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  1. Ng KT, Yap JLL
    Anaesthesia, 2018 Feb;73(2):238-247.
    PMID: 28940440 DOI: 10.1111/anae.14038
    Loop diuretics remain a fundamental pharmacological therapy to remove excess fluid and improve symptom control in acute decompensated heart failure. Several recent randomised controlled trials have examined the clinical benefit of continuous vs. bolus furosemide in acute decompensated heart failure, but have reported conflicting findings. The aim of this review was to compare the effects of continuous and bolus furosemide with regard to mortality, length of hospital stay and its efficacy profile in acute decompensated heart failure. All parallel-arm randomised controlled trials from MEDLINE, EMBASE, PubMed and the Cochrane Database of Systematic Reviews from inception until May 2017 were included. Cross-over randomised controlled trials, observational studies, case reports, case series and non-systematic reviews that involved children were excluded. Eight trials (n = 669) were eligible for inclusion. There was no difference between furosemide continuous infusion and bolus administration for all-cause mortality (four studies; n = 491; I2 = 0%; OR 1.65; 95%CI 0.93-2.91; p = 0.08) or duration of hospitalisation (six studies; n = 576; I2 = 71%; mean difference 0.27; 95%CI -1.35 to 1.89 days; p = 0.74). Continuous infusion of intravenous furosemide was associated with increased weight reduction (five studies; n = 516; I2 = 0%; mean difference 0.70; 95%CI 0.12-1.28 kg; p = 0.02); increased total urine output in 24 h (four studies; n = 390; I2 = 33%; mean difference 461.5; 95%CI 133.7-789.4 ml; p < 0.01); and reduced brain natriuretic peptide (two studies; n = 390; I2 = 0%; mean difference 399.5; 95%CI 152.7-646.3 ng.l-1 ; p < 0.01), compared with the bolus group. There was no difference in the incidence of raised creatinine and hypokalaemia between the two groups. In summary, there was no difference between continuous infusion and bolus of furosemide for all-cause mortality, length of hospital stay and electrolyte disturbance, but continuous infusion was superior to bolus administration with regard to diuretic effect and reduction in brain natriuretic peptide.
    Matched MeSH terms: Diuretics/administration & dosage*
  2. Ng KT, Velayit A, Khoo DKY, Mohd Ismail A, Mansor M
    J Cardiothorac Vasc Anesth, 2018 10;32(5):2303-2310.
    PMID: 29454528 DOI: 10.1053/j.jvca.2018.01.004
    OBJECTIVE: Fluid overload is a common phenomenon seen in intensive care units (ICUs). However, there is no general consensus on whether continuous or bolus furosemide is safer or more effective in these hemodynamically unstable ICU patients. The aim of this meta-analysis was to examine the clinical outcomes of continuous versus bolus furosemide in a critically ill population in ICUs.

    DATA SOURCES: MEDLINE, EMBASE, PubMed, and the Cochrane Database of Systematic reviews were searched from their inception until June 2017.

    REVIEW METHODS: All randomized controlled trials, observational studies, and case-control studies were included. Case reports, case series, nonsystematic reviews, and studies that involved children were excluded.

    RESULTS: Nine studies (n = 464) were eligible in the data synthesis. Both continuous and bolus furosemide resulted in no difference in all-cause mortality (7 studies; n = 396; I2 = 0%; fixed-effect model [FEM]: odds ratio [OR] 1.15 [95% confidence interval (CI) 0.67-1.96]; p = 0.64). Continuous furosemide was associated with significant greater total urine output (n = 132; I2 = 70%; random-effect model: OR 811.19 [95% CI 99.84-1,522.53]; p = 0.03), but longer length of hospital stay (n = 290; I2 = 40%; FEM: OR 2.84 [95% CI 1.74-3.94]; p < 0.01) in comparison to the bolus group. No statistical significance was found in the changes of creatinine and estimated glomerular filtration rate between both groups.

    CONCLUSIONS: In this meta-analysis, continuous furosemide was associated with greater diuretic effect in total urine output as compared with bolus. Neither had any differences in mortality and changes of renal function tests. However, a large adequately powered randomized clinical trial is required to fill this knowledge gap.

