Effects of enteral feeding with eicosapentaenoic acid, gamma-linolenic acid, and antioxidants in mechanically ventilated patients with severe sepsis and septic shock

OBJECTIVES: Enteral diets enriched with eicosapentaenoic acid (EPA), gamma-linolenic acid (GLA), and antioxidants have previously been shown to improve outcomes in patients with acute respiratory distress syndrome. Several studies using animal models of sepsis demonstrate that enteral nutrition enriched with omega-3 fatty acids reduces mortality rate. This study investigated whether an enteral diet enriched with EPA, GLA, and antioxidant vitamins can improve outcomes and reduce 28-day all-cause mortality in patients with severe sepsis or septic shock requiring mechanical ventilation. DESIGN: Prospective, double-blind, placebo-controlled, randomized trial. SETTING: Three different intensive care units of a tertiary hospital in Brazil. PATIENTS: The study enrolled 165 patients. INTERVENTIONS: Patients were randomized to be continuously tube-fed with either a diet enriched with EPA, GLA, and elevated antioxidants or an isonitrogenous and isocaloric control diet, delivered at a constant rate to achieve a minimum of 75% of basal energy expenditure x 1.3 during a minimum of 4 days. MEASUREMENTS AND MAIN RESULTS: Patients were monitored for 28 days. Patients who were fed with the study diet experienced a significant reduction in mortality rate compared with patients fed with the control diet, the absolute mortality reduction amounting to 19.4% (p = .037). The group who received the study diet also experienced significant improvements in oxygenation status, more ventilator-free days (13.4 +/- 1.2 vs. 5.8 +/- 1.0, p < .001), more intensive care unit (ICU)-free days (10.8 +/- 1.1 vs. 4.6 +/- 0.9, p < .001), and a lesser development of new organ dysfunctions (p < .001). CONCLUSIONS: In patients with severe sepsis or septic shock and requiring mechanical ventilation and tolerating enteral nutrition, a diet enriched with EPA, GLA, and elevated antioxidants contributed to better ICU and hospital outcomes and was associated with lower mortality rates.     

Benefit of an enteral diet enriched with eicosapentaenoic acid and gamma-linolenic acid in ventilated patients with acute lung injury

OBJECTIVE: To explore the effects of an enteral diet enriched with eicosapentaenoic acid (EPA), gamma-linolenic acid (GLA), and antioxidants on the respiratory profile and outcome of patients with acute lung injury. DESIGN: Single-center, prospective, randomized, controlled, unblinded study. SETTING: General intensive care department of a tertiary-care, university-affiliated hospital. PATIENTS: A total of 100 patients with acute lung injury, diagnosed according to the American-European Consensus Conference on ARDS. INTERVENTIONS: Patients were randomized to receive the standard isonitrogenous, isocaloric enteral diet or the standard diet supplemented with EPA and GLA for 14 days. MEASUREMENTS AND MAIN RESULTS: Patient demographics, Acute Physiology and Chronic Health Evaluation II score, and type of admission were noted at admission. Compared with baseline oxygenation (EPA + GLA group vs. control group), by days 4 and 7, patients receiving the EPA + GLA diet showed significant improvement in oxygenation (PaO(2)/FIO(2), 317.3 +/- 99.5 vs. 214.3 +/- 56.4 and 296.5 +/- 165.3 vs. 236.3 +/- 79.8, respectively; p < .05). Compliance was significantly higher in the EPA + GLA group observed at day 7 (55.1 +/- 46.5 vs. 35.2 +/- 20.0 mL/mbar, p < .05). No significant difference was found in nutritional variables. Resting energy expenditure was significantly higher in patients in the EPA + GLA group, but their body mass index was also higher (p < .05). A significant difference was found in length of ventilation (p < .04) in favor of the EPA + GLA group. There was no between-group difference in survival. CONCLUSIONS: In patients with acute lung injury, a diet enriched with EPA + GLA may be beneficial for gas exchange, respiratory dynamics, and requirements for mechanical ventilation.     

