Prospective observational study performed in a 24-bed medical ICU of a 1200-bed university hospital. We included and followed up all consecutive patients with cardiogenic shock and septic shock from December 2018 to June 2019. During the first three days after shock onset serum samples were collected to analyze inflammatory biomarkers (C-reactive protein (CRP), procalcitonin (PCT) and interleuquin-6 (IL-6)) and IgM antiendotoxin-core antibodies (IgM EndoCAb). The Institutional Review Board approved the study and informed consent was obtained from the patients’ relatives.

The following data were collected on study inclusion: sex, co-morbidities, severity scores prior to intubation (including Acute Physiology and Chronic Health Evaluation Score-II (APACHE-II),10 Sequential Organ Failure Assessment Score (SOFA)11 and the reason for ICU admission. Clinical, analytical, hemodynamic data and therapeutic measures along ICU stay were recorded. Nosocomial infections were pursuit by means of daily evaluation of signs and symptoms and microbiological assessment in case of clinical suspect.

Cardiogenic shock: Patients had to fulfill all this criteria: (a) Persistent hypotension (systolic blood pressure<80–90mm Hg or mean arterial pressure 30mm Hg lower than baseline); (b) Severe reduction in cardiac index (<1.8Lmin−1m−2 without support or <2.0–2.2Lmin−1m−2 with support) or severe left ventricular systolic dysfunction detected by echocardiography and adequate or elevated filling pressure assessed by pulmonary artery catheterization or by Doppler echocardiography and (c) Tissue hypoperfusion manifested by cool extremities, decreased urine output, and/or alteration in mental status.12

Septic shock: SS is defined as a subset of sepsis in which underlying circulatory and cellular metabolism abnormalities are profound enough to substantially increase mortality. Three variables must be identified: hypotension defined as mean arterial pressure less than 65mmHg, serum lactate level more than 2mmol/l and a sustained need for vasopressor therapy.13

Diagnosis of infection: Infection diagnosis was established according to the CDC criteria. In summary infection diagnosis requires the presence of some clinical criteria followed by a microbiological confirmation.14 For ventilator-associated pneumonia (VAP) two or more of the following should be present: temperature greater than 38°C, leukocytosis greater than 12,000/mm3 or leucopenia lower than 4000/mm3, or purulent respiratory secretions; plus a new or progressive pulmonary infiltrate on chest X-ray. VAP confirmation was defined by the quantitative culture of tracheobronquial aspirate≥105cfu/ml2, bronchoalveolar lavage with ≥104cfu/ml or mini bronchoalveolar lavage≥103cfu/ml.15

Blood samples were centrifuged (1500rpm, 10min) and serum was frozen at −80°C. PCT was measured by TRACE (Time-Resolved Amplified Crypate Emission) technology in a Kyptor analyzer (Brahms Diagnostica, Berlin, Germany). Measurement of CRP was performed with an immunoturbidimetric method using a commercial kit (Tina-quant CRP, Roche Diagnostics, Mannheim, Germany). IL6 was measured by electrochemiluminescence (ECL) in the Cobas 6000 (E-170), Roche Diagnostics.

Commercially available enzyme-linked immunosorbent assays were used according to the manufacturers’ protocols for measuring EndoCAb IgM (Hycult Biotech, The Netherlands). The EndoCAb ELISA was originally devised to screen blood donor plasma for high-titer antibodies to endotoxin core, which are cross-reactive with endotoxins of a number of Gram-negative bacterial species, and was then applied to a variety of clinical studies. The EndoCAb® standard median-units IgM (MU) are arbitrary and are based on medians of ranges for 1000 healthy adults; 10–90th percentile range have been established at 35–250MU/ml and mean normal value at 100MU/ml.5 According to manufactures’ instructions the kit has a detection level of 0.05MU/ml.

