AIM: To compare effects of different resuscitation fluid on microcirculation, inflammation, intestinal barrier and clinical results in severe acute pancreatitis (SAP).
METHODS: One hundred and twenty patients with SAP were enrolled at the Pancreatic Disease Institute between January 2007 and March 2010. The patients were randomly treated with normal saline (NS group), combination of normal saline and hydroxyethyl starch (HES) (SH group), combination of normal saline, hydroxyethyl starch and glutamine (SHG group) in resuscitation. The ratio of normal saline to HES in the SH and SHG groups was 3:1. The glutamine (20% glutamine dipeptide, 100 mL/d) was supplemented into the resuscitation liquid in the SHG group. Complications and outcomes including respiratory and abdominal infection, sepsis, abdominal hemorrhage, intra-abdominal hypertension, abdominal compartment syndrome (ACS), renal failure, acute respiratory distress syndrome (ARDS), multiple organ dysfunction syndrome (MODS), operation intervention, length of intensive care unit stay, length of hospital stay, and mortality at 60 d were compared. Moreover, blood oxygen saturation (SpO2), gastric intramucosal pH value (pHi), intra-abdominal pressure (IAP), inflammation cytokines, urine lactulose/mannitol (L/M) ratio, and serum endotoxin were investigated to evaluate the inflammatory reaction and gut barrier.
RESULTS: Compared to the NS group, patients in the SH and SHG groups accessed the endpoint more quickly (3.9 ± 0.23 d and 4.1 ± 0.21 d vs 5.8 ± 0.25 d, P < 0.05) with less fluid volume (67.26 ± 28.53 mL/kg/d, 61.79 ± 27.61 mL/kg per day vs 85.23 ± 21.27 mL/kg per day, P < 0.05). Compared to the NS group, incidence of renal dysfunction, ARDS, MODS and ACS in the SH and SHG groups was obviously lower. Furthermore, incidence of respiratory and abdominal infection was significantly decreased in the SH and SHG groups, while no significant difference in sepsis was seen. Moreover, less operation time was needed in the SH and SHG group than the NS group, but the difference was not significant. The mortality did not differ significantly among these groups. Blood SpO2 and gastric mucosal pHi in the SH and SHG groups increased more quickly than in the NS group, while IAP was significantly decreased in the SH and SHG group. Moreover, the serum tumor necrosis factor-α, interleukin-8 and C-reactive protein levels in the SH and SHG groups were obviously lower than in the NS group at each time point. Furthermore, urine L/M ratio and serum endotoxin were significantly lower in the SH group and further decreased in the SHG group.
CONCLUSION: Results indicated that combination of normal saline, HES and glutamine are more efficient in resuscitation of SAP by relieving inflammation and sustaining the intestinal barrier.
BACKGROUND: Critically ill patients have considerable oxidative stress. Glutamine and antioxidant supplementation may offer therapeutic benefit, although current data are conflicting.
METHODS: In this blinded 2-by-2 factorial trial, we randomly assigned 1223 critically ill adults in 40 intensive care units (ICUs) in Canada, the United States, and Europe who had multiorgan failure and were receiving mechanical ventilation to receive supplements of glutamine, antioxidants, both, or placebo. Supplements were started within 24 hours after admission to the ICU and were provided both intravenously and enterally. The primary outcome was 28-day mortality. Because of the interim-analysis plan, a P value of less than 0.044 at the final analysis was considered to indicate statistical significance.
RESULTS: There was a trend toward increased mortality at 28 days among patients who received glutamine as compared with those who did not receive glutamine (32.4% vs. 27.2%; adjusted odds ratio, 1.28; 95% confidence interval [CI], 1.00 to 1.64; P=0.05). In-hospital mortality and mortality at 6 months were significantly higher among those who received glutamine than among those who did not. Glutamine had no effect on rates of organ failure or infectious complications. Antioxidants had no effect on 28-day mortality (30.8%, vs. 28.8% with no antioxidants; adjusted odds ratio, 1.09; 95% CI, 0.86 to 1.40; P=0.48) or any other secondary end point. There were no differences among the groups with respect to serious adverse events (P=0.83).
CONCLUSIONS: Early provision of glutamine or antioxidants did not improve clinical outcomes, and glutamine was associated with an increase in mortality among critically ill patients with multiorgan failure. (Funded by the Canadian Institutes of Health Research; ClinicalTrials.gov number, NCT00133978.).
OBJECTIVE: To determine whether inclusion of glutamine, selenium, or both in a standard isonitrogenous, isocaloric preparation of parenteral nutrition influenced new infections and mortality among critically ill patients.
DESIGN: Randomised, double blinded, factorial, controlled trial.
SETTING: Level 2 and 3 (or combined) critical care units in Scotland. All 22 units were invited, and 10 participated.
