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Original Research: Critical Care |

Delirium and Circadian Rhythm of Melatonin During Weaning From Mechanical VentilationDelirium and Melatonin During Weaning: An Ancillary Study of a Weaning Trial

Armand Mekontso Dessap, MD, PhD; Ferran Roche-Campo, MD; Jean-Marie Launay, PharmD, PhD; Anais Charles-Nelson, MSc; Sandrine Katsahian, MD, PhD; Christian Brun-Buisson, MD; Laurent Brochard, MD
Author and Funding Information

From AP-HP (Drs Mekontso Dessap, Roche-Campo, and Brun-Buisson), Hôpitaux Universitaires Henri Mondor, DHU A-TVB, Service de Réanimation Médicale, Créteil, France; Université Paris Est Créteil (Drs Mekontso Dessap and Brun-Buisson), Faculté de Médecine de Créteil, IMRB, Groupe de recherche clinique CARMAS, Créteil, France; Hospital Verge de la Cinta (Dr Roche-Campo), Servei de Medicina Intensiva, Tortosa, Tarragona, Spain; AP-HP (Dr Launay), Hôpital Lariboisière, Service de Biochimie, Paris, France; INSERM (Dr Launay), Unité U942, Paris, France; AP-HP (Ms Charles-Nelson and Dr Katsahian), Hôpital Européen Georges Pompidou, Unité d’Épidémiologie et de Recherche Clinique, Paris, France; Sorbonne Universités (Ms Charles-Nelson and Dr Katsahian), UPMC INSERM UMRS1138, Centre de Recherche des Cordeliers, Paris, France; Keenan Research Centre and Critical Care Department (Dr Brochard), St. Michael’s Hospital, Toronto, ON, Canada; and Interdepartmental Division of Critical Care Medicine (Dr Brochard), University of Toronto, Toronto, ON, Canada.

CORRESPONDENCE TO: Armand Mekontso Dessap, MD, PhD, Service de Réanimation Médicale, Centre Hospitalo-Universitaire Henri Mondor, 51, avenue du Mal de Lattre de Tassigny 94 010 Créteil Cedex, France; e-mail: armand.dessap@hmn.aphp.fr


FUNDING/SUPPORT: This project was funded by the French Ministry of Health research program (Programme Hospitalier de Recherche Clinique [Contract No. 05104]).

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2015;148(5):1231-1241. doi:10.1378/chest.15-0525
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BACKGROUND:  Delirium is frequent in patients in the ICU, but its association with the outcome of weaning from mechanical ventilation has not been assessed. Circadian rhythm alteration may favor delirium. In the current study, we assessed the impact of delirium during weaning and associated alterations in the circadian rhythm of melatonin excretion.

METHODS:  This was a substudy of 70 participants of the B-type Natriuretic Peptide for the Fluid Management of Weaning trial, comparing two fluid management strategies during weaning. Patients with or without delirium (as assessed using the Confusion Assessment Method for the ICU) were compared in terms of baseline characteristics and outcomes and the circadian rhythm of melatonin excretion using the 24-h excretion of its urinary metabolite 6-sulfatoxymelatonin (aMT6s).

RESULTS:  Among the 70 patients included, 43 (61.4%) experienced delirium at the initiation of weaning. Delirium at the initiation of weaning was associated with more alcohol consumption, a greater severity of illness, and medication use before weaning (including neuromuscular blockade, antibiotics, sedatives, and narcotics). Delirium at the initiation of weaning was associated with more respiratory and neurologic complications and a reduced probability of successful extubation (Cox multivariate model hazard ratio of successful extubation = 0.54; 95% CI, 0.30-0.95; P = .03). Delirium was also associated with a significant reduction in peak, mean, amplitude, and total values of aMT6s urinary excretion during the first 24 h of weaning (general linear model F statistic = 5.81, P = .019).

CONCLUSIONS:  Delirium is frequent at the initiation of ventilator weaning. It is associated with a prolongation of weaning and an alteration in the circadian rhythm of melatonin excretion.

TRIAL REGISTRY:  ClinicalTrials.gov; No.: NCT00473148; URL: www.clinicaltrials.gov

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