Introduction

Adverse events associated with pediatric endoscopy are rare, but do occur. Published data from the Pediatric Clinical Outcomes Research Initiative (PEDS‐CORI) suggest the overall rate of complications during pediatric endoscopy is 2.3%, including a specific risk of hypoxia (1.5%) and bleeding (0.3%) [1]. Generally speaking, endoscopy complications can be categorized as involving cardiopulmonary compromise, bleeding, perforation, and infection. Children at high risk for adverse events during pediatric endoscopy are often those with underlying disorders that put them at increased risk for events that fall into these four categories.

Patients at high risk for cardiopulmonary and sedation‐related events

Cardiopulmonary events that occur during pediatric endoscopy are typically related to procedural sedation and anesthesia, which accounts for ~60% of all complications related to endoscopic procedures in children [1–3]. Cardiopulmonary events during pediatric endoscopy can range from minor to major complications, and include transient oxygen desaturation, aspiration, respiratory arrest, shock, and myocardial infarction [4]. Patients at high risk for cardiopulmonary events include those with compromised cardiopulmonary function, including decreased forced expiratory volumes (as measured by FEV₁) [5]. Specific examples of patients at high risk for sedation complications include infants <1 year of age, infants and children with congenital heart disease, pulmonary hypertension, cystic fibrosis, muscular dystrophy, and obesity [1–3].

In addition, all children with difficult airways should be recognized to be at risk for sedation‐related complications. Pediatric populations at highest risk for having difficult airways are those with craniofacial congenital abnormalities, including a large tongue, a highly arched or narrow palate, a short, thick neck, and prominent overbite, as well as those with limited range of motion of their necks [6]. Specific patient diagnoses that should elicit concern for increased cardiopulmonary risks during endoscopy include Pierre Robin syndrome, Treacher Collins’ syndrome, and patients with laryngeal atresia.

Patients with history of lung disease, including chronic aspiration or other aerodigestive disease, reactive airways, pulmonary hypertension and cystic fibrosis should be recognized to be at particular risk of ventilatory compromise during endoscopy [7]. Medications which can potentiate cardiopulmonary effects of sedation include antiseizure, psychotropic, and pain medicines [7]. Children receiving benzodiazepines or opioids on a chronic basis should be identified during preprocedure patient preparation to be at high risk for cardiopulmonary events during endoscopy [8].

Patients at high risk for bleeding

Significant bleeding is a rare adverse event of endoscopic procedures in children, and generally speaking occurs more commonly during therapeutic procedures with instrumentation [1,9,10]. Endoscopy‐related bleeding can also result from endoscope manipulation or tissue sampling. In terms of the latter, the risk of bleeding during mucosal biopsy is generally related more to patient‐specific risk factors (i.e., inflammation, coagulopathy, hemophilia) than the total number of biopsies obtained [11–13]. When bleeding is associated with endoscopy in children, it may be intraluminal or intramural. The former is typically noted during the procedure, whereas the latter may present in a delayed fashion, often after a patient has been discharged.

Bleeding can also occur with endoscope advancement, especially around blind or angulated turns, due to mucosal shearing or tearing, and is more common in certain anatomical areas. For example, the sigmoid colon may be at particular risk of intraluminal bleeding or intramural hematoma during colonoscopic advancement and loop reduction [14]. In addition, the duodenum may also be particularly vulnerable to intramural hematomas post EGD with mucosal biopsy. The incidence of EGD with biopsy‐related duodenal hematoma in children has been reported to be 1 in 1922 procedures [15]. Cases typically present as abdominal pain and/or vomiting within 72 hours post procedure [15].