Quantitative variables were presented as median with p25 and p75 quartiles. Continuous variables were compared using the Student t test for normally distributed variables and the Mann–Whitney U test for non-normally distributed variables. Categorical variables were compared using the Chi-square and the Fisher's exact tests when appropriate. The threshold for statistical tests significance was set at 5%. We use ROC curve to determinate the discriminative capacity of antibodies. The collected data were entered and analyzed in SPSS 15.0 software (SPSS, Chicago, IL).

Sixty-two consecutive patients were included in the study; twenty-five patients with SS and thirty-seven with CS. Most of the patients were male (n 43; 83%) and mean age was 59.6 [52.5–68] years. APACHE II score was 18 [11–24]. Demographic, clinical, hemodynamic and therapeutic maneuvers from both groups are depicted in Table 1.

In SS population, the most frequent infectious foci were urinary (n 8; 32%), abdominal (n 8; 32%), respiratory (n 6; 24%), soft tissue infection (n 2; 8%) and bacteremia (n 1; 4%). Microbial etiology was established in 23 patients (92%). Gram-negative bacteria (GNB) in 13 cases (52%); Escherichia coli (n 6; 46%), Pseudomonas aeruginosa (n 5; 56.5%) and Klebsiella pneumoniae (n 2; 15%). Gram-positive bacteria (GPB) in 10 cases (43.4%); Staphylococcus aureus (n 3; 30%), Enterococcus faecium (n 3; 30%), Streptococcus pneumonia (n 2; 20%), Staphylococcus epidermidis (n 1; 10%) and Streptococcus pyogenes (n 1; 10%). Any SS patient developed sepsis-associated myocardial dysfunction.

CS etiology was acute myocardial infarction in 28 cases (75.7%), followed by decompensated chronic heart failure in 8 patients (21.65%) and heart transplant rejection in one patient (2.65%). There was a clinical suspicion of infection and therefore antibiotic treatment onset and performance of microbiological study (blood cultures, respiratory sample culture or/and urine culture) in 30 CS patients (81%). Twenty-two patients (60%) had body temperature>38.3°C or <35°C; and twenty-three patients (62%) had a leukocyte count>14,000/mm3 or <4000/mm3. No infection was finally diagnosed.

Supportive interventions are depicted in Table 2.

All patients had serum PCT levels above normal values (0.5ng/ml). PCT was clearly higher in SS patients meanwhile CRP was indistinguishable between the two groups. In CS 51.4% of the cases (n=19) had at least one PCT value above 2ng/ml, and 10 patients (27%) had at least one PCT value above 5ng/ml. IL-6 was higher but not constantly in SS patients (Table 3).

All patients had antiendotoxin antibodies bellow the normal median value (100MU/ml). EndoCAb consumption was more intense in SS patients (Table 3), although twenty-two CS patients (59.5%) had IgM anti-endotoxin value bellow 10th percentile range for healthy people (Table 3). SS patients in whom a GNB was isolated presented less EndoCAb (Fig. 1) in the three days in which it was determined when compared with SS due to GPB (6.9MU/ml vs 10.9MU/ml, 8.5MU/ml vs 8.7MU/ml, 6.6MU/ml vs 8.1MU/ml), without reaching statistical significance (p=0.13, p=0.16 and p=0.23, respectively).

Figure 1.

Area under the curve (AUC) for EndoCAb IgM titters in the first day to distinguish between cardiogenic shock and septic shock. 95% IC: 0.65–0.92.

(0.09MB).

EndoCAb capability to distinguish between SS and CS patients was evaluated by means of a ROC curve. First day measurement showed an AUC 0.78, 95% IC: 0.65–0.92 (Fig. 1); the optimal cut-off point was 79.07MU/ml (sensitivity 52% (44–63%), specificity 94.6% (82–98%)).

Mortality rate was 32.2% (n=20); six SS patients (24%) and fourteen CS patients (38%) died at 30-days follow-up (Table 2). Inflammatory biomarkers and EndoCAb levels showed no differences between deceased and survivors. Deceased CS patients had higher PCT and IL6 levels than those CS patients who survived (p<0.05). Although EndoCAb levels were lower in deceased SS patients they didn’t reach statistical significance along the three days follow-up.