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Comparison of diuretics and fluid expansion in the initial treatment of patients with normotensive acute pulmonary embolism: a systematic review and meta-analysis
  1. Cláudia Febra1,2,
  2. Ana Rita Santos3,
  3. Isabel Cabrita3,
  4. Joana Bento3,
  5. João Pacheco3,
  6. Mariana Mendes3,
  7. Michael Isidro3,
  8. Rafael Batista3,
  9. Ana Margarida André Febra Moita Macedo3
  1. 1 University of Porto, Porto, Portugal
  2. 2 Department of Intensive Care, Hospital da Luz, Lisboa, Lisboa, Portugal
  3. 3 Faculdade de Medicina da Universidade do Algarve, Universidade do Algarve, Faro, Portugal
  1. Correspondence to Dr Cláudia Febra, University of Porto, Porto, Portugal; cfebra{at}


Background Right ventricular (RV) dysfunction is the main cause of death in patients with normotensive acute pulmonary embolism (PE). The optimal management for this subset of patients remains uncertain. This systematic review and meta-analysis focused on the comparison of diuretics and fluid expansion in patients with acute PE presenting with RV dysfunction and haemodynamic stability.

Methods A systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines considering only RTCs. The authors searched the traditional and grey literature through 1 November 2022. Meta-analysis used open source packages in R. Inverse variance fixed-effects models with OR as the effect measure were used for primary analyses. The main outcomes defined in this review protocol included pulmonary arterial systolic pressure (PASP), creatinine value changes and N-terminal pro-B-type natriuretic peptide during the first 24 hours.

Results Four studies with a total of 452 patients met the inclusion criteria. The baseline characteristics of patients were similar across all studies. Overall, patients receiving diuretics had a significant 24 hours reduction in pro-B-type natriuretic peptide (standard mean difference of −41.97; 95% CI −65.79 to −18.15), and PASP (standard mean difference of −5.96; 95% CI −8.06 to −3.86). This group had significantly higher creatinine levels (standard mean difference of 7.74; 95% CI 5.04 to 10.45). The quality of the studies was heterogeneous; two had a low risk of bias, and the other two had a high risk of bias.

Conclusions Very few studies have compared the efficacy and safety of diuretics and fluid expansion in normotensive patients with acute PE with RV failure. Overall, furosemide appears to reduce RV dysfunction in this subset of patients compared with fluid expansion. Further research is required to confirm these findings.

  • Meta-Analysis
  • acute care
  • acute medicine
  • effectiveness
  • pulmonary embolism

Data availability statement

All data relevant to the study are included in the article or uploaded as supplementary information.

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Data availability statement

All data relevant to the study are included in the article or uploaded as supplementary information.

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  • Handling editor Edward Carlton

  • Contributors All authors were involved with the conception, study design and analyses. ARS, IC, JB, JP, MM, MI and RB contributed to data collection and first draft of the article; CF and AM critically reviewed and revised multiple drafts of the article.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.