Stéphane Gaudry1, David Hajage2, Laurent Martin-Lefevre3, Saïd Lebbah2, Guillaume Louis4, Sébastien Moschietto5, Dimitri Titeca-Beauport6, Béatrice La Combe7, Bertrand Pons8, Nicolas de Prost9, Sébastien Besset10, Alain Combes11, Adrien Robine12, Marion Beuzelin13, Julio Badie14, Guillaume Chevrel15, Julien Bohé16, Elisabeth Coupez17, Nicolas Chudeau18, Saber Barbar19, Christophe Vinsonneau20, Jean-Marie Forel21, Didier Thevenin22, Eric Boulet23, Karim Lakhal24, Nadia Aissaoui25, Steven Grange26, Marc Leone27, Guillaume Lacave28, Saad Nseir29, Florent Poirson30, Julien Mayaux31, Karim Asehnoune32, Guillaume Geri33, Kada Klouche34, Guillaume Thiery35, Laurent Argaud36, Bertrand Rozec37, Cyril Cadoz4, Pascal Andreu38, Jean Reignier38, Jean-Damien Ricard39, Jean-Pierre Quenot40, Didier Dreyfuss41. 1. Département de réanimation médico-chirurgicale, APHP Hôpital Avicenne, Bobigny, France; Health Care Simulation Center, UFR SMBH, Université Sorbonne Paris Nord, Bobigny, France; Common and Rare Kidney Diseases, Sorbonne Université, INSERM, UMR-S 1155, Paris, France; Investigation Network Initiative-Cardiovascular and Renal Clinical Trialists, Bobigny, France. 2. INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique, AP-HP, Département de Santé Publique, Centre de Pharmacoépidémiologie (Cephepi), Sorbonne Université, Hôpital Pitié Salpêtrière, Paris, France. 3. Réanimation polyvalente, CHR départementale La Roche Sur Yon, La Roche Sur Yon, France. 4. Réanimation polyvalente, CHR Metz-Thionville Hôpital de Mercy, Metz, France. 5. Réanimation polyvalente, CHG d'Avignon Henri Duffaut, Avignon, France. 6. Réanimation médicale, CHU d'Amiens Picardie, Amiens, France. 7. Réanimation, CH de Bretagne Sud, Lorient, France. 8. Réanimation, CHU Pointe-à-Pitre-Abymes, Pointe-a-Pitre, France. 9. Réanimation médicale, Hôpital Henri Mondor, Créteil, France. 10. Université de Paris, APHP, Hôpital Louis Mourier, DMU ESPRIT, Médecine Intensive-Réanimation, Colombes, France. 11. Service de Réanimation Médicale, Sorbonne Université, Hôpital Pitié Salpêtrière, Paris, France. 12. Réanimation Soins continus, CH de Bourg-en-Bresse-Fleyriat, 01012 Bourg-en-Bresse, France. 13. Réanimation polyvalente, CH de Dieppe, Dieppe, France. 14. Réanimation polyvalente, Hôpital Nord Franche-Comte CH Belfort, Belfort, France. 15. Réanimation polyvalente, CH Sud Francilien, Corbeil Essones, France. 16. Anesthésie réanimation médicale et chirurgicale, CH Lyon Sud, Pierre Benite. 17. Réanimation polyvalente, Hôpital G. Montpied, Clermont Ferrand, France. 18. Réanimation médico-chirurgicale, CH du Mans, Le Mans, France. 19. Réanimation, Hôpital Caremeau, Nimes, France. 20. Réanimation et USC, CH Bethune Beuvry-Bermont et Gauthier, Bethune, France. 21. Réanimation médicale, Hôpital Nord, Marseille, France. 22. Réanimation et USC, CH Dr Schaffner, Lens, France. 23. Réanimation et USC, GH Carnelle Portes de l'Oise, Beaumont sur Oise, France. 24. Réanimation chirurgicale polyvalente, Hôpital Nord laennec, Nantes, France. 25. Réanimation médicale, Hôpital Georges Pompidou, Paris, France. 26. Réanimation médicale, CHU Rouen, Rouen, France. 27. Anesthésie Réanimation, Hôpital Nord, Marseille, France. 28. Réanimation médico-chirurgicale, Hôpital André Mignot, Versailles, France. 29. Réanimation médicale, CHRU de Lille, Hôpital Roger Salengro, Lille, France. 30. Département de réanimation médico-chirurgicale, APHP Hôpital Avicenne, Bobigny, France. 31. Pneumologie et Réanimation médicale, Sorbonne Université, Hôpital Pitié Salpêtrière, Paris, France. 32. Anesthésie-réanimation, Hôtel Dieu, Nantes, France. 33. Réanimation médico-chirurgicale, Hôpital Ambroise Paré, Boulogne-Billancourt, France. 34. Médecine Intensive Réanimation, Hôpital Lapeyronnie, Montpellier, France. 35. Réanimation médicale, CHU Saint Etienne, Saint Priest en Jarez, France. 36. Réanimation médicale, Hôpital Edouard Herriot, Lyon, France. 37. Réanimation CTCV, Hôpital Nord laennec, Nantes, France. 38. Médecine intensive réanimation, Hôtel Dieu, Nantes, France. 39. Université de Paris, APHP, Hôpital Louis Mourier, DMU ESPRIT, Médecine Intensive-Réanimation, Colombes, France; INSERM, IAME, U1137, Paris, France. 40. Department of Intensive Care, François Mitterrand University Hospital, Dijon, France; Lipness Team, INSERM Research Center LNC-UMR1231 and LabExLipSTIC, University of Burgundy, Dijon, France; INSERM CIC 1432, Clinical Epidemiology, University of Burgundy, Dijon, France. 41. Common and Rare Kidney Diseases, Sorbonne Université, INSERM, UMR-S 1155, Paris, France; Université de Paris, APHP, Hôpital Louis Mourier, DMU ESPRIT, Médecine Intensive-Réanimation, Colombes, France. Electronic address: didier.dreyfuss@aphp.fr.
