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R Isenmann

Publications and source records attributed to R Isenmann.

34 records · Page 2Linked to original sources

Bacterial infection and extent of necrosis are determinants of organ failure in patients with acute necrotizing pancreatitis.

BACKGROUND: The risk factors predisposing to organ failure in patients with necrotizing pancreatitis remain unclear. The relationship between the extent of pancreatic necrosis, the presence of infection and the incidence of organ failure was analysed. METHODS: In a retrospective review, the occurrence of pulmonary insufficiency, renal insufficiency, shock, sepsis/sepsis-like syndrome (SLS) and coagulopathy was evaluated in 273 patients with necrotizing pancreatitis, and a comparison was made between patients with sterile or infected necrosis. Additionally, the relation between the incidence of organ failure and extent of pancreatic parenchymal necrosis was investigated by classifying the patients into three groups according to the amount of necrotic tissue found by contrast-enhanced computed tomography (group 1, extent less than 30 per cent; group 2, 30-50 per cent; group 3, more than 50 per cent). RESULTS: Organ failure was more frequent in patients with infected necrosis than in those with sterile necrosis. Differences were found in the incidence of pulmonary insufficiency, sepsis/SLS and coagulopathy. Organ failure occurred more frequently in group 3 than in group 2 or 1 (95 versus 79 and 66 per cent; P = 0.0004). The extent of infected necrosis was not related to the incidence of organ failure (group 1, 88 per cent; group 2, 86 per cent; group 3, 96 per cent). However, there was a relation between the incidence of organ failure and the extent of sterile necrosis (group 1, 59 per cent; group 2, 74 per cent; group 3, 94 per cent; P = 0.0001). Multivariate analysis confirmed the presence of infection and the extent of necrosis as independent determinants of organ failure. CONCLUSION: The incidence of organ failure is determined by both bacterial infection and extent of necrosis. The incidence of organ failure is determined by the extent of necrotic parenchyma in patients with sterile necrosis. Infected necrosis is associated with a high incidence of organ failure irrespective of the extent of necrosis.

Acute Kidney Injury↗

Natural history of acute pancreatitis and the role of infection.

Bacterial infection of pancreatic necrotic tissue is a frequent complication of severe acute pancreatitis. Infected pancreatic necrotic tissue is observed in 30-70% of all patients suffering from necrotizing pancreatitis. It is the leading cause of deaths in severe acute pancreatitis, with mortality rates ranging from 15 to 30%. The incidence of infection increases with the extent of the necrotic areas and with the time after onset of pancreatitis. Compared to patients with sterile necrosis, those with infection of the necrotic areas have an increased mortality, and systemic complications occur more frequently. Standard treatment for infected pancreatic necrotic tissue is surgical debridement, whereas conservative management is feasible in approximately 30% of the patients with sterile necrosis. As bacterial infection of pancreatic necrotic tissue has a tremendous impact on the prognosis of the disease and on the patient's clinical course, efforts have been made to prevent it. Although clinical and experimental data provide evidence that prophylactic antibiotics have beneficial effects on the outcome and course of patients with severe acute pancreatitis, this topic has to be investigated further. General recommendations concerning the early use of antibiotics have to await the results of larger, double-blind studies.

Anti-Bacterial Agents↗

[Perioperative infection prophylaxis in gastrointestinal surgery].

Antibiotic perioperative prophylaxis is known to reduce postoperative infections and is generally administered as single-dose regimen today. Effective prophylaxis requires plasma- and tissue concentrations above the MIC of the expected bacterial spectrum throughout the whole operation from skin incision to wound closure. In longlasting operations a second dose after 4 hours is recommended. Indications for antibiotic prophylaxis are clean-contaminated or contaminated procedures according to Cruse and in patients with elevated risk of infection. Generally antibiotic prophylaxis is administered intravenously. Chinolons achieving high tissue- and plasmalevels and showing a broad antibacterial spectrum seem appropriate to be used for oral prophylaxis. In a prospective study in 36 patients pharmocokinetics of ofloxacin were measured perioperatively and proper plasma- and tissue concentrations were attained. A following prospective randomized study in 56 patients undergoing colonic or pancreatic resections oral prophylaxis did not show a higher infection rate compared with a standard intravenous prophylaxis. Therefore oral prophylaxis seems to be an attractive option, its effectivity needs to be proven by studies with sufficiently high patient numbers.

