Among 748 acute critically ill adult patients, 302 (40.4%) sepsis events were identified within initial 48 hours. The median time from onset to infection was 1 hour (range, 0.5–24). The median time from early infection to sepsis was 9.0 hours ( range, 1–48 ). 282 SAE (93.4%) were diagnosed in sepsis. Among the 282 SAE patients, the median age was 59.9 years (range, 18–91 years), 63.2% were male, and the initial median GCS score was 7(3–15) ( in the Supplementary Table 1). At initial admission, a score on the GCS of 15 had 9 (3.2%) casees, but then 8 patients rapidly progressed to a score on the GCS of 13 to 6 and the remaining case was also identified as SAE due to an abnormal EEG with a score on the GCS of 15 (Fig. 2). Thus, within initial 48 hours, the most common presenting symptom of SAE was consciousness dysfunction (99.6%, range from delirium to coma), followed by severe inflammatory storm (97.5%) and MODS ( 96.8% ). A pure or isolated brain dysfunction was rare in ICU (3.2%).
Patients data for acute critically ill with and without SAE are described in Table 1. We found that SAE patients were more likely to present with a less median time from onset to ICU, lower GCS score, lower MAP, higher SOFA score, severe inflammatory storm (SIRS ≥ 2), higher qSOFS score, acute lung injure (ALI)/adult respiratory distress syndrome (ARDS), MODS, rapid heart rate, rapid respiratory, elevated WBC, elevated blood glucose, elevated lactic acid, elevated C-reactive protein, acute pneumonia, central herniation, and unused antibiotics treatment within initial 3 hours than those without sepsis (all p < 0.05). Of note, by logistic regression analysis, early risk factors for critically ill patients with SAE are related to severe inflammatory storm (OR, 3.10; 95% CI, 2.28–4.33), higher SOFA score (OR, 1.26; 95% CI, 1.11–1.42), lower initial GCS (OR, 0.89; 95% CI, 0.83–0.96), MODS (OR, 3.57; 95% CI, 2.93–4.66), and unused antibiotic treatment within initial 3 hours (OR, 0.25; 95% CI, 0.12–0.56).( Table 2)
Table 1
Univariable analysis of patients with SAE and without SAE in initial 48 hours in ICU (n = 748)
Variable | with SAE in initial 48 h (n = 282) | without SAE in initial 48 h (n = 466) | P Value |
Male gender, n (%) Age (years,mean ± SD) Median time from onset to ICU(h, range) Initial GCS score (mean ± SD) MAP(mmHg,mean ± SD) Respiratory rate(breaths/mim,mean ± SD) Body temperature(℃, mean ± SD) Heart rate(beats/min, mean ± SD) leukocyte count (x109/l, mean ± SD) Severe inflammatory storm, n (%) Blood glucose (mmol/l, mean ± SD) Blood lactic acid (mmol/l, mean ± SD) C-reactive protein,(mg/L,range) Initial SOFA score (mean ± SD) qSOFA score(mean ± SD) ALI/ARDS(needing intubated), n (%) MODS (mean ± SD) Community-acquired acute pneumonia, n, (%) Central herniation, n (%) Uncal herniation, n (%) Unused antibiotic in initial 3 hours, n (%) Mortality in initial 48 hours,n (%) | 167(59.2) 60.5 ± 15.2 1.1(2.7) 6.5 ± 3.0 109.3 ± 31.9 19.9 ± 7.6 36.4 ± 4.9 97.8 ± 24.1 14.3 ± 5.9 275(97.5) 9.9 ± 6.9 3.4 ± 2.3 39.3(0.1–207) 4.6 ± 1.8 1.4 ± 0.6 231(81.9) 2.4 ± 0.9 221(78.4) 195(69.1) 68 (24.1) 264(93.6) 90(32.0) | 306(65.7) 59.6 ± 16.0 1.2(2.5) 7.4 ± 3.1 119.5 ± 27.6 19.8 ± 5.3 36.3 ± 5.6 83.6 ± 21.9 11.7 ± 4.6 258(55.4) 8.8 ± 3.3 2.6 ± 2.1 12.3(0.3128 3.4 ± 1.5 1.1 ± 0.4 314(67.4) 0.4 ± 1.0 326(70.0) 288(61.8) 87(18.7) 391(83.9) 98(21.0) | 0.085 0.493 < 0.001 < 0.001 < 0.001 0.022 0.805 < 0.001 < 0.001 < 0.001 0.002 < 0.001 < 0.005 < 0.001 0.001 < 0.001 < 0.001 0.013 0.049 0.078 < 0.001 < 0.005 |
Abbreviation: ICU, intensive care unit; qSOFA, quick sequential organ failure assessment; sequential [sepsis-related] organ failure. GCS, Glasgow Coma Scale; ALI: acute lung injure; ARDS: adult respiratory distress syndrome; MODS, multiple organ dysfuunction syndrome. MAP, mean arterial blood pressure; |
Table 2
Logistic regression analysis to identify the early risk factors of SAE patients in initial 48 hours in ICU (n = 748)
Variable | OR | 95% CI for OR | P Value |
Severe inflammatory storm Lower GCS scores MODS Early SOFA score Unused antibiotics treatment in initial 3 hours | 3.101 0.891 3.568 1.256 0.249 | 2.282–4.333 0.825–0.961 2.730–4.663 1.110–1.422 0.112–0.555 | < 0.001 0.003 < 0.001 < 0.001 < 0.001 |
Abbreviations: GCS, Glasgow Coma Scale; ICU, intensive care unit MODS, multiple organ dysfunction syndrome; SOFA, sequential [sepsis-related] organ failure assessment. |
In 282 SAE, the risk of death was in 32.0% (90/282) at initial 48 hours and in 69.1% (195/282) at initial 14 days in ICU. Our data shown that no-survival SAE patients were significantly associated with the community-acquired pneumonia, severe inflammatory storm, a lower GCS score, lower MAP, higher SOFA score, higher qSOFA score, higher temperature, rapid respiratory, elevated heart rate, elevated lactic acid, ALI/ARDS(requiring ventilation), central herniation, and unused antibiotic within initial 3 hours than those survival SAE patients(all p < 0.05). (Table 3). However, Cox regression risk analysis demonstrated that an adjusting and controlling factor for early survival in SAE was more likely to be related to unused antibiotic treatment within initial 3 hours (OR, 0.39; 95% CI, 0.22–0.89; p = 0.021), severe inflammatory storm (OR, 0.70; 95% CI, 0.58–0.94), lower GCS (OR, 2.7; 95% CI, 1.5–3.6), and MODS (OR, 0.37; 95% CI, 0.26–0.96). (Table 4).
