Complement depletion deteriorates clinical outcomes of severe abdominal sepsis: a conspirator of infection and coagulopathy in crime?

Jianan Ren, Yunzhao Zhao, Yujie Yuan, Gang Han, Weiqin Li, Qian Huang, Zhihui Tong, Jieshou Li, Jianan Ren, Yunzhao Zhao, Yujie Yuan, Gang Han, Weiqin Li, Qian Huang, Zhihui Tong, Jieshou Li

Abstract

Background: The complement depletion commonly occurred during sepsis, but it was often underestimated compared with severe infection or coagulation dysfunction.

Objective: This study was designed to investigate the alteration of complement system in patients with severe abdominal sepsis and evaluate the role of complement depletion in prognosis of such patients. The relationship between complement depletion and infection or coagulopathy was also explored.

Methods: Forty-five patients with severe abdominal sepsis were prospectively conducted among individuals referral to SICU. Currently recommended treatments, such as early goal-directed resuscitation, source control and antibiotics therapy, were performed. Acute physiology and chronic health evaluation II (APACHE II) and sepsis related organ failure assessment (SOFA) scores were employed to evaluate severity. Plasma levels of C3, C4, CRP, PCT, D-dimer and other parameters were detected within eight times of observation. The 28-day mortality, length of stay, and postoperative complications were compared between complement depletion and non-complement depletion groups.

Results: Within the study period, eight (17.8%) patients died, five of them suffering from complement depletion. The overall incidence of complement depletion was 64.4%. At admission, mean complement C3 and C4 levels were 0.70 and 0.13 mg/mL, respectively. Using ROC analysis for mortality prediction, the area under the curve of C3 was 0.926 (95% CI, 0.845-0.998, P<0.001), with optimal cutpoint value of 0.578 mg/mL. Complement C3 depletion was shown to be no correlation to severity scores, however, strongly correlated with elevated D-dimer, PCT concentrations and increased postoperative complications.

Conclusions: Complement C3 depletion was found to be connected to poor prognosis in severe abdominal sepsis. This depletion seems to be associated with coagulopathy and aggravated infection during sepsis, which should be paid close attention in critical care.

Trial registration: ClinicalTrials.gov NCT01568853.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1. Enrollment and Study design.
Figure 1. Enrollment and Study design.
A total of eight evaluations were performed. Patients were excluded for three medical reasons, including death within seven days after admission, blood transfusion and blood purification within the period of study. All enrolled patients were followed up for 28 days, and 28-day mortality was assessed as the primary outcome.
Figure 2. The correlation analysis between baseline…
Figure 2. The correlation analysis between baseline levels of C3 and severity scores.
(A) The relationship between C3 and APACHE II score. Data in both groups were pooled for analysis (n = 45). The linear regression indicates that the baseline levels of C3 have little correlation with APACHE II score (R2 = 0.268). (B) The relationship between C3 and SOFA score. Data in all patients were included for analysis (n = 45). The regression result shows that C3 have no correlation with SOFA score (R2 = 0.217). In addition, linear regression for each group was performed, with similar results to the pool.
Figure 3. The observed changes of complement…
Figure 3. The observed changes of complement components in management of sepsis.
These dynamic changes were directly compared between group 1 and group 2. Plasma levels of C3 (A) and C4 (B) within 28-day observation were quite different between both groups (P<0.001). The gray area indicates the normal reference range. Data present as mean ± SD.
Figure 4. The observed changes of infection…
Figure 4. The observed changes of infection and coagulation indexes in management of sepsis.
The values of each index were compared between group 1 and group 2. All data present as mean ± SD. CRP (A) and PCT (B) were utilized to evaluate the inflammatory response to sepsis. PT (C) and D-dimer (D) were employed to evaluate the coagulation function during sepsis. The gray area indicates the normal reference range.

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