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.     

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.     

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.     

Enteral nutrition with eicosapentaenoic acid, γ-linolenic acid and antioxidants in the early treatment of sepsis: results from a multicenter, prospective, randomized, double-blinded, controlled study: the INTERSEPT study

Introduction  

Enteral nutrition (EN) with eicosapentaenoic acid (EPA)/γ-linolenic acid (GLA) is recommended for mechanically ventilated patients with severe lung injury. EPA/GLA has anti-inflammatory benefits, as evidenced by its association with reduction in pulmonary inflammation, improvement in oxygenation and improved clinical outcomes in patients with severe forms of acute lung injury. This study was a prospective, multicenter, randomized, double-blinded, controlled trial designed to investigate whether EPA/GLA could have an effective role in the treatment of patients with early sepsis (systemic inflammatory response syndrome with confirmed or presumed infection and without any organ dysfunction) by reducing the progression of the disease to severe sepsis (sepsis associated with at least one organ failure) or septic shock (sepsis associated with hypotension despite adequate fluid resuscitation). Secondary outcomes included the development of individual organ failure, increased ICU and hospital length of stay, need for mechanical ventilation and 28-day all-cause mortality.     

Amino acid alterations and encephalopathy in the sepsis syndrome

OBJECTIVE: To evaluate the role of amino acid profiles in septic encephalopathy. DESIGN: Retrospective analysis. SETTING: Medical wards and medical ICU of a university hospital. PATIENTS: Patients with infections and normal mental status were compared with patients with septic shock and altered sensorium. INTERVENTIONS: Plasma amino acid levels and Acute Physiology and Chronic Health Evaluation (APACHE II) scores were determined. MEASUREMENTS AND MAIN RESULTS: Patients with septic shock and altered sensorium had higher circulating concentrations of ammonia (425 +/- 55 vs. 127 +/- 7 mmol/L) and the aromatic amino acids phenylalanine (122 +/- 19 vs. 74 +/- 3 mmol/L) and tryptophan (97 +/- 7 vs. 32 +/- 13 mmol/L), and lower levels of the branch-chain amino acid isoleucine (48 +/- 7 vs. 68 +/- 5 mmol/L) than patients with infections and normal sensorium (p less than .05). Aromatic amino acid levels correlated with APACHE II scores (R2 = .4, p less than .001) and mortality. APACHE II scores were higher in the septic shock patients (30 +/- 2 vs. 8 +/- 1, p less than .001), and these patients had a higher mortality rate (71% vs. 12%, p less than .01). Patients with septic shock who died had higher levels of ammonia (524 +/- 58 vs. 227 +/- 40 mmol/L, p less than .05) and sulfur-containing amino acids (172 +/- 31 vs. 61 +/- 7 mmol/L, p less than .05) than patients who survived. CONCLUSIONS: Plasma amino acid profiles appear to be important in septic encephalopathy and the severity of septic disease.     

Enteral nutrition-related gastrointestinal complications in critically ill patients: a multicenter study. The Nutritional and Metabolic Working Group of the Spanish Society of Intensive Care Medicine and Coronary Units.

