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ERCP and the problem of sepsis
0016-5107/82/2803-0197$02.00/0 GASTROINTESTINAL ENDOSCOPY Copyrighl © 1982 by the American Society for Gastrointestinal Endoscopy
Symposium Selected papers from the Cleveland Clinic Course UERCP: Diagnostic and Therapeutic Aspects-An International Symposium," March 19 to 21, 1981 Editors: Michael V. Sivak, Jr., MD Bernard Levin, MD
ERCP and the problem of sepsis Joseph E. Geenen, MD
A variety of complications have been associated with endoscopic retrograde cholangiopancreatography (ERCP).1-5 The most serious complication, however, has been infection or sepsis, which is usually associated with either partial obstruction of the pancreatic duct or the common bile duct. Cholangitis or pancreatic sepsis had developed in most of the patients who died after ERCP. The reported overall complication rate associated with ERCP varies between 2 and 8%.1-5 Reports have also indicated that the complication rate decreased with the experience of the endoscopist. 1
of the duodenum by the cannula or endoscope, This is most often the result of a distorted duodenal anatomy and cannulation failure, Intramural injections of contrast material usually do not result in any significant morbidity or mortality, Cholangitis is associated with ERCP in 0,06 to 0,8% of the cases,1,3 Pancreatic sepsis or abscess formation, the most serious complication associated with ERCP, occurs in 0,05 to 1.3% of ERCP examination,1,3 The mortality rate associated with ERCP is reported to vary between 0,001 and 0.08%.1-3 Most of these fatalities have been associated with bacterial infections or sepsis, either as the resu It of cholangitis or pancreatic abscess formation,
CAUSE OF SEPSIS ASSOCIATED WITH ERCP COMPLICATIONS The most common complication associated with ERCP is pancreatitis. An incidence of 0.7 to 7.4% has been reported (Table 1) .1-3, 5 Approximately 70% of all patients who undergo ERCP have increased levels of serum amylase, which return to normal in 1 to 4 days, However, the clinical picture of pancreatitis manifested by abdominal pain, fever, and leukocytosis is much less frequent. Most patients in whom clinical pancreatitis develops after ERCP are being studied for underlying pancreatic disease, The cause of the pancreatitis is unknown, but it appears to be related to the number of injections that are attempted and to the underlying condition of the pancreas, The incidence of pancreatitis seems to be inversely related to the experience of the endoscopist. Drug reactions occur within a range of 0,01 to 6%,1-3 This does not include the frequent complication of phlebitis, primarily following the intravenous injection of diazepam, Because ERCP is a more prolonged procedure, multiple and large doses of sedatives and analgesics are used, which can produce either cardiac or respiratory depression. Injury to the gastrointestinal tract is a rare complication of ERCp 1- 5 and is usually caused by perforation From the Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin, Reprint requests: Joseph E. Geenen, MD, 1333 College Avenue, Racine, Wisconsin 53403. VOLUME 28, NO.3, 1982
The association of transient bacteremia with endoscopic evaluation of the upper gastrointestinal tract has been well documented. This transient bacteremia is one potential cause of sepsis. In several reported prospective studies, the incidence of bacteremia after ERCP has been reported as low as 0%6 to as high as 14%.7 When bacteremia does occur, it has been shown that bacteria from the blood cultures are often the same kind of bacteria as in cultures from the endoscopic equipment used the procedure. This is usually the result of inadequate disinfection of endoscopes and accessory equipment. Although transient bacteremia may occur because of contaminated equipment, significant pathogenic bacterial infections rarely occur unless there is a concurrent organic obstruction of either the bile duct or the pancreatic duct or the presence of a pseudocyst. Another cause of bacteremia may be related to the presence of bacteria in the bile duct or pancreatic duct beyond a strictu re, or to bacteria in a pseudocyst of the pancreas. In patients with sclerosing cholangitis there is a significant incidence of bacteremia after ERCP because of the presence of bacteria in bile ducts above a stricture.