PARTICIPANTS: 502 adults in intensive care units and high dependency units for ≥ 48 hours, with gastrointestinal failure and requiring parenteral nutrition.
INTERVENTIONS: Parenteral glutamine (20.2 g/day) or selenium (500 μg/day), or both, for up to seven days.
MAIN OUTCOME MEASURES: Primary outcomes were participants with new infections in the first 14 days and mortality. An intention to treat analysis and a prespecified analysis of patients who received ≥ 5 days of the trial intervention are presented. Secondary outcomes included critical care unit and acute hospital lengths of stay, days of antibiotic use, and modified SOFA (Sepsis-related Organ Failure Assessment) score.
RESULTS: Selenium supplementation did not significantly affect patients developing a new infection (126/251 v 139/251, odds ratio 0.81 (95% CI 0.57 to 1.15)), except for those who had received ≥ 5 days of supplementation (odds ratio 0.53 (0.30 to 0.93)). There was no overall effect of glutamine on new infections (134/250 v 131/252, odds ratio 1.07 (0.75 to 1.53)), even if patients received ≥ 5 days of supplementation (odds ratio 0.99 (0.56 to 1.75)). Six month mortality was not significantly different for selenium (107/251 v 114/251, odds ratio 0.89 (0.62 to 1.29)) or glutamine (115/250 v 106/252, 1.18 (0.82 to 1.70)). Length of stay, days of antibiotic use, and modified SOFA score were not significantly affected by selenium or glutamine supplementation.
CONCLUSIONS: The primary (intention to treat) analysis showed no effect on new infections or on mortality when parenteral nutrition was supplemented with glutamine or selenium. Patients who received parenteral nutrition supplemented with selenium for ≥ 5 days did show a reduction in new infections. This finding requires confirmation. Trial registration Current Controlled Trials ISRCTN87144826.
OBJECTIVE: The aim of this study was to assess the clinical efficacy of alanine-glutamine dipeptide-supplemented total parenteral nutrition defined by the occurrence of nosocomial infections. Secondary parameters included Sequential Organ Failure Assessment score, hyperglycemia and insulin needs, intensive care unit and hospital length of stay, and 6-month mortality. DESIGN: Multicenter, prospective, double-blind, randomized trial. SETTING: Twelve intensive care units at Spanish hospitals. PATIENTS: One hundred twenty-seven patients with Acute Physiology and Chronic Health Evaluation II score >12 and requiring parenteral nutrition for 5-9 days. INTERVENTION: Patients were randomized to receive an isonitrogenous and isocaloric total parenteral nutrition or alanine-glutamine dipeptide-supplemented total parenteral nutrition. Nutritional needs were calculated: 0.25 g N/kg(-1)/d(-1) and 25 kcal/kg(-1)/d(-1). The study group received 0.5 g/kg(-1)/d(-1) of glutamine dipeptide and the control total parenteral nutrition group a similar amount of amino acids. Hyperglycemia was controlled applying an intensive insulin protocol with a target glycemia of 140 mg/dL. MEASUREMENTS AND MAIN RESULTS: The two groups did not differ at inclusion for the type and severity of injury or the presence of sepsis or septic shock. Caloric intake was similar in both groups. Preprotocol analysis showed that treated patients with alanine-glutamine dipeptide-supplemented total parenteral nutrition had lesser nosocomial pneumonia, 8.04 vs. 29.25 episodes-[0/00] days of mechanical ventilation (p = .02), and urinary tract infections, 2.5 vs. 16.7 episodes-[0/00] days of urinary catheter (p = .04). Intensive care unit, hospital, and 6-month survival were not different. Mean plasmatic glycemia was 149 ± 46 mg/dL in the alanine-glutamine dipeptide-supplemented total parenteral nutrition group and 155 ± 51 mg/dL in the control total parenteral nutrition group (p < .04), and mean hourly insulin dose was 4.3 ± 3.3 IU in the alanine-glutamine dipeptide-supplemented total parenteral nutrition group and 4.7 ± 3.7 IU in control total parenteral nutrition group (p < .001). Multivariate analysis showed a 54% reduction of the amount of insulin for the same levels of glycemia in the alanine-glutamine dipeptide-supplemented total parenteral nutrition group. CONCLUSIONS: Total parenteral nutrition supplemented with alanine-glutamine in intensive care unit patients is associated with a reduced rate of infectious complications and better glycemic control.
BACKGROUND: Low plasma glutamine concentration is an independent prognostic factor for an unfavourable outcome in the intensive care unit (ICU). Intravenous (i.v.) supplementation with glutamine is reported to improve outcome. In a multi-centric, double-blinded, controlled, randomised, pragmatic clinical trial of i.v. glutamine supplementation for ICU patients, we investigated outcomes regarding sequential organ failure assessment (SOFA) scores and mortality. The hypothesis was that the change in the SOFA score would be improved by glutamine supplementation.
