1Department of Global Innovative Drugs, Graduate School of Chung-Ang University, Chung-Ang University, Seoul, Korea
2Department of Laboratory Medicine, Chung-Ang University College of Medicine, Seoul, Korea
3College of Pharmacy, Chung-Ang University, Seoul, Korea
4Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, Korea
Copyright © 2023 The Korean Society of Critical Care Medicine
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Group | BIC | AIC | Patients in each predicted group (%) |
||||||
---|---|---|---|---|---|---|---|---|---|
1 | 2 | 3 | 4 | 5 | 6 | 7 | |||
2 | –1,786.28 | –1,731.37 | 43.2 | 56.8 | |||||
3 | –1,787.18 | –1,708.01 | 22.1 | 60.0 | 17.9 | ||||
4 | –1,872.80 | –1,769.37 | 0 | 43.2 | 56.8 | 0 | |||
5 | –1,916.07 | –1,788.37 | 0 | 43.2 | 0 | 56.8 | 0 | ||
6 | –1,849.98 | –1,698.02 | 0 | 8.4 | 29.5 | 48.4 | 13.7 | 0 | |
7 | –1,893.24 | –1,717.02 | 0 | 8.4 | 29.5 | 0 | 48.4 | 13.7 | 0 |
Characteristics | Group 1 (n=41) | Group 2 (n=54) | P-value |
---|---|---|---|
Age (yr) | 75 (70–84) | 78 (68–84) | 0.94 |
Sex | 0.72 | ||
Male | 22 (54) | 31 (57) | |
Female | 19 (46) | 23 (43) | |
Body mass index (kg/m2) | 21.3 (18.5–23.5) | 21.2 (18.1–24.2) | 0.93 |
Comorbidity | |||
Diabetes | 14 (34) | 26 (48) | 0.17 |
Hypertension | 25 (61) | 34 (63) | 0.84 |
Chronic heart failure | 5 (12) | 4 (7) | 0.49 |
Chronic lung disease | 7 (17) | 15 (28) | 0.22 |
Liver cirrhosis | 4 (10) | 3 (6) | 0.46 |
Chronic kidney disease | 6 (15) | 9 (17) | 0.79 |
Immunosuppression |
15 (37) | 8 (15) | 0.01 |
Nosocomial infection | 17 (42) | 16 (30) | 0.23 |
Cause of sepsis | |||
Pneumonia | 25 (61) | 29 (54) | 0.48 |
Urosepsis | 7 (17) | 13 (24) | 0.41 |
Gastrointestinal/biliary | 8 (20) | 7 (13) | 0.39 |
Bacteremia | 13 (32) | 22 (41) | 0.37 |
ARDS | 9 (22) | 12 (22) | 0.98 |
APACHE II score | 28 (20–35) | 27 (20–33) | 0.47 |
SOFA score | 12±3 | 12±3 | 0.49 |
Antibiotics | 41 (100) | 54 (100) | - |
Mechanical ventilation | 29 (71) | 37 (69) | 0.82 |
Renal replacement therapy | 13 (32) | 22 (41) | 0.37 |
Vital signs and laboratory data | |||
Body temperature (°C) | 36.9 (36.5–37.6) | 37.1 (36.6–37.6) | 0.54 |
Mean arterial pressure (mm Hg) | 59 (52–65) | 62 (54–66) | 0.26 |
Respiratory rate (breaths/min) | 30 (26–32) | 28 (25–32) | 0.38 |
PaO2/FiO2 | 194 (113–281) | 179 (113–248) | 0.67 |
Bicarbonate (mEq/L) | 21.0 (18.3–23.6) | 21.7 (17.6–24.5) | 0.51 |
Creatinine (mg/dl) | 1.3 (0.9–1.9) | 1.3 (0.9–2.3) | 0.96 |
Lymphocyte count (/mm3) | 690±644 | 810±998 | 0.60 |
Total bilirubin (mg/dl) | 0.6 (0.5–1.3) | 0.9 (0.5–1.8) | 0.41 |
C-reactive protein (mg/L) | 200±128 | 188±119 | 0.67 |
Procalcitonin (ng/ml) | 2.4 (0.7–23.4) (n=38) | 5.8 (1.6–40.5) (n=52) | 0.06 |
Lactate (mmol/L) | 1.7 (1.3–3.0) | 2.7 (1.9–4.9) | 0.02 |
Norepinephrine equivalent dose (μg/kg/min) | 0.19±0.21 | 0.29±0.24 | 0.006 |
Duration (day) | |||
Vitamin C | 3.6±0.9 | 4.4±1.2 | 0.002 |
Hydrocortisone | 4.2±2.6 | 5.0±1.9 | 0.004 |
Thiamine | 3.6±0.9 | 4.4±1.2 | 0.002 |
Time from shock onset to vitamin C protocol (hr) | 3 (1–6) | 1 (0–7) | 0.36 |
Outcomes | Group 1 (n=41) | Group 2 (n=54) | P-value |
---|---|---|---|
Mortality | |||
ICU | 16 (39.0) | 10 (18.5) | 0.03 |
28 Day | 20 (48.8) | 12 (22.2) | 0.007 |
60 Day | 20 (48.8) | 17 (31.5) | 0.09 |
Change in norepinephrine equivalent dose at day 4 (μg/kg/min) | –0.09±0.16 | –0.23±0.31 | <0.001 |
Change in SOFA score at day 4 | 0±5 | –4±3 | 0.002 |
Net fluid retention (ml) |
|||
Day 1 | 1,280 (696 to 2,791) | 1,118 (240 to 2,261) | 0.28 |
Day 4 | 180 (–338 to 1,053) (n=31) | 315 (–392 to 785) (n=54) | 0.62 |
Day 7 | 279 (–341 to 725) (n=28) | 160 (–769 to 850) (n=49) | 0.73 |
Vasopressor weaning | 31 (76) | 46 (85) | 0.24 |
Vasopressor-free day at day 28 | 26 (17 to 27) | 26 (22 to 27) | 0.55 |
