Patients who have undergone major surgery are at high risk of developing complications associated with sepsis [14, 18]; however, differentiation between postoperative SIRS and septic complications is difficult. Long-term prophylaxis with high-dose antibiotics or wide-spectrum antibiotics, which might prevent the development of sepsis, may obscure the host response and induce the development of resistance. Identification of septic patients at the beginning of the process can help in better and more specific diagnostic and therapeutic procedures and overall management. On the contrary, exclusion of sepsis might help in better and rationale antibiotics treatment.
In our study, we investigated both hematological (including TEG) and biochemical markers of sepsis, as there is a link between inflammation and coagulation (5). We also examined markers of liver dysfunction because of the important role reported to be played by the liver in sepsis. This is a very interesting finding and is, in all probability, underestimated in practice. Interestingly, levels of AST and ALT were significantly higher in the septic group of patients compared with the nonseptic group, and those changes could be detected as early as the first day after surgery and persisted to the fourth day (see Figure 1). For cutoff points for early diagnosis of development of postoperative infectious complications within 6 days of surgery see Tables 1, 2 and 3.
Our findings of higher liver enzymes levels in septic patients are in accordance with findings of others who say that liver dysfunction is common in patients with sepsis, ranging from mild elevations of serum aminotransferases to severe cholestasis [11–13, 19, 20]. However, we think that in our case liver dysfunction might rather be a cofactor participating in sepsis development. Liver has a central role in the regulation of host defenses. It serves as a source of inflammatory mediators and is a major site of the removal of bacteria and endotoxins from systemic circulation. Kupffer cells (KCs) of the liver make up 80 %-90 % of the fixed-tissue macrophages of the reticuloendothelial system. KCs take up bacteria, endotoxins and are stimulated to release a wide range of products implicated in liver injury, such as tumor necrosis factor, interleukin-1 and interleukin- 6 [12]. It is proposed that Kupffer cell phagocytic depression associated with liver dysfunction permits spread of endotoxin and inflamatory mediators and thus predisposes to sepsis and multiple organ failure.
The cause of postoperative liver dysfunction in our patients is not known. All patients had received the same kind of anaesthesia (isofluran, remifentanil, rocuronium) and postoperative care and there are some reports of isofluran side effect on liver function [21]. Transient hypotension and hypoxia cannot be ruled out and individual response of the patient to surgery can also play a part. That could have played a role in development of ,,postanaesthetic hepatitis” and subsequently in development of sepsis. Importantly, unlike the expensive tests used for detection of inflammatory markers, measurements of liver dysfunction are cheap and routinely available and can be helpful in screening of patients susceptible to sepsis for early signs of sepsis development.
Overall, the earliest markers of the development of sepsis seem to be AST and ALT. Differences in PCT and IL-6 in septic and non-septic patients with SIRS are detectable from Day 2 (see Figure 2). For cutoff points for early diagnosis of development of postoperative infectious complications within 6 days of surgery see Tables 2 and 3. Both parameters showed similar trends on subsequent days, which means that, as IL-6 is measured mostly experimentally, measurements of PCT should be sufficient to provide the necessary information. Ito and colleagues actually found that PCT is better for monitoring the development of sepsis in patients who had undergone oesophageal surgery for carcinoma; however they were able to predict sepsis one day earlier than in our study [22]. Unlike our patients though, their patients did not receive preoperative chemotherapy. In another study, Mokart and colleagues investigated PCT and IL-6 to predict sepsis development in patients who had undergone gastrointestinal or gynaecological tumour resections. They were also able to predict the development of sepsis from as early as Day 1 after surgery, although levels of IL-6 and PCT were not as high as those of our patients [7]. It should be noted, however, that unlike our patients, those patients had only undergone surgery in the abdominal cavity.
When it comes to CRP, we found significant differences between the groups from Day 3, when CRP levels in the septic group rose by comparison with those of patients in the non-septic group (see Figure 2). For cutoff points for early diagnosis of development of postoperative infectious complications within 6 days of surgery see Table 3. This finding is similar to that described by Ito, although the differences were not statistically significant in that study. Although it is questionable just how valuable this marker is for early diagnosis of sepsis, the tests are cheap and can help in sepsis diagnosis.
Surprisingly, among the coagulation parameters, only concentrations of D-dimers were statistically significantly higher during the early postoperative period (from Day 2 to Day 4). However, since the concentrations of D-dimers subsequently decreased (Figure 3A), the value of this marker for early diagnosis of sepsis is questionable.
Because this kind of operation is not very often, the sample size might be the limitation of this study. However, we were able to find some interesting laboratory changes in patients who would develop infectious complication untill the 6-th postoperative day, as soon as the 1-st postoperative day, no matter if sepsis was diagnosed on day 3 or 6. This findings could attract our attention to those patients in the risk of sepsis development more then 24 hours before sepsis diagnosis.
We also evaluated changes in pletelets count and fibrinogen level in both groups during the investigation time period, but there was no significant difference between their values (p > 0.05) (Figure 4).
Our finding of decreased fibrinolytic activity (represented by levels of LY30) in the septic group versus the non-septic group is in accordance with those of a recent study by Adamzik and colleagues. This group investigated coagulation changes in septic patients using TEG and also found decreased fibrinolytic activity [23]. In that study, TEG did not detect changes until 24 hours after severe sepsis had been diagnosed and the patients were in a much more serious condition than ours. In both our study and the Adamzik study then, patients had already developed sepsis before TEG detected changes in fibrinolysis. Thus, while TEG is useful to diagnose sepsis in later state, it is not useful for early diagnosis of sepsis or predicting which patients will go on to develop sepsis.
