2026 ESPGHAN意见书：儿童非静脉曲张性消化道出血的管理策略

POSITION STATEMENT

Endoscopy and Procedures

JPGN

# A management strategy for nonvariceal gastrointestinal bleeding in children: An ESPGHAN position paper

Mike Thomson$^{1}$ ID | Jorge Amil-Dias$^{2}$ | Amit Assa$^{3}$ | Valerio Balassone$^{4}$ | Patrick Bontems$^{5}$ | Osvaldo Borrelli$^{6}$ | Ilse Broekaert$^{7}$ | Luigi Dall'Oglio$^{4}$ | Marco Deganello Saccomani$^{8}$ | Jernej Dolinsek$^{9}$ | Simona Faraci$^{4}$ | Raoul I. Furlano$^{10}$ | Bruno Hauser$^{11}$ | Matjaž Homan$^{12}$ | Oren Ledder$^{3}$ | Erasmo Miele$^{13}$ | Priya Narula$^{1}$ | Andreia Florina Nita$^{6}$ | Salvatore Oliva$^{14}$ | Alexandra Papadopoulou$^{15}$ | Claudio Romano$^{16}$ | Dominique Schluckebier$^{1}$ | Christos Tzivinikos$^{17}$

$^{1}$Centre for Paediatric Gastroenterology and International Academy of Paediatric Endoscopy Training, Sheffield Children's Hospital NHS Foundation Trust, Sheffield, UK $^{2}$Paediatric Gastroenterology Unit, Hospital Lusiadas, Porto, Portugal

$^{3}$The Juliet Keidan Institute of Pediatric Gastroenterology and Nutrition, Shaare Zedek Medical Center, The Hebrew University, Jerusalem, Israel

$^{4}$UOC di Gastroenterologia Chirurgia ed Endoscopia Digestiva, Bambino Gesù, Ospedale Pediatrico, IRCCS, Roma, Rome, Italy

$^{5}$Hôpital Universitaire de Bruxelles, Academisch Ziekenhuis Brussel, Belgium

$^{6}$Department of Gastroenterology, Great Ormond Street Hospital for Sick Children, London, UK

$^{7}$Department of Paediatrics, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany

$^{8}$Daganello Department of Paediatrics, Woman's & Child's University Hospital of Verona, Verona, Italy

$^{9}$Department of Pediatrics, Gastroenterology Unit, University Medical Center, Maribor, Slovenia

$^{10}$Pädiatische Gastroenterologie & Ernährung, Universitäts-Kinderspital beider Basel (UKBB), Basel, Switzerland

$^{11}$Department of Paediatrics, Kidz Health Castle, University Hospital of Brussels, Brussels, Belgium

$^{12}$Department of Gastroenterology Hepatology and Nutrition, University Children's Hospital, Faculty of Medicine, University of Ljubjana, Ljubjana, Slovenia

$^{13}$Department of Translational Medical Science, Section of Pediatrics, University of Naples, Naples, Italy,

$^{1}$Pediatric Digest Endoscopy, Pediatric Gastroenterology and Liver Unit, Maternal and Child Health Department, University Hospital, Umberto I Sapienza, University of Rome, Rome, Italy

$^{15}$First Department of Pediatrics, Division of Gastroenterology and Hepatology, Children's Hospital Agia Sofia, University of Athens, Athens, Greece

$^{16}$Pediatric Gastroenterology and Cystic Fibrosis Unit, Department of Human Pathology in Adulthood and Childhood "G. Barresi", University of Messina, Messina, Italy

$^{17}$Department of Gastroenterology, Al Jalila Children's Specialty Hospital, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai, UAE

Correspondence

Mike Thomson, Centre for Paediatric Gastroenterology, Sheffield Children's Hospital, Weston Bank, Sheffield S10 2TH, UK.

Email: mthomson221168@gmail.com

KEYWORDS

endoscopy, haematemesis, haemorrhage, haemostasis, paediatric

Funding information

None

Disclaimer: Although this paper is produced by the ESPGHAN Endoscopy Working Group, it does not necessarily represent ESPGHAN policy and is not endorsed by ESPGHAN.

© 2026 European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.

THOMSON ET AL.

2

JPGN

1 | INTRODUCTION

Acute gastrointestinal bleeding (GIB) in children is often a medical emergency and it is one of few remaining that can be approached poorly with negative resultant outcomes.$^{1,2}$ No prior detailed position paper has previously been published, although the European Society of Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN)/ESGE Joint Endoscopy Guidelines included this as one area that was covered.$^{3}$ The skill base of the physicians involved in endoscopic input in this scenario is known to vary widely. This is related to the historically poor training of paediatric endoscopists (although this is rapidly changing with Hands-On Courses, etc.), to the exposure to minimal numbers of cases, to the deferment to our adult endoscopy colleagues and, until recently, to the high level of skill required to manipulate some of the accessories available. The latter has changed in the last few years with the lowering of the threshold for competency with the advent of such advances as haemostatic sprays—this and other recent advances such as over-the-scope-clips (OTSCs) will be dealt with in this paper.$^{4,5}$

The other factor contributing to poor outcome is the lack of recognition of when a child needs significant and early medical input and early endoscopic intervention. A recent scoring system, which is specific to children, has allowed identification of those children who are at most risk and, therefore, who might benefit.$^{6}$

Without up-to-date knowledge and endoscopic skills, the avoidable morbidity from GIB in children leading to significant readmission rates and even, sadly, mortality will continue.$^{7,8}$

Hence, a comprehensive examination of the available evidence combined with expert opinion of experienced practitioners in this area, drawn from the Endoscopy Working Group of the ESPGHAN, was conducted to address the major areas of clinical importance and outstanding questions in the clinical area of GIB in children.

This study will cover: (i) causes of GIB; (ii) immediate clinical response and pre-endoscopic management; (iii) which patients and clinical presentations merit urgent and semiurgent endoscopy including validated scoring systems specific to paediatrics; (iv) the timing of endoscopy; (v) techniques and accessories for cessation of variceal and nonvariceal bleeding; (vi) who should perform the endoscopy and with what training; (vii) in which patients should endoscopic reassessment predischarge be considered.

A list of relevant questions was formulated to address the most relevant issues of diagnosis and management of GIB. The literature search was then performed between October 1, 2014, and January 15, 2024, using MESH terms in PubMed, MEDLINE, EM-BASE, Cochrane Library and Scopus databases.

What is Known

* Gastrointestinal bleeding (GIB) in children can lead to significant morbidity and mortality.

* GIB is a medical emergency that should not lead to mortality or significant morbidity if the correct and prompt actions are taken.

* GIB remains the last paediatric emergency from which children may die unnecessarily with a major contribution from the lack of expertise of some medical teams.

What is New

$\bullet$ Novel haemostatic endoscopic techniques are evolving such as adherent clotting sprays, over-the-scope-clips.

* Paediatric-specific GIB endoscopic intervention scores are available which help to determine the need or otherwise for early endoscopic haemostatic intervention.

Non-English literature was excluded. The author group was divided into subgroups, and a list of references was built from the search criteria relevant to each.

Statements and recommendations were discussed in virtual meetings and an electronic vote was held to rate each of them using a six-point scale (1: strongly disagree; 2: quite disagree; 3: somewhat disagree; 4: somewhat agree; 5: quite agree; 6: strongly agree) with an opportunity to comment. These were approved if more than 80% of the participants agreed with each (grades 5–6).

Statements and recommendations were, whenever possible, based on the available evidence. When evidence from paediatric studies was not available, adult data were sought. Where there was no evidence available from randomised control trials or systematic reviews, consensus among the authors was established.

Funding was provided solely by ESPGHAN with no external funding.

Statements and recommendations are set out in Table S1 and all attained at least 80% agreement on review by the members of the Group.

2 | CAUSES OF ACUTE UPPER GASTROINTESTINAL BLEEDING (UGIB) IN CHILDREN

The aetiology of UGIB in children is heterogeneous and the exact cause depends on patient's age, co-existing disease and geographical location. In Western

THOMSON ET AL.

JPGN

countries, in fact, UGIB is mainly related to oesophageal, gastric or duoden erosions, whereas in Asia, a variceal origin is more common.$^{9-12}$ Swallowed blood from ENT sources must also be considered.

There are different ways to classify the causes of UGIB based upon: age; variceal and nonvariceal origin; and location of the bleeding. Regardless of geographic distribution, the aetiology of UGIB can be classified according to the age of presentation, but there is a considerable overlap between the causes with respect to age (Table S2).$^{9-11}$

In the first months of life, the most frequent cause of UGIB in breastfed infants is ingestion of maternal blood from nipple cutaneous damage.$^{13}$ Apt's test may distinguish maternal from infant origin. Another age-specific condition is vitamin K deficiency, especially in infants who did not receive vitamin K prophylaxis at birth.$^{14}$ Furthermore, a stress-related gastritis with ulceration may occur in critically ill newborns as well as a coagulopathy secondary to infection, liver failure or congenital coagulation factors deficiency, but these are rare.$^{15}$ Congenital anomalies, such as intestinal duplications or vascular abnormalities, should always be considered in this age group. Finally, cow's milk protein allergy (CMPA) has also been reported as a possible cause of UGIB in newborns.$^{16,17}$

In infants (due to siblings or induced illness behaviour by parents) and toddlers, caustic and foreign body ingestion (especially BBs) should be considered—hence the need for a chest X-ray at initial presentation in this age group if there is no identifiable history of cause. Gastric ulceration may be induced by medications, such as nonsteroidal anti-inflammatory drugs (NSAIDs).$^{10,15}$ Other causes include erosive oesophagitis and gastritis (e.g., Helicobacter pylori gastritis), Mallory-Weiss syndrome, characterised by vomiting-induced longitudinal tears of the distal oesophagus and VB.$^{10,15,18}$ Unusual causes of upper GIB are Dieulafoy lesions, haemangiomas, vascular malformations, tel-angiectasia, duplication cysts, vasculitis and, rarely, gastric/duodenal polyps.$^{15,19,20}$

In children and adolescents, the aetiology of GIB is similar to that of adults. The most frequent causes include erosive oesophagitis and gastritis, peptic ulcers, Mallory-Weiss tears and varices.$^{10,15,18}$ However, the unusual causes described for toddlers, although rare, should also be considered in this age group.$^{15,19,20}$ Crohn's disease has been described as a possible cause of GIB in the paediatric population, although it is unusual.$^{21}$

Congenital or acquired conditions causing structural abnormalities of blood vessels or coagulopathies can cause bleeding at any age.$^{22}$ Furthermore, the ingestion of red-coloured foods (e.g., beets, fruit juices, artificially coloured candies or drinks) can mimic the appearance of blood in vomitus and should always be considered in the differential diagnosis.$^{10}$

3 | IMMEDIATE RESPONSE IN THE EMERGENCY DEPARTMENT/ PRE-ENDOCOPIC MANAGEMENT

Regardless of the cause, assessment of patients with suspected UGIB should always begin with evaluating the patient's ABCs (airway, breathing and circulation) and vital signs. Assessment of the haemodynamic status should include vital signs, such as heart rate, blood pressure and capillary filling time, to identify the necessity for early fluid resuscitation. A baseline evaluation for detecting clues for possible diagnosis should be performed in parallel to initial management. A history of jaundice and the presence of splenomegaly suggest VB whereas epigastric pain/tenderness or a history of taking medications, such as NSAIDs, implies on the presence of gastroduodenal ulcer. Hematemesis preceded by retching or vomiting may suggest a Mallory-Weiss tear. A wide-bore cannula should be inserted intravenously to initiate fluids infusion and a nasogastric tube should be placed to check for ongoing bleeding using gastric lavage with normal saline.$^{23}$ The placement of a nasogastric tube also assists in determining the rate of gross bleeding, to clear the gastric field for subsequent endoscopic visualization and to prevent aspiration of gastric contents. The haemorrhagic risk associated with nasogastric tube insertion when rupture of oesophageal varices is suspected is unknown. There is no clear evidence allowing to recommend on the type of fluid during resuscitation. A Cochrane systematic review in adults, including 70 randomised controlled trials (RCTs), found no difference in mortality between critically ill patients who received colloids and those who received crystalloids.$^{24}$

Blood sample should be obtained for a complete blood count, coagulation panel, liver and renal function tests and blood group with cross match. All patients should be made nil per os (NPO).

In children with massive upper UGIB, transfusion with blood, platelets and clotting factors should be initiated immediately. In all other cases, the decision on blood transfusion should be made based on the full clinical picture, recognising that both over-transfusion and under-transfusion may be disadvantageous. In a study with 921 adults, a restrictive strategy of performing blood transfusion only when the haemoglobin concentration drops below 7 g/dL has shown to significantly improve outcomes in UGIB compared to a liberal transfusion strategy below 9 g/dL.$^{25}$ Blood transfusion was associated with adverse events such as increased mortality and failure of haemostasis, whereas platelet transfusion reduced the need for endoscopy in a study with 5107 adults.$^{26}$ In children, blood transfusions are usually administered to hemodynamically unstable and actively bleeding patients and if haemoglobin levels are below 7 g/dL.$^{6,11}$ The

THOMSON ET AL.

