In gastroenterology, upper gastrointestinal bleeding is considered as emergency case and constitutes for relevant and frequent clinical problem. Frequency of occurrence of non-varicose upper gastrointestinal bleeding accounts for 40-150 cases per 100000 inhabitants including 7-14% fatal cases (1). Relation between lower social-financial status of patients, their age, number of associated diseases and higher incidence and mortality caused by upper gastrointestinal bleeding has been noticed (2, 3). Source of bleeding might come from oesophagus, stomach or duodenum (up to ligament of Treitz) and might lead to wide range of symptoms such as presence of intense red blood, hematemesis, coffee grounds vomiting, bloody or tarry stools (4). Number of bleeding cases have increased over the recent years as a result of numerous intake of non-steroidal anti-inflammatory drugs, antiplatelet drugs as well as drugs which inhibit reuptake of serotonin (5). It is estimated that in 8 out from 10 cases bleeding withdraws spontaneously, other 20% accounts for persistent bleedings or its recurrences which most frequently are reasons for complications and deceases (6). Efficiency of bleeding’s and its recurrences treatment on depends on clinic which manages the problem due to the fact that appropriately equipped endoscope laboratory and personnel medical experience plays crucial role.

Aim of the work is presentation of the latest opinions on non variceal upper gastrointestinal bleeding’s managing procedures.

The work is demonstrative paper, which has been created based on worldwide and polish literature dealing with evaluation of non variceal bleeding’s intensification and risk of its recurrence, with demonstration of available endoscopic therapy, pharmacological and surgical treatment methods.


RESULTS AND DISCUSSION
The most frequent cause of non variceal upper gastrointestinal bleeding is chronic peptic ulcer disease. Ulcers situated in duodenum are the reason for every fourth bleeding case. Further are ulcers of stomach and erosive gastritis which account for 15% of bleeding sources. The most important causes of non variceal upper gastrointestinal bleeding are presented in Tabl. 1.

Table 1. Main causes of upper gastrointestinal bleeding (3).

Often, reason of bleeding determines its intensity. Identification of patients included in the group of the highest risk is relevant and enables referral to the appropriate clinics and right decisions for the most efficient treatment.

Determination of bleeding intensity and risk of its recurrence

Determination of bleeding intensification, its possible course and evaluation of risk of its recurrence is significant in further therapeutic treatment. Such information determines place of patient’s hospitalization, time of endoscope procedures, intensity of pharmacotherapy and monitoring (2, 7). Most of gastroenterologist and surgeons easily determines state of patients with signs of upper gastrointestinal bleeding; however it is recommended to use prognostic point scale according to Rockall and collaborates. Such scale makes it possible to uniform and compare results between different medical clinics. Due to the fact that this technique requires only patients age, recognition of associated diseases and measurement of arterial pressure and pulse, it is considered to be fast and easy method (8). In the initial determination of patients health state the following basic laboratory tests are also recommended : morphology (especially level of Hgb, Rbc and Tbc), blood group along with serological compatibility test, coagulation group, EKG, concentration of electrolytes (K, Na), liver function test (AST, ALP, GGTP) and renal function tests (urea, creatinine) (Tabl. 2).

Table 2. The Rockall scoring system of bleeding severity

In case of points 0-2 (bleeding intensity poor or medium, patients’ stable without vital associated diseases) risk of recurrence is low and accounts for 6%, where mortality maintains within 2%. Patients who qualified into that group might be hospitalized in departments of internal medicine and subjected to endoscopy in crash course (maximum up to 24 hours since admission) (2, 4, 9, 10). Patients, who gained points equal or higher than 3 should be monitored, submitted to hemodynamic control and endoscopy. Possible result of endoscope examination along with general parameters determine place of further hospitalization. State of emergency reflects by the fact, that patient who gained points equal and higher than 8 are in almost 40% at risk of bleeding recurrence and such cases are almost in 40% fatal. Therefore, patients with intensive bleeding, with pulse rate over 100/min, low arterial pressure below 100mm Hg and at the age over 60 years old, should be sent to the accurate department under multi specialized supervision (anesthetists, gastroenterologists, surgeons) (2, 4, 9, 10). After fluid compensation, endoscope examination should be conducted. In case of very intensive bleeding, which unable stabilization of hemodynamic status of patient, endoscope examination after administration of erythromycin at the dose of 3mg/kg b.w between 30-60 min before examining should be considered. Gastro-kinetic properties of erythromycin leads to stomach emptying from blood and clots which enables evaluation of upper gastrointestinal and reduces needs for repetition of examination which might be caused by non precise display of occurred changes (11 -13).