Abstract
BACKGROUND:Delaying renal replacement therapy (RRT) for some time in critically ill patients with severe acute kidney injury and no severe complication is safe and allows optimisation of the use of medical devices. Major uncertainty remains concerning the duration for which RRT can be postponed without risk. Our aim was to test the hypothesis that a more-delayed initiation strategy would result in more RRT-free days, compared with a delayed strategy. METHODS: This was an unmasked, multicentre, prospective, open-label, randomised, controlled trial done in 39 intensive care units in France. We monitored critically ill patients with severe acute kidney injury (defined as Kidney Disease: Improving Global Outcomes stage 3) until they had oliguria for more than 72 h or a blood urea nitrogen concentration higher than 112 mg/dL. Patients were then randomly assigned (1:1) to either a strategy (delayed strategy) in which RRT was started just after randomisation or to a more-delayed strategy. With the more-delayed strategy, RRT initiation was postponed until mandatory indication (noticeable hyperkalaemia or metabolic acidosis or pulmonary oedema) or until blood urea nitrogen concentration reached 140 mg/dL. The primary outcome was the number of days alive and free of RRT between randomisation and day 28 and was done in the intention-to-treat population. The study is registered with ClinicalTrial.gov, NCT03396757 and is completed. FINDINGS: Between May 7, 2018, and Oct 11, 2019, of 5336 patients assessed, 278 patients underwent randomisation; 137 were assigned to the delayed strategy and 141 to the more-delayed strategy. The number of complications potentially related to acute kidney injury or to RRT were similar between groups. The median number of RRT-free days was 12 days (IQR 0-25) in the delayed strategy and 10 days (IQR 0-24) in the more-delayed strategy (p=0·93). In a multivariable analysis, the hazard ratio for death at 60 days was 1·65 (95% CI 1·09-2·50, p=0·018) with the more-delayed versus the delayed strategy. The number of complications potentially related to acute kidney injury or renal replacement therapy did not differ between groups. INTERPRETATION: In severe acute kidney injury patients with oliguria for more than 72 h orblood urea nitrogen concentration higher than 112 mg/dL and no severe complication that would mandate immediate RRT, longer postponing of RRT initiation did not confer additional benefit and was associated with potential harm. FUNDING: Programme Hospitalier de Recherche Clinique.
RCT Entities:
BACKGROUND: Delaying renal replacement therapy (RRT) for some time in critically illpatients with severe acute kidney injury and no severe complication is safe and allows optimisation of the use of medical devices. Major uncertainty remains concerning the duration for which RRT can be postponed without risk. Our aim was to test the hypothesis that a more-delayed initiation strategy would result in more RRT-free days, compared with a delayed strategy. METHODS: This was an unmasked, multicentre, prospective, open-label, randomised, controlled trial done in 39 intensive care units in France. We monitored critically illpatients with severe acute kidney injury (defined as Kidney Disease: Improving Global Outcomes stage 3) until they had oliguria for more than 72 h or a blood ureanitrogen concentration higher than 112 mg/dL. Patients were then randomly assigned (1:1) to either a strategy (delayed strategy) in which RRT was started just after randomisation or to a more-delayed strategy. With the more-delayed strategy, RRT initiation was postponed until mandatory indication (noticeable hyperkalaemia or metabolic acidosis or pulmonary oedema) or until blood ureanitrogen concentration reached 140 mg/dL. The primary outcome was the number of days alive and free of RRT between randomisation and day 28 and was done in the intention-to-treat population. The study is registered with ClinicalTrial.gov, NCT03396757 and is completed. FINDINGS: Between May 7, 2018, and Oct 11, 2019, of 5336 patients assessed, 278 patients underwent randomisation; 137 were assigned to the delayed strategy and 141 to the more-delayed strategy. The number of complications potentially related to acute kidney injury or to RRT were similar between groups. The median number of RRT-free days was 12 days (IQR 0-25) in the delayed strategy and 10 days (IQR 0-24) in the more-delayed strategy (p=0·93). In a multivariable analysis, the hazard ratio for death at 60 days was 1·65 (95% CI 1·09-2·50, p=0·018) with the more-delayed versus the delayed strategy. The number of complications potentially related to acute kidney injury or renal replacement therapy did not differ between groups. INTERPRETATION: In severe acute kidney injurypatients with oliguria for more than 72 h or blood ureanitrogen concentration higher than 112 mg/dL and no severe complication that would mandate immediate RRT, longer postponing of RRT initiation did not confer additional benefit and was associated with potential harm. FUNDING: Programme Hospitalier de Recherche Clinique.
Authors: Ron Wald; William Beaubien-Souligny; Rahul Chanchlani; Edward G Clark; Javier A Neyra; Marlies Ostermann; Samuel A Silver; Suvi Vaara; Alexander Zarbock; Sean M Bagshaw Journal: Intensive Care Med Date: 2022-09-06 Impact factor: 41.787