JPGN

target haemoglobin should be between 7 and 9 g/dL as over-transfusion may increase risk of re-bleeding due to increased portal pressure.$^{27}$ Platelet transfusion should be offered to patients who are actively bleeding and have a platelet count <50 × 10$^{9}$/L.$^{28}$ If fibrinogen is <1 g/L or prothrombin time (international normalized ratio) or activated partial thromboplastin time is more than 1.5 times the normal level, fresh frozen plasma should be administered.$^{28}$

When NVB is suspected, a proton-pump inhibitor (PPI) should be commenced. There are no significant differences between the five available PPIs: esome-prazole, lansoprazole, omeprazole, pantoprazole and rabeprazole. In a single paediatric trial,$^{29}$ consecutive paediatric cases who underwent endoscopic treatment for bleeding peptic ulcers were randomised into either intravenous esomeprazole bolus every 12 h for 72 h and a routine second look endoscopy within 12–24 h (n = 63) or continuous high dose esomeprazole infusion for 72 h without endoscopic reassessment unless required due to re-bleeding (n = 64). Re-bleeding rate was comparable between the two groups, implying that continuous high-dose esomeprazole infusion may diminish the need for second-look endoscopy. More-over, comprehensive systematic reviews of RCTs in adults failed to show superiority of high-dose PPI (cumulative dose >600 mg in 72 h or a continuous infusion) to intermittent PPI infusion.$^{30,31}$ Therefore, in paediatric patients with significant UGIB, intravenous PPIs should be administered either as a bolus (of 0.5–1 mg/kg), continued every 12 h for 72 h or as a loading dose of 1 mg/kg followed by 0.1 mg/kg/h continuous infusion for 72 h.$^{32}$ In a small case-series of 12 paediatric patients with NV UGIB (four with gastro-duodenal ulcers and eight with no identified origin) receiving octreotide (1–2 µg/kg/h intravenously) during 14 episodes (treatment duration 3 h to 36 days), 50% of children had resolution of bleeding during the infusion with 29% posttreatment re-bleeding but with 50% mortality rate.$^{33}$ There is no strong evidence both in adults and in children to recommend treatment with octreotide for children with NVB.

When VB is suspected, initial pharmacological treatment is based on the use of vasoactive agents such as vasopressin, somatostatin and terlipressin, which induce splachnic vasoconstriction, therefore decreasing portal vous pressure.$^{34}$ A meta-analysis comparing the results of 30 clinical trials containing more than 3000 adult patients demonstrated that patients receiving vasoactive agents had a significantly lower risk of acute all-cause mortality and transfusion requirements$^{35}$ with comparable efficacy of somatostatin, octreotide and terlipressin. Octreotide, a synthetic analogue of somatostatin with a longer half-life, has been used to treat acute VB in small case series of children with portal hypertension.$^{33,36}$ The two studies included 21 and 13 patients (35 and 18 bleeding

episodes, respectively). Octreotide was administered at a dose range of 1-2 µg/kg/h for a variable duration of time while most patients also received an intravenous bolus dose of 1-2 µg/kg immediately before continuous infusion. In both studies, bleeding ceased in approximately 70% of episodes with a re-bleeding rate of 52% and 33%, respectively. Therefore, it is recommended that in children with acute VB, intravenous octreotide (1 µg/kg bolus and 1-2 µg/kg/h infusion) should be administered as soon as possible. In the absence of paediatric data, treatment duration should be based on adult guidelines (3-5 days).$^{37}$ Whether higher dose of octreotide (3-5 µg/kg bolus and 3-5 µg/kg/h infusion) are associated with a better outcome is still unknown. Anecdototally, adverse events such as abdominal pain have been observed.

There are no studies on the use of terlipressin (a synthetic analogue of vasopressin) in paediatric patients and, consequently, no specific dose recommendations. An expert opinion paper recommended an adult-based regimen of 2 mg intravenously followed by 1–2 mg every 4–6 h for 72 h.$^{38}$

The use of a prokinetic agent such as intravenous erythromycin or metoclopramide before an emergent upper endoscopy is controversial. A meta-analysis in adults demonstrated that prokinetic drugs were associated with reduced need for a repeat OGD (odds ratio [OR]: 0.55; 95% confidence interval [CI]: 0.32–0.94),$^{39}$ but in a later RCT, no difference between erythromycin, gastric lavage and the two combined was shown in terms of conditions for endoscopy.$^{40}$ In view of the lack of paediatric data and the absence of a strong recommendation in recent adult guidelines,$^{41}$ the use of prokinetic drugs could not be recommended in children with UGIB. An ideal pre-endoscopic approach as an algorithm is set out in Appendix S1.

3.1 | Scoring systems for endoscopic

In adults with UGIB (with or without co-morbidities), there exists reasonably reliable predictive scoring systems (Rockall, Blatchford [also known as Glasgow], Addenbrooke) to identify which patients are at high risk (of mortality, re-bleeding, need for blood transfusion, surgical intervention) and require immediate endoscopic intervention and those at low risk who can be safely discharged.$^{42-47}$ These depend on morbidity assessment and are weighted for variables such as urea level, age, presence of 'shock', presence of co-morbidities such as ischaemic cardiac disease, renal failure, malignancy and so on, and are pre-endoscopic (Blatchford and Addenbrooke's scoring systems) and full or postendoscopic (Rockall scoring system). Prospective validation of these scoring systems has occurred.$^{48-51}$ There are scoring systems specific to

THOMSON ET AL.

JPGN

particular bleeding lesions such as the APACHE score which relate to peptic ulcer bleeds.$^{52,53}$ Other systems have looked to identify those at low risk when presenting with acute UGIB.$^{54}$ Yet, other groups have looked at risk of early re-bleeding and mortality risk in UGIB.$^{55-58}$ A prospective comparison study identified the Forrest classification (FC) as the most accurate in predicting rebleeding rate and mortality.$^{59}$

These have not been applied to children presenting with UGIB as most of the physiological and haematological/biochemical parameters on which they are based are not applicable to children. Indeed, pathologies leading to UGIB also differ between age groups.

The only validated UGIB scoring system available in paediatrics is the Sheffield scoring system, which is described in Table S3.$^{6}$

Important clinical parameters and predictors that emerged are set out in Table S3. Using a number of constructed models weighted for importance per each parameter's calculated potential to differentiate the child who would need endoscopic haemostatic techniques to be employed or not, it was then possible to devise an ideal scoring system with maximum positive predictive value (PPV), negative predictive value (NPV), sensitivity and specificity which could be robust, practical in the emergency setting and reliably predictive for endoscopic intervention. The multiple regression analysis allowed modelling with a number of different numerical importance assigned to each statistically differentiating parameter, and these were tested for PPV, NPV, sensitivity and specificity until the best model for these was arrived at.$^{6}$

Clinical scoring systems, of course, are no substitute for clinical assessment of a child's requirement for therapeutic intervention, but this emergency is slightly different from others in that it involves a decision for therapeutic intervention which most paediatricians first coming into contact with the child are, not unreasonably, unable to objectively provide. Ongoing prospective validation is occurring.

3.2 | Timing of endoscopic intervention

Substantial number of studies are addressing the timing of endoscopy in adults with UGIB with or without comorbidities.$^{60-72}$ However, underlying pathology in children is different, therefore, simple extrapolation of data could not properly address this challenge. Until recently, studies evaluating UGIB in children are scarce and rely on retrospective data.$^{73-75}$ There are a number of systematic reviews and meta-analyses allowing robust conclusions for adults,$^{76-83}$ from which it can be inferred that while early endoscopy (<24 h from admission) is associated with reduced transfusion requirements, very early endoscopy (<6-12 h) in some studies may not show any benefit in terms mortality,

rebleeding or need for surgery.$^{84-87}$ However, different definitions for time intervals of endoscopic intervention (e.g., urgent, very-early, early, standard, elective, delayed, late) were used in different studies. Very early (<12 h) upper gastrointestinal (GI) endoscopy is considered in patients with high-risk clinical features such as haemodynamic instability (tachycardia, hypotension) persisting despite ongoing attempts at volume resuscitation, in-hospital bloody emesis/nasogastric aspirate or contraindication to discontinuation of anticogulant therapy.$^{84}$

The European Society for Gastrointestinal Endoscopy (ESGE) in its 2015 Guidelines recommended early (≤24 h) upper GI endoscopy following successful haemodynamic resuscitation.$^{27}$ However, several years later an International Consensus Group in 2019 recommended endoscopy within 24 h after presentation for adult patients with acute UGIB.$^{41}$ While, for patients who are at high risk of further bleeding or death, the consensus group could not make a recommendation for or against performing endoscopy within 12 h versus performing endoscopy at a later time. It seems that in patients with major comorbidities, the first few hours of hospitalisation might be best utilized to optimize treatment of the comorbidities, which may include correction of severe anaemia, reversal of anticoagulants and investigation for possible infection requiring rapid treatment with antibiotics. However, this should not delay the endoscopy in patients with severe hemodynamic instability who are unresponsive to intensive resuscitation.$^{65}$

Although it is important that paediatric gastroenterologists are aware of these studies and the current recommendations for adults presenting with GIB, extrapolation to children should be done only with caution. When facing a child with AUBIG, the decision as to whether immediate endoscopic intervention is needed or if a child is at low risk and can be safely discharged home should be based on reliable parameters described in a previous section focusing on scoring systems.$^{6}$ Scoring systems should not replace the clinical assessment of a child's requirement for therapeutic intervention and the timing of endoscopy should always be based on careful clinical (re)assessment by an experienced endoscopist.$^{3}$ Depending on whether the local organisation recognizes the lack of 24/7 availability of qualified paediatric endoscopists in many centres, this may also be done by consulting an adult endoscopist who works closely with the paediatric gastroenterologist.$^{2,3}$ Out of hours, GIB services for adults are now well established and can help where available.

Before further reliable studies on acute UGIB (AUGIB) in children are conducted, we should continue to follow the existing joint paediatric gastrointestinal endoscopy guidelines published by the ESPGHAN and ESGE, which recommend that endoscopy should occur

THOMSON ET AL.

JPGN

early (<12 h) in variceal or non-variceal AUGIB cases requiring continuous circulatory support or in which large hematemesis or melena occur.$^{88,89}$ Performing OGD within 24 h is recommended in AUGIB cases requiring transfusion, where an acute drop of 20 g/L is identified, and in those who are stable but whose bleeding score is above a recognized threshold/validated score for likely need for endoscopic intervention.$^{6}$

Lower GIB (LGIB) is not considered to be an emergency in the majority of cases. Indeed, urgent colonoscopy does not reduce the rate of mortality, bleeding, identification of the bleeding source or need for surgery in adult patients with ALGIB.$^{77}$ Paediatric data are absent, however ESPGHAN and ESGE suggest that urgent therapeutic ileo-colonoscopy (IC) is usually not needed in lower GIB unless it is severe enough to cause circulatory compromise but diagnostic IC is needed as early as possible and when considered safe to perform.$^{3}$

4 | WHICH EQUIPMENT AND WHICH ENDOSCOPISTS?

The indications and technical aspects of therapeutic endoscopy for GIB are the same in children and adults. The main difference is the smaller calibre of paediatric endoscopy equipment needed to assess a smaller and more angulated anatomy in infants and young children.$^{90}$ A suggested 'toolbox' for the ideal equipment to allow for successful haemostasis in the majority of situations is set out in Table S4. The endoscopic treatments available for GIB, such as injection, thermal coagulation, band ligation and mechanical clipping, can also be performed in children above 10 kg of body weight. However, the main disparities in the management of GIB between children and adults are due to the limitations of paediatric equipment in some procedures. In most paediatric patients older than 12 months or in patients weighing more than 10–15 kg, gastroscopes with an outer diameter (OD) of 8 mm or larger may be used. For upper endoscopy in children weighing less than 10–15 kg, gastroscopes with an OD of 4.9–6.0 mm (ultrathin) are preferred, particularly for those weighing less than 5 kg. For therapeutic cases, use of a larger gastroscope may be required, but passage may not be feasible in the smallest patients. Therapeutic gastroscopes (OD: 10.9–12.9 mm) should usually be avoided in children weighing less than 10–15 kg because of the risk of mucosal injury, perforation and tracheal compression.$^{91}$ As for the haemostatic technique, mechanical clips are not compatible with paediatric upper endoscopes, with injection monotherapy being the most commonly used technique. In older children weighing at least 10 kg and tolerating a standard adult endoscope, band ligation can replace sclerotherapy to

treat bleeding varices.$^{92,93}$ Indications for thermal coagulation with contact and noncontact devices in children include bleeding ulcers and vascular lesions and most bipolar and heater probes can only fit through a standard adult endoscope. In contrast, the non-contact thermal modality, APC, has probes that are small enough to fit through the 2.0-mm working channel of the paediatric endoscope.$^{88,94}$ (Table S5) OTSCs have had recent exposure and success in children with point bleeding, that is, that from anastomotic ulcers.$^{89}$ Every paediatric endoscopy unit should have a fully equipped and stocked endoscopic haemostasis toolbox with all the accessories for injection, thermal and mechanical therapy (Table S4).$^{88}$ Recently, topical agents have been increasingly used to treat non-variceal UGIB in adults. An example of a topical agent is TC-325, also known as Hemospray® (Cook Medical, Winston-Salem).$^{4}$ Other topical haemostatic sprays/ powders include Endo-Clot®, Ankaferd Blood Stopper® and Inha University-Endoscopic Wound Dressing a new gel called Purastat®.

Endoscopic competency is defined as the minimum level of knowledge, skill and expertise required to safely and competently perform an endoscopy as an independent physician. GIB is one of the most common indications for urgent paediatric endoscopy.$^{3}$ The training guidelines recently issued by the NASPHGAN recommend 15 techniques for controlling VB and NVB to achieve proficiency.$^{95}$ The procedures for control of bleeding were classified to a level 2 competency requirement as per the recent ESPGHAN Position Paper on Training in Paediatric Endoscopy.$^{96}$ This suggests that acquiring adequate skills might require alternative training opportunities for fellows, either through computer-aided simulations, animal models, or training in adult endoscopy units. Educational programmes should ensure a curriculum for therapeutic endoscopy that includes the approach to the management of NVB. Skills specific to haemorrhage control include injection, clipping and the use of electrocautery and APC, as well as the application of endoscopic haemostatic powders and gels.$^{97-99}$

4.1 | Nonvariceal endoscopic intervention

Appendix S2 sets out an algorithm for endoscopic haemostatic therapy dependent on aetiology.