Enteral nutrition with eicosapentaenoic acid,gamma-linolenic acid,and antioxidants reduces alveolar inflammatory mediators and protein influx in patients with acute respiratory distress syndrome

OBJECTIVE: Previously, we showed that acute respiratory distress syndrome patients fed an enteral diet containing eicosapentaenoic acid and gamma-linolenic acid and elevated antioxidants (EPA+GLA; Oxepa) had significantly reduced pulmonary inflammation, increased oxygenation, and improved clinical outcomes. In a subset of acute respiratory distress syndrome patients from this trial, we performed a preliminary examination of the potential mechanisms underlying these clinical improvements by retrospectively testing the hypothesis that enteral feeding with EPA+GLA could reduce alveolar-capillary membrane protein permeability and the production of interleukin (IL)-8, IL-6, tumor necrosis factor-alpha, and leukotriene B4 that are responsible, in part, for pulmonary inflammation. DESIGN: Prospective, randomized, double-blind, controlled clinical trial. SETTING: Intensive Care Unit of the Ohio State University Medical Center. PATIENTS: A total of 67 patients were enrolled who met defined criteria for acute lung injury/acute respiratory distress syndrome. INTERVENTIONS: A total of 43 of 67 evaluable patients randomly received either EPA+GLA or an isonitrogenous, isocaloric standard diet that was tube fed at a minimum caloric delivery of 75% of basal energy expenditure times 1.33 for at least 4 to 7 days. MEASUREMENTS AND MAIN RESULTS: Bronchoalveolar lavage (BAL) was performed at baseline and study days 4 and 7 to obtain BAL fluid (BALF) for measurement of total protein, ceruloplasmin, and transferrin, total neutrophil count, IL-8, IL-6, tumor necrosis factor-alpha, and leukotriene B4. Oxygenation, measured as Pao2/Fio2, was assessed before BAL. Patients fed EPA+GLA had a significant reduction in BALF ceruloplasmin and IL-8 during the study as compared with patients fed the control diet. BALF levels of total protein, neutrophils, and leukotriene B4 tended to decrease in EPA+GLA patients over the course of the study as compared with control patients. BALF levels of IL-6 declined similarly during the study in both groups. A trend toward a reduction in BALF tumor necrosis factor-alpha was observed on study day 7 in the EPA+GLA group as compared with control patients. Significant improvements in oxygenation (Pao2/Fio2) occurred in EPA+GLA patients on study day 4 as compared with controls. Correlation analysis revealed significant relationships between BALF neutrophil counts and indices of alveolar-capillary membrane protein permeability, IL-8, and leukotriene B4. CONCLUSIONS: This preliminary investigation showing a decrease in BALF levels of IL-8 and leukotriene B4 and the associated reduction of BALF neutrophils and alveolar membrane protein permeability in acute respiratory distress syndrome patients fed EPA+GLA support, in part, the potential mechanisms underlying the previously described clinical improvements with this diet. Additional controlled studies are needed to confirm these findings.     

Effect of enteral feeding with eicosapentaenoic acid, gamma-linolenic acid, and antioxidants in patients with acute respiratory distress syndrome. Enteral Nutrition in ARDS Study Group.

