Hypoperfusion context as a predictor of 28-d all-cause mortality in septic shock patients: A comparative observational study

doi:10.12998/wjcc.v11.i16.3765

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World Journal of Clinical Cases

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

Observational Study

World J Clin Cases. Jun 6, 2023; 11(16): 3765-3779
Published online Jun 6, 2023. doi: 10.12998/wjcc.v11.i16.3765

Table 1 Comparison of Group 1 and Group 2

Variable	Group 1			Group 2			P value
Variable	mean ± SD	Min-Max	Median (Q1-Q3)	mean ± SD	Min-Max	Median (Q1-Q3)	P value
Age	62.34 ± 14.32	20-92	64 (56-73)	61.03 ± 15.10	25-82	66.5 (52-72)	0.843
APACHE II	20.82 ± 5.47	9-32	20 (17-25)	23.78 ± 5.41	8-33	24 (21-28)	0.002^a
SOFA score	9.26 ± 4.22	2-18	8 (6-13)	8.88 ± 3.44	4-16	8 (6-11.75)	0.751
Hemoglobin	11.24 ± 6.30	7.1-16.70	10.2 (9.10-12.20)	10.26 ± 1.93	7.1-16	10.25 (8.75-11.7)	0.299
TLC	12.37 ± 7.92	0.1-46.50	11.9 (6.70-16.70)	12.56 ± 9.34	1.4-42.80	9.65 (6.5-16.65)	0.668
Platelet count	2.17 ± 1.01	0.1-5.26	1.98 (1.63-2.78)	2.08 ± 0.72	0.25-3.18	2.02 (1.61-2.75)	0.904
Serum bilirubin	1.84 ± 2.78	0.16-18.57	0.8 (0.55-1.6)	1.68 ± 2.24	0.28-10.93	0.81 (0.41-1.84)	0.507
Serum albumin	3.0 ± 0.60	1.5-4.4	2.9 (2.60-3.50)	2.9 ± 0.60	1.7-4	2.9 (2.30.-3.40)	0.584
INR	1.35 ± 0.36	0.95-3.83	1.28 (1.12-1.49)	1.31 ± 0.30	1.01-2.52	1.26 (1.08-1.44)	0.323
Creatinine	1.59 ± 1.31	0.2-10.50	1.3 (0.70-1.90)	1.34 ± 0.91	0.20-4.20	1.15 (0.6-1.85)	0.265
Urea	51.68 ± 34.75	7.8-229	41.7 (29.70-64.60)	54.12 ± 35.30	3.3-157	44 (33.1-69.88)	0.565
Heart rate	104.15 ± 15.44	64-156	107 (94-114)	106.73 ± 15.65	70-137	112 (98-118.75)	0.216
SBP	101.6 ± 22.16	50-166	102 (90-117)	99.5 ± 21.53	60-133	102 (81-117.75)	0.629
DBP	56.92 ± 15.26	24-97	58 (45-66)	58.58 ± 15.65	36-90	59 (44-68.75)	0.685
MAP	71.62 ± 16.08	31-106	70 (64-82)	72.5 ± 16.47	44-103	70.5 (61.75-87)	0.808
Lactate at 0 h	4.87 ± 1.69	2.1-9.70	4.6 (3.50-5.90)	4.76 ± 1.75	2.3-9.8	4.15 (3.5-5.65)	0.594
Lactate at 3 h	4.22 ± 2.0	1.3-12.00	3.6 (2.80-5.20)	3.82 ± 2.06	1.9-12.40	3.4 (2.45-4.10)	0.16
Lactate at 6 h	3.91 ± 3.01	0.6-14.10	2.8 (2.0-4.60)	3.88 ± 3.48	0.9-16.70	2.7 (2.0-4.20)	0.7
CRT at 0 h	5.14 ± 2.16	2-12	5 (3-7)	2.25 ± 0.67	1-3	2 (2-3)	< 0.001^a
CRT at 3 h	4.72 ± 2.68	1.0-13.00	4 (3-7)	3.55 ± 2	2-9	3 (2-4)	0.011^a
CRT at 6 h	4.50 ± 3.30	1.0-13.00	3 (2-7)	3.88 ± 3.22	1-13	3 (2-4)	0.255
ScvO₂ at 0 h	64.5 ± 9.10	42.8-74.20	70.4 (56.40-71.80)	71.8 ± 1.30	68.1-74.0	71.8 (70.9-72.70)	< 0.001^a
ScvO₂ at 3 h	60.1 ± 7.0	36.8-73.70	60.8 (56.70-64.70)	63.8 ± 4.70	52.8-73.50	63.6 (61.7-67.3)	0.002^a
ScvO₂ at 6 h	58.6 ± 9.0	36.7-89.20	60.2 (52.30-64.90)	62.4 ± 6.80	42.3-71.0	63.7 (58.7-68.3)	0.010^a
P(cv-a)CO₂ at 0 h	6.63 ± 1.78	2.9-9.80	7.2 (5-7.9)	4.24 ± 0.84	2.8-5.80	4.2 (3.6-4.86)	< 0.001^a
P(cv-a)CO₂ at 3 h	5.81 ± 2.03	2.6-12.30	5.5 (4.10-7)	5.05 ± 1.51	2.7-10	4.4 (4-5.98)	0.035^a
P(cv-a)CO₂ at 6 h	5.70 ± 2.30	2.6-12.40	5.1 (4-60.5)	5.88 ± 6.88	2.6-47	4.3 (3.6-6.375)	0.059
Lactate clearance at 3 h	10.2 ± 38.5	(-183.3-57.7)	22.7 (-7.30-36.0)	18.3 ± 29.8	(-103.3-58.2)	26.7 (5.4-36.4)	0.332
Lactate clearance at 6 h	15.3 ± 76.0	(-433.3-100.0)	39.6 (5.1-57.1)	20.3 ± 54.8	(-173.8-76.9)	39.1 (2.4-57.9)	0.973

