Kristian Strand

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 Ringer's 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 Ringer's 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 Ringer's 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 Ringer's acetate. (Funded by the Danish Research Council and others; 6S ClinicalTrials.gov number, NCT00962156.).

BACKGROUND: Intravenous fluids are recommended for the treatment of patients who are in septic shock, but higher fluid volumes have been associated with harm in patients who are in the intensive care unit (ICU). METHODS: In this international, randomized trial, we assigned patients with septic shock in the ICU who had received at least 1 liter of intravenous fluid to receive restricted intravenous fluid or standard intravenous fluid therapy; patients were included if the onset of shock had been within 12 hours before screening. The primary outcome was death from any cause within 90 days after randomization. RESULTS: We enrolled 1554 patients; 770 were assigned to the restrictive-fluid group and 784 to the standard-fluid group. Primary outcome data were available for 1545 patients (99.4%). In the ICU, the restrictive-fluid group received a median of 1798 ml of intravenous fluid (interquartile range, 500 to 4366); the standard-fluid group received a median of 3811 ml (interquartile range, 1861 to 6762). At 90 days, death had occurred in 323 of 764 patients (42.3%) in the restrictive-fluid group, as compared with 329 of 781 patients (42.1%) in the standard-fluid group (adjusted absolute difference, 0.1 percentage points; 95% confidence interval [CI], -4.7 to 4.9; P = 0.96). In the ICU, serious adverse events occurred at least once in 221 of 751 patients (29.4%) in the restrictive-fluid group and in 238 of 772 patients (30.8%) in the standard-fluid group (adjusted absolute difference, -1.7 percentage points; 99% CI, -7.7 to 4.3). At 90 days after randomization, the numbers of days alive without life support and days alive and out of the hospital were similar in the two groups. CONCLUSIONS: Among adult patients with septic shock in the ICU, intravenous fluid restriction did not result in fewer deaths at 90 days than standard intravenous fluid therapy. (Funded by the Novo Nordisk Foundation and others; CLASSIC ClinicalTrials.gov number, NCT03668236.).

BACKGROUND: Patients in the intensive care unit (ICU) require huge resources because of the dysfunction of several of their vital organs. The heterogeneity and complexity of the ICU patient have generated interest in systems able to measure severity of illness as a method of predicting outcome, comparing quality-of-care and stratification for clinical trials. METHODS: By searching Medline and EMBASE for publications describing scoring systems in the ICU, the most frequently used systems, defined as resulting in more than 50 references, are included in this review. Scoring systems belong to one of four classes prognostic, single-organ failure, trauma scores and organ dysfunction (OD). The different systems are described and discussed. RESULTS: Three different prognostic scoring systems, including several versions, four single OD scores and three OD scores, were included in this review. CONCLUSION: Different forms of scoring systems are frequently used in the ICU. They have become a necessary tool to describe ICU populations and to explain differences in mortality. As there are several pitfalls related to the interpretation of the numbers supplied by the systems, they should not be used without knowledge on the science of severity scoring.

BACKGROUND: Hypothermia, acidosis and coagulopathy have long been considered critical combinations after severe injury. The aim of this review was to give a clinical update on this triad in severely injured patients. METHODS: A non-systematic literature search on hypothermia, acidosis and coagulopathy after major injury was undertaken, with a focus on clinical data from the past 5 years. RESULTS: Hypothermia (less than 35 °C) is reported in 1·6-13·3 per cent of injured patients. The occurrence of acidosis is difficult to estimate, but usually follows other physiological disturbances. Trauma-induced coagulopathy (TIC) has both endogenous and exogenous components. Endogenous acute traumatic coagulopathy is associated with shock and hypoperfusion. Exogenous effects of dilution from fluid resuscitation and consumption through bleeding and loss of coagulation factors further add to TIC. TIC is present in 10-34 per cent of injured patients, depending on injury severity, acidosis, hypothermia and hypoperfusion. More expedient detection of coagulopathy is needed. Thromboelastography may be a useful point-of-care measurement. Management of TIC is controversial, with conflicting reports on blood component therapy in terms of both outcome and ratios of blood products to other fluids, particularly in the context of civilian trauma. CONCLUSION: The triad of hypothermia, acidosis and coagulopathy after severe trauma appears to be fairly rare but does carry a poor prognosis. Future research should define modes of early detection and targeted therapy.