4.2 | The FC

The FC was developed about 50 years ago in an attempt to standardize the characterisation of peptic ulcers in adults.$^{27,100}$ FC has been used for decades for risk stratification for nonvariceal ulcer bleeding, but no

THOMSON ET AL.

JPGN

specific classifications exist for paediatric NVB. However, it is also of utmost importance to identify paediatric patients at risk for persistent ulcer bleeding, re-bleeding and mortality. We therefore suggest to use the FC in paediatric patients with non-variceal ulcer bleeding due to lack of other standardized classifications.

FC is defined as follows: FCla spurting haemorrhage, FClb oozing haemorrhage, FCla nonbleeding visible vessel, FClIb an adherent clot, FClIc flat pigmented spot, and FClII clean base ulcer$^{86,101,102}$ (Table S6). However, perception and interpretation of FC vary among different endoscopists.$^{103}$ Studies have shown that the presence of an ulcer endoscopically classified as FC la or FC Ib is an independent risk factor for persistent bleeding or re-bleeding.$^{104-110}$ Stigmata recognition and identification, as well as interobserver agreement, may be less than optimal, although the data are conflicting, and therefore representing a potential limitation of FC.$^{111,112}$ Apart from FC, there exist alternative endoscopic characteristics of peptic ulcers that can anticipate unfavourable results and/or ineffective endoscopic treatment. These encompass the following: ulcers exceeding 2 cm in size, large-size (>2 cm) nonbleeding visible viable vessels, presence of blood in the gastric lumen, and ulcer location on the posterior duodenal wall or the proximal lesser curvature of the stomach.$^{53,104,105,108,113,114}$

A systematic analysis of RCTs comparing endoscopic haemostasis with nonendoscopic haemostasis revealed the effectiveness of endoscopic haemostasis in preventing persistent or recurrent bleeding in actively bleeding ulcers (FC Ia, FC Ib: relative risk [RR]: 0.29, 95% CI: 0.20-0.43; number needed to treat [NNT] 2, 95% CI: 2-2) and ulcers with a nonbleeding visible vessel (FC IIa: RR: 0.49, 95% CI: 0.40-0.59; NNT 5, 95% CI: 4-6).$^{115}$ Regarding the additional benefit of acid suppression in combination with endoscopic haemostasis, a RCT and subsequent meta-analysis demonstrated the clear advantage of combining endoscopic haemostasis with PPI therapy over PPI therapy alone. This combination was effective in preventing recurrent ulcer bleeding and the need for surgery in patients with FC IIa and FC IIb ulcers.$^{116,117}$ The appropriateness of endoscopic treatment for FC IIb ulcers (adherent clot) remains controversial due to conflicting data. A study examining the natural progression of FC IIb ulcers that did not receive endoscopic haemostasis found that 25% of patients experienced rebleeding within 30 days of follow-up.$^{118}$ In patients with FC IIb ulcers, RCTs and a meta-analysis comparing medical therapy alone with endoscopic haemostasis demonstrated a significant advantage for endoscopic haemostasis in reducing ulcer rebleeding (8.2% vs. 24.7%, p<0.01), although there was no difference in the need for surgery or mortality.$^{119-121}$ However, in a separate RCT conducted by Sung et al., no instances of ulcer rebleeding

were reported in patients with adherent clots who received medical therapy alone, although the number of such patients in the trial was limited (n = 24.$^{116}$ Furthermore, a meta-analysis exclusively focused on RCTs showed no benefit for endoscopic haemostasis in patients with an adherent clot (RR: 0.31, 95% CI: 0.06–1.77).$^{122}$ In patients with peptic ulcers exhibiting a flat pigmented spot (FC IIc) or clean base (FC III), rebleeding is infrequent, and therefore, endoscopic haemostasis does not provide a significant advantage.$^{86,101,102}$

ESGE is addressing the diagnostic and management of non-variceal UGIB, with practical recommendations based on FC, which we suggest to be used also in paediatric population given the lack of dedicated classifications.$^{27}$ Appendix S3 sets out the endoscopic approaches to the different FC ulcers encountered.

4.3 | Remove the clot?

An adherent clot presents a challenge for the endoscopist. On one hand, an adherent clot (FC IIb) is considered a high-risk finding of rebleeding,$^{123,124}$ on the other hand, the clot may also serve to contain the active bleed and clot removal may exacerbate bleeding. ESGE guidelines recommend that one consider removing the clot and treat the underlying lesion, yet also providing an option to manage medically with high dose PPI for 72 h.$^{97}$ The decision as to how to proceed depends largely on the skill-set and confidence of the endoscopist. Due to the less frequent exposure of paediatric endoscopists to acute GIB than our adult colleagues,$^{1}$ clot removal should be considered only by more experienced endoscopists and/or with a support from adult colleagues. When clot removal is performed, it is recommended to initially inject 1:10,000 to 1:20,000 diluted adrenaline circumferentially at the base of the clot, followed by cold polyp snare to remove the clot,$^{27}$ ensuring that appropriate endoscopic haemostasis equipment is on hand for rapid management.

Injection therapy for NV UGIB is simple, widely used, and the cheapest haemostatic modality. Several studies demonstrated the efficacy and safety of diluted-adrenaline at the site of bleeding. It reduces blood flow by temporary creating local tamponade, vaso-constriction and improved platelet aggregation.$^{125}$

Endoscopic injection is performed using needles with an outer sheath and an inner hollow-core needle. It consists of injection of diluted adrenaline with saline to 1:10,000–1:20,000 in 0.5–2.0 mL aliquots into the mucosa surrounding the bleeding point until haemostasis is achieved. The ideal injection volume is unknown but should not be unlimited, because the systemic absorption of adrenaline occurring during endoscopy. Liou et al.

8

JPGN

THOMSON ET AL.

suggest in adults incremental doses up to a total of 30 mL to prevent re-bleeding.$^{97,126}$

Adrenaline injection should not be used as monotherapy but in conjunction with other endoscopic treatment. The combination treatment enhances the synergistic effect produced by adrenaline plus thermal (contact and noncontact) or mechanical therapy (clipping) or sclerosant agents.$^{127,128}$

In a meta-analysis, Bacarat et al. reported that adrenaline injection is effective in achieving primary haemostasis, but inferior to a combination treatment in terms of re-bleeding and surgery.$^{129,130}$

Saline injection causes local temporary tamponade. In studies comparing adrenaline monotherapy with other modalities, saline injection alone is associated with higher recurrent bleeding rates compared with other therapies. In a randomised trial with 100 patients with high-risk bleeding ulcers, recurrent bleeding occurred more often with saline monotherapy compared with thermal coagulation (29% vs. 12%).$^{122}$

The addition to adrenaline of sclerosing agents such as ethanol, ethanolamine or polidocanol would be advantageous in theory.$^{131}$ However, clinical trials have not definitively demonstrated a benefit for this combination therapy; these products can cause tissue necrosis and, therefore, facilitate the onset of complications. While no longer commonly performed, injection of absolute ethanol is another treatment option that is inexpensive and easy to perform. Ethanol causes tissue dehydration and fixation predisposing to ulceration, thrombosis and possible perforation. There exist minimal data on this approach in children.$^{132}$

4.4 | Argon plasma coagulation (APC)

APC is a thermal haemostasis technique available for non-variceal gastro-intestinal (GI) bleeding in adults and children.$^{133}$ Argon gas is ionised by a monopolar high frequency current which then fills the small gap between the electrode on the probe and the target tissue. The released energy induces contactless coagulation and dissection without carbonisation or evaporation. The depth is proportional to the application time and power setting and usually does not exceed 3 mm hence a lower risk of perforation (Figure 1).

Other advantages compared to bi- or multipolar probes are a larger area of coagulation and the availability of very thin probes (1.5 mm) for small calibre paediatric endoscopes, enable the use even in neonates and younger children. Pathologies amenable to its use in children include haemangiomata and angiosdysplasia.$^{134,135}$ It is important to avoid too close an application to the mucosa as the direct contact between the probe and the mucosa carries a minimal risk of perforation. Moreover, repeated long application should be avoided as the accumulated gas can stretch

  the bowel wall leading to potential discomfort of the patient.

4.5 | Haemostatic clips

Haemostatic clips are very useful in cases of localized bleeding. Metal clips are very effective in controlling active haemorrhage from a bleeding vessel for instance in a peptic ulcer base, Dieulafoy lesion, Mallory-Weiss tear and a polypectomy site.$^{136-138}$ Single-use pre-loaded rotatable two-pronged clips, which can be reopened and repositioned up to five times, are commercially available (Figure 2). An endoscope with a 2.8 mm biopsy channel is necessary to apply a standard clipping device, which consists of a metal cable within a metal coil sheath covered by a 2.2 mm Teflon catheter. Hence, its use is precluded in infants below 8 kg or so due to the need of larger endoscope in a

THOMSON ET AL.

JPGN

9

 FIGURE 3 Application of haemostatic endoclip.

smaller infant below 8 kg or so. (Table S5) The key aspects for a successful application of a clipping device include: good visibility of the bleeding point; precise positioning of the clip on a target lesion; full opening of the clip before deployment; minimal extension of the clipping device beyond the tip of the endoscope; and avoidance of excessive force while imbedding the clip into the tissue before deployment (Figure 3). The most challenging scenario for haemostatic clip therapy is bleeding from a large ulcer on the posterior wall of the duodenal bulb, or the superior duodenal angle.$^{137}$ Rotating the patient into prone or supine position and use of a double-channel therapeutic endoscope may improve visibility and navigation of the scope in front of the bleeding vessel to secure the optimal condition for clip deployment. The positioning of a clip proximal to the snare position before snare polypectomy is a useful preventative manoeuvre, which can avoid post-polypectomy haemorrhage.$^{139,140}$

4.6 | OTSCs

OTSC technology combines strong and large tissue grasping with different anchor mechanisms while allowing blood flow to the healing tissue (Figures 4A,B and 5). OTSCs are available in different sizes (clip/hood diameter: 8.5/11, 10.5/12, 11.5/14 mm) to fit a preloaded cap to different endoscope outer diameters. The intubation diameter of the system is an issue in children smaller than 18 kg in respect of safe oesophageal intubation (Table S5).

The reliability of OTSC in non-variceal UGIB (NVUGIB) in adults is well described. In a series of 41 adults with NVB, technical success was 100%.$^{141}$ A systematic review with a pooled meta-analysis of eight studies including 1050 patient (355 treated with OTSC vs. 695 treated with standard therapy) demonstrated

 FIGURE 4 (A) OTSC®. (B) Delivery device for the OTSC®. OTSC, over-the-scope-clip.

 FIGURE 5 Application of the OTSC® to a mucosal bleeding lesion. OTSC, over-the-scope-clip.

that OTSC consistently reduces the risk of re-bleeding within 30 days when compared with any conventional therapy (RR: 0.34, 95% CI: 0.23–0.50, p < 0.00001).$^{142}$ Another meta-analysis including 58 studies reported that the clinical success of OTSC in NVUGIB varies from 57% to 100%.$^{143}$

The experience in children is limited. A retrospective multicentric database of 20 paediatric patients treated with OTSC for different reasons (mean age 12 years, range 5–17) reported a technical success of 95% and a clinical success of 90%.$^{5}$ In a retrospective series including 11 children with NVUGIB (median weight 39 kg, range 17.4–85.8 kg), technical success and haemostasis were achieved in all cases and there were no complications.$^{144}$ Effectiveness is not established for chronic GIB (e.g., anastomotic ulcers). Data about long-term retained clips are also lacking.

10

JPGN

THOMSON ET AL.

4.7 | Cautery and settings

Thermocoagulation may be performed with a variety of equipment, including the heater probe, monopolar coagulator, bipolar/multipolar coagulators and the APC. A summary of thermocoagulation techniques/ settings is indicated in Supporting Information.

When applying contact thermal therapy, the endoscopist should use, when possible, a 10F probe. Generator settings of 25–30 J per pulse for 4–5 pulses for a total of 100–150 J should be used with a heater probe, and 15–20 W are recommended for bipolar/multipolar probes. Forceful contact using the probe should be applied for an extended period (at least 8 s), with the tip of the scope as close as possible to the treatment site to ensure complete obliteration of the culprit vessel. Failure to obliterate the culprit vessel may cause bleeding during treatment or increase the risk for re-bleeding. Excellent visualization is paramount to successful haemostasis and endoscopes with dedicated water jet should be used to treat nonvariceal GIB.$^{145}$

4.8 | The principles of electrocautery

Electrocautery utilizes thermal energy to achieve haemostasis by coagulating blood vessels and sealing tissue. The procedure involves the controlled application of an electric current through a specialized device, such as a bipolar or monopolar cautery unit. When applied to the bleeding site, the heat generated by the current helps controlling the bleeding by promoting coagulation.

