UDK 616.32/.34-005.1-072.1/.2
COBISS.SR-ID 283223564

Uzrok krvarenja iz gornjih partija digestivnog trakta i hitna gastroskopija u urgentnom centru KC Kragujevac
(The causes of upper gastrointestinal bleeding and urgent gastroscopy at the center for emergency medicine of the Clinical Center Kragujevac)

Biljana Milojković Kicevska (1), Zoran Kovačević (1), Mirjana A. Janićijević Petrović (2),
Katarina Janićijević (2)

(1) DEPARTMENT OF INTERNAL MEDICINE, CLINICAL CENTRE OF KRAGUJEVAC, KRAGUJEVAC, SERBIA; (2) DEPARTMENT OF OPHTHALMOLOGY, FACULTY OF MEDICAL SCIENCES, UNIVERSITY OF KRAGUJEVAC, KRAGUJEVAC, SERBIA
 

INTRODUCTION

Gastrointestinal bleeding is defined by the appearance of blood in the digestive tube. The clinical manifestation of bleeding depends on the site of bleeding, the severity of bleeding, and the existence of co-morbidities, and it is divided into bleeding from the upper (90%) and bleeding from the lower intestinal tract (10%) [1, 2, 3]. In the case of a hemodynamic unstable patient, the measures that are applied are the hemodynamic restitution with infusion solution, oxygen therapy, and reimbursement of blood derivatives, with constant monitoring of vital parameters. Emergency esophagogastroscopy is the method of choice and is conducted according to the protocol in the first 12-24 hours [4]. Endoscopic examinations, as a special type of examinations, or within fiber pan-endoscopy, are carried out for diagnostic and interventional purposes (operative-therapeutic) [4]. The most common indications for diagnostic and therapeutic endoscopy of the upper gastrointestinal tract are: pyrosis or persistent pain despite medication therapy, dysphagia, odynophagia, the evaluation of the symptoms of hematemesis or hidden bleeding after surgery, the evaluation of abnormal contrast radiography, biopsy of gastric ulcers and neo-plastic lesions [4, 5]. Specific indications are foreign body extraction and assessment of the degree of mucosal lesions after the caustic ingestion and the control of pre-malignant conditions, Barrett's esophagus and gastric polyps [5, 6, 7]. Contraindications are: acute respiratory and cardiovascular insufficiency; coma and delirium types of different origin; acute corrosive changes in the esophagus; indiscipline and lack of cooperation of the patient during the examination. Eight hours prior to the intervention the patient must not take anything by mouth, except in emergencies, if acute bleeding in the upper parts of the digestive tube occurs, in which case immediately after the arrival and hospitalization, the nasogastric tube is placed into the patient; this not only has the diagnostic role, but also a role in preparing a patient for urgent esophagogastroduodenoscopy as well [8]. Esophagogastroduodenoscopy allows inspection of the upper segment of the gastrointestinal tract, thus called upper pan-endoscopy. Endoscopic examination analyzes lumen, motility, the appearance of mucosa, and taking biopsy of cytological samples or aspirates from the lumen [9]. Esophageal and cardiac cancers are endoscopic observed, as well as the changes such as plaque, nodular thickening or ulcerative lesions. Gastric lesions which are endoscopic identified: congenital abnormalities, vascular malformations, postoperative mucosal changes, foreign bodies, hiatus hernia, pyloric stenosis which is observed due to pyloric hypertrophy or inflammation. Gastric inflammatory lesions are common findings on the endoscopy and include various forms: gastritis, fresh ulceration or infiltrative process, such as an eosinophilic granuloma. Vascular lesions: gastric varices, arteriovenous gastric ectasia, angiodysplasia and "watermelon stomach" are identified as bleeding sites [10]. Of all the sources of bleeding from the upper intestine, one third accounts for the esophagus (36%), the varicose veins of the esophagus, then Mallory-Weiss syndrome, esophageal cancer, and esophagitis. Another third (about 37%) belongs to the sources from the stomach, where the most common are ulcer and erosive gastritis, and less often gastric cancer. The remaining 27% of cases of bleeding belong to the duodenum, where the most common is ulcer, the rare diverticular bleeding, or the bleeding from multiple duodenal erosions [11].