OBJECTIVES: Recent studies in animal models of sepsis-induced acute respiratory distress syndrome (ARDS) have shown that a low-carbohydrate, high-fat diet combining the anti-inflammatory and vasodilatory properties of eicosapentaenoic acid (EPA; fish oil), gamma-linolenic acid (GLA; borage oil) (EPA+GLA), and antioxidants improves lung microvascular permeability, oxygenation, and cardiopulmonary function and reduces proinflammatory eicosanoid synthesis and lung inflammation. These findings suggest that enteral nutrition with EPA+GLA and antioxidants may reduce pulmonary inflammation and may improve oxygenation and clinical outcomes in patients with ARDS. DESIGN: Prospective, multicentered, double-blind, randomized controlled trial. SETTING: Intensive care units of five academic and teaching hospitals in the United States. PATIENTS: We enrolled 146 patients with ARDS (as defined by the American-European Consensus Conference) caused by sepsis/pneumonia, trauma, or aspiration injury in the study. INTERVENTIONS: Patients meeting entry criteria were randomized and continuously tube-fed either EPA+GLA or an isonitrogenous, isocaloric standard diet at a minimum caloric delivery of 75% of basal energy expenditure x 1.3 for at least 4-7 days. MEASUREMENTS AND MAIN RESULTS: Arterial blood gases were measured, and ventilator settings were recorded at baseline and study days 4 and 7 to enable calculation of PaO2/FIO2, a measure of gas exchange. Pulmonary neutrophil recruitment was assessed by measuring the number of neutrophils and the total cell count in bronchoalveolar lavage fluid at the same time points. Clinical outcomes were recorded. Baseline characteristics of 98 evaluable patients revealed that key demographic, physiologic, and ventilatory variables were similar at entry between both groups. Multiple bronchoalveolar lavages revealed significant decreases (approximately 2.5-fold) in the number of total cells and neutrophils per mL of recovered lavage fluid during the study with EPA+GLA compared with patients fed the control diet. Significant improvements in oxygenation (PaO2/FIO2) from baseline to study days 4 and 7 with lower ventilation variables (FIO2, positive end-expiratory pressure, and minute ventilation) occurred in patients fed EPA+GLA compared with controls. Patients fed EPA+GLA required significantly fewer days of ventilatory support (11 vs. 16.3 days; p = .011), and had a decreased length of stay in the intensive care unit (12.8 vs. 17.5 days; p = .016) compared with controls. Only four of 51 (8%) patients fed EPA+GLA vs. 13 of 47 (28%) control patients developed a new organ failure during the study (p = .015). CONCLUSIONS: The beneficial effects of the EPA+GLA diet on pulmonary neutrophil recruitment, gas exchange, requirement for mechanical ventilation, length of intensive care unit stay, and the reduction of new organ failures suggest that this enteral nutrition formula would be a useful adjuvant therapy in the clinical management of patients with or at risk of developing ARDS.     

Preemptive randomized,double-blind study with lornoxicam in gynecological surgery

AIM: Lornoxicam is a non opioid analgesic belonging to the oxicam group. The aim of this study was to determine whether lornoxicam has a preemptive analgesic effect. METHODS: This study was carried out in a randomized, double-blind fashion with 66 patients divided into three groups undergoing gynecological operations. Group I was administered 8 mg of lornoxicam i.v. preoperatively followed by an 8-mg bolus every 8 h for a total dose of 24 mg in the first 24 h. Group II was administered 8 mg of lornoxicam i.v. bolus before the end of the operation followed by 8 mg every 8 h for a total dose of 24 mg in the first 24 h. Group III was administered placebo before and after the operation and for the first 24 h. The effectiveness was assessed postoperatively using the visual analogue scale (at rest, on exertion) and by calculating the total analgesic consumption of morphine hydrochloride in the first 24 h following operation.Vital signs and side effects were documented. RESULTS: Groups I and II demonstrated significantly reduced pain scores compared to group III at various points in time.Group I also demonstrated a weakly significant reduction in analgesic consumption of morphine hydrochloride postoperatively compared to groups II and III. CONCLUSION: Lornoxicam administered preemptively appears to improve the quality of postoperative analgesia and lead to reduced consumption of opioid analgesics postoperatively in patients undergoing gynecological operations.     

不同剂量精氨酸强化的肠内营养对创伤危重患者的支持作用

目的探讨不同剂量精氨酸强化的肠内营养对创伤危重患者的支持作用。方法选择骨科创伤危重患者(简明创伤评分AIS为3~10分)60例,随机分为对照组和试验Ⅰ、Ⅱ、Ⅲ组,在经口肠内营养支持的基础上,分别给予精氨酸0 g·kg-1·d-1、0.1 g·kg-1·d-1、0.3 g·kg-1·d-1、0.5 g·kg-1·d-1,连续作用14 d,观察患者胃肠道耐受和创口感染情况,于作用前后检测营养指标(总蛋白、前白蛋白、血清白蛋白)、免疫指标(Ig A、Ig G、Ig M),并记录住院时间。结果与对照组相比,试验Ⅰ、Ⅱ、Ⅲ组前白蛋白升高在干预第8天、第15天显著(P<0.05);试验Ⅱ、Ⅲ组血清白蛋白、总蛋白升高在干预第8天、第15天显著(P<0.05),而Ig A、Ig G改善只在干预第15天具有统计学意义(P<0.05),且两组患者创口感染改善明显,住院时间显著缩短。结论精氨酸强化的肠内营养可改善创伤危重患者的营养、免疫状况及创口感染,其中添加0.3 g·kg-1·d-1精氨酸组效果最佳。     

