Effects of octreotide on acute necrotizing pancreatitis in rabbits

AIM: To assess the role of oxygen-derived free radicals and cytokines in the pathogenesis of taurocholic acid-induced acute pancreatitis, and to evaluate the preventive effects of octreotide towards the development of acute pancreatitis. METHODS: Acute pancreatitis was induced in male New Zealand white rabbits by retrograde injection of 0.8 mL/kg·b·m, of 50 g/L sodium taurocholate(NaTC) in the pancreatic duct. Sham-operated animals served as control. Octreotide 1 mglkg·b.m.was administered subcutaneously before the induction of pancreatitis. Blood was taken from the jugular vein before and at 1, 3, 6, 12 and 24 h after pancreatitis induction.Serum activities of amylase, IL-6 and TNF-α and levels of malonyl dialdehyde (MDA), glutathione (GSH), glutathione peroxidase (GPx), catalase and superoxide dismutase (Mn-,Cu-,and Zn-SOD) in pancreatic tissue were measured.RESULTS: Serum TNF-α and IL-6 levels increased significantly 3 h after the onset of pancreatitis, and then returned to control level. The tissue concentration of MDA was significantly elevated at 24 h, while the GSH level and GP-x, catalase, Mn-SOD, Cu-, Zn-SOD activities were all significantly decreased in animals with pancreatitis as compared to the control. Octreotide pretreatment significantly reversed the changes in cytokines and reactive oxygen metabolites. Octreotide treatment did not alter the serum amylase activity and did not have any beneficial effects on the development of histopathological changes.CONCLUSION: Oxygen-derived free radicals and proinflammatory cytokines are generated at an early stage of NaTc-induced acute pancreatitis in rabbits. Prophylac ticoctreotide treatment can prevent release of cytokines and generation of reactive oxygen metabolites, but does not have any beneficial effects on the development of necrotizing pancreatitis.     

Somatostatin and octreotide in acute pancreatitis: the never-ending story

The role of somatostatin and octreotide in the treatment of acute pancreatitis has been studied in the last two decades. We describe the physiologic activities of somatostatin and octreotide and their action on pancreas secretion. Results of experimental studies on the action of somatostatin and octreotide in some models of acute pancreatitis are discussed as well as the results of clinical studies on the effects of the two drugs in human acute pancreatitis. On the basis of these data, we suggest that somatostatin and octreotide should not be recommended for the prevention and treatment of acute pancreatitis.     

A case of octreotide acetate-induced acute pancreatitis]

A 56-year-old man was admitted to our hospital in July 2000 because of epigastralgia and back pain with past history of repeated upper abdominal pain due to acute pancreatitis since 1995. Abdominal computed tomography on admission showed a swelling in the pancreas head and several large pancreatic pseudocysts. He was diagnosed as acute pancreatitis based on abdominal pain, elevated pancreatic enzymes and computed tomography finding, and given 50 microg octreotide subcutaneously for the treatment of pancreatic pseudocysts. Within 3 hours after octreotide injection, he complained of upper abdominal pain and had an elevated serum amylase level. Abdominal pain disappeared after cessation of octreotide injection and the patient was discharged free from abdominal pain. Octreotide might cause acute pancreatitis by inducing spasm of the sphincter of Oddi. Careful check-up of the patients might be needed during treatment with octreotide.     

Effects of octreotide in acute hemorrhagic necrotizing pancreatitis in rats

BACKGROUND AND AIM: Octreotide is considered to reduce exocrine pancreatic secretion in acute hemorrhagic necrotizing pancreatitis decreasing pancreatic autodigestion. The aim of this study was to determine whether octreotide also has antioxidative effects in acute pancreatitis. Additionally time and dose of application were of interest. METHOD: Ninety male Sprague-Dawley rats were randomized into six groups (n = 15). Group 1 underwent a laparotomy, and animals in groups 2-6 received intraductal glycodeoxycholic acid followed by intravenous cerulein. Groups 3 and 4 were injected with 0.5 mg octreotide, while groups 5 and 6 received continuous intravenous infusion of 0.05 mg octreotide/h for 10 h. Treatment was initiated 6 hours after induction of pancreatitis (IP) in groups 3 and 5, and 14 h after IP in groups 4 and 6. At 24 h after IP all animals were killed and each pancreas was analyzed histopathologically. In addition, levels of pancreatic lipid peroxidation protective enzymes glutathione-peroxidase (GSH-Px) and superoxide dismutase (SOD) as well as lipid peroxidation via thiobarbituric acid reactive substances (TBARS) were determined. RESULTS: Early bolus application of octreotide reduced severity of histopathological changes in acute pancreatitis and decreased lipid peroxidation in pancreatic tissue samples; however, late bolus application and continuous intravenous infusion did not influence pancreatitis or lipid peroxidation. CONCLUSION: Octreotide seems to have a dose- and time-dependent effect on histopathology and lipid peroxidation in a model of pancreatitis in rats.     

