We previously reported no significant difference in intraoperative blood loss after adjustment for confounding factors by propensity score matching in patients taking AT drugs undergoing emergency gastrointestinal surgery in a single institution[9]. In this study with a nationwide large-scale cohort, we focused on patients with generalized peritonitis, which needed surgical intervention immediately and was frequently accompanied by septic shock and coagulopathy. While this study shows a statistically significant increase in blood loss in patients taking AT drugs, the difference is minimal and likely of no clinical significance. AT drugs had a minimal influence on intraoperative blood loss in patients undergoing emergency surgery for generalized peritonitis after adjustment for confounding factors by propensity score matching. To the best of our knowledge, this is the first report to demonstrate safety for patients taking AT drugs with regard to perioperative bleeding and thrombotic complications, who undergo emergency gastrointestinal surgery for generalized peritonitis.
There is a wide range of opinions about the perioperative use of AT drugs. The American College of Surgeons’ guideline recommends cessation of aspirin for 7 to 10 days before procedures with a high risk for bleeding such as gastrointestinal surgery[5], while the Society of Thoracic Surgeons guidelines recommends continuation of aspirin monotherapy in patients undergoing non-cardiac surgery[6]. The difference in the guidelines is at least partially due to the low quality of available evidence[14–18]. The incidence of difficulty obtaining intraoperative hemostasis is rarely mentioned in existing studies. The present study results shows that AT drugs were not related to difficult intraoperative hemostasis during emergency surgery for generalized peritonitis because the increase in intraoperative blood loss and rate of blood transfusions was not clinically significant although it was statistically significant. Due to study design in patients undergoing emergency surgery, a randomized controlled study cannot be carried out. The results of this nationwide study have important implications for the clinical management of patients taking AT drugs who undergo emergency gastrointestinal surgery.
Generalized peritonitis is frequently associated with systemic sepsis and is considered by some to make operative procedures more complicated, with increased blood loss due to widespread inflammation[2, 19, 20]. Increased intraoperative blood loss has unfavorable effects on immune function[21–23], and is associated with major complications or a worse prognosis[24, 25]. When performing gastrointestinal surgery on patients with generalized peritonitis, surgical outcomes including intraoperative blood loss, mortality and postoperative morbidities, tend to be worse compared to performing surgery on patients without generalized peritonitis[26, 27]. This study shows that in patients with generalized peritonitis, the effect of taking AT drugs on intraoperative blood loss and rate of blood transfusions was minimal and any increased risk of postoperative bleeding and thrombotic related complications was acceptable.
In this study, several methods of analysis gave similar results to support the conclusion that the effect of taking AT drugs was minimal. The type of surgical procedure or surgical approach, which have a high impact on intraoperative blood loss in this study, were reported as important factors associated with intraoperative blood loss in previous studies[28–31]. Therefore, less invasive procedures and surgical approach should be selected if there is no difference in mortality and morbidity expected for a particular patient. When selecting the procedure and surgical approach, taking AT drugs alone should not be a major factor in the decision-making process based on these results. For example, recent studies suggest that in patients with colorectal perforation, peritoneal lavage or laparoscopic surgery should be selected rather than open resection, if the situation permits, with no significant differences in mortality or the rate of serious complications between these procedures and surgical approaches[32–34]. Surgeons should manage patients with generalized peritonitis balancing the surgical curability of the disease and the feasibility of the selected procedure and surgical approach, and do not need to place undue emphasis on the use of AT drugs in some patients.
This study has acknowledged limitations. First, this study includes patients who take all types of AT drugs including antiplatelet drugs and anticoagulant drugs because the database used in this study does not distinguish among the types of AT drugs. Different mechanisms may confer different effects on intraoperative blood loss. Second, although propensity score matching is used to decrease the bias between the two groups, this study is retrospective and not blinded. Third, safety as an outcome is hard to quantify. We judged the primary outcome of this study as not clinically significant and safety because the differences in relative risks of outcomes are minimal though statistically significant. Fourth, the use of antidotes and the timing of restarting AT drugs was at the discretion of the primary surgeon, and are unknown in this study. Although the exact number of patients given vitamin K, which needs some time to normalize the PT-INR, is unknown, it would likely not be effective as an antidote for emergency surgery. Prothrombin complex concentrate and antidotes of direct oral anticoagulant were not approved yet in Japan during the study period. Therefore, we believe the effect of antidotes on the results of this study are minimal. Finally, the judgment to perform the operation and the choice of procedure is at the discretion of the individual surgeon, which could result in bias. For a patient taking AT drugs with a high risk of bleeding, surgeons might choose a less invasive procedure, or non-operative therapy, which they would not choose if the patient did not take AT drugs.