At first glance, the question in our title might strike you as unusual. To be honest, I too had never considered introducing diuretics during the acute phase of intermediate-risk pulmonary embolism (PE) management. Historically, the use of diuretics has been generally avoided due to potential risks associated with depressing right ventricular (RV) function and the resulting abrupt loss of cardiac output (CO). In fact, many of us have likely used volume expansion, aiming to increase the cardiac index in PE patients. The 2019 ESC guidelines suggest a modest (≤500 mL) fluid challenge in patients with low central venous pressure (CVP), though this recommendation is based on the results of a small studies conducted in the 1990s. There are concerns that volume expansion can reduce cardiac output through excessive septal paradoxical motion. New evidence has surfaced that proposes diuretics inn certain situations, known for their capacity to reduce RV preload, may have advantages over volume expansion in the management of PE.
Key Studies and Findings
A critical study (The Diuretic Versus Placebo in Pulmonary Embolism [DiPER]) spearheading this new viewpoint is a randomized controlled trial (RCT) led by Lim and colleagues. They aimed to compare the safety and effectiveness of a single intravenous (IV) bolus of 80mg furosemide against a placebo in 276 normotensive patients diagnosed with intermediate-risk PE.
In their study, the furosemide group saw a greater proportion of patients reaching the primary efficacy outcome, which comprised a set of parameters including increased urine output, regulated heart rate, adequate systolic blood pressure (BP), and satisfactory oxygen saturation. The relative risk of reaching this outcome was 1.30, indicating a 30% higher likelihood in the furosemide group compared to the placebo group (p = 0.021) .
However, the study also revealed that furosemide did not affect the concentrations of B-type natriuretic peptide (BNP) or N-terminal pro B-type natriuretic peptide (NT-proBNP), nor did it change the RV/LV diameter ratio as seen on echocardiography. Additionally, furosemide was found to elevate creatinine levels and reduce systolic BP 24 hours after administration, suggesting that the chosen dosage might have been excessive .
Another open-label randomized controlled trial further investigated the role of diuretic therapy (DT) versus volume expansion (VE) in the early management of intermediate high-risk pulmonary embolism (PE) patients with right ventricular (RV) dysfunction. In this study, sixty patients were divided into two groups, receiving either DT or VE. Troponin kinetics were similar between the two groups. However, the DT group showed a higher decrease in systolic pulmonary artery pressure and inferior vena cava diameter at 4 hours post-randomization and faster B-type natriuretic peptide (BNP) normalization. Although there were no changes in echocardiographic RV dysfunction parameters, the study suggests that DT may expedite RV function improvement, a finding which warrants further investigation in subsequent trials .
When dealing with patients suffering from pulmonary embolism (PE), the primary clinical concern is right ventricular dysfunction (RVD), rather than systemic overload. This is a significant distinction, as it greatly influences the therapeutic approach and the mechanisms through which we can improve patient outcomes.
In this context, the use of diuretics emerges as a complex decision. Diuretics work by decreasing preload — one of the key determinants of ventricular function. In normal circumstances, reducing preload can lead to a decrease in ventricular filling and thus, cardiac output. However, in PE patients with RVD, the overloaded state of the right ventricle due to the embolism makes this relationship more nuanced. Decreasing preload through diuretics might relieve some of the pressure on the right ventricle, potentially improving its function.
On the flip side, there's a possibility that reducing preload too much could lead to inadequate ventricular filling, worsening hemodynamic stability. This balance is delicate and can vary from patient to patient, highlighting the potential risk of inducing further hemodynamic deterioration.
Therefore, until more comprehensive research is conducted to determine the safety and efficacy of diuretic therapy in PE patients, the decision between utilizing diuretic therapy or volume loading must remain largely empirical. This decision will depend on a variety of factors, including the individual patient's hemodynamic status, the severity of RVD, and the potential risks and benefits associated with each approach. As such, clinical judgment, frequent monitoring, and careful consideration of the patient's evolving clinical picture will continue to be essential in managing these complex cases.
Lim, P, Delmas, C, Sanchez, O, Meneveau, N, Rosario, R, Bouvaist, H, et al. Diuretic vs. placebo in intermediate-risk acute pulmonary embolism: a randomized clinical trial. Eur Hear J Acute Cardiovasc Care. (2022) 11:2–9. doi: 10.1093/ehjacc/zuab082. Link
Ferrari, E, Sartre, B, Labbaoui, M, Heme, N, Asarisi, F, Redjimi, N, et al. Diuretics versus volume expansion in the initial Management of Acute Intermediate High-Risk Pulmonary Embolism. Lung. (2022) 200:179–85. doi: 10.1007/s00408-022-00530-5 Link