Beneficial effect of octreotide treatment in acute pancreatitis in rats

Summary Conclusions Octreotide treatment contributes to the regulation of tumor necrosis factor (TNF) production in sodium taurocholate-induced acute necrotizing pancreatitis in rats. Owing to its complex effect, octreotide can partially ameliorate the deleterious consequences of acute necrotizing pancreatitis. Elevated TNF and interleukin-6 (IL-6) levels in the peritoneal fluid may be considered a consequence of the activation of peritoneal macrophages. Background The effects of octreotide on exocrine pancreatic function have been investigated in numerous studies, but little attention has been paid to its influence on cytokine production in acute pancreatitis. Methods Acute pancreatitis was induced by the retrograde injection of taurocholic acid into the pancreatic duct in male Wistar rats. Serum amylase activity, wet pancreatic weight/body weight (pw/bw) ratio, and TNF and IL-6 levels were measured. Four μg/kg of octreotide was administered subcutaneously at the time of induction of pancreatitis and 24 or 48 h later. Rats were sacrificed 6, 24, 48, or 72 h after the operation. Results The serum amylase level and pancreatic weight to body weight ratio were decreased significantly in the octreotide-treated group. The serum TNF level was decreased significantly in the octreotide-treated group as compared with the control group at 6, 24, and 48 h (0.6±1.5, 2.0±3.3, and 0 vs. 50±15.5, 37.5 ±18.4, and 13.1±12.5 U/mL, respectively). The ascites TNF level was decreased to 0 in the octreotide-treated group and was elevated in the control group at 72 h (28.0±49.0 U/mL). IL-6 production in ascites was extremely high in both groups at 6 h (80,000±43, 817 pg/mL and 58, 500±33 335 pg/mL), but the difference was not significant.     

Continuous intravenous octreotide treatment for acute experimental pancreatitis

BACKGROUND: The efficacy of octreotide, the synthetic analogue of the hormone somatostatin, for the treatment of acute pancreatitis is controversial. Octreotide has been commonly administered in subcutaneous bolus injections; however, continuous intravenous infusion may be advantageous for acute conditions. METHODS: Acute experimental pancreatitis was induced in rats by intraparenchymal injections of 1 ml 10% sodium taurocholate, and octreotide (1 microg/kg/h, dissolved in physiological solution, intravenously was started 4 h later and continuously infused for 48 h. Physiological solution infusions, in identical volumes, were used in the controls. The following parameters were examined: mortality; macroscopic and histological damage; hematocrit; plasma pH; acid-base balance; serum glucose; calcium, and amylase. RESULTS: Octreotide treatment had a striking effect on mortality: 8.3 versus 91.6% in the treatment and control groups, respectively (p < 0.001). Octreotide also ameliorated pancreatic edema and intestinal dilatation, and had significant beneficial effects on histopathological damage and the biochemical alterations which are associated with acute pancreatitis. CONCLUSIONS: Continuous intravenous octreotide infusion is a potentially efficacious therapeutic method for acute pancreatitis.     

善得定治疗急性胰腺炎临床对照分析

目的 探讨善得定治疗急性胰腺炎的临床疗效。方法 将34例急性胰腺炎患者随机分为2组,17例用善得定每小时25μg,另17例不用善得定,对照临床症状改善情况及Ranson预后指标。结果 善得定治疗组中腹痛完全消失者较多,镇痛药应用较少,且48h后不良预后指标较少,包括血球压积降低10％以上和血钙＜8mg/dL的患者显著少于对照组。结论 用善得定治疗急性胰腺炎可减轻症状,减少并发症,并防止病情恶化。     

