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.).

Does goal-directed fluid therapy affect postoperative orthostatic intolerance?: A randomized trial.

BACKGROUND: Early mobilization is important for postoperative recovery but is limited by orthostatic intolerance (OI) with a prevalence of 50% 6 h after major surgery. The pathophysiology of postoperative OI is assumed to include hypovolemia besides dysregulation of vasomotor tone. Stroke volume-guided fluid therapy, so-called goal-directed therapy (GDT), corrects functional hypovolemia, and the authors hypothesized that GDT reduces the prevalence of OI after major surgery and assessed this in a prospective, double-blinded trial. METHODS: Forty-two patients scheduled for open radical prostatectomy were randomized into standard fluid therapy (control group) or GDT groups. Both groups received a fixed-volume crystalloid regimen supplemented with 1:1 replacement of blood loss with colloid, and in addition, the GDT group received colloid to obtain a maximal stroke volume (esophageal Doppler). The primary outcome was the prevalence of OI assessed with a standardized mobilization protocol before and 6 h after surgery. Hemodynamic and hormonal orthostatic responses were evaluated. RESULTS: Twelve (57%) versus 15 (71%) patients in the control and GDT groups (P = 0.33), respectively, demonstrated OI after surgery, group difference 14% (CI, -18 to 45%). Patients in the GDT group received more colloid during surgery (1,758 vs. 1,057 ml; P = 0.001) and reached a higher stroke volume (102 vs. 89 ml; P = 0.04). OI patients had an increased length of hospital stay (3 vs. 2 days; P = 0.02) and impaired hemodynamic and norepinephrine responses on mobilization. CONCLUSION: GDT did not reduce the prevalence of OI, and patients with OI demonstrated impaired cardiovascular and hormonal responses to mobilization.

Long-term outcomes in patients with severe sepsis randomised to resuscitation with hydroxyethyl starch 130/0.42 or Ringer's acetate.

PURPOSE: We assessed long-term mortality and hospitalisation in patients with severe sepsis resuscitated with hydroxyethyl starch (HES) or Ringer's acetate. METHODS: This was an investigator-initiated, parallel-grouped, blinded randomised trial using computer-generated allocation sequence and centralised allocation data that included 804 patients with severe sepsis needing fluid resuscitation in 26 general intensive care units (ICUs) in Scandinavia. Patients were allocated to fluid resuscitation using either 6% HES 130/0.42 or Ringer's acetate during ICU admission. We assessed mortality rates at 6 months, 1 year and at the time of longest follow-up and days alive and out of hospital at 1 year. RESULTS: The vital status of all patients was obtained at a median of 22 (range 13-36) months after randomisation. Mortality rates in the HES versus Ringer's groups at 6 months were 53.3 (212/398 patients) versus 47.5% (190/400) [relative risk 1.12; 95% confidence interval (CI) 0.98-1.29; P = 0.10], respectively; at 1 year, 56.0 (223/398) versus 51.5% (206/400) (1.09; 95% CI 0.96-1.24; P = 0.20), respectively; at the time of longest follow-up, 59.8 (238/398) versus 56.3% (225/400) (1.06; 95% CI 0.94-1.20; P = 0.31), respectively. Percentage of days alive and out of hospital at 1 year in the HES versus Ringer's groups was 24 (0-87 days) versus 63% (0-90) (P = 0.07). CONCLUSIONS: The long-term mortality rates did not differ in patients with severe sepsis assigned to HES 130/0.42 versus Ringer's acetate, but we could not reject a 24% relative increased or a 4% relative decreased mortality at 1 year with HES at the 95% confidence level.

Effects of hydroxyethyl starch in subgroups of patients with severe sepsis: exploratory post-hoc analyses of a randomised trial.

PURPOSE: It has been speculated that certain subgroups of sepsis patients may benefit from treatment with hydroxyethyl starch (HES) 130/0.42, specifically in the earlier resuscitation of patients with more severely impaired circulation. METHODS: This was a post-hoc, subgroup analysis of all 798 patients with severe sepsis randomised in the 6S trial according to time from ICU admission to randomisation, surgery and fluids given prior to randomisation and markers of shock at randomisation. Intervention effects estimated as risk ratios were analysed between the HES versus Ringer's acetate groups to detect subgroup heterogeneity of the effects on 90-day mortality. Multiple logistic regression was used to adjust for risk factors. RESULTS: Most baseline characteristics were comparable between the HES and Ringer's acetate groups in the different subgroups. There was no heterogeneity in the intervention effect on 90-day mortality in the following subgroups: randomisation earlier than 4 h after ICU admission versus later (test of interaction P = 0.85), surgery versus no surgery (P = 0.42), colloids given versus not given (P = 0.57), <2 l of crystalloids given prior to randomisation vs. >2 l (P = 0.88) or plasma lactate >4 mmol/l versus <4 mmol/l (P = 0.54), hypotension versus no hypotension (P = 0.32) or use of vasopressor or inotropic agents at randomisation versus no use (P = 0.10). CONCLUSIONS: The increased 90-day mortality observed in patients with severe sepsis resuscitated with HES 130/0.42 did not appear to depend on time course, surgery or fluids given prior to randomisation or on markers of shock at randomisation. As the analyses were planned post hoc and their power is reduced, the results should be interpreted with caution.