58. Complications of Upper Gastrointestinal Endoscopy

Brian J. Dunkin, M.D., F.A.C.S.

A. General Considerations

Flexible upper gastrointestinal endoscopy is a safe procedure with a com- plication rate well below 2% and a mortality rate of 0.004%. The incidence of complications increases when biopsy, polypectomy, or other invasive diagnostic or therapeutic maneuvers are performed. Proper preparation for esophagogastroduodenoscopy (EGD) begins with a thorough history and physical examination. Both physician and patient should understand the indications for the procedure and possible complications. Patients who undergo EGD are frequently older and may have multiple medical prob- lems or be taking medications that increase the risk of complications. General risk factors include advancing age, history of cardiac disease, or history of chronic obstructive pulmonary disease. Specific problems that are likely to be encountered and the manner in which they increase risk are given in Table 58.1. 1. Cardiopulmonary complications. Although the overall complication rate from EGD is low, 40% to 46% of serious complications are car- diopulmonary, related to hypoxemia, vasovagal reflexes, and relative hypotension. a. Hypoxemia is common. Up to 15% of patients experience a decrease in oxygen saturation below 85% during EGD. i. Cause and prevention. Hypoxemia is due to sedation and to encroachment upon the airway. ii. Recognition and management. Routine monitoring of oxygen saturation gives the diagnosis (remember that hyper- carbia is usually present before oxygen desaturation is observed). Supplemental oxygen should be administered but may result in carbon dioxide retention if chronic obstructive pulmonary disease is present. Constant observation by a second individual who monitors vital signs, oxygen satura- tion, and level of consciousness (and reminds the patient to take periodic deep breaths) can help minimize this problem. A jaw thrust maneuver, performed by this assistant, will often improve airflow and oxygen saturation. Remove the endoscope if necessary. b. Bradycardia i. Cause and prevention. The vasovagal reflex from gastric distention or pressure against the stomach wall from the endoscope can trigger bradycardia and hypotension. Pre- 618 B.J. Dunkin

Table 58.1. Medical problems that may increase the risk of EGD. Medical problem Nature of complication Valvular heart disease Bacterial endocarditis Diabetes Hypoglycemia (due to NPO status) Liver disease Oversedation (inability to metabolize narcotics and benzodiazepines) Depression Hypertensive crisis (monoamine oxidase inhibitors react with meperidine) Renal insufficiency Oversedation, seizures (inability to excrete normeperidine, a meperidine metabolite) Cardiac dysrhythmias Dysrhythmia, hypotension Obesity, chronic obstructive Hypoxemia, hypercarbia, carbon dioxide pulmonary disease retention Bleeding diatheses Bleeding

treatment with atropine combats the bradycardia, but the resulting tachycardia may increase myocardial oxygen demand. Patients who are taking b-adrenergic-blockers may be unable to manifest a tachycardia in response to pain and hypovolemia. This relative bradycardia then contributes to hypotension (see item c). ii. Recognition and management. Continuous electrocardio- graphic monitoring allows early recognition. Evacuation of gastric air and reduction of gastric wall pressure from the endoscope is the first intervention. If this is unsuccessful, atropine is generally the drug of choice. Further manage- ment should follow advanced cardiac life support (ACLS) protocols. c. Hypotension i. Cause and prevention. Hypovolemia, cardiac dysrhyth- mias, myocardial ischemia, drug interactions, and overseda- tion are all potential causes. Monitoring, adequate hydration, and attention to medications and level of sedation are all crucial. Take a careful history, including medication usage, prior to EGD. ii. Recognition and management. Frequent blood pressure checks during the procedure and in the recovery phase will allow early detection. Administer a fluid bolus and search for other treatable causes (e.g., bradycardia). 2. Medications that cause bleeding diatheses. Many medications have the potential to cause bleeding problems. A list of common medica- tions, problems, and suggestions for management follows. a. Aspirin irreversibly poisons platelets, and the effect lasts until new platelets have replaced the affected platelets. With an average life span of 10 days in the circulation, a significant replacement 58. Complications of Upper Gastrointestinal Endoscopy 619