善得定治疗急性胰腺炎临床对照分析

目的探讨善得定治疗急性胰腺炎的临床疗效。方法将３４例急性胰腺炎患者随机分为２组,１７例用善得定每ｈｒ２５ｕｇ,另１７例不用善得定,对照临床症状改善情况及Ｒａｎｓｏｎ预后指标。结果善得定治疗组中腹痛完全消失者较多,镇痛药应用较少,且４８ｈｒ后不良预后指标较少,包括血球压积降低１０％以上和血钙＜８ｍｇ／ｄｌ的患者显著少于对照组。结论用善得定治疗急性胰腺炎可减轻症状,减少并发症,并防止病情恶化。     

Controlled trial of high-dose octreotide in treatment of acute pancreatitis

Nineteen consecutive patients with acute pancreatitis were sequentially allocated to treatment with high-dose octreotide (N=9) or to act as controls (N=10). All other aspects of treatment were similar and were according to a strict treatment protocol. There was no significant difference between the two groups on admission with regard to recognized criteria of poor prognosis. The octreotide-treated group required significantly less analgesia and after 48 hr developed significantly fewer poor prognostic indicators, including falls in hematocrit of >10%, in serum albumin to <32 g/liter, and in serum calcium to <2.00 mmol/liter. Falls in arterial PO₂ to <10 kPa, in serum albumin of >20%, and in hemoglobin of >2 g/dl were also significantly less frequent. There was a trend towards improvement in the octreotide-treated group in every other physiological and radiological indicator of disease severity. High-dose octreotide may reduce the severity of acute pancreatitis.     

The role of octreotide and somatostatin in acute and chronic pancreatitis

Acute pancreatitis may follow a mild or a severe course. Whereas mild or edematous pancreatitis is a self-limiting disease with a low complication rate and low death rate, morbidity and mortality in severe or necrotizing pancreatitis are still unacceptably high. The major problem is the lack of a specific drug, especially in the early phase of the disease, to interfere with the systemic inflammatory response syndrome and to limit or prevent complications of the disease. Although the initiating pathophysiological process is not known, the destruction of the gland ('autodigestion') by digestive enzymes may be responsible for disease progression. Inhibition of pancreatic activity, which reduces exocrine secretion and further prevents the release and activation of enzymes, was therefore suggested as a specific treatment concept. The results of clinical investigations using somatostatin or its analogue are controversial, since all these trials had low statistical power. In a recent multicenter randomized controlled study with a large number of patients (n = 302) (and an adequate level of disease severity), no benefit of octreotide on progression or outcome was found. Chronic pancreatitis is characterized by an irreversible destruction of the exocrine and endocrine pancreatic parenchyma leading to maldigestion and diabetes. Pain, which may be caused by increased ductal pressure, is one of the most dominant symptoms in chronic pancreatitis. However, no beneficial effects on pain with pancreatic exocrine secretion-inhibiting drugs have been demonstrated. Treatment of other complications of the disease (pseudocyst formation, fistula and pancreatic ascites), with somatostatin or octreotide has given conflicting results. However, in a prophylactic clinical setting (e.g. elective pancreatic surgery) the inhibition of exocrine pancreatic secretion reduces complications.     

JPN Guidelines for the management of acute pancreatitis: medical management of acute pancreatitis

The basic principles of the initial management of acute pancreatitis are adequate monitoring of vital signs, fluid replacement, correction of any electrolyte imbalance, nutritional support, and the prevention of local and systemic complications. Patients with severe acute pancreatitis should be transferred to a medical facility where adequate monitoring and intensive medical care are available. Strict cardiovascular and respiratory monitoring is mandatory for maintaining the cardiopulmonary system in patients with severe acute pancreatitis. Maximum fluid replacement is needed to stabilize the cardiovascular system. Prophylactic antibiotic administration is recommended to prevent infectious complications in patients with necrotizing pancreatitis. Although the efficacy of the intravenous administration of protease inhibitors is still a matter of controversy, there is a consensus in Japan that a large dose of a synthetic protease inhibitor should be given to patients with severe acute pancreatitis in order to prevent organ failure and other complications. Enteral feeding is superior to parenteral nutrition when it comes to the nutritional support of patients with severe acute pancreatitis. The JPN Guidelines recommend, as optional measures, blood purification therapy and continuous regional arterial infusion of a protease inhibitor and antibiotics, depending on the patient’s condition.     