^aDenotes statistical significance.

Group 1 referred to patients with hyperlactatemia in a hypoperfusion context. Group 2 referred to patients with hyperlactatemia in a non-hypoperfusion context. APACHE: Acute Physiology and Chronic Health Evaluation; CRT: Capillary refill time; DBP: Diastolic blood pressure; INR: International normalized ratio; MAP: Mean arterial pressure; P(cv-a)CO₂: Central venous-arterial pCO₂ gradient; Q1: First quartile; Q3: Third quartile; SBP: Systolic blood pressure; ScvO₂: Central venous oxygen saturation; SOFA: Sequential Organ Failure Assessment; TLC: Total leukocyte count; SD: Standard deviation.

Table 2 Comparison of baseline patient characteristics between Group 1 and Group 2

Characteristics	Group 1		Group 2		Total		P value
Characteristics	Frequency	%	Frequency	%	Frequency	%	P value
Sex
Female	43	45%	20	50%	63	95%	0.614
Male	52	55%	20	50%	72	105%
Comorbidities
DM	30	32%	12	30%	42	31%	0.856
HTN	39	41%	15	38%	54	40%	0.700
COPD	6	6%	5	13%	11	8%	0.393
CLD	7	7%	4	10%	11	8%	0.868
CKD	12	13%	8	20%	20	15%	0.271
Malignancy	7	7%	4	10%	11	8%	0.868
CAD	8	8%	6	15%	14	10%	0.403
Others IMM	5	5%	2	5%	7	5%	1.000
Source of infection
Intra-abdominal infection	27	28%	12	30%	39	29%	0.853
Bacteremia	11	12%	3	8%	14	10%	0.689
Pneumonia	30	32%	11	28%	41	30%	0.638
UTI	12	13%	8	20%	20	15%	0.271
Others	10	11%	2	5%	12	9%	0.484
Unknown	5	5%	4	10%	9	7%	0.529

Group 1 referred to patients with hyperlactatemia in a hypoperfusion context. Group 2 referred to patients with hyperlactatemia in a non-hypoperfusion context. CAD: Coronary artery disease; CKD: Chronic kidney disease; CLD: Chronic liver disease; COPD: Chronic obstructive pulmonary disease; DM: Diabetes mellitus; HTN: Hypertension; IMM: Immunocompromised diseases; UTI: Urinary tract infection.

