|Year : 2023 | Volume
| Issue : 1 | Page : 21-26
Comparison of clinical effect of octreotide and pituitrin in treatment of upper gastrointestinal hemorrhage in cirrhosis
Yanli Zhu1, Yihua Ren2, Chunmei Li3, Zhaoming Si2, Nannan Chi1
1 Department of Gastroenterology, The First Affiliated Hospital of Jiamusi University, Jiamusi, Heilongjiang, China
2 Department of General Surgery, The First Affiliated Hospital of Jiamusi University, Jiamusi, Heilongjiang, China
3 Department of Infectious Disease, The First Affiliated Hospital of Jiamusi University, Jiamusi, Heilongjiang, China
|Date of Submission||14-Aug-2021|
|Date of Decision||07-Feb-2023|
|Date of Acceptance||08-Feb-2023|
|Date of Web Publication||20-Mar-2023|
No. 348 De Xiang Street, Department of Gastroenterology, The First Affiliated Hospital of Jiamusi University, Jiamusi, Heilongjiang 154002
Source of Support: None, Conflict of Interest: None
OBJECTIVE: The objective of the study was to compare and observe the therapeutic effect of octreotide and pituitrin in upper gastrointestinal hemorrhage caused by cirrhosis.
MATERIALS AND METHODS: In this prospective, randomized, open, single-blind, controlled, and single-center study, patients with upper gastrointestinal hemorrhage induced by cirrhosis were divided into control group (treated with pituitrin) and experimental group (treated with octreotide). The effective time, hemostasis time, and average bleeding volume of the two groups were observed and recorded, and the incidence of adverse reactions, rebleeding rate, and total effective rate of the two groups were compared.
RESULTS: One hundred and thirty-two patients with upper gastrointestinal hemorrhage caused by cirrhosis were included from March 2017 to September 2018. By a single-blind method, the patients were randomly divided into control group (n = 66) and experimental group (n = 66). Compared with the control group, the effective time and hemostasis time of the drug were significantly shorter in the experimental group, whereas the average bleeding volume of patients was lower (average P < 0.05). Compare with the control group, the total effective rate was higher in the experimental group, whereas the incidence of adverse reactions was lower (average P < 0.05). During 1-year follow-up, early and late rebleeding rates and hemorrhage-related mortality between the two groups have no difference (average P > 0.05).
CONCLUSION: In the treatment of upper gastrointestinal hemorrhage in cirrhosis, octreotide is superior to pituitrin, with advantages of quick onset, short hemostasis time, and less adverse reactions, which is helpful to control the rebleeding rate and bleeding-related mortality.
Keywords: Clinical efficacy, liver cirrhosis, octreotide acetate injection, pituitrin, upper gastrointestinal hemorrhage
|How to cite this article:|
Zhu Y, Ren Y, Li C, Si Z, Chi N. Comparison of clinical effect of octreotide and pituitrin in treatment of upper gastrointestinal hemorrhage in cirrhosis. Indian J Pharmacol 2023;55:21-6
|How to cite this URL:|
Zhu Y, Ren Y, Li C, Si Z, Chi N. Comparison of clinical effect of octreotide and pituitrin in treatment of upper gastrointestinal hemorrhage in cirrhosis. Indian J Pharmacol [serial online] 2023 [cited 2023 May 31];55:21-6. Available from: https://www.ijp-online.com/text.asp?2023/55/1/21/372163
| » Introduction|| |
Liver cirrhosis is a kind of chronic, progressive, and diffuse liver disease induced by a variety of different etiologies, which is common and frequent in clinical gastroenterology. With the aggravation of the disease, liver cirrhosis is likely to be complicated with upper gastrointestinal bleeding, which has a serious roles in patient's physical and mental health, and difficulties of treatment increase significantly. Esophageal gastric varices caused by increased portal vein pressure are the main mechanism of upper gastrointestinal bleeding in liver cirrhosis, which is characterized by sudden, hematemesis and danger, and is often accompanied by bloody stool symptoms. Patients' vital signs such as blood pressure, pulse, and body temperature are extremely unstable and excessive bleeding can further cause hemorrhagic shock and endanger their life. According to statistics, the clinical mortality of liver cirrhosis with sudden upper gastrointestinal hemorrhage is as high as 30%–70%. It has significance to investigate clinically feasible and effective hemostatic measures and treatment plans to control the disease progression and reduce the mortality. Drug hemostasis is effective in liver cirrhosis and upper gastrointestinal hemorrhage therapy, but there are still some controversies over which drug regimen to choose. Hence, the study investigated application effect of octreotide and pituitrin through comparative analysis.
