E. Bölke

Endovascular stent-graft placement versus conventional open surgery in infrarenal aortic aneurysm: a prospective study on acute phase response and clinical outcome

BACKGROUND For the treatment of aortic aneurysm, stent-graft implantation is an alternative method to open surgery. There is no study comparing both methods with regard to endotoxaemia, the acute phase cascade, and clinical outcome. METHODS In this prospective study, we enrolled 40 patients (34 males, 6 females; mean age 72.1+/-7.5 [58-92] years) with infrarenal abdominal aortic aneurysm who underwent aortic surgery. Comparable groups of patients were treated with open (n=20) or endovascular (n=20) stent-graft implantation. To characterize the inflammatory response, plasma levels of endotoxin, endotoxin-neutralizing capacity (ENC), interleukin-6 (IL-6), C-reactive protein (CRP), and white blood cell count were determined. In all patients, measurements were performed on admission, skin suture, 4 h and from the first to fifth postoperative day. As parameters for the clinical outcome, we assessed daily temperature, lung function, pain, duration of postoperative hospital stay, and morbidity. Wilcoxon rank test was used for statistical analysis. RESULTS In both groups, a significant increase of endotoxin plasma levels and a decrease of ENC was found already after skin incision. IL-6 levels peaked 4 h postoperatively in both groups, whereas CRP rose at the first postoperative day, reaching a maximum at day 2. Conventionally operated patients had significantly higher plasma levels of endotoxin, IL-6, and CRP and lower ENC during and after surgery than patients with stent-graft implantation. Moreover, patients with endovascular stent grafting had significant less postoperative pain, less restriction of total vital capacity, a shorter hospital stay, and a lower morbidity. CONCLUSIONS Endovascular stent grafting of infrarenal aortic aneurysm seems to be superior not only in terms of the inflammatory response but also in overall clinical outcome.

Time-scale of interleukin-6, myeloid related proteins (MRP), C reactive protein (CRP), and endotoxin plasma levels during the postoperative acute phase reaction.

During goitre surgery (25 patients) and after major abdominal surgery (52 patients), we studied the plasma levels of endotoxin, interleukin-6 (IL-6), C reactive protein (CRP), and the so called myeloid-related proteins (MRP), MRP8, MRP14, and the heterocomplex of both single proteins, MRP8/MRP14 in three intervals: pre-, intra-, and postoperative. We observed that CRP levels began to increase on the first postoperative day, reaching a maximum on day 2 (median levels of 185 mg/L after major surgery and 77 mg/L after goitre surgery). IL-6 levels peaked at the end of the operation, remaining elevated for 6 h following abdominal surgery (299 pg/mL) and peaked on day 1 after goitre surgery (63 pg/mL). An increase in MRP8/MRP14 levels began toward the end of abdominal surgery, and maximum levels were recorded until 5 days after the operation (5,695 μg/L). Plasma levels were significantly elevated 2 and 6 h after minor surgery (3,619 μg/L), while no changes were observed in the plasma levels of MRP8 and MRP14. Evidence of significant endotoxemia was found after the induction of anesthesia in the abdominal surgery group (.13 endotoxin units (EU)/mL) and after skin incision (.07 EU/mL) in the thyroid surgery group. The observed time sequence, starting with the release of bacterial products at an early stage, followed by the secondary stimulation of factors inherent to the acute phase led us to conclude that certain bacterial compounds, probably deriving from the gastrointestinal tract, trigger the postoperative acute phase reaction and are responsible for the activation of monocytes/macrophages and granulocytes.

New aspects concerning the regulation of the postoperative acute phase reaction during cardiac surgery

During a cardio-pulmonary bypass, as well as post-operatively, high levels of endotoxin, interleukin-6 (Il-6) and C-reactive protein (CRP) were measured in 30 patients. A significant increase in endotoxin plasma level occurred during surgery, culminating in a peak during reperfusion. Plasma levels of endotoxin continued to be slightly raised until the fifth day after surgery, whereas those of Il-6 rose at the time the operation came to an end and were at their highest 6 h later. CRP levels were also high, post-operatively, and were markedly raised on day 2. A definite, statistically significant correlation between the plasma levels of endotoxin and Il-6 during the operation was established, leading us to conclude that the endotoxin liberated during cardiac surgery acts as the main trigger in the release of Il-6 and thus induces the post-operative acute phase reaction. There was no evidence of a correlation between CRP and endotoxin or Il-6 plasma levels.