For easier classification of changes in endoscopic picture and better determination of risk for non-variceal upper gastrointestinal bleeding’s recurrence, it is advisable to apply modified Forrest scale. Tabl. 3 presents mentioned scale along with estimated risk for bleeding recurrence (14).

Table 3. The Forrest classification of severity of bleeding from the ulcer and the risk of reebleeding depending on the endoscopic picture.

According to the presented data, the best benefits from endoscope examination refers to patients being at the highest risk of bleeding recurrence, which means patients with active bleeding (according to Forest scale Ia and Ib) and those with visible non-bleeding blood vessel (Forrest IIa). Management of cases where changes with indirect risk for bleeding have been reported raises controversy (for example clots covering change which is source of bleeding) (Forrest IIb). Formation of thrombus reflects appropriate course of healing and its elimination might prolong formation process as well as to cause dangerous secondary bleeding (15, 16). On the other side, blood vessel which is responsible for bleeding and which should be subjected to endoscope haemostatic procedures is usually located under thrombus. Two ways of management are recommended by experts. First includes adrenaline injection into central region of clot and subsequent removal of thrombus by using loop or Dormin equipment, whereas second approach deals with anti – rinse of clot. In second case, if procedure is not possible to be conducted, it might be left without endoscopic treatment. (15, 17, 18). Patients with the lowest risk of recurrence (red trait at the bottom of ulcer without visible vessel Forrest IIc, or plain ulcer’s bottom Forrest III) do not require endoscopic treatment, because in this case conservative therapy is efficient (19, 20).

Resuscitation and monitoring of patients

Resuscitation procedures depend on patients’ health state and intensity of bleeding. Refilling of infusion fluids and maintenance of appropriate arterial pressure is basis of treatment methods. In case of patients with low intensity of bleeding, with good general health condition and without crucial risk’s factors, intravenous access, hydratation, maintenance of patients at diet 0 (zero), hourly measurements of arterial pressure and pulse as well as control of diuresis is said to be appropriate management.

Patients with intensive bleeding, being in serious general condition or with numerous risk factors should be provided with double intravenous access (peripheral veins or central access), should be subjected to catheter and be maintained at diet 0. Patients qualified in that group should also have constant control of heart beating rate, arterial pressure, respiration, oxygen saturation and EKG. Hourly diuresis and central venous pressure should be controlled in order to evaluate compensation of fluids. Diuresis below 300ml/hour and central venous pressure above 5 cm H2O indicates appropriate fluids compensations (7). Usually, accurate compensation of hemodynamic parameters requires transfusion of 1500-2000 ml of isotonic salt solution or compound electrolyte solution. Non accurate filling of vascular bed after transfusion procedures indicates applications of blood replacing agents or blood transfusion. Transfusion of blood or blood replacing agents in not recommended when based only on hemoglobin level because active bleeding is dynamic process and changes which it can cause in hemodynamics do not always reflect in laboratory tests. (Despite intensive lost of blood in the first period of bleeding, level of hemoglobin might maintain unchanged.) Transfusion should be considered in case of associated diseases as well as in case of bleeding reflected by profuse bloody vomiting or bloody vomiting along with shock. Blood transfusion is highly recommended for patients with tachycardia exceeding 120 beat per minute and/or tachypnoe exceeding 30 breaths per minute. This means 30% loss of circulating blood. Tabl. 4 presents appropriate compensation of hemodynamic state (RR, pulse, diuresis, and central venous pressure) related to amount of lost blood (21).