| » Materials and Methods|| |
This study was an open, single-center, single-blind, randomized controlled, and prospective study, which was carried out under the approval of the ethics committee and with the informed consent of patients and their families. From March 2017 to September 2018, a total of 132 patients with upper gastrointestinal hemorrhage induced by liver cirrhosis were enrolled in the study. The inclusion criteria were: (1) the patient was diagnosed with the first upper gastrointestinal hemorrhage in liver cirrhosis, which met relevant diagnostic criteria; (2) age: 30–70-year-old; gender: unlimited; (3) patients voluntarily accepted the drug treatment and signed the informed consent before enrolling. The exclusion criteria were: (1) there was severe dysfunction of liver and kidney organs; (2) primary liver cancer; (3) upper gastrointestinal hemorrhage caused by a peptic ulcer, gastric cancer, and other reasons; (4) those who suffer from mental illness and cannot communicate normally. Moreover, the rejection criteria were that the falloff patients were taken follow-up visits within 1 year since postdischarge.
A total of 132 patients with upper gastrointestinal hemorrhage caused by cirrhosis were randomly divided into control group (n = 66) and experimental group (n = 66). After admission, all patients were treated with regular symptomatic treatment, such as fluid replacement, correction of water-electrolyte disorder, maintenance of acid–base balance, inhibition of gastric acid secretion, Vitamin K supplementation, liver protection, and blood transfusion. On this basis, the control group was treated with pituitrin (Manufacturer: Nanjing Xinbai Pharmaceutical Co., Ltd.; Approval No: Gyzz h2026637; Specification: 1 ml: 6 U), followed by intravenous injection of 6U, then 500 ml glucose injection (concentration 5%) was added with pituitrin 36U intravenous infusion. In the experimental group, 0.1 mg of octreotide acetate injection (Manufacturer: Beijing Baiao Pharmaceutical Co., Ltd.; Approval No: Gyzz h20061309; Specification: 1 ml: 0.1 mg) was added to 20 ml of sodium chloride solution (concentration 0.9%) for intravenous administration, and then 500 ml of sodium chloride solution or glucose injection was added to 0.5 mg of octreotide for intravenous administration at a rate of 30–50 μg/h. The vital signs and adverse reactions, such as heart rate, pulse, blood pressure, and bleeding volume, were closely monitored for 3–7 days.
The mean time of drug onset, hemostasis time, and upper gastrointestinal bleeding volume in each group was observed and recorded. The positive stool occult blood test indicated that the daily blood loss of the patient's digestive tract was ≥5 ml; the black stool indicated that the blood loss was 50–70 ml; the hematemesis indicated that stored blood volume was 250–300 ml, the hemoglobin decreased by 1 g, and the blood loss was about 400 ml, which generally evaluated by the same doctor.
Furthermore, we recorded the total effective rate, which was the sum of the significant effect and effective rate. The excellent suggested that hemostasis was successful within 24 h after treatment, and no evidence of active bleeding was found (blood pressure was stable, heart rate was <90 times/min, stool was yellow, and gastroscope confirmed that bleeding stopped), hemoglobin content was normal, and blood urea nitrogen value stopped rising. The effective suggested that hemostasis was successful within 24–72 h after treatment, and no evidence of active bleeding was found. Furthermore, the invalid suggested that the symptoms of bleeding, hematemesis, or black stool still exist after 72 h of treatment, the blood pressure, heart rate, and pulse are unstable, and the hemoglobin content continues to decrease or tends to decrease.
Besides, the early rebleeding and bleeding-related mortality were observed and recorded. Early rebleeding suggested that upper gastrointestinal bleeding occurs again within 72 h–6 weeks after effective contrast of bleeding symptoms, whereas late rebleeding suggested that upper gastrointestinal bleeding occurs again after effective contrast of bleeding symptoms for 6 weeks. Moreover, the bleeding-related mortality suggested that all cases are followed up for 1 year, and the incidence of death directly caused by rebleeding is counted.
