular, interstitial, and alveolar fluid overload underlies the transition from compensated to acutely decompensated heart failure and loop diuretics are the mainstay of treatment. Adverse effects and resistance to loop diuretics received much attention while the contribution of a depressed cardiac output to diuretic resistance was downplayed., Recent Findings: Analysis of experience with positive inotropic agents, especially dobutamine, indicates that enhancement of cardiac output is not consistently associated with increased renal blood flow. However, urinary output and renal sodium excretion increase likely due to dobutamine-mediated decrease in renal and systemic reduced activation of sympathetic nervous- and renin-angiotensin-aldosterone system. Mechanical circulatory support with left ventricular assist devices ascertained the contribution of low cardiac output to diuretic resistance and the pathogenesis and progression of kidney disease in acutely decompensated heart failure. Diuretic resistance commonly occurs in acutely decompensated heart failure. However, failure to resolve fluid overload despite high doses of loop diuretics should alert to the presence of a low cardiac output state., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Whether acetazolamide, a carbonic anhydrase inhibitor that reduces proximal tubular sodium reabsorption, can improve the efficiency of loop diuretics, potentially leading to more and faster decongestion in patients with acute decompensated heart failure with volume overload, is unclear., Methods: In this multicenter, parallel-group, double-blind, randomized, placebo-controlled trial, we assigned patients with acute decompensated heart failure, clinical signs of volume overload (i.e., edema, pleural effusion, or ascites), and an N-terminal pro-B-type natriuretic peptide level of more than 1000 pg per milliliter or a B-type natriuretic peptide level of more than 250 pg per milliliter to receive either intravenous acetazolamide (500 mg once daily) or placebo added to standardized intravenous loop diuretics (at a dose equivalent to twice the oral maintenance dose). Randomization was stratified according to the left ventricular ejection fraction (≤40% or >40%). The primary end point was successful decongestion, defined as the absence of signs of volume overload, within 3 days after randomization and without an indication for escalation of decongestive therapy. Secondary end points included a composite of death from any cause or rehospitalization for heart failure during 3 months of follow-up. Safety was also assessed., Results: A total of 519 patients underwent randomization. Successful decongestion occurred in 108 of 256 patients (42.2%) in the acetazolamide group and in 79 of 259 (30.5%) in the placebo group (risk ratio, 1.46; 95% confidence interval [CI], 1.17 to 1.82; P<0.001). Death from any cause or rehospitalization for heart failure occurred in 76 of 256 patients (29.7%) in the acetazolamide group and in 72 of 259 patients (27.8%) in the placebo group (hazard ratio, 1.07; 95% CI, 0.78 to 1.48). Acetazolamide treatment was associated with higher cumulative urine output and natriuresis, findings consistent with better diuretic efficiency. The incidence of worsening kidney function, hypokalemia, hypotension, and adverse events was similar in the two groups., Conclusions: The addition of acetazolamide to loop diuretic therapy in patients with acute decompensated heart failure resulted in a greater incidence of successful decongestion. (Funded by the Belgian Health Care Knowledge Center; ADVOR ClinicalTrials.gov number, NCT03505788.)., (Copyright © 2022 Massachusetts Medical Society.)

Background: Tolvaptan (TLV) is reported to improve diuretic effects in patients with chronic kidney disease (CKD) when furosemide (FUR) is not sufficiently effective. However, it is not clear whether TLV addition is effective for advanced CKD patients with heart failure., Methods: An open-label, parallel-group randomized trial was performed. The subjects were 33 patients with CKD stage G3-G5 who had fluid overload despite taking 20-100 mg/day FUR. They were divided into two groups: a group administered 15 mg/day TLV plus their original FUR dose for 7 days (TLV group), and a group administered 120-200 mg/day FUR (i.e., 100 mg/day over their previous dose) for 7 days (FUR group)., Results: The mean change in urine volume was significantly higher in the TLV group compared to the FUR group (637 ml vs 119 ml; p < 0.05). The difference was greater when the urine osmolality before treatment was high. Serum creatinine was increased only in the FUR group. The incidence of worsening renal function (WRF) was significantly lower in the TLV group (18.8% vs 58.8%; p < 0.05). Serum sodium decreased significantly in the FUR group, but did not change in the TLV group., Conclusions: In patients with advanced CKD with fluid overload, the addition of TLV achieved a significantly higher urine volume with less adverse effects on renal function compared with increasing the dose of FUR. The efficacy and safety of TLV were higher in patients who had higher urine osmolality and lower serum sodium before treatment., Clinical Trial Registration: UMIN000014763., (© 2022. The Author(s).)

Understanding physiologic water balance and homeostasis mechanisms in the neonate is critical for clinicians in the NICU as pathologic fluid accumulation increases the risk for morbidity and mortality. In addition, once this process occurs, treatment is limited. In this review, we will cover fluid homeostasis in the neonate, explain the implications of prematurity on this process, discuss the complexity of fluid accumulation and the development of fluid overload, identify mitigation strategies, and review treatment options., Competing Interests: AUTHOR DISCLOSURE Drs Slagle, Gist, Starr, Hemmelgarn, Goldstein, and Kent have disclosed no financial relationships relevant to this article. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device., (Copyright © 2022 by the American Academy of Pediatrics.)

In Covid-19, systemic disturbances may progress due to development of cytokine storm and dysregulation of and plasma osmolarility due to high release of pro-inflammatory cytokines and neuro-hormonal disorders. Arginine vasopressin (AVP) which is involve in the regulation of body osmotic system, body water content, blood pressure and plasma volume, that are highly disturbed in Covid-19 and linked with poor clinical outcomes. Therefore, this present study aimed to find the potential association between AVP serum level and inflammatory disorders in Covid-19. It has been observed by different recent studies that physiological response due to fever, pain, hypovolemia, dehydration, and psychological stress is characterized by activation release of AVP to counter-balance high blood viscosity in Covid-19 patients. In addition, activated immune cells mainly T and B lymphocytes and released pro-inflammatory cytokines stimulate discharge of stored AVP from immune cells, which in a vicious cycle trigger release of pro-inflammatory cytokines. Vasopressin receptor antagonists have antiviral and anti-inflammatory effects that may inhibit AVP-induced hyponatremia and release of pro-inflammatory cytokines in Covid-19. In conclusion, release of AVP from hypothalamus is augmented in Covid-19 due to stress, high pro-inflammatory cytokines, high circulating AngII and inhibition of GABAergic neurons. In turn, high AVP level leads to induction of hyponatremia, inflammatory disorders, and development of complications in Covid-19 by activation of NF-κB and NLRP3 inflammasome with release of pro-inflammatory cytokines. Therefore, AVP antagonists might be novel potential therapeutic modality in treating Covid-19 through mitigation of AVP-mediated inflammatory disorders and hyponatremia., (Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background: Cisplatin-associated electrolyte dysregulation is a prevalent therapy-related adverse effect. There are numerous electrolyte-supplemented hydration regimens that have been evaluated, however these studies focused on the development of nephrotoxicity. The objective of this study was to characterize the impact of magnesium and potassium-supplemented hydration during cisplatin administration on subsequent magnesium and potassium imbalances., Methods: A single-region retrospective study from central Texas at Baylor Scott & White Cancer Clinics who were treated with two or more cycles of cisplatin were included. Standard hydration for this study was defined as normal saline before and after cisplatin along with potassium chloride 10 mEq and magnesium sulfate 1 g added to the cisplatin bag., Results: A total of 477 patients were included in the study with376 patients receiving the standard hydration. Overall, 17 percent of patients experienced a potassium level below 3.5 mEq/L, but no major depletion was observed. Thirty-three percent of the patients experienced a magnesium level below 1.8 mg/dL, and time to first rescue magnesium supplementation was 4 weeks., Conclusion: Our study demonstrated despite routine magnesium and potassium supplementation in hydration, magnesium imbalances were observed. Potassium levels post cisplatin administration were maintained with minimal routine supplementation in hydration.