CHOLANGITIS Two surveys of ERCP complications reveal an incidence of cholangitis of 0.6 to 0.8%.1,3 Bilbao et al. 1 reported 72 cases (0.8%) of cholangitis in 8681 patients who underwent ERCP examination. Eight patients 197
Table 1. Complications of endoscopic retrograde cholangiopancreatographya Types Pancreatitis Drug reaction Instrument injury Cholangitis Pancreatic sepsis pseudocyst a
Incidence range (%)
0.7-7.4 0.1-0.6 0.07-0.3 0.6-0.8 0.5-1.3
Data from References 1 to 5.
(10%) who had cholangitis died. In the American Society for Gastrointestinal Endoscopy (A/S/G/E) survey3 of 3884 ERCP examinations, there were 25 cases (0.6%) of cholangitis. In this series, two of the patients (8%) who had cholangitis died. In these two large series of patients with cholangitis after ERCP, almost all had bile duct obstruction caused by stricture, stone, or tumor. Cholangitis rarely occurs unless there is a preexisting partial obstruction of the biliary tree. Cholangitis usually occurs within 72 hours after an ERCP examination, most often in patients with poor drainage of contrast material from the biliary tree. The onset of cholangitis is often dramatic with chills, fever, and hypotension. The organisms most frequently isolated are Escherichia coli or Pseuodomonas aeruginosa.
PANCREATIC SEPSIS ABSCESS Pancreatic phlegmon or abscess usually follows the injection of contrast material into a pseudocyst or beyond a pancreatic duct stricture. The stricture may be the result of a tumor or inflammatory mass. Bilbao et al. 1 reported 25 cases of (0.03%) of pancreatic infection following 8681 ERCP examinations. Five (20%) of these patients in whom infections developed after ERCP died. Tumor obstruction was the cause of the sepsis in four of the five fatalities; the fifth death was due to a pseudocyst abscss. In the A/S/G/E survey,3 there were two cases of pancreatic infection in 3884 examinations. There were two deaths; these patients were found to have carcinoma of the pancreas at autopsy.
ETIOLOGY OF CHOLANGITIS AND PANCREATIC SEPSIS The major mechanisms implicated in the etiology of cholangitis or pancreatic sepsis after ERCP are (1) contaminated endoscopes, cannulas, water bottles, and contrast material; (2) partial organic obstruction of pancreatic duct or biliary tree, and (3) overfilling of contrast material beyond a stricture site or into a pancreatic pseudocyst. Polymicrobial sepsis of the pancreaticobiliary tree after the use of contaminated equipment has been recently reported. 8 Transmission of bacteria (P. aeruginosa) by an infected water bottle has been reported by Martin et al. 9 The risk of infection is obviously greater in patients with decreased host resistance to infections. Greene et al. 1O reported two patients with acute leukemia in whom Pseudomonas septicemia followed endoscopy. The instrument used subse198
quently yielded enteric organisms, including Pseudomonas on bacterial culture. Patients with biliary stasis may have infected bile prior to ERCP examination. Flemma et al. 11 found infected bile in more than 65% of patients with obstruction of the biliary tree at the time of surgery. Thus, cholangitis and septicemia may result from dissemination of bacteria already present in the bile above a stricture. Cannulation and injection of contrast material could result in disruption of liver cells with transmission of biliary contents directly into the hepatic sinusoids, thereby causing septicemia. 12 Bacteria may also be present in a pseudocyst or behind a pancreatic duct partially obstructed by a stricture or tumor. "Overfilling" a pseudocyst with contrast material or placing contrast material beyond a partially obstructed pancreatic duct may cause disruption of small pancreatic ducts and subsequent abscess formation or septicemia.