Table 3 Comparison of survivors and non-survivors

Variable	Non-Survivors			Survivors			P value
Variable	mean ± SD	Min-Max	Median (Q1-Q3)	mean ± SD	Min-max	Median (Q1-Q3)	P value
Age	62.41 ± 14.61	28-82	66 (55.5-74.0)	61.82 ± 14.55	20-92	64 (53.75-71.25)	0.653
APACHE II	23.93 ± 4.91	14-32	24 (20.5-28.0)	21.08 ± 5.64	8-33	21 (17.00-25.25)	0.012^a
SOFA score	10.38 ± 4.71	2-17	11 (6-15)	8.81 ± 3.73	2-18	8 (6-11)	0.094
HB	12.2 ± 11.0	7.2-16.7	10 (8.8-12.0)	10.6 ± 2.0	7.1-16.9	10.3 (9.1-12.0)	0.493
TLC	10.0 ± 6.9	0.2-24.3	8.5 (5.4-13.8)	13.1 ± 8.6	0.1-46.5	11.9 (6.8-16.7)	0.101
PLT	1.99 ± 0.89	0.25-4.08	1.83 (1.58-2.01)	2.18 ± 0.95	0.10-5.26	2.10 (1.65-2.78)	0.188
SBIL	1.02 ± 0.84	0.28-4.70	0.78 (0.57-1.27)	2.00 ± 2.90	0.16-18.57	0.8 (0.5-2.0)	0.489
SALB	2.4 ± 0.4	1.6-3.1	2.3 (2.1-2.7)	3.1 ± 0.6	1.5-4.4	3.1 (2.7-3.5)	< 0.001^a
INR	1.28 ± 0.29	0.97-2.14	1.18 (1.09-1.31)	1.36 ± 0.36	0.95-3.83	1.30 (1.12-1.48)	0.099
CREAT	2.08 ± 0.95	0.50-4.90	1.80 (1.50-2.40)	1.36 ± 1.23	0.20-10.50	1.10 (0.60-1.80)	< 0.001^a
Urea	61.24 ± 44.91	9.90-229.00	45.60 (30.50-86.70)	49.99 ± 31.30	3.30-168.90	41.83 (30.10-61.60)	0.280
HR	107.00 ± 15.22	70-128	112 (98-118)	104.34 ± 15.58	64-156	106.50 (94.00-116.00)	0.228
SBP	94.66 ± 22.81	60-138	90 (74-116)	102.71 ± 21.45	50-166	102 (90-118)	0.065
DBP	52.41 ± 14.21	26-87	50 (41-60)	58.77 ± 15.41	24-97	60.00 (46.00-69.25)	0.060
MAP	66.24 ± 16.61	31-101	67.0 (53.0-76.5)	73.42 ± 15.74	33-106	71 (64-85)	0.057
Lactate at 0 h	5.20 ± 1.72	2.10-9.40	5.20 (4.0-5.70)	4.74 ± 1.69	2.30-9.80	4.40 (3.40-5.90)	0.151
Lactate at 3 h	5.54 ± 2.14	2.40-10.70	5.20 (3.80-6.70)	3.71 ± 1.80	1.30-12.40	3.40 (2.50-4.20)	< 0.001^a
Lactate at 6 h	6.61 ± 3.35	2.10-14.60	6.30 (3.90-8.60)	3.21 ± 2.70	0.60-16.70	2.45 (1.90-3.30)	< 0.001^a
CRT at 0 h	5.07 ± 2.46	2-12	5 (3-7)	4.07 ± 2.18	1-9	3 (2-6)	0.040^a
CRT at 3 h	6.38 ± 2.95	2-13	6 (4-8)	3.82 ± 2.14	1-10	3 (2-5)	< 0.001^a
CRT at 6 h	7.10 ± 4.10	2-13	9 (3-11)	3.63 ± 2.64	1-13	2.5 (2.0-5.0)	< 0.001^a
ScvO₂ at 0 h	68.30 ± 7.80	43.20-73.90	71.9 (70.2-72.8)	66.20 ± 8.50	42.80-74.20	70.80 (58.90-71.90)	0.033^a
ScvO₂ at 3 h	61.90 ± 7.10	45.80-73.50	62.8 (58.9-66.2)	61.00 ± 6.50	36.80-73.70	61.70 (57.80-64.90)	0.304
ScvO₂ at 6 h	58.10 ± 11.80	36.70-89.20	58.9 (49.7-66.2)	60.2 ± 7.60	37.90-71.0	61.90 (56.10-65.90)	0.299
P(cv-a)CO₂ at 0 h	6.50 ± 1.90	2.80-9.40	7.3 (4.9-7.9)	5.70 ± 1.90	2.80-9.80	5.50 (4.20-7.40)	0.036^a
P(cv-a)CO₂ at 3 h	7.00 ± 2.10	3.40-12.30	6.5 (5.6-8.6)	5.20 ± 1.60	2.7-11.0	4.8 (4.0-6.2)	< 0.001^a
P(cv-a)CO₂ at 6 h	7.10 ± 2.50	2.60-10.80	7.4 (4.9-9.2)	5.40 ± 4.50	2.60-8.70	4.70 (3.60-5.80)	< 0.001^a
Lactate clearance at 3 h	(-10.20 ± 35.10)	(-88.10-40.40)	(-8.6) (-37.1-24.7)	18.80 ± 34.20	(-183.30-58.20)	26.80 (7.30-37.20)	< 0.001^a
Lactate clearance at 6 h	(-28.70 ± 72.80)	(-187.0-100.0)	(-46.4) (-61.5-29.9)	29.20 ± 64.40	(-433.80-81.30)	44.90 (23.40-58.70)	< 0.001^a