Anti-Bacterial Agents↗

Adaptation of the human pancreas to inhibition of luminal proteolytic activity.

BACKGROUND & AIMS: Feedback regulation of pancreatic enzyme secretion is well established in animals, and their pancreases are able to adapt to intraduodenal inhibition of pancreatic enzymes by proteinase inhibitors such as Camostate (FOY-305; Schwarz GmbH, Monheim, Germany). In this study, we addressed whether similar adaptive changes occur in the human pancreas after 4 weeks of 2 g/day Camostate application. METHODS: Before, at the end of, and 2 weeks after 4-week Camostate treatment (four times 500 mg daily), pancreatic changes were analyzed with the use of a secretin-cerulein test, a test-meal stimulation, cholecystokinin plasma measurement, and standardized ultrasonographic investigations of the pancreas. RESULTS: Duodenal trypsin output after secretion stimulation was significantly increased (+44%; P < 0.01) and duodenal bicarbonate output decreased 22% (P < 0.05) after 4 weeks of Camostate application. The size of the pancreatic head (vertical) increased 8% (P < 0.05) at week 4 and decreased to pretreatment values 2 weeks after treatment (week 6). The other three diameters measured (head oblique, body, and tail) showed a similar pattern. Stimulated cholecystokinin plasma levels 15 minutes after application of a standard test meal increased 62% (P < 0.05). CONCLUSIONS: The human pancreas adapts to oral application of the proteinase inhibitor Camostate. These findings support the theory that feedback control of the exocrine pancreas operates in humans.

Adaptation, Physiological↗

Infections complicating pancreatitis: diagnosing, treating, preventing.

The most important risk factor in patients suffering from acute necrotizing pancreatitis is pancreatic infection, a factor that determines the course of the disease, its therapeutic management, and its outcome. The bacterial infection route is very likely via the colon. In patients with acute pancreatitis, the infection rate is about 40 to 70% within the first 3 wks. Bacteria most frequently found are those from the gastrointestinal tract: Escherichia coli, Pseudomonas species, Streptococcus fecalis, Enterococcus, and Staphylococcus aureus. Screening methods for infected necrotizing pancreatitis include fine needle puncture by ultrasonography or computed tomographic guidance with Gram staining and culture of the aspirate. We previously investigated different broad-spectrum antibiotics with regard to their efficacy at preventing infection. This analysis indicated that antibiotics have different efficacy factors based on pharmacodynamic properties. Imipenem and quinolones, in combination with metronidazole, are the drugs of choice for treating or preventing pancreatic infection, whereas aminoglycosides do not enter the pancreas and therefore are not indicated. Based on increasing evidence that patients with acute necrotizing pancreatitis will benefit by early and appropriate antibiotic therapy, we altered the approach in such patients with an immediate start of antibiotic therapy continued for at least 14 days. We have found a reduction of the infection rate to 33% (11/32) in the third week after the onset of the disease. This treatment of the infection and the possibility of delaying operative intervention resulted in optimal surgical conditions. However, further prospective, controlled, and randomized studies are necessary to determine which antibiotics and antimycotic therapeutic regimens should be chosen.

Anti-Bacterial Agents↗

Surgical treatment of acute pancreatitis.

The most important diagnostic step in the management of patients with severe acute pancreatitis is discrimination between interstitial-oedematous and necrotizing pancreatitis. Surgical decision-making is based on clinical, bacteriological and contrast-enhanced CT-data. Persisting or progressive systemic or local organ complications occurring despite ICU-treatment are indicators for surgical management. Patients suffering from sepsis syndrome, cardiovascular shock, multisystemic organ failure syndrome, surgical acute abdomen and persisting or progressing ileus should be treated surgically. The surgical technique is based on careful necrosectomy or debridement in combination with continuous or repeated surgical evacuation of necrotic tissue, bacteria and biologically active compounds. Necrosectomy and postoperative continuous local lavage resulted in a hospital mortality of 17% in necrotizing pancreatitis, conservative management of necrotizing pancreatitis in a hospital mortality of 6.3%. In 1442 patients treated in a 14-year period the overall hospital mortality was 4.4%.

Acute Disease↗

[Antibiotic use in necrotizing pancreatitis. Results of a controlled study].