Fluconazole improves survival in septic shock: a randomized double-blind prospective study

OBJECTIVE: To demonstrate whether fluconazole reduces multiple organ failure and mortality in early septic shock (<24 hrs). DESIGN: A prospective randomized double-blind study. SETTING: A medical and surgical adult intensive care unit in a tertiary referral center. PATIENTS: Values were obtained from 71 general adult intensive care unit patients. INTERVENTIONS: During a 2.5-yr period, December 1998-June 2001, 71 patients with septic shock attributed to either nosocomial pneumonia (n = 37) or intra-abdominal sepsis (n = 34) were admitted to our intensive care unit and met the criteria of early septic shock and were entered into this study. All patients were randomized by our clinical pharmacist to receive daily either 200 mg of fluconazole in isotonic saline (fluconazole group = 32) or isotonic saline alone (placebo group = 39) intravenously during the course of their septic shock. MEASUREMENTS AND MAIN RESULTS: All patients were closely monitored with pulmonary artery catheters and parameters to calculate daily organ dysfunction and Acute Physiology and Chronic Health Evaluation II scores. There was a highly significant increase in 30-day survival in the fluconazole-treated patients compared with the placebo patients (78% vs. 46%). However, fluconazole was found to be more effective in patients with septic shock attributed to intra-abdominal sepsis than to nosocomial pneumonia. Increased survival in the intra-abdominal sepsis clinical category was mirrored by a significantly lower number of organ failures in the treated group compared with the placebo group whereas the number of organ failures in the fluconazole group attributed to nosocomial pneumonia were not significantly increased compared with the control group. The septic shock state was considered in all cases to be attributed to bacterial and not to disseminated yeast infection with the exception of one patient in the control group who was admitted with candidemia. The mechanisms by which fluconazole exerts its protective effect against septic shock in patients is far from clear. However, fluconazole has been shown to enhance bactericidal activity of neutrophils and also to inhibit transmigration and adhesion of neutrophils in capillaries of distant organs. CONCLUSIONS: The development of organ failure and mortality in septic shock was significantly reduced by fluconazole given intravenously. The mechanism of action of fluconazole in reducing multiple organ dysfunction in this group of patients may be attributed to the ability of fluconazole to increase recruitment, improve bactericidal activity of neutrophils, and to contain microorganisms locally.     

Clindamycin versus chloramphenicol in treatment of anaerobic infections: a prospective, randomized, double-blind study

Seventy patients with substantiated anaerobic infections were treated parenterally with clindamycin or chloramphenicol in a prospective, double-blind, randomized study. No significant differences in clinical response or toxicity were noted between the two groups of patients.     

早期肠内营养支持改善重型颅脑外伤患者胃肠道功能的研究

目的探讨应用预消化型短肽制剂实施早期肠内营养支持（EEN）,对重型颅脑外伤患者胃肠道功能的影响。方法将重型颅脑外伤患者随机分为研究组（n=45）和对照组（n=45）,研究组于入ICU后24～48h开始肠内营养（EN）．予预消化型短肽制剂,对照组于入ICU7d后开始EN。比较两组其入院第1、7、14天的血白蛋白（A）、血前白蛋白（PA）、血红蛋白（Hb）、肱三头肌皮皱厚度（TSF）、上臂周径（AMC）指标变化,并观察两组的胃肠道功能状况。结果入院第7天,研究组各指标较对照组下降缓慢,其中PA两组比较,差异有统计学意义（t=1．67,P〈0．05）,第14天,两组的A、PA、Hb、TSF、AMC指标有所回升,但差异均无统计学意义（t分别=1．29、1．24、0．76、0．68、1．30,P均〉0．05）。研究组较对照组的胃肠道功能障碍（上消化道出血、胃潴留、腹泻、反流）发生率低,两组间的差异有统计学意义（x^2分别=5．87、3．85、4．44、4．11,P均〈0．05）。结论预消化型短肽制剂实施EEN,能改善重型颅脑外伤患者的胃肠道功能。     

