Perioperative, immunsuppressive Therapie mit Tacrolimus im Rahmen von Darmresektionen bei Patientinnen und Patienten mit Morbus Crohn – eine retrospektive, unizentrische Analyse

At the university hospital of Marburg, we perform a perioperative, immunosuppressive treatment with intravenous Tacrolimus for 10-14 days in patients with Crohn’s disease, who need intestinal resection. Our goal is to reduce active bowel inflammation to stabilize the anastomosis and prevent postoperative, intraabdominal septic complications, like anastomosis-leakage. As far as we know, the perioperative application of intravenous Tacrolimus in patients with Crohn’s disease has not been researched much. Therefore, the aim of this study is to analyze our experience retrospectively to see if this therapy was beneficial for our patients or not. We structured the study methodically into two parts. In the first part, we described our population and aspects of the tacrolimus-therapy. Additionally, we compared exploratively patients with and without tacrolimus therapy. For the second part, we used logistic regression to analyze whether Tacrolimus had an impact on postoperative, infectious complications. We included 86 patients in our study, of whom 30 patients (34,88%) received Tacrolimus and 56 patients (65,12%) did not. In median, 1mg/day of Tacrolimus was given for 11 days. In 23% of our patients tacrolimus blood-levels were measured, which showed a median level of 12 µg/l. Adverse events occurred in three patients. The most common adverse events were neurological nature with headache and paresthesia. In three patients the dose was adapted, in two patients the treatment with tacrolimus was paused and one patient stopped the therapy completely. There were significant differences in patients with and without tacrolimus therapy. Before the surgery, patients with tacrolimus therapy showed significantly more often a penetrating disease behavior, according to the Montreal classification, with inflammatory complications such as fistula and abscesses. Further, the very serve preoperative complication sepsis was significantly more frequent among patients with tacrolimus therapy. On the contrary patients with tacrolimus therapy showed significantly less often a stricturing disease behavior in comparison to patients without tacrolimus therapy. These differences in inflammatory burden were also noticeable regarding laboratory inflammation markers and clinical symptoms. Patients with tacrolimus therapy showed significant higher levels of CRP and were significant more often symptomatic at the time of admission in hospital. In addition, the preoperative medication was significantly different between those two groups. Patients with tacrolimus therapy received significant more often steroids, even in a high dose of 20mg per day or more. However, patients with tacrolimus therapy used significant less frequently biologicals like infliximab. In terms of operative parameters, patients with tacrolimus therapy had significantly more often an emergency operation and postoperative treatment on either an intensive- or intermediate care station. Regarding postoperative complications, intra-abdominal fluid collection was found to be the only postoperative complication, which was significant more often in patients with tacrolimus therapy. There were no further significant differences in postoperative complications between patients with and without tacrolimus therapy. To address the further post-hospital course of our patients, we could not identify significant differences between the two groups in terms of clinical or endoscopical recurrence. In simple regression analysis, we were able to identify preoperative sepsis, ASA score of 3 or more, emergency surgery, stoma formation, CRP level at the time of admission, sex, postoperative duration of stay and the treatment on an IMC/ICU to be significant variables with impact on postoperative, infectious complications. Tacrolimus showed no significant association to postoperative, infectious complications. Furthermore, in multiple logistic regression CRP at admission, stoma- formation, sex, postoperative duration of stay, ASA score of 3 or more and emergency surgery showed a significant effect on postoperative, infectious complications. Tacrolimus was still not a significant variable throughout all six regression models. Keeping the low number of patients in mind, we can carefully conclude that we did not find any signs of tacrolimus having a negative or positive impact on postoperative, infectious complications in our population. We worked out some interesting differences between patients with and without tacrolimus therapy and thus getting a better picture of patients receiving tacrolimus in this not well-known setting. Regarding this matter, we can summarize that tacrolimus was applied in patients who showed a more complicated disease with high inflammatory burden and preexisting steroid therapy. Further, we were able to show that adverse events were considerable rare and of low severity. Therefore, we cannot conclude that our form of perioperative treatment with tacrolimus preserved a serious harm to our patients. Yet, we were also not able to identify any benefit from the tacrolimus treatment for our patients, which makes the indication for tacrolimus in this setting debatable. Further studies with higher numbers of patients are needed to identify positive or negative effects of tacrolimus in the perioperative setting. Our study can be seen as a basis for these further studies.