In addition, the adverse reactions, including headache, chest distress, palpitation, nausea and vomiting, abdominal pain, abdominal distention, high blood pressure, and so on, were observed and recorded.
The data collected from the study were sorted out and established in Excel software. Statistical analysis was conducted via SPSS 20.0 software (IBM Co., Ltd, Armonk, State of New York New York, USA). Continuous data were described as x ± s, whereas the categorical data were described as percentage. The difference between groups was analyzed via Student's t-test or Chi-squared test. P < 0.05 was considered to be statistically significant.
| » Results|| |
A total of 132 patients with upper gastrointestinal hemorrhage caused by cirrhosis were randomly divided into control group (n = 66) and experimental group (n = 66), with an average age of 53.28 ± 11.34 and 52.96 ± 12.17, respectively [Table 1]. No significant difference between the two groups in average age, gender composition, and liver function (Child–Pugh) grading before treatment was observed [all P > 0.05, [Table 1]].
|Table 1: Comparison of general data of the control group and experimental group|
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As shown in [Table 2], compared with the control group, the average time of onset and hemostasis in the experimental group was significantly shorter, whereas the average amount of bleeding was lower (all P < 0.05). Besides, compared with the control group, the total effective rate in the experimental group was significantly higher [P < 0.05, [Table 3] and [Figure 1]].
|Figure 1: Comparison of total effective rate of therapy of two groups of drugs|
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|Table 2: Comparison of onset time, hemostasis time, and average amount of bleeding of two groups of drugs (x̄±S)|
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|Table 3: Comparison of total effective rate of therapy of two groups of drugs n (%)|
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It was found that adverse reaction incidence between the two groups was different [Table 4] and [Figure 2]. Compare with the experimental group, incidence of headache in the control group was higher, while no difference in the incidence of chest distress, palpitation, nausea and vomiting, stomachache and abdominal distension, and elevation of blood pressure between the two groups [P < 0.05, [Figure 2] and [Table 4]].
|Table 4: Comparison of adverse reaction of two groups of therapies n (%)|
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During the follow-up period, there was no loss of follow-up in both groups. As shown in [Table 5], during 1-year follow-up, no significant difference was observed in the early and late rebleeding rate and mortality between the two groups (all P > 0.05).
|Table 5: Comparison of rebleeding rate and bleeding-related case fatality rate of two groups n (%)|
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| » Discussions|| |
Liver cirrhosis, as a chronic liver disease of the digestive system, usually starts insidiously and develops slowly. Its pathological features are mainly manifested as diffuse fibrosis of liver tissue, accompanied by changes of pseudolobule and regenerative nodule. In the late stage, liver dysfunction, portal hypertension, and various complications occur. Upper gastrointestinal hemorrhage is a common serious complication in the course of liver cirrhosis, which is often fierce, large amount of bleeding, and dangerous. The difficulty of clinical treatment is significantly increased, and the risk of death is significantly increased. As a terminal stage of chronic liver disease, liver cirrhosis can be induced by various causes. The morbidity and mortality in China are at a high level, and it is also a common and fatal cause globally. The incidence of cirrhosis complicated with upper gastrointestinal hemorrhage is also increasing year by year. The treatment measures mainly include endoscopic hemostasis, compression hemostasis with three cavities and two capsules, and hemostasis with drugs. Although endoscopic hemostasis can obtain good hemostasis effect, it is difficult to operate in the emergency treatment process, and other organs may be damaged due to many uncertain factors. Besides, the use of three-cavity and two-capsule tube compression hemostasis will not only make patients feel pain, but also easily cause local tissue degeneration and necrosis. The three-cavity and two-capsule tube is also easy to slide out of the lumen, thus pressing the throat to cause dyspnea or asphyxia. In addition, this hemostasis method has a high probability of rebleeding after extubation, and its clinical application is, obviously, limited. Thus, it can be seen that drugs are the most feasible and optimal treatment plan during the emergency treatment of upper gastrointestinal hemorrhage, which is of great significance to save patients' lives and strive for treatment opportunities. It is the key to reduce the pressure of portal vein and collateral circulation by effective hemostasis combined with relevant symptomatic treatment.
