Tissue oxygen saturation is predictive of lactate clearance in patients with circulatory shock

We conducted a prospective observational study in a 15-bed medical ICU in a tertiary teaching hospital. The study protocol was approved by the institutional review board of Peking Union Medical College Hospital. Informed consents were obtained from the patients or relatives.

Study Population

All consecutive patients admitted for circulatory shock with a serum lactate level of 3.0 mmol/L or more were included. Circulatory shock was defined as systolic blood pressure less than 90 mm Hg or mean arterial pressure was less than 70 mm Hg, patients with evidence of tissue hypoperfusion (including but not limited to oliguria, skin mottling, altered mental status, cool peripheries, hyperlactatemia, etc.) [20]. All patients younger than 18 years old or pregnancy were excluded.

Investigated parameters

Demographic data, chronic comorbidities, Sequential Organ Failure Assessment (SOFA), shock type, and infection site were recorded on admission. Four sites of StO2 (masseter, deltoid, thenar, and knee), vital signs, blood lactate (arterial), arterial and central venous blood gas were recorded simultaneously within 48 h of ICU admission. And patients were still in state of shock at the moment of measurement after resuscitation was complete according to the Surviving Sepsis Guidelines [21]. Blood lactate concentration was measured repeatedly after 6 h from baseline when StO2 was initially monitored. A central line was placed in internal jugular vein in patients to allow for central venous blood sampling. Radial artery or femoral artery was cannulated in all patients for invasive blood pressure monitoring (IntelliVue Patient Monitor MP 70 (Philips Medical System, Boeblingen, Germany). Arterial and venous blood gases with lactate were measured immediately using GEM Premier 4000 blood gas analyzer (Instrumentation Laboratory, Bedford, Mass). StO2 was measured at right side of the masseter, deltoid, thenar, and knee sites by the Noninvasive cerebral oximetry monitor, BRS-1 with four 40-mm depth infrared probes (Casibrain Techonology Inc, Beijing, CHN). The StO2 values were recorded after 1 min of measurement when the signal was stable. Survival was followed-up during 14 days.

Definitions

Clearance of Lactate (cLac) was calculated as a change in blood lactate levels (%) after 6 h from baseline when StO2 was initially monitored [22]. The formula is as follows:

[(0 h-Lactate − 6 h-Lactate)/ 0 h-Lactate] × 100%. A positive value indicates a decrease in lactate rate.

Additionally, patients were divided into lactate clearance group and lactate non-clearance group. Lactate clearance was defined as 6-hour lactate clearance more than 10% [22].

Mean StO2 was the mean value of the four sites StO2. A BSA-weighted StO2 was calculated from four sites of StO2 (masseter, deltoid, thenar and knee), based on the rules of nines, which is a method used to quantify the area of affected skin in burns victims [23]. Masseter StO2 represented head, accounting for 9%, deltoid and thenar StO2 represented arms and torso, accounting for 45%, and knee StO2 represented legs, accounting for 46% (Fig S1).

The formulation was as follows:

masseter StO2 × 9% + (deltoid StO2 + thenar StO2) × (18% + 27%)/ 2 + knee StO2 × 46%

The Septic Shock 3.0 definition was used to define septic shock in the study [24].

Statistical analysis

On the basis of previous study, area under the receiver operating curves (AUROC) of StO2 for prediction of lactate clearance was expected to be 0.814. Total sample size required was 34 (17 in each group), with a power of 90% and α = 5% (two-sided). Values were presented as the mean (SD) or median (interquartile range (IQR)) for continuous variables as appropriate and as percent for categorical variables. Comparisons between groups were made using the chi-square test or Fisher’s exact test for categorical variables and Student’s t-test or the Mann–Whitney U test for continuous variables, as appropriate. All correlations among parameters were calculated as Spearman’s correlation, including correlation between StO2 in different sites, as well as correlations between StO2 , lactate clearance, MAP and norepinephrine dose. We evaluated correlations of StO2 in different sites using Spearman rank coefficients and visualized the relationships with heatmap. AUROC curves for lactate clearance was computed using the trapezoidal rule. The confidence interval (CI) were determined by the bootstrap technique, and comparison was made as described in DeLong [25]. The analysis of ROC is corrected for confounding factors including norepinephrine dose and mean arterial pressure (MAP). The category-free net reclassification improvement (NRI) was performed to quantify improvement offered by BSA-weighted StO2 [26]. Subgroup analysis was conducted based on patients with septic shock. All statistical analyses were performed using R (version 4.0.0, R studio, Boston, MA). GraphPad Prism 9.0 was used to graph results.

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