【美国医学会杂志】营养不良内科住院患者的营养支持与结局：系统回顾与荟萃分析
在急症期间，营养疗法广泛用于营养不良或有营养不良风险内科住院患者。但是，就我们所知，尚无全面性试验表明该疗法有效并有利于患者。
因此，瑞士和加拿大的研究者发表于《美国医学会杂志·内科学分册》（JAMA Internal Medicine）的随机临床试验（RCT）系统回顾中，评估了营养支持对营养不良或有营养不良风险内科住院患者结局的影响。
2015年3月10日至2015年9月16日，研究者根据事先确定的Cochrane方案，系统检索了Cochrane Library、MEDLINE和EMBASE中1982年10月5日至2014年4月30日期间在不同国家（欧洲为主）比较营养支持（包括营养会诊、口服和肠内喂养）对内科住院患者影响的RCT。
两位回顾者各自提取研究特征、方法和结局的数据，通过讨论解决不一致。
主要研究结局为死亡率，次要结局包括医院获得性感染、非择期再入院、功能性结局、住院天数、每日热量和蛋白质摄入量和体重变化。
研究者纳入了22项RCT共3736例受试者，纳入的RCT异质性高，研究质量总体偏低，偏倚风险大多不明。干预组患者与对照组患者相比，体重、热量摄入量、蛋白质摄入量显著增加（平均差：0.72kg、397kcal、20.0g/d；95% CI：0.23～1.21kg、279～515kcal、12.5～27.1g/d）。干预组患者和对照组患者的死亡率（9.8%比10.3%；比值比[OR]：0.96；95% CI：0.72～1.27）、医院获得性感染（总体：6.0%比7.6%；OR：0.75；95% CI：0.50～1.11）、功能性结局（Barthel指数平均差：0.33分；95% CI：-0.88至1.55分）或住院天数（平均差：-0.42d；95% CI：-1.09至0.24d）未见差异。干预组非择期再入院显著减少（20.5%比29.6%；风险比：0.71；95% CI：0.57～0.87）。
该研究结果表明，在内科住院患者中，营养支持可增加热量、蛋白质摄入量和体重。但是，对临床结局总体影响不大（除了非择期再入院）。因此，亟需高质量的RCT填补这一空白。
JAMA Intern Med. 2016;176(1):43-53.
Nutritional Support and Outcomes in Malnourished Medical Inpatients: A Systematic Review and Meta-analysis.
Bally MR, Blaser Yildirim PZ, Bounoure L, Gloy VL, Mueller B, Briel M, Schuetz P.
University Department of Medicine, Clinic for Endocrinology/Metabolism/Clinical Nutrition, Kantonsspital Aarau, Aarau, Switzerland.
Medical Faculty of the University of Basel, Basel, Switzerland.
General Medicine, Dr M. Deppeler, Zollikofen, Switzerland.
Basel Institute for Clinical Epidemiology and Biostatistics, Department of Clinical Research, University Hospital Basel, Basel, Switzerland.
Institute of Nuclear Medicine, University Hospital Bern, Bern, Switzerland.
Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada.
IMPORTANCE: During acute illness, nutritional therapy is widely used for medical inpatients with malnutrition or at risk for malnutrition. Yet, to our knowledge, no comprehensive trial has demonstrated that this approach is effective and beneficial for patients.
OBJECTIVE: To assess the effects of nutritional support on outcomes of medical inpatients with malnutrition or at risk for malnutrition in a systematic review of randomized clinical trials (RCTs).
DATA SOURCES: The Cochrane Library, MEDLINE, and EMBASE. The study dates were October 5, 1982, to April 30, 2014, in various (mostly European) countries. The dates of our analysis were March 10, 2015, to September 16, 2015.
STUDY SELECTION: Based on a prespecified Cochrane protocol, we systematically searched RCTs investigating the effects of nutritional support (including counseling and oral and enteral feeding) in medical inpatients compared with a control group.
DATA EXTRACTION: Two reviewers extracted data on study characteristics, methods, and outcomes. Disagreement was resolved by consensus.
MAIN OUTCOMES AND MEASURES: The primary study outcome was mortality. Secondary outcomes included hospital-acquired infections, nonelective readmissions, functional outcome, length of hospital stay, daily caloric and protein intake, and weight change.