Despite evidence highlighting harms of fluid overload, minimal guidance exists on counteraction via utilization of diuretics in the de-resuscitation phase. While diuretics have been shown to decrease net volume and improve clinical outcomes in the critically ill, a lack of standardization surrounding selection of diuretic regimen or monitoring of de-resuscitation exists. Current monitoring parameters of de-resuscitation often rely on clinical signs of fluid overload, end organ recovery and other biochemical surrogate markers which are often deemed unreliable. The majority of evidence suggests that achieving a net-negative fluid balance within 72 h after shock resolution may be of benefit; however, approaches to such goal are uncertain. Loop diuretics are a widely available type of diuretic for removal of volume in patients with sufficient kidney function, with the potential for adjunct diuretics in special circumstances. At present, administration of diuretics within the broad critically ill population fails to find uniformity and often efficacy. Given the lack of randomized controlled trials in this susceptible population, we aim to provide a thorough therapeutic understanding of diuretic pharmacotherapy which is necessary in order to achieve desired goal of fluid balance and improve overall outcomes., Competing Interests: Declaration of Competing Interest The authors have no potential or actual conflicts of interest as it pertains to this work., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objectives: To assess tolvaptan's efficacy and safety in critical care patients with volume overload., Methods: Prospective observational study. Twenty-eight patients in the recovery phase from multiple organ failure and with volume overload refractory to conventional therapy treated with tolvaptan were included., Results: Patients received an initial daily dose of 3.75 (n=1), 7.5 (n=8) and 15 (n=19) mg of tolvaptan. Median treatment duration was 2 days (range: 1 to 12). All patients presented an increase in 24 hours diuresis after the first dose (median increase from baseline (IQR)=1114 (285-1943) mL), with a median net daily fluid loss of 1007 mL (456-2380) mL after 24 hours. High diuretic efficacy (daily fluid loss higher than 0.5 L with tolvaptan first dose) was detected in 18 patients (64.3%). Initial hyponatraemia was present in 16 (57.1%) patients, while overly rapid correction with tolvaptan treatment occurred in two patients without clinical consequences. Two patients presented hypophosphataemia after treatment., Conclusion: Tolvaptan is an effective therapeutic option in critically ill patients with volume overload refractory to conventional diuretics. Further studies are required to evaluate its safety profile and its effect on short-term outcomes and mortality., Competing Interests: Competing interests: PR and MJB have participated in training courses with funding from the laboratory Otsuka Pharmaceutical Europe., (© European Association of Hospital Pharmacists 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Infants after cardiopulmonary bypass are exposed to increasing inflammatory mediator release and are at risk of developing fluid overload. The aim of this pilot study was to evaluate the impact of passive peritoneal drainage on achieving negative fluid balance and its ability to dispose of inflammatory cytokines., Methods: From September 2014 to November 2016, infants undergoing STAT category 3, 4, and 5 operations were randomized to receive or not receive intraoperative prophylactic peritoneal drain. We analyzed time to negative fluid balance and perioperative variables for each group. Pro- and anti-inflammatory cytokines were measured from serum and peritoneal fluid in the passive peritoneal drainage group and serum in the control group postoperatively., Results: Infants were randomized to prophylactic passive peritoneal drain group (n = 13) and control (n = 12). The groups were not significantly different in pre- and postoperative peak lactate levels, postoperative length of stay, and mortality. Peritoneal drain patients reached time to negative fluid balance at a median of 1.42 days (interquartile range [IQR]: 1.00-2.91), whereas the control at 3.08 (IQR: 1.67-3.88; P = .043). Peritoneal drain patients had lower diuretic index at 72 hours, median of 2.86 (IQR: 1.21-4.94) versus 6.27 (IQR: 4.75-11.11; P = .006). Consistently, tumor necrosis factor-α, interleukin (IL)-4, IL-6, IL-8, IL-10, and interferon-γ were present at higher levels in peritoneal fluid than serum at 24 and 72 hours. However, serum cytokine levels in peritoneal drain and control group, at 24 and 72 hours postoperatively, did not differ significantly., Conclusions: The prophylactic passive peritoneal drain patients reached negative fluid balance earlier and used less diuretic in early postoperative period. The serum cytokine levels did not differ significantly between groups at 24 and 72 hours postoperatively. However, there was no significant difference in mortality and postoperative length of stay.

Objective: Administration of diuretics has been shown to assist fluid management and improve clinical outcomes in the critically ill post-shock resolution. Current guidelines have not yet included standardization or guidance for diuretic-based de-resuscitation in critically ill patients. This study aimed to evaluate the impact of a multi-disciplinary protocol for diuresis-guided de-resuscitation in the critically ill., Methods: This was a pre-post single-center pilot study within the medical intensive care unit (ICU) of a large academic medical center. Adult patients admitted to the Medical ICU receiving mechanical ventilation with either (1) clinical signs of volume overload via chest radiography or physical exam or (2) any cumulative fluid balance ≥ 0 mL since hospital admission were eligible for inclusion. Patients received diuresis per clinician discretion for a 2-year period (historical control) followed by a diuresis protocol for 1 year (intervention). Patients within the intervention group were matched in a 1:3 ratio with those from the historical cohort who met the study inclusion and exclusion criteria., Results: A total of 364 patients were included, 91 in the protocol group and 273 receiving standard care. Protocolized diuresis was associated with a significant decrease in 72-h post-shock cumulative fluid balance [median, IQR - 2257 (- 5676-920) mL vs 265 (- 2283-3025) mL; p < 0.0001]. In-hospital mortality in the intervention group was lower compared to the historical group (5.5% vs 16.1%; p = 0.008) and higher ICU-free days (p = 0.03). However, no statistically significant difference was found in ventilator-free days, and increased rates of hypernatremia and hypokalemia were demonstrated., Conclusions: This study showed that a protocol for diuresis for de-resuscitation can significantly improve 72-h post-shock fluid balance with potential benefit on clinical outcomes.