MATERIAL AND METHODS

The study was conducted at the Clinical Center Kragujevac, by combining retrospective and prospective research methodology. The study included 200 patients, who were reported to the outpatients’ department of the Center for Emergency Medicine of the Clinical Center with clinical signs of bleeding from the upper parts of the digestive tract (hematemesis, melena). Patients were presented with their rights and obligations that they assumed for participating in the study, as well as the potential risks and disadvantages of the study. In addition to the detailed anamnesis and an initial examination, complete laboratory analysis, emergency and contol esophago-gastroduodenoscopy and echosonography of the abdomen were performed for each patient. Apart from determining the clinical and laboratory parameters, specific demographic data of patients were collected: age, sex, profession, place of residence, associated disease and intake of medication, as well as information about any possible episodes of previous bleeding from the gastrointestinal tract. The patients of both sexes, aged 16 to 80 years, were included. Including criteria was: the patients with symptoms of bleeding of the upper parts of the digestive tract (hematemesis, melena) and the patients who had signed a voluntary consent for the endoscopic procedure. Excluding criteria was: the patients under 16, pregnant or lactating women, the patients with malignancies on cytostatic therapy, the patients with other life-threatening conditions and the ones who refused endoscopy. The study used the "convenience" sample (subjects that met criteria were included in succession). The information on basic patients’ characteristics were analyzed and presented using descriptive statistics method. For continuous variables, the mean values ± standard deviation were used, minimum and maximum, if the data followed a normal distribution, or the median and percentiles if the data did not follow a normal distribution, while the frequency (percentages) was used for categorical variables. All the data were analyzed using the IBM statistics SPSS version 21 software.

RESULTS

The distribution of patients by gender was 40% of females and 60% of males. The average age of patients was 68.64 years with a standard deviation of 14.3 years. The oldest patient was 94 years old, the youngest 25 years old. Based on the average age of the patients (68.64 ± 14.3) these were elderly patients. Out of the 200 patients, 92 patients (46.5%) had hematemesis, 152 patients (76.8%) had melena, while 46 patients (23.2%) had both symptoms. The average value and standard deviation value of hemoglobin, platelet count, INR (international normalized ratio of prothrombin time) are shown in Table 1.

Table 1. The average value and standard deviation value of hemoglobin,
platelet count and INR
Tabela 1. Srednje vrednosti i standardne devijacije, hemoglobina, broja trombocita i INR

The average time elapsed from the first esophago-gastroduodenoscopy in the study participants was 6.5 hours. In 54 patients (27.3%), the presence of acute bleeding was revealed by endoscopy, in 10 patients (5.1%) the existence of Mallory-Weiss syndrome, in 46 patients (23.2%) the existence of erosive changes. In the majority of the patients 164 (82.8%), the presence of ulcerative changes of different localization and the degree of damage was found.
The Forrest classification of endoscopic observed bleeding is shown in Graph 1

Graph 1. The Forrest classification of endoscopic observed bleeding
Grafikon 1. Forrest Klasifikacija endoskopski utvrđenog krvarenja

The localization of identified ulcerative changes on the esophagus were 22 (11.1%), stomach 116 (58.6%) and duodenum 32 (16.3). In 60 patients with an ulcerative change at the level of the stomach, the change was located in the gastric antrum, which is 52% of all gastric ulcers. The infiltrates in histological "bioptate" preparations collected during endoscopies, were observed in 16 patients (8.1%). Only 6 patients (3%) had polypoid changes. Endoscopic treatment was performed in 44 patients (22.2%), whereby the various forms of this treatment were applied evenly, such as the usage of adrenaline locally, the placement of mechanical hemo-clips or a combination of previous two. In 38 patients (86.4%) endoscopic treatment was successful, while in 6 patients (13.6%) a surgical intervention was required. After endoscopic examination it was determined that in 14 patients there was an immediate need for surgical intervention. In 20 patients (10.1%) the issue was about re-bleeding, which meant that in their medical histories there were records of previous gastrointestinal bleeding. The exposure to factors associated with the occurrence of bleeding in the gastrointestinal tract is shown in the Graphs 2, 3, 4, 5.

