Albumin Level is Associated with Short-Term and Long-Term Outcomes in Sepsis Patients Admitted in the ICU: A Large Public Database Retrospective Research

Figures & data

Table 1 Baseline Characteristics of the Study Population

Albumin (g/dL) (Quartiles)
Variables	Total	Q1 (≤2.3)	Q2 (2.4–2.7)	Q3 (2.8–3.1)	Q4 (≥3.2)
Number	5357	1073	1584	1261	1439
Age(years)	66.00 (55.00–76.00)	64.00 (54.00–75.00)	66.00 (55.00–76.00)	66.00 (56.00–77.00)	66.00 (55.00–76.00)
Gender (n,%)
Male	3068 (57.27%)	572 (53.31%)	893 (56.38%)	744 (59.00%)	859 (59.69%)
Female	2289 (42.73%)	501 (46.69%)	691 (43.62%)	517 (41.00%)	580 (40.31%)
Comorbidities (n,%)
Hypertension	1105 (20.63%)	235 (21.90%)	317 (20.01%)	268 (21.25%)	285 (19.81%)
CAD	489 (9.13%)	81 (7.55%)	134 (8.46%)	129 (10.23%)	145 (10.08%)
Renal disease	239 (4.46%)	54 (5.03%)	59 (3.72%)	50 (3.97%)	76 (5.28%)
Diabetes	164 (3.06%)	23 (2.14%)	52 (3.28%)	47 (3.73%)	42 (2.92%)
Vital signs
HR (beats/min)	97.00 (83.00–112.00)	100.00 (85.00–114.00)	99.00 (84.00–114.00)	96.00 (81.00–112.00)	96.00 (81.00–110.00)
RR (beats/min)	21.00 (17.00–25.00)	21.00 (17.00–26.00)	21.00 (17.00–25.00)	20.00 (17.00–25.00)	21.00 (17.00–25.00)
SBP (mmHg)	111.00 (97.00–128.00)	109.00 (96.00–125.00)	110.00 (97.00–127.00)	111.00 (96.00–127.00)	113.00 (98.00–132.00)
DBP (mmHg)	63.00 (53.00–74.00)	62.00 (52.00–73.00)	63.00 (52.00–73.00)	63.00 (53.00–74.00)	63.00 (53.00–77.00)
Laboratory variables
ALT (IU/L)	30.00 (17.00–67.00)	27.00 (15.00–58.00)	31.00 (17.00–69.00)	31.00 (17.00–75.00)	29.00 (17.00–67.00)
AST (IU/L)	45.00 (25.00–103.00)	45.00 (25.00–104.00)	47.00 (26.00–103.00)	45.00 (24.00–102.00)	41.00 (24.00–101.00)
PT (s)	15.40 (13.30–20.10)	16.00 (13.90–20.40)	15.65 (13.50–19.90)	15.10 (13.20–19.80)	14.80 (12.80–20.55)
TT (s)	32.90 (28.70–40.70)	34.60 (29.50–43.20)	33.25 (28.90–41.00)	32.40 (28.50–39.40)	32.30 (28.20–39.90)
RBC (*10^12/L)	3.44 (2.92–3.99)	3.25 (2.78–3.71)	3.34 (2.87–3.84)	3.49 (2.98–4.00)	3.72 (3.12–4.22)
WBC (*10^9/L)	12.30 (7.60–18.30)	13.30 (8.10–19.80)	12.80 (7.70–19.10)	12.00 (7.40–17.60)	11.40 (7.50–16.70)
Total bilirubin (umol/L)	13.68 (6.84–32.49)	13.68 (6.84–37.62)	13.68 (6.84–34.20)	11.97 (6.84–27.36)	13.68 (6.84–32.49)
Total calcium (mmol/L)	2.00 (1.87–2.15)	1.90 (1.75–2.02)	1.97 (1.85–2.10)	2.02 (1.90–2.15)	2.12 (2.00–2.25)
