通气支持的休克成年患者低热量与标准热量及蛋白质喂养的比较：一项随机、对照、多中心、开放标签、平行组试验（NUTRIREA-3）

Low versus standard calorie and protein feeding in ventilated adults with shock: a randomised, controlled, multicentre, open-label, parallel-group trial (NUTRIREA-3).

作者信息

Reignier Jean, Plantefeve Gaetan, Mira Jean-Paul, Argaud Laurent, Asfar Pierre, Aissaoui Nadia, Badie Julio, Botoc Nicolae-Vlad, Brisard Laurent, Bui Hoang-Nam, Chatellier Delphine, Chauvelot Louis, Combes Alain, Cracco Christophe, Darmon Michael, Das Vincent, Debarre Matthieu, Delbove Agathe, Devaquet Jérôme, Dumont Louis-Marie, Gontier Olivier, Groyer Samuel, Guérin Laurent, Guidet Bertrand, Hourmant Yannick, Jaber Samir, Lambiotte Fabien, Leroy Christophe, Letocart Philippe, Madeux Benjamin, Maizel Julien, Martinet Olivier, Martino Frédéric, Maxime Virginie, Mercier Emmanuelle, Nay Mai-Anh, Nseir Saad, Oziel Johanna, Picard Walter, Piton Gael, Quenot Jean-Pierre, Reizine Florian, Renault Anne, Richecoeur Jack, Rigaud Jean-Philippe, Schneider Francis, Silva Daniel, Sirodot Michel, Souweine Bertrand, Tamion Fabienne, Terzi Nicolas, Thévenin Didier, Thiery Guillaume, Thieulot-Rolin Nathalie, Timsit Jean-Francois, Tinturier Francois, Tirot Patrice, Vanderlinden Thierry, Vinatier Isabelle, Vinsonneau Christophe, Voicu Sebastian, Lascarrou Jean-Baptiste, Le Gouge Amélie

机构信息

Movement, Interactions, Performance, UR 4334, Nantes Université, Nantes, France; Médecine Intensive Réanimation, CHU de Nantes, Hôtel-Dieu, Nantes, France.

Service de Médecine Intensive Réanimation, Centre Hospitalier d'Argenteuil, Argenteuil, France.

出版信息

Lancet Respir Med. 2023 Jul;11(7):602-612. doi: 10.1016/S2213-2600(23)00092-9. Epub 2023 Mar 20.

DOI:10.1016/S2213-2600(23)00092-9

PMID:36958363

Abstract

BACKGROUND

The optimal calorie and protein intakes at the acute phase of severe critical illness remain unknown. We hypothesised that early calorie and protein restriction improved outcomes in these patients, compared with standard calorie and protein targets.

METHODS

The pragmatic, randomised, controlled, multicentre, open-label, parallel-group NUTRIREA-3 trial was performed in 61 French intensive care units (ICUs). Adults (≥18 years) receiving invasive mechanical ventilation and vasopressor support for shock were randomly assigned to early nutrition (started within 24 h after intubation) with either low or standard calorie and protein targets (6 kcal/kg per day and 0·2-0·4 g/kg per day protein vs 25 kcal/kg per day and 1·0-1·3 g/kg per day protein) during the first 7 ICU days. The two primary endpoints were time to readiness for ICU discharge and day 90 all-cause mortality. Key secondary outcomes included secondary infections, gastrointestinal events, and liver dysfunction. The trial is registered on ClinicalTrials.gov, NCT03573739, and is completed.

FINDINGS

Of 3044 patients randomly assigned between July 5, 2018, and 8 Dec 8, 2020, eight withdrew consent to participation. By day 90, 628 (41·3%) of 1521 patients in the low group and 648 (42·8%) of 1515 patients in the standard group had died (absolute difference -1·5%, 95% CI -5·0 to 2·0; p=0·41). Median time to readiness for ICU discharge was 8·0 days (IQR 5·0-14·0) in the low group and 9·0 days (5·0-17·0) in the standard group (hazard ratio [HR] 1·12, 95% CI 1·02 to 1·22; p=0·015). Proportions of patients with secondary infections did not differ between the groups (HR 0·85, 0·71 to 1·01; p=0·06). The low group had lower proportions of patients with vomiting (HR 0·77, 0·67 to 0·89; p<0·001), diarrhoea (0·83, 0·73 to 0·94; p=0·004), bowel ischaemia (0·50, 0·26 to 0·95; p=0·030), and liver dysfunction (0·92, 0·86-0·99; p=0·032).

INTERPRETATION

Compared with standard calorie and protein targets, early calorie and protein restriction did not decrease mortality but was associated with faster recovery and fewer complications.

FUNDING

French Ministry of Health.

摘要

背景

严重危重病急性期的最佳热量和蛋白质摄入量仍不清楚。我们假设，与标准热量和蛋白质目标相比，早期热量和蛋白质限制可改善这些患者的预后。

方法

在法国61个重症监护病房（ICU）进行了务实、随机、对照、多中心、开放标签、平行组NUTRIREA - 3试验。接受有创机械通气和血管升压药支持以治疗休克的成年人（≥18岁）被随机分配接受早期营养（插管后24小时内开始），在最初7个ICU日期间采用低或标准热量和蛋白质目标（每天6千卡/千克和每天0.2 - 0.4克/千克蛋白质，对比每天25千卡/千克和每天1.0 - 1.3克/千克蛋白质）。两个主要终点是准备好从ICU出院的时间和第90天的全因死亡率。关键次要结局包括继发感染、胃肠道事件和肝功能障碍。该试验已在ClinicalTrials.gov上注册，注册号为NCT03573739，且已完成。

结果

在2018年7月5日至2020年12月8日期间随机分配的3044例患者中，8例撤回参与同意书。到第90天，低目标组1521例患者中有628例（41.3%）死亡，标准目标组1515例患者中有648例（42.8%）死亡（绝对差异 -1.5%，95%置信区间 -5.0至2.0；p = 0.41）。低目标组准备好从ICU出院的中位时间为8.0天（四分位间距5.0 - 14.0），标准目标组为9.0天（5.0 - 17.0）（风险比[HR]1.12，95%置信区间1.02至1.22；p = 0.015）。两组继发感染患者的比例无差异（HR 0.85，0.71至1.01；p = 0.06）。低目标组呕吐（HR 0.77，0.67至0.89；p<0.001）、腹泻（0.83，0.73至0.94；p = 0.004）、肠道缺血（0.50，0.26至0.95；p = 0.030）和肝功能障碍（0.92，0.86 - 0.99；p = 0.032）的患者比例较低。