Are Central Venous Lactate and Arterial Lactate Interchangeable

Supplemental Digital Content # 2 Are central venous lactate and arterial lactate interchangeable? A human retrospective study.

a- Comparison of bias between central venous (Lactcv) and arterial lactates (Lacta) in patients with and without acute respiratory distress syndrome

As shown in Figure E1, the bias between Lactcv and Lacta was not different for venous-arterial blood pairs either sampled from patients with acute respiratory distress syndrome (ARDS) (185 pairs) or from patients without ARDS (488 pairs): 0.021 (95%CI: 0.001 to 0.04) versus -0.065

(95%CI: -0.16 to -0.009), respectively. The lower and upper limits of agreement were -0.46 mmol/L (95%CI: -0.53 to -0.40) and 0.51 mmol/L (95%CI: 0.44 to 0.58) for ARDS patients and

-1.42 mmol/L (95%CI: -2.06 to -1.17) and 1.29 mmol/L (95%CI: 1.10 to 1.74) for the non

ARDS patients.

Figure E1

ARDS patients non ARDS patients 3 2 1 0 -1 Lact minus Lact vc a -2 -3 (mmol/L) -4 -5 -6 0 5 10 0 5 10 15 20 25

Average of Lact and Lact (mmol/L) vc a

1 Figure E1 legend

Title: Bias between central venous (Lactcv) and arterial lactates (Lacta) in patients with and without acute respiratory distress syndrome (ARDS)

Legend: Bland and Altman plot showing the very similar Lactcv/Lacta bias between ARDS patients (left panel) and non ARDS patients (right panel). Black horizontal lines represent the mean bias. Dashed horizontal lines represent the lower and upper limits of agreement. ARDS: acute respiratory distress syndrome.

2 b- Comparison of bias between central venous (Lactcv) and arterial lactates (Lacta) in patients with and without lung infection

As shown in Figure E2, the bias between Lactcv and Lacta was not different for venous-arterial blood pairs either sampled from patients with lung infection (346 pairs) or from patients without lung infection (327 pairs): -0.010 (95%CI: -0.044 to 0.017) versus -0.076 (95%CI: -0.202 to

0.003), respectively (p>0.05). The limits of agreement were -0.86 (95%CI: -1.063 to -0.75) to

+0.84 (95%CI: 0.751 to 0.998) mmol/L for patients with lung infection and -1.54 (95%CI:

-2.294 to -1.217) to +1.39 (95%CI: 1.153 to 1.899) mmol/L for patients without lung infection.

Figure E2

3 2 1 0 -1 Lact minus Lact vc a -2 (mmol/L) -3 -4 -5 -6 0 5 10 15 20 25

Average of Lact and Lact (mmol/L) vc a

3 Figure E2 legend

Title: Bias between central venous (Lactcv) and arterial lactates (Lacta) in patients with and without lung infection

Legend: Bland and Altman plot showing the very similar mean Lactcv/Lacta bias between patients with and without lung infection as represented by two superimposed thick dashed lines. Black horizontal lines represent the lower and upper limits of agreement for patients with lung infection.

Thin dashed horizontal lines represent the lower and upper limits of agreement for patients without lung infection.

Circles represent data of the patients without lung infection. Open squares represent the data of the patients with lung infection

4 c- Discriminatory power of central venous lactate to detect different cut-off values of

arterial lactate, compared between ARDS and non-ARDS patients, and between patients

with ou without lung infection.

The areas under the receiver operating characteristics curve (AUC) for central venous lactate

(Lactcv) to detect an arterial lactate level (Lacta) above 2 mmol/L or above 4 mmol/L were similar

in ARDS and non ARDS patients and in patients with or without lung infection (p>0.05):

ARDS Non ARDS Lung infection No lung infection

Number of patients in each group 40 148 86 101

Number of Lactcv/Lacta pairs measured per group 185 488 346 327

Performance of Lactcv to detect Lacta above 2 mmol/L: AUC (95%CI)** 0.99 0.98 0.97 0.99 (0.977 to 0.997) (0.966 to 0.99) (0.96 to 0.99) (0.97 to 0.997)

Performance of Lactcv to detect Lacta above 4 mmol/L: AUC (95%CI) 0.99 0.98 0.96 0.99 (0.978 to 1) (0.954 to 0.994) (0.91to 0.995) (0.98 to 0.998) AUC: mean area under the receiver operating characteristics curve estimated by bootstrapping;

95%CI: 95% confidence interval (see text for definition); Lacta: arterial lactate level; Lactcv:

central venous arterial lactate level