Lactate is Associated with Increased 30-Day Mortality in Critically Ill Patients with Alcohol Use Disorder

Figures & data

Table 1 Baseline Characteristics of Critically Ill Patients with AUD

	Survivors	Non-Survivors	P
Clinical parameters	1073	223
Age, years	52.6 (43.4–61.2)	57.6 (48.8–68)	<0.001
Gender, n(%)			0.873
Female	264 (24.6)	56 (25.1)
Male	809 (75.4)	167 (74.9)
Ethnicity, n(%)			0.081
White	768 (71.6)	155 (69.5)
Black	82 (7.6)	10 (4.5)
Other	223 (20.8)	58 (26)
SBP, mmHg	119.9 (108.1–113.7)	109.8 (100.3–124.6)	<0.001
Heart rate, beats/min	91.5 (80.9–103.8)	92.2 (81.2–105.7)	0.651
Respiratory rate, beats/min	18.7 (16.3–21.7)	20 (17.2–23.8)	<0.001
Laboratory parameters
Lactate	1.5 (1.1–2.2)	2.1 (1.5–3.2)	<0.001
Bicarbonate, mmol/L	21 (18–24)	19 (15–22)	<0.001
Anion gap, mmol/L	12 (11–14)	14 (12–17)	<0.001
Creatinine, mg/L	0.8 (0.6–1.1)	1.1 (0.8–1.9)	<0.001
Glucose, mg/dl	104 (89–123)	104 (83–125)	0.427
WBC, 10^9/L	9 (6.1–12.1)	10 (6–15.9)	0.005
Hemoglobin, g/dl	10.3 (8.8–12)	9.7 (8.2–11.2)	0.002
Platelet, 10^9/L	152 (98–215)	101 (55–187)	<0.001
PT, second	13.6 (12.6–15.1)	15.9 (13.8–19.8)	<0.001
Comorbidities, n%
Congestive heart failure	80 (7.5)	15 (6.7)	0.704
Atrial fibrillation	141 (13.1)	50 (22.4)	0.001
Renal disease	57 (5.3)	26 (11.7)	<0.001
Liver disease	325 (30.3)	145 (65.0)	<0.001
Respiratory failure	519 (48.4)	151 (67.7)	<0.001
Malignancy	113 (10.5)	27 (12.1)	0.49
Sepsis	229 (21.3)	106 (47.5)	<0.001
Scoring systems
SOFA	5 (3–7)	9 (6–12)	<0.001
SAPS-II	32 (25–42)	49 (40–58)	<0.001
Vasoactive drug use, n%	367 (34.2)	139 (62.3)	<0.001
Length of ICU stay, days	5.2 (3–10.1)	5.8 (3.5–10.2)	0.213

Abbreviations: AUD, alcohol use disorder; ICU, intensive care unit; SBP, systolic blood pressure; WBC, white blood cell; PT, prothrombin time; SOFA, sequential organ failure assessment; SAPS II, simplified acute physiology score II.

Table 2 Baseline Characteristics of the Study Population with Different Lactate Level

		Lactate (mmol/l)
Characteristics	Tertile 1 (n=432)	Tertile 2 (n=432)	Tertile 3 (n=432)	P
	Lactate<1.3	1.3≤Lactate<2	Lactate≧2	value
Age, years	53.6 (44.5–62.3)	53.9 (45.5–63.1)	52 (42.9–61)	0.068
Gender, n(%)				0.858
Female	110 (25.5)	107 (24.8)	103 (23.8)
Male	322 (74.5)	325 (75.2)	329 (76.2)
Ethnicity, n(%)				0.563
White	315 (72.9)	311 (72)	298 (69)
Black	33 (7.6)	29 (6.7)	30 (6.9)
Other	84 (19.5)	92 (21.3)	104 (24.1)
SBP, mmHg	119 (107.3–133.4)	117.8 (107.1–131.4)	119.5 (106.1–132)	0.515
Heart rate, beats/min	89.7 (79.9–102.6)	91.7 (81.2–103.7)	91.7 (81.2–103.7)	0.005
Respiratoryrate, beats/min	18.8 (16.4–21.6)	18.8 (16.4–22)	19.2 (16.5–22.6)	0.430
Laboratory parameters
Bicarbonate, mmol/L	22 (19–25)	21 (18–24)	20 (16–23)	<0.001
Anion gap, mmol/L	12 (10–13)	12 (11–14)	14 (12–16)	<0.001
Creatinine, mg/L	0.8 (0.6–1)	0.9 (0.7–1.3)	0.8 (0.6–1.3)	<0.001
Glucose, mg/dl	99 (88–115)	107 (90–125.5)	107 (88–127)	<0.001
WBC, 10^9/L	9.1 (6.3–12.1)	9.2 (6.3–13.2)	9.1 (5.9–13.1)	0.808
Hemoglobin, g/dl	10.1 (8.9–11.6)	10.1 (8.5–12.1)	10.4 (8.8–12.3)	0.275
Platelet, 10^9/L	159 (107–227)	136 (84–198)	132 (70–201)	<0.001
PT, second	13.4 (12.4–14.8)	14 (12.9–14.9)	14.5 (12.8–17.8)	<0.001
Comorbidities, n%
Congestive heart failure	37 (8.6)	36 (8.3)	22 (5.1)	0.091
Atrial fibrillation	63 (14.6)	75 (17.4)	53 (12.3)	0.107
Renal disease	27 (6.3)	27 (6.3)	29 (6.7)	0.95
Liver disease	94 (21.8)	181 (41.9)	195 (45.1)	<0.001
Respiratory failure	238 (55.1)	209 (48.4)	223 (51.6)	0.142
Malignancy	43 (10)	53 (12.3)	44 (10.2)	0.483
Sepsis	97 (22.5)	98 (22.7)	140 (32.4)	<0.001
Scoring systems
SOFA	5 (3–7)	6 (4–9)	6 (3–10)	<0.001
SAPS-II	32 (26–41)	36 (28–46)	37 (26–49)	<0.001
Vasoactive drug use, n%	164 (38)	167 (38.7)	175 (40.5)	0.73
Length of ICU stay, days	5.6 (3.0–10.6)	5.1 (3–10)	5.1 (3–10)	0.611
30-day mortality, n(%)	35 (8.1)	71 (16.4)	117 (21.1)	<0.001