OBJECTIVE: To evaluate the frequency of gastrointestinal complications (GICs) in a prospective cohort of critically ill patients receiving enteral nutrition and to assess its effect on nutrient administration and its relationship to the patient's outcome. DESIGN: Multicenter, prospective cohort study. SETTING: Thirty-seven multidisciplinary intensive care units (ICUs) in Spain. PATIENTS: Prospective cohort of 400 consecutive patients admitted to the ICU and receiving enteral nutrition. INTERVENTIONS: Noninterventional, follow-up study. MEASUREMENTS AND MAIN RESULTS: Enteral nutrition-related GICs and their management were defined by consensus before data collection. A set of variables related to enteral nutrition administration and the presence of GICs was recorded. During the 1-month study period, 400 patients were enrolled, and a total of 3,778 enteral feeding days were analyzed. The mean time of enteral nutrition was 9.6+/-0.4 days. Mean elapsed time from ICU admission to the start of enteral feeding was 3.1+/-0.2 days. A total of 265 patients (66.2%) received a standard polymeric formula, and 132 (33.8%) received a disease-specific one. Enteral feeds were administered mainly through a nasogastric tube (91%). One or more GICs were presented by 251 patients (62.8%) during the feeding course. The frequency of each particular GIC was as follows: high gastric residuals, 39%; constipation, 15.7%; diarrhea, 14.7%; abdominal distention, 13.2%; vomiting, 12.2%; and regurgitation, 5.5%. Enteral nutrition withdrawal as a consequence of noncontrollable GICs occurred in 15.2% of patients. The volume ratio (expressed as the ratio between administered and prescribed volumes) was calculated daily and was used as an index of diet administration efficacy. Patients with GICs had a lower volume ratio than did patients without GICs (63.1+/-1.20% vs. 93.3+/-0.3%) (p < .001), a longer length of stay (20.6+/-1.2 vs. 15.2+/-1.3 days) (p < .01), and higher mortality (31% vs. 16.1%) (p < .001). CONCLUSIONS: The frequency of enteral nutrition-related GICs in critically ill patients is high. High gastric residuals is the most frequent GIC. These complications decreased nutrient intake and, if persistent, could expose the patients to undernutrition. Enteral feeding gastrointestinal intolerance seems to have an evolutive effect in prolonging the ICU stay and increasing patient mortality.     

Early enteral immunonutrition in patients with severe sepsis

OBJECTIVE: To compare the mortality of critically ill patients given either enteral feeding with an immune-enhancing formula or parenteral nutrition (PN). We report the results of a planned interim analysis on patients with severe sepsis which was undertaken earlier than planned once a meta-analysis suggested excess mortality in patients with severe sepsis given enteral immunonutrition. DESIGN: Randomised multicentre unblinded controlled clinical trial. SETTING: Thirty-three General Intensive Care Units in Italy. PATIENTS AND PARTICIPANTS: Among the 237 recruited patients, 39 had severe sepsis or septic shock; 21 of them received PN. INTERVENTIONS: Eligible patients received either total PN or enteral nutrition, the latter containing extra L-arginine, omega-3 fatty acids, vitamin E, beta carotene, zinc, and selenium. MEASUREMENTS AND RESULTS: The primary endpoint for the subgroup analysis on patients with severe sepsis was mortality on Intensive Care Unit (ICU). The ICU mortality of patients with severe sepsis given enteral nutrition (EN) was higher than for those given PN (44.4% vs 14.3%; p=0.039). More patients given EN than patients given PN still had severe sepsis when they died (38.9% vs 9.5%, p=0.055). Recruitment of patients with severe sepsis was subsequently stopped. CONCLUSIONS: Our results show that enteral immunonutrition, compared to PN, may be associated with excess mortality in patients with severe sepsis.     

The patient-related costs of care for sepsis patients in a United Kingdom adult general intensive care unit.

OBJECTIVE: To determine the patient-related costs of care for critically ill patients with severe sepsis or early septic shock. DESIGN: Retrospective, longitudinal, observational study during a 10-month period. SETTING: Adult general intensive care unit (ICU) in a university hospital located in the United Kingdom. PATIENTS: The study population consisted of 213 patients admitted consecutively to the ICU during a 10-month period. Thirty-six patients were identified using standard definitions as having developed sepsis and analyzed by group (according to the day on which sepsis was diagnosed): Group 1 patients were septic at admission to ICU (n = 16); group 2 patients were septic on their second day in the ICU (n = 10); and group 3 patients developed sepsis after their second day in the ICU (n = 10). One hundred and seventy-seven ICU patients without sepsis were used as the comparative group (group 4). INTERVENTIONS: None. MAIN RESULTS: Patient-related costs of care, length of ICU stay, and ICU and hospital mortality rates were compiled.The median daily costs of care for patients in groups 1, 2, and 3 were $930.74 (interquartile range $851.59-$1,263.96); $814.47 ($650.89-$1,123.06), and $1,079.39 ($705.02-$1,295.96), respectively; these were significantly more than the group 4 patient's daily cost of $750.38 ($644.10-$908.55) (p < .01). The median total cost of treating the group 4 patients was $1,666.87 ($979.71-$2,772.03), significantly less than for the patients with sepsis (p < .01). The difference in total costs of care between the sepsis groups was also significant (p < .05), with a group 1 patient costing $3,801.55 ($1,865.28-$11,676.08), a group 2 patient costing $13,089.17 ($5,792.94-$22,235.18), and a group 3 patient costing $17,962.78 ($13,030.83-$28,546.73). Patients in groups 1, 2, and 3 stayed in the ICU for 3.3 days (1.3-11.3), 16.5 days (8.9-22), and 16.1 days (10.9-9), respectively. Significant differences were found among the three groups (p < 0.05), as well as between the patients with sepsis and those without (p < 0.001), whose median length of stay was 1.9 days (0.9-3.6). The ICU mortality rates were 50% each for groups 1 and 2, 60% for group 3, and 20% for group 4. Only one patient with sepsis and 16 patients without sepsis died in the hospital ward, producing overall mortality rates of 56% for group 1 and 29% for group 4. CONCLUSIONS: Patients with severe sepsis or early septic shock had a high mortality rate, spent prolonged periods of time in the ICU, and were significantly more expensive to treat than nonsepsis ICU patients.     