METHODS: Patients (n=413) given nutrition by an enteral and/or a parenteral route with the aim of providing full nutrition were included within 72 h after ICU admission. Glutamine was supplemented as i.v. l-alanyl-l-glutamine, 0.283 g glutamine/kg body weight/24 h for the entire ICU stay. Placebo was saline in identical bottles. All included patients were considered as intention-to-treat patients. Patients given supplementation for >3 days were considered as predetermined per protocol (PP) patients.
RESULTS: There was a lower ICU mortality in the treatment arm as compared with the controls in the PP group, but not at 6 months. For change in the SOFA scores, no differences were seen, 1 (0,3) vs. 2 (0.4), P=0.792, for the glutamine group and the controls, respectively.
CONCLUSION: In summary, a reduced ICU mortality was observed during i.v. glutamine supplementation in the PP group. The pragmatic design of the study makes the results representative for a broad range of ICU patients.
BACKGROUND: We sought to investigate the effect of IV alanyl-glutamine supplementation on plasma glutathione levels in severely traumatized patients receiving enteral nutrition.
METHODS: Forty adult patients with severe trauma according to the Injury Severity Score >20 were enrolled in this randomized, controlled study. The patients were assigned to two groups: Group G received 0.5 g x kg(-1) x d(-1) of alanyl-glutamine dipeptide supplementation IV, and Group C received a control solution without alanyl-glutamine for 7 days. Blood samples were taken for analysis of glutathione before the initiation of supplementation and on the 3rd, 7th, and 10th days of feeding.
RESULTS: Total plasma glutathione levels significantly increased in Group G when compared with Group C on Days 7 and 10 (1.34 +/- 0.20 microM vs 1.13 +/- 0.14 microM, and 1.38 +/- 0.19 microM vs 1.12 +/- 0.16 microM) (P < 0.001).
CONCLUSIONS: This study demonstrates that IV alanyl-glutamine supplementation for 7 days increases total plasma glutathione levels in critically ill trauma patients receiving standard enteral nutrition.
To compare effects of different resuscitation fluid on microcirculation, inflammation, intestinal barrier and clinical results in severe acute pancreatitis (SAP).
METHODS:
One hundred and twenty patients with SAP were enrolled at the Pancreatic Disease Institute between January 2007 and March 2010. The patients were randomly treated with normal saline (NS group), combination of normal saline and hydroxyethyl starch (HES) (SH group), combination of normal saline, hydroxyethyl starch and glutamine (SHG group) in resuscitation. The ratio of normal saline to HES in the SH and SHG groups was 3:1. The glutamine (20% glutamine dipeptide, 100 mL/d) was supplemented into the resuscitation liquid in the SHG group. Complications and outcomes including respiratory and abdominal infection, sepsis, abdominal hemorrhage, intra-abdominal hypertension, abdominal compartment syndrome (ACS), renal failure, acute respiratory distress syndrome (ARDS), multiple organ dysfunction syndrome (MODS), operation intervention, length of intensive care unit stay, length of hospital stay, and mortality at 60 d were compared. Moreover, blood oxygen saturation (SpO2), gastric intramucosal pH value (pHi), intra-abdominal pressure (IAP), inflammation cytokines, urine lactulose/mannitol (L/M) ratio, and serum endotoxin were investigated to evaluate the inflammatory reaction and gut barrier.
RESULTS:
Compared to the NS group, patients in the SH and SHG groups accessed the endpoint more quickly (3.9 ± 0.23 d and 4.1 ± 0.21 d vs 5.8 ± 0.25 d, P < 0.05) with less fluid volume (67.26 ± 28.53 mL/kg/d, 61.79 ± 27.61 mL/kg per day vs 85.23 ± 21.27 mL/kg per day, P < 0.05). Compared to the NS group, incidence of renal dysfunction, ARDS, MODS and ACS in the SH and SHG groups was obviously lower. Furthermore, incidence of respiratory and abdominal infection was significantly decreased in the SH and SHG groups, while no significant difference in sepsis was seen. Moreover, less operation time was needed in the SH and SHG group than the NS group, but the difference was not significant. The mortality did not differ significantly among these groups. Blood SpO2 and gastric mucosal pHi in the SH and SHG groups increased more quickly than in the NS group, while IAP was significantly decreased in the SH and SHG group. Moreover, the serum tumor necrosis factor-α, interleukin-8 and C-reactive protein levels in the SH and SHG groups were obviously lower than in the NS group at each time point. Furthermore, urine L/M ratio and serum endotoxin were significantly lower in the SH group and further decreased in the SHG group.
CONCLUSION:
Results indicated that combination of normal saline, HES and glutamine are more efficient in resuscitation of SAP by relieving inflammation and sustaining the intestinal barrier.
