Elevated PCT values during the first 2 days after trauma are more likely to be indicative of trauma impact than of an ongoing status of sepsis because multiple events such as surgery, massive transfusion, and intensive care therapy might influence the PCT concentration.
A long-lasting elevated concentration of PCT in the post-traumatic period, or its repeated increase, is a good marker of developing complications of sepsis.
Mediators of inflammation have been postulated as playing a key role in being responsible for life-threatening complications of multiple trauma patients. PCT is a useful biomarker for diagnosing (bacterial) sepsis; however, elevated PCT in the first days after trauma may be observed in conditions other than sepsis because multiple events such as surgery, massive transfusion, and intensive care therapy might influence its concentration.
A recent literature review on PCT use in trauma-acute care surgery in adult patients performed by Parli et al. showed the importance of this biomarker in identifying infection in trauma and post-operative acute care surgery but no standard approach was recommended [
57]. In a prospective study including hospitalized patients with multiple trauma, serum PCT levels were measured in 45 patients: in the 24th hour of observation, a statistically significant increase of PCT concentration versus initial levels were recorded in all patients, then PCT levels decreased significantly whereas PCT concentrations in patients who had complications or died were significantly greater [
58]. Liu et al. [
59] analyzed blood samples of 30 children with acute trauma: the patients with sepsis showed higher levels of PCT than those with and without systemic inflammatory response syndrome (SIRS) and the healthy controls (
p < 0.05): the peak level of PCT was observed on day 2 after trauma with a positive correlation with trauma severity acting as an independent predictor for post-trauma sepsis and SIRS. In another prospective study in 94 patients with consecutive trauma > or = 16 years who were admitted to the ICU for an expected stay of > 24 h, patients with trauma presented an early and significant increase in PCT at the moment of septic complications compared with concentrations measured 1 day before the diagnosis of sepsis: 0.85 vs. 3.32 ng/ml for PCT (
p < 0.001) and 135 vs. 175 mg/L for CRP (
p = ns) [
60]. In another Japanese retrospective series of 75 patients with ISS > 16, the multivariate logistic regression analysis showed that packed red blood cell (PRBC) transfusion was the only independent risk factor for a higher PCT levels on day 1 (
p = 0.04) confirming that PCT was not a useful infection biomarker in the first days after trauma [
61]. A larger retrospective series including 405 patients demonstrated that trauma leads to increased PCT plasma levels dependent on the severity of injury, with peak values on days 1 and 3 (
p < .05) and a continuous decrease within 21 days after trauma: however, the highest PCT plasma concentrations early after injury were observed in patients with sepsis (6.9 ± 2.5 ng/L; day 1) or severe MODS (5.7 ± 2.2 ng/L; day 1) with a sustained increase (
p < .05) for 14 days compared with patients with an uneventful posttraumatic course (1.1 ± 0.2 ng/L); moreover, these increased PCT plasma levels during the first 3 days after trauma predicted (
p < .0001; logistic regression analysis) severe SIRS, sepsis, and MODS [
62]. In an US prospective clinical study, PCT was measured from 74 patients with multiple injuries: PCT significantly increased during the first two posttraumatic days in patients with severe multiple injuries (
n = 24, day 1: 3.37 ± 0.92 ng/L; day 2: 3.27 ± 0.97 ng/L) as compared with patients with identical Injury Severity Score but without abdominal injury (day 1: 0.6 ± 0.18 ng/L; 0.61 ± 0.21 ng/L) [
62]. Maier et al. enrolled 73 adult trauma patients admitted to the intensive care unit in a prospective case study: they noted that PCT increased only moderately in most patients and peaked at days 1–2 after trauma, the concentrations rapidly declining thereafter: complications such as sepsis, infection, blood transfusion, prolonged intensive care unit treatment, and poor outcome were more frequent in patients with initially high PCT (> 1 ng/L), whereas increases of CRP showed no positive correlation. These researchers concluded that in patients with multiple trauma due to an accident, the PCT level provides more information than the CRP level since only moderate amounts of PCT are induced, and higher concentrations correlate with more severe trauma and a higher frequency of various complications, including sepsis and infection [
63]. In another interesting prospective study, two different groups of patients were studied: one with acute trauma but no clinical evidence of sepsis and the other with clinical evidence of sepsis. Patients with high initial PCT levels (> 2 ng/ml) in severe trauma cases had poor outcomes and risk of developing complications: the difference in PCT levels between days 1 and 4 in group two patients was statistically significant (
p = 0.006) [
64]. In a US Trauma Center, 102 patients were analyzed in 1 year: mean PCT levels were higher for patients with sepsis versus systemic inflammation response syndrome (SIRS) (
p < 0.0001). Moreover, subjects with PCT values of 5 ng/L or higher showed an increased mortality when compared with those with a PCT of less than 5 ng/L in a univariate analysis (OR, 3.65; 95%,CI 1.03–12.9;
p = 0.04); in the multivariate logistic analysis, PCT was found to be the only significant predictor for sepsis (odds ratio, 2.37; 95% confidence interval, 1.23–4.61,
p = 0.01) [
65,
66]. This evidence is also confirmed in acute traumatic spinal cord injury patients as showed by Nie et al. who collected 339 cases: 26 (7.7%) of 339 subjects experienced postoperative infectious complication. Patients with infection showed significantly higher PCT levels compared with non-infection (both
p < 0.01): multivariate logistic regression analysis showed that PCT and CRP levels were independent predicators for postoperative infection. The area under the receiver operating characteristics curve (ROC) of PCT and CRP were 0.82 (95% CI, 0.74–0.91) and 0.68 (95%CI, 0.57–0.78), respectively. A PCT cutoff of 0.1 ng/L had a reasonable sensitivity of 92% to exclude an infection and ABs can be initially withheld: however, in patients with PCT level above 0.5 ng/L, a rapid initiation of ABs may be warranted [
67]. Haasper et al. reported during 1 year 94 patients with an injury severity score (ISS) of 16: PCT was better than IL-6 in predicting the development of sepsis showing significant higher plasma levels in group with sepsis from the first day after trauma [
68]. In another study, 113 adult multiple-trauma patients admitted to ICU in the first 24 h after trauma were included. Mean PCT and CRP levels were both significantly higher on day 7 compared to day 1 and the final assessment day in patients with an ISS > 20. PCT levels were significantly higher in cases with sepsis, severe sepsis, or septic shock compared with cases who developed SIRS; however, CRP levels were significantly higher only in cases with severe sepsis or septic shock, but not in cases with sepsis alone. These data supported the observation that PCT levels may be a better indicator than CRP levels in the early diagnosis of septic complications in patients with multiple trauma [
69]. Another large series grouping a total of 1757 consecutive trauma patients with an ISS > 16 admitted over a 10-year period showed elevated early serum PCT on days 1 to 5 after trauma strongly associated with the subsequent development of sepsis (
p < 0.01) but not with non-septic infections. The kinetics of IL-6 was similar to those of PCT but did differentiate between infected and non-infected patients after day 5 [
70]. In another case control study, PCT, CRP, and IL-6 levels in serum of patients at admission (T1), 12 h after admission (T2), 3 days after admission (T3), and on day 7 (T4) were studied: the serum CRP at the T4 time period was significantly lower than both the T1 and T2 time periods (
p < 0.05). There were differences in serum PCT, CRP, and IL-6 between the good prognosis and the poor prognosis group at the time of T1–T4 (
p < 0.05). The expression levels of PCT, CRP, and IL-6 in the serum of patients with poor prognosis were higher than those with good prognosis (
p < 0.05) [
71].