Table 4. Hypovolemic shock: manifestations and fluid resuscitation.

Endoscopic therapy

Endoscopy conducted among patients with upper gastrointestinal bleeding is the most important diagnostic and medical tool. It enables inhibition of active bleeding, decrease of recurrence percentage, surgical procedures as well as mortality rate caused by bleedings. (2, 4, 22). However, some certain restrictions in application of endoscopic manners should be taken into consideration. Despite lack of detailed contraindications for endoscopic procedures, it has to be realized that in case of non-sufficient efficiency of mentioned techniques, they should not be applied. However, some circumstances such as solid bleeding from vessels with large diameter along with significant drop in morphology, large diameter of ulcer niche, bleeding source located on posterior wall of pyloric cap or in upper part of lesser curvature of stomach indicate efficiency limits of the mentioned techniques (23 - 25). Endoscopic methods of bleeding tamponage include injection methods, mechanical techniques and contact or non-contact coagulation.

Injection techniques include needle administration of certain substances either in the region of bleeding or directly into its source. Tabl. 5 presents substances which can be used in the mentioned techniques.

Table 5. Substances used in injection endoscopic therapy.

Solution of adrenalin in saline with concentration of 1:10000 is the most frequently used substance (26). Tamponage takes place due to compression caused by cisterns formulated as result of administrating substances around place of bleeding (tamponage) as well as due to specific activity of certain substances. Sclerosant substances (polidocanol, alcohol) cause inflammation reaction and clot in vascular lumen, whereas thrombin and fibrin seal up place of bleeding. However, experience in applying methods different than administration of adrenaline is not documented enough and there are no proves that their usage might be more efficient. Adrenaline in dose of 5-15ml leads to 95% suppression of non variceal upper gastrointestinal bleeding; however recurrences occur in almost in 20% of cases (26 - 28).

Mechanical methods of tamponage include usage of haemostatic clips. They close bleeding vessel through mechanical compression. Endoscopic loops also refers to mechanical techniques, however they are not widely applied (angiodysplasia, Dieulafoys’s lesion) (29, 30). Haemostatic clips have the widest range of applications and can be used in case of all types of bleeding changes, particularly in case of pulsating bleedings or non – bleeding visible vessels. Tightening up bleeding vessels along with surrounded tissue is optimal method for clip applications. Changes located on posterior wall of pyloric cap or on lesser curvature of stomach are especially difficult for clip usage. Such method is technically complicated and it requires experienced personnel. However this method is as efficient as thermo-coagulation techniques and more effective than injections (31 - 33).

Thermo-coagulation methods can be divided into contact and non-contact. The first one includes usage of heater probe, mono and bipolar coagulation probes. Non contact methods include argon plasma coagulation APC and Nd-Y laser. Suppression of bleeding occurs as results of coagulation of destroyed tissues surrounding bleeding vessel. Thermo-coagulation techniques can inhibit bleeding in similar percentage as injections (4, 31). Any of contact method does not show superiority to the other. There also no evidence for higher efficiency of non-contact methods when comparing to contact one.

Endoscope methods for treatment of non - variceal upper gastrointestinal bleeding do not present any significant difference in their efficiencies of bleeding suppression and in prevention of recurrences. Choice of treatment technique should mainly depend on accessibility of given method as well as on experience of personnel conducting procedure. Combination of different methods is advisable in certain cases. Higher effectiveness of double therapy when compared to mono-therapy has been proved. It is especially recommended to combine injection technique either with coagulation methods or with mechanical homeostasis (34 - 37).

When, after efficient endoscopic treatment, recurrences of bleeding occur, control endoscopy should be taken into consideration. It is recommended to make at least one attempt for another endoscopic therapy on condition that endoscope image and general health state of patients makes it possible (2, 7). In case of further recurrences, surgical treatment seems to be more efficient. It is estimated that around 20-25% of patients with bleeding recurrence, treated with endoscope methods, require surgical treatment (38). Factors which indicate risk for recurrence are the same as in case of unsuccessful first treatment. These mean: bleeding changes with high risk according to Forrets scale, solidity of bleeding, large diameter of ulcer niche and bad, general health state of patients (39, 40).

