ABSTRACT
BACKGROUND: The Scandinavian Starch for Severe Sepsis/Septic Shock (6S) trial showed increased 90-day mortality with hydroxyethyl starch (HES) 130/0.42 vs. Ringer's acetate. To explore the underlying pathophysiology, we compared early changes in plasma cytokine concentrations between patients resuscitated with HES vs. Ringer's acetate. METHODS: In a subgroup of 226 patients from the 6S trial, we calculated delta plasma concentrations of tumour necrosis factor alpha (TNF-α), interleukin (IL)-6 and IL-10 from randomization to day 2. We used multiple linear and logistic regression analyses to assess differences between the groups and associations between delta cytokine concentrations and 90-day mortality, respectively. RESULTS: Baseline characteristics and day 2 mortality were comparable between the groups. We observed similar delta cytokine concentrations in the HES vs. Ringer's group (mean difference in delta TNF-α: -1.5 pg/ml (95% CI, -4.9 to 1.9), P = 0.39; IL-6: 36.0 pg/ml (-24.1 to 96.1), P = 0.24; IL-10: -3.9 pg/ml (-21.1 to 28.9), P = 0.76). In all included patients, we observed a linear relationship between increases in TNF-α and 90-day mortality (P = 0.005). CONCLUSION: Resuscitation with HES 130/0.42 vs. Ringer's acetate did not appear to affect plasma concentrations of TNF-α, IL-6 or IL-10 differently during the first days after randomization into the 6S trial. In the overall cohort, increases in TNF-α were associated with increased 90-day mortality. Although interpretation should be done with caution, it seems unlikely that the increased mortality observed with the use HES in the 6S trial is signalled by early changes in three biomarkers of systemic inflammation.
Subject(s)
Cytokines/blood , Hydroxyethyl Starch Derivatives/therapeutic use , Isotonic Solutions/therapeutic use , Sepsis/blood , Sepsis/therapy , Aged , Cohort Studies , Double-Blind Method , Female , Fluid Therapy , Humans , Interleukin-10/blood , Interleukin-6/blood , Male , Middle Aged , Resuscitation , Sepsis/mortality , Systemic Inflammatory Response Syndrome/blood , Tumor Necrosis Factor-alpha/bloodABSTRACT
BACKGROUND: We aimed to detail the effects of hydroxyethyl starch (HES) vs. Ringer's on kidney function including the interaction with mortality in post-hoc analyses as resuscitation with HES 130/0.42 increased mortality in the Scandinavian Starch for Severe Sepsis/Septic Shock (6S) trial. METHODS: In all 798 randomised patients, we assessed the incidence and effect on mortality of acute kidney injury (AKI) in the HES vs. Ringer's acetate groups using the Kidney Disease: Improving Global Outcome criteria. We also assessed the intervention effect on time to and duration of renal replacement therapy (RRT). RESULTS: At baseline, the intervention groups were similar. The maximal AKI stage was higher in the HES vs. Ringer's group within the first 5 days after randomisation (P = 0.03), the average difference being 0.2 points (P < 0.01). An increase in AKI stage was associated with mortality (hazard ratio (HR) 1.35; 95% CI 1.22 to 1.49; P < 0.01). Significantly, more patients in the HES group received RRT within the first 5 days (P = 0.01), and the time to initiation of RRT was also shorter compared with the Ringer's group (HR 1.40; 95% CI 1.01-1.93; P = 0.04). The intervention effect of HES on mortality was reduced when adjusting for AKI stage as a time-dependent covariate (P = 0.15). CONCLUSION: In patients with severe sepsis, HES appeared to increase the rate of severe AKI and use of RRT within the first 5 days. The increased mortality observed with HES may have been partly mediated through acute kidney impairment.
Subject(s)
Acute Kidney Injury/mortality , Fluid Therapy/methods , Hydroxyethyl Starch Derivatives/therapeutic use , Plasma Substitutes/therapeutic use , Sepsis/mortality , Sepsis/therapy , Adult , Aged , Comorbidity , Female , Humans , Incidence , Isotonic Solutions/therapeutic use , Male , Middle Aged , Prospective Studies , Renal Replacement Therapy/statistics & numerical data , Scandinavian and Nordic Countries/epidemiology , Time FactorsABSTRACT
The caregiving literature has focused on European-American caregivers who are providing care to spouses or parents with Alzheimer's disease. The article reports ethnographic research exploring aspects of caregiving by rural African-American mothers for adult children with human immunodeficiency virus (HIV) disease. Eight African-American mothers were interviewed to elicit cultural domains of caregiving. Two major domains were a personal relationship with God and God's will. Taken together, these domains framed the context in which African-American mothers understood HIV disease, provided care, and resolved the death of their adult child.
