Indications for use of the drug Octreotide
Acromegaly (control of the main manifestations of the disease and a decrease in the level of growth hormone and somatomedin C in the blood plasma in cases where the effect of surgical treatment, radiation therapy and treatment with dopamine agonists is not sufficient); relief of symptoms of endocrine tumors of the digestive tract and pancreas: carcinoid tumors with the presence of carcinoid syndrome; VIPs; glucagonomas; gastrinomas/Zollinger-Ellison syndrome (usually in combination with H2-histamine receptor blockers); insulinomas (to control hypoglycemia in the preoperative period, as well as for maintenance therapy); somatoliberins; refractory diarrhea in patients with AIDS; prevention of complications after pancreatic surgery; stopping bleeding and preventing re-bleeding from esophageal varices in patients with cirrhosis of the liver (in combination with specific therapeutic measures, for example, endoscopic sclerotherapy).
Special instructions for the use of the drug Octreotide
In case of a pituitary tumor that secretes growth hormone, strict medical supervision of patients receiving octreoid is necessary, since it is possible that the size of the tumors may increase with the development of such a serious complication as a narrowing of the visual fields. When treating endocrine tumors of the digestive tract and pancreas with octreotide, in rare cases a sudden relapse of the disease may occur. In patients with insulinoma during treatment with octreoid, an increase in the severity and duration of hypoglycemia may be observed. In diabetic patients receiving insulin, Octreoid may reduce the need for insulin. There is no experience with the use of Octreoid during pregnancy and lactation; during this period the drug is prescribed only for absolute indications.
Material and methods
The multicenter study included 204 patients with severe pancreatic necrosis who were treated in the surgical departments of the Yaroslavl Regional Clinical Hospital (from 1996 to 2011), City Hospital No. 1 of Vologda (from 2005 to 2010), and City Hospital No. 2 of Kostroma (from 2008). to 2009) and city hospital No. 1 of Rybinsk (from 2008 to 2009).
The criteria for inclusion of patients in the study were the following: 1) detection of necrosis of the pancreas and parapancreatic tissue during surgery; 2) the presence of necrosis of the pancreas and parapancreatic tissue at the autopsy of deceased non-operated patients; 3) the presence of fluid formation with sequestration in non-operated patients according to the results of ultrasound, computed tomography and magnetic resonance imaging; 4) severity of the condition upon admission, 9 or more points on the APACHE II scale.
The criteria for excluding patients from the study were: 1) the presence of a malignant neoplasm; 2) absence of necrosis of the pancreas during surgery, during autopsies of dead bodies, during ultrasound examination, MRI, CT; 3) the severity of the condition at admission is less than 9 points on the APACHE II scale.
An important condition for the study was a complete sample of patients with severe pancreatic necrosis for the entire calendar year in each of the indicated hospitals, which actually made it possible to consider it prospective based on the condition at a point in time in the past [2].
During the study, we used the international classification of acute pancreatitis, according to which the predicted severity of the disease was determined [4].
At the beginning of the study, a traditional analysis approach was used, similar to that used by W. Uhl et al. [9]. The patients were divided into two groups: main ( n
=114), in which octreotide was used in standard doses (100 mcg 3 times a day subcutaneously and intramuscularly), and a control group (
n
=90), in which the drug was not used. Mortality rates and the prevalence of necrosis in the study and control groups were compared using univariate statistical methods. To correctly interpret the results obtained, the groups were additionally (unlike the study by W. Uhl et al.) compared with respect to other potential predictors (severity factors upon admission to hospital and treatment factors), which could also influence the outcome of the disease.
Necrosis involving one of the sections of the pancreas or a significant volume of parapancreatic tissue was considered widespread. The prevalence of necrosis was determined during surgery or (in non-operated patients) based on autopsy results. In addition, pancreatic necrosis was considered focal in patients whose cure did not require surgical intervention.
Factors of severity of the condition were age (number of years), gender (1 - male, 0 - female), severity of organ dysfunction on the APACHE II scale (in points), body temperature (°C), pulse rate (per 1 min), mean arterial pressure (in mm Hg), respiratory rate (in 1 min), level of consciousness according to the Glasgow scale (in points), number of blood leukocytes (thousand 109/l), band neutrophils (in %), level in blood creatinine (in mg/dl), potassium (in mmol/l), sodium (in mmol/l), glucose (in mmol/l), partial blood oxygen tension (in mmHg), blood pH values . These parameters were assessed upon admission.
