Proteins are an essential part of medical nutrition therapy in critically ill patients. Guidelines almost universally recommend a high protein intake without robust evidence supporting its use. Using a large international database, we modelled associations between the hazard rate of in-hospital death and live hospital discharge (competing risks) and three categories of protein intake (low: < 0.8 g/kg per day, standard: 0.8–1.2 g/kg per day, high: > 1.2 g/kg per day) during the first 11 days after ICU admission (acute phase). Time-varying cause-specific hazard ratios (HR) were calculated from piece-wise exponential additive mixed models. We used the estimated model to compare five different hypothetical protein diets (an exclusively low protein diet, a standard protein diet administered early (day 1 to 4) or late (day 5 to 11) after ICU admission, and an early or late high protein diet). Of 21,100 critically ill patients in the database, 16,489 fulfilled inclusion criteria for the analysis. By day 60, 11,360 (68.9%) patients had been discharged from hospital, 4,192 patients (25.4%) had died in hospital, and 937 patients (5.7%) were still hospitalized. Median daily low protein intake was 0.49 g/kg [IQR 0.27–0.66], standard intake 0.99 g/kg [IQR 0.89– 1.09], and high intake 1.41 g/kg [IQR 1.29–1.60]. In comparison with an exclusively low protein diet, a late standard protein diet was associated with a lower hazard of in-hospital death: minimum 0.75 (95% CI 0.64, 0.87), and a higher hazard of live hospital discharge: maximum HR 1.98 (95% CI 1.72, 2.28). Results on hospital discharge, however, were qualitatively changed by a sensitivity analysis. There was no evidence that an early standard or a high protein intake during the acute phase was associated with a further improvement of outcome. Provision of a standard protein intake during the late acute phase may improve outcome compared to an exclusively low protein diet. In unselected critically ill patients, clinical outcome may not be improved by a high protein intake during the acute phase. Study registration ID number ISRCTN17829198

中文翻译：

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危重患者的蛋白质摄入和结果：使用分段指数加性混合模型分析大型国际数据库

蛋白质是重症患者医学营养治疗的重要组成部分。指南几乎普遍推荐高蛋白质摄入量，但没有强有力的证据支持其使用。使用大型国际数据库，我们模拟了住院死亡和出院（竞争风险）的危险率与三类蛋白质摄入量（低：< 0.8 g/kg/天，标准：0.8–1.2 g/ kg/d，高：> 1.2 g/kg/d）在 ICU 入院后的前 11 天（急性期）。从分段指数加性混合模型计算随时间变化的特定原因风险比 (HR)。我们使用估计模型比较了五种不同的假设蛋白质饮食（完全低蛋白饮食，ICU 入院后早期（第 1 至 4 天）或晚期（第 5 至 11 天）给予标准蛋白质饮食，以及早期或晚期高蛋白饮食）。在数据库中的 21,100 名危重患者中，有 16,489 名符合分析的纳入标准。到第 60 天，11,360 例（68.9%）患者已出院，4,192 例（25.4%）在医院死亡，937 例（5.7%）仍在住院。每日低蛋白摄入量中位数为 0.49 g/kg [IQR 0.27–0.66]，标准摄入量为 0.99 g/kg [IQR 0.89–1.09]，高摄入量为 1.41 g/kg [IQR 1.29–1.60]。与完全低蛋白饮食相比，晚期标准蛋白饮食与较低的院内死亡风险相关：最低 0.75 (95% CI 0.64, 0.87)，以及更高的出院风险：最高 HR 1.98 ( 95% CI 1.72, 2.28)。然而，出院的结果，通过敏感性分析进行了质的改变。没有证据表明在急性期早期标准或高蛋白质摄入与结果的进一步改善有关。与完全低蛋白饮食相比，在急性晚期提供标准蛋白质摄入可能会改善结果。在未经选择的重症患者中，急性期高蛋白摄入可能不会改善临床结果。研究注册ID号ISRCTN17829198 在未经选择的重症患者中，急性期高蛋白摄入可能不会改善临床结果。研究注册ID号ISRCTN17829198 在未经选择的重症患者中，急性期高蛋白摄入可能不会改善临床结果。研究注册ID号ISRCTN17829198