4.9 | Probes for electrocautery application

Heater probes are available in two sizes: the small 2.4-mm probe is used with a 2.8-mm channel endoscope, and the large 3.2-mm probe can be used in an endoscope with a 3.7-mm channel. Multipolar probes (MPEC) (BICAP, ACMI, MA; Gold Probe, Microvasive, MA) are also available in 2.4- and 3.2-mm sizes. The use of laser requires an at least 2.8-mm channel. The probes for the APC are available in two sizes: 2.3 and 3.2 mm (Table S5).$^{145}$

4.10 | Heater probe

The heater probe is composed of a Teflon-coated hollow aluminium cylinder with an inner heater coil with a maximum internal temperature (Figure 6). A thermocoupling device at the tip of the probe maintains a constant temperature. Probe activation results in delivery of a

preselected amount of energy in Joules to the probe tip. Once the pulse has been initiated, the duration of activation is predetermined.$^{146}$ The probe reaches its operational temperature of 250°C by 0.2 s and cools by 0.5 s. Tissue coagulation occurs by direct heat transfer. The probe is water perfused to prevent tissue adherence, an advantage over monopolar coagulation. There are small (2.4 mm) and large (3.2 mm) diameter probes. The probe is passed through the therapeutic channel of the endoscope. In case of UGIB, the patient should be positioned so that the blood flows away from the ulcer base if possible, to allow optimal probe application. Heater probe coagulation is performed by initially tamponading the bleeding vessel by direct firm pressure using the heater probe, and then by coagulating the vessel. This technique, which is fundamental to the efficacy of a heater probe use, is known as coaptive coagulation. If a twin-channel instrument is used, the endoscopist is able to tamponade the bleeding with the probe while simultaneously suctioning in the region of the ulcer base. Coagulation is usually performed in adults at 2-4 successive 30 J pulses.$^{146}$

4.11 | Electrocoagulation

There are two primary types of electrocoagulation probes: monopolar probes and bipolar or multipolar probes (MPEC) (Figures 6 and 7). In monopolar coagulation, a continuous or intermittent current is applied through the tip or side of the probe, while the patient's ground plate conducts the current. The tissue in contact with the probe's tip generates high-temperature heat, leading to tissue coagulation, col-lagen contraction and vessel shrinkage. For vessels with a diameter less than 1 mm, the electrode is placed directly on the vessel, and pressure is applied to coapt it. With larger vessels, the coagulating current is applied circumferentially until bleeding ceases. Typically, a midrange setting is used, applying pulses of 1-2 s per pulse at a distance of 2-3 mm from the vessel. This approach ensures adequate haemostasis

 FIGURE 6 Heater probe.

THOMSON ET AL.

JPGN

 by treating a ring of tissue around the bleeding point, aiming to achieve haemostasis of the underlying artery rather than the overlying clot.$^{145}$ However, monopolar coagulation has two significant challenges. First, regulating the depth of the burn is challenging, particularly in the colon, which increases the risk of perforation. Cases of deep necrosis, perforation and delayed massive bleeding have been reported with monopolar electrocoagulation. Second, nonirrigated systems often experience electrode adherence to the underlying tissue at the treated site, leading to poor visibility. Additionally, the tip of the probe needs frequent cleaning due to the accumulation of coagulum during the electrocoagulation process. Due to these limitations, the bipolar probe or MPEC is commonly preferred.

4.12 | Argon plasma coagulator (APC)

The APC (see section above) is a noncontact electro-coagulation device that results in delivery of high-frequency monopolar current through ionised gas (argon plasma) to targeted tissue$^{27}$ (Figure 1). The system requires a high-frequency monopolar electro-surgical generator, an argon gas source, disposable flexible probes, a grounding pad, and foot controls that result in synchronous gas release and electrical current delivery. The probes, consisting of a Teflon tube with a tungsten monopolar electrode contained in a ceramic nozzle close to the distal end of the probe, are 2.3 or 3.2 mm outer diameter and are available in lengths of 220 or 440 cm. Probes are available to direct plasma either parallel or perpendicular to the axis of the catheter. Gas flow rates can be varied from 0.5 to 7.0 L/min, the power settings vary from 0 to 155 W, and the generator voltage ranges from 5000 to 6500 V. Argon

gas passes through the coagulation probe with an electrode at its tip. The electrode is activated by the foot switch resulting in a flow of electrically activated ionized gas from the probe to the tissue. Ionization of the gas and the presence of a return electrode (the grounding pad) results in conduction of the spark to the nearest contact point. Arrival of the current at the tissue results in coagulation. If no electrical energy is discharged by arcing to nearby tissue, then no ignition occurs, and activation of the foot switch results only in insufflation of inert argon gas. After thermal coagulation, a thin superficial electrically insulating zone of desiccation occurs. After desiccation, the electrical resistance of the treated area increases, prompting the current to move to another area of lower resistance (i.e., an untreated area).$^{27}$ The depth of coagulation is dependent on the power setting, the gas flow rate, the duration of application and the distance between the probe tip and the target tissue. The non-contact nature of the technique makes it possible to treat large areas rapidly, in comparison with the heater probe or MPEC. The treatment involves multiple sessions spaced over several weeks to allow for healing. In adults, low power settings and gas flow rates are used typically ranging from 20 to 50 W and 0.8–1.0 L/min, respectively. Vascular malformations should be treated until the mucosa turns whitish but not charred. Some precautions are necessary when dealing with right-sided colonic lesions to reduce the risk of perforation. Children may require adjustments in the treatment due to differences in gas flow rates. Postprocedure management for upper GI lesions may involve fasting, dietary restrictions and use of proton pump inhibitor for several weeks. Repeat sessions are scheduled in 4–6 weeks for vascular lesions. Besides vascular lesions, APC can be used in combination with injection therapy for adults with peptic ulcer bleeding and high-risk stigmata. The effectiveness of APC combined with adrenaline is comparable to a combination of heater probe and adrenaline injection. To ensure optimal use of the APC, a settings allow for closer tissue contact and prevent arcing of the current. It is essential to clear the surface of liquid and blood before treatment to achieve adequate results. The correct technique involves painting the surface to be treated by extending the probe and moving the endoscope shaft. Contact between the probe tip and tissue should be avoided to prevent deep tissue injury.

4.13 | Hot biopsy forceps

Another coagulation device commonly used in the colon is the hot biopsy forceps. These forceps serve a dual purpose by enabling both biopsy and coagulation of small sessile colonic polyps while preserving histological features after coagulation. They have also demonstrated

THOMSON ET AL.

JPGN

effectiveness in treating vascular ectasias. To utilize these forceps, a minimum 2.8 mm endoscopic channel is required. This technique combines the principles of endoscopic biopsy and monopolar electrocoagulation, necessitating patient grounding. The procedure begins by grasping the lesion including polyps up to 5 mm with the jaw of insulated biopsy forceps. Subsequently, the forceps are used to elevate the mucosa, separating it from the colonic muscular layer. A brief electrocoagulating current is then applied through the forceps to the mucosa and occasionally the submucosa. This results in coagulation at the base of the lesion while preserving the histological integrity of the specimen. The coagulation mode is typically set with no cutting at a power setting of 10–15 W for 1–2 s in the distance of 2–8 mm between the probe tip and tissue is recommended. The lower power caecum and ascending colon. In the left colon, higher power settings of 15–20 W for 2 s may be used. For small angiomata of the colon, a similar technique can be employed for 1–2 s. It is important to note that higher power settings or longer application times have been associated with an increased risk of perforation, particularly in the right colon.$^{147}$

4.14 | Considerations and safety measures using electrocautery

While electrocautery is generally safe and effective, several considerations must be taken into account:

1. Proper patient selection: thorough evaluation and identification of the bleeding source are crucial for successful electrocautery application;

2. Operator expertise: electrocautery should be performed by experienced healthcare professionals who are familiar with the technique and associated risks; and

3. Monitoring and follow-up: postprocedure monitoring is essential to assess the efficacy of electrocautery and ensure that any potential complications are promptly addressed.

Electrocautery represents a valuable tool in managing GIB in children. Its ability to achieve haemostasis through targeted thermal energy application makes it a preferred modality in various clinical scenarios. However, proper patient selection, operator expertise and diligent monitoring are essential to ensure optimal outcomes and minimize complications.

4.15 | Haemostatic topical applications

4.15.1 | Hemospray®

A number of topical applications for endoscopic haemostasis are now available. Hemospray® is an inorganic

powder that, on contact with an actively bleeding site, absorbs water and forms a mechanical plug over the bleeding site, immobilising the blood and promoting clot formation$^{148}$ (Figure 8). The powder is administered by means of a carbon dioxide-powered delivery system through a catheter inserted through the working channel of an endoscope and sprayed on the bleeding site under the guidance of the endoscope without directly touching the tissue. It is not allergenic because it does not contain human or animal proteins, it is not absorbed by the body and passes through the lower GI tract within 72 h. He-mospray® is sprayed on the bleeding area in short bursts of 1–2 s until the bleeding source is completely covered with the powder and haemostasis is achieved. The advantages of these techniques over other endoscopic haemostatic devices are that they are a non-thermal method that do not require direct contact with the source of bleeding, thus minimizing the risk of tissue injury. The technique requires minimal endoscopic skills and can be performed by less experienced endoscopists, which is important considering that GIB is an emergency associated with high mortality if haemostasis is not achieved. Equipment failures are not common. The only problem that can occur is that the first catheter becomes blocked by moisture in the endoscope channel or in the intestinal lumen. In this case, the endoscopist can use the second catheter that is included in the pack. To avoid this problem, the endoscopist must flush the endoscope channel vigorously with air before inserting the catheter, avoiding direct contact of the catheter tip with fluids or mucosa.$^{4}$

Hemospray® is an effective haemostatic agent for many types of arterial bleeding, such as gastric ulcers, angiotelectasias, Dieulafoy lesions and other haemorrhagic diseases of the upper GI tract, but also bleeding after polypectomy$^{4}$,$^{149}$,$^{150}$ (Figure 9A,B). To assess the efficacy of topical haemostatic agents (THAs) in achieving haemostasis Karna et al. conducted a systematic review and meta-analysis to evaluate the efficacy of THAs for malignancy-related GIB.$^{151}$ Of the 355 citations found, 16 studies involving 530 patients were included. Primary haemostasis was achieved in 94.1% (95% CI: 9.5–96.0). Early re-bleeding was observed in 13.9% (95% CI: 9.7–19.4) and delayed re-bleeding in 11.4% (95% CI: 5.8–21.1). Aggregate re-bleeding was observed in 24.2% (95% CI: 18.5–31.0). GIB-related mortality occurred in 5.9% (95% CI: 2.2%–14.8%). Yau et al. conducted a retrospective study on the safety and efficacy of Hemospray® and examined the medical records of 19 patients who were treated with Hemos-pray® for UGIB.$^{149}$ The bleeding was due to peptic ulcers in 12 (63.2%) patients, Dieulafoy lesions in 2 (10.5%), mucosal erosion in 1 (5.3%), angiodysplastic lesions in 1 (5.3%), ampullectomy in 1 (5.3%), poly-pectomy in 1 (5.3%) and an unidentified lesion in one (5.3%). The lesions showed spurting bleeding in 4 (21.1%) patients, oozing bleeding in 11 (57.9%) and no

THOMSON ET AL.

JPGN

13

 active bleeding in 4 (21.1%). Hemospray® was given as monotherapy in 2 (10.5%) patients, as initial treatment in 1 (5.3%) and as rescue treatment in 16 (84.2%). Hemospray® was applied prophylactically to non-bleeding lesions in 4 (21.1%) patients and therapeutically to bleeding lesions in 15 (78.9%). The authors stated that acute haemostasis was achieved in 14 out of 15 (93.3%) patients, while 7 out of 18 (38.9%) patients experienced re-bleeding within 7 days. Potential adverse events occurred in two (10.5%) patients, including visceral perforation and splenic infarction. Sulz et al. prospectively studied the efficacy and safety of Hemospray® in 16 consecutive patients with active GIB.$^{152}$ The rate of successful initial haemostasis was 93.75% (15/16; salvage therapy 92.85% [13/14]; monotherapy 100% [2/2]). The re-bleeding rate within 7 days was 12.5% (2/16). One patient in whom inter-ventional radiology also failed had to undergo surgery as salvage therapy.

Masci et al. conducted a MEDLINE search for articles evaluating the efficacy and safety of traditional endoscopic haemostasis techniques and also the use of Hemospray® in relation to FC.$^{153}$ Patients with Forrest 1a–1b ulcers were treated with Hemospray® either as a single therapy or in combination with other endoscopic techniques. The mean initial haemostasis success rate for Forrest 1a–1b ulcers, which are difficult-to-treat bleeding ulcers, was 92.8% and the mean re-bleeding rate was 13.3%. All (100%) 13 patients treated with Hemospray® achieved initial haemostasis, while 3/10 showed re-bleeding with no treatment-related adverse events.

In a multicentre study in 10 European centres, 30 patients with bleeding ulcers and 33 with other NVUGIB pathologies were treated with Hemospray®. Fifty-five (87%) were treated with Hemospray® as monotherapy of whom 47 [85%; 95% CI: 76%-94%] achieved primary haemostasis with a re-bleeding rate at 7 days of 15% (95% CI: 5%-25%).$^{154}$ The rate

 of primary haemostasis for TC-325 in patients with ulcer bleeding was 76% (95% CI: 59%–93%). Eight patients, who would otherwise have required either surgery or interventional radiology, were treated with TC-325 as second-line therapy after other endoscopic treatments failed. Haemostasis was achieved in all of them with the additional administration of Hemospray®.$^{154}$ Holster et al. reported that haemostasis was achieved in all nine unselected patients with lower bleeding by the use of Hemospray®, while re-bleeding occurred in 2 (22%).$^{150}$ Cahyadi et al.$^{155}$ performed a retrospective analysis of data from 52 patients with UGIB who received Hemos-pray®: 18/52 (34.6%) patients for bleeding from peptic ulcers and 13/52 patients (25%) for bleeding after intervention. Hemospray® was used as monotherapy in 23/52 (44.2%) patients and as rescue therapy in 29/52 (55.8%) patients. Immediate haemostasis was achieved in 51/52 (98.1%) patients. Recurrent bleeding within 3 and 7 days was observed in 22/51 (43.1%) and 25/51 (49%) patients, respectively. Overall clinical success was 56.9% at day 3% and 51% at Day 7. Overall mortality was 15.4% (eight patients), bleeding-related mortality was 3.8% (two patients). There were no treatment-related adverse events.$^{155}$

Hussein et al. reported initial haemostasis in 178/202 patients (88%), while re-bleeding occurred in 26/154 (17%). Combination therapy of haemostatic sprays with other endoscopic modalities was associated with lower 30-day mortality (16%, $p < 0.05$) compared with monotherapy or rescue therapy.$^{156}$

JPGN

THOMSON ET AL.