Table 3
Comparison of initial clinical conditions of SAE patients with survival and non-survival in initial 48 hrs in ICU (n = 282)
Variable | Non-survival (n = 90) | Surviva (n = 192) | P Value |
Male gender, n (%) Age (years,mean ± SD Initial GCS score (mean ± SD) MAP(mmHg,mean ± SD) Respiratory rate(breaths/mim,mean ± SD) Body temperature(℃, mean ± SD) Heart rate(beats/min, mean ± SD) leukocyte count (x109/l, mean ± SD) Blood glucose (mmol/l, mean ± SD) Blood lactic acid (mmol/l, mean ± SD) C-reactive protein,(mg/L,range) Initial SOFA score (mean ± SD) qSOFA score(mean ± SD) Severe inflammatory storm, (mean ± SD) ALI/ARDS ( intubated), n (%) MODS(mean ± SD) Central herniation, n (%) Uncal herniation, n (%) Unused antibiotic in initial 3 hours,n (%) | 62(68.9) 60.0 ± 16.4 5.6 ± 2.8 105.0 ± 40.9 16.4 ± 8.7 37.3 ± 4.4 95.7 ± 24.9 14.1 ± 0.7 8.9 ± 3.9 3.6 ± 2.7 97(63-169.3) 5.0 ± 2.1 1.4 ± 0.6 2.7 ± 1.1 80(88.9) 3.4 ± 1.0 65(72.2) 17(18.9) 89(98.9) | 124(64.6) 55.5 ± 16.0 6.7 ± 3.0 111 ± 27.9 20.8 ± 6.7 38.3 ± 1.2 98.1 ± 23.2 14.1 ± 0.5 9.9 ± 8.1 3.2 ± 2.0 83.4(34.6-110.2) 4.3 ± 1.7 1.4 ± 0.6 2.6 ± 1.0 151(78.6) 2.3 ± 1.1 113(58.9) 52(27.1) 175(91.1) | 0.503 0.044 < 0.005 0.140 < 0.001 0.004 0.432 0.932 0.977 0.152 0.073 0.005 0,940 0.028 0.040 0.000 0.032 0.181 0.016 |
Abbreviation: ICU, intensive care unit; SOFA, sequential [sepsis-related] organ failure assessment; qSOFA, quick sequential organ failure assessment; GCS, Glasgow Coma Scale; MAP, mean arterial lood pressure; ALI: acute lung injure; ARDS: adult respiratory distress syndrome; MODS, multiple organ dysfuunction syndrome. |
Table 4
Cox regression analysis in acute critically ill patients with SAE and without SAE initial 48 hrs in ICU (n = 282) .
Variable | OR | 95% CI for OR | p value |
Lower GCS score Severe inflammatory storm MODS Unused antibiotic within initial 3 h | 2.675 0.703 0.371 0.393 | 1.526–3.557 0.577–0.939 0.257–0.959 0.223–0.887 | 0.000 0.008 0.000 0.021 |
Abbreviations: ICU, intensive care unit.; GCS, Glasgow Coma Scale; MODS, multiple organ dysfuunction syndrome. |
Kaplan-Meier survival curves showed that early risk of bad survival in SAE at the initial 48 hours was significantly associated with infection patients who unused antibiotics treatment within the first 3 hours when compared with those used antibiotic treatment within first 3 hours (Log Rank, 6.7; p = 0.010). (Fig. 3)
By Kaplan-Meier survival curves analysis, the early risk of bad outcome in SAE at the initial 14 days was also significantly associated with infection patients who unused antibiotic treatment within first 3 hours when compared with those used antibiotic treatment within first 3 hours (Log Rank, 15.0; p = 0.000).