Dynamic nomogram predicts sepsis risk in patients with acute liver failure: Analysis of intensive care database with external validation

Table 1 Baseline characteristics of patients with acute liver failure patients in the Medical Information Mart for Intensive Care database and external cohort

Characteristics	MIMIC cohort				FMCPH cohort (n = 228)
	Total (n = 510)	Sepsis (n = 387)	Non-sepsis (n = 123)	P value
Patient demographics
Age (year)	61.0 (48.2-73.0)	68.0 (52.5-75.0)	59.0 (48.0-71.0)	0.003	58.0 (47.5-70.5)
Male	325 (63.72)	248 (64.00)	77 (62.60)	0.849	173 (75.87)
Vital signs
MAP	78.0 (72.5-84.4)	77.0 (72.2-83.7)	79.3 (73.2-85.7)	0.071	77.4 (70.5-83.2)
Heart rate	88.1 (76.3-101.7)	89.3 (77.9-103.9)	84.5 (71.7-93.2)	0.005	85.9 (74.4-98.6)
Respiratory rate	20.5 (17.2-24.3)	20.9 (17.3-24.9)	19.2 (16.9-22.5)	< 0.001	20.2 (17.0-23.8)
Electrolytes and metabolic indicators
Na	138.6 (135.8-141.2)	139.0 (136.3-141.8)	137.6 (134.6-140.0)	< 0.001	137.0 (133.0-141.0)
Ca	7.9 (7.3-8.4)	7.8 (7.3-8.4)	8.2 (7.7-8.6)	< 0.001	7.6 (7.4-8.5)
K	4.8 (4.2-5.4)	4.9 (4.4-5.8)	4.7 (4.2-5.3)	0.014	4.8 (4.5-5.1)
Cl	101.6 (98.2-105.6)	101.7 (98.3-105.8)	101.2 (97.9-104.4)	0.098	100.9 (98.1-104.8)
Anion gap	19.5 (16.0-25.0)	20.0 (16.0-26.0)	17.0 (14.5-22.0)	< 0.001	18.3 (15.7-25.6)
Glucose	135.3 (112.4-167.0)	140.6 (115.8-170.8)	121.6 (104.2-151.2)	< 0.001	138.19 (116.2-169.2)
HbA1c	5.7 (5.3-6.4)	5.8 (5.3-6.8)	5.6 (5.3-5.8)	0.103	5.7 (5.2-6.3)
Fibrinogen	231.1 (159.4-340.4)	226.9 (159.5-343.5)	232.2 (157.3-322.1)	0.766	227.4 (152.7-337.2)
Granulocytes	0.9 (0.6-1.4)	0.9 (0.6-1.5)	0.7 (0.5-1.4)	0.019	0.9 (0.6-1.3)
CK	478.5 (142.5-1739.8)	561.5 (169.0-1922.4)	276.0 (114.5-1056.8)	0.026	486.4 (134.0-1817.5)
CRP	74.8 (25.8-133.8)	77.9 (36.5-145.4)	56.2 (18.2-113.7)	0.378	80.7 (24.1-125.0)
Blood routine examination
WBC	15.5 (11.0-21.5)	16.2 (12.2-22.7)	13.1 (8.3-18.2)	< 0.001	16.3 (11.9-23.9)
Neu	10.2 (7.2-15.3)	10.5 (7.6-15.9)	8.6 (5.8-12.5)	0.002	10.8 (7.0-14.8)
RBC	3.2 (2.8-3.8)	3.1 (2.8-3.7)	3.3 (2.9-4.0)	0.033	3.8 (2.6-4.1)
RDW	15.9 (14.3-18.4)	16.2 (14.4-18.4)	15.4 (14.0-17.6)	0.023	14.8 (13.6-17.3)