Abbreviations: AUD, alcohol use disorder; ICU, intensive care unit; SBP, systolic blood pressure; WBC, white blood cell; PT, prothrombin time; SOFA, sequential organ failure assessment; SAPS II, simplified acute physiology score II.

Figure 1 The relationship between lactate and 30-day mortality in critically ill patients with AUD. The dotted lines on both sides represent 95% confidence interval.

Table 3 The Association Between Lactate and 30-Day Mortality

Lactate	Non-Adjusted		Model I		Model II
	OR (95% CIs) P value		OR (95% CIs) P value		OR (95% CIs)	P value
Tertile 1	1.0 (ref)		1.0 (ref)		1.0 (ref)
Tertile 2	2.2 (1.5, 3.4)	<0.001	2.2 (1.4, 3.4)	<0.001	1.6 (1.0, 2.6)	0.042
Tertile 3	4.2 (2.8, 6.3)	<0.001	4.6 (3.0, 7.0)	<0.001	2.7 (1.7, 4.4)	<0.001
Continuous	1.6 (1.5, 1.8)	<0.001	1.7 (1.5, 1.9)	<0.001	1.4 (1.2, 1.6)	<0.001

Notes: a: model I covariates were adjusted for age, sex and ethnicity. b: model II covariates were adjusted for age, sex, ethnicity, SOFA, SAPS-II, liver disease, renal disease, atrial fibrillation, respiratory failure, sepsis, anion gap, creatine, hemoglobin, platelet, bicarbonate, WBC, PT, systolic blood pressure, respiratory rate and vasoactive drug use.

Abbreviations: OR, odds ratio; CI, confidence interval.

Figure 2 ROC curves for the prediction of mortality in critically ill patients with AUD. The area under curve of lactate, SOFA and SAPS-II were 0.672, 0.7413, and 0.7883 respectively.

Abbreviations: SOFA, sequential organ failure assessment; SAPS-II, simplified acute physiology score II.

Table 4 Subgroup Analysis of the Associations Between Lactate and 30-Day All-Cause Mortality

	N	Lactate<1.3 (ref)	1.3≤Lactate<2 OR (95% CIs)	Lactate≥2 OR (95% CIs)	P for Interaction
Gender					0.456
F	320	Ref	3.5 (1.3, 9.4)	6.3 (2.3, 17.1)
M	976	Ref	1.7 (1.0, 3.0)	3.1 (2.9, 5.2)
Ethnicity					0.622
White	924	Ref	2.1 (1.2, 3.5)	3.2 (1.9, 5.4)
Black	92	Ref	0.1 (0.0, 3.6)	2.8 (0.2, 48.4)
Other	280	Ref	2.0 (0.7, 5.5)	5.0 (2.0, 12.8)
CHF					0.408
No	1201	Ref	2.1 (1.3, 3.4)	3.7 (2.3, 5.8)
Yes	95	Ref	1.7 (0.3, 8.3)	1.4 (0.2, 7.9)
AF					0.439
No	1105	Ref	1.9 (1.1, 3.2)	3.8 (2.3, 6.3)
Yes	191	Ref	2.0 (0.8, 5.1)	1.8 (0.7, 5.1)
Renal disease					0.628
No	1213	Ref	2.0 (1.2, 3.3)	3.5 (2.2, 5.6)
Yes	83	Ref	2.4 (0.5, 12.3)	3.9 (0.8, 18.7)
Liver disease					0.019
No	826	Ref	1.1 (0.6, 2.1)	2.1 (1.2, 3.8)
Yes	470	Ref	4.3 (2.0, 9.6)	6.7 (3.1, 14.6)
Malignancy					0.493
No	1156	Ref	2.1 (1.3, 3.5)	3.8 (2.3, 6.2)
Yes	140	Ref	1.2 (0.3, 4.6)	2.0 (0.6, 7.2)
Respiratory failure					0.493
No	626	Ref	1.5 (0.7, 3.2)	2.8 (1.3, 5.8)
Yes	670	Ref	2.2 (1.3, 3.9)	3.7 (2.2, 6.5)
Sepsis					0.098
No	961	Ref	1.7 (1.0, 2.9)	3.0 (1.8, 5.2)
Yes	335	Ref	2.6 (1.1, 6.2)	4.0 (1.8, 9.0)
Vasoactive drug					0.275
No	790	Ref	3.1 (1.5, 6.8)	4.5 (2.1, 9.5)
Yes	506	Ref	1.3 (0.7, 2.4)	3.0 (1.7, 5.2)

Abbreviations: OR, odds ratio; CI, confidence interval.