Background: We have previously investigated the fate of administered bicarbonate infused as a hypertonic solution in animals with each of the 4 chronic acid-base disorders. Those studies did not address the fate of sodium, the coadministered cation., Methods: We examined baseline total body water (TBW), Na+ space, HCO3- space, and urinary sodium and bicarbonate excretion after acute hypertonic NaHCO3 infusion (1-N solution, 5 mmol/kg body weight) in dogs with each of the 4 chronic acid-base disorders. Observations were made at 30, 60, and 90 min postinfusion. Retained sodium that remains osmotically active distributes in an apparent space that approximates TBW. Na+ space that exceeds TBW uncovers nonosmotic sodium storage., Results: Na+ space approximated TBW at all times in normal and hyperbicarbonatemic animals (metabolic alkalosis and respiratory acidosis), but exceeded TBW by ~30% in hypobicarbonatemic animals (metabolic acidosis and respiratory alkalosis). Such osmotic inactivation was detected at 30 min and remained stable. The pooled data revealed that Na+ space corrected for TBW was independent of the initial blood pH but correlated with initial extracellular bicarbonate concentration (y = -0.01x + 1.4, p= 0.002). The fate of administered sodium and bicarbonate (internal distribution and urinary excretion) was closely linked., Conclusions: This study demonstrates that hypobicarbonatemic animals have a Na+ space that exceeds TBW after an acute infusion of hypertonic NaHCO3 indicating osmotic inactivation of a fraction of retained sodium. In addition to an expanded Na+ space, these animals have a larger HCO3- space compared with hyperbicarbonatemic animals. Both phenomena appear to reflect the wider range of titration of nonbicarbonate buffers (Δ pH) occurring during NaHCO3- loading whenever initial [HCO3-]e is low. The data indicate that the fate of administered bicarbonate drives the internal distribution and the external disposal of sodium, the co-administered cation, and is responsible for the early, but non-progressive, osmotic inactivation of a fraction of the retained sodium., (© 2020 S. Karger AG, Basel.)

Aim: Sodium-glucose cotransporter 2 (SGLT2) inhibitors are an antihyperglycemic drug with diuretic properties. We recently reported that an SGLT2 inhibitor ameliorated extracellular fluid expansion with a transient increase in urinary Na + excretion. However, the effects of SGLT2 inhibitors on fluid distribution in comparison to conventional diuretics remain unclear., Methods: Forty chronic kidney disease patients with fluid retention (average estimated glomerular filtration rate 29.2 ± 3.2 mL/min per 1.73 m 2 ) were divided into the SGLT2 inhibitor dapagliflozin (DAPA), loop diuretic furosemide (FR) and vasopressin V2 receptor antagonist tolvaptan (TLV). The body fluid volume was measured on days 0 and 7 using a bioimpedance analysis device., Results: In all three groups, body weight was significantly and similarly decreased, and urine volume numerically increased for 7 days. Bioimpedance analysis showed that the changes in intracellular water were similar, but that there were significant changes in the extracellular water (ECW) (DAPA -8.4 ± 1.7, FR -12.5 ± 1.3, TLV -7.4 ± 1.5%, P = 0.048). As a result, the change in the ratio of ECW to total body water in the DAPA group was significantly smaller than that in the FR group, but numerically larger than that in the TLV group (DAPA -1.5 ± 0.5, FR -3.6 ± 0.5, TLV -0.5 ± 0.4%, P < 0.001)., Conclusion: Sodium-glucose cotransporter 2 inhibitor DAPA predominantly decreased the ECW with a mild increase in urine volume, but the change in the ECW/total body water was smaller than that in patients treated with FR, and larger than that in patients treated with TLV, suggesting that the effects of SGLT2 inhibitors on fluid distribution may differ from those of conventional diuretics., (© 2018 Asian Pacific Society of Nephrology.)

The genetic background of a mouse strain determines its susceptibility to disease. C57BL/6J and Balb/CJ are two widely used inbred mouse strains that we found react dramatically differently to angiotensin II and high-salt diet (ANG II + Salt). Balb/CJ show increased mortality associated with anuria and edema formation while C57BL/6J develop arterial hypertension but do not decompensate and die. Clinical symptoms of heart failure in Balb/CJ mice gave the hypothesis that ANG II + Salt impairs cardiac function and induces cardiac remodeling in male Balb/CJ but not in male C57BL/6J mice. To test this hypothesis, we measured cardiac function using echocardiography before treatment and every day for 7 days during treatment with ANG II + Salt. Interestingly, pulsed wave Doppler of pulmonary artery flow indicated increased pulmonary vascular resistance and right ventricle systolic pressure in Balb/CJ mice, already 24 h after ANG II + Salt treatment was started. In addition, Balb/CJ mice showed abnormal diastolic filling indicated by reduced early and late filling and increased isovolumic relaxation time. Furthermore, Balb/CJ exhibited lower cardiac output compared with C57BL/6J even though they retained more sodium and water, as assessed using metabolic cages. Left posterior wall thickness increased during ANG II + Salt treatment but did not differ between the strains. In conclusion, ANG II + Salt treatment causes early restriction of pulmonary flow and reduced left ventricular filling and cardiac output in Balb/CJ, which results in fluid retention and peripheral edema. This makes Balb/CJ a potential model to study the adaptive capacity of the heart for identifying new disease mechanisms and drug targets.

Introduction: Balanced fluid replacement solutions can possibly reduce the risks for electrolyte imbalances, for acid-base imbalances, and thus for renal failure. To assess the intraoperative change of base excess (BE) and chloride in serum after treatment with either a balanced gelatine/electrolyte solution or a non-balanced gelatine/electrolyte solution, a prospective, controlled, randomized, double-blind, dual centre phase III study was conducted in two tertiary care university hospitals in Germany., Material and Methods: 40 patients of both sexes, aged 18 to 90 years, who were scheduled to undergo elective abdominal surgery with assumed intraoperative volume requirement of at least 15 mL/kg body weight gelatine solution were included. Administration of study drug was performed intravenously according to patients need. The trigger for volume replacement was a central venous pressure (CVP) minus positive end-expiratory pressure (PEEP) <10 mmHg (CVP <10 mmHg). The crystalloid:colloid ratio was 1:1 intra- and postoperatively. The targets for volume replacement were a CVP between 10 and 14 mmHg minus PEEP after treatment with vasoactive agent and mean arterial pressure (MAP) > 65 mmHg., Results: The primary endpoints, intraoperative changes of base excess -2.59 ± 2.25 (median: -2.65) mmol/L (balanced group) and -4.79 ± 2.38 (median: -4.70) mmol/L (non-balanced group)) or serum chloride 2.4 ± 1.9 (median: 3.0) mmol/L and 5.2 ± 3.1 (median: 5.0) mmol/L were significantly different (p = 0.0117 and p = 0.0045, respectively). In both groups (each n = 20) the investigational product administration in terms of volume and infusion rate was comparable throughout the course of the study, i.e. before, during and after surgery., Discussion: Balanced gelatine solution 4% combined with a balanced electrolyte solution demonstrated significant smaller impact on blood gas analytic parameters in the primary endpoints BE and serum chloride when compared to a non-balanced gelatine solution 4% combined with NaCl 0.9%. No marked treatment differences were observed with respect to haemodynamics, coagulation and renal function., Trial Registration: ClinicalTrials.gov (NCT01515397) and clinicaltrialsregister.eu, EudraCT number 2010-018524-58., Competing Interests: This study was supported by a restricted grant of B. Braun Meldungen AG, Germany. GM received honoria for consulting and research grants by B. Braun Melsungen AG and Adrenomed, lecture fees by B. Braun Melsungen AG. KZ has received payments for lectures and consulting from B. Braun Melsungen AG and Fresenius Kabi as well as funding for a clinical trial. PM has received payments for lectures and consulting from B. Braun Melsungen AG and Fresenius Kabi as well as funding for a clinical trial. RR received honoria for consulting from Fresenius; he received lecture fees from Fresenius and B. Braun Melsungen AG and is Editor-in-Chief of Der Anaesthesist and editor of the European Journal of Anaesthesiology. TS received honoria for board membership by Astellas Pharma GmbH, lecture fees by Astellas Pharma, Bayer Health Care, B. Braun Melsungen AG and Astra Zeneca and research grants by Bayer Health Care and Astellas Pharma GmbH. All the other authors declare that they have no competing interests. This does not alter our adherence to PLOS One policies on sharing data and materials.