HCT	28.9 (26.3-34.4)	28.6 (26.1-33.8)	30.9 (27.3-36.6)	0.003	27.8 (24.9-35.0)
HGB	9.4 (8.5-11.3)	9.3 (8.4-11.0)	10.0 (8.8-12.3)	0.004	9.1 (8.1-12.2)
PLT	151.9 (93.3-210.1)	144.4 (88.2-207.4)	170.0 (107.8-224.2)	0.042	155.0 (101.0-269.0)
HCO3-	17.0 (13.0-21.0)	16.0 (12.0-20.0)	19.0 (15.5-22.0)	< 0.001	18.0 (14.5-22.5)
Blood gas analysis
PaO2	95.8 (69.9-124.2)	96.9 (74.2-123.4)	92.0 (53.0-132.0)	0.161	91.0 (74.0-117.2)
PaCO2	39.5 (35.6-43.7)	39.8 (35.7-43.7)	39.0 (34.5-43.2)	0.229	32.5 (27.8-36.0)
Renal function indicators
BUN	30.2 (18.9-42.3)	31.9 (20.2-46.7)	28.6 (16.0-40.9)	0.090	30.7 (17.7-38.7)
Cr	1.6 (1.0-2.5)	1.7 (1.1-2.6)	1.3 (0.8-1.9)	< 0.001	1.6 (1.0-2.2)
Liver function indicators
AST	333.5 (120.3-1079.6)	347.3 (127.8-1144.5)	276.8 (82.5-805.5)	0.027	315.0 (97.5-1010.5)
TBil	1.5 (0.7-4.8)	1.5 (0.7-6.0)	1.3 (0.7-2.4)	0.036	1.4 (0.8-3.8)
LDH	593.1 (356.4-1234.3)	647.4 (378.6-1385.0)	466.6 (307.5-877.9)	< 0.001	623.0 (387.4-1197.4)
Lactate	2.7 (1.9-4.4)	2.8 (2.0-4.7)	2.4 (1.8-3.5)	0.012	2.4 (1.6-3.3)
ALT	271.0 (80.9-752.7)	285.1 (90.0-765.0)	266.4 (67.8-741.2)	0.394	327.5 (79.5-896.8)
ALB	3.0 (2.6-3.4)	2.9 (2.6-3.3)	3.2 (2.8-3.5)	< 0.001	3.0 (2.5-3.3)
Coagulation function indicators
PT	18.4 (14.8-24.2)	18.4 (14.9-24.6)	18.1 (14.6-23.2)	0.526	19.2 (14.3-28.2)
INR	1.7 (1.4-2.2)	1.8 (1.6-2.2)	1.7 (1.5-2.1)	0.456	2.6 (1.7-3.9)
First day of ICU admission
CRRT	63 (12.4)	56 (14.5)	7 (5.7)	0.016	24 (10.5)
Vasopressin	85 (16.7)	79 (20.4)	8 (6.5)	< 0.001	28 (12.3)
Vasoactive agents	41 (8.0)	29 (7.5)	12 (9.8)	0.539	17 (7.5)
Mechanical ventilation	355 (69.6)	284 (73.4)	71 (57.7)	0.002	138 (60.5)
Severity Score
MELD	23.0 (16.0-31.0)	23.0 (17.0-33.0)	20.0 (14.0-27.5)	< 0.001	23.4 (21.0-33.9)
SAPS II	44.0 (34.0-57.0)	46.0 (36.0-58.0)	37.0 (29.0-50.0)	< 0.001	40.5 (31.0-54.5)
SIRS	3.0 (2.0-3.0)	3.0 (2.0-4.0)	3.0 (2.0-3.0)	< 0.001	3.0 (2.0-3.0)
SOFA	9.0 (6.0-11.0)	9.0 (7.0-12.0)	5.0 (4.0-8.0)	< 0.001	9.0 (6.0-10.0)
Outcome
28-day mortality	220 (43.1)	185 (47.8)	35 (28.5)	< 0.001	144 (63.1)
90-day mortality	257 (50.4)	207 (53.5)	50 (40.7)	0.017	163 (71.5)