In cases other than recurrence of bleeding, routine endoscopic control is not recommended within 24-48 hours since first examination. It is also not recommended in case of uncompleted first examination and ineffective enoscopic therapy.

Pharmacotherapy

Pharmacological treatment is relevant part of upper gastrointestinal bleeding’s therapy as well as important management aiming at prevention of risk for bleeding recurrence. The major goal of therapy is efficient inhibition of hydrochloric acid’s secretion in stomach. This creates optimal condition for homoeostasis because accuracy of its elements depends on high pH values (increased platelet aggregation, suppression of degradation process of previously created platelet, removal of proteolytic influence of pepsin on thrombus) (41 - 43). Data available in literature confirms usage of proton pump inhibitors IPP as the most accurate for maintenance of pH above 6 through at least 72 hours. Comparing to histamine receptor antagonist H2 and placebo, IPP shows significantly better efficiency in prevention of bleeding recurrence (45 - 49). IPP also decreases mortality rate related to bleeding recurrence by 2-3% within the group of patients being at the highest risk of bleeding recurrences. (Active bleeding or/and visible non-bleeding vessels) (45, 49, 50). Moreover, application of IPP decreases the need for blood transfusion as well as it shortens time of hospitalization and percentage of surgical procedures (44, 51). Over the recent years, intravenous administration of IPP products has been considered to possibly stop active bleeding from digestive ulcers, to help in formation of clots and its stabilization. Some of the research works present indirect proves for benefits coming from IPP therapy applied immediately after recognition of bleedings from upper gastrointestinal (52). Stronger activity of IPP on group of patients with Asiatic origin than on those with Caucasian origin, is proved by available researches. Such difference can be overcome by administration of esomeprazol which in clinical trails showed the highest efficiency in keeping stomach pH at level >6. Ross and collaborates in their work claim that intravenously administrated esmoperazol is more effective than omeprazol, raberprazol, lanzoprazol and pantoprazol (53, 54).

Some scientists admit that for optimal prevention of non variceal bleeding recurrences, IPP should be administrated intravenously. Recommended dose is 80mg in bolus and subsequently through next 72 hours dosage of 8mg/hour (2, 7). Other publications do not show significant differences between influences of administration way (oral or intravenous) on efficient prevention of bleeding recurrence (44, 48).

In case of active bleeding which is not successfully inhibited and in case of high risk for recurrence of bleeding from digestive ulcer, application of IPP in bolus at the dose of 80mg with subsequent constant 72 hours administration at the dosage of 8mg per hour is recommended by working group associated with gastroenterologist adviser. For patients included in the group of medium risk for recurrence, it is suggested to administrate IPP intravenously at the dose of 40mg every 12 hour. (Forrest IIb, Forrest IIc). In case of patients with low risk for bleeding recurrences, working group advises oral administration of IPP at the dose of 40mg every 12 hour (55). Many of the paper works mention frequent, inappropriate application of IPP which causes decrease of predicted results as well as leads to unnecessary expenses (56 - 60).

It is observed, that the best efficiency of IPP activity refers to bleedings from digestive ulcers. (Does not depend on localization). The latest works suggest that decrease of occurrence of highly risk complications is possible on condition that IPP are used few hours before endoscopic procedures. Such approach reduces percentage of necessary endoscopic techniques (61).

Due to significantly lower efficiency in inhibition of bleeding recurrences, routine usage of H2 antagonist is not recommended (62). Most probably, low effectiveness of this group of medicines comes from fast adjustment of tolerance created even within 1-2 days of administration (63, 64). H2 blockers are accepted for use in case of lack of proton pump inhibitors. Among other medicines which might be use for suppression of upper gastrointestinal bleedings are: neutralizing and protective drugs, somatostatin, and vasopressin, antibiotics used for Helicobacter pylori eradication, cyclonamine, gastro-thrombin, and vitamin K (65). Somatostatin and analogue, due to its lower efficiency when comparing to IPP, is not recommended for routine application in treatment of upper gastrointestinal bleedings (66). However, somatostatin due to its properties for decreasing visceral blood flow, is recommended in case endoscopy can not be carried out (lack of equipment or personnel) in case of patients with contraindications for endoscopy or those with non regulated hemodynamic disorders (67).

