Background
Methods
Patients
Patients’ management
Categorization of patients
Definition of infection
Collection of data
Statistical analysis
Results
One of four patients admitted in the ICU with a suspicion of septic shock had no infection identified at 24 h of shock onset
All patients (n = 508) | EC-SS (n = 374) | Non EC-SS (n = 134) |
P
| |
---|---|---|---|---|
Age and gender | ||||
Age, years | 68 (59–79) | 67 (58–80) | 68 (61–78) | 0.81 |
Male gender | 297 (58) | 219 (59) | 78 (58) | >0.99 |
Comorbidities | ||||
Chronic respiratory disease | 21 (4) | 17 (5) | 4 (3) | 0.44 |
Chronic heart failure | 34 (7) | 22 (6) | 12 (9) | 0.22 |
Chronic kidney disease | 46 (9) | 33 (9) | 13 (10) | 0.76 |
Cirrhosis | 49 (10) | 35 (9) | 14 (10) | 0.71 |
Recent malignant hemopathy | 34 (7) | 27 (7) | 7 (5) | 0.43 |
Recent cancer | 63 (12) | 43 (11) | 20 (15) | 0.30 |
Diabetes mellitus | 132 (26) | 87 (23) | 45 (34) | 0.019 |
HIV infection | 17 (3) | 11 (3) | 6 (4) | 0.40 |
Obesity | 71 (14) | 54 (14) | 17 (13) | 0.62 |
Cerebrovascular disease | 55 (11) | 37 (10) | 18 (13) | 0.26 |
Immunosuppressive therapy | 54 (11) | 41 (11) | 13 (10) | 0.68 |
Immunosuppression statusa
| 132 (26) | 95 (25) | 37 (28) | 0.62 |
No coexisting comorbid conditions | 154 (30) | 119 (32) | 35 (26) | 0.22 |
Clinical data within 24 h of inclusion and antibiotic therapy | ||||
Maximal temperature, °C | 38.2 (37.3–39.0) | 38.4 (37.4 − 39.1) | 37.9 (36.9 − 38.6) | <0.0001 |
Minimal temperature, °C | 36.1 (35.2–37.0) | 36.2 (35.4–37.0) | 36.0 (34.6–36.8) | 0.006 |
Glasgow Coma Scale | 14 (11–15) | 15 (12–15) | 13 (9–15) | 0.002 |
SAPS2 | 58 (47–73) | 58 (45–72) | 59 (50–75) | 0.34 |
Delay admission-inclusion, hours | 1 (0–6) | 2 (0–7) | 1 (0–4) | 0.33 |
Delay inclusion -ATB1, hours | 0 (0–1) | 0 (0–1) | 0 (0–1) | 0.28 |
Delay inclusion -ATB2, hours | 0 (0–2) | 0 (0–2) | 0 (0–2) | 0.59 |
Number of ATB administered at 3 h | 2 (1–2) | 2 (1–2) | 2 (1–2) | 0.09 |
Number of ATB administered at 24 h | 2 (2–3) | 2 (2–3) | 2 (1–3) | 0.050 |
Biological data within 24 h of inclusion | ||||
Leukocyte count, 103.mm−3
| 16.5 (9.9–24.6) | 17.1 (9.8–24.9) | 15.9 (9.9–23.0) | 0.62 |
Platelets count, 103/mm−3
| 156 (85–243) | 156 (81–45) | 155 (92–236) | 0.72 |
C-reactive protein, mg/Lb
| 166 (87 − 265) | 178 (110 − 288) | 108 (48–179) | <0.0001 |
Procalcitonin, ng/mLc
| 7.6 (1.3–37.9) | 19.6 (3.7–56.5) | 1.6 (0.7–7.8) | <0.0001 |
Serum urea, mmol/L | 14.0 (8.7–21.7) | 13.6 (8.7–20.0) | 16.0 (9.1–24.0) | 0.16 |
Serum creatinine, μmoL/L | 187 (114–296) | 187 (115–275) | 198 (107–347) | 0.13 |
Prothrombin time, % | 58 (41–72) | 58 (42–72) | 56 (38–72) | 0.72 |
Arterial lactate, mmol/L | 3.5 (2.0–7.0) | 3.4 (2.0–6.1) | 3.6 (2.0–10.0) | 0.13 |
Patients with non EC-SS underwent more diagnostic testing
Patients with non EC-SS had predominantly non-infectious disease
Causes | Number (%) |
---|---|
Late-confirmed septic shock (LC-SS), n/total study sample (%) | 37/134 (28) |
Pleuro-pulmonary | 13/37 (35) |
Urinary tract | 6/37 (16) |
Abdomen | 4/37 (11) |
Liver and biliary tract | 4/37 (11) |
Primary bloodstream infection | 4/37 (11) |
Skin and soft tissues | 2/37 (5) |
Endocarditis | 1/37 (3) |
Bone-joint | 1/37 (3) |
Central nervous system | 1/37 (3) |
Endovascular stent infection | 1/37 (3) |
Septic shock mimickers (SSM), n/total study sample (%) | 59/134 (44) |
Adverse effects of drugs | 22/59 (37) |
Metformin | 10 |
Angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers | 4 |
