A multi-center double-blind trial was performed on 48 patients with severe acute pancreatitis. All patients were treated with intraperitoneal lavage. One group (n = 22) was also treated with high doses of the protease inhibitor, aprotinin (Trasylol; Bayer AG, Leverkusen, Germany) administered intraperitoneally. Eight patients died, giving a total mortality of 16.6%. No difference was observed between the two groups. Altogether, 12 patients were operated on, corresponding to 25%. In the group not treated with aprotinin, 6 patients were operated on because of pancreatic necrosis, compared with none in the treated group. The difference was statistically significant. There were no significant differences between the two groups with regard to organ failure or other complications. It was concluded that aprotinin counteracts the development of pancreatic necrosis when given intraperitoneally in high doses to patients with severe acute pancreatitis, thus reducing the need for surgical intervention in these patients.
Levels of leukocyte elastase and neutrophil protease 4 (NP4(3)) in plasma and peritoneal exudate were studied in 25 patients with severe, acute pancreatitis. Pancreatitis was diagnosed from the clinical picture and an increased serum amylase level. The diagnosis was verified by computerized tomography, ultrasound, and findings at operation or autopsy. Peritoneal exudate on admission contained high concentrations of leukocyte elastase (6100 +/- 2000 micrograms/l) and NP4(3) (2310 +/- 900 micrograms/l). High initial levels were found also in plasma, which contained 659 +/- 110 micrograms/l of leukocyte elastase and 254 +/- 33 micrograms/l of NP4(3). The levels in plasma were still increased 3 weeks after the acute attack, also in the absence of complications, indicating that the resolution of acute pancreatitis is a protracted process. Plasma levels of both leukocyte proteases were persistently increased in patients with pancreatic abscess, in contrast to the gradual decrease seen in patients with a pseudocyst or uncomplicated recovery. The levels were increased already before the abscess was diagnosed clinically, which indicates that determinations of leukocyte elastase and NP4(3) may be helpful in detecting this complication. A pathophysiologic role for leukocyte proteases in the development of severe, acute pancreatitis should be considered.
Forty-eight patients with severe acute pancreatitis were treated with intraperitoneal lavage in a double-blind randomized multi-center trial. One group (aprotinin group, n = 22) was also treated intraperitoneally with high doses of the protease inhibitor aprotinin. In the group not treated with aprotinin (control group), 6 patients were operated on because of pancreatic necrosis, compared with none in the treated group. Complement activation and the acute phase response were studied with measurements of anaphylatoxin C3a, C1 inhibitor (C1 Inh), interleukin 6 (IL-6), and C-reactive protein (CRP). The control group had higher plasma levels of C3a and lower levels of C1 Inh compared with the aprotinin group. The differences were statistically significant for C3a but not for C1 Inh. Both groups had high plasma levels of IL-6 and CRP. There were no differences between the groups in CRP levels, but the control group had higher IL-6 levels (not statistically significant) than the aprotinin group. This was caused by very high levels in the 6 patients operated on because of pancreatic necrosis, indicating that IL-6 could be a good plasma marker of pancreatic necrosis. The results also show that massive antiprotease treatment reduces complement activation, as illustrated by the lower C3a levels in the aprotinin group. The lower C1 Inh levels in the control group could have been caused by an increased consumption of the inhibitor.
Plasma levels of the plasma protease inhibitor alpha-2-macroglobulin (alpha 2-M) were followed for 7 days in 90 patients subjected to various surgical procedures. Alpha 2-M was found to decrease strictly in parallel with the decrease seen for haemoglobin and albumin levels in all patients. Changes were most pronounced after extensive operations; total hip replacement (n = 7), pulmonary resection (n = 11), extensive colo-rectal resection (n = 15), and less pronounced after 'minor' operations; mastectomy (n = 23) proximal gastric vagotomy (n = 5) and moderate colo-rectal resection (n = 29). Levels were lowest on the second to third postoperative day, whereafter they slowly returned to normal, preoperative levels during the 7-day study period. Functional and quantitative alpha 2-M levels almost paralleled each other throughout the 7 days studied. Chromogenic peptide substrate assays indicated circulating plasmin-alpha 2-M complexes, while no protease-alpha 2-M complexes could be demonstrated using sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) or isoelectric focusing (IEF) analyses. Local accumulation and consumption of proteins within wounded tissues, together with haemodilution, were probably the major factors responsible for the decreased plasma levels seen. It is concluded that the plasma levels of alpha 2-M decrease after major elective surgery strictly in parallel with the decrease seen in haemoglobin and albumin levels, and that circulating plasmin-alpha 2-M complexes are probable. The decrease seems to be graded, that is, proportional to the extent of the operative trauma, similar to the postoperative increase seen in positive acute-phase proteins. Thus, alpha 2-M cannot be used as an internal, unchanged plasma protein standard for other protein changes seen after trauma.
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