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The perioperative use of inhaled prostacyclins in cardiac surgery: a systematic review and meta-analysis

Utilisation périopératoire de prostacyclines par inhalation en chirurgie cardiaque : une revue systématique et méta-analyse

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Abstract

Purpose

Perioperative pulmonary hypertension (PH) is an independent risk factor for morbidity and mortality in cardiac surgery. While inhaled prostacyclins (iPGI2s) are an established treatment of chronic PH, data on the efficacy of iPGI2s in perioperative PH are scarce.

Methods

We searched PubMed, Embase, the Web of Science, CENTRAL, and the grey literature from inception until April 2021. We included randomized controlled trials investigating the use of iPGI2s in adult and pediatric patients undergoing cardiac surgery with an increased risk of perioperative right ventricle failure. We assessed the efficacy and safety of iPGI2s compared with placebo and other inhaled or intravenous vasodilators with random-effect meta-analyses. The primary outcome was mean pulmonary artery pressure (MPAP). Secondary outcomes included other hemodynamic parameters and mortality.

Results

Thirteen studies were included, comprising 734 patients. Inhaled prostacyclins significantly decreased MPAP compared with placebo (standardized effect size, 0.46; 95% confidence interval [CI], 0.11 to 0.87; P = 0.01) and to intravenous vasodilators (1.26; 95% CI, 0.03 to 2.49; P = 0.045). Inhaled prostacyclins significantly improved the cardiac index compared with intravenous vasodilators (1.53; 95% CI, 0.50 to 2.57; P = 0.004). In contrast, mean arterial pressure was significantly lower in patients treated with iPGI2s vs placebo (−0.39; 95% CI, −0.62 to 0.16; P = 0.001), but higher than in patients treated with intravenous vasodilators (0.81; 95% CI, 0.29 to 1.33; P = 0.002). With respect to hemodynamics, iPGI2s had similar effects as other inhaled vasodilators. Mortality was not affected by iPGI2s.

Conclusion

The results of this systematic review and meta-analysis show that iPGI2s improved pulmonary hemodynamics with similar efficacy as other inhaled vasodilators, but caused a significant small decrease in arterial pressure when compared with placebo, indicating spill-over into the systemic circulation. These effects did not affect clinical outcomes.

Study registration date

PROSPERO (CRD42021237991); registered 26 May 2021.

Résumé

Objectif

L’hypertension pulmonaire (HTAP) périopératoire est un facteur de risque indépendant de morbidité et de mortalité en chirurgie cardiaque. Bien que l’inhalation de prostacyclines (iPGI2) constitue un traitement établi de l’HTAP chronique, les données sur l’efficacité de ce traitement en cas d’HTAP périopératoire sont rares.

Méthode

Nous avons effectué des recherches dans les bases de données PubMed, Embase, Web of Science, CENTRAL et dans la littérature grise depuis leur création jusqu’en avril 2021. Nous avons inclus des études randomisées contrôlées portant sur l’utilisation de l’iPGI2 chez la patientèle adulte et pédiatrique bénéficiant d’une chirurgie cardiaque avec un risque accru d’insuffisance ventriculaire droite périopératoire. Nous avons évalué l’efficacité et l’innocuité des iPGI2 par rapport à un placebo et à d’autres vasodilatateurs inhalés ou intraveineux avec des méta-analyses à effets aléatoires. Le critère d’évaluation principal était la pression artérielle pulmonaire moyenne (PAPm). Les critères d’évaluation secondaires incluaient d’autres paramètres hémodynamiques et la mortalité.

Résultats

Treize études portant sur 734 patient·es ont été incluses. Les prostacyclines inhalées ont diminué de manière significative la PAPm par rapport au placebo (taille d’effet standardisée, 0,46; intervalle de confiance [IC] à 95 %, 0,11 à 0,87; P = 0,01) et aux vasodilatateurs intraveineux (1,26; IC 95 %, 0,03 à 2,49; P = 0,045). Les prostacyclines inhalées ont significativement amélioré l’index cardiaque par rapport aux vasodilatateurs intraveineux (1,53; IC 95 %, 0,50 à 2,57; P = 0,004). En revanche, la pression artérielle moyenne était significativement plus faible chez les patient·es traité·es par iPGI2 vs placebo (−0,39; IC 95 %, −0,62 à 0,16; P = 0,001), mais plus élevée que chez les personnes traitées par vasodilatateurs intraveineux (0,81; IC 95 %, 0,29 à 1,33; P = 0,002). En ce qui concerne l’hémodynamie, les iPGI2 ont eu des effets similaires à ceux des autres vasodilatateurs inhalés. La mortalité n’a pas été affectée par les iPGI2.

Conclusion

Les résultats de cette revue systématique et méta-analyse montrent que les iPGI2 ont amélioré l’hémodynamie pulmonaire avec une efficacité similaire à celle des autres vasodilatateurs inhalés, mais ont entraîné une diminution légère mais significative de la pression artérielle par rapport au placebo, indiquant un débordement dans la circulation systémique. Ces effets n’ont pas affecté les résultats cliniques.

Enregistrement de l’étude

PROSPERO (CRD42021237991); enregistrée le 26 mai 2021.

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Author contributions

Berend Marcus and Steffen Rex helped in the study design, study conduction, data collection, data analysis, and manuscript preparation. Frederik Marynen helped in the study design, study conduction, data collection, and manuscript preparation. Steffen Fieuws helped in the study design, data analysis, and manuscript preparation. Dieter Van Beersel and Filip Rega helped with the data analysis and manuscript preparation.

Disclosures

Filip Rega has a research grant from Medtronic and is a consultant to AtriCure and Corcym. Steffen Rex has received speaking fees from Orion Pharma, Nordic Pharma, and Edwards Lifesciences. He has been member of advisory boards for Paion, Nordic Pharma, Orion Pharma, and Aerogen. He has received an unrestricted research grant from Nordic Pharma.

Funding statement

This research was solely funded by departmental sources and received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

Data availability statement

All data supporting the findings of this study are available within the article and in the Electronic Supplementary Material, and from the corresponding author on reasonable request. The protocol is available online on PROSPERO with the registration number CRD42021237991.

Editorial responsibility

This submission was handled by Dr. Philip M. Jones, Deputy Editor-in-Chief, Canadian Journal of Anesthesia/Journal canadien d’anesthésie.

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Author notes

  1. Berend Marcus and Frederik Marynen have contributed equally.

Authors and Affiliations

  1. Department of Anesthesiology, Universitair Ziekenhuis Leuven, Leuven, Belgium

    Berend Marcus MD, Frederik Marynen MD, Dieter Van Beersel MD & Steffen Rex MD, PhD

  2. Department of Cardiovascular Sciences, Group Biomedical Sciences, Katholieke Universiteit Leuven, Leuven, Belgium

    Steffen Fieuws PhD, Dieter Van Beersel MD, Filip Rega MD, PhD & Steffen Rex MD, PhD

  3. Leuvens Biostatistiek en Statistische Bioinformatica Centrum, Katholieke Universiteit Leuven, Leuven, Belgium

    Steffen Fieuws PhD

  4. Department of Cardiac Surgery, Universitair Ziekenhuis Leuven, Leuven, Belgium

    Filip Rega MD, PhD

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Marcus, B., Marynen, F., Fieuws, S. et al. The perioperative use of inhaled prostacyclins in cardiac surgery: a systematic review and meta-analysis. Can J Anesth/J Can Anesth 70, 1381–1393 (2023). https://doi.org/10.1007/s12630-023-02520-4

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