24 Aug 12
By A M Puskarich
Curr Op Crit Care 2012;18:295-300
Numerous implementation studies have demonstrated the benefit of bundled care in the initial treatment of patients with severe sepsis and septic shock, but the relative value of each component of these bundles remains uncertain. Recent studies have attempted to further define the optimal supportive and adjunctive treatments for these patients.
The choice of optimal intravenous resuscitation fluid for the emergency treatment of severe sepsis remains uncertain. Albumin appears safe, although safety concerns have arisen regarding the use of hydroxyethyl starch. Norepinephrine and vasopressin appear superior to dopamine as vasopressors of choice. Several studies have successfully incorporated lactate clearance into resuscitation strategies, albeit with differing protocols. Although corticosteroids may hasten improvement, there does not appear to be a mortality benefit in heterogeneous patients with sepsis, leaving their role uncertain.
Recent negative studies have questioned the role of previously promising adjunctive treatments. However, recent clinical trials and meta-analytic data continue to refine the relative importance of various components of sepsis bundles.
23 Aug 12
By A Perner, N Haase, A Guttormsen, J Tenhunen, G Klemenzson, A Åneman, K Madsen, et al for the 6S Trial Group and the Scandinavian Critical Care Trials Group
N Engl J Med 2012; 367:124-134
Hydroxyethyl starch (HES) 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.
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.
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.
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.
21 Aug 12
By R Sherwin, A Garcia, R Bilkovski
J Emerg Med. 2012;43:7-12.
The management of septic shock has undergone a significant evolution in the past decade. A number of trials have been published to evaluate the efficacy of low-dose corticosteroid administration in patients with septic shock.
The Sepsis Sub-committee of the American Academy of Emergency Medicine Clinical Practice Committee performed an extensive search of the contemporary literature and identified seven relevant trials.
Six of the seven trials reported a mortality outcome of patients in septic shock. Analysis of the data revealed that the relative risk (RR) of 28-day all-cause mortality in septic shock patients who received low-dose corticosteroids was 0.92 (95% confidence interval [CI] 0.79–1.07). All seven trials reported data concerning shock reversal or the withdrawal of vasopressors. Pooled results revealed that the RR of shock reversal is 1.17 (95% CI 1.07–1.28), which suggests that there may be significant improvement in shock reversal after corticosteroid administration. It is important to understand that two of the seven studies reviewed were disproportionately represented and accounted for 799 of 1005 patients (80%) considered for this recommendation.
The evidence suggests that low-dose corticosteroids may reverse shock faster; however, mortality is not improved for the overall population.
12 Jul 12
By S H Smith and A Perner
Critical Care 2012, 16:R76
Patients with septic shock require fluid, but the optimum amount is unknown. Therefore we assessed patient characteristics and outcome associated with fluid volume in unselected patients with septic shock including those with three days of shock.
We conducted a prospective, multicenter, observational study of all adult patients with septic shock during a 3-month study period at six general ICUs: three in university hospitals and three in regional hospitals. After day 1 and 3 of shock, patients were divided into two groups according to the overall median fluid volumes. Characteristics between these groups were compared using non-parametric and Chi-square statistics.
The 164 included patients received median 4.0 l (IQR 2.3-6.3) of fluid during the first day of septic shock. Patients receiving higher volumes (> 4.0 l) on day 1 had higher p-lactate (3.4 (2.2-5.5) vs. 2.0 (1.6-3.0) mmol l-1, P < 0.0001) compared to those receiving lower volumes. In contrast simplified acute physiology score (SAPS) II (54 (45-64) vs. 54 (45-67), P = 0.73), sequential organ failure assessment (SOFA) score (11 (9-13) vs. 11 (9-13), P = 0.78) and 90-day mortality (48 vs. 53%, P = 0.27) did not differ between groups. The 95 patients who still had shock on day 3 had received 7.5 l (4.3 – 10.8) of fluid by the end of day 3. Patients receiving higher volumes (> 7.5 l) had higher p-lactate (2.6 (1.7-3.4) vs. 1.9 (1.6-2.4) mmol l-1, P < 0.01) on day 3 and lower 90-day mortality (40 vs. 62%, P = 0.03) than those receiving lower volumes in spite of comparable admission SAPS II (53 (46-67) vs. 55 (49-62), P = 0.47) and SOFA scores on day 3 (10 (8-13) vs. 11 (10-14), P = 0.33).
In this cohort of unselected ICU patients with septic shock, initial fluid volume was not associated with mortality. In patients with shock for three days or more, higher fluid volumes including crystalloids, colloids and blood products were associated with reduced mortality.