Diuretic versus placebo in normotensive acute pulmonary embolism with right ventricular enlargement and injury: a double-blind randomised placebo controlled study. Protocol of the DiPER study

Abstract

IntroductionIn acute pulmonary embolism (PE), poor outcome is usually related to right ventricular (RV) failure due to the increase in RV afterload. Treatment of PE with RV failure without shock is controversial and usually relies on fluid expansion to increase RV preload. However, several studies suggest that fluid expansion may worsen acute RV failure by increasing RV dilation and ischaemia, and increase left ventricular compression by RV dilation. By reducing RV enlargement, diuretic treatment may break this vicious circle and provide early improvement in normotensive patients referred for acute PE with RV failure.Methods and analysisThe Diuretic versus placebo in Pulmonary Embolism with Right ventricular enlargement trial (DiPER) is a prospective, multicentre, randomised (1:1), double-blind, placebo controlled study assessing the superiority of furosemide as compared with placebo in normotensive patients with confirmed acute PE and RV dilation (diagnosed on echocardiography or CT of the chest) and positive brain natriuretic peptide result. The primary end point will be a combined clinical criterion derived from simplified Pulmonary Embolism Severity Index (PESI) score and evaluated at 24 h. It will include: (1) urine output >0.5 mL/kg/min for the past 24 h; (2) heart rate <110 bpm; (3) systolic blood pressure >100 mm Hg and (4) arterial oxyhaemoglobin level >90%. Thirty-day major cardiac events defined as death, cardiac arrest, mechanical ventilation, need for catecholamine and thrombolysis, will be evaluated as a secondary end point. Assuming an increase of 30% in the primary end point with furosemide and a β risk of 10%, 270 patients will be required.Ethics and disseminationEthical approval was received from the ethical committee of Ile de France (2014-001090-14). The findings of the trial will be disseminated through peer-reviewed journals, and national and international conference presentations.Trial registration numberNCT02268903.

Right Ventricular Function, Peripheral Edema, and Acute Kidney Injury in Critical Illness

“…Fluid-restrictive strategies are now being clinically tested, and a small trial showing a benefit of fluid-restrictive strategies on renal function 26 is now being reproduced in a large, multicenter, randomized controlled study. 27 …”

Peripheral Edema, Central Venous Pressure, and Risk of AKI in Critical Illness

“…Expanding into the pericardial sack and causing paradoxical septal movement, the failing right ventricle impinges on the left ventricle, decreasing its compliance and output. In an interesting preliminary study of patients with acute right ventricular dysfunction due to pulmonary embolus, diuretic therapy was associated with better renal function compared with those who received fluid (30), prompting the design of a larger study of the utility of diuretics in acute right ventricular dysfunction (31). Whether diuretic therapy might improve renal outcomes in those with more chronic right ventricular dysfunction has not been explored.…”

Management of Right Ventricular Failure in Pulmonary Embolism

“…[16][17][18] A prospective multicenter blinded randomized trial is currently ongoing to compare the effects of diuresis and volume expansion in acute intermediate-risk PE. 19 In the interim, the authors favor judicious use of volume expansion to achieve euvolemia, while monitoring for and avoiding other conditions that may excessively reduce RV preload, such as pericardial effusions and cardiac arrhythmias.…”