ADH is a hormone secreted by neurohypophysis that plays different roles based on the target organ. At the renal level, this peptide is capable of causing electrolyte-free water absorption, thus playing a key role in the hydro-electrolytic balance. There are pathologies and disorders that jeopardize this balance and, in this field, ADH receptor inhibitors such as Vaptans could play a key role. By inhibiting the activation pathway of vasopressin, they are potentially useful in euvolemic and hypervolemic hypotonic hyponatremia. However, clinical trials in heart failure have not given favourable results on clinical outcomes. Even in SIADH, despite their wide use, there is no agreement by experts on their use. Since vaptans inhibit the cAMP pathway in tubular cells, their use has been proposed to inhibit cystogenesis. A clinical trial has shown favourable effects on ADPKD progression. Because vaptans have been shown to be effective in models of renal cysts disorders other than ADPKD, their use has been proposed in diseases such as nephronophthisis and recessive autosomal polycystic disease. Other possible uses of vaptans could be in kidney transplantation and cardiorenal syndrome. Due to the activity of ADH in coagulation and haemostasis, ADH's activation pathway by Desmopressin Acetate could be a useful strategy to reduce the risk of bleeding in biopsies in patients with haemorrhagic risk., (Copyright by Società Italiana di Nefrologia SIN, Rome, Italy.)

Background: Large networks of interstitial glycosaminoglycans help to regulate water and electrolyte homeostasis. The relation between dermal interstitial alterations and occurrence of edema in heart failure patients with reduced ejection fraction (HFrEF) is unknown. We hypothesize that in HFrEF patients (1) interstitial glycosaminoglycan density is increased, (2) changes in the interstitial glycosaminoglycan network are associated with interstitial fluid accumulation, and (3) there is a link between the interstitial glycosaminoglycan network and the renin-angiotensin-aldosterone system., Methods and Results: Two punch biopsies of the skin were obtained in healthy subjects (n=18) and HFrEF patients (n=29). Alcian blue staining and immunostaining for the angiotensin II type 1 receptor was performed. After obtaining tissue water content, total interstitial glycosaminoglycan (uronic acid) and sulfated glycosaminoglycan were quantified. A venous blood sample, clinical examination, and echocardiography were obtained. A significantly higher interstitial glycosaminoglycan content was observed in HFrEF patients compared with healthy subjects (uronic acid: 13.0±4.2 versus 9.6±1.6 μg/mg; P =0.002; sulfated glycosaminoglycan: 14.1 [11.7; 18.1] versus 10.0 [9.1; 10.8] μg/mg; P <0.001). Uronic acid and sulfated glycosaminoglycan density were strongly associated with tissue water content and peripheral edema (uronic acid: ρ=0.66; P <0.0001 and sulfated glycosaminoglycan: τ=0.58; P <0.0001). Expression of the angiotensin II type 1 receptor was found on dermal cells, although use of angiotensin-converting enzyme inhibitors/angiotensin receptor blocker was associated with significantly lower levels of interstitial glycosaminoglycans in HFrEF patients., Conclusions: Interstitial glycosaminoglycan concentration is significantly increased in HFrEF patients compared with healthy subjects and correlated with tissue water content and clinical signs of volume overload. A better appreciation of the interstitial compartment might improve management of volume overload in HF., (© 2018 American Heart Association, Inc.)

Introduction and Objectives: The optimal treatment of patients with acute heart failure (AHF) and cardiorenal syndrome type 1 (CRS-1) is far from being well-defined. Arterial hypoperfusion in concert with venous congestion plays a crucial role in the pathophysiology of CRS-I. Plasma carbohydrate antigen 125 (CA125) has emerged as a surrogate of fluid overload in AHF. The aim of this study was to evaluate the clinical usefulness of CA125 for tailoring the intensity of diuretic therapy in patients with CRS-1., Methods: Multicenter, open-label, parallel clinical trial, in which patients with AHF and serum creatinine ≥ 1.4mg/dL on admission will be randomized to: a) standard diuretic strategy: titration-based on conventional clinical and biochemical evaluation, or b) diuretic strategy based on CA125: high dose if CA125 > 35 U/mL, and low doses otherwise. The main endpoint will be renal function changes at 24 and 72hours after therapy initiation. Secondary endpoints will include: a) clinical and biochemical changes at 24 and 72hours, and b) renal function changes and major clinical events at 30 days., Results: The results of this study will add important knowledge on the usefulness of CA125 for guiding diuretic treatment in CRS-1. In addition, it will pave the way toward a better knowledge of the pathophysiology of this challenging situation., Conclusions: We hypothesize that higher levels of CA125 will identify a patient population with CRS-1 who could benefit from the use of a more intense diuretic strategy. Conversely, low levels of this glycoprotein could select those patients who would be harmed by high diuretic doses., (Copyright © 2017 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)

Platinum chemotherapy, particularly cisplatin, is commonly associated with electrolyte imbalances, including hypomagnesemia, hypokalemia, hypophosphatemia, hypocalcemia and hyponatremia. The corpus of literature on these dyselectrolytemias is large; the objective of this review is to synthesize the literature and summarize the mechanisms responsible for these particular electrolyte disturbances in the context of platinum-based treatment as well as to present the clinical manifestations and current management strategies for oncologists and primary care physicians, since the latter are increasingly called on to provide care for cancer patients with medical comorbidities. Correct diagnosis and effective treatment are essential to improved patient outcomes.

