The Prognostic Value

THE PROGNOSTIC VALUE

OF MUSCLE StO2 IN SEPTIC PATIENTS

ELECTRONIC SUPPLEMENTARY MATERIAL

Jacques Creteur, Tiziana Carollo, Giulia Soldati, Gustavo Buchele, Daniel De Backer, Jean-Louis Vincent

From the Department of Intensive Care, Erasme University Hospital, Free University of

Brussels, Belgium

1 METHODS

Study population

Treatment for septic shock

Treatment for septic shock was standardized, including vasopressor agents (dopamine up to

20 μg/kg/min and, if needed, addition of norepinephrine) to maintain a mean arterial pressure

>65 mmHg, in addition to repeated fluid challenges with crystalloids or colloids to optimize stroke volume and to minimize the need for vasopressor agents. Several indicators were used to trigger fluid challenge, including pulse pressure variations, decrease in stroke volume, and/or pulmonary artery occlusion pressure (PAOP) until stroke volume reached a plateau. If needed, dobutamine was added at a dose up to 20 μg/kg/min.

Study protocol

StO2 curve characteristics - Reproducibility The coefficients of variability for the determination of the slope and the Δ were calculated in 8 healthy volunteers, in whom these variables were evaluated five times, one hour apart, and in 8 septic patients in whom they were evaluated three times, one hour apart. These coefficients were 7.8% (from 2.5 to 12.7%) in healthy volunteers and 8.9% (from 4.5 to 13.9%) in septic patients, for the determination of the slope, and 10.2% (from 4.2 to 13.7%) in healthy volunteers and 9.2% (from 5.1 to 11.3%) in septic patients, for the determination of the Δ

Statistical Analysis

Data were analyzed using SPSS 13.0 for Windows (SPSS Inc., 2004) and StatView program

(StatView for Window, version 5; SAS Institute, Cary, NC). A Kolmogorov-Smirnov test was used to verify the normality of distribution of continuous variables. Discrete variables are expressed as counts (percentage) and continuous variables as means ± SD or median (25th –

75th percentiles). For demographics and clinical characteristics of the study groups, differences between groups were assessed using a chi-square, Fisher’s exact test, student t-

2 test, Mann-Whitney U test, analysis of variance followed by Tukey (honestly significant difference, HSD) test, or a Kruskal-Wallis test followed by a Mann-Whitney U test with adjustment for multiple comparisons. For the StO2 curve variables in the different study groups, analysis of variance followed by a Tukey (HSD) test with adjustment for multiple comparisons or a Kruskal-Wallis test were used. Linear regression was used to assess the correlation between slope and mean arterial pressure, arterial blood lactate, body mass index, hemoglobin, temperature, dose of analgesic and sedative drugs, and doses of vasopressor agents. The predictive value on outcome of the slope was calculated using a receiver operator characteristic (ROC) curve, and the AUC was computed. The analysis of repeated measurements with mixed-model, followed by LSD (least significant difference) tests, was used to evaluate the difference in the evolution of slope over time and between groups

(survivors and non survivors). We considered a p value < 0.05 to be significant.

3 FIGURE LEGENDS

Fig. 1 (ESM): Example of StO2 curves in a healthy volunteer (black line) and in a septic patient (gray line).

Fig. 2 (ESM): Slope in septic patients without shock (n = 24) and with shock (n = 48).

Significant difference at 0.05 level vs septic patients with shock.

Fig. 3 (ESM). Absence of correlation between slope and doses of norepinephrine in patients with sepsis with shock (n = 48).