Graph 2. The exposure to factors associated with the occurrence of bleeding in gastrointestinal tract
Grafikon 2. Izloženost faktorima povezanim sa pojavom krvarenja iz gastrointestinalnog trakta

Graph 3.The exposure to factors associated with the occurrence of bleeding in the gastrointestinal tract
Grafikon 3. Izloženost faktorima povezanim sa pojavom krvarenja iz gastrointestinalnog trakta


Graph 4.The exposure to factors associated with the occurrence of bleeding in gastrointestinal tract
Grafikon 4. Izloženost faktorima povezanim sa pojavom krvarenja iz gastrointestinalnog trakta


Graph 5.The exposure to factors associated with the occurrence of bleeding in gastrointestinal tract
Grafikon 5. Izloženost faktorima povezanim sa pojavom krvarenja iz gastrointestinalnog trakta

Taking all comorbidities into account, hypertension is the most common - 30.4% of all participants in the study, or 50% of all the patients with some of the co-morbidities. Risk factors: aspirin (39.4%), other non-steroidal anti-inflammatory medicaments (36.4%), smoking and stress in (23.2%) of patients.

DISCUSSION

Bleeding from the digestive tract is a serious clinical problem which in most cases requires hospitalization. Due to the dramatic clinical picture and requirements for urgent therapeutic and diagnostic procedures, acute gastrointestinal bleedings are among the high priorities of pre-hospital and hospital treatments. The patients with a single episode of ulcer bleeding have twice the risk of new bleeding in their lifetime, while the patients with two episodes of bleeding have more than 35% chance of re-bleeding [12]. In the treatment of these patients, the most important are endoscopic haemostasis in order to avoid unnecessary surgery, and medicaments that reduce the acidity of the gastric juice (proton pump inhibitors). Between 3% and 15% of bleeding episodes are treated surgically [13]. Risk factors are mainly related to socio-demographic characteristics of the patients and their life habits, but risk factors are also represented by a certain group of medicaments. Oral anticoagulants, antithrombotics, corticosteroids and non-steroidal anti-inflammatory medicaments are distinguished as the most important groups. Non-steroidal anti-inflammatory drugs have significant potential for the provocation of bleeding of the upper parts of the digestive system and taking this parameter into account, the drugs from the group of selective inhibitors of cyclooxygenase2 [13, 14] are significantly safer. The most dangerous bleeding from the digestive tract may be caused by oral anticoagulants, in cases of inadequate adjustments of their doses according to the value of INR. Bleeding from the upper parts of the digestive system caused by the action of oral anticoagulants requires urgent endoscopy. The first step in the treatment of all the patients with bleeding from the digestive tract is a rapid assessment of the severity of bleeding, immediately followed by the measures of liquid volume reimbursement which include an initial fluid administration through wide intravenous lines [13, 14]. With bleeding from the upper parts of the digestive system under conditions of the highest quality of treatment, progress in the diagnostics and non-surgical methods of haemostasis, technological advances in the field of intensive care, mortality rate is 7-10% and has not changed for the last forty years [14, 15]. The level of mortality because of the bleeding from the upper parts of the digestive system requires urgent diagnostic and therapy [15]. Duodenal ulcers are definitely the leading cause of bleeding from the upper parts of the digestive tract [16]. Two traditional types of endoscopic therapy are the adrenaline therapy and the clip-based therapy [17, 18]. Esophago-gastroduodenoscopy is an efficient method for the diagnosis and treatment of the patients with bleeding from the upper parts of digestive tract [19]. In our study, esophago-gastroduodenoscopy was administered relatively quickly, with an average time of 6.5 hours from the beginning of bleeding. The world generally accepts the trend that endoscopy is the first line of treatment to stop the bleeding from the upper parts of the gastrointestinal tract. Endoscopic methods are often supplemented by using the anti-secretory therapy, although there are experts who believe that the administration of erythromycin as a prokinetic may have a positive influence on hemostasis from the gastrointestinal tract [20]. Contemporary guides advise the use of proton pump inhibitors and erythromycin, as adjuvant therapy for endoscopy with the purpose of hemostasis [21]. In spite of the high efficiency and effectiveness, endoscopic methods are still not able to reduce mortality caused by the digestive tract bleeding [22]. Despite the fact that several new endoscopic methods are presently still in the experimental phase [22, 23] and that the current results indicate that these methods are more efficient than existing endoscopic methods, it is important to emphasize that even these advanced endoscopic techniques are not followed by a reduction in mortality. The most important advantage of new endoscopic methods compared to conventional ones, in addition to undoubtedly higher efficiency, is the lower rate of complications, since the endoscopy is often known to be accompanied by the appearance of perforations and iatrogenic bleeding [23]. When referring to the certainty that endoscopic methods do not reduce mortality in patients with bleeding from the upper part of the digestive tract, it is important to note that in these patients death occurs not as a result of unsuccessful endoscopic therapy, but mainly because of the characteristics of these patients: elderly patients usually die due to the inability of the body to cope with the problems associated with the blood loss due to bleeding [24, 25]. When it comes to the implementation of pharmaco-economic aspects of endoscopy as a therapeutic option to stop the bleeding from the digestive system, the results of study that was carried out are in favor of the fact that endoscopy is a cost-effective therapeutic measure. Endoscopy is much more cost-effective than surgical operations. Surgery should be undertaken when endoscopy does not lead to the expected results. It has been shown that, from the pharmaco-economic point of view, a combination of the endoscopic methods with proton pump inhibitors can be considered to be cost-effective [26].
Esophagogastroduodenoscopy is the basic endoscopic method to stop bleeding from the upper parts of the digestive tract. Pharmaco-economic studies have shown that the implementation of these measures has an excellent cost-efficiencyratio. Today, there is a large number of endoscopic methods in the experimental phase, which should reduce the incidence of complications.In cases when the bleeding does not stop after endoscopic measures, immediate surgical intervention is indicated.