^aDenotes statistical significance.

APACHE: Acute Physiology and Chronic Health Evaluation; CREAT: Creatinine; CRT: Capillary refill time; DBP: Diastolic blood pressure; HB: Hemoglobin; HR: Heart rate; INR: International normalized ratio; MAP: Mean arterial pressure; P(cv-a)CO₂: Central venous-arterial pCO₂ gradient; PLT: Platelet; Q1: First quartile; Q3: Third quartile; SALB: Serum albumin; SBIL: Serum bilirubin; SBP: Systolic blood pressure; ScvO₂: Central venous oxygen saturation; SD: Standard deviation; SOFA: Sequential Organ Failure Assessment; TLC: Total leukocyte count.

Table 4 Area under the curve to predict 28-d mortality for various perfusion markers at specified intervals

Test result variable	Area	Std. Error	P value	Asymptomatic 95%CI
Test result variable	Area	Std. Error	P value	Lower bound	Upper bound
Lactate at 0 h	0.587	0.058	0.133	0.499	0.671
Lactate at 3 h	0.776	0.048	< 0.001^a	0.696	0.843
Lactate at 6 h	0.845	0.04	< 0.001^a	0.772	0.902
Lactate clearance at 3 h	0.754	0.053	< 0.001^a	0.672	0.824
Lactate clearance at 6 h	0.834	0.041	< 0.001^a	0.76	0.893
CRT at 0 h	0.623	0.056	0.028^a	0.536	0.705
CRT at 3 h	0.768	0.047	< 0.001^a	0.688	0.837
CRT at 6 h	0.757	0.054	< 0.001^a	0.675	0.827
ScvO₂ at 0 h	0.630	0.062	0.035^a	0.542	0.711
ScvO₂ at 3 h	0.562	0.064	0.325	0.474	0.648
ScvO₂ at 6 h	0.565	0.072	0.367	0.476	0.651
P(cv-a)CO₂ at 0 h	0.627	0.060	0.033^a	0.540	0.709
P(cv-a)CO₂ at 3 h	0.754	0.052	< 0.001^a	0.673	0.824
P(cv-a)CO₂ at 6 h	0.736	0.060	< 0.001^a	0.652	0.808

^aDenotes statistical significance.