An immune-enhancing enteral diet reduces mortality rate and episodes of bacteremia in septic intensive care unit patients

OBJECTIVE: To determine whether early enteral feeding in a septic intensive care unit (ICU) population, using a formula supplemented with arginine, mRNA, and omega-3 fatty acids from fish oil (Impact), improves clinical outcomes, when compared with a common use, high protein enteral feed without these nutrients. DESIGN: A prospective, randomized, multicentered trial. SETTING: ICUs of six hospitals in Spain. PATIENTS: One hundred eighty-one septic patients (122 males, 59 females) presenting for enteral nutrition in an ICU. INTERVENTIONS: Septic ICU patients with Acute Physiology and Chronic Health Evaluation (APACHE) II scores of > or =10 received either an enteral feed enriched with arginine, mRNA, and omega-3 fatty acids from fish oil (Impact), or a common use, high protein control feed (Precitene Hiperproteico). MEASUREMENTS AND MAIN RESULTS: One hundred seventy-six (89 Impact patients, 87 control subjects) were eligible for intention-to-treat analysis. The mortality rate was reduced for the treatment group compared with the control group (17 of 89 vs. 28 of 87; p < .05). Bacteremias were reduced in the treatment group (7 of 89 vs. 19 of 87; p = .01) as well as the number of patients with more than one nosocomial infection (5 of 89 vs. 17 of 87; p = .01). The benefit in mortality rate for the treatment group was more pronounced for patients with APACHE II scores between 10 and 15 (1 of 26 vs. 8 of 29; p = .02). CONCLUSIONS: Immune-enhancing enteral nutrition resulted in a significant reduction in the mortality rate and infection rate in septic patients admitted to the ICU. These reductions were greater for patients with less severe illness.     

Clinical predictors and outcomes for patients requiring tracheostomy in the intensive care unit.