PREVENTION OF SEPSIS IN ERCP The risk of transmission of nosocomial pathogens by contaminated endoscopes or accessory equipment has been well documented. It is, therefore, important to adhere to strict disinfectant techniques. The cannula and accessory equipment, if not disposable, should be gas sterilized following each procedure. Effective disinfection of the endoscope with gluteraldehyde or iodophors should be done between procedures and also at the end of the day. Monthly bacterial cultures of the procedure room surfaces and the accessory equipment are recommended. The efficacy of prophylactic antibiotics, either added to the contrast material or administered systemically, is still unproved. The results of controlled clinical study, with and without gentamicin added to ERCP contrast material, suggest that gentamicin did not reduce the frequency of infections. 13 However, this study was inconclusive because many of the patients with duct obstruction received systemic antibiotics, and the rate of infection was too low to show a significant difference between the two groups. Because of the increased incidence of sepsis in patients with partially obstructed ducts or pseudocyst, Silvis et al. 14 have advocated the use of systemic antibiotics administered prophylactically or immediately after ERCP examination. To prevent sepsis caused by overfilling a partially obstructed duct, only a small amount of contrast material should be injected beyond the obstruction or into a pseudocyst of the pancreas. Whenever a poorly drained pseudocyst becomes overfilled during injection of contrast, or if contrast material is injected beyond a stricture of the common bile duct or pancreatic duct, close observation and possibly early surgical intervention are recommended.
CONCLUSION The incidence of sepsis after ERCP examinations is approximately 1%. Almost all of the cases of infection are associated with cholangitis or pancreatic sepsis. The mortality of patients in whom sepsis developed varies between 1.6 and 20%. The major factors contribGASTROINTESTINAL ENDOSCOPY
uting to sepsis include the use of contaminated equipment, injection of contrast material beyond a stricture of the bile duct or pancreatic duct, and overfilling a pancreatic pseudocyst with contrast material. Prevention of sepsis requires proper disinfection of the endoscope and endoscopic equipment, use of systemic antibiotics when obstruction of ,either duct is proven or suspected, and surgical drainage of an obstructed duct or pseudocyst. Attention to these principles should markedly reduce the danger of septic complications following ERCP.
6.
7.
8. 9.
10.
REFERENCES 1. BILBAO MK, DOTTER CT, LEE TG, KATON RM: Complications of endoscopic retrograde cholangiopancreatography (ERCP): study of 10,000 cases. Gastroenterology 40:314, 1976 2. IHRE T, HELLERS G: Complications of endoscopic retrograde cholangiopancreatography. Acta Chir Scand 143:167, 1977 3. NEBEL ET, SILVIS SE, ROGERS G, SUGAWA C. MANDELSTAM P: Complications associated with endoscopic retrograde cholangiopancreatography: results of the 1974 A/S/G/E survey. Gastrointest Endosc 22:34, 1975 4. SHAHMIR M, SCHUMAN BM: Complications of fiberoptic endoscopy. Gastrointest Endosc 26:86, 1980 5. ZIMMON DS, FALKENSTEIN DB, RICCOBONO C. AARON B: Compli-
The intraductal secretin test: an adjunct to ERCP James A. Gregg, MD Endoscopic retrograde cholangiopancreatography (ERCP) has provided the endoscopist with an important means of determining the morphology of the pancreatic and bile ducts. Cannulation of the ampulla also permits manometric assessment of the choledochal and pancreatic sphincters and enables the endoscopists to perform an intraductal secretin test (IDST) to measure the secretory function of the pancreas. Secretin testing is particularly important in those patients with recurrent upper abdominal pain and suspected pancreatitis in whom the results of all other diagnostic studies, including ERCP, are negative, since abnormalities in pancreatic secretion frequently precede morphological changes in the pancreatic duct. The pure pancreatic juice (PPJ) obtained by endoscopic cannulation after secretin 1-3 or secretin and cholecystokinin-pancreazymin (CCK-PZ) stimulation 4,5 can be studied for flow rate,2,4 electrolytes,4, 6 enzymes,!,8 tumor antigens,2,8 cytology,9,10 and bacteria,11 The effects of various drugs and hormones on pancreatic secretion can also be investigated, and PPJ can be subjected to new studies that may better determine the presence and type of pancreatic disease. Such studies using PPJ provide more information about the pancreas than those using duodenal juice (DJ) obtained during duodenal secretin test (DST), since PPJ is not mixed with bile or intestinal juice and has not undergone activation of pancreatic enzymes Reprint requests: James A. Gregg, MO, 110 Francis Street, Boston, Massachusetts 02215, VOLUME 28, NO.3, 1982
11. 12.