The first paediatric study assessing the efficacy and safety of Hemospray® in children with UGIB was carried out by Thomson et al.$^{4}$ The authors reported a total of 20 applications of Hemospray® in 17 patients (eight boys) age 6.5 years (2 days to 17.75 years) and 29 age-matched patients treated with conventional end-haemostatic techniques. The haemostatic spray group achieved an initial haemostasis of 100% with a re-bleeding rate of 18%, with a failure rate after reapplication of only 6% and no adverse events. The conventional group achieved a similar initial haemostasis of 100%, with a re-bleeding rate of 24% and a failure rate of 7% requiring surgical intervention.

4.15.2 | Starch-derived haemostatic spray (EndoClot®)

A starch-derived haemostatic spray (EndoClot®, Polysaccharide Hemostatic System [PHS]) consists of absorbable haemostatic polysaccharides which, when sprayed onto a bleeding site, absorb fluid and increase the concentration of platelets, red blood cells and clotting factors at the bleeding site, promoting the clotting cascade that ends in a gelled matrix that adheres to the bleeding site. The latter is rapidly degraded within a few days by human enzymes, especially amylase. The device consists of a delivery catheter, a powder/air mixing chamber connected to a powder dispenser and an air compressor (Figure 10). Endoclot® is FDA-approved for haemostasis of nonvariceal GIB, with the exception of bleeding ulcers of FC la classification with spurting bleeding. There are only a few studies assessing the efficacy and safety of starch-derived haemostatic spray. Prei et al. assessed EndoClot® in a prospective observational trial in 58 patients

   with acute UGB.$^{157}$ The efficacy of EndoClot® was evaluated 72 h and 1 week after use in 70 patients with AGIB: 58 (83%) had UGIB and 12 (17%) had LGIB. In the upper GI tract, treatment success was achieved in 30/47 (64%) patients (95% CI: 50%~76%) after primary use and in all (100%) patients after failure of established techniques (95% CI: 70%~100%). In patients LGIB, haemostasis was achieved in 10/12 (83%) of cases (95% CI: 54%~97%). Re-bleeding occurred in 8/70 (11%), while EndoClot® served as a bridge to surgery in 7/70 (10%). The authors claimed that EndoClot® achieved effective haemostasis either as monotherapy or in combination with other techniques, with better efficacy in diffuse or extensive bleeding or when the access to the bleeding vessel was difficult. Park et al. conducted a prospective study of 30 patients with UGIB treated with EndoClot® and compared them with 60 patients with upper GIB treated with conventional therapy.$^{158}$ The authors evaluated the rate of successful haemostasis and re-bleeding between the two groups both after and before propensity score matching using the Glasgow-Blatchford score and the FC. Baseline patient characteristics, including comorbidities, vital signs and bleeding scores, were similar in the two groups. The rates of immediate haemostasis, 7-day and 30-day re-bleeding, were also similar in the two groups before and after matching. In the subgroup analysis, no significant differences in immediate haemostasis or re-bleeding rates were observed between PHP as monotherapy and PHP in combination with a conventional haemostatic method. The authors claimed no significant PHP-related complications or mortality 30 days after therapy. Vitali et al. conducted a comparison of efficacy and safety between Hemospray® and EndoClot®.$^{159}$ The majority (89%) of applications were in the upper GI tract: peptic ulcer disease (35%), oesophageal varices (7%), tumour bleeding (11.7%), reflux oesophagitis (8.7%) and diffuse bleeding and erosion (15.3%). Overall, short-term success was achieved in 125 patients (81%) and long-term in 81 patients (67%). Re-bleeding occurred in 27%. In 72 (47%) patients, Hemospray® was used as haemostatic rescue therapy. In that case, the short- and long-term success rates were 81% and 64%, respectively, with re-bleeding occurring in 32%. As primary haemostatic therapy, short- and long-term success were 82% and 69% respectively, with rebleeding occurring in 22%. Hemospray® was used more frequently for upper GIB ($p = 0.04$). The authors concluded that both haemostatic powders are able to provide effective haemostasis with no differences in short or long-term success and re-bleeding rate (Figure 11).

FIGURE 10 Endoclot® haemostatic gel.

THOMSON ET AL.

JPGN


4.15.3 | Tissue adhesives

Tissue adhesives are compounds that can be used for haemostasis, wound closure or fistula repair. The main classes of tissue adhesives are cyanoacrylate glue, fibrin glue and thrombin. Cyanoacrylate glue is mainly used for endoscopic control of bleeding gastric varices and less commonly for haemostasis of other bleeding lesions. Fibrin glue (fibrinogen and thrombin) and thrombin have been used endoscopically for haemostasis in nonvariceal UGIB.$^{160}$

4.15.4 | Cyanoacrylate glue

Cyanoacrylate is a monomer that rapidly polymerises on contact with hydroxyl ions forming a hard adhesive, which may be used for obliterating a gastric varix. Cyanoacrylate glue can be mixed with Lipiodol, an oily contrast agent, before injection. Some cyanoacrylates (e.g., Dermabond, Ethicon, Somerville, NJ; Glubran, Aspide Medical, La Talaudière, France) polymerise more slowly and, therefore, do not require the use of Lipiodol for injection. We should note that cyanoacrylate glue is not currently approved by the Food and Drug Administration for this indication. Moreover, there is a risk of severe complications, such as embolism.

The exact procedure for the injection of cyanoacrylate glue in gastric varices is not standardised. Seewald et al. performed a retrospective study showing good efficacy and safety of the injection technique, injection volume and ratio of Histoacryl/Lipiodol mixture reported by Soehendra et al.$^{161-163}$ The procedure was the following: N-butyl-2-cyanoacrylate (Histocryl; B. Braun Dexon) was mixed with Lipiodol (Guerbert) in a ratio of 0.5-0.8 mL. Up to a maximum of 1 mL of the mixture was injected with a large-gauge sclerotherapy needle into the gastric varix strictly intra-varieal to avoid ulceration using a 2 mL syringe with Luer lock (Becton, Dickinson and Company) to allow rapid injection and prevent splashing. Larger volumes should be avoided as they may increase the risk of embolism. While the needle is still in the varix, 0.8 mL of distilled water or saline was used to flush out the channel. The needle was then withdrawn and flushed with distilled water to keep it patent. The authors suggested to cover the tip of the endoscope with silicone before injecting the glue to avoid damage. Additionally, Lipiodol alone

can be injected into the working channel of the endoscope to coat it and prevent adhesion of the glue.

4.15.5 | Fibrin sealants

Fibrin sealants contain two components: highly purified, freeze-dried human fibrinogen with factor XIII and a starter solution with human thrombin. The component solutions are reconstituted with sterile water in two separate syringes immediately before use. When mixed, these agents form a clot by mimicking the final phase of the physiological clotting cascade. In this process, fibrin monomers are formed first, which then combine to form a more cross-linked fibrin polymer.

Fibrin glue is commercially available in the following preparations: Tisseel (Baxter), Evicel (Johnson & Johnson) and Hemaseel (Hemacure), which are approved for topical application and haemostasis but not for intravascular injection. They are administered via double-lumen catheters inserted through the biopsy channel of the endoscope. Fibrinogen and thrombin are injected via a double-plunger syringe that allows these two components to be mixed. It should be noted, however, that the concentrations of thrombin and fibrinogen in the above commercial preparations vary. For example, Tisseel, Evicel and Vistaseal have fibrinogen concentrations of 70, 55–85 and 80 mg/mL, respectively, compared with 2.5–25 mg/mL for cryo-precipitate (unmanipulated). If rapid clot formation (5–10 s) is desired, thrombin concentrations of 500–1000 NIH units should be used.

4.15.5.1 | Thrombin

Thrombin promotes the conversion of fibrinogen to fibrin, resulting in a local fibrin clot. It consists of a bovine-derived matrix of gelatin granules mixed with a human-derived thrombin component to form a gel-like complex. However, human-derived thrombin is currently also available commercially and from local blood banks to replace bovine thrombin. It is a liquid preparation delivered topically to a bleeding lesion through a catheter by a method similar to the use of fibrin sealant. A newer all-in-one package with human thrombin and prefilled sodium chloride syringe, with no refrigeration required, Floseal (Baxter), has been used for haeostasis in surgical cases.$^{164}$ Kubba et al. compared the use of adrenaline epinephrine with the combination of epinephrine with thrombin in 140 patients with severe GIB from peptic ulcers.$^{165}$ The combination of epinephrine and thrombin achieved sustained haeostasis more often than epinephrine alone, with a decrease in the need for blood transfusions and a significant reduction in mortality. In contrast, Balanzo et al. failed to show superiority of the combination of epinephrine with thrombin compared to epinephrine alone in 140 patients with bleeding peptic ulcers,

JPGN

THOMSON ET AL.

although the effect may be attributed to the use of lower doses of thrombin compared to the previous study (150–300 IU vs. 600–100 IU).$^{166}$ The concerns about using bovine-derived thrombin is that it can be highly immunogenic due to its biological nature, while recombinant thrombin may be less immunogenic although cross-reactions in case of previous exposure of the patient to other types of thrombin may occur. The concern regarding human thrombin is for transmitting blood-borne pathogens, such as HIV and viral hepatitis.

5 | WHEN AND IN WHOM TO RE-ENDOSCOPE?

There is limited paediatric literature available to guide this decision-making. ESPGHAN Guidelines exist for timing of repeat surveillance endoscopies in children with variceal UGIB and highlight the importance of clinical judgement to determine the interval, which may be influenced by underlying diagnosis, co-morbidity, severity of varices and risk of repeated general anaesthesia and provide guidance on suggested timing.$^{3}$ While such Guidelines exist for variceal UGIB, similar guidelines on when repeat endoscopy may be required for children with nonvariceal UGIB do not exist. However, in those with a high risk of re-bleeding, particularly if there is doubt about adequate haemos-tasis after first endoscopy, or if there is bleeding post any therapeutic procedure (e.g., polypectomy), repeat endoscopy should be considered.

In a large prospective adult study of patients with acute nonvariceal UGIB, presentation with symptoms of haemodynamic instability at admission and patients on anticoagulant, antithrombotic or NSAIDs were associated with a second-look endoscopy with no significant association with time from admission to endoscopy or bleeding presentation.$^{3}$ Site of bleeding may influence the rate of re-bleeding as well as pathology.$^{4}$ Although the Sheffield scoring system has been developed to predict the need for endoscopic therapy AUGIB in children,$^{6}$ paediatric scoring systems are needed to predict the need for repeat endoscopy in children when there is a high risk of re-bleeding. If a lesion identified at initial endoscopy requires follow-up evaluation (e.g. an isolated Dieulafoy lesion), then tattooing the area may facilitate later reassessment.$^{3}$ Endoscopy in Paediatric patients is recommended in patients with VB from grade 2 or 3 varices.$^{3}$

6 | OCCULT AND OBSCURE GI BLEEDING

When the origin of the GI bleeding is undetermined, perplexing or hidden then this is termed 'obscure' and when GI bleeding is not obvious but suspected it is termed

'occult'. These are often very difficult patients to investigate and a high degree of suspicion and low threshold for investigation must exist. Hb may be chronically low, may drop following obvious or reported bleeding, or may be normal if the blood loss is persistent but in smaller amounts. Generally and as a first step, standard upper GI endoscopy and ilecolonoscopy are indicated depending on whether haematemesis or maelaena or PR blood loss predominate. If normal then a repeat endoscopic assessment within 24 h of a bleed affords the highest chance of identifying a source. Subsequent or delayed endoscopy risks missing mucosal sources which can heal rapidly, which persists the 'obscure' nature and origin of the Gl bleeding. If the clinical situation persists and repeat standard endoscopic assessments are apparently normal then, in the presence of continuing symptoms, a wireless capsule endoscopy may be suggested (although this may occur if indicated at the repeat standard endoscopy). If the source remains obscure with ongoing haematemesis/PR blood/melaena (with or without Hb drop) then further investigation is merited and may include Doppler ultra-sound, MRI, MRE, GI bleeding scans, CT abdominal scans, CT angiograms or formal angiograms, Meckel's isotope scans (associated with a high false negative rate), balloon-assisted enteroscopy, laparoscopy and/or laparotomy-assisted enteroscopy.

If mucosal abnormality is still not identified or a source is not found then alternate reasons for ongoing symptoms should be considered, for example, drug ingestion, coagulation or platelet disorders (careful history should have raised this suspicion) and occasionally carer misreporting or over reporting of symptoms, especially if not corroborated by medical professionals—which enters the sphere of potential fictitious or induced illness (FII). Other diagnoses may include origin from other systems, for example, ENT, respiratory or gynaecological with inaccurate reporting of the exact blood loss observed. A more comprehensive treatise on this important area is outwith the scope of this document.

7 | CONCLUSIONS

Key to safe approaches in this situation is the appropriate initial management ahead of endoscopy. The choices of when, where, in whom and by whom, endoscopy should occur are then made. This is an attempt to collate all the evidence available for the management, mainly endoscopic but also in preparation for endoscopy and its clinical appropriateness, of acute GIB in children. In the main, this has tried to focus on available paediatric evidence but where lacking or insufficient then inference is drawn from adult-based studies and literature. Where evidence is still lacking, in a very small proportion of the recommendations then expert opinion is relied upon. The authors believe that this represents the most

THOMSON ET AL.

JPGN

17

comprehensive assessment of this area in children that is so far available.