β-blockers | 2 |
Propofol | 2 |
Othersa
| 4 |
Vascular | 12/59 (20) |
Acute mesenteric ischemia | 12 |
Arterial | 10 |
Venous | 2 |
Malignancies | 9/59 (15) |
Lymphoma | 3 |
Solid tumor (including one Marastic endocarditis) | 4 |
Tumor lysis syndrome | 2 |
Inflammatory diseases | 5/59 (8) |
Hemophagocytic lymphohistiocytosis | 2 |
Drug rash with eosinophilia and systemic symptoms | 1 |
Catastrophic antiphospholipid syndrome | 1 |
Cholesterol embolization syndrome | 1 |
Metabolic disorders | 4/59 (7) |
Acute adrenal insufficiency | 2 |
Diabetic ketoacidosis | 2 |
Acute pancreatitis | 4/59 (7) |
Miscellaneous | 3/59 (5) |
Abdominal compartment syndrome | 1 |
Air embolismb
| 1 |
“Reventilation” syndrome | 1 |
Shock of unknown origin (SUO), n/total study sample (%) | 38/134 (28 %) |
Day-60 mortality was not different between EC-SS and non EC-SS patients
All patients (n = 508) | EC-SS (n = 374) | Non EC-SS (n = 134) |
P
| |
---|---|---|---|---|
Tracheal intubation | 397 (78) | 294 (79) | 103 (77) | 0.67 |
ARDS | 167 (33) | 143 (38) | 24 (18) | <0.0001 |
Renal replacement therapy | 145 (28) | 95 (25) | 50 (37) | 0.009 |
Steroids for septic shocka
| 197 (39) | 143 (38) | 54 (40) | 0.67 |
ECMO | 8 (2) | 5 (1) | 3 (2) | 0.44 |
Duration of tracheal intubation, days | 4 (1 − 9) | 4 (1 − 9) | 4 (0 − 6) | 0.19 |
Duration of vasopressors support, days | 3 (2 − 5) | 3 (2 − 5) | 3 (2 − 6) | 0.55 |
Duration of ICU stay, days | 7 (4 − 14) | 7 (4 − 24) | 7 (4 − 21) | 0.69 |
ICU mortality | 188 (37) | 139 (37) | 49 (37) | 0.90 |
Follow-up duration, days | 29 (7 − 96) | 30 (8 − 91) | 25 (6 − 113) | 0.75 |
Mortality over the follow-up period | 232 (46) | 166 (44) | 66 (49) | 0.33 |
Variables | Univariable analysis | Multivariable analysisa
| ||
---|---|---|---|---|
HR (95 % CI) |
P
| HR (95 % CI) |
P
| |
Categorization of shock | ||||
EC-SS | 1 | - | - | |
Non EC-SS | 0.87 (0.65–1.16) | 0.34 | ||
Cirrhosis | ||||
No | 1 | 1 | ||
Yes | 2.04 (1.42–2.93) | <0.0001 | 2.45 (1.63–3.69) | <0.0001 |
Cancer | ||||
No | 1 | 1 | ||
Yes | 1.62 (1.15–2.28) | 0.006 | 1.91 (1.32–2.75) | <0.001 |
Chronic respiratory failure | ||||
No | 1 | 1 | ||
Yes | 2.16 (1.30–3.59) | 0.003 | 2.45 (1.41–4.26) | 0.002 |
Age >68 years | ||||
No | 1 | 1 | ||
Yes | 1.47 (1.14–1.91) | <0.0001 | 1.73 (1.30–2.30) | <0.0001 |
SAPS2 > 58 | ||||
No | 1 | 1 | ||
Yes | 3.01 (2.28–3.96) | <0.0001 | 1.94 (1.43–2.64) | <0.0001 |
PT ratio <50% | ||||
No | 1 | 1 | ||
Yes | 1.96 (1.50–2.55) | <0.0001 | 1.41 (1.05–1.91) | 0.024 |
Mechanical ventilation | ||||
No | 1 | 1 | ||
Yes | 3.65 (2.33–5.72) | <0.0001 | 2.53 (1.57–4.09) | <0.0001 |
Lactate, per point in mmol/L | 1.09 (1.07–1.11) | <0.0001 | 1.06 (1.04–1.09) | <0.0001 |
Sensitivity analysis assessing the validity of the results in the subgroup of patients meeting the criteria of the Sepsis-3 definition
Discussion
Conclusion
Key messages
-
One quarter of the patients admitted to the ICU on suspicion of septic shock had no infection identified 24 h after onset of shock.
-
Almost half of the patients with no infection identified 24 h after onset of shock had a non-infectious disease that mimicked sepsis.
-
The main causes of septic shock mimickers were adverse effects of drugs, malignancies, acute mesenteric ischemia and inflammatory diseases.
-
Outcomes did not differ between patients with and without early-confirmed septic shock.
-
Seven percent of the patients admitted to the ICU on suspicion of septic shock had shock of unknown origin.