Management in case of unsuccessful endoscopic and pharmacological treatment

In case, applied endoscopic techniques and pharmacotherapy was not successful in inhibition of primary bleeding from upper gastrointestinal or in its recurrences, surgical treatment or radiological procedures are recommended. Surgical treatment is also suggested in case of solid bleeding without identification of its source or in case when localization of bleeding source unable endoscopic procedures (lesser curvature of stomach, posterior wall of pyloric cap). Choice of surgical technique depends on localization of bleeding’s source, on age and health state of patients. In group of older patients with associated diseases and with high risk for bleeding recurrences (arterial bleeding, visible vessel with diameter >2mm, undesired localization of bleeding’s source, need for transfusion of more than 5 units of blood) it is recommended to apply surgical therapy after first endoscopic tamponage procedure. In case of urgent surgical intervention, all other endoscopic attempts significantly increase mortality rate (68 - 70). Progress in treatment of ulcer disease, thanks to usage of proton pumps inhibitors, transfer surgical treatment from the resection one (71, 72) into more sparing one (excision of ulceration, legation of vessel) designed more for suppression of bleeding than for treatment of ulcer disease (68 - 70).

Application of radiological methods is not popular; however it might become alternative to traditional surgical methods. Procedure includes embolization of either stomach – duodenum artery (in case of bleeding source located in duodenum) or left stomach artery (in case of bleedings from stomach). As embolic agents the following substances can be used: acrylic paste, micro particles of polyvinyl alcohol or geolfoam (73, 74). Percentage of recurrences accounts for 10% and efficiency for 50-80%. It is said to be positive, especially that patients who undergo embolization are usually after two endoscopic attempts (75, 76).


SUMMARY
Management of patients with symptoms of non-variceal upper gastrointestinal bleeding consists of few stages. Immediately after admission and evaluation of health state, hemodynamic compensation and monitoring of patients parameters has to be carried out. Application of nose-stomach probe should be considered, because determination of obtained secretion might determine further management. Based on clinical examination, patients should be qualified either to group with high or low risk of bleeding’s recurrences and mortality rate (77). In group of high risk, endoscopic procedure should be conducted just after hemodynamic compensation and intravenous administration of IPP at high dose. In group of patients with lower risk, endoscopic diagnosis should be carried out within 24 hours since admission. Active bleeding or visible vessels with large diameter obtained in endoscopic examination, indicates endoscopic treatment. Suppression of hydrochloric acid secretion by usage of proton pump inhibitors is vital part of pharmacological treatment. In group of high risk, treatment with IPP should be continued intravenously through next 72 hours, and subsequently oral administration should be applied. All patients with non-variceal upper gastrointestinal bleeding should be submitted for examination of Helicobacter pylori presence. In case of positive result, bacteria have to be eradicated (78).

When ulcer niche is source of bleeding, treatment with IPP product within 4-8 weeks is necessary (79, 80). Surgical therapy should be considered when solid bleeding occurs and localization of its source is difficult to be identified. It is also recommended in case of active bleeding appearing after unsuccessful primary endoscopic procedure or possibly after secondary procedure in case of recurrence. Surgical treatment is also advisable when sources of bleeding are inaccessible for endoscopic treatment.

Way of non variceal upper gastrointestinal bleeding has changed over the recent years. Designed standards make it possible to properly evaluate patient’s health state and correctly implement most accurate treatment methods. Moreover, they also enable to optimize treatment process, to improve its efficiency and decrease expense of hospitalization. Right cooperation between different specialists (gastroenterologist, surgeon, anesthetist, radiologist,) dealing with patients and between different clinic with varied references, is very important.

Conflict of interest statement: None declared.


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