Jørgen Wiis

Hydroxyethyl starch 130/0.42 versus Ringer's acetate in severe sepsis.

BACKGROUND Hydroxyethyl starch (HES) [corrected] is widely used for fluid resuscitation in intensive care units (ICUs), but its safety and efficacy have not been established in patients with severe sepsis. METHODS In this multicenter, parallel-group, blinded trial, we randomly assigned patients with severe sepsis to fluid resuscitation in the ICU with either 6% HES 130/0.42 (Tetraspan) or Ringers acetate at a dose of up to 33 ml per kilogram of ideal body weight per day. The primary outcome measure was either death or end-stage kidney failure (dependence on dialysis) at 90 days after randomization. RESULTS Of the 804 patients who underwent randomization, 798 were included in the modified intention-to-treat population. The two intervention groups had similar baseline characteristics. At 90 days after randomization, 201 of 398 patients (51%) assigned to HES 130/0.42 had died, as compared with 172 of 400 patients (43%) assigned to Ringers acetate (relative risk, 1.17; 95% confidence interval [CI], 1.01 to 1.36; P=0.03); 1 patient in each group had end-stage kidney failure. In the 90-day period, 87 patients (22%) assigned to HES 130/0.42 were treated with renal-replacement therapy versus 65 patients (16%) assigned to Ringers acetate (relative risk, 1.35; 95% CI, 1.01 to 1.80; P=0.04), and 38 patients (10%) and 25 patients (6%), respectively, had severe bleeding (relative risk, 1.52; 95% CI, 0.94 to 2.48; P=0.09). The results were supported by multivariate analyses, with adjustment for known risk factors for death or acute kidney injury at baseline. CONCLUSIONS Patients with severe sepsis assigned to fluid resuscitation with HES 130/0.42 had an increased risk of death at day 90 and were more likely to require renal-replacement therapy, as compared with those receiving Ringers acetate. (Funded by the Danish Research Council and others; 6S ClinicalTrials.gov number, NCT00962156.).

Lower versus Higher Hemoglobin Threshold for Transfusion in Septic Shock

BACKGROUND Blood transfusions are frequently given to patients with septic shock. However, the benefits and harms of different hemoglobin thresholds for transfusion have not been established. METHODS In this multicenter, parallel-group trial, we randomly assigned patients in the intensive care unit (ICU) who had septic shock and a hemoglobin concentration of 9 g per deciliter or less to receive 1 unit of leukoreduced red cells when the hemoglobin level was 7 g per deciliter or less (lower threshold) or when the level was 9 g per deciliter or less (higher threshold) during the ICU stay. The primary outcome measure was death by 90 days after randomization. RESULTS We analyzed data from 998 of 1005 patients (99.3%) who underwent randomization. The two intervention groups had similar baseline characteristics. In the ICU, the lower-threshold group received a median of 1 unit of blood (interquartile range, 0 to 3) and the higher-threshold group received a median of 4 units (interquartile range, 2 to 7). At 90 days after randomization, 216 of 502 patients (43.0%) assigned to the lower-threshold group, as compared with 223 of 496 (45.0%) assigned to the higher-threshold group, had died (relative risk, 0.94; 95% confidence interval, 0.78 to 1.09; P=0.44). The results were similar in analyses adjusted for risk factors at baseline and in analyses of the per-protocol populations. The numbers of patients who had ischemic events, who had severe adverse reactions, and who required life support were similar in the two intervention groups. CONCLUSIONS Among patients with septic shock, mortality at 90 days and rates of ischemic events and use of life support were similar among those assigned to blood transfusion at a higher hemoglobin threshold and those assigned to blood transfusion at a lower threshold; the latter group received fewer transfusions. (Funded by the Danish Strategic Research Council and others; TRISS ClinicalTrials.gov number, NCT01485315.).