Background: There is no echocardiographic predictor of the effectiveness of tolvaptan in patients with heart failure (HF). The aim of this study was to investigate the echocardiographic predictor of responders to tolvaptan in patients with HF., Methods: This observational study consisted of 62 consecutive in-hospital patients with HF who received tolvaptan with volume overload despite standard therapies. The echocardiography data were obtained within 1 week before the administration of tolvaptan. Tolvaptan responders were defined as those having a body weight decrease from baseline >1 kg on the morning of day 8., Results: The mean age of the 62 patients was 75.1 ± 13.9 years, and 45 patients (72.6%) were considered to be responders. Tricuspid annular plane systolic excursion (TAPSE) was significantly higher (17.1 ± 3.8 vs. 13.0 ± 3.9 mm; p = 0.0004) and the tricuspid valve regurgitation pressure gradient (33.3 ± 14.6 vs. 44.9 ± 12.2 mmHg; p = 0.007) and estimated right atrium pressure (7.8 ± 4.2 vs. 10.3 ± 4.5 mmHg; p = 0.043) were significantly lower in the Responder group than in the Non-responder group. In a multivariate logistic regression analysis, TAPSE was found to be an independent predictor of response (odds ratio 1.28; 95% confidence interval 1.03-1.60). According to the receiver operating characteristics analysis, the area under the curve of TAPSE was the largest among the parameters measured by echocardiography. The cut-off value for TAPSE to predict responders was determined to be 17.0 mm (sensitivity = 56.8%, specificity = 94.1%)., Conclusions: TAPSE is a simple predictor of the effectiveness of tolvaptan in patients with HF.

Introduction: The relationship between hypertension and fluid overload in pre-dialysis CKD patients need to be elucidated. Current study aimed to find relationship between fluid overload and hypertension along with prescribed diuretic therapy using bioimpedance spectroscopy (BIS)., Methodology: A prospective observational study was conducted by inviting pre-dialysis CKD patients. Fluid overload was assessed by BIS., Results: A total of 312 CKD patients with mean eGFR 24.5 ± 11.2 ml/min/1.73 m 2 were enrolled. Based on OH value ≥7 %, 135 (43.3 %) patients were hypervolemic while euvolemia was observed in 177 (56.7 %) patients. Patients were categorized in different regions of hydration reference plot (HRP) generated by BIS i.e., 5.1 % in region-N (normal BP and fluid status), 20.5 % in region I (hypertensive with severe fluid overload), 29.5 % in region I-II (hypertensive with mild fluid overload), 22 % in region II (hypertensive with normohydration), 10.2 % in region III (underhydration with normal/low BP) and 12.5 % in region IV (normal BP with severe fluid overload). A total of 144 (46 %) patients received diuretics on basis of physician assessment of BP and edema. Maximum diuretics 100 (69.4 %) were prescribed in patients belonging to regions I and I-II of HRP. Interestingly, a similar number of diuretic prescriptions were observed in region II (13 %) and region IV (12 %). Surprisingly, 7 (4.9 %) of patients in region III who were neither hypervolemic nor hypertensive were also prescribed with diuretics., Conclusion: BIS can aid clinicians to categorize CKD patients on basis of their fluid status and provide individualized pharmacotherapy to manage hypertensive CKD patients.

Background: In patients with acute heart failure (AHF), dyspnea relief is the most immediate goal. Renal dysfunction, diuretic resistance, and hyponatremia represent treatment impediments., Objectives: It was hypothesized that the addition of tolvaptan to a background diuretic improved dyspnea early in patients selected for an enhanced vasopressin antagonism response., Methods: In a double-blind trial, patients were randomized to tolvaptan 30 mg/day or placebo. Study entry required hospitalization within the previous 36 h, active dyspnea, and any of the following: 1) estimated glomerular filtration rate <60 ml/min/1.73 m 2 ; 2) hyponatremia; or 3) diuretic resistance (urine output ≤125 ml/h following intravenous furosemide ≥40 mg). The primary endpoint was a 7-point change in self-assessed dyspnea at 8 and 16 h, using a novel standardized approach., Results: We randomized 250 patients. There was no difference in the primary endpoint of day 1 dyspnea reduction, despite significantly greater weight reduction with tolvaptan (-2.4 ± 2.1 kg vs. -0.9 ± 1.8 kg; p < 0.001). At day 3, dyspnea reduction was greater with tolvaptan (p = 0.01). There were 2 significant treatment-by-subgroup interactions: patients without elevated jugular venous pressure and those without ascites showed directional favorability of tolvaptan over placebo for the primary endpoint compared with patients with these findings., Conclusions: Despite rapid and persistent weight loss with tolvaptan compared with placebo, in patients with AHF who were selected for greater potential benefit from vasopressin receptor inhibition, tolvaptan was not associated with greater early improvement in dyspnea. Apparent subsequent differences in dyspnea warrant further exploration of the temporal relationship between diuresis and dyspnea relief and a possible clinical role for tolvaptan. (Randomized, Double-Blind, Placebo Controlled Study of the Short Term Clinical Effects of Tolvaptan in Patients Hospitalized for Worsening Heart Failure With Challenging Volume Management [SECRET of CHF]; NCT01584557)., (Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objective: To investigate the efficacy of the selective vasopressin V 2 -receptor antagonist tolvaptan in postoperative fluid management after cardiovascular surgery using cardiopulmonary bypass., Design: A retrospective cohort study., Setting: A tertiary care center., Participants: The study comprised 99 patients undergoing cardiovascular surgery using cardiopulmonary bypass., Interventions: Oral tolvaptan was administered after surgery., Measurements and Main Results: Fifty-one patients treated with tolvaptan were compared with 48 patients treated with intravenous diuretics. Urine volume, the time interval until the patients' body weight returned to the preoperative value, and the length of oxygen dependency after extubation were assessed as surrogate markers for resolution of fluid overload. Urine output on postoperative days 1 and 2 was significantly higher in the tolvaptan-treated patients (29.2 v 20.1 mL/kg/day, p = 0.001; 43.0 v 27.4 mL/kg/day, p<0.001, respectively). Postoperative body weight returned to baseline in 49 tolvaptan-treated patients compared with 33 patients treated with intravenous diuretics (96.1% v 68.8%, p<0.001). Among those with successful body weight reduction, the time interval was shorter in the tolvaptan-treated patients (5 v 7 days, p = 0.006). The length of oxygen dependency after extubation also was shorter in the tolvaptan-treated patients (2 v 3 days, p = 0.006). The urine osmolarity reduction rate before and 4 hours after the first dose of tolvaptan emerged as a significant predictor of its efficacy with a cutoff point of 33.7%, sensitivity of 0.73, and specificity of 0.67 (p = 0.030)., Conclusion: Tolvaptan facilitated early improvement of postoperative fluid overload after cardiovascular surgery., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The article presents the analysis of the intensive therapy through the correction of persistent hypernatremia in neurosurgical patients after removal of brain tumors. The aim of this work was to evaluate the effectiveness of Sterofundin in the framework of complex therapy of hypernatremia in neurosurgical patients after removal of brain tumors. We analyzed the dynamics of the concentrations of sodium, potassium, chorus of the plasma, anion gap and buffer bases in the postoperative period of these patients. For obtaining reliable results, the patients were divided into groups according to the nature of the treatment: Sterofundin and symptomatic correction of hypotonic solution of sodium chloride, saluretic and Verospiron respectively. In a comparison between the groups, a distinct difference in the speed of regression of hypernatremia and durability of the achieved effect was observed. In case of treatment with Sterofundin there was a significant decrease of hypernatremia by the end of the second day of the postoperative period without tendency to re-raise. The prevalence of hypotonic solutions of sodium chloride and potassium-sparing saluretics in intensive care allowed reducing the sodium concentration non-persistently to the fourth day on the background of significant fluctuations in its concentration. The use of Sterofundin in complex therapy of electrolyte disturbances, particularly of hypernatremia in neurosurgical patients after removal of brain tumors, is reflected in the form of significant regression of increased sodium concentration in plasma compared with the method of use "hypotonic" hemodilution, saluretics and potassium-sparing diuretics.