RESULTS: We included 22 RCTs with a total of 3736 participants. Heterogeneity across RCTs was high, with overall low study quality and mostly unclear risk of bias. Intervention group patients significantly increased their weight (mean difference, 0.72 kg; 95% CI, 0.23-1.21 kg), caloric intake (mean difference, 397 kcal; 95% CI, 279-515 kcal), and protein intake (mean difference, 20.0 g/d; 95% CI, 12.5-27.1 g/d) compared with control group patients. No differences between intervention group patients and control group patients were found with respect to mortality (9.8% vs 10.3%; odds ratio [OR], 0.96; 95% CI, 0.72-1.27), hospital-acquired infections (overall, 6.0% vs 7.6%; OR, 0.75; 95% CI, 0.50-1.11), functional outcome (mean Barthel index difference, 0.33 point; 95% CI, -0.88 to 1.55 points), or length of hospital stay (mean difference, -0.42 days; 95% CI, -1.09 to 0.24 days). Nonelective readmissions were significantly decreased by the intervention (20.5% vs 29.6%; risk ratio, 0.71; 95% CI, 0.57-0.87).
CONCLUSIONS AND RELEVANCE: In medical inpatients, nutritional support increases caloric and protein intake and body weight. However, there is little effect on clinical outcomes overall except for nonelective readmissions. High-quality RCTs are needed to fill this gap.
PMID: 26720894
DOI: 10.1001/jamainternmed.2015.6587
Invited Commentary:
JAMA Intern Med. 2016;176(1):53-4.
Nutritional Support on the Medical Wards-Thought for Food.
Kushner JP, Lacy JA, Gay SR.
Division of Digestive Diseases, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio.
Division of Trauma and Critical Care, Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, Ohio.
Malnutrition lurks in the background, if not the forefront, of hospitalized patients. More than one-third of patients are seen in the hospital with varying degrees of malnutrition,[1] and far too many experience further nutritional deterioration during their stay and convalescence. We have become more alert to this challenge ever since the shocking revelations in 1974 by Butterworth[2] that the issue of nutrition of inpatients was frequently neglected. Well before that, suboptimal nutrition states were closely associated with poor outcomes.[3] However, 40 years after our eyes were opened to this long-ignored issue, we struggle to identify appropriate patients and efficacious nutritional interventions.
Malnutrition has been defined as a subacute or chronic state of nutrition in which a combination of varying degrees of overnutrition or undernutrition and inflammatory activity have led to deleterious changes in body composition and diminished function. While early and mild effects on appetite, intake, and metabolism are beneficial physiological responses in a host undergoing an inflammatory challenge, prolongation of these effects can eventually lead to impaired defenses and function, with worse outcomes. Nutritional interventions have the potential to offset some of the excessive losses and deficiencies but can also result in undesired consequences if delivered at the wrong time, in the wrong form, or by the wrong way. Nowhere has this dilemma been more clearly demonstrated than in critical care populations receiving overzealous deliveries of glucose, fat, and other nutrients via the parenteral route, resulting in hyperglycemia, immunosuppression, and negative outcomes.[4] Most of our current knowledge and subsequent recommendations for nutritional intervention have come from studies of critical care or surgical populations, among whom time points, interventions, and end points can be more clearly defined and controlled. There is still controversy as to the optimal timing, route, and composition of nutritional interventions. Less well delineated are outcomes and recommendations for polymorbid hospitalized general medical patients. These patients often are seen with varying degrees of chronic malnutrition exacerbated by acute or chronic medical illness, and they may have coexisting conditions, each presenting challenges to the nutritional and metabolic milieu. As in other clinical settings, malnutrition and ongoing suboptimal food intake have been associated with failure to thrive, higher rates of infection, and greater hospital length of stay, readmission, and mortality, as well as increased health care costs. Well-designed intervention studies with clear outcomes in this population are more challenging, making guidelines difficult to design.