CONFLICT OF INTEREST STATEMENT

Mike Thomson has received no funding from Reckitt-Benckeiser for serving on their GOR Advisory Panel. Patrick Bontems declares honoraria from Abbvie, Avanos, Bicodex, Danone, Neste and Sanofi. Christos Tzivinikos declares a travel grant in 2020 from Olympus. The remaining authors declare no conflicts of interest.

ORCID

Mike Thomson https://orcid.org/0000-0003-1721-6732

REFERENCES

1. Thomson M. There is no excuse for mortality due to lack of competency and training of paediatric endoscopists in gastrointestinal bleeding therapy in 2018. J Pediatr Gastroenterol Nutr. 2018;67(6):684-688.

2. Thomson M, Belsha D. Endoscopic management of acute gastrointestinal bleeding in children: time for a radical rethink. J Pediatr Surg. 2016;51(2):206-210.

3. Thomson M, Tringali A, Dumonceau JM, et al. Paediatric gastrointestinal endoscopy: European Society for Paediatric Gastroenterology Hepatology and Nutrition and European Society of Gastrointestinal Endoscopy guidelines. J Pediatr Gastroenterol Nutr. 2017;64(1):133-153.

4. Thomson M, Urs A, Narula P, Rao P, Belsha D. The use and safety of a novel haemostatic spray in the endoscopic management of acute nonvariceal upper gastrointestinal bleeding in children. J Pediatr Gastroenterol Nutr. 2018;67(3):e47-e50.

5. Sharma S, Barakat M, Urs A, et al. Applicability, efficacy, and safety of over-the-scope clips in children. Gastrointest Endosc. 2022;95(3):489-499.

6. Thomson MA, Leton N, Belsha D. Acute upper gastrointestinal bleeding in childhood: development of the sheffield scoring system to predict need for endoscopic therapy. J Pediatr Gastroenterol Nutr. 2015;60:632-636.

7. Attard TM, Miller M, Pant C, Thomson M. Readmission after gastrointestinal bleeding in children: a retrospective cohort study. J Pediatr. 2017;184:106-113.e4.

8. Attard TM, Miller M, Pant C, Kumar A, Thomson M. Mortality associated with gastrointestinal bleeding in children: a retrospective cohort study. World J Gastroenterol. 2017;23(9): 1608-1617.

9. Cleveland K, Ahmad N, Bishop P, Nowicki M. Upper gastro-intestinal bleeding in children: an 11-year retrospective endoscopic investigation. World J Pediatr. 2012;8(2):123-128.

10. Romano C, Oliva S, Martelloss S, et al. Pediatric gastrointestinal bleeding: perspectives from the Italian Society of Pediatric Gastroenterology. World J Gastroenterol. 2017; 23(8):1328-1337.

11. Owensby S, Taylor K, Wilkins T. Diagnosis and management of upper gastrointestinal bleeding in children. J Am Board Fam Med. 2015;28(1):144-145.

12. Poddar U. Diagnostic and therapeutic approach to upper gastrointestinal bleeding. Paediat Int Child Health. 2019; 39(1):18-22.

13. Bulstrode NW, Cuckow PM, Spitz LS. Neonatal gastrointestinal pseudohemorrhage. J R Coll Surg Edin. 1998; 43(5):355-356.

14. Burke CW. Vitamin K deficiency bleeding: overview and considerations. J Pediatr Health Care. 2013;27(3):215-221.

15. Lirio RA. Management of upper gastrointestinal bleeding in children. Gastrointest Endosc Clin N Am. 2016;26(1): 63-73.

16. Fox VL. Gastrointestinal bleeding in infancy and childhood. Gastroenterol Clin North Am. 2000;29(1):37-66.

17. Zaher MM, Ahmed EM, Morsy AA. Case report: hematemesis could be an unusual presentation of cow's milk protein allergy in children in Egypt. Egypt J Immunol. 2014;21:39-43.

18. Ba-k-Romaniszyn L, Malecka-Panas E, Czkwianianc E, Planeta-Malecka I. Mallory-Weiss syndrome in children. Dis Esophagus. 1999;12(1):65-67.

19. Itani M, Alsaied T, Charafeddine L, Yazbeck N. Dieulafoy's lesion in children. J Pediatr Gastroenterol Nutr. 2010;51(5):672-674.

20. Soukoulis IW, Liang MG, Fox VL, Mulliken JB, Alomari AI, Fishman SJ. Gastrointestinal infantile hemangioma: presentation and management. J Pediatr Gastroenterol Nutr. 2015; 61(4):415-420.

21. Pongprasobchai S, Nimitvilai S, Chasawat J, Manatsathit S. Upper gastrointestinal bleeding etiology score for predicting variceal and non-variceal bleeding. World J Gastroenterol. 2009;15(9):1099-1104.

22. Fishman SJ, Burrows PE, Leichtner AM, Mulliken JB. Gastrointestinal manifestations of vascular anomalies in childhood: varied etologies require multiple therapeutic modalities. J Pediatr Surg. 1998;33(7):1163-1167.

23. Palamidessi N. Sinert R, Falzon L, Zehtabchi S. Nasogastric aspiration and lavage in emergency department patients with hemoatechzia or melena without hematemesis. Acad Emerg Med. 2010;17:126-132.

24. Perel P, Roberts I, Ker K. Colloids versus crystalloids for fluid resuscitation in critically ill patients. Cochrane Database Syst Rev. 2013:CD000567. doi:10.1002/14651858.CD000567.pub6

55. Villanueva C, Colomo A, Bosch A, et al. Transfusion strategies for acute upper gastrointestinal bleeding. N Engl J Med. 2013; 368:11-21.

26. Fabricius R. Svenningsen P, Hillingsø J, Svendsen LB, Sillesen M. Effect of transfusion strategy in acute non-variceal upper gastrointestinal bleeding: anationwide study of 5861 hospital admissions in Denmark. World J Surg. 2016;40:1129-1136.

27. Gralnek I, Dumonceau JM, Kuipers E, et al. Diagnosis and management of nonvariceal upper gastrointestinal hemorrhage: European Society of Gastrointestinal Endoscopy (ESGE) guideline. Endoscopy. 2015;47:a1-46.

28. Dworzynski K, Pollit V, Kelsey A, Higgins B, Palmer K. Management of acute upper gastrointestinal bleeding: summary of NICE guidance. BMJ. 2012;344:e3412.

29. Belei O, Olariu L, Puiu M, et al. Continuous esomeprazole infusion versus bolus administration and second look endoscopy for the prevention of rebleeding in children with a peptic ulcer. Revista Española de Enfermedades Digestivas. 2018; 110:352-357.

30. Neumann I, Letelier L, Rada G, et al. Comparison of different regimens of proton pump inhibitors for acute peptic ulcer bleeding. Cochrane Database Syst Rev. 2013: CD007999.

3. Sachar H, Vaidya K, Laine L. Intermittent vs continuous proton pump inhibitor therapy for high-risk bleeding ulcers: a systematic review and meta-analysis. JAMA Int Med. 2014;174: 1755-1762.

32. Solana MJ, López-Herce J. Pharmacokinetics of intravenous omeprazole in critically ill paediatric patients. Eur J Clin Pharmacol. 2010;66:323-330.

33. Eroglu Y, Ericark KM, Whitingon PF, et al. Octreotide therapy for control of acute gastrointestinal bleeding in children. J Pediatr Gastroenterol Nutr. 2004;38:41-47.

THOMSON ET AL.

JPGN

34. Garcia-Tsao G, Sanyal AJ, Grace ND, Carey W. Prevention and management of gastroesophageal varices and variceal hemorrhage in cirrhosis. Hepatology. 2007;46:922-938. 35. Wells M, Chande N, Adams P, et al. Meta-analysis: vasoactive medications for the management of acute variceal bleeds. Aliment Pharmacol Ther. 2012;35:1267-1278. 36. Koul P, Totapally B, Raszynski A. Continuous octreotide infusion for treatment of upper gastrointestinal bleeding due to portal hypertension in children: an observational study from pediatric intensive care unit. J Pediatr Intensive Care. 2012;1:99-103. 37. Liver EAftSot. EASL clinical practice guidelines for the management of patients with decompensated cirrhosis. J Hepatol. 2018;69(2):406-460. 38. Shneider BL, Bosch J, De Franchis R, et al. Portal hypertension in children: expert pediatric opinion on the report of the Baveno v consensus workshop on methodology of diagnosis and therapy in portal hypertension. Pediatr Tranplant. 2012;16:426-437. 39. Barkun AN, Bardou M, Martel M, Gralnek IM, Sung JJY. Prokinetics in acute upper GI bleeding: a meta-analysis. Gastrointest Endosc. 2010;72:1138-1145. 40. Pateron D, Vicaut E, Debuc E, et al. Erythromycin infusion or gastric lavage for upper gastrointestinal bleeding: a multicenter randomized controlled trial. Ann Emerg Med. 2011;57:892-589. 41. Barkun AN, Almadi M, Kuipers EJ, et al. Management of nonvariceal upper gastrointestinal bleeding: guideline recommendations from the International Consensus Group. Ann Intern Med. 2019;171:805-822. 42. Rockall TA, Logan RF, Devlin HB, Northfield TC. Risk assessment after acute upper gastrointestinal haemorrhage. Gut. 1996;38:316-321. 43. Blatchford O, Murray WR, Blatchford M. A risk score to predict need for treatment for uppergrointestinal haemorrhage. Lancet. 2000;356:1318-1321. 44. Saeed ZA, Ramirez FC, Hepps KS, Cole RA, Graham DY. Prospective validation of the Baylor bleeding score for predicting the likelihood of rebleeding after endoscopic hemos-stasis of peptic ulcers. Gastrointest Endosc. 1995;41:561-565. 45. Provenzale D, Sandler RS, Wood DR, et al. Development of a scoring system to predict mortality from upper gastrointestinal bleeding. Am J Med Sci. 1987;294:26-32. 46. Saeed ZA, Winchester CB, Michaletz PA, Woods KL, Graham DY. A scoring system to predict rebleeding after endoscopic therapy of nonvariceal upper gastrointestinal hemorrhage, with a comparison of heat probe and ethanol injection. Am J Gastroenterol. 1993;88:1842-1849. 47. Pimpl W, Boeckl O, Waclawiczek HW, Heinerman M. Estimation of the mortality rate of patients with severe gastro-duodenal hemorrhage with the aid of a new scoring system. Endoscopy. 1987;19:101-106. 48. Vreeburg EM, Terwee CB, Snel P, et al. Validation of the rockall risk scoring system in upper gastrointestinal bleeding. Gut. 1999;44:331-335. 49. Enns RA. Validation of the rockall scoring system for outcomes from non-variceal upper gastrointestinal bleeding in a Canadian setting. World J Gastroenterol. 2006;12(48):7779-7785. 50. Custódio Lima J, Garcia Montes C, Kibune Nagasako C, et al. Performance of the Rockall scoring system in pre-dicting the need for intervention and outcomes in patients with nonvariceal upper gastrointestinal bleeding in a Brazilian setting: a prospective study. Digestion. 2013;88(4):252-257. 51. Bessa X, Ocallaghan E, Balleste B, et al. Applicability of the Rockall score in patients undergoing endoscopic therapy for upper gastrointestinal bleeding. Dig Liver Dis. 2006;38(1):12-17.

52. Schein M, Gecelter G. APACHE II score in massive upper gastrointestinal haemorrhage from peptic ulcer: prognotic value and potential clinical applications. J Br Surg. 1989;76: 733-736. 53. Lin HJ, Perg CL, Lee FY, Lee CH, Lee SD. Clinical courses and predictors for rebleeding in patients with peptic ulcers and non-bleeding visible vessels: a prospective study. Gut. 1994; 35:1389-1393. 54. Bordley DR. Early clinical signs identify low-risk patients with acute upper gastrointestinal hemorrhage. JAMA. 1985;253: 3282-3285. 55. Katschinski B, Logan R, Davies J, Faulkner G, Pearson J, Langman M. Prognostic factors in upper gastrointestinal bleeding. Dig Dis Sci. 1994;39:706-712. 56. Clason AE, Macleod DAD, Elton RA. Clinical factors in the prediction of further haemorrhage or mortality in acute upper gastrointestinal haemorrhage. J Br Surg. 1986;73: 985-987. 57. Branicki FJ, Coleman SY, Fok PJ, et al. Bleeding peptic ulcer: a prospective evaluation of risk factors for rebleeding and mortality. World J Surg. 1990;14:262-269. 58. Garripali A, Mondardini A, Turco D, Martinoglio P, Secreto P, Ferrari A. Hospitalization for peptic ulcer bleeding: evaluation of a risk scoring system in clinical practice. Dig Liver Dis. 2000; 32(7):577-582. 59. Kim BJ, Park MK, Kim SJ, et al. Comparison of scoring systems for the prediction of outcomes in patients with non-variceal upper gastrointestinal bleeding: a prospective study. Dig Dis Sci. 2009;54(11):2523-2529. 60. Bjorkman DJ, Zaman A, Fennerty MB, Lieberman D, Disario JA, Guesst-Warnick G. Urgent vs. elective endoscopy for acute non-variceal upper-GI bleeding: an effectiveness study. Gastrointest Endosc. 2004;60(1):1-8. 61. Lim C, Ahmed M. The optimal timing for urgent endoscopy in nonvariceal upper gastrointestinal bleeding. Endoscopy. 2011;43(11):1018. 62. de Groot NL, Bosman JH, Siersema PD, van Oijen MGH, Bredenoord AJ, RASTA Study Group. Admission time is associated with outcome of upper gastrointestinal bleeding: results of a multicentre prospective cohort study. Aliment Pharmacol Ther. 2012;36(5):477-484. 63. Jairath V, Kahan B, Logan R, et al. Outcomes following acute nonvariceal upper gastrointestinal bleeding in relation to time to endoscopy: results from a nationwide study. Endoscopy. 2012;44(8):723-730. 64. Kumar NL, Cohen AJ, Nayor J, Claggett BL, Saltzman JR. Timing of upper endoscopy influences outcomes in patients with acute nonvariceal upper GI bleeding. Gastrointest Endosc. 2017;85(5):945-952.e1. 65. Laursen SB, Leontiadis Gl, Stanley AJ, Møller MH, Hansen JM, Schaffaltzky de Muckadell OB. Relationship between timing of endoscopy and mortality in patients with peptic ulcer bleeding: a nationwide cohort study. Gastrointest Endosc. 2017;85(5):936-944.e3. 66. Cho SH, Lee YS, Kim YJ, et al. Outcomes and role of urgent endoscopy in high-risk patients with acute nonvariceal gastrointestinal bleeding. Clin Gastroenterol Hepatol. 2018;16(3): 370-377. 67. Alexandrino G, Domingues TD, Carvalho R, Costa MN, Lourenço LC, Reis J. Endoscopy timing in patients with acute gastrointestinal bleeding. Clin Endosc. 2019;52(1): 47-52. 68. Saleem SA, Kudaravalli P, Riaz S, et al. Outcomes of upper gastrointestinal bleeding based on time to endoscopy: a retrospective study. Cureus. 2020;12(3):e7325. 69. Guo CLT, Wong SH, Lau LHS, et al. Timing of endoscopy for acute upper gastrointestinal bleeding: a territory-wide cohort study. Gastrointest Endosc. 2017;81:544-1550.