Background: Despite promising role of diuretics to manage fluid overload among chronic kidney disease (CKD) patients, their use is associated with adverse renal outcomes. Current study aimed to determine the extent of renal deterioration with diuretic therapy., Methods: A total 312 non-dialysis dependent CKD (NDD-CKD) patients were prospectively followed-up for one year. Fluid overload was assessed via bioimpedance spectroscopy. Estimated GFR (eGFR) was calculated from serum creatinine values by using Chronic Kidney Disease- Epidemiology Collaboration (CKD-EPI) equation., Results: Out of 312 patients, 64 (20.5%) were hypovolemic while euvolemia and hypervolemia were observed in 113 (36.1%) and 135 (43.4%) patients. Overall 144 patients were using diuretics among which 98 (72.6%) were hypervolemic, 35 (30.9%) euvolemic and 11 (17.2%) were hypovolemic. The mean decline in estimated GFR of entire cohort was -2.5 ± 1.4 ml/min/1.73m2 at the end of follow up. The use of diuretics was significantly associated with decline in eGFR. A total of 36 (11.5%) patients initiated renal replacement therapy (RRT) and need of RRT was more profound among diuretic users., Conclusions: The use of diuretics was associated with adverse renal outcomes indicated by decline in eGFR and increasing risk of RRT initiation in our cohort of NDD-CKD patients. Therefore, it is cautiously suggested to carefully prescribe diuretics by keeping in view benefit versus harm for each patient.

True resistant hypertension must be distinguished from apparent resistant hypertension, of which important causes include medication nonadherence, illicit drug use, and alcoholism. Ambulatory blood pressure monitoring should be considered to rule out white coat hypertension. The pathogenesis is multifactorial, but the 2 pivotal factors include volume excess and the myriad effects of aldosterone. Aldosterone increases vascular tone because of endothelial dysfunction and enhances the pressor response to catecholamines. It also plays a crucial role in vascular remodeling of small and large arteries. Aldosterone also promotes collagen synthesis, which leads to increased arterial stiffness and elevation of blood pressure. Because aldosterone has been demonstrated to modulate baroreflex resetting, in cases of severe hypertension, there would be fewer compensatory mechanisms available to offset the blood pressure elevation., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Aim: To elucidate influencing factors of treatment response, then tolvaptan has been approved in Japan for liquid retention., Methods: We herein conducted this study to clarify the influencing factors in 40 patients with decompensated liver cirrhosis complicated by liquid retention. Tolvaptan was administered at a dosage of 7.5 mg once a day for patients with conventional diuretic-resistant hepatic edema for 7 d. At the initiation of tolvaptan, the estimated hepatic venous pressure gradient (HVPG) value which was estimated portal vein pressure was measured using hepatic venous catheterization. We analyzed the effects of tolvaptan and influencing factors associated with treatment response., Results: Subjects comprised patients with a median age of 65 (range, 40-82) years. According to the Child-Pugh classification, class A was 3 patients, class B was 19, and class C was 18. Changes from the baseline in body weight were -1.0 kg (P = 2.04 × 10(-6)) and -1.3 kg (P = 1.83 × 10(-5)), respectively. The median HVPG value was 240 (range, 105-580) mmH2O. HVPG was only significant influencing factor of the weight loss effect. When patients with body weight loss of 2 kg or greater from the baseline was defined as responders, receiver operating characteristic curve analysis showed that the optimal HVPG cutoff value was 190 mmH2O in predicting treatment response. The response rate was 87.5% (7/8) in patients with HVPG of 190 mmH2O or less, whereas it was only 12.5% (2/16) in those with HVPG of greater than 190 mmH2O (P = 7.46 × 10(-4)). We compared each characteristics factors between responders and non-responders. As a result, HVPG (P = 0.045) and serum hyaluronic acid (P = 0.017) were detected as useful factors., Conclusion: The present study suggests that tolvaptan in the treatment of liquid retention could be more effective for patients with lower portal vein pressure.

Background: The purpose of this study was to determine the prevalence of hypomagnesemia in patients undergoing thyroidectomy and evaluate the relationship of hypomagnesemia with transient and severe hypocalcemia., Materials and Methods: This was a prospective observational study of 50 patients undergoing thyroidectomy. Blood samples were collected pre- and postoperatively for calcium, albumin, magnesium, phosphorous and parathormone (PTH). Signs, symptoms of hypocalcemia and volume of intravenous fluids used perioperatively were documented. The statistical analysis was performed using STATA I/C 10.1., Results: Preoperatively, twelve patients (24 %) had hypomagnesemia and one (2 %) hypocalcemia. On the first postoperative day, hypomagnesemia was seen in 70 % and hypocalcemia in 30 %. A similar trend was observed in the fall and rise of postoperative calcium and magnesium values (p = 0.41). Severe hypocalcemia was present in three patients (6 %). All three patients had a very low postoperative PTH (<2 pg/ml). Among them, two patients (66 %) had hypomagnesemia and their hypocalcemia responded to intravenous magnesium correction. Significant risk factors for postoperative hypocalcemia include a higher volume of fluid used perioperatively and low postoperative PTH (<8 pg/ml) (p = 0.01 and 0.03, respectively)., Conclusion: Preoperative hypomagnesemia (24 %) was prevalent in this cohort of patients. Postoperative hypomagnesemia is a common event (70 %) following total thyroidectomy, and magnesium levels tend to mimic the calcium levels postoperatively. The cause of hypocalcemia post-thyroidectomy in this study is mainly a factor of parathyroid function and fluid status. Severe hypocalcemia is a rare event, and hypomagnesemia is associated in the majority of these patients. The role of magnesium correction to alleviate severe hypocalcemia needs to be further studied.