Of the treatment predictors, methods of antibacterial prophylaxis were assessed and compared (aminoglycosides, penicillins and first generation cephalosporins - code 1; third and fourth generation cephalosporins - code 2; fluoroquinolones and carbopenems - code 3), frequency of use of quamatel (1 - used, 0 - not used ), anti-enzyme therapy (1 - used, 0 - not used), early nutritional support (1 - used, 0 - not used), nutritional support for purulent complications (1 - used, 0 - not used).
The results of treatment of patients in the main and control groups were compared only if there were no significant differences between these groups in the above-mentioned factors of severity of the condition and treatment factors. Differences were considered significant if the p
for the criterion used was below 0.05.
We used t
-test for a normal distribution of the attribute value,
U
-test when comparing groups with a non-normal distribution of the attribute value, and the χ2 test when comparing groups according to a qualitative attribute.
At the second stage of the study, an alternative version of the analysis was used, which did not require the formation of comparison groups and their randomization, as in the study by W. Uhl et al. - determining the combined influence of factors on the outcome of treatment. The result was a model for predicting the probability of an event occurring (a change in the outcome of treatment) based on the existing factors of the severity of the condition upon admission to the hospital and the factors of the treatment provided.
To assess the dynamics of mortality, the Cox proportional hazards model was used. Its peculiarity was the assessment of the influence of these parameters in each case of completed observation of the life of patients, i.e. until the moment of death.
The cumulative influence of factors on the prevalence of necrosis was assessed using logistic regression.
When selecting variables in the model for regression analysis, the backward elimination method was used [2].
The influence of the predictors included in the model and the accuracy of the entire model as a whole were considered significant if the p
χ2 criteria were less than the critical value (0.05) for all included factors and for the model as a whole.
The degree of influence of the predictor was determined by the value of the regression coefficient. Its larger numerical values indicated a greater power of influence. The direction of influence was assessed by the sign of the coefficient. With a negative value of the regression coefficient, the influence of the parameter of the severity of the condition or treatment was considered inversely dependent, i.e., its increase reduced the probability of death; with a positive value of the coefficient, an increase in the effect of the factor indicated an increase in the probability of death.
Statistical processing of the material was carried out using the StatSoft, Inc. program. (2007), Statistica version 8.0 and MedCalc version 10.5.0.0.
Side effects of the drug Octreotide
Possible pain, itching or burning sensation, redness and swelling at the injection site, anorexia, nausea, vomiting, cramping abdominal pain, bloating, flatulence, loose stools, diarrhea and steatorrhea, phenomena resembling acute intestinal obstruction (progressive bloating, severe pain in the epigastric region, muscle protection), formation of gallstones (with long-term use in 10–20% of patients), acute pancreatitis, hair loss, liver dysfunction, including acute hepatitis without cholestasis, hyperbilirubinemia, accompanied by increased alkaline levels phosphatases, γ-glutamyltransferases and, to a lesser extent, transaminases, decreased glucose tolerance, persistent hyperglycemia or hypoglycemia (with long-term use).
Use of the drug Octreotide
For acromegaly, octreotide is first administered at 0.05–0.1 mg subcutaneously at intervals of 8 or 12 hours. Subsequently, the dose is selected individually. Typically, the optimal daily dose is 0.2–0.3 mg. The maximum dose of 1.5 mg per day should not be exceeded. If after 3 months of treatment there is no sufficient reduction in growth hormone levels and improvement in the clinical picture of the disease, therapy should be discontinued. For endocrine tumors of the digestive tract and pancreas, octreotide is administered subcutaneously at an initial dose of 0.05 mg 1–2 times a day. Subsequently, depending on the achieved clinical effect, the effect on the levels of hormones produced by the tumor (in the case of carcinoid tumors, the effect on the excretion of 5-hydroxyindoleacetic acid in the urine), and tolerability, the dose of octreotide can be gradually increased to 0.1–0.2 mg 3 once a day. In exceptional cases, higher doses may be required. Maintenance doses are selected individually. For refractory diarrhea in patients with AIDS, octreotide is administered subcutaneously at an initial dose of 0.1 mg 3 times a day. If after 1 week of treatment the symptoms of diarrhea do not disappear, the dose should be increased individually up to 0.25 mg 3 times a day. Dose adjustment is carried out taking into account the dynamics of bowel movements and tolerability of the drug. If no improvement occurs within 1 week of treatment with octreotide at a dose of 0.25 mg 3 times daily, therapy should be discontinued. To prevent complications after pancreatic surgery, 0.1 mg is administered subcutaneously 3 times a day for 7 consecutive days starting from the day of surgery (at least 1 hour before laparotomy). For bleeding from varicose veins of the esophagus, a dose of 25 mcg/hour is administered by continuous intravenous infusion for 5 days.
