重症患者の栄養って難しいですよね。「使える腸管は早期から使う」というのは受け入れられていると思いますが、至適カロリーやタンパク量といった栄養目標というのは、恐らく個々の病態やベースラインの栄養状態、タイミングなどによっても変わってくるのでしょう。

人工呼吸管理されているショック患者における標準カロリー・タンパク目標と低カロリー・タンパク目標を比較したオープンラベルのRCT（NUTRIREA-3）の結果です。

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

Reignier J, Plantefeve G, Mira JP, et al. Lancet Respir Med. 2023;11(7):602-612.

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.

PMID: 36958363

ICU入室後の1週間は、低カロリー（6 kcal/kg/day）・低タンパク（0.2〜0.4 g/kg/day）の栄養目標も許容されそうです。むしろ嘔吐・下痢・腸管虚血・肝障害を減らせる可能性があり、（特に元の栄養状態が良好なら）積極的に栄養の増量を目指す必要はないのかもしれません。ただし、8日目からは両群とも30 kcal/kg/day・1.2〜2.0 g/kg/dayの栄養目標に変更となっている点には注意が必要です。

ちなみにこの研究では基本的に実体重を用いていますが、肥満（BMI >30）の時はBMI 30として体重を計算し、逆に痩せ（BMI <18.5）の場合は実体重と理想体重の平均を使用していました。体重50kgだとすると300 kcal/day・10〜20 g/dayで、よく使われる栄養剤だとペプタメンAFちょうど1本200 mLで300 kcal・19 gとなりますね（COIはありません）。いわゆるtrophic feedingとしても少ない印象ですが、急性期の内因性エネルギーを考慮すれば十分なのかもしれません。