Clinical studies have shown that no matter what kind of chronic liver disease causes cirrhosis, when the course of the disease enters the decompensated stage, a series of symptoms including form portal hypertension and increased pressure of the portal vein followed by complex portal collateral circulation such as esophageal fundus varices. The rupture of esophageal gastric varices is the main cause of sudden upper gastrointestinal bleeding and causes the highest mortality. Esophageal fundus varices can lead to increase of blood volume, reflux injury of gastric juice, and esophageal mucosa. At this time, the increase of intraperitoneal pressure or injury stimulated by hard food and other factors may cause blood vessel rupture and bleeding. If the hemostasis measures cannot be taken in time and the amount of bleeding is too large, it may lead to hemorrhagic shock or death. According to the survey, about 30%–50% of patients with cirrhosis are bleeding due to esophageal fundus varices rupture, and half of them may have upper gastrointestinal bleeding again within 1–2 years after treatment. Both octreotide acetate and pituitrin will effectively reduce the pressure of the portal vein and reduce bleeding. Pituitrin is a water-soluble component extracted from the posterior pituitary of pigs and cows. It contains oxytocin and vasopressin. The former is mainly used to stimulate the contraction of uterine smooth muscle, whereas the latter is also called antidiuretic urea, which may reduce the amount of urine in animals and has a significant effect of the contraction of visceral blood vessels, capillaries, and raising blood pressure. The main mechanism of this product for the treatment of esophagogastric varices is to contract internal arteries and small blood vessels, reduce the blood flow of the internal organs, promote the decrease of the internal pressure of esophagogastric varices, stimulate the contraction of the lower segment of the venous plexus, effectively reduce the blood flow of the vein, increase lower esophageal sphincter tension, and finally achieve a goal of hemostasis. However, due to the low drug selectivity of pituitrin, it may cause systemic vasoconstriction in patients, which can cause serious adverse reactions such as myocardial ischemia, arrhythmia, and cerebrovascular accident, thus increasing the risk of upper gastrointestinal rebleeding.
Octreotide is a synthetic octapeptide ring compound. Its drug action is similar to that of natural endogenous somatostatin, but its half-life period is longer than that of natural somatostatin, and its effect is stronger and longer. After intravenous administration, octreotide will quickly take effect, selectively reduce the blood flow and pressure of portal vein and collateral circulation, so as to inhibit the secretion of glucagon, and to some extent, prevent glucagon from expanding the internal vessels. Compared with pituitrin, octreotide has the advantages of quick onset and strong selectivity, which greatly avoids the serious adverse reactions caused by systemic vasoconstriction. In addition, octreotide can keep platelet aggregation, clear pepsin activity, has good hemostatic effect, and has little effect on systemic hemodynamics. At present, this product has become the first choice in the treatment of upper gastrointestinal bleeding caused by esophageal fundus varices rupture in cirrhosis. According to the research data, 66 patients in the experimental group had better drug onset time, hemostasis time, and average bleeding volume index, which confirmed that octreotide acetate had a faster onset time and shorter hemostasis time than pituitrin. Besides, in the experimental group, the total effective rate was significantly increased, and the adverse reactions decreased, indicating that octreotide treatment plan was conducive to improving the efficacy and clinical safety. In addition, in the control group, the rebleeding rate increased, and one patient died of rebleeding within 1 year after treatment, but no significant difference was observed between the two groups, suggesting that octreotide acetate treatment had little effect on upper gastrointestinal rebleeding in patients with liver cirrhosis.
| » Conclusion|| |
Octreotide acetate injection has the advantages of rapid onset, short hemostasis time, and less adverse reactions in the treatment of upper gastrointestinal hemorrhage in cirrhosis, and its clinical effect is significantly better than pituitrin, which has positive significance in the control of rebleeding rate and decrease of the mortality related to hemorrhage.
Financial support and sponsorship
Scientific Research Project of Heilongjiang Provincial Health and Family Planning Commission (No. 2017-390).
Conflicts of interest
There are no conflicts of interest.
| » References|| |
Molina TL, Krisl JC, Donahue KR, Varnado S. Gastrointestinal bleeding in left ventricular assist device: Octreotide and other treatment modalities. ASAIO J 2018;64:433-9.
