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1.
Impact of loop diuretics on critically ill patients with a positive fluid balance.
Libório, AB, Barbosa, ML, Sá, VB, Leite, TT
Anaesthesia. 2020;:e134-e142
Abstract
The impact of the use of loop diuretics to prevent cumulative fluid balance in non-oliguric patients is uncertain. This is a retrospective study to estimate the association of time-averaging loop diuretic exposure in a large population of non-cardiac, critically ill patients with a positive fluid balance (> 5% of body weight). The exposure was loop diuretic and the main outcomes were 28-day mortality, severe acute kidney injury and successful mechanical ventilation weaning. Time-fixed and daily time-varying variables were evaluated with a marginal structural Cox model, adjusting bias for time-varying exposure and the presence of time-dependent confounders. A total of 14,896 patients were included. Patients receiving loop diuretics had better survival (unadjusted hazard ratio 0.56, 95%CI 0.39-0.81 and baseline variables adjusted hazard ratio 0.53, 95%CI 0.45-0.62); after full adjusting, loop diuretics had no association with 28-day mortality (full adjusted hazard ratio 1.07, 95%CI 0.74-1.54) or with reducing severe acute kidney injury occurrence during intensive care unit stay - hazard ratio 1.05 (95%CI 0.78-1.42). However, we identified an association with prolonged mechanical ventilation (hazard ratio 1.59, 95%CI 1.35-1.89). The main results were consistent in the sub-group analysis for sepsis, oliguria and the study period (2002-2007 vs. 2008-2012). Also, equivalent doses of up to 80 mg per day of furosemide had no significant association with mortality. After adjusting for time-varying variables, the time average of loop diuretic exposure in non-cardiac, critically ill patients has no association with overall mortality or severe acute kidney injury; however, prolonged mechanical ventilation is a concern.
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2.
Association of hyponatraemia and renal function in type 1 cardiorenal syndrome.
Liang, W, He, X, Xue, R, Wei, F, Dong, B, Wu, Z, Owusu-Agyeman, M, Wu, Y, Zhou, Y, Dong, Y, et al
European journal of clinical investigation. 2020;(9):e13269
Abstract
BACKGROUND Hyponatraemia predicts type 1 cardiorenal syndrome in acute decompensated heart failure patients, which associates with poor outcome. Recovery from hyponatraemia has been found to associate with better outcome in acute decompensated heart failure patients, but its prognostic value regarding renal function remains unknown. METHODS We performed a secondary analysis of CARRESS-HF trial, and all patients included had worsening renal function (≥0.3 mg/dL increase in serum creatinine than the nadir). The serum sodium levels of patients were evaluated at baseline and day 4 and day 7 after randomization. Patients were grouped according to the status of hyponatraemia: recovery from hyponatraemia; no hyponatraemia; persistent hyponatraemia; and new-onset hyponatraemia. Their associations with persistent worsening renal function (serum creatinine ≥ 0.3 mg/dL higher than the nadir at discharge) were explored. RESULTS A total of 118 patients suffered from persistent worsening renal function. Baseline hyponatraemia was not associated with persistent worsening renal function (odds ratio = 0.495, P = .086). Patients in the recovery from hyponatraemia group had a lowest risk of persistent worsening renal function among the study population. Further, baseline serum sodium level was not associated with the risk of persistent worsening renal function (odds ratio = 1.055, P = .233), while the increases in serum sodium level at day 4 (odds ratio = 0.858, P = .003) and at day 7 (odds ratio = 0.821, P < .001) significantly predicted a lower risk of persistent worsening renal function. CONCLUSIONS Recovery from hyponatraemia associates with a lower risk of persistent worsening renal function, suggesting that hyponatraemia correction may improve renal outcomes in acute decompensated heart failure patients with type 1 cardiorenal syndrome.
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3.
The Cardiorenal Syndrome in Heart Failure.
Costanzo, MR
Heart failure clinics. 2020;(1):81-97
Abstract
Abnormal fluid handling leads to physiologic abnormalities in multiple organ systems. Deranged hemodynamics, neurohormonal activation, excessive tubular sodium reabsorption, inflammation, oxidative stress, and nephrotoxic medications are important drivers of harmful cardiorenal interactions in patients with heart failure. Accurate quantitative measurement of fluid volume is vital to individualizing therapy for such patients. Blood volume analysis and pulmonary artery pressure monitoring seem the most reliable methods for assessing fluid volume and guiding decongestive therapies. Still the cornerstone of decongestive therapy, diuretics' effectiveness decreases with progression of heart failure. Extracorporeal ultrafiltration, an alternative to diuretics, has been shown to reduce heart-failure events.