THOMSON ET AL.

JPGN

19

70. Mousa N, Abdel-Razik A, Sheta T, et al. Endoscopic management of acute esophageal variceal bleeding within 12 hours of admission is superior to 12-24 hours. Br J Biomed Sci. 2021;78(3):130-134. 71. Kim J, Gong EJ, Seo M, et al. Timing of endoscopy in patients with upper gastrointestinal bleeding. Sci Rep. 2022;12(1):6833. 72. Yan X, Leng Z, Xu Q, Zhang Z, Xu M, Li J. The influences of timing of urgent endoscopy in patients with acute variceal bleeding: a cohort study. BMC Gastroenterol. 2022;22(1):506. 73. Carneiro de Moura M, Chen S, Kamath BM, Ng VL, Ling SC. Acute variceal bleeding causes significant morbidity. J Pediatr Gastroenterol Nutr. 2018;67(3):371-376. 74. Bello FPS, Cardoso S, Tannuri AC, Preto-Zamperlini M, Schvartsman C, Farhat SCL. Acute upper gastrointestinal bleeding due to portal hypertension in children: what is the best timing of endoscopy? Dig Liver Dis. 2022;54(1):63-68. 75. Bose P, Jacobs AS, Cordova JG, Gray BW, Huff KA, Molleston JP. Endoscopy in infants with gastrointestinal bleeding has limited diagnostic or therapeutic benefit. J Pediatr Gastroenterol Nutr. 2022;75(4):514-520. 76. Lau JYW, Yu Y, Tang RSY, et al. Timing of endoscopy for acute gastrointestinal bleeding. N Eng J Med. 2020; 382(14):1299-1308. 77. Seth A, Khan MA, Nollan R, et al. Does urgent colonoscopy improve outcomes in the management of lower gastrointestinal bleeding? Am J Med Sci. 2017;353(3):298-306. 78. Anvari S, Lee Y, Yu J, Doumouras AG, Khan KJ, Hong D. Urgent versus standard colonoscopy for management of acute lower gastrointestinal bleeding: a systematic review and meta-analysis of randomized controlled trials. J Clin Gastroenterol. 2020;54(6):493-502. 79. Jung DH, Huh CW, Kim NJ, Kim BW. Optimal endoscopy timing in patients with acute variceal bleeding: a systematic review and meta-analysis. Sci Rep. 2020;10(1):4046. 80. Kherad O, Restellini S, Almadi M, et al. Systematic review with meta-analysis: limited benefits from early colonoscopy in acute lower gastrointestinal bleeding. Aliment Pharmacol Ther. 2020;52(5):774-788. 81. Merola E, Michielan A, de Pretis G. Optimal timing of endoscopy for acute upper gastrointestinal bleeding: a systematic review and meta-analysis. Intern Emerg Med. 2021;16(5):1331-1340. 82. Tarar ZI, Zafar MU, Farooq U, Ghous G, Shoukat HMH, Kuwajima V. Does performing endoscopy sooner have an impact on outcomes in patients with acute nonvariceal upper gastrointestinal hemorrhage? A systematic review. Cureus. 2021;13(7):e16092. 83. Bai L, Jiang W, Cheng R, Dang Y, Min L, Zhang S. Does early endoscopy affect the clinical outcomes of patients with acute nonvariceal upper gastrointestinal bleeding? A systematic review and meta-analysis. Gut Liver. 2023;17(4):566-580. doi:10.5009/gnl220291 84. Lee JG, Turnipseed S, Romano PS, et al. Endoscopy-based triage significantly reduces hospitalization rates and costs of treating upper GI bleeding: a randomized controlled trial. Gastrointest Endosc. 1999;50(6):755-761. 85. Cooper GS, Chak A, Connors AF, Harper DL, Rosenthal GE. The effectiveness of early endoscopy for upper gastrointestinal hemorrhage: a community-based analysis. Med Care. 1998;36(4):462-474. 86. Gralnek IM, Barkun AN, Bardou M. Management of acute bleeding from a peptic ulcer. N Engl J Med. 2008;359(9):928-937. 87. Spiegel BMR, Vakil NB, Ofman JJ. Endoscopy for acute nonvariceal upper gastrointestinal tract hemorrhage: is sooner better? A systematic review. Arch Intern Med. 2001;161(11):1393-1404.

88. Pai N, Manfredi MA. Endoscopic management of gastrointestinal bleeding in pediatrics. Tech Gastrointest Endosc. 2013;15:18-24. 89. Braclaugh H, Girach A, Rao P, et al. Anastomotic ulcers: a tertiary centre experience of endoscopic management techniques. J Pediatroenterol Nutr. 2021;73(3):329-332. 90. Gilger MA. Gastroenterologic endoscopy in children: past, present, and future. Curr Opin Pediatr. 2001;13:429-434. 91. Rodriguez SA, Banerjee S, Desilets D, et al. Ultrathin endoscopes. Gastrointest Endosc. 2010;71:893-898. 92. Fox VL, Carr-Locke DL, Connors PJ, et al. Endoscopic ligation of esophageal varices in children. J Pediatr Gastroenterol Nutr. 1995;20:202-208. 93. Qureshi W, Adler DG, Davila R, et al. ASGE guideline: the role of endoscopy in the management of variceal hemorrhage, updated July 2005. Gastrointest Endosc. 2005;62:651-655. 94. Banc-Husu A, Ahmad N, Chandrasekhara V, et al. Therapeutic endoscopy for the control of non-variceal upper gastrointestinal bleeding in children: a case series. J Pediatr Gastroenterol Nutr. 2017;64:e88-91. 95. Lerner DG, Li BU, Mamula P, et al. Challenges in meeting fellowship procedural guidelines in pediatric therapeutic endoscopy and liver biopsy. J Pediatr Gastroenterol Nutr. 2014;58:27-33. 96. Broekaert I, Tzivinikos C, Narula P, et al. European Society for Paediatric Gastroenterology, Hepatology and Nutrition position paper on training in paediatric endoscopy. J Pediatr Gastroenterol Nutr. 2020;70(1):127-140. 97. Gralnek IM, Stanley AJ, Morris AJ, et al. Endoscopic diagnosis and management of nonvariceal upper gastrointestinal hemorrhage/orrhage (NVUGIH): European Society of Gastrointestinal Endoscopy (ESGE) guideline - update 2021. Endoscopy. 2021;53(3):300-332. 98. Lightdale JR, Acosta R, Shergill AK, et al. Modifications in endoscopic practice for pediatric patients. Gastrointest Endosc. 2014;79(5):699-710. 99. Pall H, Lerner D, Khlevner J, et al. Developing the pediatric gastrointestinal endoscopy unit: a clinical report by the endoscopy and procedures committee. J Pediatr Gastroenterol Nutr. 2016;63(2):295-306. 100. Forrest JH, Finlayson NDC, Shearman DJC. Endoscopy in gastrointestinal bleeding. Lancet. 1974;304:394-397. 101. Barkun AN, Bardou M, Kuipers EJ, et al. International consensus recommendations on the management of patients with nonvariceal upper gastrointestinal bleeding. Ann Intern Med. 2010;152:101-113. 102. Laine L, Jensen DM. Management of patients with ulcer bleeding. Am J Gastroenterol. 2012;107:345-360. 103. Yen HH, Wu PY, Wu TL, et al. Forrest classification for bleeding peptic ulcer: a new look at the old endoscopic classification. Diagnostics. 2022;12(5):1066. 104. Chung I, Kim E, Lee M, et al. Endoscopic factors predisposing to rebleeding following endoscopic hemostasis in bleeding peptic ulcers. Endoscopy. 2001;33:969-975. 105. Guglielmi A, Ruzzenente A, Sandri M, et al. Risk assessment and prediction of rebleeding in bleeding gastroduodenal ulcer. Endoscopy. 2002;34:778-786. 106. Zaragoza AM, Tenías JM, Llorente MJ, Alborch A. Prognostic factors in gastrointestinal bleeding due to peptic ulcer: construction of a predictive model. J Clin Gastroenterol. 2008;42:786-790. 107. Marmo R, Del Piano M, Rotondano G, et al. Mortality from nonulcer bleeding is similar to that of ulcer bleeding in high-risk patients with nonvariceal hemorrhage: a prospective database study in Italy. Gastrointest Endosc. 2012;75:263-272.e1. 108. Bratanic A, Pulijz Z, Ljubicicz N, et al. Predictive factors of rebleeding and mortality following endoscopic hemostasis in

THOMSON ET AL.

JPGN

THOMSON ET AL.

bleeding peptic ulcers. Hepato Gastroenterol. 2013;60: 112-117. 109. Sung JJY, Barkun A, Kuipers EJ, et al. Intravenous esomeprazole for prevention of recurrent peptic ulcer bleeding: a randomized trial. Ann Intern Med. 2009;150:455-464. 110. de Groot N, van Oijen M, Kessels K, et al. Reassessment of the predictive value of the Forrest classification for peptic ulcer rebleeding and mortality: can classification be simplified? Endoscopy. 2013;46:46-52. 111. Lau JYW, Sung JJY, Chan ACW, et al. Stigmata of hemorrhage in bleeding peptic ulcers: an interobserver agreement study among international experts. Gastrointest Endosc. 1997;46:33-36. 112. Mondardini A, Barletti C, Rocca G, et al. Non-variceal upper gastrointestinal bleeding and Forrest's classification: diagnostic agreement between endoscopists from the same area. Endoscopy. 1998;30:508-512. 113. Elmunzer BJ, Young SD, Inadomi JM, Schoenfeld P, Laine L. Systematic review of the predictors of recurrent hemorrhage after endoscopic hemostatic therapy for bleeding peptic ulcers. Am J Gastroenterol. 2008;103:2625-2632. 114. Cheng CL, Lin CH, Kuo CJ, et al. Predictors of rebleeding and mortality in patients with high-risk bleeding peptic ulcers. Dig Dis Sci. 2010;55:2577-2583. 115. Laine L, McQuaid KR. Endoscopic therapy for bleeding ulcers: an evidence-based approach based on meta-analyses of randomized controlled trials. Clin Gastroenterol Hepatol. 2009;7:33-47. 116. Sung JJY, Chan FKL, Lau JYW, et al. The effect of endoscopic therapy in patients receiving omprazole for bleeding ulcers with nonbleeding visible vessels or adherent clots: a randomized comparison. Ann Intern Med. 2003;139:237-243. 117. Andriulli A, Annese V, Caruso N, et al. Proton-pump inhibitors and outcome of endoscopic hemostasis in bleeding peptic ulcers: a series of metaanalyses. Am J Gastroenterol. 2005;100:207-219. 118. Lin HJ, Wang K, Perng CL, Lee FY, Lee CH, Lee SD. Natural history of bleeding peptic ulcers with a tightly adherent blood clot: a prospective observation. Gastrointest Endosc. 1996;43:470-473. 119. Jensen DM, Kovacs TOG, Jutabha R, et al. Randomized trial of medical or endoscopic therapy to prevent recurrent ulcer hemorrhage in patients with adherent clots. Gastroenterology. 2002;123:407-413. 120. Bleau BL, Gostout CJ, Sherman KE, et al. Recurrent bleeding from peptic ulcer associated with adherent clot: a randomized study comparing endoscopic treatment with medical therapy. Gastrointest Endosc. 2002;56:1-6. 121. Kahi CJ, Jensen DM, Sung JJY, et al. Endoscopic therapy versus medical therapy for bleeding peptic ulcer with adherent clot: a meta-analysis. Gastroenterology. 2005;129:855-862. 122. Laine L, Estrada R. Randomized trial of normal saline solution injection versus bipolar electrocoagulation for treatment of patients with high-risk bleeding ulcers: is local tamponade enough? Gastrointest Endosc. 2002;55(1):6-10. 123. Jensen DM, Eklund S, Persson T, et al. Reassessment of rebleeding risk of forrest IB (Ozoying) peptic ulcer bleeding in a large international randomized trial. Am J Gastroenterol. 2017;112(3):441-446. 124. Jensen DM, Ohning GV, Kovacs TOG, et al. Doppler endoscopic probe as a guide to risk stratification and definitive hemostasis of peptic ulcer bleeding. Gastrointest Endosc. 2016;83(1):129-136. 125. Lai KH, Peng SN, Guo WS, et al. Endoscopic injection for the treatment of bleeding ulcers: local tamponade or drug effect? Endoscopy. 1994;26:338-341.