CI: Confidence interval; CRT: Capillary refill time; P(cv-a)CO₂: Central venous-arterial pCO₂ gradient; ScvO₂: Central venous oxygen saturation.

Table 5 Cutoff values of perfusion markers at specified intervals

Marker	Cutoff value	Sensitivity	Specificity	PPV	NPV	Accuracy	P value
Lactate at 0 h	> 4.9	55.2%	63.2%	29.1%	83.8%	61.5%	0.074
Lactate at 3 h	> 4.2	65.5%	77.4%	44.2%	89.1%	74.8%	< 0.001^a
Lactate at 6 h	> 4.1	74.1%	84.9%	55.6%	92.8%	82.7%	< 0.001^a
Lactate clearance at 3 h	≤ -20.6 (≥ 20.6% from baseline)	44.8%	93.4%	65.0%	86.1%	83.0%	< 0.001^a
Lactate clearance at 6 h	≤ -46.4 (≥ 46.4% from baseline)	55.6%	94.3%	71.4%	89.3%	86.5%	< 0.001^a
CRT at 0 h	> 4	55.2%	67.9%	32.0%	84.7%	65.2%	0.022^a
CRT at 3 h	> 4	69.0%	70.8%	39.2%	89.3%	70.4%	< 0.001^a
CRT at 6 h	> 8	51.9%	94.3%	70.0%	88.5%	85.7%	< 0.001^a
ScvO₂ at 0 h	> 71.7	55.2%	71.7%	34.8%	85.4%	68.2%	0.007^a
ScvO₂ at 3 h	> 61.7	69.0%	53.8%	29.0%	86.4%	57.0%	0.03^a
ScvO₂ at 6 h	≤ 58.9	55.6%	65.1%	28.9%	85.2%	63.2%	0.05
P(cv-a)CO₂ at 0 h	> 7.6	44.8%	81.1%	39.4%	84.3%	73.3%	0.004^a
P(cv-a)CO₂ at 3 h	> 5.9	72.4%	73.6%	42.9%	90.7%	73.3%	< 0.001^a
P(cv-a)CO₂ at 6 h	> 6.4	63.0%	83.0%	48.6%	89.8%	79.0%	< 0.001^a

^aDenotes statistical significance.

CRT: Capillary refill time; NPV: Negative predictive value; P(cv-a)CO₂: Central venous-arterial pCO₂ gradient; PPV: Positive predictive value; ScvO₂: Central venous oxygen saturation.

Table 6 Stepwise logistic regression to predict 28-d all-cause mortality

Step		B	S.E.	Wald test	df	Significance	Exp(B)	95%CI for Exp(B)
Step		B	S.E.	Wald test	df	Significance	Exp(B)	Lower	Upper
1^a	Lactate at 6 hours	0.302	0.073	17.230	1	0.000	1.353	1.173	1.561
1^a	Constant	-2.731	0.421	42.115	1	0.000	0.065
2^b	Creatinine	0.416	0.194	4.595	1	0.032	1.515	1.036	2.216
	Lactate at 6 hours	0.295	0.071	17.091	1	0.000	1.344	1.168	1.546
	Constant	-3.416	0.552	38.348	1	0.000	0.033

^aVariable(s) entered on step 1: lactate at 6 h.

^bVariable(s) entered on step 2: baseline creatinine. CI: Confidence interval; df: Degree of freedom; S.E.: Standard error.

Citation: Kataria S, Singh O, Juneja D, Goel A, Bhide M, Yadav D. Hypoperfusion context as a predictor of 28-d all-cause mortality in septic shock patients: A comparative observational study. World J Clin Cases 2023; 11(16): 3765-3779
URL: https://www.wjgnet.com/2307-8960/full/v11/i16/3765.htm
DOI: https://dx.doi.org/10.12998/wjcc.v11.i16.3765