Endotoxin release and endotoxin neutralizing capacity during colonoscopy

In 38 patients who underwent elective colonoscopy, endotoxin and endotoxin neutralizing capacity (ENC) were determined by use of the limulus--amebocyte--lysate test. A control group of 10 patients, prepared for colonoscopy, were sampled in the same manner as the study group prior to endoscopy. Elevated endotoxin plasma levels were only found when comparing the plasma levels before endoscopy with the highest levels available during endoscopy. The timed endotoxin plasma levels did not change significantly by use of the conventional limulus amebocyte test. However, ENC was found to decrease significantly 5 min after the onset of endoscopy. Maximal values were reached at the end of colonoscopy which recovered completely 24 h later. These results, obtained in a population which did not receive any infusions, demonstrate that the half life of endotoxin in the circulation seems to be very short and therefore endotoxin cannot itself be detected. On the other hand, small amounts of endotoxin reaching the blood stream are able to reduce ENC which can be analyzed by a modified limulus--amebocyte--lysate test. With the use of ENC and plasma endotoxin determinations, we are able to show significant endotoxemia during a minimal invasive procedure such as colonoscopy.

Determination of Endotoxin-Neutralizing Capacity of Plasma in Postsurgical Patients

In 92 patients who underwent abdominal and goiter surgery endotoxin and endotoxin-neutralizing capacity (ENC) were determined in plasma preoperatively and daily postoperatively. Endotoxin plasma levels started to increase on day 1 in patients who were laparotomized. Correspondingly ENC was reduced during the 1st postoperative week. Even on the 1st postoperative day determination of ENC made the differentiation between patients possible who showed an uneventful course and patients who developed pneumonia, pulmonary failure, or mental disorders. Furthermore the need for diuretics in order to maintain sufficient renal function was associated with lower ENC during days 1-3. Endotoxin plasma levels were significantly elevated in patients who developed pneumonia during days 1-4, whereas the occurrence of pulmonary failure was only correlated with elevated endotoxin levels on day 3. Endotoxemia was pronounced in patients needing diuretics on days 1, 4, and 5. In patients who underwent goiter surgery ENC changed significantly as found for endotoxin plasma values during the postoperative course. Determination of endotoxin and especially ENC with the use of the limulus amebocyte lysate test turned out to be a reliable method correlating with impending complications at least in postsurgical patients.

Endotoxin-induced cytokine release from whole blood - similarities between monocyte dysfunction in septic disease and during postoperative acute phase response

Plasma levels of endotoxin, TNFα, interleukin-1β (IL-1β), and interleukin-6 (IL-6) as well as the endotoxin-induced release of these cytokines from whole blood were determined in 20 patients after elective aseptic surgery and eight patients suffering from septic disease. Blood samples were drawn before surgery as well as once daily over 7 days postoperatively. Endotoxin plasma levels increased on the day of the operation from 0.025 ± 0.005 EU/ml to 0.099 ± 0.022 EU/ml and remained elevated for 1 day. No changes were noted in the plasma levels of TNFα and IL-1. Levels of IL-6 increased to 198 ± 52 pg/ml on the day of the operation, while the release of TNFα and IL-6 markedly declined after whole blood was stimulated with endotoxin. The difference between basal and stimulated TNF values amounted to 505 ± 129 pg/ml preoperatively and 132 ± 41 pg/ml after the operation and 297 ± 28 pg/ml and 137 ± 43 pg/ml for IL-6. From the second day of the postoperative period onwards, the endotoxin-induced release of IL-6 was higher than the preoperative values. The results of whole blood stimulation in patients with sepsis were similar to those achieved directly after elective surgery. The cytokine release of TNFα, IL-1β, and IL-6 was reduced. We conclude that, during the early aseptic acute phase reaction, the changes in the functioning of monocytes resemble - qualitatively - those occurring during septic disease, and that this may be related to endotoxemia originating in the gastrointestinal tract.