Unique features of the third portion of the duodenum have been hypothesized to account for this anatomical location being particularly vulnerable to hematoma, including a relatively fixed retroperitoneal position, adjacency to the lumbar spine, a lack of well‐developed retroperitoneal serosal layer, and a rich submucosal vascular plexus susceptible to shearing forces during biopsy acquisition [16,17]. As such, it has been theorized that one may be able to decrease the risk of a duodenal hematoma by avoiding extension of the biopsy forceps more than 2–3 cm beyond the endoscope tip, thereby decreasing the chances of stripping of the mucosa from the immobile bowel wall behind it [18,19].

Specific patient co‐morbidities that may increase the risk of duodenal hematoma include leukemia and history of hematopoetic bone marrow transplant [19–21]. Underlying coagulation disorders may also predispose to intramural duodenal hematoma [22]. Once a hematoma occurs, it generally requires about three weeks to resolve, unless surgical evacuation is performed.

Patient risk factors for bleeding during endoscopy also include anemia, thrombocytopenia, coagulopathy, and use of certain medications. Pediatric patient populations at increased risk of bleeding complications during endoscopic procedures include those with bone marrow failure or hematological malignancies, history of hematopoietic stem cell transplant (HSCT), end‐stage liver disease, disorders of coagulation and those taking antithrombotic medications. Antithrombotic agents carry varying degrees of bleeding risks, and include anticoagulants (heparin, low molecular weight heparin, and warfarin) and antiplatelet medications (nonsteroidal antiinflammatory drugs, aspirin, clopidrogrel, ticlopidine, and glycoprotein IIb/IIIa inhibitors).

Finally, it is reasonable to assume that co‐morbidities of uremia, hypoalbuminemia, or a recent bleeding event may confer additional risk of bleeding in children related to platelet dysfunction [23–25].

Patients at high risk for perforation

Perforation during endoscopy can be defined as instrumental injury leading to a defect in the wall of the bowel, with evidence of air or luminal contents outside the GI tract [5]. The reported incidence of perforation during pediatric endoscopy is 0.06–0.3% [26], and perforation is generally classified as large or small.

Large perforations usually result from injury from the shaft of the endoscope. Risk factors for large perforations include large intracolonic loops, particularly when formed in the rectosigmoid region, and often involve the antimesenteric side of the bowel [27]. Presentation of large perforations is immediate, and patients will have peritoneal signs. Computed tomography (CT) scans will demonstrate extraluminal free air.

In comparison, small perforations are usually due to the endoscope tip and can occur when advancing through a turn with a “sliding by” technique [27]. Therapeutic maneuvers, such as hot snare polypectomy and sphincterotomy, can also result in small focal perforations. Presentation of small perforations can be delayed by hours to days with nonspecific abdominal pain and tenderness [27].

Generally speaking, patients with intestinal strictures may be at risk for perforation in part due to intermittent obstruction that occurs mechanically when a colonoscope traverses a stricture. With air unable to pass distally around the endoscope, it will accumulate in the proximal colon, stretching the mucosa and decreasing wall strength. In addition, patients with both primary and secondary pseudoobstruction leading to massive dilated bowel (e.g., spinal muscular atrophy, metabolic disorders) should be recognized to be at increased risk of perforation during endoscopic procedures [28]. This includes increased risk for perforation during therapeutic decompression, which should be mitigated by employing CO₂ and performing intermittent suctioning [28,29].

A number of other factors may increase a patient’s risk for perforation. These include using a larger endoscope in small patients, poor or compromised endoscopic visualization, and impaired bowel wall strength [30]. It is important to recognize that performance of endoscopic procedures in small children may require larger endoscopes, with larger working channels and greater availability of endoscopic accessories [31]. For example, to control gastrointestinal bleeding in neonates and young infants, a larger gastroscope than standard neonatal scopes is needed to use bipolor electrocautery or hemostatic clips [31]. Also, to successfully perform colonoscopy in infants and small children, gastroscopes may be used, which may be stiff and relatively large for a small child’s intestinal lumen [2]. Although patient–endoscope mismatch may be unavoidable, it is prudent to recognize the increased risks of perforation and proceed accordingly.

