The Serum Citrulline and D-Lactate are Associated with Gastrointestinal Dysfunction and Failure in Critically Ill Patients

Figures & data

Table 1 Baseline Characteristics of Patients and Healthy Control (HC)

Characteristic	HC N = 41	Gastrointestinal Dysfunction (GID) N = 67	Gastrointestinal Failure (GIF) N = 43	P value
Age (y)	48.56±16.31	51.36±17.50	49.07±23.66
<50	22	36	27	0.3159
≥50	19	31	16
Gender (cases)
Male	18	33	25	0.2304
Female	23	34	18
APACHE-II score	-	12.34±2.26	18.77±3.60	<0.001#
SOFA score	-	3.92±1.49	7.86±1.85	<0.001#
LPS (pg/mL)	2.35±0.72	5.27±0.99	8.91±2.97	<0.001*#
D-Lactate (μmol/L)	8.17±2.14	16.29±5.33	22.26±9.1	<0.001*#
Citrulline (μmol/L)	15.66±2.81	13.13±1.96	10.04±2.36	<0.001*#

Notes: *P < 0.001 vs HC, #P < 0.001 vs GID.

Abbreviation: LPS, lipopolysaccharide.

Figure 1 Correlation analysis between the serum levels of citrulline, D-lactate, and lipopolysaccharide (LPS) and the APACHE-II and SOFA scores. (A) Citrulline was negatively correlated with APACHE-II score; (B) citrulline was negatively correlated with SOFA score; (C) D-lactate was positively correlated with APACHE-II score; (D) D-lactate was positively correlated with SOFA score; (E) LPS was positively correlated with APACHE-II score; (F) LPS was positively correlated with SOFA score.

Figure 2 Citrulline serum level was elevated while D-lactate and lipopolysaccharide (LPS) serum levels were reduced in critically ill patients after treatment. (A) There were 52 out of 67 patients in the gastrointestinal dysfunction (GID) group and 33 out of 43 patients in the gastrointestinal failure (GIF) group displayed an increase in citrulline serum level after treatment. ***P < 0.001 vs Prior-treatment; (B) there were 48 out of 67 patients in the GID group and 34 out of 43 patients in the GIF group exhibited a decrease in D-lactate serum level after treatment. *P < 0.05 vs Prior-treatment; (C) there were 43 out of 67 patients in the GID group and 27 out of 43 patients in the GIF group showed an increase in LPS serum level after treatment. *P < 0.05 vs Prior-treatment.

Table 2 Logistic Regression Analysis Was Performed to Analyze the Association Between the Serum Biomarkers (Citrulline, D-Lactate, and LPS) and Gastrointestinal Dysfunction (GID)

Projects	B	Sig.	Exp (B)	95% CI for Exp (B)
Citrulline (μmol/L)	−0.399	0.000	0.671	0.558–0.807
D-Lactate (μmol/L)	0.751	0.000	2.120	1.541–2.916

Table 3 Logistic Regression Analysis Was Performed to Analyze the Association Between the Serum Biomarkers (Citrulline, D-Lactate, and LPS) and Gastrointestinal Failure (GIF)

Projects	B	Sig.	Exp (B)	95% CI for Exp (B)
Citrulline (μmol/L)	−0.963	0.000	0.382	0.242–0.604
D-Lactate (μmol/L)	0.821	0.001	2.272	1.413–3.653

Table 4 Diagnostic Accuracies of Serum Biomarkers of Gastrointestinal Dysfunction (GID) and Gastrointestinal Failure (GIF)

	Groups	Cutoff	Sensitivity (%)	Specificity (%)	AUC	95% CI	P value
	HC-GID	13.80	67.16	70.73	0.7472	0.6506–0.8438	<0.0001
Citrulline	GID-GIF	11.38	67.44	80.60	0.8112	0.693–0.9319	<0.0001
	HC-GIF	12.27	74.42	87.08	0.9314	0.8828–0.9800	<0.0001
	HC-GID	10.54	83.58	87.8	0.9337	0.8344–0.9753	<0.0001
D-Lactate	GID-GIF	23.25	72.09	88.06	0.8770	0.8071–0.9468	<0.0001
	HC-GIF	10.56	86.05	87.80	0.9512	0.9064–0.9961	<0.0001

Abbreviations: HC, healthy control; AUC, area under the ROC curve.

Figure 3 Diagnostic value of serum citrulline or D-lactate in gastrointestinal failure (GID) and gastrointestinal failure (GIF). (A–C) ROC curve analysis was used to assess the value of serum citrulline to distinguish GID from healthy control (HC), GIF from GID, or GIF from HC; (D–F) ROC curve analysis was used for evaluating the value of serum D-lactate to distinguish GID from HC, GIF from GID, or GIF from HC.

Table 5 Diagnostic Accuracies of Combinations of Serum Citrulline and D-Lactate of Gastrointestinal Dysfunction (GID) and Gastrointestinal Failure (GIF)

Groups	Cutoff	Sensitivity (%)	Specificity (%)	AUC	95% CI	P value
HC-GID	0.7049	91.04	97.56	0.9698	0.9356–1.004	<0.0001
GID-GIF	0.5381	76.74	92.65	0.9210	0.8642–0.9778	<0.0001
HC-GIF	0.4870	95.35	97.56	0.9943	0.9834–1.005	<0.0001

Abbreviations: HC, healthy control; AUC, area under the ROC curve.

Figure 4 Diagnostic value of serum citrulline combined with serum D-lactate in the diagnosis of gastrointestinal failure (GID) and gastrointestinal failure (GIF). (A–C) ROC curve analysis was used to assess the combination of serum citrulline and serum D-lactate to distinguish GID from healthy control (HC), GIF from GID, or GIF from HC.