Feinberg Joshua, Nielsen Emil Eik, Korang Steven Kwasi, Halberg Engell Kirstine, Nielsen Marie Skøtt, Zhang Kang, Didriksen Maria, Lund Lisbeth, Lindahl Niklas, Hallum Sara, Liang Ning, Xiong Wenjing, Yang Xuemei, Brunsgaard Pernille, Garioud Alexandre, Safi Sanam, Lindschou Jane, Kondrup Jens, Gluud Christian, Jakobsen Janus C
Copenhagen Trial Unit, Centre for Clinical Intervention Research, Department 7812, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, Copenhagen, Denmark, 2100.
Centre for Evidence-Based Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China.
Cochrane Database Syst Rev. 2017 May 19;5(5):CD011598. doi: 10.1002/14651858.CD011598.pub2.
The prevalence of disease-related malnutrition in Western European hospitals is estimated to be about 30%. There is no consensus whether poor nutritional status causes poorer clinical outcome or if it is merely associated with it. The intention with all forms of nutrition support is to increase uptake of essential nutrients and improve clinical outcome. Previous reviews have shown conflicting results with regard to the effects of nutrition support.
To assess the benefits and harms of nutrition support versus no intervention, treatment as usual, or placebo in hospitalised adults at nutritional risk.
We searched Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, MEDLINE (Ovid SP), Embase (Ovid SP), LILACS (BIREME), and Science Citation Index Expanded (Web of Science). We also searched the World Health Organization International Clinical Trials Registry Platform (www.who.int/ictrp); ClinicalTrials.gov; Turning Research Into Practice (TRIP); Google Scholar; and BIOSIS, as well as relevant bibliographies of review articles and personal files. All searches are current to February 2016.
We include randomised clinical trials, irrespective of publication type, publication date, and language, comparing nutrition support versus control in hospitalised adults at nutritional risk. We exclude trials assessing non-standard nutrition support.
We used standard methodological procedures expected by Cochrane and the Cochrane Hepato-Biliary Group. We used trial domains to assess the risks of systematic error (bias). We conducted Trial Sequential Analyses to control for the risks of random errors. We considered a P value of 0.025 or less as statistically significant. We used GRADE methodology. Our primary outcomes were all-cause mortality, serious adverse events, and health-related quality of life.
We included 244 randomised clinical trials with 28,619 participants that met our inclusion criteria. We considered all trials to be at high risk of bias. Two trials accounted for one-third of all included participants. The included participants were heterogenous with regard to disease (20 different medical specialties). The experimental interventions were parenteral nutrition (86 trials); enteral nutrition (tube-feeding) (80 trials); oral nutrition support (55 trials); mixed experimental intervention (12 trials); general nutrition support (9 trials); and fortified food (2 trials). The control interventions were treatment as usual (122 trials); no intervention (107 trials); and placebo (15 trials). In 204/244 trials, the intervention lasted three days or more.We found no evidence of a difference between nutrition support and control for short-term mortality (end of intervention). The absolute risk was 8.3% across the control groups compared with 7.8% (7.1% to 8.5%) in the intervention groups, based on the risk ratio (RR) of 0.94 (95% confidence interval (CI) 0.86 to 1.03, P = 0.16, 21,758 participants, 114 trials, low quality of evidence). We found no evidence of a difference between nutrition support and control for long-term mortality (maximum follow-up). The absolute risk was 13.2% in the control group compared with 12.2% (11.6% to 13%) following nutritional interventions based on a RR of 0.93 (95% CI 0.88 to 0.99, P = 0.03, 23,170 participants, 127 trials, low quality of evidence). Trial Sequential Analysis showed we only had enough information to assess a risk ratio reduction of approximately 10% or more. A risk ratio reduction of 10% or more could be rejected.We found no evidence of a difference between nutrition support and control for short-term serious adverse events. The absolute risk was 9.9% in the control groups versus 9.2% (8.5% to 10%), with nutrition based on the RR of 0.93 (95% CI 0.86 to 1.01, P = 0.07, 22,087 participants, 123 trials, low quality of evidence). At long-term follow-up, the reduction in the risk of serious adverse events was 1.5%, from 15.2% in control groups to 13.8% (12.9% to 14.7%) following nutritional support (RR 0.91, 95% CI 0.85 to 0.97, P = 0.004, 23,413 participants, 137 trials, low quality of evidence). However, the Trial Sequential Analysis showed we only had enough information to assess a risk ratio reduction of approximately 10% or more. A risk ratio reduction of 10% or more could be rejected.Trial Sequential Analysis of enteral nutrition alone showed that enteral nutrition might reduce serious adverse events at maximum follow-up in people with different diseases. We could find no beneficial effect of oral nutrition support or parenteral nutrition support on all-cause mortality and serious adverse events in any subgroup.Only 16 trials assessed health-related quality of life. We performed a meta-analysis of two trials reporting EuroQoL utility score at long-term follow-up and found very low quality of evidence for effects of nutritional support on quality of life (mean difference (MD) -0.01, 95% CI -0.03 to 0.01; 3961 participants, two trials). Trial Sequential Analyses showed that we did not have enough information to confirm or reject clinically relevant intervention effects on quality of life.Nutrition support may increase weight at short-term follow-up (MD 1.32 kg, 95% CI 0.65 to 2.00, 5445 participants, 68 trials, very low quality of evidence).