Patients with inflammatory bowel disease may be at high risk for perforation due to intestinal strictures and mucosal inflammation, which may compromise wall strength. This risk can be compounded when patients are on high‐dose steroids, which can decrease bowel wall thickness and strength [32]. High‐dose steroid use can also mask and delay the onset of peritoneal symptoms [33]. It is therefore important to have a high suspicion for bowel perforation in patients receiving high‐dose steroids who develop persistent abdominal pain post endoscopy.

There are two additional specific conditions which may increase patient risks for endoscopic perforation: recessive dystrophic epidermolysis bullosa (RDEB) and type 4 (vascular type) Ehlers–Danlos syndrome (EDS) [34,35]. In children with severe generalized RDEB, epithelial and mucosal scarring due to even minimal manipulation or abrasion is a significant risk, and can occur with taping of the skin or with establishment of a secure airway [36,37]. Ideally, specially designed adhesives should be used exclusively, and careful decision making about airway management should occur prior to the procedure [37]. When performing upper endoscopy in children with RDEB, it is particularly important to recognize that esophageal scarring can lead to esophageal stricturing [38]. If dilation in RDEB is pursued, a conservative target of no more than three times the stricture diameter during any one procedure should be preferentially performed via endoscopic radial force balloons with fluoroscopic guidance [35].

Patients with EDS type IV (vascular type) have an extremely high risk of bowel perforation and GI bleeding during endoscopy [34]. EDS type IV accounts for 5% of EDS prevalence and has an autosomal dominant inheritance pattern. Complications associated with endoscopy, particularly colonic perforations, have higher rates in children and teenagers [34,39–41]. Therefore endoscopic procedures should be considered in type IV EDS only if necessary and performed with extreme caution.

Acquired patient risk factors for endoscopic perforation include certain types of ingestions, history of prior perforation, prolonged procedures and hemopoietic stem cell transplant [42]. In particular, compromised mucosal wall strength may increase risks of esophageal perforation in patients with caustic ingestion, disk battery ingestion, and tracheal‐esophageal atresia surgical anastomotic sites [42,43].

Warning signs associated with perforation include pain out of proportion to exam, persistent tachycardia, atypical use of pain medication, as well as fever and pain lasting beyond a few hours [42]. Initial imaging should include a KUB and left lateral decubitus (LLD) radiograph. The patient should ideally be in the LLD position for 5–10 minutes. If the imaging is normal, repeat imaging or CT scan should be considered.

Patients at high risk for endoscopy‐related infections

Adverse events associated with infection are infrequent during pediatric endoscopy, but have been well described [44]. They may result from either exposing patients to infectious agents through the use of contaminated equipment (exogenous transmission) or by creating a portal of entry through which host flora may set up infection (endogenous transmission) [44,45]. Generally speaking, rates of postprocedural infectious events are dependent on the fidelity of postprocedural equipment processing, the presence of patient‐specific risk factors such as a compromised immune system, and the nature of the procedure being performed.

Risk factors for procedure‐related infections

Certain therapeutic interventions, such as stricture dilation, sclerotherapy, and esophageal banding, are associated with increased rates of bacteremia. In turn, prophylaxis during these procedures in certain high‐risk patient groups (i.e., those with profound neutropenia) is recommended [49,56]. Another high‐risk group of children for infectious complications is those undergoing placement of percutaneous endoscopic gastrostomy (PEG) tubes. Society guidelines currently list a grade 1A recommendation to administer parenteral cefazolin (or equivalent) 30 minutes prior to the placement of PEGs [49]. Antibiotic prophylaxis should also be provided when complete relief of biliary obstruction via endoscopic retrograde cholangiopancreatograhy (ERCP) may not be achieved, such as in the setting of patients with primary sclerosing cholangitis or hilar tumors, as well as in patients requiring biliary interventions after liver transplantation; stenting in the setting of biliary malignancy; and when a combined percutaneous‐endoscopic approach is undertaken [49,57].