13.
14.
cations of endoscopic retrograde cholangiopancreatography: Gastroenterology 69:303, 1975 Low DE, MICFIKIER AB, KENNEDY IK, STIVER HG: Infectious complications of endoscopic retrograde cholangiopancreatography: a prospective assessment. Arch Intern Med 140:1076, 1980 PARKER HW, GEENEN IE, BJORK H, STEWART ET: A prospective analysis of fever and bacteremia following ERCP. Gastrointest Endosc 25:102, 1979 ELSON CO, HATTORI K, BLACKSTONE MO: Polymicrobial sepsis following ERCP. Gastroenterology 69:507, 1975 MARTIN TR, SILVIS SE, VENNES 1A: The reduction of septic complications following ERCP in obstructed patients (abstract). Clin Res 24:566A, 1976 GREENE WH, MOODY M, HARTLEY R, EFFMAN E, AISNER J, YOUNG VM, WIERNIK PH: Esophagoscopy as a source of Pseudomonas aeruginosa sepsis in patients with acute leukemia: the need for sterilization of endoscopes. Gastroenterology 67:912, 1974 FLEMMA RJ, FLINT LM, OSTERHOUT S, SHINGLETON WW: Bacteriologic studies of biliary tract infection. Ann Surg 166:563, 1967 BICKMAN DE: Route of flow and micropathology resulting from retrograde intrabiliary injection of Indian ink and ferritin in experimental animals. Gastroenterology 67:234, 1974 MARTIN TR, GEENEN lE, RASKIN lB, ET AL: The reduction of septic complications following ERCP in obstructed patients (abstract). Gastrointest Endosc 25:43, 1979 SILVIS SE, VENNES lA, ROHRMANN CA: Endoscopic pancreatography in the evaluation of patients with suspected pancreatic pseudocyst. Am J Gastroenterology 61:452, 1974
by enterokinase. Secretin testing can be performed at the time of routine ERCP or in conjunction with upper gastrointestinal endoscopy. The IDST is not time consuming and can be performed by anyone with adequate ERCP experience. When performed in conjunction with ERCP, it is probably best to do the study prior to contrast injection, since the effects of pancreatic duct opacification on pancreatic secretion are unknown, Unfortunately, when the IDST and ERCP are done in this sequence, there is efflux of contrast material from the pancreatic duct immediately after cannula withdrawal; this is a result of active pancreatic secretion.