Provision of protein and energy in relation to measured requirements in intensive care patients

BACKGROUND & AIMS Adequacy of nutritional support in intensive care patients is still a matter of investigation. This study aimed to relate mortality to provision, measured requirements and balances for energy and protein in ICU patients. DESIGN Prospective observational cohort study of 113 ICU patients in a tertiary referral hospital. RESULTS Death occurred earlier in the tertile of patients with the lowest provision of protein and amino acids. The results were confirmed in Cox regression analyses which showed a significantly decreased hazard ratio of death with increased protein provision, also when adjusted for baseline prognostic variables (APACHE II, SOFA scores and age). Provision of energy, measured resting energy expenditure or energy and nitrogen balance was not related to mortality. The possible cause-effect relationship is discussed after a more detailed analysis of the initial part of the admission. CONCLUSION In these severely ill ICU patients, a higher provision of protein and amino acids was associated with a lower mortality. This was not the case for provision of energy or measured resting energy expenditure or energy or nitrogen balances. The hypothesis that higher provision of protein improves outcome should be tested in a randomised trial.

Transfusion requirements in septic shock (TRISS) trial - comparing the effects and safety of liberal versus restrictive red blood cell transfusion in septic shock patients in the ICU: protocol for a randomised controlled trial

BackgroundTransfusion of red blood cells (RBC) is recommended in septic shock and the majority of these patients receive RBC transfusion in the intensive care unit (ICU). However, benefit and harm of RBCs have not been established in this group of high-risk patients.Methods/DesignThe Transfusion Requirements in Septic Shock (TRISS) trial is a multicenter trial with assessor-blinded outcome assessment, randomising 1,000 patients with septic shock in 30 Scandinavian ICUs to receive transfusion with pre-storage leuko-depleted RBC suspended in saline-adenine-glucose and mannitol (SAGM) at haemoglobin level (Hb) of 7 g/dl or 9 g/dl, stratified by the presence of haematological malignancy and centre. The primary outcome measure is 90-day mortality. Secondary outcome measures are organ failure, ischaemic events, severe adverse reactions (SARs: anaphylactic reaction, acute haemolytic reaction and transfusion-related circulatory overload, and acute lung injury) and mortality at 28 days, 6 months and 1 year.The sample size will enable us to detect a 9% absolute difference in 90-day mortality assuming a 45% event rate with a type 1 error rate of 5% and power of 80%. An interim analysis will be performed after 500 patients, and the Data Monitoring and Safety Committee will recommend the trial be stopped if a group difference in 90-day mortality with P ≤0.001 is present at this point.DiscussionThe TRISS trial may bridge the gap between clinical practice and the lack of efficacy and safety data on RBC transfusion in septic shock patients. The effect of restrictive versus liberal RBC transfusion strategy on mortality, organ failure, ischaemic events and SARs will be evaluated.Trial registrationClinicalTrials.gov: NCT01485315. Registration date 30 November 2011. First patient was randomised 3 December 2011.

Long term end-stage renal disease and death following acute renal replacement therapy in the ICU

In ICU the need for acute renal replacement therapy (RRT) associates with high mortality and risk of end‐stage renal disease (ESRD), but there are limited long‐term data. We investigated these outcomes and their risk factors.

Pantoprazole in Patients at Risk for Gastrointestinal Bleeding in the ICU

BACKGROUND Prophylaxis for gastrointestinal stress ulceration is frequently given to patients in the intensive care unit (ICU), but its risks and benefits are unclear. METHODS In this European, multicenter, parallel‐group, blinded trial, we randomly assigned adults who had been admitted to the ICU for an acute condition (i.e., an unplanned admission) and who were at risk for gastrointestinal bleeding to receive 40 mg of intravenous pantoprazole (a proton‐pump inhibitor) or placebo daily during the ICU stay. The primary outcome was death by 90 days after randomization. RESULTS A total of 3298 patients were enrolled; 1645 were randomly assigned to the pantoprazole group and 1653 to the placebo group. Data on the primary outcome were available for 3282 patients (99.5%). At 90 days, 510 patients (31.1%) in the pantoprazole group and 499 (30.4%) in the placebo group had died (relative risk, 1.02; 95% confidence interval [CI], 0.91 to 1.13; P=0.76). During the ICU stay, at least one clinically important event (a composite of clinically important gastrointestinal bleeding, pneumonia, Clostridium difficile infection, or myocardial ischemia) had occurred in 21.9% of patients assigned to pantoprazole and 22.6% of those assigned to placebo (relative risk, 0.96; 95% CI, 0.83 to 1.11). In the pantoprazole group, 2.5% of patients had clinically important gastrointestinal bleeding, as compared with 4.2% in the placebo group. The number of patients with infections or serious adverse reactions and the percentage of days alive without life support within 90 days were similar in the two groups. CONCLUSIONS Among adult patients in the ICU who were at risk for gastrointestinal bleeding, mortality at 90 days and the number of clinically important events were similar in those assigned to pantoprazole and those assigned to placebo. (Funded by Innovation Fund Denmark and others; SUP‐ICU ClinicalTrials.gov number, NCT02467621.)