    Matched MeSH terms: Diuretics/administration & dosage
  3. Asmah BJ, Wan Nazaimoon WM, Norazmi K, Tan TT, Khalid BA
    Horm. Metab. Res., 1997 Nov;29(11):580-3.
    PMID: 9479560 DOI: 10.1055/s-2007-979105
    The effect of thyroid hormones on the renin-angiotensin-aldosterone system has not been fully resolved. Highly specific immunoassays for measurement of renin, aldosterone, free T4 (fT4), free T3 (fT3) and ultrasensitive TSH enables a direct and more accurate measurement of these hormones. We investigated the relationship between plasma renin, aldosterone and thyroid hormones in the basal state and after intravenous frusemide. This is a cross-sectional study involving 37 patients with thyrotoxicosis, 42 rendered euthyroid with normal fT4, fT3 and TSH levels, 17 with euthyroid levels of fT4 and fT3 but suppressed TSH, and 11 with hypothyroidism. Basal plasma renin was significantly higher in thyrotoxicosis (63.4 +/- 9.8 microU/ml, mean +/- SEM) compared to euthyroid (32.7 +/- 4.4 microU/ml) and hypothyroid (26.7 +/- 9.8 microU/ml). Basal plasma renin for euthyroid with suppressed TSH (41.0 +/- 7.4 microU/ml) was significantly higher than hypothyroid (p = 0.02). Basal plasma aldosterones were not significantly different except for suppressed TSH (157.7 +/- 13 pg/ml), which was higher than normal (109.9 +/- 10.4 pg/ml; p = 0.04). Following frusemide, plasma renin and aldosterone were significantly increased in all groups. Plasma renin was highly correlated to fT3 (r = 0.405, p < 0.001), total T3 (r = 0.359, p < 0.001), fT4 (r = 0.331, p < 0.001) and TSH (r = 0.300, p < 0.001) in the basal state, but less to total T4 (r = 0.248, p < 0.01). Plasma renin correlated poorly to serum aldosterone (r = 0.212, p < 0.03). This study clearly showed that regulation of renin was mainly influenced by fT3, and that aldosterone response to frusemide was blunted in thyrotoxicosis despite normal electrolytes.
    Matched MeSH terms: Diuretics/administration & dosage
  4. Kanchanasurakit S, Saokaew S, Siriplabpla W, Arsu A, Boonmak W, Watcharasiriphong W
    J Clin Pharm Ther, 2020 Oct;45(5):997-1005.
    PMID: 32012317 DOI: 10.1111/jcpt.13123
    WHAT IS KNOWN AND OBJECTIVE: Hyponatremia is a common side effect of thiazide diuretics that can lead to increased mortality and hospitalization. A rapid and accurate screening tool is needed for rapid and appropriate management. In this study, we report on the development of a simple clinical screening tool for hyponatremia using thiazide diuretics.

    METHODS: This nested case-control study was performed by collecting data from 1 January 2015 to 30 June 2017. Univariable and multivariable logistic regressions were used to identify potential risk factors. The regression coefficients were converted into item scores by dividing each regression coefficient with the minimum coefficient in the model and rounding to the nearest integer. This value was then summed to the total score. The prediction power of the model was determined by the area under the receiver operating characteristic curve (AuROC).

    RESULTS AND DISCUSSION: Six clinical risk factors, namely age ≥65 years, benzodiazepine use, history of a cerebrovascular accident, dose of hydrochlorothiazide ≥25 mg, female sex and statin use, were included in our ABCDF-S score. The model showed good power of prediction (AuROC 81.53%, 95% confidence interval [CI]: 78%-84%) and good calibration (Hosmer-Lemeshow X2  = 23.20; P = .39). The positive likelihood ratios of hyponatremia in patients with low risk (score ≤ 6) and high risk (score ≥ 8) were 0.26 (95% CI: 0.21-0.32) and 3.89 (95% CI: 3.11-4.86), respectively.

    WHAT IS NEW AND CONCLUSION: The screening tool with six risk predictors provided a useful prediction index for thiazide-associated hyponatremia. However, further validation of the tool is warranted prior to its utilization in routine clinical practice.

    Matched MeSH terms: Diuretics/administration & dosage
  5. Joseph P, Pais P, Dans AL, Bosch J, Xavier D, Lopez-Jaramillo P, et al.
    Am Heart J, 2018 Dec;206:72-79.
    PMID: 30342297 DOI: 10.1016/j.ahj.2018.07.012
    BACKGROUND: It is hypothesized that in individuals without clinical cardiovascular disease (CVD), but at increased CVD risk, a 50% to 60% reduction in CVD risk could be achieved using fixed dose combination (FDC) therapy (usually comprised of multiple blood-pressure agents and a statin [with or without aspirin]) in a single "polypill". However, the impact of a polypill in preventing clinical CV events has not been evaluated in a large randomized controlled trial.

    METHODS: TIPS-3 is a 2x2x2 factorial randomized controlled trial that will examine the effect of a FDC polypill on major CV outcomes in a primary prevention population. This study aims to determine whether the Polycap (comprised of atenolol, ramipril, hydrochlorothiazide, and a statin) reduces CV events in persons without a history of CVD, but who are at least at intermediate CVD risk. Additional interventions in the factorial design of the study will compare the effect of (1) aspirin versus placebo on CV events (and cancer), (2) vitamin D versus placebo on the risk of fractures, and (3) the combined effect of aspirin and the Polycap on CV events.

    RESULTS: The study has randomized 5713 participants across 9 countries. Mean age of the study population is 63.9 years, and 53% are female. Mean INTERHEART risk score is 16.8, which is consistent with a study population at intermediate CVD risk.

    CONCLUSION: Results of the TIP-3 study will be key to determining the appropriateness of FDC therapy as a strategy in the global prevention of CVD.

    Matched MeSH terms: Diuretics/administration & dosage
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