METHODOLOGY Preparation for the IDST is the same as for ERCP with the exception that the patient is not given antispasmodics, ganglionic blocking agents,12 or glucagon,! since these compounds significantly reduce secretory flow rates, enzyme secretion, and concentration. Diazepam itself does not appear to affect these parameters. 12 After proper orientation of the duodenoscope to the papilla, secretin (1 unit/kg of body wt) is administered intravenously as a bolus without prior skin testing. Flow of PPJ begins within 30 to 60 sec and reaches peak levels in several minutes. The pancreatic juice secreted during the first few minutes should not be used for diagnostic studies, since it represents primarily "washout" of duct contents. This fluid is high in protein and low in bicarbonate (HC0 3-). From 5 to 10 min after injection, peak secretory flow rates (PSFR) are stable, but protein secretion may vary slightly. To avoid any minute to minute changes in protein con199
Symposium Selected papers from the Cleveland Clinic Course UERCP: Diagnostic and Therapeutic Aspects-An International Symposium," March 19 to 21, 1981 Editors: Michael V. Sivak, Jr., MD Bernard Levin, MD
ERCP and the problem of sepsis Joseph E. Geenen, MD
A variety of complications have been associated with endoscopic retrograde cholangiopancreatography (ERCP).1-5 The most serious complication, however, has been infection or sepsis, which is usually associated with either partial obstruction of the pancreatic duct or the common bile duct. Cholangitis or pancreatic sepsis had developed in most of the patients who died after ERCP. The reported overall complication rate associated with ERCP varies between 2 and 8%.1-5 Reports have also indicated that the complication rate decreased with the experience of the endoscopist. 1
of the duodenum by the cannula or endoscope, This is most often the result of a distorted duodenal anatomy and cannulation failure, Intramural injections of contrast material usually do not result in any significant morbidity or mortality, Cholangitis is associated with ERCP in 0,06 to 0,8% of the cases,1,3 Pancreatic sepsis or abscess formation, the most serious complication associated with ERCP, occurs in 0,05 to 1.3% of ERCP examination,1,3 The mortality rate associated with ERCP is reported to vary between 0,001 and 0.08%.1-3 Most of these fatalities have been associated with bacterial infections or sepsis, either as the resu It of cholangitis or pancreatic abscess formation,
CAUSE OF SEPSIS ASSOCIATED WITH ERCP COMPLICATIONS The most common complication associated with ERCP is pancreatitis. An incidence of 0.7 to 7.4% has been reported (Table 1) .1-3, 5 Approximately 70% of all patients who undergo ERCP have increased levels of serum amylase, which return to normal in 1 to 4 days, However, the clinical picture of pancreatitis manifested by abdominal pain, fever, and leukocytosis is much less frequent. Most patients in whom clinical pancreatitis develops after ERCP are being studied for underlying pancreatic disease, The cause of the pancreatitis is unknown, but it appears to be related to the number of injections that are attempted and to the underlying condition of the pancreas, The incidence of pancreatitis seems to be inversely related to the experience of the endoscopist. Drug reactions occur within a range of 0,01 to 6%,1-3 This does not include the frequent complication of phlebitis, primarily following the intravenous injection of diazepam, Because ERCP is a more prolonged procedure, multiple and large doses of sedatives and analgesics are used, which can produce either cardiac or respiratory depression. Injury to the gastrointestinal tract is a rare complication of ERCp 1- 5 and is usually caused by perforation From the Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin, Reprint requests: Joseph E. Geenen, MD, 1333 College Avenue, Racine, Wisconsin 53403. VOLUME 28, NO.3, 1982
The association of transient bacteremia with endoscopic evaluation of the upper gastrointestinal tract has been well documented. This transient bacteremia is one potential cause of sepsis. In several reported prospective studies, the incidence of bacteremia after ERCP has been reported as low as 0%6 to as high as 14%.7 When bacteremia does occur, it has been shown that bacteria from the blood cultures are often the same kind of bacteria as in cultures from the endoscopic equipment used the procedure. This is usually the result of inadequate disinfection of endoscopes and accessory equipment. Although transient bacteremia may occur because of contaminated equipment, significant pathogenic bacterial infections rarely occur unless there is a concurrent organic obstruction of either the bile duct or the pancreatic duct or the presence of a pseudocyst. Another cause of bacteremia may be related to the presence of bacteria in the bile duct or pancreatic duct beyond a strictu re, or to bacteria in a pseudocyst of the pancreas. In patients with sclerosing cholangitis there is a significant incidence of bacteremia after ERCP because of the presence of bacteria in bile ducts above a stricture.
CHOLANGITIS Two surveys of ERCP complications reveal an incidence of cholangitis of 0.6 to 0.8%.1,3 Bilbao et al. 1 reported 72 cases (0.8%) of cholangitis in 8681 patients who underwent ERCP examination. Eight patients 197
Table 1. Complications of endoscopic retrograde cholangiopancreatographya Types Pancreatitis Drug reaction Instrument injury Cholangitis Pancreatic sepsis pseudocyst a
Incidence range (%)
0.7-7.4 0.1-0.6 0.07-0.3 0.6-0.8 0.5-1.3
Data from References 1 to 5.
