PDF(Pubmed)
Abstract：
Delivering higher doses of protein to mechanically ventilated critically ill patients did not improve patient outcomes and may have caused harm. Longitudinal urea measurements could provide additional information about the treatment effect of higher protein doses. We hypothesised that higher urea values over time could explain the potential harmful treatment effects of higher doses of protein.
We conducted a reanalysis of a randomised controlled trial of higher protein doses in critical illness (EFFORT Protein). We applied Bayesian joint models to estimate the strength of association of urea with 30-day survival and understand the treatment effect of higher protein doses.
Of the 1301 patients included in EFFORT Protein, 1277 were included in this analysis. There were 344 deaths at 30 days post-randomisation. By day 6, median urea was 2.1 mmol/L higher in the high protein group (95% CI 1.1-3.2), increasing to 3.0 mmol/L (95% CI 1.3-4.7) by day 12. A twofold rise in urea was associated with an increased risk of death at 30 days (hazard ratio 1.34, 95% credible interval 1.21-1.48), following adjustment of baseline characteristics including age, illness severity, renal replacement therapy, and presence of AKI. This association persisted over the duration of 30-day follow-up and in models adjusting for evolution of organ failure over time.
The increased risk of death in patients randomised to a higher protein dose in the EFFORT Protein trial was estimated to be mediated by increased urea cycle activity, of which serum urea is a biological signature. Serum urea should be taken into consideration when initiating and continuing protein delivery in critically ill patients.
gov Identifier: NCT03160547 (2017-05-17).
We conducted a reanalysis of a randomised controlled trial of higher protein doses in critical illness (EFFORT Protein). We applied Bayesian joint models to estimate the strength of association of urea with 30-day survival and understand the treatment effect of higher protein doses.
Of the 1301 patients included in EFFORT Protein, 1277 were included in this analysis. There were 344 deaths at 30 days post-randomisation. By day 6, median urea was 2.1 mmol/L higher in the high protein group (95% CI 1.1-3.2), increasing to 3.0 mmol/L (95% CI 1.3-4.7) by day 12. A twofold rise in urea was associated with an increased risk of death at 30 days (hazard ratio 1.34, 95% credible interval 1.21-1.48), following adjustment of baseline characteristics including age, illness severity, renal replacement therapy, and presence of AKI. This association persisted over the duration of 30-day follow-up and in models adjusting for evolution of organ failure over time.
The increased risk of death in patients randomised to a higher protein dose in the EFFORT Protein trial was estimated to be mediated by increased urea cycle activity, of which serum urea is a biological signature. Serum urea should be taken into consideration when initiating and continuing protein delivery in critically ill patients.
gov Identifier: NCT03160547 (2017-05-17).
摘要：
背景：向机械通气的危重病患者提供较高剂量的蛋白质并不能改善患者的预后，可能会造成伤害。纵向尿素测量可以提供关于较高蛋白质剂量的治疗效果的额外信息。我们假设，随着时间的推移，更高的尿素值可以解释高剂量蛋白质的潜在有害治疗效果。
方法：我们对危重病患者高剂量蛋白质（EFFORT蛋白）的随机对照试验进行了再分析。我们应用贝叶斯联合模型来估计尿素与30天生存的关联强度，并了解更高蛋白质剂量的治疗效果。
结果：在EFFORT蛋白中包含的1301例患者中，1277被包括在该分析中。随机化后30天有344例死亡。到第6天，高蛋白组的尿素中位数为2.1mmol/L（95％CI1.1-3.2），到第12天增加到3.0mmol/L（95％CI1.3-4.7）。尿素的两倍升高与30天死亡风险增加相关（危险比1.34，95%可信区间1.21-1.48），在调整包括年龄在内的基线特征后，疾病严重程度,肾脏替代疗法,AKI的存在。这种关联在30天随访期间以及在调整器官衰竭随时间演变的模型中持续存在。
结论：在EFFORT蛋白试验中，随机分配给较高蛋白质剂量的患者死亡风险增加估计是由尿素循环活性增加介导的。其中血清尿素是一种生物特征。在开始和继续进行危重患者的蛋白质输送时，应考虑血清尿素。
结果：政府标识符：NCT03160547（2017-05-17）。
方法：我们对危重病患者高剂量蛋白质（EFFORT蛋白）的随机对照试验进行了再分析。我们应用贝叶斯联合模型来估计尿素与30天生存的关联强度，并了解更高蛋白质剂量的治疗效果。
结果：在EFFORT蛋白中包含的1301例患者中，1277被包括在该分析中。随机化后30天有344例死亡。到第6天，高蛋白组的尿素中位数为2.1mmol/L（95％CI1.1-3.2），到第12天增加到3.0mmol/L（95％CI1.3-4.7）。尿素的两倍升高与30天死亡风险增加相关（危险比1.34，95%可信区间1.21-1.48），在调整包括年龄在内的基线特征后，疾病严重程度,肾脏替代疗法,AKI的存在。这种关联在30天随访期间以及在调整器官衰竭随时间演变的模型中持续存在。
结论：在EFFORT蛋白试验中，随机分配给较高蛋白质剂量的患者死亡风险增加估计是由尿素循环活性增加介导的。其中血清尿素是一种生物特征。在开始和继续进行危重患者的蛋白质输送时，应考虑血清尿素。
结果：政府标识符：NCT03160547（2017-05-17）。
