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High–normal versus low–normal mean arterial pressure thresholds in critically ill patients: a systematic review and meta-analysis of randomized trials

Seuils de pression artérielle moyenne normale à élevée par rapport à normale à faible chez la patientèle gravement malade : revue systématique et méta-analyse d’études randomisées

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Abstract

Purpose

Targeted blood pressure thresholds remain unclear in critically ill patients. Two prior systematic reviews have not shown differences in mortality with a high mean arterial pressure (MAP) threshold, but there have been new studies published since. Thus, we conducted an updated systematic review and meta-analysis of randomized controlled trials (RCTs) that compared the effect of a high–normal vs low–normal MAP on mortality, favourable neurologic outcome, need for renal replacement therapy, and adverse vasopressor-induced events in critically ill patients.

Source

We searched six databases from inception until 1 October 2022 for RCTs of critically ill patients targeted to either a high–normal vs a low–normal MAP threshold for at least 24 hr. We assessed study quality using the revised Cochrane risk-of-bias 2 tool and the risk ratio (RR) was used as the summary measure of association. We used the Grading of Recommendations Assessment, Development, and Evaluation framework to assess the certainty of evidence.

Principal findings

We included eight RCTs with 4,561 patients. Four trials were conducted in patients following out-of-hospital cardiac arrest, two in patients with distributive shock requiring vasopressors, one in patients with septic shock, and one in patients with hepatorenal syndrome. The pooled RRs for mortality (eight RCTs; 4,439 patients) and favourable neurologic outcome (four RCTs; 1,065 patients) were 1.06 (95% confidence interval [CI], 0.99 to 1.14; moderate certainty) and 0.99 (95% CI, 0.90 to 1.08; moderate certainty), respectively. The RR for the need for renal replacement therapy (four RCTs; 4,071 patients) was 0.97 (95% CI, 0.87 to 1.08; moderate certainty). There was no statistical between-study heterogeneity across all outcomes.

Conclusion

This updated systematic review and meta-analysis of RCTs found no differences in mortality, favourable neurologic outcome, or the need for renal replacement therapy between critically ill patients assigned to a high–normal vs low–normal MAP target.

Study registration

PROSPERO (CRD42022307601); registered 28 February 2022.

Résumé

Objectif

Les seuils de pression artérielle ciblés demeurent incertains chez les patient·es gravement malades. Deux revues systématiques antérieures n’ont pas montré de différences dans la mortalité avec un seuil élevé de pression artérielle moyenne (PAM), mais de nouvelles études ont été publiées depuis. Pour cette raison, nous avons réalisé une revue systématique mise à jour et une méta-analyse d’études randomisées contrôlées (ERC) comparant l’effet d’une PAM normale élevée vs normale faible sur la mortalité, les devenirs neurologiques favorables, la nécessité d’un traitement substitutif de l’insuffisance rénale et les événements indésirables induits par les vasopresseurs chez les patient·es gravement malades.

Sources

Nous avons effectué des recherches dans six bases de données depuis leur création jusqu’au 1er octobre 2022 pour trouver des ERC portant sur des patient·es gravement malades chez lesquel·les un seuil de PAM normale élevée ou normale faible a été ciblé pendant au moins 24 heures. Nous avons évalué la qualité des études à l’aide de l’outil de risque de biais 2 révisé de Cochrane, et le risque relatif (RR) a été utilisé comme mesure sommaire de l’association. Nous avons utilisé le système de notation GRADE (Grading of Recommendations Assessment, Development, and Evaluation) pour évaluer la certitude des données probantes.

Constatations principales

Nous avons inclus huit ERC portant sur 4561 personnes traitées. Quatre études ont été menées chez des patient·es à la suite d’un arrêt cardiaque hors de l’hôpital, deux chez des patient·es présentant un choc distributif nécessitant des vasopresseurs, une chez des patient·es présentant un choc septique et une chez des patient·es atteint·es d’un syndrome hépato-rénal. Les RR combinés pour la mortalité (huit ERC; 4439 personnes) et les devenirs neurologiques favorables (quatre ERC; 1065 personnes) étaient respectivement de 1,06 (intervalle de confiance [IC] à 95 %, 0,99 à 1,14; certitude modérée) et de 0,99 (IC 95 %, 0,90 à 1,08; certitude modérée). Le RR pour le besoin de traitement substitutif de l’insuffisance rénale (quatre ERC; 4071 patient·es) était de 0,97 (IC 95 %, 0,87 à 1,08; certitude modérée). Il n’y avait pas d’hétérogénéité statistique entre les études pour tous les critères d’évaluation.

Conclusion

Ces revue systématique et méta-analyse mises à jour des ERC n’ont révélé aucune différence dans la mortalité, les devenirs neurologiques favorables ou la nécessité d’un traitement substitutif de l’insuffisance rénale entre les patient·es gravement malades assigné·es à une cible de PAM normale élevée vs normale faible.

Enregistrement de l’étude

PROSPERO (CRD42022307601); enregistrée le 28 février 2022.

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Authors’ contributions

All authors contributed to the study conception, design, and production. The literature search was performed by Kiran J. K. Rikhraj, Claire Ronsley, and Donald E. G. Griesdale while data analysis was performed by Donald E. G. Griesdale. All authors were involved in production and critical revision of the manuscript.

Disclosures

All authors declare that they have no conflicts of interest related to this work.

Funding statement

Donald E. G. Griesdale is supported by the Michael Smith Foundation for Health Research Health Professional Investigator award (Vancouver, BC, Canada). Mypinder Sekhon is supported by the Michael Smith Foundation for Health Research Health Professional Investigator award and the Vancouver Coastal Health Research Institute Clinician Scientist award (both, Vancouver, BC, Canada).

Editorial responsibility

This submission was handled by Dr. Alexis F. Turgeon, Associate Editor, Canadian Journal of Anesthesia/Journal canadien d’anesthésie.

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Authors and Affiliations

  1. Department of Emergency Medicine, Faculty of Medicine, The University of British Columbia, Vancouver, BC, Canada

    Kiran J. K. Rikhraj MD & Claire Ronsley MD

  2. Division of Critical Care Medicine, Department of Medicine, Faculty of Medicine, The University of British Columbia, Vancouver, BC, Canada

    Mypinder S. Sekhon MD, PhD, Anish R. Mitra MD, MPH & Donald E. G. Griesdale MD, MPH

  3. Department of Anesthesiology, Pharmacology & Therapeutics, Faculty of Medicine, The University of British Columbia, Vancouver, BC, Canada

    Donald E. G. Griesdale MD, MPH

  4. Centre for Clinical Epidemiology and Evaluation, Vancouver Coastal Health Research Institute, Vancouver, BC, Canada

    Donald E. G. Griesdale MD, MPH

  5. Department of Emergency Medicine, Vancouver General Hospital, 899 West 12th Avenue, Vancouver, BC, V5Z 1M9, Canada

    Kiran J. K. Rikhraj MD

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  1. Kiran J. K. Rikhraj MD
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Correspondence to Kiran J. K. Rikhraj MD.

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Rikhraj, K.J.K., Ronsley, C., Sekhon, M.S. et al. High–normal versus low–normal mean arterial pressure thresholds in critically ill patients: a systematic review and meta-analysis of randomized trials. Can J Anesth/J Can Anesth 70, 1244–1254 (2023). https://doi.org/10.1007/s12630-023-02494-3

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