effect can be noted after about 7 days. Aspirin should be stopped 1 week prior to the procedure if possible. If therapy is performed, aspirin should not be restarted for another 14 days. b. Other nonsteroidal anti-inflammatory drugs (NSAIDs) also inhibit platelet function, but the effect is variable and reversible. Piroxicam (Feldene) has an effect similar to aspirin in duration. Most other NSAIDs can be stopped 48 hours prior to the procedure. c. Warfarin is another drug commonly encountered in the EGD patient. As in open surgery, there is no consensus about its periprocedure management. Anticoagulated patients undergoing diagnostic EGD alone are not at increased risk for bleeding. Those undergoing therapeutic EGD, however, may be. There are basically four options for management of anticoagulated patients undergoing therapeutic EGD: stop the warfarin with no parenteral anticoagulation coverage (heparin or low-molecular-weight heparin), stop the warfarin with parenteral anticoagulation coverage, continue warfarin at the usual dose, or continue at a reduced dose. In deciding which option to choose, it is important to assess the patient’s risk for a thromboembolic complication when anticoagulation medication is withdrawn and to be clear on the indications for a therapeutic EGD. Patients at highest risk for thromboembolism are those with mechanical heart valves, coro- nary artery disease with persistent exertional angina, and overt arterial disease at more than one site, as well as those with a history of experiencing a thromboembolic event while anticoag- ulated. The risk–benefit ratio of the four anticoagulation options must be individualized for each patient. d. Ticlopidine (Ticlid) is commonly given to patients with cardio- vascular problems. It retards platelet aggregation. A single dose will effect the platelets for 4 to 36 hours. The bleeding time is maximally increased after 5 to 6 days of therapy and will take 4 to 8 days to normalize after stopping the drug. The drug should therefore be managed the same as aspirin. In an emergency situ- ation, the time to normalization of the bleeding time can be decreased to less than 2 hours by administering intravenous methylprednisolone. e. Clopidogral (Plavix) inhibits platelet aggregation and is fre- quently used in patients with cardiovascular or cerebralvascular disease. Inhibition of platelet aggregation can be seen within 2 hours of a single dose, with steady state reached at 3 to 7 days. This drug irreversibly inhibits platelet function and should be managed similar to aspirin. 3. Infectious complications a. Endocarditis, infection of prostheses (including joint prosthe- ses), systemic infection. Both diagnostic and therapeutic EGD have been demonstrated to cause bacteremia. Certain groups of patients are considered at risk and should receive antibiotics prior to endoscopic procedures (Table 58.2). Carefully seek any past 620 B.J. Dunkin

Table 58.2. American Society for Gastrointestinal Endoscopy (ASGE) recom- mendations for antibiotic prophylaxis for endoscopic procedures. Antibiotic Patient condition Procedure prophylaxis Prosthetic valve, Stricture dilation, varix Recommended history of endocarditis, sclerosis, ERCP for systemic-pulmonary obstructed biliary tree shunt, synthetic vascular Other endoscopic Insufficient data to graft <1 year old procedures including make firm EGD and colonoscopy recommendation; (with or without biopsy endoscopists may or polypectomy), choose on case- variceal ligation by-case basis Cirrhosis and ascites, Stricture dilation, varix Insufficient data to immunocompromised sclerosis, ERCP for make firm patient obstructed biliary tree recommendation; endoscopists may choose on case- by-case basis Other endoscopic Not recommended procedures including EGD and colonoscopy (with or without biopsy or polypectomy), variceal ligation Prosthetic joint or All endoscopic Not recommended orthopedic prosthesis procedures ERCP: endoscopic retrograde cholangiopancreatography.