Prophylaxis of migraine with oral magnesium: results from a prospective, multi-center, placebo-controlled and double-blind randomized study

In order to evaluate the prophylactic effect of oral magnesium, 81 patients aged 18–65 years with migraine according to the International Headache Society (IHS) criteria (mean attack frequency 3.6 per month) were examined. After a prospective baseline period of 4 weeks they received oral 600 mg (24 mmol) magnesium (trimagnesium dicitrate) daily for 12 weeks or placebo. In weeks 9–12 the attack frequency was reduced by 41.6% in the magnesium group and by 15.8% in the placebo group compared to the baseline (p <0.05). The number of days with migraine and the drug consumption for symptomatic treatment per patient also decreased significantly in the magnesium group. Duration and intensity of the attacks and the drug consumption per attack also tended to decrease compared to placebo but failed to be significant. Adverse events were diarrhea (18.6%) and gastric irritation (4.7%). High-dose oral magnesium appears to be effective in migraine prophylaxis.     

Olive oil based nutrition in multiple trauma patients: a pilot study

Objective A negative effect of hyperglycemia on clinical outcome has been proposed for patients treated under intensive care conditions. So far, however, the safety and effect of fat based nutrition regimen, especially of olive oil based emulsions, have not been systematically studied.Design and setting Prospective, open-labeled, randomized, pilot study in a 14-bed surgical intensive care unit.Patients and interventions Thirty-three consecutive, severe multiple trauma patients (injury severity score 31.6±11.5) were included; 18 (L group) received a parenteral lipid-based nutrition; 15 (G group) were given a standard parenteral glucose-based nutrition.Measurements and results The energy expenditure (EE) showed no difference between groups and no significant difference between the energy intake/EE ratio. The daily mean energy intake was lower in the L group (17.9±6.3 kcal/kg) than in the G group (22.3±4.2 kcal/kg). Triglycerides and nitrogen balance showed no significant differences between groups. The L group had significantly lower blood glucose (L 7.4±1.6, G 8.7±1.6 mmol/l), carbon dioxide production, and minute volume and shorter duration of mechanical ventilation (L 13.0±8.9, G 20.4±7.0 days), and stay in the ICU (L 17.9±11.2, G 25.1±7.0 days).Conclusions Our findings suggest a good tolerance, a decrease in blood glucose, clinically relevant shortening of ICU stay, and shorter time on mechanical ventilation for patients treated with olive oil based than with conventional glucose-heavy nutrition.Electronic Supplementary Material Supplementary material is available in the online version of this article at: This study was funded by the German Berufsgenossenschaften (Employers Liability Insurance Association) and Baxter Deutschland GmbH.     

严重闭合性腹部创伤术后中药序贯法肠内营养治疗的初步研究

目的 观察应用中药序贯法肠内营养(SEN)治疗的价值.方法 50例严重闭合性腹部创伤术后患者随机分为SEN组(22例)和全胃肠外营养(TPN)组(28例).术后SEN组经营养管滴入自拟中药汤剂固脱清腑汤;TPN组经颈内静脉输注营养液,两组其余治疗原则相同.观察两组患者术后应激性高血糖发生情况、胰岛素用量、血培养结果、排气及排便时间、下床活动时间、术后住院时间、术后并发症、血清白蛋白、C-反应蛋白(CRP)、肝肾功能、电解质的变化.结果 SEN组术后24 h内血糖>11.1 mmol/L的患者数显著少于TPN组(10比24,P<0.01),术后胰岛素用量明显少于TPN组[(9.3±4.7)U/d比(29.5±11.9)U/d,P<0.05],术后排气时间[(41.3±14.8)h比(75.2±22.3)h]、排便时间[(66.2±19.9)h比(98.1±34.7)h]及住院时间[(14.3±5.5)d比(27.5±8.8)d]也均较TPN组缩短(P<0.05或P<0.01);同时,SEN组术后9 d血清白蛋白水平显著高于TPN组[(38.12±3.33)g/L比(33.75±4.25)g/L,P<0.01],术后并发症发生例数少于TPN组(7比17,P<0.05).结论 SEN可能对控制严重闭合性腹部创伤术后患者应激性高血糖的发生、改善患者营养状况、缩短术后恢复时间、减少术后并发症的发生有益.     