重症急性胰腺炎的早期处理

重症急性胰腺炎起病凶险,病死率较高。对重症急性胰腺炎的早期识别及早期治疗有助于减少器官衰竭、感染等并发症的发生,降低病死率。该文从早期病情评估、早期病情监测及早期治疗3个方面介绍重症急性胰腺炎的早期处理,以期提高临床医生对重症急性胰腺炎早期诊治的认识。     

Changing concepts in the surgical management of acute pancreatitis.

Most episodes of acute pancreatitis are mild and self-limiting, but severe disease complicated by multiple system organ failure develops in up to 20% of cases. Early detection of those patients who subsequently develop necrotizing pancreatitis allows the start of supportive treatment in the intensive care unit before organ failure occurs. Conservative treatment in the intensive care unit, including the administration of intravenous antibiotics, is the gold standard. Surgery is indicated in patients with infected pancreatic necrosis but not in patients with sterile necrosis in the absence of deteriorating multi-organ failure despite maximal intensive care unit treatment, or other specific surgical complications. At our institution, out of 44 patients with necrotizing pancreatitis 29 (66%) had sterile necrosis and were managed conservatively while 15 (34%) had infected pancreatic necrosis and were treated by necrosectomy and continuous closed retroperitoneal lavage. There were two deaths resulting in an overall mortality of 5% in patients with severe acute pancreatitis.     

奥曲肽对急性坏死性胰腺炎炎症介质的调节作用

目的 观察奥曲肽对急性坏死胰腺炎（ＡＮＰ）大鼠肿瘤坏死因子ａ（ＴＮＦａ）、一氧化氮（ＮＯ）和内毒素等炎症介质的影响,并探讨其对ＡＮＰ大鼠的治疗作用。方法 ＳＤ大鼠９３只,随机分为３组：ＡＮＰ生理盐水处理组（ＡＮＰ＋ＮＳ组）、ＡＮＰ奥曲肽治疗组（ＡＮＰ＋奥曲肽组）和假手术组（ＳＯ组）。观察各组大鼠的平均存活时间和存活率、血清淀粉酶活性、腹水量、胰腺系数及病理形态变化;测定血浆内毒素、血清ＴＮＦａ及血     

Modern management of acute pancreatitis

There is a rising incidence of acute pancreatitis in the United States. Numerous clinical prognostic scoring systems have been developed, including the BISAP score. Vigorous fluid resuscitation remains a cornerstone of early management of acute pancreatitis. Cross-sectional imaging in the early phase of evaluation has not been associated with improvement of outcomes. There is no role for prophylactic antibiotics in early management. However, there is growing emphasis on the identification and treatment of extrapancreatic infections. Enteral nutrition in severe acute pancreatitis has reduced mortality, systemic infection, and multiorgan dysfunction compared to parenteral nutrition. Conservative management consisting of percutaneous drainage and delayed surgical intervention is now favored for local complications, such as infected necrosis. These developments have contributed to improved outcomes for patients with acute pancreatitis.     

Nutritional management of acute pancreatitis

Most patients with acute pancreatitis have mild to moderate disease and require no specialized nutritional support. Twenty percent to 30% have severe cases, resulting in a catabolic hypermetabolic state, and these patients may require early aggressive nutritional support. Traditionally, this support has been in the form of total parenteral nutrition. However, recent data suggest that enteral nutrition infused into the jejunum is feasible, well tolerated, associated with fewer complications, and significantly less expensive than parenteral nutrition. The pathophysiology of gut function in acute pancreatitis and the rationale and evidence for parenteral and enteral nutritional support are reviewed herein. An algorithm on the nutritional management of acute pancreatitis is suggested.     

Early management of acute pancreatitis

Acute pancreatitis is the most common gastro-intestinal indication for acute hospitalization and its incidence continues to rise. In severe pancreatitis, morbidity and mortality remains high and is mainly driven by organ failure and infectious complications. Early management strategies should aim to prevent or treat organ failure and to reduce infectious complications. This review addresses the management of acute pancreatitis in the first hours to days after onset of symptoms, including fluid therapy, nutrition and endoscopic retrograde cholangiography. This review also discusses the recently revised Atlanta classification which provides new uniform terminology, thereby facilitating communication regarding severity and complications of pancreatitis.