history of endocarditis, valvular heart disease, or recent valve or vascular replacement surgery. An acceptable prophylactic regimen for these high-risk patients is 2g of parenteral ampicillin and 1.5mg/kg gentamicin (up to 80mg) 30 minutes before the procedure. This should be followed by a single 1.5-g dose of oral amoxicillin 6 hours after the procedure. One gram of parenteral vancomycin may be substituted for the preprocedure ampicillin, with omission of the post procedure amoxicillin in patients aller- gic to penicillin. b. Transmission of infection. Strict adherence to proper disinfec- tion procedures is important to avoid iatrogenic transmission of bacterial or viral infection. i. Pseudomonas aeruginosa infections caused by contami- nated scopes or water bottles have been frequently reported and have a high mortality rate. 58. Complications of Upper Gastrointestinal Endoscopy 621

ii. Contamination by Salmonella, Helicobacter, and Mycobac- terium has also been documented. iii. Viral infections have not been documented convincingly, and to date there has been no evidence of colonization of an endoscope with HIV and no reports of transmitting HIV to a patient from a contaminated scope. 4. Aspiration. Topical anesthesia, gastric distention, and sedation all increase the risk of aspiration during EGD. Yankauer suction must be available to clear secretions and emesis. Patient position is important: the left lateral decubitus position with the head slightly elevated reduces the risk of aspiration. Patients requiring emergent endoscopy or a supine position for the procedure (e.g., PEG placement) are less able to protect their airway. Consider intubation for patients under- going EGD for bleeding or foreign body removal. 5. Complications of conscious sedation. Take a careful history with attention to patient allergies, medications, and comorbidities. Use the smallest amount of sedation that will provide the desired effect. Narcotics and benzodiazepines in combination are more likely to produce cardiopulmonary complications than either drug given alone. Flumazenil (reversibly inhibits benzodiazepines) and Narcan (reversibly inhibits opiate analgesics) should be readily accessible before the start of the procedure. Remember that these drugs have a shorter half-life than the benzodiazepine or narcotic being inhibited. Therefore, a patient who is awake and responsive after receiving Narcan or flumazenil may again become unresponsive when the drug wears off.

B. Complications of Diagnostic EGD

Mechanical complications of diagnostic EGD include esophageal perfora- tion and dislodgment of teeth. 1. Esophageal perforation a. Cause and prevention. The risk of esophageal perforation from diagnostic EGD is 0.03% and most frequently occurs at the cervical esophagus. Risk factors include anterior cervical osteophytes, Zenker’s diverticulum, esophageal stricture or web, or a cervical rib. Most cervical esophageal perforations occur during rigid endoscopy, or with blind passage of a flexible endo- scope. Gentle passage under direct visual control is the best way to prevent perforation. Perforation can occur at any level at which there is a stricture or other pathology. Retching with an over- insufflated stomach and the endoscope occluding the gastro- esophageal junction (GEJ) can result in Mallory-Weiss tears or esophageal perforation. Avoid this by adequate sedation, limiting insufflation, and removing the endoscope from the GEJ if the patient starts to retch. 622 B.J. Dunkin

b. Recognition and management. Cervical pain, crepitus, and cellulitis are all signs of a high esophageal perforation. Distal perforations cause chest pain. The diagnosis is confirmed by water-soluble contrast esophagram. Cervical esophageal perfo- rations can usually be managed with antibiotics and withholding oral intake, or by cervical exploration and drainage. Rarely is primary repair or diversion necessary. Distal esophageal perfo- ration may require immediate surgical drainage or repair. 2. Dislodgment of teeth or dentures a. Cause and prevention. Avoid this problem by removing any den- tures before introducing the scope. Place a bite block to protect the teeth and the instrument. b. Recognition and management. The problem is usually recog- nized by the patient. Obtain a posteroanterior and lateral chest x-ray to exclude aspiration. Remove aspirated foreign bodies immediately (bronchoscopy). Ingested teeth will pass without incident. Ingested dental appliances may or may not, depending on size. Repeat endoscopy and removal may be needed (see Chapter 52, Section D, Foreign Body Removal).