126. Liou TC. Optimal injection volume of epinephrine for endoscopic treatment of peptic ulcer bleeding. World J Gastroenterol. 2006; 12(19):3108. 127. Barkun AN, Martel M, Toubouti Y, Rahme E, Bardou M. Endoscopic hemostasis in peptic ulcer bleeding for patients with high-risk lesions: a series of meta-analyses. Gastrointest Endosc. 2009;69:786-799. 128. Marmo R, Rotondano G, Piscopo R, Bianco MA, D'Angella R, Cipolletta L. Dual therapy versus mono- therapy in the endoscopic treatment of high-risk bleeding ulcers: a meta-analysis of controlled trials. Am J Gastroenterol. 2007;102:279-289. 129. Vergara M, Bennett C, Calvet X, et al. Epinephrine injection versus epinephrine injection and a second endoscopic method in high-risk bleeding ulcers. Cochrane Database Syst Rev. 2014;30(6):CD0005584. 130. Baracat F, Moura E, Bernardo W, et al. Endoscopic hemostasis for peptic ulcer bleeding: systematic review and meta-analyses of randomized controlled trials. Surg Endosc. 2016; 30:2155-2168. 131. Croffie J, Somogyi L, Chuttani R, et al. Clerrosing agents for use in GI endoscopy. Gastrointest Endosc. 2007;66:1-6. 132. Yabe K, Kouchi K, Takenouchi A, Matsuoka A, Kudou W, Nakata C. Current status and future challenges in the endoscopic management of non-variceal upper gastrointestinal bleeding in children. Pediatr Surg Int. 2020;36:1451-1458. 133. Gershman G, Thomson M. Practical Pediatric Gastrointestinal Endoscopy. 3rd edn. John Wiley & Sons Ltd; 2021. 134. Lee YA, Chun P, Hwang EH, Lee YJ, Kim CW, Park JH. Gastric hemangioma treated with argon plasma coagulation in a newborn infant. Pediatr Gastroenterol Hepatol Nutr. 2017; 20(2):134-137. 135. Yeh PJ, Le PH, Chen CC, Chao HC, Lai MW. Application of argon plasma coagulation for gastrointestinal angiodysplasia in children - experience from a tertiary center. Front Pediatr. 2022;10:867632. 136. Akay T, Leblebi M. Comparison of high and low-dose epinephrine & endoclip application in peptic ulcer bleeding: a case series analysis observational study. Medicine (Baltimore). 2021;100(52):e28480. 137. Ljubicic N. Endoclips vs large or small-volume epinephrine in peptic ulcer recurrent bleeding. World J Gastroenterol. 2012; 18(18):2219-2224. 138. Karaahmet F, Kılincalp S, Coskun Y, et al. The efficiency of endoclips in maintaining the gastrointestinal bleeding-related Dieulafoy's lesion. Wien Klin Wochenschr. 2016;128:700-705. 139. Luigiano C, Ferrara F, Ghersi S, et al. Endoclip-assisted resection of large pedunculated colorectal polyps: technical aspects and outcome. Dig Dis Sci. 2010;55(6):1726-1731. 140. Mizukami T, Hiroyuki I, Hibi T. Anchor clip technique helps in easy prevention of post-polymectomy hemorrhage of large colonic polyps. Digest Endosc. 2010;22(4):366-369. 141. Qiu J, Xu J, Zhang Y, et al. Over-the-scope clip applications as first-line therapy in the treatment of upper non-variceal gastrointestinal bleeding, perforations, and fistulas. Front Med. 2022;9:1-10. 142. Bapaye J, Bhalla V, Shehadah A, Chathuranga Ramanayake D, Okolo p. Safety and efficacy of over the scope clips (OTSC) versus standard therapy for non-variceal upper gastrointestinal bleeding; a systematic review and meta-analysis. Gastrointest Endosc. 2022;95(6):AB465. 143. Weiland T, Rohrer S, Schmidt A, et al. Efficacy of the OTSC system in the treatment of GI bleeding and wall defects: a PMCF meta-analysis. Minim Invasive Ther Allied Technol. 2020;29(3):121-139. 144. Tran P, Carroll J, Barth BA, Channabasappa N, Troendle DM. Over the scope clips for treatment of acute nonvariceal gastrointestinal bleeding in children are safe and effective. J Pediatr Gastroenterol Nutr. 2018;67(4):458-463.

THOMSON ET AL.

JPGN

145. Mullady DK, Wang AY, Waschke KA. AGA clinical practice update on endoscopic therapies for non-variceal upper gastrointestinal bleeding: expert review. Gastroenterology. 2020; 159(3):1120-1128. 146. Nelson DB, Barkun AN, Block KP, et al. Endoscopic homo-static devices. Gastrointerest Endosc. 2001;54:833-840. 147. Gilbert D, DiMarino A, Jensen D, et al. Status evaluation: hot biopsy forceps. American Society for Gastrointestinal Endoscopy Technology Assessment Committee. Gastrointerest Endosc. 1992;38:753-756. 148. Holster I, van Beusekom H, Kuipers E, Leebeek F, de Maat M, Tjwa E. Effects of a hemostatic powder Hemospray® on coagulation and clot formation. Endoscopy. 2015;47(7): 638-645. 149. Yau AHL, Ou G, Galorport C, et al. Safety and efficacy of Hemospray® in upper gastrointestinal bleeding. Can J Gastroenterol Hepatol. 2014;28(2):72-76. 150. Holster I, Brullet E, Kuipers E, Campo R, Fernández-Atutxa A, Tjwa E. Hemospray® treatment is effective for lower gastrointestinal bleeding. Endoscopy. 2013;46(1):75-78. 151. Karna R, Deliwala S, Ramgopal B, et al. Efficacy of topical hemostatic agents in malignancy-related Gl bleeding: a systematic review and meta-analysis. Gastrointerest Endosc. 2023; 97:202-208.e8. 152. Sulz M, Frei R, Meyenberger C, Bauerfeind P, Semadeni GM, Gubler C. Routine use of Hemospray® for gastrointestinal bleeding: prospective two-center experience in Switzerland. Endoscopy. 2014;46:619-624. 153. Masci E, Arena M, Morandi E, Viaggi P, Mangiavillano B. Upper gastrointestinal active bleeding ulcers: review of literature on the results of endoscopic techniques and our experience with Hemospray®. Scand J Gastroenterol. 2014;49: 1290-1295. 154. Smith LA, Stanley AJ, Bergman JJ, et al. Hemospray® application in nonvariceal upper gastrointestinal bleeding: results of the survey to evaluate the application of Hemospray® in the luminal tract. J Clin Gastroenterol. 2014;48:e89-e92. 155. Cahyadi O, Bauder M, Meier B, Caca K, Schmidt A. Effectiveness of TC-325 (Hemospray®) for treatment of diffuse or refractory upper gastrointestinal bleeding - a single center experience. Endosc Int Open. 2017;05:E1159-E1164. 156. Hussein M, Alzoubaidi D, Lopez MF, et al. Hemostatic spray powder TC-325 in the primary endoscopic treatment of peptic ulcer-related bleeding: multicenter international registry. Endoscopy. 2021;53(36):36-43. 157. Preiß JC, Barmeyer C, Bürgel N, et al. EndoClot polysaccharide hemostatic system in nonvariceal gastrointestinal bleeding: results of a prospective multicenter observational pilot study. J Clin Gastroenterol. 2016;50:e95-e100.

158. Park JC, Kim Y.J, Kim EH, et al. Effectiveness of the polysaccharide hemostatic powder in non-variceal upper gastrointestinal bleeding: using propensity score matching. J Gastroenterol Hepatol. 2018;33:1500-1506. 159. Vital F, Naegel A, Atreya R, et al. Comparison of Hemospray® and Endoclot™ for the treatment of gastrointestinal bleeding. World J Gastroenterol. 2019;25:1592-1602. 160. Yasser M, Bhat Y, Banerjee S, et al. ASGE Technology Committee, tissue adhesives: cyanoacrylate glue and fibrin sealant. Gastrointest Endosc. 2013;78(2):209-215. 161. Seewald S, Ang TL, Imazu H, et al. A standardized injection technique and regimen ensures success and safety of N-butyl-2-cyanoacrylate injection for the treatment of gastric fundal varices (with videos). Gastrointest Endosc. 2008;68:447-454. 162. Soehendra N, Nam VC, Grimm H, Kempeneers I. Endoscopic obliteration of large esophagogastric varices with bucrylate. Endoscopy. 1986;18(25):25-26. 163. Soehendra N, Grimm H, Nam VC, Brückner M. [10 years' experience with endoscopic sclerotherapy of esophagogastric varices]. Chirurg. 1989;60:594-598. 164. Farinella E, Ronca P, La Mura F, et al. Upper gastrointestinal massive bleeding successfully treated intra-operatively with a collagen and thrombin-based high-viscosity gel for haemos-tasis. Case report. G. Chirar. 2010;31:186-190. 165. Kubba A, Murphy W, Palmer K. Endoscopic injection for bleeding peptic ulcer: a comparison of adrenaline alone with adrenaline plus human thrombin. Gastroenterology. 1996; 111(3):623-628. 166. Balanzó J, Villanueva C, Sainz S, et al. Injection therapy of bleeding peptic ulcer. A prospective, randomized trial using epinephrine and thrombin. Endoscopy. 1990;22(4):157-159.

SUPPORTING INFORMATION

Additional supporting information can be found online in the Supporting Information section at the end of this article.

How to cite this article: Thomson M, Amil-Dias J, Assa A, et al. A management strategy for nonvariceal gastrointestinal bleeding in children: an ESPGHAN position paper. J Pediatr Gastroenterol Nutr. 2026;1-21. doi:10.1002/jpn3.70278

145. Mullady DK, Wang AY, Waschke KA. AGA clinical practice update on endoscopic therapies for non-variceal upper gastrointestinal bleeding: expert review. Gastroenterology. 2020; 159(3):1120-1128. 146. Nelson DB, Barkun AN, Block KP, et al. Endoscopic homo-static devices. Gastrointerest Endosc. 2001;54:833-840. 147. Gilbert D, DiMarino A, Jensen D, et al. Status evaluation: hot biopsy forceps. American Society for Gastrointestinal Endoscopy Technology Assessment Committee. Gastrointerest Endosc. 1992;38:753-756. 148. Holster I, van Beusekom H, Kuipers E, Leebeek F, de Maat M, Tjwa E. Effects of a hemostatic powder Hemospray® on coagulation and clot formation. Endoscopy. 2015;47(7): 638-645. 149. Yau AHL, Ou G, Galorport C, et al. Safety and efficacy of Hemospray® in upper gastrointestinal bleeding. Can J Gastroenterol Hepatol. 2014;28(2):72-76. 150. Holster I, Brullet E, Kuipers E, Campo R, Fernández-Atutxa A, Tjwa E. Hemospray® treatment is effective for lower gastrointestinal bleeding. Endoscopy. 2013;46(1):75-78. 151. Karna R, Deliwala S, Ramgopal B, et al. Efficacy of topical hemostatic agents in malignancy-related Gl bleeding: a systematic review and meta-analysis. Gastrointerest Endosc. 2023; 97:202-208.e8. 152. Sulz M, Frei R, Meyenberger C, Bauerfeind P, Semadeni GM, Gubler C. Routine use of Hemospray® for gastrointestinal bleeding: prospective two-center experience in Switzerland. Endoscopy. 2014;46:619-624. 153. Masci E, Arena M, Morandi E, Viaggi P, Mangiavillano B. Upper gastrointestinal active bleeding ulcers: review of literature on the results of endoscopic techniques and our experience with Hemospray®. Scand J Gastroenterol. 2014;49: 1290-1295. 154. Smith LA, Stanley AJ, Bergman JJ, et al. Hemospray® application in nonvariceal upper gastrointestinal bleeding: results of the survey to evaluate the application of Hemospray® in the luminal tract. J Clin Gastroenterol. 2014;48:e89-e92. 155. Cahyadi O, Bauder M, Meier B, Caca K, Schmidt A. Effectiveness of TC-325 (Hemospray®) for treatment of diffuse or refractory upper gastrointestinal bleeding - a single center experience. Endosc Int Open. 2017;05:E1159-E1164. 156. Hussein M, Alzoubaidi D, Lopez MF, et al. Hemostatic spray powder TC-325 in the primary endoscopic treatment of peptic ulcer-related bleeding: multicenter international registry. Endoscopy. 2021;53(36):36-43. 157. Preiß JC, Barmeyer C, Bürgel N, et al. EndoClot polysaccharide hemostatic system in nonvariceal gastrointestinal bleeding: results of a prospective multicenter observational pilot study. J Clin Gastroenterol. 2016;50:e95-e100.

相关指南

• （2024）成人腹腔高压和腹腔间隔室综合征诊治急诊专家共识 · 麻醉与急重症 2024
• 2020 WSES指南：急性结石性胆囊炎的诊断和治疗 · 消化内科 2020
• 中国老年高血压管理指南2023 · 心血管内科 2023
• 免疫抑制宿主重症肺炎诊断与治疗专家共识 · 呼吸内科 2026
• 复杂性腹腔感染碳青霉烯类耐药细菌诊治专家共识（2025版） · 感染与传染病 2025
• 2023 SICUT指南：高危、重症和不适合手术的急性胆囊炎患者的管理 · 消化内科 2023
• （2024）重症急性胰腺炎中西医结合诊疗指南 · 消化内科 2024
• 2024 ESC 房颤管理指南 · 心血管内科 2024