(10%) who had cholangitis died. In the American Society for Gastrointestinal Endoscopy (A/S/G/E) survey3 of 3884 ERCP examinations, there were 25 cases (0.6%) of cholangitis. In this series, two of the patients (8%) who had cholangitis died. In these two large series of patients with cholangitis after ERCP, almost all had bile duct obstruction caused by stricture, stone, or tumor. Cholangitis rarely occurs unless there is a preexisting partial obstruction of the biliary tree. Cholangitis usually occurs within 72 hours after an ERCP examination, most often in patients with poor drainage of contrast material from the biliary tree. The onset of cholangitis is often dramatic with chills, fever, and hypotension. The organisms most frequently isolated are Escherichia coli or Pseuodomonas aeruginosa.
PANCREATIC SEPSIS ABSCESS Pancreatic phlegmon or abscess usually follows the injection of contrast material into a pseudocyst or beyond a pancreatic duct stricture. The stricture may be the result of a tumor or inflammatory mass. Bilbao et al. 1 reported 25 cases of (0.03%) of pancreatic infection following 8681 ERCP examinations. Five (20%) of these patients in whom infections developed after ERCP died. Tumor obstruction was the cause of the sepsis in four of the five fatalities; the fifth death was due to a pseudocyst abscss. In the A/S/G/E survey,3 there were two cases of pancreatic infection in 3884 examinations. There were two deaths; these patients were found to have carcinoma of the pancreas at autopsy.
ETIOLOGY OF CHOLANGITIS AND PANCREATIC SEPSIS The major mechanisms implicated in the etiology of cholangitis or pancreatic sepsis after ERCP are (1) contaminated endoscopes, cannulas, water bottles, and contrast material; (2) partial organic obstruction of pancreatic duct or biliary tree, and (3) overfilling of contrast material beyond a stricture site or into a pancreatic pseudocyst. Polymicrobial sepsis of the pancreaticobiliary tree after the use of contaminated equipment has been recently reported. 8 Transmission of bacteria (P. aeruginosa) by an infected water bottle has been reported by Martin et al. 9 The risk of infection is obviously greater in patients with decreased host resistance to infections. Greene et al. 1O reported two patients with acute leukemia in whom Pseudomonas septicemia followed endoscopy. The instrument used subse198
quently yielded enteric organisms, including Pseudomonas on bacterial culture. Patients with biliary stasis may have infected bile prior to ERCP examination. Flemma et al. 11 found infected bile in more than 65% of patients with obstruction of the biliary tree at the time of surgery. Thus, cholangitis and septicemia may result from dissemination of bacteria already present in the bile above a stricture. Cannulation and injection of contrast material could result in disruption of liver cells with transmission of biliary contents directly into the hepatic sinusoids, thereby causing septicemia. 12 Bacteria may also be present in a pseudocyst or behind a pancreatic duct partially obstructed by a stricture or tumor. "Overfilling" a pseudocyst with contrast material or placing contrast material beyond a partially obstructed pancreatic duct may cause disruption of small pancreatic ducts and subsequent abscess formation or septicemia.