In this issue of JAMA Internal Medicine, Bally and colleagues[5] present an appropriately conducted meta-analysis of trials addressing nutritional intervention in malnourished medical inpatients. They analyzed 22 randomized clinical trials of more than 3700 patients that looked primarily at polymorbid medical inpatients between 1989 and 2014. High heterogeneity across the studies was seen, as well as some unknown biases. As expected, nutritional intervention groups (mostly oral supplements or counseling, with fewer receiving enteral tube feeding) had greater intake and weight gain than control arms, but the primary outcome of mortality and important secondary outcomes of infections, physical function, or hospital length of stay were not aided by nutritional intervention. There was a trend to a shorter length of stay in a subgroup of already malnourished patients. Nonelective readmissions in the intervention groups were statistically less, with a number needed to treat of 23. Overall, even with the potential for publication and attrition bias, the benefits of nutritional intervention in this population appear to be modest. However, while the hospital readmission rate was not the primary outcome of this meta-analysis, the improvement seen presents a potentially important piece of evidence to support nutritional intervention in light of rising health care costs in the 21st century. To date, there have been limited cost-effective analyses of nutritional intervention in medical inpatients,[6] perhaps a topic in need of further investigation.
Earlier, Potter et al[7] examined 30 randomized trials of routine oral or enteral protein supplementation in a meta-analysis of more than 2000 adults. They found improved nutritional indexes but an uncertain trend to reduced mortality, hampered by publication bias and trial methods. The population was composed of both healthy elderly outpatients and a mix of surgical and medical inpatients using predominantly oral supplementation. Subgroup analysis showed a less impressive mortality benefit for supplementation in medical patients. The large Cochrane Collaboration meta-analysis by Milne et al[8] examined oral nutritional supplementation in more than 10,000 elderly patients in 62 trials. The majority were hospitalized patients. Again, nutritional status improved with intervention, but other beneficial outcomes were not demonstrated because of problems with study methods and quality. Reduced mortality in the already malnourished subgroup was suggested. Inadequate duration of supplementation was cited as a potential drawback. A large systematic review of randomized trials of oral or tube-fed supplementation by Koretz et al[9] found benefits with oral supplementation only in the already malnourished elderly among medical patients.
Joint Commission on Accreditation of Healthcare Organizations regulations have prompted more rigorous nutritional screening in hospitalized patients.[10] In turn, a number of organizations have promulgated pathways and guidelines not only for screening and assessment of all hospitalized patients but also for nutritional intervention. However, the recommendations outside of the critical care or perioperative arena in many cases are based on low levels of evidence, derived from trials that fail to provide clear-cut evidence of beneficial and cost-effective nutritional intervention.
Several challenges remain. Our present-day practices may result in mishandling the delicate balance of nutritional, metabolic, and immune system function, to our patients' detriment. Current composition and timing of nutritional therapy may be suboptimal. Oral supplements and some tube feedings contain significant amounts of sugar, corn syrup solids, and maltodextrin, which may affect glycemic index and other responses. Continuous tube feeding and parenteral nutrition may potentially desynchronize a range of anabolic metabolic processes. The relationships among nutrition, activity, and physical therapy to optimize nutrient and growth effect may be underappreciated.
Medical inpatients represent a diverse group with complicated needs, and it may not be possible to make broad recommendations across this population. We should continue to strive for high-quality randomized studies that more clearly delineate appropriate target populations for nutritional intervention and, with that, the specific route, type, and amount of nutrition that results in the best outcome. Even for the less invasive and less expensive option of dietary counseling and oral supplements, we must be sure that these methods also avoid unwanted negative effects and meet cost-effective standards. The exciting challenge of defining optimal nutritional interventions for specific situations continues.
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Casaer MP, Mesotten D, Hermans G, et al. Early versus late parenteral nutrition in critically ill adults. N Engl J Med. 2011;365(6):506-517.
Bally MR, Blaser Yildirim PZ, Bounoure L, et al. Nutritional support and outcomes in malnourished medical inpatients: a systematic review and meta-analysis. JAMA Intern Med. 2016;176(1):43-53.
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Potter J, Langhorne P, Roberts M. Routine protein energy supplementation in adults: systematic review. BMJ. 1998;317(7157):495-501.
Milne AC, Potter J, Vivanti A, Avenell A. Protein and energy supplementation in elderly people at risk from malnutrition. Cochrane Database Syst Rev. 2009;(2):CD003288.
Koretz RL, Avenell A, Lipman TO, Braunschweig CL, Milne AC. Does enteral nutrition affect clinical outcome? a systematic review of the randomized trials. Am J Gastroenterol. 2007;102(2):412-429.
Mueller C, Compher C, Ellen DM; American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.) Board of Directors. A.S.P.E.N. clinical guidelines: Nutrition screening, assessment, and intervention in adults. JPEN J Parenter Enteral Nutr. 2011;35(1):16-24.
PMID: 26720103
DOI: 10.1001/jamainternmed.2015.7062