Creatinine (umol/L)	123.76 (79.56–203.32)	114.92 (70.72–203.32)	114.92 (79.56–203.32)	123.76 (79.56–203.32)	123.76 (88.40–194.48)
Urea nitrogen (mmol/L)	4.64 (2.98–7.96)	4.98 (2.98–8.13)	4.81 (2.98–8.13)	4.81 (3.15–7.96)	4.48 (2.82–7.63)
RDW (%)	15.60 (14.20–17.50)	16.00 (14.60–18.00)	15.70 (14.30–17.50)	15.50 (14.20–17.20)	15.30 (14.00–17.20)
Hemoglobin (g/dL)	10.20 (8.70–11.80)	9.60 (8.20–11.10)	10.00 (8.60–11.40)	10.30 (8.90–11.90)	11.00 (9.20–12.50)
Hematocrit (%)	31.50 (27.10–36.20)	29.90 (25.70–34.20)	30.55 (26.50–35.00)	32.00 (27.70–36.50)	34.00 (28.80–38.30)
Bicarbonate (mmol/L)	21.00 (18.00–25.00)	20.00 (17.00–24.00)	21.00 (18.00–24.00)	21.00 (18.00–25.00)	22.00 (19.00–25.00)
PLT (*10^9/L)	182.00 (115.00–265.00)	189.00 (108.00–295.00)	181.00 (113.00–262.50)	180.00 (119.00–259.00)	180.00 (118.00–252.00)
AG (mmol/L)	16.00 (13.00–19.00)	15.00 (12.00–18.00)	15.00 (13.00–18.00)	16.00 (13.00–19.00)	17.00 (14.00–20.00)
Chloride (mmol/L)	103.00 (98.00–107.00)	104.00 (99.00–109.00)	103.00 (99.00–108.00)	103.00 (98.00–108.00)	101.00 (96.00–105.00)
Sodium (mmol/L)	138.00 (134.00–141.00)	137.00 (133.00–141.00)	138.00 (134.00–141.00)	138.00 (135.00–141.00)	137.00 (134.00–141.00)
INR	1.40 (1.20–1.90)	1.50 (1.30–1.90)	1.40 (1.20–1.80)	1.40 (1.20–1.80)	1.40 (1.20–1.90)
Lactate (mmol/L)	2.00 (1.40–3.20)	2.20 (1.40–3.50)	2.00 (1.40–3.00)	1.90 (1.30–3.10)	2.00 (1.40–3.20)
Scoring systems (IQR)
APACHEII	12.00 (9.00–15.00)	12.00 (10.00–16.00)	12.00 (9.00–15.00)	12.00 (9.00–15.00)	12.00 (9.00–15.00)
SOFA	3.00 (2.00–5.00)	3.00 (2.00–5.00)	3.00 (2.00–5.00)	3.00 (2.00–4.00)	3.00 (2.00–5.00)
Clinical outcomes (days)
LOS in ICU	5.40 (2.44–11.84)	6.77 (3.05–13.09)	5.26 (2.58–11.52)	4.64 (2.18–10.74)	5.30 (2.23–11.91)
LOS in hospital	12.92 (7.05–22.71)	14.27 (7.68–23.85)	13.02 (7.39–22.57)	11.77 (6.64–20.70)	12.74 (6.98–23.26)
28-day mortality (n,%)	1569 (29.29%)	440 (41.01%)	446 (28.16%)	325 (25.77%)	358 (24.88%)
60-day mortality (n,%)	1817 (33.92%)	487 (45.39%)	512 (32.32%)	376 (29.82%)	442 (30.72%)
180-day mortality (n,%)	1966 (36.70%)	521 (48.56%)	553 (34.91%)	409 (32.43%)	483 (33.56%)
1-year mortality (n,%)	2020 (37.71%)	525 (48.93%)	571 (36.05%)	424 (33.62%)	500 (34.75%)

Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; CAD, coronary artery disease; SBP, systolic blood pressure; DBP, diastolic blood pressure; HR, heart rate; RR, respiratory rate; WBC, white blood cells; PLT, platelet; RDW, red blood cell distribution width; RBC, red blood cells; PT, prothrombin time; TT, thrombin time; AG, anion gap; INR, international normalized ratio; SOFA, sequential organ failure assessment; APACHE, acute physiology and chronic health evaluation; LOS, length of stay; ICU, intensive care unit; IQR, interquartile ranges.

Figure 1 Flow chart and study design.

Table 2 Univariate Analysis for Short-Term and Long-Term Outcomes in Sepsis

Variables	Univariable (OR,95% CI) (28-Day Mortality)	Univariable (OR,95% CI) (60-Day Mortality)	Univariable (OR,95% CI) (180-Day Mortality)	Univariable (OR,95% CI) (1-Year Mortality)
Age (years)	1.02 (1.01, 1.02)	1.01 (1.01, 1.02)	1.01 (1.01, 1.02)	1.01 (1.01, 1.02)
Gender
Male	Ref.	Ref.	Ref.	Ref.
Female	0.99 (0.88, 1.12)	1.07 (0.95, 1.19)	1.02 (0.91, 1.14)	1.00 (0.89, 1.11)
Hypertension
No	Ref.	Ref.	Ref.	Ref.
Yes	0.95 (0.82, 1.10)	0.90 (0.78, 1.04)	0.89 (0.78, 1.03)	0.88 (0.77, 1.01)
CAD
No	Ref.	Ref.	Ref.	Ref.
Yes	1.13 (0.93, 1.38)	1.23 (1.02, 1.49)	1.26 (1.04, 1.52)	1.30 (1.07, 1.56)
Diabetes
No	Ref.	Ref.	Ref.	Ref.
Yes	0.62 (0.43, 0.91)	0.68 (0.48, 0.97)	0.71 (0.50, 0.99)	0.70 (0.50, 0.98)
Renal disease
No	Ref.	Ref.	Ref.	Ref.
Yes	1.38 (1.05, 1.81)	1.48 (1.14, 1.92)	1.61 (1.24, 2.09)	1.59 (1.23, 2.06)
HR (beats/min)	1.00 (1.00, 1.00)	1.00 (1.00, 1.00)	1.00 (1.00, 1.00)	1.00 (1.00, 1.00)
RR (beats/min)	1.01 (1.01, 1.02)	1.01 (1.00, 1.02)	1.01 (1.00, 1.02)	1.01 (1.00, 1.02)
SBP (mmHg)	1.00 (0.99, 1.00)	1.00 (0.99, 1.00)	1.00 (0.99, 1.00)	1.00 (0.99, 1.00)
DBP (mmHg)	1.00 (0.99, 1.00)	1.00 (0.99, 1.00)	1.00 (0.99, 1.00)	1.00 (0.99, 1.00)
ALT (IU/L)	1.00 (1.00, 1.00)	1.00 (1.00, 1.00)	1.00 (1.00, 1.00)	1.00 (1.00, 1.00)
AST (IU/L)	1.00 (1.00, 1.00)	1.00 (1.00, 1.00)	1.00 (1.00, 1.00)	1.00 (1.00, 1.00)
PT (s)	1.02 (1.01, 1.02)	1.02 (1.01, 1.02)	1.01 (1.01, 1.02)	1.01 (1.01, 1.02)
TT (s)	1.01 (1.01, 1.01)	1.01 (1.01, 1.01)	1.01 (1.01, 1.01)	1.01 (1.01, 1.01)
RBC (*10^12/L)	0.82 (0.76, 0.89)	0.78 (0.73, 0.85)	0.78 (0.73, 0.84)	0.77 (0.72, 0.83)
WBC (*10^9/L)	1.00 (1.00, 1.01)	1.00 (1.00, 1.01)	1.00 (0.99, 1.00)	1.00 (0.99, 1.00)
Total bilirubin (umol/L)	1.06 (1.04, 1.07)	1.06 (1.05, 1.08)	1.06 (1.04, 1.07)	1.06 (1.04, 1.07)
Total calcium (mmol/L)	1.06 (1.00, 1.12)	1.10 (1.04, 1.17)	1.12 (1.06, 1.19)	1.13 (1.07, 1.20)
Creatinine (umol/L)	1.06 (1.03, 1.09)	1.05 (1.02, 1.08)	1.05 (1.02, 1.09)	1.06 (1.03, 1.10)
Urea nitrogen (mmol/L)	1.01 (1.01, 1.01)	1.01 (1.01, 1.01)	1.01 (1.01, 1.01)	1.01 (1.01, 1.01)
RDW (%)	1.14 (1.12, 1.17)	1.17 (1.14, 1.19)	1.17 (1.15, 1.20)	1.17 (1.15, 1.20)
Hemoglobin (g/dL)	0.96 (0.93, 0.98)	0.94 (0.92, 0.97)	0.94 (0.92, 0.96)	0.94 (0.91, 0.96)
Hematocrit (%)	0.99 (0.98, 1.00)	0.98 (0.98, 0.99)	0.98 (0.97, 0.99)	0.98 (0.97, 0.99)
Bicarbonate (mmol/L)	0.99 (0.98, 1.00)	1.00 (0.98, 1.01)	1.00 (0.99, 1.01)	1.00 (0.99, 1.01)
PLT (*10^9/L)	1.00 (1.00, 1.00)	1.00 (1.00, 1.00)	1.00 (1.00, 1.00)	1.00 (1.00, 1.00)
AG (mmol/L)	1.05 (1.04, 1.06)	1.04 (1.03, 1.05)	1.04 (1.03, 1.05)	1.04 (1.03, 1.05)
Chloride (mmol/L)	0.98 (0.97, 0.98)	0.98 (0.97, 0.98)	0.97 (0.97, 0.98)	0.98 (0.97, 0.98)
Sodium (mmol/L)	0.99 (0.98, 1.00)	0.99 (0.98, 1.00)	0.98 (0.98, 0.99)	0.99 (0.98, 0.99)
INR	1.17 (1.12, 1.23)	1.17 (1.12, 1.23)	1.15 (1.10, 1.21)	1.15 (1.10, 1.21)
Lactate (mmol/L)	1.20 (1.17, 1.24)	1.19 (1.16, 1.23)	1.17 (1.14, 1.20)	1.17 (1.14, 1.20)
Albumin (g/dL)	0.67 (0.61, 0.74)	0.72 (0.66, 0.79)	0.74 (0.67, 0.81)	0.75 (0.69, 0.82)
SOFA	1.21 (1.18, 1.25)	1.21 (1.18, 1.25)	1.20 (1.17, 1.24)	1.21 (1.18, 1.25)
APACHEII	1.09 (1.07, 1.10)	1.08 (1.07, 1.10)	1.08 (1.07, 1.10)	1.08 (1.07, 1.10)

Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; CAD, coronary artery disease; SBP, systolic blood pressure; DBP, diastolic blood pressure; HR, heart rate; RR, respiratory rate; WBC, white blood cells; PLT, platelet; RDW, red blood cell distribution width; RBC, red blood cells; PT, prothrombin time; TT, thrombin time; AG, anion gap; INR, international normalized ratio; APACHE, acute physiology and chronic health evaluation; SOFA, sequential organ failure assessment; OR, odds ratio; CI, confidential interval.

Table 3 The Threshold Effect for Analysis Between Albumin and Clinical Outcomes

	Number (%)	OR (95% CI)
28-day mortality
Model I: The linear model	5357 (100%)	0.61 (0.54, 0.69)
Model II: Two-segment non-linear model
The turning point of albumin (g/dL)
≤2.6 (slope 1)	2318 (43.27%)	0.41 (0.32, 0.52)
>2.6 (slope 2)	3039 (56.73%)	0.79 (0.66, 0.94)
Slope 2 to slope 1		1.93 (1.35, 2.75)
Predicted at 2.6		−1.01 (−1.11, −0.91)
P for the log-likelihood ratio test		<0.001
60-day mortality
Model I: The linear model		0.66 (0.59, 0.73)
Model II: Two-segment non-linear model
The turning point of albumin (g/dL)
≤2.6 (slope 1)	2318 (43.27%)	0.38 (0.30, 0.48)
>2.6 (slope 2)	3039 (56.73%)	0.90 (0.76, 1.07)
Slope 2 to slope 1		2.39 (1.69, 3.37)
Predicted at 2.6		−0.85 (−0.94, −0.75)
P for the log-likelihood ratio test		<0.001
180-day mortality
Model I: The linear model		0.67 (0.60, 0.75)
Model II: Two-segment non-linear model
The turning point of albumin (g/dL)
≤2.6 (slope 1)	2318 (43.27%)	0.35 (0.28, 0.45)
>2.6 (slope 2)	3039 (56.73%)	0.97 (0.82, 1.14)
Slope 2 to slope 1		2.73 (1.95, 3.84)
Predicted at 2.6		−0.75 (−0.85, −0.66)
P for the log-likelihood ratio test		<0.001
1-year mortality
Model I: The linear model		0.68 (0.61, 0.76)
Model II: Two-segment non-linear model
The turning point of albumin (g/dL)
≤2.6 (slope 1)	2318 (43.27%)	0.38 (0.29, 0.48)
>2.6 (slope 2)	3039 (56.73%)	0.96 (0.82, 1.13)
Slope 2 to slope 1		2.55 (1.82, 3.58)
Predicted at 2.6		−0.70 (−0.79, −0.60)
P for the log-likelihood ratio test		<0.001

Notes: Model I and II adjusted for: age; gender; HR; SBP; DBP; RR; renal disease; CAD; diabetes; hypertension; AG; ALT, AST, PT; TT; RBC; WBC; total bilirubin; total calcium; bicarbonate; creatinine; chloride; lactate; hematocrit; hemoglobin; PLT; RDW; urea nitrogen; sodium; INR; SOFA; APACHEII.

Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; CAD, coronary artery disease; SBP, systolic blood pressure; DBP, diastolic blood pressure; HR, heart rate; RR, respiratory rate; WBC, white blood cells; PLT, platelet; RDW, red blood cell distribution width; RBC, red blood cells; PT, prothrombin time; TT, thrombin time; AG, anion gap; INR, international normalized ratio; APACHE, acute physiology and chronic health evaluation; SOFA, sequential organ failure assessment; OR, odds ratio; CI, confidential interval.

Figure 2 Smooth fitting curves demonstrated the non-linear relationships between albumin level and mortalities of 28-day (A), 60-day (B), 180-day (C) and 1-year (D).

Figure 3 Kaplan–Meier analysis for cumulative hazard of 1-year in sepsis based on quartiles of albumin level (Q1-Q4).