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A narrative review of pharmacologic de-resuscitation in the critically ill.
Bissell, BD, Donaldson, JC, Morris, PE, Neyra, JA
Journal of critical care. 2020;:156-162
Abstract
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.
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5.
Higher Diuretic Requirements in Acute Heart Failure With Admission Hyponatraemia Versus Normonatraemia.
Omar, HR, Guglin, M
Heart, lung & circulation. 2020;(2):233-241
Abstract
BACKGROUND Diuretic requirements in patients with acute decompensated heart failure (ADHF) and hyponatraemia versus normonatraemia on admission has not been previously explored. METHODS The Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) trial dataset was utilised to examine the characteristics and diuretic requirements of patients with ADHF with hyponatraemia or normonatraemia on admission. RESULTS Patients with ADHF and admission hyponatraemia (n = 103, average Na 130.2 meq/L) had a higher degree of congestion evident in higher frequency of jugular venous distension (JVD) >12 cmH2O (p = 0.007), 2+ lower extremity oedema (p = 0.001), and higher right atrial pressure (p = 0.007), compared with normonatraemic patients (n = 327, average Na 138.6 meq/L). Despite a similar baseline furosemide dose in both groups (median 200 mg), the hyponatraemia group received higher in-hospital furosemide (280 vs. 200 mg, in both groups, respectively, p < 0.001) which represented a higher percentage of furosemide utilisation relative to baseline, compared with the normonatraemia group (33% vs 0%, in both groups respectively, p = 0.007). With in-hospital diuresis, the Na level of hyponatraemic subjects started significantly increasing at discharge and up to 6 months after randomisation-all relative to baseline. Hyponatraemic patients had significantly lower systolic blood pressure (SBP) longitudinally at multiple time points compared with normonataremic patients, but it did not further decrease despite the higher furosemide dose in the former group. CONCLUSION Patients with ADHF and hyponatraemia on admission had a higher degree of congestion and required higher doses of furosemide, compared with normonatraemic subjects. The lower Na and SBP in this instance should not lead to withholding or minimising diuretic dosage which should rather be dictated by volume status.
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6.
Dapagliflozin and Diuretic Use in Patients With Heart Failure and Reduced Ejection Fraction in DAPA-HF.
Jackson, AM, Dewan, P, Anand, IS, Bělohlávek, J, Bengtsson, O, de Boer, RA, Böhm, M, Boulton, DW, Chopra, VK, DeMets, DL, et al
Circulation. 2020;(11):1040-1054
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Abstract
BACKGROUND In the DAPA-HF trial (Dapagliflozin and Prevention of Adverse-Outcomes in Heart Failure), the sodium-glucose cotransporter 2 inhibitor dapagliflozin reduced the risk of worsening heart failure and death in patients with heart failure and reduced ejection fraction. We examined the efficacy and tolerability of dapagliflozin in relation to background diuretic treatment and change in diuretic therapy after randomization to dapagliflozin or placebo. METHODS We examined the effects of study treatment in the following subgroups: no diuretic and diuretic dose equivalent to furosemide <40, 40, and >40 mg daily at baseline. We examined the primary composite end point of cardiovascular death or a worsening heart failure event and its components, all-cause death and symptoms. RESULTS Of 4616 analyzable patients, 736 (15.9%) were on no diuretic, 1311 (28.4%) were on <40 mg, 1365 (29.6%) were on 40 mg, and 1204 (26.1%) were taking >40 mg. Compared with placebo, dapagliflozin reduced the risk of the primary end point across each of these subgroups: hazard ratios were 0.57 (95% CI, 0.36-0.92), 0.83 (95% CI, 0.63-1.10), 0.77 (95% CI, 0.60-0.99), and 0.78 (95% CI, 0.63-0.97), respectively (P for interaction=0.61). The hazard ratio in patients taking any diuretic was 0.78 (95% CI, 0.68-0.90). Improvements in symptoms and treatment toleration were consistent across the diuretic subgroups. Diuretic dose did not change in most patients during follow-up, and mean diuretic dose did not differ between the dapagliflozin and placebo groups after randomization. CONCLUSIONS The efficacy and safety of dapagliflozin were consistent across the diuretic subgroups examined in DAPA-HF. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03036124.