C. Complications of Therapeutic EGD

1. Therapeutic endoscopy for nonvariceal bleeding is associated with few complications. One risk of major concern is precipitation of bleeding from a nonbleeding ulcer, but this occurs in only 5% of cases. Complications of specific modalities used for control of bleeding are as follows. a. Injection therapy. Bleeding peptic ulcers can be controlled by injection of epinephrine with or without a sclerosant or cyano- acrylate. Plasma epinephrine levels increase four- to fivefold within minutes of injection of epinephrine but return to baseline within 20 minutes. These levels may be higher in patients with liver disease. Only one case of asymptomatic hypertension and ventricular tachycardia has been reported after epinephrine injection. Sclerosing agents can (rarely) cause full-thickness necrosis, obstructive jaundice, and intramural hematoma. Cyanoacrylate (“superglue”) is nontoxic with minimal side effects and has been found to be efficacious in nonvariceal bleed- ing. The main risk with its use is damage to the endoscope from inadvertent application in the working channel. b. Cauterization (thermal therapy). The use of heater probes, multipolar probes, and argon plasma coagulation (APC) all have low rates of treatment-induced bleeding and perforation. Monopolar cautery is generally avoided because of a high inci- dence of full-thickness injury. c. Other modalities. Early experience with endoscopic clips demonstrates that they are safe and efficacious, but perhaps not 58. Complications of Upper Gastrointestinal Endoscopy 623

as good as thermal therapy. Variceal band ligators have been used for Dieulafoy lesions with good success. 2. Therapeutic EGD for variceal bleeding has become commonplace with approximately a 90% success rate at controlling the initial bleed- ing episode. The primary complications are stricture, perforation, and bleeding. a. Esophageal variceal banding (EVB). The incidence of stricture (0%), perforation (0.7%), bleeding from ulceration at the banding site (2.6–7.8%), aspiration pneumonia (1%), peritonitis (4%), and mortality (1%) are all lower than with sclerotherapy. Chest pain is common after EVB and may be related to esophageal spasm. Historically, EVB had the additional risk of requiring the use of an overtube to facilitate multiple passes of the endoscope. This is not needed with multiband ligators and has subsequently elimi- nated the risk of perforation. b. Esophageal variceal sclerotherapy (EVS). Complications occur in 20% to 40% of cases with up to 2% mortality. The most common serious complications are stricture formation (11.8%), perforation (4.3%), bleeding from ulceration at the injection site (12.7%), and pneumonia (6.8%). Chest pain, pleural effusions, pulmonary infiltrates, and bacteremia can each occur in 44% to 50% of patients. 3. Dilatation of strictures is primarily performed for esophageal lesions, although dilatation of nonesophageal lesions is becoming more fre- quent and is associated with a very low complication rate. This section concentrates on the complication of esophageal dilatation. There are two methods of dilatation: placement of a guide-wire across the stricture (under endoscopic or fluoroscopic guidance) followed by advancement of a bougie dilator, and transendoscopic balloon dilata- tion with or without the use of a guidewire. These techniques appear to be equally safe and efficacious. The risk of developing a complica- tion from endoscopic dilatation is more dependent on the underlying pathology than the technique of dilatation, provided proper technique is followed (see Chapter 52). Perforation is the most feared compli- cation, with an overall incidence of 0.2% for all techniques and pathol- ogy (Table 58.3). Esophageal dilatation results in bacteremia in up to

Table 58.3. Type of stricture and risk of perforation following dilatation. Type of stricture Risk of perforation (%) Benign peptic 0.1–0.3 Malignant 9–24 Radiation induced 0–3.6 Caustic 0–15.4 (0.8%/dilatation) Anastomotic 0 Achalasia 0–6.6 624 B.J. Dunkin