Dexamethasone to prevent postextubation airway obstruction in adults: a prospective,randomized, double-blind,placebo-controlled study

Introduction  

Prophylactic steroid therapy to reduce the occurrence of postextubation laryngeal edema is controversial. Only a limited number of prospective trials involve adults in an intensive care unit. The purpose of this study was to ascertain whether administration of multiple doses of dexamethasone to critically ill, intubated patients reduces or prevents the occurrence of postextubation airway obstruction. Another specific objective of our study was to investigate whether an after-effect (that is, a transient lingering benefit) exists 24 hours after the discontinuation of dexamethasone.     

早期肠内营养对重症监护室重症颅脑外伤患者炎症因子的影响分析

目的探讨对重症监护室重症颅脑外伤患者采用早期肠内营养对患者炎症因子、免疫功能、营养状况的影响。方法选择2016年2月至2018年3月我院重症监护室收治的重症颅脑外伤患者50例,按照随机数字表法分为肠外组和肠内组各25例。肠外组给予肠外营养支持,肠内组给予早期肠内营养支持,比较两组患者的炎症因子、免疫功能、营养状况改善情况。结果治疗后,两组白介素(IL)-2、IL-6、IL-8、肿瘤坏死因子(TNF)-α水平均较治疗前降低,且肠内组比肠外组下降幅度更大(P<0.05);两组IgG、IgM、IgA、TLC及血红蛋白、前白蛋白、白蛋白水平均较治疗前升高,肠内组比肠外组升高幅度更大(P<0.05)。结论对重症监护室重症颅脑外伤患者中采用早期肠内营养,能降低患者炎症因子,提高患者自身的免疫能力,值得临床上进行推广。     

早期要素肠内营养与肠外、肠内阶段性营养治疗急性重症胰腺炎的对比研究

目的:探讨早期肠内要素营养(early enteral elemental nutrition,EEN)与肠外营养(parenteral nutrition,PN)、肠内营养(enteral nutrition,EN)阶段性营养支持对急性重症胰腺炎(Severe acute pancreatitis,SAP)的疗效及临床价值.方法:将45例临床SAP患者随机分为两组,分别接受早期肠内营养(EEN)和阶段性营养支持治疗.观察其血清白蛋白、淀粉酶水平、胃肠功能,比较其并发症、感染率、住院时间和住院费用.结果:两组血清白蛋白水平变化和淀粉酶水平比较无统计学意义(P＞0.05),EEN组肠道蠕动恢复较早,且并发症、感染率、住院时间和费用低于阶段性营养支持组(P＜0.05).结论:在SAP的治疗中,72 h之内行EEN能减少并发症,改善患者预后.     

早期肠内营养在以严重腹部外伤为主的多发伤患者术后的应用

目的　探讨早期肠内营养在多发伤患者中的应用价值。方法　对本院收治的 2 1例以严重腹部外伤为主的多发伤患者术后实施早期肠内营养。术后第 1天和第 14天分别测定血清白蛋白、前白蛋白、转铁蛋白 ,T淋巴细胞表面抗原和CRP ,并进行比较。结果　所有患者术后 2周的血清白蛋白、前白蛋白、转铁蛋白、CD3+ 、CD4+ 和CD4+ CD8+ 等比术后第 1日明显增加 (P <0 0 5 ) ,CRP和CD8+ 明显下降 (P <0 0 5 ) ,而且无严重感染发生。结论　术后早期肠内营养在以严重腹部外伤为主的多发伤患者中运用是安全可行并有价值的