Over the past decades, hypomagnesemia (serum Mg(2+) <0.7 mmol/L) has been strongly associated with type 2 diabetes mellitus (T2DM). Patients with hypomagnesemia show a more rapid disease progression and have an increased risk for diabetes complications. Clinical studies demonstrate that T2DM patients with hypomagnesemia have reduced pancreatic β-cell activity and are more insulin resistant. Moreover, dietary Mg(2+) supplementation for patients with T2DM improves glucose metabolism and insulin sensitivity. Intracellular Mg(2+) regulates glucokinase, KATP channels, and L-type Ca(2+) channels in pancreatic β-cells, preceding insulin secretion. Moreover, insulin receptor autophosphorylation is dependent on intracellular Mg(2+) concentrations, making Mg(2+) a direct factor in the development of insulin resistance. Conversely, insulin is an important regulator of Mg(2+) homeostasis. In the kidney, insulin activates the renal Mg(2+) channel transient receptor potential melastatin type 6 that determines the final urinary Mg(2+) excretion. Consequently, patients with T2DM and hypomagnesemia enter a vicious circle in which hypomagnesemia causes insulin resistance and insulin resistance reduces serum Mg(2+) concentrations. This Perspective provides a systematic overview of the molecular mechanisms underlying the effects of Mg(2+) on insulin secretion and insulin signaling. In addition to providing a review of current knowledge, we provide novel directions for future research and identify previously neglected contributors to hypomagnesemia in T2DM., (© 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.)

Objective: Sodium retention occurs commonly in cardiac and liver disease, requiring the administration of diuretics to restore fluid balance. Whether obesity is associated with sodium retention has not been fully evaluated., Methods: In a large single-center cohort of critically ill patients, we evaluated whether admission body mass index was associated with the administration of either oral or intravenous diuretics during the intensive care unit (ICU) stay., Main Results: Of 7724 critically ill patients, 3946 (51.1%) were prescribed diuretics during the ICU stay. Overweight, class I obesity, and class II/III obesity were associated with a 1.35 (95% confidence interval [CI], 1.20-1.53; P < .001), 1.56 (95% CI, 1.35-1.80; P < .001), and 1.91 (95% CI, 1.61-2.26; P < .001) adjusted risk of receiving diuretics within the ICU, respectively. In adjusted analysis, a 5-kg/m(2) increment of body mass index was associated with a 1.19 (95% CI, 1.14-1.23; P < .001) increased adjusted risk of within-ICU diuretics. Among those patients receiving loop diuretics, obese patients received significantly larger daily diuretic doses., Conclusion: Critically ill obese patients are more likely to receive diuretics during their stay in the ICU and to receive higher dosages of diuretics. Our data suggest that obesity is an independent risk factor for sodium retention., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Sodium retention is a major clinical feature of nephrotic syndrome. The mechanisms responsible for sodium retention in this setting have been a subject of debate for years. Excessive sodium retention occurs in some individuals with nephrotic syndrome in the absence of activation of the renin-angiotensin-aldosterone system, suggesting an intrinsic defect in sodium excretion by the kidney. Recent studies have provided new insights regarding mechanisms by which sodium transporters are activated by factors present in nephrotic urine. These mechanisms likely have a role in the development of hypertension in nephrotic syndrome, where hypertension may be difficult to control, and provide new therapeutic options for the management of blood pressure and edema in the setting of nephrotic syndrome., (Copyright © 2015 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose of Review: With the failure of multiple trials to identify a successful therapy for heart failure with preserved ejection fraction (HFpEF), attention has shifted to defining specific phenotypes within the HFpEF spectrum in an effort to develop a targeted approach to treatment. Here we summarize the most recent studies investigating the pathophysiology and clinical features of HFpEF, and discuss recent clinical trials in the context of developing treatments that look toward the underlying cause of this disorder., Recent Findings: Advances in basic science and clinical research have further characterized HFpEF, identifying multiple pathophysiological mechanisms that ultimately lead to exercise intolerance and volume overload. The success of small studies focused on specific subsets of the HFpEF population has promoted the concept that there may not be one treatment strategy that can universally be applied to HFpEF., Summary: HFpEF is associated with significant morbidity and mortality and accounts for approximately half of patients with chronic heart failure. HFpEF is a complex disease, encompassing a diverse cohort of patients and marked by the presence of multiple etiological mechanisms. The failure to develop successful therapies for the management of HFpEF may be because of inadequate standardization of the HFpEF diagnosis, overly broad inclusion criteria and inadequate differentiation of disease subtypes. Given the heterogeneity among patients with HFpEF, much of the current research is focused on understanding of pathophysiology and identifying disease phenotypes that may respond to a targeted treatment approach. Several newer approaches, including neprilysin inhibition and device therapy, offer promise for a new era of HFpEF treatment.

Significant improvements in the morbidity and mortality associated with chronic heart failure have been gained with the use ACE inhibitors, angiotensin receptor blockers, mineralocorticoid receptor antagonists, and diuretics. However, the use of these agents is often limited by their propensity to precipitate worsening renal function and hyperkalemia, particularly in patients with chronic kidney disease. Several pharmacologic agents have been developed in recent years that utilize the gastrointestinal tract as an alternate route for drug absorption, electrolyte exchange, and drug and electrolyte elimination. The existing data establishing the safety and efficacy of these novel agents will be the focus of this review.

One quarter of patients hospitalized for heart failure are readmitted within 30 days, perhaps related to ineffective decongestion. Limited data exist guiding the extent and duration of diuresis in patients hospitalized for heart failure. The objective of this review was to determine the prognostic value of hemoconcentration, or the relative increase in the cellular elements in blood, in patients hospitalized for heart failure and to clarify its role in guiding inpatient diuretic practices. Six post hoc retrospective studies from 2010 to 2013 were available for review. Hemoconcentration was consistently associated with markers of aggressive fluid removal, including higher diuretic dosing and reduced body weight, but increased risk of in-hospital worsening renal function. Despite this, hemoconcentration was associated with improved short-term mortality and rehospitalization. Hemoconcentration is a practical, readily available, noninvasive, economically feasible strategy to help guide diuresis and monitor congestion relief in patients hospitalized for worsening heart failure. Clinicians should strongly consider using changes in hemoglobin and hematocrit as an adjunct to other available measures of decongestion and clinical acumen in inpatient heart failure care., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objectives: To describe the efficacy of intravenous colistin on clinical and microbiological outcomes in preterm infants with nosocomial sepsis in neonatal intensive care unit (NICU) and define adverse events observed with this treatment., Methods: The records of preterm infants who received colistin with or without positive cultures in the NICU were retrospectively reviewed. Patients were evaluated for response to therapy and side effects., Results: A total of 21 preterm infants with medians of 28 weeks (23-36) gestational age and 870 g (620-2,650) birth weight were included. The median duration and dose of colistin therapy were 9 days (3-26) and 3 mg/kg/d (2-5). Recovery rate in patients including all with/without positive culture was 81% (17/21). Microbiological clearance by colistin was 69% (9/13). The major side effect observed was acute kidney injury (19%). At least 24% of infants required electrolyte supplementation during the colistin therapy. Magnesium levels were significantly lower at the end of the colistin therapy (p < 0.001). Acute kidney injury and electrolyte disturbances including hypomagnesemia were reversible in all surviving patients., Conclusion: We suggest that renal function tests and serum electrolytes should be monitored closely and replaced in case of any need during the colistin therapy in preterm infants., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Background: Standard treatment practice for the hypotensive patient with poor tissue perfusion is rapid volume resuscitation; in some scenarios, such as septic shock, this is performed with targeted goal-directed endpoints within 6 h of presentation. As a result, patients often develop significant positive fluid accumulation, which has been associated with poor outcomes above certain thresholds., Methods: The aim of the current paper is to provide guidance for active pharmacological fluid management in the patient with, or at risk for, clinically significant positive fluid balance from either resuscitation for hypovolaemic shock or acute decompensated heart failure., Results: We develop rationale for pharmacological fluid management targets (prevention of worsening fluid accumulation, achievement of slow vs rapid net negative fluid balance) in the context of phases of critical illness provided in the earlier Acute Dialysis Quality Initiative 12 papers., (© The Author 2014. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: The Acute Dialysis Quality Initiative (ADQI) dedicated its Twelfth Consensus Conference (2013) to all aspects of fluid therapy, including the management of fluid overload (FO). The aim of the working subgroup 'Mechanical fluid removal' was to review the indications, prescription, and management of mechanical fluid removal within the broad context of fluid management of critically ill patients., Methods: The working group developed a list of preliminary questions and objectives and performed a modified Delphi analysis of the existing literature. Relevant studies were identified through a literature search using the MEDLINE database and bibliographies of relevant research and review articles., Results: After review of the existing literature, the group agreed the following consensus statements: (i) in critically ill patients with FO and with failure of or inadequate response to pharmacological therapy, mechanical fluid removal should be considered as a therapy to optimize fluid balance. (ii) When using mechanical fluid removal or management, targets for rate of fluid removal and net fluid removal should be based upon the overall fluid balance of the patient and also physiological variables, individualized, and reassessed frequently. (iii) More research on the role and practice of mechanical fluid removal in critically ill patients not meeting fluid balance goals (including in children) is necessary., Conclusion: Mechanical fluid removal should be considered as a therapy for FO, but more research is necessary to determine its exact role and clinical application., (© The Author 2014. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