OBJECTIVE: To identify clinical predictors for tracheostomy among patients requiring mechanical ventilation in the intensive care unit (ICU) setting and to describe the outcomes of patients receiving a tracheostomy. DESIGN: Prospective cohort study. SETTING: Intensive care units of Barnes-Jewish Hospital, an urban teaching hospital. PATIENTS: 521 patients requiring mechanical ventilation in an ICU for >12 hours. INTERVENTIONS: Prospective patient surveillance and data collection. MEASUREMENTS AND MAIN RESULTS: The main variables studied were hospital mortality, duration of mechanical ventilation, length of stay in the ICU and the hospital, and acquired organ-system derangements. Fifty-one (9.8%) patients received a tracheostomy. The hospital mortality of patients with a tracheostomy was statistically less than the hospital mortality of patients not receiving a tracheostomy (13.7% vs. 26.4%; p = .048), despite having a similar severity of illness at the time of admission to the ICU (Acute Physiology and Chronic Health Evaluation [APACHE] II scores, 19.2 +/- 6.1 vs. 17.8 +/- 7.2; p = .173). Patients receiving a tracheostomy had significantly longer durations of mechanical ventilation (19.5 +/- 15.7 days vs. 4.1 +/- 5.3 days; p < .001) and hospitalization (30.9 +/- 18.1 days vs. 12.8 +/- 10.1 days; p < .001) compared with patients not receiving a tracheostomy. Similarly, the average duration of intensive care was significantly longer among the hospital nonsurvivors receiving a tracheostomy (n = 7) compared with the hospital nonsurvivors without a tracheostomy (n = 124; 30.9 +/- 16.3 days vs. 7.9 +/- 7.3 days; p < .001). Multiple logistic regression analysis demonstrated that the development of nosocomial pneumonia (adjusted odds ratio [AOR], 4.72; 95% confidence interval [CI], 3.24-6.87; p < .001), the administration of aerosol treatments (AOR, 3.00; 95% CI, 2.184.13; p < .001), having a witnessed aspiration event (AOR, 3.79; 95% CI, 2.30-6.24; p = .008), and requiring reintubation (AOR, 2.21; 95% CI, 1.54-3.18; p = .028) were variables independently associated with patients undergoing tracheostomy and receiving prolonged ventilatory support. Among the 44 survivors receiving a tracheostomy in the ICU, 38 (86.4%) were alive 30 days after hospital discharge and 31 (70.5%) were living at home. CONCLUSIONS: Despite having longer lengths of stay in the ICU and hospital, patients with respiratory failure who received a tracheostomy had favorable outcomes compared with patients who did not receive a tracheostomy. These data suggest that physicians are capable of selecting critically ill patients who most likely will benefit from placement of a tracheostomy. Additionally, specific clinical variables were identified as risk factors for prolonged ventilatory assistance and the need for tracheostomy.     

Increased morbidity with increased pulmonary albumin flux in sepsis-related adult respiratory distress syndrome.

OBJECTIVE: To determine the feasibility of utilizing a scintigraphic technique to differentiate patients with adult respiratory distress syndrome due to sepsis syndrome from control volunteers and patients with congestive heart failure. Gamma scintigraphy was compared with chest roentgenograms to predict mortality rate and morbidity in adult respiratory distress syndrome (ARDS) patients. DESIGN: Prospective study. SETTING: University hospital ICUs. PATIENTS: Thirty-five control volunteers, 19 patients with congestive heart failure, 30 patients with a diagnosis of sepsis. MEASUREMENTS AND MAIN RESULTS: All patients were infused iv with technetium 99m-labeled albumin and underwent computerized gamma-scintigraphic analysis with a portable gamma camera. Lung-to-heart ratio of tracer was calculated and expressed as the slope index. Increase in slope index indicated increased pulmonary albumin flux. Slope index was no different in controls compared with congestive heart failure patients, unless the pulmonary artery occlusion pressure (PAOP) was greater than 30 mm Hg. Patients with a diagnosis of sepsis had an overall increased slope index compared with the other groups. A subgroup of patients in the septic group had a normal slope index. Septic patients with an increased slope index had a significantly (p less than .01) longer duration of mechanical ventilation (36 +/- 5 vs. 7 +/- 1 days), spent longer in the ICU (67 +/- 9 vs. 11 +/- 1 days), and had a longer hospital stay (113 +/- 20 vs. 35 +/- 5 days) than septic patients with a normal slope index. CONCLUSIONS: Gamma scintigraphy successfully differentiated between control volunteers and patients with congestive heart failure with PAOP less than 30 mm Hg from patients with sepsis-induced ARDS. Although all of the patients with a clinical diagnosis of septic ARDS had similar impairments in oxygenation and chest roentgenograms, those patients with a significantly increased pulmonary albumin flux (greater than 2 SD above control mean) had a markedly increased morbidity.     

