Heller Axel R, Rössler Susann, Litz Rainer J, Stehr Sebastian N, Heller Susanne C, Koch Rainer, Koch Thea
Department of Anesthesiology and Critical Care Medicine, The University Hospital Carl Gustav Carus, Dresden, Germany.
Crit Care Med. 2006 Apr;34(4):972-9. doi: 10.1097/01.CCM.0000206309.83570.45.
Supplementation of clinical nutrition with omega-3 fatty acid in fish oil exerts immune-modulating and organ-protective effects, even after short-term application. The aim of this study was to evaluate dose-dependent effects of parenteral supplementation of a 10% fish oil emulsion (Omegaven, Fresenius-Kabi, Bad Homburg, Germany) on diagnosis- and organ failure-related outcome.
Prospective, open label, multiple-center trial.
A total of 661 patients from 82 German hospitals receiving total parenteral nutrition for > or =3 days were enrolled in this study. The sample included 255 patients after major abdominal surgery, 276 with peritonitis and abdominal sepsis, 16 with nonabdominal sepsis, 59 after multiple trauma, 18 with severe head injury, and 37 with other diagnoses. The primary study end point was survival; secondary end points were length of hospital stay and use of antibiotics with respect to the primary diagnosis and the extent of organ failure. Multiple quasi-linear and logistic regression models were used for calculating diagnosis-related fish oil doses associated with best outcome.
The patients enrolled in this survey were (mean +/- sd) 62.8 +/- 16.5 yrs old, with a body mass index of 25.1 +/- 4.2 and Simplified Acute Physiology Score (SAPS) II score of 32.2 +/- 13.6. Length of hospital stay was 29.1 +/- 18.7 days (12.5 +/- 14.8 days in the intensive care unit). Total parenteral nutrition, including fish oil (mean, 0.11 g.kg(-1).day(-1)), was administered for 8.7 +/- 7.5 days and lowered hospital mortality as predicted by Simplified Acute Physiology Score II from 18.9% (95% confidence interval, 17.4-20.4%) to 12.0% (p < .001). The fish oil dose.kg.day did correlate with beneficial outcome (intensive care unit stay, hospital stay, mortality). Fish oil had the most favorable effects on survival, infection rates, and length of stay when administered in doses between 0.1 and 0.2 g.kg(-1).day(-1). Lower antibiotic demand by 26% was observed when doses of 0.15-0.2 g.kg(-1).day(-1) were infused as compared with doses of <0.05 g.kg(-1).day(-1). After peritonitis and abdominal sepsis, multiple quasi-linear regression models revealed a fish oil dose for minimizing intensive care unit stay of 0.23 g.kg(-1).day(-1) and an inverse linear relationship between dosage and intensive care unit stay in major abdominal surgery.
Administration of omega-3 fatty acid may reduce mortality, antibiotic use, and length of hospital stay in different diseases. Effects and effect sizes related to fish oil doses are diagnosis dependent. In view of the lack of substantial study literature concerning diagnosis-related nutritional single-substrate intervention in the critically ill, the present data can be used in formulating hypotheses and may serve as reference doses for randomized, controlled studies, which may, for instance, confirm the value of omega-3 fatty acid in the adjunctive therapy of peritonitis and abdominal sepsis.
即使短期应用，通过鱼油补充临床营养中的ω-3脂肪酸也能发挥免疫调节和器官保护作用。本研究的目的是评估肠外补充10%鱼油乳剂（Omegaven，费森尤斯卡比公司，德国巴特洪堡）对诊断及器官功能衰竭相关结局的剂量依赖性影响。
前瞻性、开放标签、多中心试验。
本研究纳入了来自德国82家医院的661例接受全肠外营养≥3天的患者。样本包括255例腹部大手术后患者、276例腹膜炎和腹部脓毒症患者、16例非腹部脓毒症患者、59例多发伤患者、18例重度颅脑损伤患者以及37例其他诊断患者。主要研究终点为生存；次要终点为住院时间以及针对主要诊断和器官功能衰竭程度使用抗生素的情况。采用多个准线性和逻辑回归模型计算与最佳结局相关的诊断特异性鱼油剂量。
本调查纳入的患者年龄为（平均±标准差）62.8±16.5岁，体重指数为25.1±4.2，简化急性生理学评分（SAPS）II评分为32.2±13.6。住院时间为29.1±18.7天（重症监护病房为12.5±14.8天）。包括鱼油（平均0.11 g·kg⁻¹·天⁻¹）在内的全肠外营养给予8.7±7.5天，使简化急性生理学评分II预测的医院死亡率从18.9%（95%置信区间，17.4 - 20.4%）降至12.0%（p < 0.001）。鱼油剂量（g·kg·天）与有益结局（重症监护病房住院时间、住院时间、死亡率）相关。当以0.1至0.2 g·kg⁻¹·天⁻¹的剂量给予鱼油时，对生存、感染率和住院时间的影响最为有利。与剂量<0.05 g·kg⁻¹·天⁻¹相比，当输注剂量为0.15 - 0.2 g·kg⁻¹·天⁻¹时，抗生素需求量降低了26%。在腹膜炎和腹部脓毒症后，多个准线性回归模型显示，使重症监护病房住院时间最短的鱼油剂量为0.23 g·kg⁻¹·天⁻¹，且在腹部大手术中剂量与重症监护病房住院时间呈负线性关系。
给予ω-3脂肪酸可能降低不同疾病的死亡率、抗生素使用量和住院时间。与鱼油剂量相关的效应和效应大小取决于诊断。鉴于缺乏关于危重症患者诊断特异性营养单底物干预的大量研究文献，目前的数据可用于提出假设，并可作为随机对照研究的参考剂量，例如，这类研究可能会证实ω-3脂肪酸在腹膜炎和腹部脓毒症辅助治疗中的价值。