Wang CY, Hu DS, Wen J, Lu W, Li J. Upper gastrointestinal bleeding caused by exfoliative esophagitis in one patient with hepatitis B cirrhosis. Zhonghua Gan Zang Bing Za Zhi 2017;25:868-9.
Shuai J, Ying L, Chang-Xue J, Biao Z. Application of degree of portal systemic shunting in assessing upper gastrointestinal bleeding in patients with schistosomiasis cirrhosis. Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi 2017;29:286-9.
Martins NB, Chaput KJ, Stawicki SP, Modi R. Octreotide as an adjunct in the management of arterial gastrointestinal bleeding: Should it be considered in refractory cases of obscure origin? Int J Crit Illn Inj Sci 2017;7:8-11.
] [Full text]
Thabut D, D'Amico G, Tan P, De Franchis R, Fabricius S, Lebrec D, et al.
Diagnostic performance of Baveno IV criteria in cirrhotic patients with upper gastrointestinal bleeding: Analysis of the F7 liver-1288 study population. J Hepatol 2010;53:1029-34.
Zhang J, Ying H, Wei L, Hong LJ. Effect of nucleoside analogues in the treatment of hepatitis B cirrhosis and its effect on Th17 cell. Eur Rev Med Pharmacol Sci 2017;21:416-20.
Wedi E, von Renteln D, Gonzalez S, Tkachenko O, Jung C, Orkut S, et al.
Use of the over-the-scope-clip (OTSC) in non-variceal upper gastrointestinal bleeding in patients with severe cardiovascular comorbidities: A retrospective study. Endosc Int Open 2017;5:E875-82.
Rassameehiran S, Teerakanok J, Suchartlikitwong S, Nugent K. Utility of the shock index for risk stratification in patients with acute upper gastrointestinal bleeding. South Med J 2017;110:738-43.
Jiang S, Li W, Zhou S. Safety and clinical efficacy of three types stents of transjugular intrahepatic porto-systemic shunt in treatment of cirrhosis with portal hypertension. Chin J Intervent Imaging Ther 2017;14:343-6.
Dalezis P, Trafalis DT, Geromichalos GD, Pissimissis N, Panagiotopoulou D, Galaktidou G, et al.
Adriamycin in combination with dexamethasone and octreotide lacks activity on the treatment of a 4T1 metastatic breast cancer model. Anticancer Drugs 2017;28:489-502.
Orloff MJ, Isenberg JI, Wheeler HO, Haynes KS, Horacio JB, Rapier R, et al.
Portal-systemic encephalopathy in a randomized controlled trial of endoscopic sclerotherapy versus emergency portacaval shunt treatment of acutely bleeding esophageal varices in cirrhosis. Ann Surg 2009;250:598-610.
Rössle M, Schultheiss M. Timing of the treatment of portal vein thrombosis in patients with cirrhosis: A German hepatologist's perspective. J Transl Int Med 2018;6:11-5.
Gai XD, Wu WF. Effect of entecavir in the treatment of patients with hepatitis B virus-related compensated and decompensated cirrhosis. Exp Ther Med 2017;14:3908-14.
Bucsics T, Hoffman S, Grünberger J, Schoder M, Matzek W, Stadlmann A, et al.
ePTFE-TIPS vs. repetitive LVP plus albumin for the treatment of refractory ascites in patients with cirrhosis. Liver Int 2018;38:1036-44.
Wang Y, Wang W, Jin K, Fang C, Lin Y, Xue L, et al.
Somatostatin receptor expression indicates improved prognosis in gastroenteropancreatic neuroendocrine neoplasm, and octreotide long-acting release is effective and safe in Chinese patients with advanced gastroenteropancreatic neuroendocrine tumors. Oncol Lett 2017;13:1165-74.
Luna-Gutiérrez M, Hernández-Jiménez T, Serrano-Espinoza L, Pea-Flores A, and Soto-Abundiz A.
Freeze-dried multi-dose kits for the fast preparation of 177 Lu-Tyr 3 -octreotide and 177 Lu-PSMA (inhibitor) under GMP conditions. J Radioanal Nucl Chem 2017.
[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]