CONCLUSION

The most common cause of bleeding is gastroduodenal ulcer and erosion in three quarters of cases. and the most common symptom was melena present in 152 patients. Hemorrhages from the upper parts of the digestive tract are most commonly caused by peptic ulcers, more common in older, male patients. Risk factors are associated with the occurrence of bleeding in gastrointestinal tract mainly related to socio-demographic characteristics of the patients and their life habits, but risk factors are also represented by a certain group of medicaments. Oral anticoagulants, antithrombotics, corticosteroids and non-steroidal anti-inflammatory medicaments are distinguished as the most important groups. The first form of diagnosis and therapy is endoscopy, with an efficacy greater than 70%. Endoscopic therapy was administered to 44 patients, with 38 patients (86.4%) resulting in arresting bleeding. Two traditional types of endoscopic therapy are the adrenaline therapy and the clip-based therapy.

Conflict of interest: The authors report no conflict of interest.

REFERENCES:

1. Napier KJ, Scheerer M, Misra S. Esophageal cancer: A Review of epidemiology, pathogenesis, staging workup and treatment modalities. World Journal of Gastrointestinal Oncology. 2014;6(5):112-120.
2. Thorsen K, Søreide JA, Kvaløy JT, Glomsaker T, Søreide K. Epidemiology of perforated peptic ulcer: Age- and gender-adjusted analysis of incidence and mortality. World Journal of Gastroenterology: WJG. 2013;19(3):347-354.
3. Lau JY, Sung J, Hill C, Henderson C, Howden CW, Metz DC. Systematic review of the epidemiology of complicated peptic ulcer disease: incidence, recurrence, risk factors and mortality. Digestion.2011;84:102–113.
4. Ganz RA. A review of new surgical and endoscopic therapies for gastroesophageal reflux disease. Gastrology and hepatology. 2016;12(7):424-431.
5. Park KS. Evaluation and Management of Caustic Injuries from Ingestion of Acid or Alkaline Substances.Clinical Endoscopy. 2014;47(4):301-307.
6. Arabi NA, Musaad AM, Mohammed FAH, Ahmed EE, Abdelaziz MSE. Acute lower gastrointestinal bleeding in Sudanese patients: a study on 301 patients in a specialized centre. Arab J Gastroenterol. 2018;19(2):84-87.
7. Huh WJ, Coffey RJ, Washington MK. Ménétrier’s Disease: Its Mimickers and Pathogenesis. Journal of Pathology and Translational Medicine. 2016;50(1):10-16.
8. Expert Panels on Vascular Imaging and Gastrointestinal Imaging: Singh-Bhinder N, Kim DH, Holly BP, et al. ACR Appropriateness Criteria(®) Nonvariceal Upper Gastrointestinal Bleeding. J Am CollRadiol. 2017;14(5S):S177-S188.
9. EbrahimiBakhtavar H, MortezaBagi HR, Rahmani F, Shahsavari Nia K, Ettehadi A. Clinical Scoring Systems in Predicting the Outcome of Acute Upper Gastrointestinal Bleeding; a Narrative Review. Emerg (Tehran). 2017;5(1):e36.
10. Busch M, Schneider A, Lankisch T, von Hahn T. Acute hemorrhage in the upper gastrointestinal tract. Internist (Berl). 2017;58(3):226-232.
11. Strömdahl M, Helgeson J, Kalaitzakis E. Emergency readmission following acute upper gastrointestinal bleeding. Eur J GastroenterolHepatol.2017;29(1):73-77.