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Acute kidney injury.
Reis, T
Revista da Associacao Medica Brasileira (1992). 2020;(Suppl 1):s68-s74
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Urea for Chronic Hyponatremia.
Rondon-Berrios, H
Blood purification. 2020;(1-2):212-218
Abstract
BACKGROUND Hyponatremia is the most common electrolyte disorder encountered clinically. While acute and/or severe hyponatremia is commonly associated with significant symptoms, milder and more chronic forms of hyponatremia remain clinically inconspicuous. Recent evidence suggests that even milder forms of hyponatremia are associated with increased morbidity and mortality. Despite this, currently available treatments for chronic hyponatremia lack data on efficacy and/or have important limitations related to patient nonadherence, adverse side effects, and/or significant costs. Consequently, there is a clear need for investigation of alternative treatments for this common condition. SUMMARY Small case series conducted in Europe since the early 1980s suggest that urea, an oral osmotic diuretic that increases urinary water excretion, is safe and effective for the treatment of chronic hyponatremia. In 2016, a novel formulation of urea became available in the United States. Our group recently reported the first and only study describing the efficacy and safety of this American formulation of oral urea among hospitalized patients with hyponatremia. Key Messages: Oral urea appears to be an effective, safe, and well-tolerated therapeutic strategy in the management of chronic hyponatremia.
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Effects of hydrochlorothiazide on drainage volume and seroma formation in deep inferior epigastric perforator flap breast reconstruction: Randomized controlled trial.
Suh, YC, Oh, TM, Lee, YH, Kim, EK, Han, HH, Eom, JS
Journal of plastic, reconstructive & aesthetic surgery : JPRAS. 2020;(4):663-672
Abstract
BACKGROUND Seroma is a recognized complication encountered at the reconstructed breast and donor site after abdominal-based breast reconstruction. Seroma is caused by lymphatic channel disruption and the formation of a large space between the deep fascia during flap elevation. Surgical techniques to preserve the lymphatics and secure the closure of the donor site can reduce seroma formation. This study investigated the safety and effectiveness of the diuretic hydrochlorothiazide at reducing interstitial fluid accumulation and seroma formation during deep inferior epigastric perforator (DIEP) flap breast reconstruction. METHODS Sixty patients with breast cancer who underwent skin- or nipple-sparing mastectomy and DIEP flap reconstruction were enrolled between August 2016 and June 2017. The patients were randomly assigned to receive either 25 mg per day of hydrochlorothiazide from the second to the twentieth day after surgery (treatment) or no diuretic (control). The clinicopathological characteristics, drainage time, and drainage volume were statistically compared between the two groups. RESULTS The average total drainage volume at the donor site was 291 mL in the treatment group and 434 mL in the control group (p = 0.003). The differences in body mass index and flap weight between the two groups were not statistically significant (p = 0.879 and p = 0.963, respectively). No hypotension or electrolyte imbalance was noted during the follow-up. CONCLUSIONS Intake of 25 mg per day of hydrochlorothiazide tablets effectively reduced the total abdominal drainage volume and removal time of indwelling drains. However, the adverse effects should be further investigated in a large population and multiracial cohort before using hydrochlorothiazide for seroma prevention.
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10.
Pathophysiology of Drug-Induced Hypomagnesaemia.
Katopodis, P, Karteris, E, Katopodis, KP
Drug safety. 2020;(9):867-880
Abstract
Magnesium (Mg2+) is the second most abundant intracellular and fourth extracellular cation found in the body and is involved in a wide range of functions in the human cell and human physiology. Its role in most of the enzyme processes (ATP-ases)-stabilisation of nucleic acids (DNA, RNA), regulation of calcium and potassium ion channels, proliferation, glucose metabolism and apoptosis-make it one of the most important cations in the cell. Three pathogenetic mechanisms are mainly implicated in the development of hypomagnesaemia: reduced food intake, decreased intestinal absorption and increased renal excretion of Mg2+. This review presents the function of Mg2+, how it is handled in the kidney and the drugs that cause hypomagnesaemia. The frequency and the number of drugs like diuretics and proton-pump inhibitors (PPIs) that are used daily in medical practice are discussed in order to prevent and treat adverse effects by providing an insight into Mg2+ homeostasis.