Development of ionized hypomagnesemia is associated with higher mortality rates

OBJECTIVE: Previous studies have shown a wide variation in the prevalence of total serum hypomagnesemia in intensive are unit (ICU) patients and in associated mortality rates. As the ionized part of magnesium is the active portion, we sought to define the prevalence of ionized hypomagnesemia in critically ill patients and to evaluate its relationship with organ dysfunction, length of stay, and mortality. DESIGN: Prospective observational study. SETTING: A 31-bed, medical-surgical, university hospital ICU. PATIENTS: A total of 446 consecutive patients admitted to the ICU over a 3-month period. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The ionized magnesium level (normal value, 0.42-0.59 mmol/L) was measured at admission and then every day until discharge from the ICU. At admission, 18% of patients had ionized hypomagnesemia, 68% had normal ionized magnesium levels, and 14% had ionized hypermagnesemia. There was no significant difference in the length of stay or in the mortality rate between these three groups of patients. Hypomagnesemic patients more frequently had total and ionized hypocalcemia, hypokalemia, and hypoproteinemia. A total of 23 patients developed ionized hypomagnesemia during their ICU stay; these patients had higher Acute Physiology And Chronic Health Evaluation II (14.9 +/- 5.4 vs. 11.0 +/- 6.2) and Sequential Organ Failure Assessment (SOFA; 7.1 +/- 5.4 vs. 3.9 +/- 2.8) scores at admission (p <.01 for both), a higher maximum SOFA score during their ICU stay (10.0 +/- 5.6 vs. 4.4 +/- 3.2, p <.01), a higher prevalence of severe sepsis and septic shock (57 vs. 11%, p <.01), a longer ICU stay (15.4 +/- 15.5 vs. 2.8 +/- 4.7 days, p <.01), and a higher mortality rate (35% vs. 12%, p <.01) than the other patients. The major risk factors for developing hypomagnesemia during the ICU stay were a prolonged ICU stay, treatment with diuretics, and sepsis. CONCLUSION: Development of ionized hypomagnesemia during an ICU stay is associated with a worse prognosis. It is often associated with the use of diuretics and the development of sepsis. Monitoring of ionized magnesium levels may have prognostic, and perhaps therapeutic, implications.     

感染性休克集束治疗对病死率影响的前瞻性临床研究

目的 探讨集束治疗对感染性休克患者病死率的影响.方法 采用前瞻性研究方法,将2007年1月-2008年6月重症加强治疗病房(ICU)收治的成人感染性休克患者分为培训前(2007年1-9月)和培训后(2007年10月-2008年6月)两个阶段进行感染性休克集束治疗.分析6 h及24 h感染性休克集柬治疗各指标与预后的关系;采用多元回归分析方法,筛选出集束治疗对感染性休克预后影响的独立相关因素,并研究两个阶段感染性休克集束治疗的依从性、机械通气时间、ICU住院时间以及28 d病死率.结果 研究期间共收治符合条件的感染性休克患者100例,其中培训前51例,培训后49例;存活36例,死亡64例.多元回归分析显示,6 h早期目标导向治疗(EGDT)、24 h EGDT是与感染性休克28 d病死率相关的两个独立保护因素,优势比(OR)分别为0.046和0.120(P均<0.01).培训后集束治疗依从性均有明显提高,其中6 h EGDT和24 h EGDT分别从19.6%、35.3%提升至55.1%、65.3%(P均<0.01).培训后机械通气时间[(166.6±156.4)h比(113.6±73.6)h3、ICU住院时间[(9.4±7.6)d比(6.0±3.9)d]及28 d病死率(72.5%比55.1%)较培训前明显缩短(P<0.05或P<0.01).结论 继续教育培训可提高医务人员对感染性休克集束治疗的依从性,降低感染性休克患者的病死率.     