Forced fluid removal in intensive care patients with acute kidney injury: The randomised FFAKI feasibility trial

Accumulation of fluids is frequent in intensive care unit (ICU) patients with acute kidney injury and may be associated with increased mortality and decreased renal recovery. We present the results of a pilot trial assessing the feasibility of forced fluid removal in ICU patients with acute kidney injury and fluid accumulation of more than 10% ideal bodyweight.

Long Term Mortality And Risk of End-Stage Renal Disease Following Acute Rrt in Icu Patients

In the intensive care unit (ICU) the need for acute renal replacement therapy (aRRT) is associated with high mortality and risk of end-stage renal disease (ESRD). We investigated long term mortality and progression to ESRD in ICU patients requiring aRRT and factors associated to these.

Consecutive daily measurements of luminal concentrations of lactate in the rectum in septic shock patients.

In a recent study we found no difference in the concentrations of luminal lactate in the rectum between nonsurvivors and survivors in early septic shock (<24 h). This study was initiated to investigate if there are any changes in the concentrations of luminal lactate in the rectum during the first 3 days of septic shock and possible differences between nonsurvivors and survivors. Methods. We studied 22 patients with septic shock in this observational study. Six to 24 h after the onset of septic shock the concentration of lactate in the rectal lumen was estimated by 4 h equilibrium dialysis (day 1). The rectal dialysis was repeated on day 2 and day 3. Results. The concentration of lactate in the rectal lumen did not change over the 3 days in neither nonsurvivors nor survivors. Rectal luminal and arterial lactate concentrations were not different. Conclusion. There was no change in the concentration of lactate in the rectal lumen over time in patients with septic shock. Also, there was no difference between nonsurvivors and survivors.

OP031 PROVISION OF PROTEIN AND ENERGY IN RELATION TO MEASURED REQUIREMENTS IN INTENSIVE CARE PATIENTS – ASSOCIATIONS WITH MORTALITY

Methods: Twenty-fourSwiss male mice were randomly divided into four groups: glutamine group (GLN), glutamine + L-NAME group (LN), sham group and intestinal obstruction group (IO). The glutamine animals received glutamine solution (500mg×kg 1×d 1) by gavage for 7 days before surgery, while L-NAME animals received glutamine plus L-NAME (nitric oxide synthase inhibitor) 10mg/kg. The diet was isocaloric and isoproteic. On the 8th day, the animals were gavaged with a suspension containing 108 UFC/mL of E. coli labeled with 99mTc. Ninety minutes later, the animals were anesthetized and terminal ileum was isolated and ligated. The sham group underwent laparotomy only. The animals were anesthetized 18 h after surgery for blood collection and were then euthanized. Blood, mesenteric lymph nodes (MLN), liver, spleen and lungs were removed for radioactivity determination. The small intestine was removed, suspended in saline buffer and centrifuged. The supernatant fluid was collected for IgA determination by ELISA. Statistical analyses were performed using KruscalWallis and ANOVA. Significance was considered when p 0.05. Results: BT was significantly higher in LN and IO groups, while animals that received only glutamine showed significantly reduced levels of BT in all investigated organs when compared with IO and LN groups (p < 0.05). SIgA levels were similar for GLN and LN groups (1185.5±108; 1346±155.1 respectively) and higher (p < 0.05) than IO group (622±75.5). Conclusion: L-NAME increased BT, suggesting that NO is an important substrate derived from glutamine which prevents BT.