50% of patients; prophylactic antibiotics should be given to prevent endocarditis (see earlier: Section A). Hematemesis occurs in 1 to 1.5% of patients but is usually self-limited; hemorrhage requiring transfu- sion is rare. 4. Endoscopic placement of esophageal stents is most commonly per- formed for palliation of obstructing tumors and is sometimes preceded by dilatation. Perforation is most frequently associated with the dilata- tion and it is therefore recommended to avoid dilatation unless absolutely necessary. Complications from the stent itself include erosion with perforation, bleeding, migration, tumor ingrowth with recurrent obstruction, food impaction, and aspiration. Stents placed in the very proximal or distal esophagus are associated with the highest rates of complication. Stents in the cervical esophagus, close to the upper esophageal sphincter, can cause difficulty with swallowing, globus, and predispose to aspiration. Those across the GEJ can cause gastroesophageal reflux with esophagitis and aspiration. The risk of aspiration is minimized by maintaining the patient in a “head-up” position or by using stents with antireflux valves. Esophagitis is managed with H2-blocker therapy or proton pump inhibitors. Recur- rent obstruction is minimized with the use of covered stents and treated with laser or argon plasma coagulator ablation of the tumor ingrowth, or placement of a second stent through the first.

D. Complications of Percutaneous Endoscopic Gastrostomy and Jejunostomy

Large cumulative retrospective studies have reported that 10 to 43% of both adult and pediatric patients have at least one complication following PEG placement. Pneumoperitoneum is a frequent occurrence after percutaneous gastros- tomy. This is the result of air escaping around the puncturing needle, wire, or tube. Routine x-ray films are unwarranted. Air in the abdominal cavity has been shown to last for up to 5 weeks after PEG placement. Patients found to have pneumoperitoneum after gastrostomy must be clinically evaluated. In the absence of abdominal tenderness, leukocytosis, or fever, there is no need for further evaluation. Good skin care is important after gastrostomy. It is common to see a foreign body reaction around the tube with some exudate or granulation tissue. Swab the exudate away with hydrogen peroxide and leave the site open to air. Cauter- ize granulation tissue with silver nitrate. Avoid occlusive dressings; these may lead to skin maceration. Other more significant complications are as follows. 1. Wound infections are common. a. Cause and prevention. Contamination with oral and gastric flora contribute to the incidence of wound infection (particularly with a “pull” and “push” technique). Wound problems can also result 58. Complications of Upper Gastrointestinal Endoscopy 625

from excess tension on the tube (causing pressure necrosis) and a small skin incision (which fails to allow egress of bacte- ria). The incidence is significantly decreased with a single pro- phylactic dose of antibiotic decreased (from 26% to 2% in one study). b. Recognition and management. Signs and symptoms of wound infection include erythema around the gastrostomy tube site several days after the procedure, local tenderness, slight edema of the skin, low-grade fever, and leukocytosis. Incision and drainage of the area under local anesthesia most often resolves the problem. Failure to identify and treat this problem at an early stage can result in necrotizing infections of the abdominal wall and death. 2. Buried bumper syndrome (extrusion of the head of the tube from the gastric lumen into the subcutaneous tissue). a. Cause and prevention. Excessive tension is the cause. Do not tighten up the bumper in an attempt to prevent leakage around the tube, and do not place dressings under the skin anchoring device. At all times, avoid excess pressure and tension. b. Recognition and management. This condition may cause wound infection or leakage of gastric juice and feedings into the peri- toneal cavity or subcutaneous tissues. Remove the gastrostomy tube, place the patient on nasogastric suction, and treat the patient with parenteral antibiotics until the gastrostomy tract inflamma- tion and skin necrosis resolve. 3. Leakage of feedings into the peritoneal cavity is one of the most serious complications. a. Cause and prevention. Leakage is usually the result of separa- tion of the gastric and abdominal walls and often is due to necro- sis of the gastric wall from excessive tension on the catheter. Premature dislodgment of the tube from the gastric lumen (before a tract has formed) or malposition of the tube during attempted reinsertion may also cause this problem. b. Recognition and management. Patients who develop abdominal tenderness, fever, or leukocytosis should be evaluated for leak- age and the resultant peritonitis. This is done by instilling water-soluble contrast material into the gastrostomy tube under fluoroscopic guidance. Intraperitoneal extravasation indicates something has gone awry. If the contrast study indicates that the head of the tube remains in the stomach and that the extravasa- tion is around it, the tube can usually be salvaged by inserting a nasogastric tube, placing the PEG to drainage, and administering intravenous fluids and antibiotics. If the contrast study reveals complete separation of the gastric and abdominal walls with dis- lodgment of the tube from the stomach, the tube should be pulled from the abdominal wall and the treatment just described insti- tuted. A patient whose PEG has been pulled out inadvertently less than 2 weeks from the time of insertion should be treated simi- larly. If at any time the patient’s condition begins to deteriorate 626 B.J. Dunkin