Septic shock and multiple organ failure

OBJECTIVE: To assess the frequency and mortality rates of septic shock in ICU patients and the clinical course of multiple organ failure associated with septic shock. DESIGN: Retrospective case survey. SETTING: Tertiary care center. PATIENTS: During a 2-yr period, 2,469 consecutive intensive care patients were studied regarding the frequency and hospital mortality rates of septic shock. A subset of 1,311 patients was further analyzed for the occurrence of organ system failures within 48 hrs of the onset of septic shock and again 4 to 7 days later. MEASUREMENTS AND MAIN RESULTS: The frequency rate of septic shock was 1.9% (n = 48), with a mortality rate of 72.9% (n = 35) in patients with septic shock. Deaths due to septic shock represented 14.6% of all deaths in the ICU during the study period. Eighteen patients died within 72 hrs of the onset of septic shock. Refractory hypotension was the cause of death in 15 of these 18 patients. Beyond 72 hrs, multiple organ failure accounted for eight of 17 deaths. The mean +/- SD number of organ systems failing at 48 hrs was 3.3 +/- 1.3 in survivors and 4.0 +/- 1.1 in nonsurvivors, and at 4 to 7 days was 2.1 +/- 1.5 in survivors and 4.0 +/- 1.5 in nonsurvivors (p less than .05). None of the specific organ system failures had prognostic value. The number of organ system failures was not related to the duration of hypotension, but had a weak correlation (r2 = .26, p less than .05) with the duration of vasoactive treatment at 4 to 7 days. The prolonged need for norepinephrine therapy was associated with an increased occurrence of renal failure. Thirty (62.5%) patients had positive blood cultures and a mortality rate similar to the mortality rate of patients with negative blood cultures. Patients with negative blood cultures died more often with hypotension (p less than .02). CONCLUSIONS: Septic shock is a major cause of death in intensive care patients. Refractory hypotension is a main cause of early deaths. Later on, multiple organ failure becomes the primary clinical problem and cause of mortality.     

Direct costs of severe sepsis in three German intensive care units based on retrospective electronic patient record analysis of resource use

OBJECTIVE: To determine the direct costs of severe sepsis patients in German intensive care units (ICUs). DESIGN: Retrospective electronic data analysis. SETTING: Three adult intensive care units (surgical/medical) in three university hospitals in Germany. PATIENTS: 385 patients identified by standard definitions as suffering from severe sepsis. MEASUREMENTS AND RESULTS: A bottom-up approach was used to determine the direct ICU cost on actual resource use (medication, laboratory tests, microbiological analysis, disposables, and clinical procedures) for patients with severe sepsis. To determine the total direct costs, center-specific personnel and basic bed ("hotel") costs were added to total resources consumed. Average hospital mortality of severely septic patients was 42.6%. Mean ICU length of stay (LOS) was 16.6 days. Survivors stayed on average 4 days longer than nonsurvivors. The mean direct ICU costs of care were 23,297+/-18,631 euros per patient and 1,318 euros per day. In comparison, average daily charges being paid for an ICU patient by the health care system in Germany are 851 euros (based on official statistics). Nonsurvivors were more expensive than survivors in total direct costs (25,446 vs. 21,984 euros) and in per day direct cost (1,649 vs. 1,162 euros). Medication makes up the largest part of the direct costs, followed by expenses for personnel. CONCLUSIONS. Patients with severe sepsis have a high ICU mortality rate and long ICU LOS and are substantially expensive to treat. Nonsurviving septic patients are more costly than survivors despite shorter ICU LOS. This is due to higher medication costs indicating increased efforts to keep patients alive.     

IgMA-enriched immunoglobulin in neutropenic patients with sepsis syndrome and septic shock: a randomized, controlled, multiple-center trial

OBJECTIVE: To evaluate the effect of intravenous IgMA-enriched immunoglobulin (ivIGMA) therapy on mortality in neutropenic patients with hematologic malignancies and sepsis syndrome or septic shock. DESIGN: Multiple-center, prospective randomized, controlled study. SETTING: Six university hospitals in Germany. PATIENTS: Patients were 211 neutropenic patients with sepsis syndrome or septic shock after chemotherapy for severe hematologic disorders between 1992 and 1999. INTERVENTIONS: Patients received 1300 mL of ivIGMA (7.8 g IgM, 7.8 g IgA, and 49.4 g IgG) infused intravenously within a period of 72 hrs or human albumin according to the same schedule as ivIGMA. MEASUREMENTS AND MAIN RESULTS: All-cause mortality at 28 days, sepsis-related mortality at 28 days, all-cause mortality at 60 days, mortality from septic shock, and mortality from microbiologically proven Gram-negative sepsis and septic shock were recorded. Immunoglobulin had no benefit over human albumin. The 28-day mortality rate was 26.2% and 28.2% in the ivIGMA and control patients, respectively (difference, 2.0% [95% confidence interval, -10.2 to 14.2 percentage points]). Likewise, the 60-day mortality rate did not differ between both arms (29.6% vs. 34.7% in the ivIGMA and control patients, respectively). Mortality rates in patients with sepsis syndrome (17.1% vs. 16.7%) and septic shock (51.9% vs. 54.8%) were also found to be similar between both groups. CONCLUSIONS: Intravenous ivIGMA had no beneficial effects in neutropenic patients with hematologic malignancies and sepsis syndrome and septic shock.     