12. Nelms DW, Pelaez CA.The Acute Upper Gastrointestinal Bleed.SurgClin North Am. 2018;98(5):1047-1057.
13. Dinçer D, UlukalKarancı E, Akın M, Adanır H.NSAID, antiaggregant, and/or anticoagulant-related upper gastrointestinalbleeding: Is there any change in prophylaxis rate after a 10-year period? Turk J Gastroenterol. 2019;30(6):505-510.
14. Wang J, Cui Y, Wang J, Chen B, He Y, Chen M. Clinical epidemiological characteristics and change trend of upper gastrointestinal bleeding over the past 15 years. Zhonghua Wei Chang Wai KeZaZhi. 2017;20(4):425-431.
15. Chandnani S, Rathi P, Sonthalia N, Udgirkar S, Jain S, Contractor Q, et al. Comparison of risk scores in upper gastrointestinalbleeding in western India: A prospective analysis. Indian J Gastroenterol. 2019;38(2):117-127.
16. Minakari M, Badihian S, Jalalpour P, Sebghatollahi V. Etiology and outcome in patients with upper gastrointestinal bleeding: Study on 4747 patients in the central region of Iran. J GastroenterolHepato.l 2017;32(4):789-796.
17. Dinelli M, Omazzi B, Andreozzi P, Zucchini N, Redaelli A, Manes G. First clinical experiences with a novel endoscopic over-the-scope clip system. EndoscInt Open. 2017;5(3):E151-E156.
18. Lamberts R, Koch A, Binner C, Zachäus M, Knigge I, Bernhardt M, Halm U. Use of over-the-scope clips (OTSC) for hemostasis in gastrointestinal bleeding in patients under antithrombotic therapy. EndoscInt Open. 2017;5(5):E324-E330.
19. Dakik HK, Srygley FD, Chiu ST, Chow SC, Fisher DA. Clinical Performance of Prediction Rules and Nasogastric Lavage for the Evaluation of Upper Gastrointestinal Bleeding: A Retrospective Observational Study. Gastroenterol Res Pract. 2017;2017:3171697.
20. Park SW, Cho E, Jun CH, et al.Upper gastrointestinal ectopic variceal bleeding treated with various endoscopic modalities: Case reports and literature review. Medicine (Baltimore). 2017;96(1):e5860.
21. Fujishiro M, Iguchi M, Kakushima N, et al. Guidelines for endoscopic management of non-variceal upper gastrointestinal bleeding. Dig Endosc. 2016;28(4):363-378.
22. Speir EJ, Ermentrout RM, Martin JG.Management of Acute Lower GastrointestinalBleeding.Tech VascIntervRadiol.2017;20(4):258-262.
23. Jung K, Moon W. Role of endoscopy in acute gastrointestinalbleeding in real clinical practice: An evidence-based review. World J GastrointestEndosc. 2019;11(2):68-83.
24. Toews I, George AT, Peter JV, Kirubakaran R, Fontes LES, Ezekiel JPB, Meerpohl JJ. Interventions for preventing upper gastrointestinalbleeding in people admitted to intensive care units. Cochrane Database Syst Rev. 2018;6:CD008687.
25. Gao JY, Chen JF, Su H, Fang HY, Wu LP, Han YJ, Wang XM.Acute Massive GastrointestinalBleeding in the Elderly.J Coll Physicians Surg Pak. 2018;28(6):S78-S80.
26. Meltzer AC, Ward MJ, Gralnek IM, Pines JM. The cost-effectiveness analysis of video capsule endoscopy compared to other strategies to manage acute upper gastrointestinal hemorrhage in the ED. Am J Emerg Med.2014;32(8):823-832.