or signs of peritonitis worsen, exploratory laparotomy or laparoscopy with operative repair should be performed. 4. Gastrocolic fistula has rarely been known to occur after percutaneous gastrostomy. a. Cause and prevention. This fistula may be due to puncture of the colon at the time of gastrostomy or pinching of the colon between the gastric and abdominal walls with subsequent necro- sis of the colonic wall and fistula formation. It is prevented by careful technique. Laparoscopic visualization (described in Chapter 24) may be useful in difficult cases. b. Recognition and management. This complication usually becomes apparent after several weeks with the development of severe diarrhea following feedings. It may be documented with an upper gastrointestinal series or barium enema. In nearly all cases, the condition may be treated by removing the gastrostomy tube. The fistula closes rapidly once the tube has been removed. 5. Progressive enlargement of the stoma around the gastrostomy tube may occur in some patients. a. Cause and prevention. Excessive tension, poor nutritional status, and excess movement of the tube at skin level can cause this problem. As previously mentioned, excess tension is to be avoided. Minimize tube mobility by securing the tube or using a stabilizing device. b. Recognition and management. The problem is easily recognized by leakage of gastric juice and feedings around the tube. Replac- ing the gastrostomy tube with a larger size provides only a short- term solution, as the tract generally continues to enlarge. A better solution is to remove the tube entirely and allow the tract to close. When the tract contracts, insert a new tube and stabilize it at the skin level. 6. Neoplastic seeding (to skin around the gastrostomy tube) has been reported when PEG placement for both oropharyngeal and esophageal cancers. This is not an issue when the gastrostomy is placed for palli- ation in a patient with limited life span. It should be kept in mind, however, when gastrostomy placement is planned prior to neoadjuvant therapy. There may be advantages to using an introducer technique in this setting, but this has not been tested.

E. Selected References

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ASGE recommendations for antibiotic prophylaxis for endoscopic procedures. Gastro- intest Endosc 1995;42(6):633. Cook DJ, Guyatt GH, Salena BJ, et al. Endoscopic therapy for acute nonvariceal upper gastrointestinal hemorrhage: a meta-analysis. Gastroenterology 1992;102:139. Jain NK, Larson DE, Schroeder KW, et al. Antibiotic prophylaxis for percutaneous endo- scopic gastrostomy. A prospective, randomized, double-blind clinical trial. Ann Intern Med 1987;107:824–828. Lee JG, Lieberman DA. Complications related to endoscopic hemostasis techniques. Gastrointest Endosc Clin North Am 1996;6(2):305–321. Marks JM. Esophagogastroduodenoscopy. In: Ponsky JL, ed. Complications of Endoscopic and Laparoscopic Surgery. Prevention and Management. Philadelphia: Lippincott- Raven, 1997;13–28. Ponsky JL, Dunkin BJ. Percutaneous endoscopic gastrostomy. In: Yamada T, ed. Textbook of Gastroenterology. Philadelphia: Lippincott-Raven, 1997. Preclik G, Grune S, Leser HG, et al. Prospective, randomized, double blind trial of pro- phylaxis with single dose of co-amoxiclav before PEG. Br J Surg 1999;319:881–884. Repici A, Ferrari A, DeAngelis C, et al. Adrenaline plus cyanoacrylate injection for treat- ment of bleeding peptic ulcers after failure of conventional endoscopic haemostasis. Dig Liver Dis 2002;34(5):349–355. Silvis SE, Nebel O, Rogers G, et al. Endoscopic complications. Results of the 1974 American Society of Gastrointestinal Endoscopy Survey. JAMA 1976;235:928.