Hemodynamics after endoscopic submucosal injection of epinephrine in a porcine model

Background and study aims: Endoscopic submucosal injection of epinephrine may cause systemic effects on the cardiovascular system. The aim of this experimental study was to assess systemic hemodynamic changes after submucosal injection of epinephrine during upper gastrointestinal endoscopy in a porcine model.

Methods: Measurements were taken from 12 pigs under general anesthesia. During gastroscopy 5 mL of normal saline, and 2.5 mL and 5 mL of epinephrine (1:10 000) were injected into the submucosal layers of the gastric antrum, corpus, and distal esophagus. After each injection, the cardiac index and global end diastolic volume index (GEDVI, reflecting preload) were measured every 3 minutes by transpulmonary thermodilution for a minimum of 12 minutes. The following parameters were also recorded: heart rate, mean arterial pressure (MAP), and systemic vascular resistance index (SVRI, reflecting afterload).

Results: Significant hemodynamic changes were observed after submucosal injection of epinephrine into the esophagus, including heart rate (maximum + 4 %) and MAP (maximum – 4 %) after injection of 2.5 mL epinephrine, and stronger changes in heart rate (maximum + 13 %), cardiac index (maximum + 21 %), MAP (maximum – 4 %), and SVRI (maximum – 12 %) after the injection of 5 mL epinephrine. After submucosal injection of epinephrine into the gastric antrum and corpus, hemodynamic effects were less evident. Here significant changes were observed in heart rate (maximum + 3 %), MAP (maximum – 2 %), cardiac index (maximum + 7 %), and SVRI (maximum – 8 %) only after the injection of 5 mL epinephrine into the antrum.

Conclusion: Endoscopic submucosal injection of epinephrine is associated with changes in systemic hemodynamic parameters, especially when performed in the esophagus, and the procedure might therefore induce harmful side effects.