BACKGROUND AND OBJECTIVE: The clinical course and death rate in acute necrotizing pancreatitis (ANP) are largely determined by septic complications as part of bacterial invasion of the necrotic tissues. It remains unclear whether antibiotic prophylaxis reduces bacterial invasion of the necroses or septic complications. It was, therefore, the aim of this study to evaluate the effect of prophylactic administration of antibiotics to patients with ANP. PATIENTS AND METHODS: In a prospective randomized study 13 patients with ANP and sterile necroses (quantified by contrast-enhanced computed tomography) were given twice daily 200 mg ofloxacin and twice daily 500 mg metronidazole intravenously. The results were compared to those in a control group of patients with ANP (n = 13) who had not initially received antibiotics. In both patient groups fine-needle biopsies of the necrotic areas were performed on days 1, 3, 5, 7 and 10. If there was evidence of infection, antibiotics were then also given to patients of the control group. RESULTS: The extent of the necroses was the same, 40%, in both groups. These necroses became infected in a median of 9.5 (treated group) and 10 days (untreated group). The clinical course, documented by the APACHE II score, showed significant improvement under antibiotic treatment (days 1-5-10: scores 15-13.0-9.5). In the (initially untreated) control group the clinical condition deteriorated significantly (days 1-5-10: score 11.5-15.0-16.0). The changes from days 1 to 5, 5 to 10 and 1 to 10 were highly significant (Wilcoxon test, P < 0.01). None of the patients in the antibiotic group died within the first 3 weeks, but 2 of the 13 in the control group died. CONCLUSION: Antibiotic prophylaxis neither prevented nor delayed bacterial infection of the necrotic pancreas. But it significantly improved the clinical course if started before the onset of infection of the pancreatic necroses.

Adult↗

Influence of etiology on the course and outcome of acute pancreatitis.

It has been supposed that there are differences with regard to clinical course and outcome due to the underlying etiological factor in acute pancreatitis. Therefore, the objective of this study was to analyze the severity of the disease, serum enzymes, indicators of necrosis, systemic complications, and mortality in acute pancreatitis with regard to the etiology. One hundred ninety patients with acute pancreatitis (127 male, 63 female) were studied prospectively and subdivided into three etiological groups: (i) alcohol, (ii) gallstones, and (iii) other causes and idiopathic acute pancreatitis. Severity scores (Ranson and Bank) and findings by contrast-enhanced computed tomography were similar in all three groups. Analysis of serum enzymes [lipase, aspartate aminotransferase (ASAT)] and indicators of necrosis (C-reactive protein, alpha 1-antitrypsin, alpha 2-macroglobulin, and lactate dehydrogenase) showed only for ASAT within 24 h significantly higher levels in biliary acute pancreatitis in comparison with the other groups. There were no differences in the rate of infected pancreatic necrosis and mortality in alcohol-related acute pancreatitis (31 and 5.3%), biliary acute pancreatitis (38 and 10%) and acute pancreatitis due to other etiological factors (43 and 5.5%). In conclusion, this study clearly showed that once the pathogenetic mechanisms have initiated the disease, the course and outcome of acute pancreatitis are not influenced by the underlying etiological factor.

Acute Disease↗

[Prognosis in pancreatic carcinoma].

Pancreatic cancer is one of the most frequent carcinomas of the human gastrointestinal tract. despite considerable progress in diagnosis, its prognosis has remained unchanged during the last years. Up to now, there is no possibility to screen patients for pancreatic carcinomas, and the symptoms of the disease are uncharacteristic and often misleading. Surgical treatment, with resection of the tumor is the only chance for cure, but for experienced pancreatic surgeons, an advanced tumor stage at the time of operation is a common finding. Large studies reveal the poor prognosis of the disease. Only 20-30% of all patients suffering from pancreatic cancer can be operated with curative intention. In 80-85% of all cases, the tumor has spread into peripancreatic lymph nodes. Thus, mean 5-years survival rates of 3 to 5% are commonly reported, and the median survival time after establishment of diagnosis is 4-6 months. Improvements in surgical technique and postoperative patient's care have led to an impressive decrease in the formerly considerable morbidity and mortality after pancreatic resection. If the tumor can be resected at an early stage and the regional lymph nodes are not involved, median 5-years survival rates of 20-40% are commonly reported. Further approaches include more radical surgical procedures with dissection of the entire peripancreatic region and resection of the upper abdominal blood vessels. Whether this new technique or a combination of operation, radiation and chemotherapy will improve the prognosis of the disease remains unclear. Large clinical trials are necessary to prove these assumptions.