Ventilator weaning | 14 (48) (n=29) | 24 (65) (n=37) | 0.18 |
Ventilator-free day at day 28 | 10±11 (n=29) | 13±11 (n=37) | 0.19 |
Length of stay (day) | |||
ICU | 6 (2 to 14) | 9 (5 to 18) | 0.03 |
Hospital | 22 (16 to 49) | 31 (17 to 50) | 0.07 |
Superinfection | 8 (20) | 14 (26) | 0.46 |
Characteristics | Unadjusted HR (95% CI) | P-value | Adjusted HRa) (95% CI) | P-value |
---|---|---|---|---|
Age | 1.02 (0.99–1.05) | 0.28 | ||
Male | 0.91 (0.47–1.73) | 0.91 | ||
Body mass index | 0.97 (0.90–1.04) | 0.43 | ||
Diabetes | 0.93 (0.48–1.78) | 0.82 | ||
Hypertension | 1.02 (0.52–1.97) | 0.97 | ||
Chronic heart failure | 1.38 (0.49–3.89) | 0.55 | ||
Chronic lung disease | 1.10 (0.52–2.34) | 0.80 | ||
Liver cirrhosis | 1.11 (0.34–3.61) | 0.87 | ||
Chronic kidney disease | 0.73 (0.28–1.86) | 0.50 | ||
Immunosuppressionb) | 2.28 (1.16–4.49) | 0.02 | 1.03 (0.43–2.45) | 0.95 |
Nosocomial infection | 2.17 (1.14–4.15) | 0.02 | 1.51 (0.76–3.03) | 0.24 |
Pneumonia | 1.75 (0.88–3.48) | 0.11 | ||
Urosepsis | 0.53 (0.21–1.37) | 0.19 | ||
Gastrointestinal/biliary | 0.63 (0.22–1.77) | 0.38 | ||
Bacteremia | 1.22 (0.63–2.36) | 0.55 | ||
ARDS | 1.78 (0.89–3.54) | 0.10 | ||
APACHE II score | 1.11 (1.06–1.16) | <0.001 | 1.09 (1.04–1.14) | <0.001 |
SOFA score | 1.23 (1.09–1.39) | 0.001 | 1.06 (0.90–1.25) | 0.51 |
Mechanical ventilation | 4.52 (1.60–12.79) | 0.004 | 1.30 (0.35–4.78) | 0.69 |
Renal replacement therapy | 2.73 (1.42–5.22) | 0.002 | 2.02 (0.96–4.24) | 0.06 |
Lymphocyte count | 1.00 (1.00–1.00) | 0.55 | ||
C-reactive protein | 1.00 (1.00–1.00) | 0.85 | ||
Lactate | 1.08 (0.96–1.21) | 0.19 | ||
Norepinephrine equivalent dose | 0.34 (0.06–1.88) | 0.22 | ||
Vitamin C duration | 0.83 (0.60–1.14) | 0.24 | ||
Thiamine duration | 0.83 (0.60–1.14) | 0.24 | ||
Hydrocortisone duration | 1.17 (1.03–1.34) | 0.02 | 1.14 (1.01–1.30) | 0.04 |
Time from shock onset to vitamin C protocol | 1.01 (0.96–1.05) | 0.77 | ||
IL-6 | 1.00 (1.00–1.00) | 0.73 | ||
TNF-α | 1.01 (0.00–1.01) | 0.16 | ||
IL-10 | 1.00 (1.00–1.00) | 0.04 | 1.00 (1.00–1.00) | 0.17 |
Group 2 | 0.48 (0.25–0.92) | 0.03 | 0.32 (0.16–0.64) | 0.001 |
The optimal model (the two-group model suggested) was considered based on the pattern of results and the balancing of BIC values and subgroup sizes. BIC: Bayesian information criterion; AIC: Akaike information criterion; GBMTM: group-based multi-trajectory modeling.
Values are presented as median (interquartile range), number (%), or mean±standard deviation. ARDS: acute respiratory distress syndrome; APACHE: Acute Physiology and Chronic Health Evaluation; SOFA: Sequential Organ Failure Assessment; PaO2: arterial partial pressure of oxygen; FiO2: fraction of inspired oxygen. Immunosuppression includes malignancies, human immunodeficiency virus infection, severe neutropenia, or administration of immunosuppressive therapy.
Values are presented as number (%), mean±standard deviation, or median (interquartile range). ICU: intensive care unit; SOFA: Sequential Organ Failure Assessment. Net fluid retention is calculated as the difference between intake and output of all fluids (urine volume, dialysis volume, drainage volume, and stool weight).
HR: hazard ratio; CI: confidence interval; ARDS: acute respiratory distress syndrome; APACHE: Acute Physiology and Chronic Health Evaluation; SOFA: Sequential Organ Failure Assessment; IL: interleukin; TNF: tumor necrosis factor. Adjusted for immunosuppression, nosocomial infection, APACHE II score, SOFA score, mechanical ventilation, renal replacement therapy, hydrocortisone duration, IL-10, and inclusion in group 2; b) Immunosuppression includes malignancies, human immunodeficiency virus infection, severe neutropenia, or administration of immunosuppressive therapy.