Septic shock in patients with cirrhosis: hemodynamic and metabolic characteristics and intensive care unit outcome.

OBJECTIVES: To examine the hemodynamic and metabolic characteristics and ICU outcome of septic shock in patients with cirrhosis. DESIGN: Prospective, comparative study. Measurements performed in the first 24 hrs of septic shock. SETTING: A general hospital ICU. PATIENTS: Twelve patients with cirrhosis and 23 patients without cirrhosis admitted for septic shock. MEASUREMENTS AND MAIN RESULTS: Arterial pressure was measured using an arterial catheter. Pulmonary arterial and right atrial pressures were measured by using a pulmonary artery catheter. Cardiac output was determined by using the thermodilution method. Pulmonary arterial L-lactate plasma concentrations were measured using an automated spectrophotometer, and blood temperature was measured using a cardiac output computer. Arterial and mixed venous PO2, PCO2, and pH values were measured by using specific electrodes. Oxygen saturations and hemoglobin concentrations were measured using a hemoximeter. Patients with cirrhosis had decompensated liver disease (grade C of the Child-Pugh classification). The number of Gram-negative infections and therapeutic interventions were similar in both groups. Patients with cirrhosis had higher cardiac indices (5.14 +/- 0.52 [SE] vs. 3.91 +/- 0.30 L/min/m2, p less than .05), plasma lactate concentrations (9.0 +/- 2.0 vs. 5.2 +/- 0.7 mmol/L, p less than .05) and ICU mortality rates (100% vs. 43%, p less than .05), and lower blood temperatures (35.5 +/- 0.6 vs. 37.6 +/- 0.2 degrees C, p less than .05) than patients without cirrhosis. Systemic vascular resistance, arterial pressure, pulmonary arterial pressure, oxygen delivery and consumption, and arterial and mixed venous acid-base status were not significantly different between the two groups. CONCLUSIONS: In patients with cirrhosis, septic shock was characterized by severe liver dysfunction, low blood temperature, marked increases in cardiac index and lactic acidemia, and a 100% ICU mortality rate. These findings should be taken into account if patients with cirrhosis are to be included in controlled studies on septic shock.     

Implementation of a bundle of quality indicators for the early management of severe sepsis and septic shock is associated with decreased mortality

OBJECTIVE: The purpose of this study was to examine the outcome implications of implementing a severe sepsis bundle in an emergency department as a quality indicator set with feedback to modify physician behavior related to the early management of severe sepsis and septic shock. DESIGN: Two-year prospective observational cohort. SETTING: Academic tertiary care facility. PATIENTS: Patients were 330 patients presenting to the emergency department who met criteria for severe sepsis or septic shock. INTERVENTIONS: Five quality indicators comprised the bundle for severe sepsis management in the emergency department: a) initiate central venous pressure (CVP)/central venous oxygen saturation (Scvo2) monitoring within 2 hrs; b) give broad-spectrum antibiotics within 4 hrs; c) complete early goal-directed therapy at 6 hrs; d) give corticosteroid if the patient is on vasopressor or if adrenal insufficiency is suspected; and e) monitor for lactate clearance. MEASUREMENTS AND MAIN RESULTS: Patients had a mean age of 63.8 +/- 18.5 yrs, Acute Physiology and Chronic Health Evaluation II score 29.6 +/- 10.6, emergency department length of stay 8.5 +/- 4.4 hrs, hospital length of stay 11.3 +/- 12.9 days, and in-hospital mortality 35.2%. Bundle compliance increased from zero to 51.2% at the end of the study period. During the emergency department stay, patients with the bundle completed received more CVP/Scvo2 monitoring (100.0 vs. 64.8%, p < .01), more antibiotics (100.0 vs. 89.7%, p = .04), and more corticosteroid (29.9 vs. 16.2%, p = .01) compared with patients with the bundle not completed. In a multivariate regression analysis including the five quality indicators, completion of early goal-directed therapy was significantly associated with decreased mortality (odds ratio, 0.36; 95% confidence interval, 0.17-0.79; p = .01). In-hospital mortality was less in patients with the bundle completed compared with patients with the bundle not completed (20.8 vs. 39.5%, p < .01). CONCLUSIONS: Implementation of a severe sepsis bundle using a quality improvement feedback to modify physician behavior in the emergency department setting was feasible and was associated with decreased in-hospital mortality.     