Epidermal Growth Factor↗

The risk of pancreaticointestinal anastomosis can be predicted preoperatively.

The risk of developing postoperative complications following pancreatic resection depends mainly on how difficult it is to perform a proper pancreaticointestinal anastomosis. We have evaluated the serum pancreolauryl test, a rapid tubeless pancreatic function test, as a simple preoperative predictor of the degree of pancreatic fibrosis. Degree of fibrosis in turn provides an indirect parameter for the difficulties of performing a proper and safe pancreaticointestinal anastomosis. In 35 patients (21 chronic pancreatitis, 14 pancreatic tumors) undergoing major pancreatic resection, we found a negative correlation (r = -0.75, p < 0.001) between the degree of fibrosis at the resection margin and the serum pancreolauryl test results. Patients with chronic pancreatitis had a significantly higher degree of fibrosis at the resection margin (59 +/- 22 vs. 34 +/- 25%; X +/- SD; p < 0.01) and lower fluorescein serum concentrations (2.6 +/- 1.9 vs. 4.3 +/- 2.1 micrograms/ml; X +/- SD; p < 0.01) in comparison with patients with pancreatic tumors. These findings indicate that the degree of pancreatic fibrosis, the difficulties of performing a proper pancreaticointestinal anastomosis, and subsequently the potential risk of postoperative complications can easily be predicted preoperatively.

Adult↗

Pancreatic necrosis: an early finding in severe acute pancreatitis.

Despite the clinical importance of pancreatic necrosis in the course of acute pancreatitis, little is known about when it develops. Serum C-reactive protein (CRP) is a reliable parameter with a high deduction rate for pancreatic necrosis. We analyzed 199 patients with acute pancreatitis. The development of pancreatic necrosis was ascertained by a daily measurement of serum CRP in 45 patients with contrast-enhanced computed tomographic-proven necrotizing pancreatitis. In all 45 cases, the criteria for pancreatic necrosis were satisfied within the first 4 days of the onset of symptoms. This indicates that pancreatic necrosis is an early finding that develops within hours.

Acute Disease↗

Human pancreatic tissue concentration of bactericidal antibiotics.

Pancreatic infection represents the most important cause of fatal outcome in human acute pancreatitis. In a comparative analysis, human pancreatic tissue concentrations of 10 different bactericidal antibiotics were determined in 89 patients undergoing pancreatic surgery. Concentrations of the antibiotics were determined in the blood and pancreatic tissue using high-pressure liquid chromatography. Pancreatic tissue concentrations 120 minutes after intravenous administration were as follows: mezlocillin, 19.0 mg/kg; piperacillin, 20.3 mg/kg; cefotaxime, 9.1 mg/kg; ceftizoxime, 7.9 mg/kg; netilmicin, 0.4 mg/kg; tobramycin, 0.4 mg/kg; ofloxacin, 1.7 mg/kg; ciprofloxacin, 0.9 mg/kg; imipenem, 6.0 mg/kg; metronidazole, 3.5 mg/kg. Three groups of antibiotics were established: group A, substances with low tissue concentrations (netilmicin, tobramycin), which were below the minimal inhibitory concentrations of most bacteria found in pancreatic infection; group B, antibiotics with pancreatic tissue concentrations which were sufficient to inhibit some but not all bacteria in pancreatic infection (mezlocillin, piperacillin, ceftizoxime, cefotaxime); group C, substances with high pancreatic tissue levels as well as high bactericidal activity against most of the germs present in pancreatic infection (ciprofloxacin, ofloxacin, imipenem). These data could serve as the basis for adequate antibiotic prophylaxis or treatment of pancreatic infection.

Adult↗

Penetration of ciprofloxacin into the human pancreas.

The aim of this study was to determine the concentrations of ciprofloxacin in human pancreatic tissue and juice. Concentrations were measured by high-pressure liquid chromatography (HPLC). Two hundred mg of ciprofloxacin were administered as a short i.v. infusion (30 min). The median ciprofloxacin concentrations 140 min (median) after the start of infusion in pancreatic tissue as well as in pancreatic juice were 0.9 mg/kg (mg/l). The penetration ratio was 1.0 for pancreatic tissue and 0.83 for pancreatic juice. With regard to the minimal inhibitory concentrations (MIC) for the respective bacteria, ciprofloxacin seems to be an appropriate drug for the treatment of septic complications in necrotizing pancreatitis. Future clinical trials are necessary to prove this assumption.

Adult↗