AUTHORS' CONCLUSIONS: There is low-quality evidence for the effects of nutrition support on mortality and serious adverse events. Based on the results of our review, it does not appear to lead to a risk ratio reduction of approximately 10% or more in either all-cause mortality or serious adverse events at short-term and long-term follow-up.There is very low-quality evidence for an increase in weight with nutrition support at the end of treatment in hospitalised adults determined to be at nutritional risk. The effects of nutrition support on all remaining outcomes are unclear.Despite the clinically heterogenous population and the high risk of bias of all included trials, our analyses showed limited signs of statistical heterogeneity. Further trials may be warranted, assessing enteral nutrition (tube-feeding) for different patient groups. Future trials ought to be conducted with low risks of systematic errors and low risks of random errors, and they also ought to assess health-related quality of life.
据估计，西欧医院中与疾病相关的营养不良患病率约为30%。对于营养状况不佳是导致临床结局更差，还是仅仅与之相关，目前尚无共识。所有形式的营养支持的目的都是增加必需营养素的摄入量并改善临床结局。以往的综述显示，关于营养支持的效果存在相互矛盾的结果。
评估营养支持与不干预、常规治疗或安慰剂相比，对有营养风险的住院成年人的益处和危害。
我们检索了Cochrane图书馆中的Cochrane对照试验中心注册库（CENTRAL）、MEDLINE（Ovid SP）、Embase（Ovid SP）、LILACS（BIREME）和科学引文索引扩展版（Web of Science）。我们还检索了世界卫生组织国际临床试验注册平台（www.who.int/ictrp）、ClinicalTrials.gov、将研究转化为实践（TRIP）、谷歌学术以及BIOSIS，以及综述文章的相关参考文献和个人文件。所有检索截至2016年2月。
我们纳入了随机临床试验，无论其出版物类型、出版日期和语言如何，比较营养支持与有营养风险的住院成年人的对照。我们排除了评估非标准营养支持的试验。
我们采用了Cochrane和Cochrane肝胆组预期的标准方法程序。我们使用试验领域来评估系统误差（偏倚）的风险。我们进行了试验序贯分析以控制随机误差的风险。我们将P值小于或等于0.025视为具有统计学意义。我们使用了GRADE方法。我们的主要结局是全因死亡率、严重不良事件和健康相关生活质量。
我们纳入了244项随机临床试验，共28,619名参与者，符合我们的纳入标准。我们认为所有试验都存在高偏倚风险。两项试验占所有纳入参与者的三分之一。纳入的参与者在疾病方面具有异质性（20个不同的医学专科）。实验性干预措施包括肠外营养（86项试验）、肠内营养（管饲）（80项试验）、口服营养支持（55项试验）、混合实验性干预（12项试验）、一般营养支持（9项试验）和强化食品（2项试验）。对照干预措施包括常规治疗（122项试验）不干预（107项试验）和安慰剂（15项试验）。在204/244项试验中，干预持续三天或更长时间。我们没有发现营养支持与对照在短期死亡率（干预结束时）方面存在差异的证据。基于风险比（RR）为0.94（95%置信区间（CI）0.86至1.03，P = 0.16，21,758名参与者，114项试验，低质量证据），对照组的绝对风险为8.3%，干预组为7.8%（7.1%至8.5%）。我们没有发现营养支持与对照在长期死亡率（最长随访期）方面存在差异的证据。基于RR为0.93（95%CI 0.88至0.99，P = 0.03，23,170名参与者，127项试验，低质量证据），对照组的绝对风险为13.2%，营养干预后为12.2%（11.6%至13%）。试验序贯分析表明，我们只有足够的信息来评估风险比降低约10%或更多的情况。可以排除风险比降低10%或更多的情况。我们没有发现营养支持与对照在短期严重不良事件方面存在差异的证据。基于RR为0.93（95%CI 0.86至1.01，P = 0.07，22,087名参与者，123项试验，低质量证据），对照组的绝对风险为9.9%，营养组为9.2%（8.5%至10%）。在长期随访中，严重不良事件风险降低了1.5%，从对照组的15.2%降至营养支持后的13.8%（12.9%至14.7%）（RR 0.91，95%CI 0.85至0.97，P = 0.004，23,413名参与者，137项试验，低质量证据）。然而，试验序贯分析表明，我们只有足够的信息来评估风险比降低约10%或更多的情况。可以排除风险比降低10%或更多的情况。单独对肠内营养进行试验序贯分析表明，肠内营养可能会降低不同疾病患者在最长随访期的严重不良事件。我们在任何亚组中都未发现口服营养支持或肠外营养支持对全因死亡率和严重不良事件有有益影响。只有16项试验评估了健康相关生活质量。我们对两项在长期随访中报告欧洲五维健康量表效用评分的试验进行了荟萃分析，发现营养支持对生活质量影响的证据质量非常低（平均差（MD）-0.01，95%CI -0.03至0.01；3961名参与者，两项试验）。试验序贯分析表明，我们没有足够的信息来确认或排除对生活质量的临床相关干预效果。营养支持可能会在短期随访中增加体重（MD 1.32 kg，95%CI 0.65至2.00，5445名参与者，68项试验，极低质量证据）。
关于营养支持对死亡率和严重不良事件影响的证据质量较低。根据我们的综述结果，在短期和长期随访中，营养支持似乎不会使全因死亡率或严重不良事件的风险比降低约10%或更多。对于确定有营养风险的住院成年人，在治疗结束时营养支持使体重增加的证据质量非常低。营养支持对所有其他结局的影响尚不清楚。尽管纳入试验的临床人群具有异质性且所有试验都存在高偏倚风险，但我们分析显示统计异质性迹象有限。可能需要进一步开展试验，评估针对不同患者群体的肠内营养（管饲）。未来的试验应该在系统误差风险低和随机误差风险低的情况下进行，并且还应该评估健康相关生活质量。
