This study analyses of the relationship between outcomes of TBI patients requiring surgery and immediate postoperative coagulopathy using a survival analysis, and it analyzed the potential risk factors causing immediate postoperative coagulopathy. We found that immediate postoperative coagulopathy (adjusted HR, 1.466; 95% CI, 1.007–2.133; P = 0.046) was identified as an independent risk factor for survival following TBI. The 1-year survival rate of TBI patients suffering from immediate postoperative coagulopathy was 0.595, whereas that of patients without immediate postoperative coagulopathy was 0.759. The risk factors that contributed to immediate postoperative coagulopathy included abnormal ALT and RBC at admission, infusion of crystalloid solution > 2900 mL, infusion of colloidal solution > 1100 mL, and intraoperative bleeding > 950 mL.
In the log-rank test, we found that immediate postoperative coagulopathy was significantly associated with the survival of TBI patients (P = 0.002). In the Cox regression model analysis, immediate postoperative coagulopathy was identified as an independent risk factor. Age, GCS, AIS(head), pupil reaction, effaced basal cisterns, and coagulopathy at admission were adjusted. The prognostic model, IMPACT (International Mission for Prognosis and Clinical Trial), has shown that three most prognostic predictors: age, GCS, and pupillary reactivity, which all were adjusted in our prognostic model. Older age was analyzed as a significant predictor of prognosis in TBI[26, 27], which was also showed in our study. Undoubtedly, the GCS score and AIS(head), which described the severity of TBI patients, are crucial factors affecting long-term survival, as previous shown. In the log-rank test, coagulopathy at admission was identified as a risk factor in our study. However, it showed no significance in the Cox regression model analysis. Meanwhile, postoperative coagulopathy was an independent risk factor for long-term survival, which indicated that postoperative coagulopathy is of great clinical importance and worthy of further attention.
A previous study showed that delayed or sustained trauma-induced coagulopathy was more frequently associated with unfavorable outcome than early, short-lasting coagulopathy. Postoperative coagulopathy, as a delayed or more specific form, was also related to prognosis in our study. We also found that the incidence of postoperative coagulopathy was much higher than that of coagulopathy at admission (50.64% vs 18.59%), which further indicated that postoperative coagulopathy might have profound clinical significance. We did not include preoperative coagulation dysfunction because of the particularity of patients with traumatic brain trauma undergoing surgery. Most of these patients requiring surgery were operated on within a few hours of admission. Preoperative coagulation function will overlap to some extent. In light of this, it is reasonable that we did not include preoperative coagulation function.
Overall, 312 TBI patients underwent surgery and completed follow-up, with a 1-year survival rate of 0.676 and a 3-year survival rate of 0.628. Interestingly, we found that the 1-year survival rate decreased rapidly to 0.676, while the 3-year survival rate decreased by only 0.048 (Fig. 1). This suggests that TBI patient deaths in those who underwent surgery were concentrated in the first year. In other words, if the patient made it through the first year, his or her chances of survival were high. The 1-year and 3-year survival rates of TBI patients suffering from postoperative coagulopathy were 0.595 and 0.551, respectively, which were accordingly below the overall survival rate. In contrast, the 1-year and 3-year survival rates of TBI patients with normal coagulation were 0.759 and 0.708, respectively, which were accordingly above the overall survival rate (Fig. 1).
Since immediate postoperative coagulopathy was identified as an independent risk factor for long-term survival, we next discussed the underlying risk factors for coagulopathy. Abnormal ALT and RBC at admission were identified as independent risk factors for immediate postoperative coagulopathy, which suggested that abnormal liver function and hypovolemia might lead to immediate postoperative coagulopathy. Interestingly, some perioperative factors, including the infusion of crystalloid solution > 2900 mL, colloidal solution > 1100 mL or their sum > 3450 mL, and the net-fluid-input > 2425 mL, were risk factors for postoperative coagulation disorders. On the one hand, the infusion of large amounts of fluid results in the dilution of coagulation factors in the plasma. On the other hand, whether the input of a large amount of fluid during surgery will cause the further release of brain-derived molecules to the circulatory system of the whole body and further aggravate coagulation disorders remains a question that deserves additional attention and research, because of the basic experimental evidence that pro-coagulant molecules (such as tissue factors, phosphatidylserine, cardiolipin, and vWF) are released from damaged brain tissue [28–30]. In this study, there were no definite ratios between crystal infusion and colloid infusion, and there was no significant difference between the two groups (data not shown).
Interestingly, intraoperative infusion of colloidal solution > 1100 mL or intraoperative infusion of crystalloid solution > 2900 mL were identified as independent risk factors in the multivariate logistic regression analysis. Previous studies have shown that large amounts of colloid and can affect body coagulation functions[31–33], which was also confirmed in this study. Furthermore, we found that when the intraoperative input of colloidal fluid was more than 1100 mL, the impact on postoperative coagulation was significant. This threshold was derived from the ROC curve. However, this conclusion was drawn from our retrospective study. Therefore, it is necessary to carry out prospective clinical trials to study the infusion of colloids in patients with craniocerebral trauma.
There are currently no clear guidelines for fluid management during craniocerebral trauma surgery, although there are some other guidelines for surgical fluid management [31, 34, 35]. How to maintain the balance between wet and dry conditions is a question we all need to consider, especially in TBI, because we do not know whether the high perfusion of fluid during surgery will cause secondary damage to the brain. Just as our research provides evidence for the management of fluids during surgery, more evidence-based prospective experiments are needed to explore this issue. We need a model or algorithm to calculate the most appropriate fluid intake for patients with craniocerebral trauma that can maintain cerebral and systemic perfusion as well as avoid secondary injury to the brain caused by elevated cranial pressure owing to high perfusion. This appropriate fluid intake will maximize the benefit of patients.
There were several limitations in our study. First, this was a retrospective cohort study. Retrospective articles are not a substitute for prospective randomized controlled trials. Second, other data that we did not recorded may have affected our analysis. For example, information about prehospital treatment could not be recorded, as this was a retrospective article. Third, only APTT, INR, and platelet counts were recorded and regarded as crucial factors to define coagulopathy, and other coagulation-related variables were not enrolled. However, most of the current research on TBI-induced coagulopathy includes these three factors; thus, it is reasonable to some extent. This study focused on the relationship between immediate postoperative coagulopathy and the long-term survival of TBI patients, and the role of late postoperative coagulopathy is worth of further exploration.