Amiloride 10mg/5ml / Furosemide 125mg/5ml oral suspension

BackgroundIn patients with respiratory failure, loop diuretics remain the cornerstone of the treatment to maintain fluid balance, but resistance is common.AimTo determine the efficacy and safety of common diuretic combinations in critically ill patients with respiratory failure.MethodsWe searched MEDLINE, Embase, Cochrane Library and PROSPERO for studies reporting the effects of a combination of a loop diuretic with another class of diuretic. A meta-analysis using mean differences (MD) with 95% confidence interval (CI) was performed for the 24-h fluid balance (primary outcome) and the 24-h urine output, while descriptive statistics were used for safety events.ResultsNine studies totalling 440 patients from a total of 6510 citations were included. When compared to loop diuretics alone, the addition of a second diuretic is associated with an improved negative fluid balance at 24 h [MD: -1.06 L (95%CI: -1.46; -0.65)], driven by the combination of a thiazide plus furosemide [MD: -1.25 L (95%CI: -1.68; -0.82)], while no difference was observed with the combination of a loop-diuretic plus acetazolamide [MD: -0.40 L (95%CI: -0.96; 0.16)] or spironolactone [MD: -0.65 L (95%CI: -1.66; 0.36)]. Heterogeneity was high and the report of clinical and safety endpoints varied across studies.ConclusionBased on limited evidence, the addition of a second diuretic to a loop diuretic may promote diuresis and negative fluid balance in patients with respiratory failure, but only when using a thiazide. Further larger trials to evaluate the safety and efficacy of such interventions in patients with respiratory failure are required.

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ObjectiveTo gain initial insight into the efficacy to lower intracranial pressure (ICP), side effects, and effects on cognition of five drugs commonly used to treat idiopathic intracranial hypertension (IIH).BackgroundLimited clinical data exist for the treatment for IIH. Impaired cognition is recognized in IIH and can be exacerbated by medications.MethodsThis human experimental medicine study was a secondary analysis that focused on an unblinded randomized, sequential, cross-over extension of a previously completed randomized controlled trial. This study evaluated females with active IIH, recruited from University Hospital Birmingham, UK. Participants were treated, in randomized order, for 2 weeks with acetazolamide, amiloride, furosemide, spironolactone, and topiramate; assessment was at baseline and 2 weeks with a minimum 1-week drug washout between drugs. The primary outcome was change in ICP at 2 weeks post-drug administration. The cognitive evaluation was an exploratory study of the trial. ICP was recorded with telemetric, intraparenchymal ICP monitors (Raumedic, Hembrechts, Germany). Adverse events were recorded, and cognition was assessed utilizing the National Institutes of Health Toolbox Cognitive Battery.ResultsFourteen participants were recruited and evaluated by intention-to-treat analysis. Mean (standard deviation) body mass index was 37.3 (7.0) kg/m2 and ICP was 33.2 (7.1) cm cerebrospinal fluid (CSF) at baseline. ICP fell with four drugs (mean [standard error (SE)]), acetazolamide -3.3 (1.0) mmHg, p = 0.001, furosemide -3.0 (0.9) mmHg, p = 0.001, spironolactone -2.7 (0.9) mmHg, p = 0.003, and topiramate -2.3 (0.9) mmHg, p = 0.010. There was no significant difference between drugs. Side effects were common with acetazolamide (100%, 11/11) and topiramate (93%, 13/14). Baseline cognitive performance was impaired, T-score (mean [SE]) 37.2 (2.6). After treatment, there was a further significant reduction in the fluid cognition domain (ability to process and integrate) with acetazolamide (mean T-score [SE]), -5.0 (2.6), p = 0.057 and topiramate -4.1 (2.0), p = 0.061.ConclusionsAcetazolamide, furosemide, spironolactone, and topiramate marginally reduced ICP. While their effects were not significant, this study was not powered to detect a difference between drugs. Participants reported significant side effects with acetazolamide and topiramate including cognitive decline. Cognitive measures were impaired by acetazolamide and topiramate. Therapeutics with greater efficacy and a favorable side effect profile are an unmet need in the treatment of IIH.

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Hypertension is highly prevalent in patients with obstructive sleep apnea (OSA), and fluid retention with its nighttime rostral distribution is one potential mechanism. We tested whether or not diuretics differ from amlodipine in their impact on echocardiographic parameters. Patients with moderate OSA and hypertension were randomized to receive diuretics (chlorthalidone plus amiloride) or amlodipine daily for 8 weeks. We compared their effects on left and right ventricular global longitudinal strain (LV-GLS and RV-GLS, respectively), on LV diastolic parameters, and on LV remodeling. In the 55 participants who had echocardiographic images feasible for strain analysis, all echocardiographic parameters were within normal ranges. After 8 weeks, the 24 h blood pressure (BP) reduction values were similar, while most echocardiographic metrics were kept unchanged, except for LV-GLS and LV mass. In conclusion, the use of diuretics or amlodipine had small and similar effects on echocardiographic parameters in patients with moderate OSA and hypertension, suggesting that they do not have important effects on mediating the interaction between OSA and hypertension.

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Diuretics remain the cornerstone therapy of critically ill patients with volume overload as a result of cardiac failure, acute kidney injury or aggressive fluid resuscitation. This review summarises the principles of applied renal physiology, describing the mechanisms of action, the clinical applications, and the adverse effects of commonly used diuretics during critical illness. Loop diuretics, and in particular furosemide, remain the most popular, despite evidence of any effect on mortality or, indeed, on the need for renal replacement therapy. The efficacy of loop diuretics after administration depends on three factors. Firstly, the tubular concentration of the diuretic: continuous infusion of furosemide seems to provide a higher and more stable tubular concentration of furosemide with respect to bolus injection. Secondly, the interaction with albumin both in the plasma and in the renal tubule: despite a strong physiological rationale supporting this approach, albumin supplementation in hypoalbuminaemic patients does not seem to result in a higher diuretic efficacy. Thirdly, diuretic resistance, which can be addressed by optimising loop diuretic dose and by using combination therapy with other agents, including thiazides or thiazide-like diuretics or carbonic anhydrase inhibitors. These drugs constitute a useful adjunct to overcome loop diuretic resistance. Other agents such as distal potassium-sparing diuretics and osmotic diuretics can also be considered. The latter have been used successfully in hypokalaemia, rhabdomyolysis-associated acute kidney injury or to prevent ischaemia-reperfusion injury in kidney transplantation. Finally, this review provides the basic concepts of the interplay between acid-base equilibrium and diuretic therapy.

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