Endocan, a new endothelial marker in human sepsis

OBJECTIVES: a) To evaluate in septic patients the blood levels of endocan, a circulating proteoglycan, which regulates leukocyte function-associated antigen-1/intercellular adhesion molecule-1 interactions in vitro; b) to determine whether endocan could be used as a diagnostic and prognostic marker in sepsis in the intensive care unit; and c) to study kinetics of endocan secretion by endothelial cells in vitro after stimulation by soluble mediators involved in sepsis. DESIGN: Prospective observational study. SETTING: Intensive care unit of the University Hospitals of Lille, France, and Geneva, Switzerland. PATIENTS: All patients admitted to the intensive care unit over a 6-month period with clinical evidence of severe sepsis or septic shock. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: In vitro, we showed a sustained endocan secretion by endothelial cells after stimulation by lipopolysaccharide and tumor necrosis factor-alpha. Circulating levels of endocan measured in 63 patients admitted to the intensive care unit with sepsis were significantly elevated compared with 20 healthy donors and seven patients with systemic inflammatory response syndrome: 2.71 +/- 4.88 ng/mL vs. 0.77 +/- 0.44 ng/mL vs. 0.68 +/- 1.03 ng/mL (median +/- interquartile range, p < .001). Endocan levels were higher in patients with septic shock (6.11 +/- 12.99 ng/mL, n = 22) than in patients with severe sepsis (1.97 +/- 7.8 ng/mL, n = 12) or sepsis (1.95 +/- 1.63 ng/mL, n = 29). Measurement of endocan at intensive care unit admission revealed higher levels in nonsurvivors (n = 12) than in patients still alive 10 days later (n = 51, 6.98 +/- 13.8 vs. 2.45 +/- 4.09, p < .01). CONCLUSIONS: These results suggest that in septic patients, endocan blood level is related to the severity of illness and the outcome of the patient and may represent a novel endothelial cell dysfunction marker.     

Early enteral immunonutrition vs. parenteral nutrition in critically ill patients without severe sepsis: a randomized clinical trial

Objectives We compared early parenteral nutrition (PN) and early enteral immunonutrition (iEN) in critically ill patients, distinguishing those with and without severe sepsis or septic shock (SS) on admission to intensive care units (ICUs).Design and setting Multicenter, randomized, unblinded clinical trial in 33 Italian general ICUs.Patients and participants The study included 326 patients, 287 of whom did not have SS on ICU admission. Eligibility criteria excluded the two tails in the spectrum of critical conditions, i.e., patients either too well or too ill. Of the patients recruited 160 were randomized to iEN (142 without SS) and 166 to PN (145 without SS).Interventions Patients were randomized to two arms: early iEN or early PN.Measurements and results Primary endpoint was 28-day mortality for all patients and the occurrence of SS during ICU stay for patients admitted without such condition. While 28-day mortality did not differ between iEN and PN (15.6% vs. 15.1%), patients without SS who received iEN had fewer episodes of severe sepsis or septic shock (4.9% vs. 13.1%). ICU length of stay was 4 days shorter in patients given iEN.Conclusions Compared to parenteral nutrition iEN appears to be beneficial in critical patients without severe sepsis or septic shock. Parenteral nutrition in these patients should be abandoned, at least when enteral nutrition can be administered, even at an initial low caloric content.Electronic supplementary material The electronic reference of this article is . The online full-text version of this article includes electronic supplementary material. This material is available to authorised users and can be accessed by means of the ESM button beneath the abstract or in the structured full-text article. To cite or link to this article you can use the above reference.The complete list of study participants is reported in the Electronic Supplementary Material, part AThe authors represent the Italian Group for the Evaluation of Interventions in Intensive Care Medicine.