MIMIC: Medical Information Mart for Intensive Care; MAP: Mean arterial pressure; CK: Creatine kinase; CRP: C-reactive protein; Neu: Neutrophils; RDW: Red cell distribution width; HCT: Hematocrit; HGB: Hemoglobin; PLT: Platelet; BUN: Blood urea nitrogen; Cr: Creatinine; AST: Aspartate aminotransferase; TBil: Total bilirubin; LDH: Lactate dehydrogenase; ALT: Alanine aminotransferase; ALB: Albumin; PT: Prothrombin time; INR: International normalized ratio; CRRT: Continuous renal replacement therapy; MELD: Model for end-stage liver disease; SAPS II: Simplified acute physiology score II; SIRS: Systemic inflammatory response syndrome; SOFA: Sequential organ failure assessment; FMCPH: The Fifth Medical Center of Chinese PLA General Hospital; HbA1c: Glycated hemoglobin; ICU: Intensive care unit.

Table 2 Risk factors for sepsis in patients with acute liver failure from the Medical Information Mart for Intensive Care derivation cohort

Parameters	Univariate		Multivariate
	OR (95%CI)	P value	OR (95%CI)	P value
Age (year)	0.984 (0.972-0.996)	0.007	1.016 (1.003-1.028)	0.017
Male	1.066 (0.713-1.622)	0.766
Heart rate	1.016 (1.004-1.027)	0.006
Respiratory rate	1.081 (1.033-1.131)	< 0.001
Na	1.098 (1.048-1.153)	< 0.001
Ca	0.718 (0.575-0.896)	0.003
K	1.317 (1.062-1.633)	0.012
Anion gap	1.085 (1.048-1.123)	< 0.001
Glucose	1.007 (1.002-1.012)	0.006
Granulocytes	1.652 (1.139-2.391)	0.008
WBC	1.076 (1.044-1.112)	< 0.001
Neu	1.081 (1.036-1.128)	< 0.001
RBC	0.765 (0.579-1.012)	0.058
PLT	0.998 (0.996-1.015)	0.085
RDW	1.065 (0.994-1.141)	0.074
HGB	0.877 (0.796-0.967)	0.008
TBil	1.054 (1.015-1.096)	0.007	1.047 (1.008-1.088)	0.017
LDH	1.000 (1.000-1.001)	0.001	1.001 (1.000-1.001)	< 0.001
Cr	1.343 (1.106-1.632)	0.003
Lactate	1.129 (1.032-1.237)	0.009
ALB	0.385 (0.248-0.599)	< 0.001	0.436 (0.274-0.692)	0.003
PH	0.004 (0.003-0.103)	< 0.001
HCO3-	0.910 (0.873-0.948)	< 0.001
Mechanical ventilation	2.019 (1.323-3.082)	< 0.001	1.985 (1.269-3.105)	0.003
Vasopressin	3.687 (1.728-7.869)	< 0.001
Vasoactive	0.749 (0.374-1.517)	0.423

Neu: Neutrophils; RDW: Red cell distribution width; HGB: Hemoglobin; PLT: Platelet; Cr: Creatinine; TBil: Total bilirubin; LDH: Lactate dehydrogenase; ALB: Albumin; OR: Odds ratio.

Table 3 Predictive value of various scoring models for sepsis risk in patients with acute liver failure in the internal derivation, validation cohort, and external validation cohort

Predictive model	Youden index	Cutoff	SEN	SPE	PPV	NPV	Brier score	R2 value	P value in H-L test
Derivation set in MIMIC cohort
SIALF model	0.573	0.726	0.770	0.802	0.924	0.527	0.128	0.411	0.989
SOFA	0.386	6.500	0.781	0.605	0.861	0.468	0.157	0.183	0.620
SIRS	0.183	2.500	0.729	0.453	0.807	0.348	0.180	0.022	0.022
Validation set in MIMIC cohort (internal validation)
SIALF model	0.600	0.717	0.815	0.786	0.918	0.589	0.087	0.665	0.943
SOFA	0.384	7.500	0.694	0.690	0.869	0.433	0.160	0.202	0.752
SIRS	0.265	2.500	0.718	0.548	0.824	0.397	0.178	0.082	0.088
FMCPH cohort (external validation)
SIALF model	0.553	0.719	0.784	0.769	0.918	0.518	0.078	0.703	0.801
SOFA	0.183	7.500	0.778	0.405	0.805	0.366	0.158	0.182	0.421
SIRS	0.352	2.500	0.650	0.703	0.874	0.388	0.177	0.045	0.067

SEN: Sensitivity; SPE: Specificity; PPV: Positive predictive value; NPV: Negative predictive value; H-L test: Hosmer-Lemeshow goodness-of-fit test; MIMIC: Medical Information Mart for Intensive Care; FMCPH: The Fifth Medical Center of Chinese PLA General Hospital; SIALF: Sepsis in acute liver failure; SOFA: Sequential organ failure assessment; SIRS: Systemic inflammatory response syndrome.