• References

• 1 Cappell MS, Friedel D. Acute nonvariceal upper gastrointestinal bleeding: endoscopic diagnosis and therapy. Med Clin North Am 2008; 92: 511-550
• 2 Cook DJ, Guyatt GH, Salena BJ et al. Endoscopic therapy for acute nonvariceal upper gastrointestinal hemorrhage: a meta-analysis. Gastroenterology 1992; 102: 139-148
• 3 Chung SC, Leung JW, Steele RJ et al. Endoscopic injection of adrenaline for actively bleeding ulcers: a randomised trial. Br Med J 1988; 296: 1631-1633
• 4 Steele RJ, Park KG, Crofts TJ. Adrenaline injection for endoscopic haemostasis in non-variceal upper gastrointestinal haemorrhage. Br J Surg 1991; 78: 477-479
• 5 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
• 6 Chiu PW, Sung JJ. Acute nonvariceal upper gastrointestinal bleeding. Curr Opin Gastroenterol 2010; 26: 425-428
• 7 Vergara M, Calvet X, Gisbert JP. Epinephrine injection versus epinephrine injection and a second endoscopic method in high risk bleeding ulcers. Cochrane Database Syst Rev 2007; 18 CD005584
• 8 Hirao M, Masuda K, Asanuma T et al. Endoscopic resection of early gastric cancer and other tumors with local injection of hypertonic saline-epinephrine. Gastrointest Endosc 1988; 34: 264-269
• 9 Tanaka M, Ono H, Hasuike N et al. Endoscopic submucosal dissection of early gastric cancer. Digestion 2008; 77: 23-28
• 10 Huber W, Umgelter A, Reindl W et al. Volume assessment in patients with necrotizing pancreatitis: a comparison of intrathoracic blood volume index, central venous pressure, and hematocrit, and their correlation to cardiac index and extravascular lung water index. Crit Care Med 2008; 36: 2348-2354
• 11 Della Rocca G, Costa MG, Pietropaoli P. How to measure and interpret volumetric measures of preload. Curr Opin Crit Care 2007; 13: 297-302
• 12 Chung SC, Leung JW, Steele RJ et al. Endoscopic injection of adrenaline for actively bleeding ulcers: a randomised trial. Br Med J (Clin Res Ed) 1988; 296: 1631-1633
• 13 Thomopoulos KC, Vagenas KA, Vagianos CE et al. Changes in aetiology and clinical outcome of acute upper gastrointestinal bleeding during the last 15 years. Eur J Gastroenterol Hepatol 2004; 16: 177-182
• 14 Arasaradnam RP, Donnelly MT. Acute endoscopic intervention in non-variceal upper gastrointestinal bleeding. Postgrad Med J 2005; 81: 92-108
• 15 Uraoka T, Saito Y, Yamamoto K et al. Submucosal injection solution for gastrointestinal tract endoscopic mucosal resection and endoscopic submucosal dissection. Drug Des Devel Ther 2009; 2: 131-138
• 16 Probst A, Maerkl B, Bittinger M et al. Gastric ischemia following endoscopic submucosal dissection of early gastric cancer. Gastric Cancer 2010; 13: 58-61
• 17 Hilzenrat N, Lamoureux E, Alpert L. Gastric ischemia after epinephrine injection for upper GI bleeding in a patient with unsuspected amyloidosis. Gastrointest Endosc 2003; 58: 307-308
• 18 Loperfido S, Patelli G, La Torre L. Extensive necrosis of gastric mucosa following injection therapy of bleeding peptic ulcer. Endoscopy 1990; 22: 285-286
• 19 Sugai K, Kajiwara E, Mochizuki Y et al. Intramural duodenal hematoma after endoscopic therapy for a bleeding duodenal ulcer in a patient with liver cirrhosis. Intern Med 2005; 44: 954-957
• 20 Rohrer B, Schreiner J, Lehnert P et al. Gastrointestinal intramural hematoma, a complication of endoscopic injection methods for bleeding peptic ulcers: a case series. Endoscopy 1994; 26: 617-621
• 21 Bedford RA, van Stolk R, Sivak MV Jr et al. Gastric perforation after endoscopic treatment of a Dieulafoy’s lesion. Am J Gastroenterol 1992; 87: 244-247
• 22 Pescatore P, Jornod P, Borovicka J et al. Epinephrine versus epinephrine plus fibrin glue injection in peptic ulcer bleeding: a prospective randomized trial. Gastrointest Endosc 2002; 55: 348-353
• 23 Villaneuva C, Balanzo J, Espinos JC et al. Endoscopic injection therapy of bleeding ulcer: a prospective and randomized comparison of adrenaline alone or with polidocanol. J Clin Gastroenterol 1993; 17: 195-200
• 24 Gevers AM, De Goede E, Simoens M et al. A randomized trial comparing injection therapy with hemoclip and with injection combined with hemoclip for bleeding ulcers. Gastrointest Endosc 2002; 55: 466-469
• 25 von Delius S, Thies P, Umgelter A et al. Hemodynamics after endoscopic submucosal injection of epinephrine in patients with nonvariceal upper gastrointestinal bleeding: a matter of concern. Endoscopy 2006; 38: 1284-1288
• 26 Liou TC, Lin SC, Wang HY et al. Optimal injection volume of epinephrine for endoscopic treatment of peptic ulcer bleeding. World J Gastroenterol 2006; 12: 3108-3113
• 27 Sung JY, Chung SC, Low JM et al. Systemic absorption of epinephrine after endoscopic submucosal injection in patients with bleeding peptic ulcers. Gastrointest Endosc 1993; 39: 20-22
• 28 Stevens PD, Lebwohl O. Hypertensive emergency and ventricular tachycardia after endoscopic epinephrine injection of a Mallory-Weiss tear. Gastrointest Endosc 1994; 40: 77-78
• 29 Tønnesen H, Puggaard L, Braagaard J et al. Stress response to endoscopy. Scand J Gastroenterol 1999; 34: 629-631
• 30 Adachi W, Yazawa K, Owa M et al. Quantification of cardiac stress during EGD without sedation. Gastrointest Endosc 2002; 55: 58-64
• 31 Hoffman BB, Lefkowitz RJ. Catecholamines, sympathomimetic drugs, and adrenergic receptor antagonists. In: Hardman JG, Limbird LE, Gilman AG, eds. The pharmacological basis of therapeutics. New York: McGraw-Hill; 2001. 10. edn. 215-268
• 32 LeVeen HH, Diaz C, Falk G et al. A proposed method to interrupt gastrointestinal bleeding: preliminary report. Ann Surg 1972; 175: 459-465
• 33 Loizou LA, Bown SG. Endoscopic treatment for bleeding peptic ulcers: randomised comparison of adrenaline injection and adrenaline injection + Nd:YAG laser photocoagulation. Gut 1991; 32: 1100-1103
• 34 Steele RJ, Park KG, Crofts TJ. Adrenaline injection for endoscopic haemostasis in non-variceal upper gastrointestinal haemorrhage. Br J Surg 1991; 78: 477-479
• 35 Park KG, Steele RJ, Masson J. Endoscopic injection of adrenaline for benign oesophageal ulcer haemorrhage. Br J Surg 1994; 81: 1317-1318
• 36 Liou TC, Chang WH, Wang HY et al. Large-volume endoscopic injection of epinephrine plus normal saline for peptic ulcer bleeding. J Gastroenterol Hepatol 2007; 22: 996-1002
• 37 Park CH, Lee SJ, Park JH et al. Optimal injection volume of epinephrine for endoscopic prevention of recurrent peptic ulcer bleeding. Gastrointest Endosc 2004; 60: 875-880
• 38 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
• 39 Marmo R, Rotondano G, Piscopo R et al. Dual therapy versus monotherapy in the endoscopic treatment of high-risk bleeding ulcers: a meta-analysis of controlled trials. Am J Gastroenterol 2007; 102: 279-289
• 40 Barkun AN, Martel M, Toubouti Y et al. Endoscopic hemostasis in peptic ulcer bleeding for patients with high-risk lesions: a series of meta-analyses. Gastrointest Endosc 2009; 69: 786-799