The vasopressin V2 receptor antagonist (Tolvaptan) is a new diuretic that selectively promotes the excretion of water. It has been reported to be effective for patients in cardiology, but there have been no reports of its use in the perioperative period after cardiac surgery. We report the usefulness of Tolvaptan for postoperative fluid management in a patient with severe mitral regurgitation due to ischemic cardiomyopathy. Marked improvement was achieved after administration of Tolvaptan for heart failure in the postoperative period.

The human body is two-thirds water. The ability of ensuring the proper amount of water inside the body is essential for the survival of mammals. The key event for maintenance of body water balance is water reabsorption in the kidney collecting ducts, which is regulated by aquaporin-2 (AQP2). AQP2 is a channel that is exclusively selective for water molecules and never allows permeation of ions or other small molecules. Under normal conditions, AQP2 is restricted within the cytoplasm of the collecting duct cells. However, when the body is dehydrated and needs to retain water, AQP2 relocates to the apical membrane, allowing water reabsorption from the urinary tubule into the cell. Its impairments result in various water balance disorders including diabetes insipidus, which is a disease characterized by a massive loss of water through the kidney, leading to severe dehydration in the body. Dysregulation of AQP2 is also a common cause of water retention and hyponatremia that exacerbate the prognosis of congestive heart failure and hepatic cirrhosis. Many studies have uncovered the regulation mechanisms of AQP2 at the single-molecule level, the whole-body level, and the clinical level. In clinical practice, urinary AQP2 is a useful marker for body water balance (hydration status). Moreover, AQP2 is now attracting considerable attention as a potential therapeutic target for water balance disorders which commonly occur in many diseases.

Objective: Refeeding syndrome can occur in several contexts of relative malnutrition in which an overaggressive nutritional support is started. The consequences are life threatening with multiorgan impairment, and severe electrolyte imbalances. During refeeding, glucose-involved insulin secretion causes abrupt reverse of lipolysis and a switch from catabolism to anabolism. This creates a sudden cellular demand for electrolytes (phosphate, potassium, and magnesium) necessary for synthesis of adenosine triphosphate, glucose transport, and other synthesis reactions, resulting in decreased serum levels. Laboratory findings and multiorgan impairment similar to refeeding syndrome also are observed in acute thiamine deficiency. The aim of this study was to determine whether thiamine deficiency was responsible for the electrolyte imbalance caused by tubular electrolyte losses., Methods: We describe two patients with leukemia who developed acute thiamine deficiency with an electrolyte pattern suggestive of refeeding syndrome, severe lactic acidosis, and evidence of proximal renal tubular dysfunction., Results: A single thiamine administration led to rapid resolution of the tubular dysfunction and normalization of acidosis and electrolyte imbalance. This demonstrated that thiamine deficiency was responsible for the electrolyte imbalance, caused by tubular electrolyte losses., Conclusions: Our study indicates that, despite sharing many laboratory similarities, refeeding syndrome and acute thiamine deficiency should be viewed as separate entities in which the electrolyte abnormalities reported in cases of refeeding syndrome with thiamine deficiency and refractory lactic acidosis may be due to renal tubular losses instead of a shifting from extracellular to intracellular compartments. In oncologic and malnourished patients, individuals at particular risk for developing refeeding syndrome, in the presence of these biochemical abnormalities, acute thiamine deficiency should be suspected and treated because it promptly responds to thiamine administration., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Purpose: The aim of this study was to evaluate the effectiveness of oral n-acetyl cysteine, as a potential nephroprotective agent, in preventing and/or attenuating amphotericin B-induced electrolytes imbalances., Methods: During a one year period, patients were to receive conventional amphotericin b for any indication for at least one week and were randomly allocated to receive either placebo or 600 mg oral n-acetyl cysteine twice daily during the treatment course of amphotericin b. Demographic and clinical data of the study population were gathered. Different aspects of amphotericin b nephrotoxicity including decrease of glomerular filtration rate, hypokalemia, hypomagnesemia, renal magnesium and potassium wasting were assessed. Each patient was monitored for any adverse reaction to n-acetyl cysteine. Sixteen and 14 patients in the n-acetyl cysteine and placebo groups completed the study, 3incidences of hypokalemia (75 % versus 70 %; P = 0.724) and hypomagnesemia (30 % versus 20 %; P = 0.468) did not differ significantly between placebo and NAC groups, respectively. Although the rate of AmB nephrotoxicity was higher in the placebo than in the NAC group (60 % versus 40 %), this difference was not statistically significant (P = 0.209) even after adjusting for probable associated factors of amphotericin b nephrotoxicity (P = 0.206). The incidence as well as time of onset of electrolyte abnormalities also did not differ significantly between placebo and n-acetyl cysteine groups. About 44 % of n-acetyl cysteine recipients experienced new onset nausea and a mild unpleasant taste during the study., Conclusion: Oral n-acetyl cysteine during the amphotericin B treatment course was not significantly effective in preventing or mitigating different features of its nephrotoxicity including decrease of glomerular filtration rate, hypokalemia, hypomagnesemia, and renal potassium as well as magnesium wasting.