PREVENTION OF SEPSIS IN ERCP The risk of transmission of nosocomial pathogens by contaminated endoscopes or accessory equipment has been well documented. It is, therefore, important to adhere to strict disinfectant techniques. The cannula and accessory equipment, if not disposable, should be gas sterilized following each procedure. Effective disinfection of the endoscope with gluteraldehyde or iodophors should be done between procedures and also at the end of the day. Monthly bacterial cultures of the procedure room surfaces and the accessory equipment are recommended. The efficacy of prophylactic antibiotics, either added to the contrast material or administered systemically, is still unproved. The results of controlled clinical study, with and without gentamicin added to ERCP contrast material, suggest that gentamicin did not reduce the frequency of infections. 13 However, this study was inconclusive because many of the patients with duct obstruction received systemic antibiotics, and the rate of infection was too low to show a significant difference between the two groups. Because of the increased incidence of sepsis in patients with partially obstructed ducts or pseudocyst, Silvis et al. 14 have advocated the use of systemic antibiotics administered prophylactically or immediately after ERCP examination. To prevent sepsis caused by overfilling a partially obstructed duct, only a small amount of contrast material should be injected beyond the obstruction or into a pseudocyst of the pancreas. Whenever a poorly drained pseudocyst becomes overfilled during injection of contrast, or if contrast material is injected beyond a stricture of the common bile duct or pancreatic duct, close observation and possibly early surgical intervention are recommended.
CONCLUSION The incidence of sepsis after ERCP examinations is approximately 1%. Almost all of the cases of infection are associated with cholangitis or pancreatic sepsis. The mortality of patients in whom sepsis developed varies between 1.6 and 20%. The major factors contribGASTROINTESTINAL ENDOSCOPY
uting to sepsis include the use of contaminated equipment, injection of contrast material beyond a stricture of the bile duct or pancreatic duct, and overfilling a pancreatic pseudocyst with contrast material. Prevention of sepsis requires proper disinfection of the endoscope and endoscopic equipment, use of systemic antibiotics when obstruction of ,either duct is proven or suspected, and surgical drainage of an obstructed duct or pseudocyst. Attention to these principles should markedly reduce the danger of septic complications following ERCP.
6.
7.
8. 9.
10.
REFERENCES 1. BILBAO MK, DOTTER CT, LEE TG, KATON RM: Complications of endoscopic retrograde cholangiopancreatography (ERCP): study of 10,000 cases. Gastroenterology 40:314, 1976 2. IHRE T, HELLERS G: Complications of endoscopic retrograde cholangiopancreatography. Acta Chir Scand 143:167, 1977 3. NEBEL ET, SILVIS SE, ROGERS G, SUGAWA C. MANDELSTAM P: Complications associated with endoscopic retrograde cholangiopancreatography: results of the 1974 A/S/G/E survey. Gastrointest Endosc 22:34, 1975 4. SHAHMIR M, SCHUMAN BM: Complications of fiberoptic endoscopy. Gastrointest Endosc 26:86, 1980 5. ZIMMON DS, FALKENSTEIN DB, RICCOBONO C. AARON B: Compli-
The intraductal secretin test: an adjunct to ERCP James A. Gregg, MD Endoscopic retrograde cholangiopancreatography (ERCP) has provided the endoscopist with an important means of determining the morphology of the pancreatic and bile ducts. Cannulation of the ampulla also permits manometric assessment of the choledochal and pancreatic sphincters and enables the endoscopists to perform an intraductal secretin test (IDST) to measure the secretory function of the pancreas. Secretin testing is particularly important in those patients with recurrent upper abdominal pain and suspected pancreatitis in whom the results of all other diagnostic studies, including ERCP, are negative, since abnormalities in pancreatic secretion frequently precede morphological changes in the pancreatic duct. The pure pancreatic juice (PPJ) obtained by endoscopic cannulation after secretin 1-3 or secretin and cholecystokinin-pancreazymin (CCK-PZ) stimulation 4,5 can be studied for flow rate,2,4 electrolytes,4, 6 enzymes,!,8 tumor antigens,2,8 cytology,9,10 and bacteria,11 The effects of various drugs and hormones on pancreatic secretion can also be investigated, and PPJ can be subjected to new studies that may better determine the presence and type of pancreatic disease. Such studies using PPJ provide more information about the pancreas than those using duodenal juice (DJ) obtained during duodenal secretin test (DST), since PPJ is not mixed with bile or intestinal juice and has not undergone activation of pancreatic enzymes Reprint requests: James A. Gregg, MO, 110 Francis Street, Boston, Massachusetts 02215, VOLUME 28, NO.3, 1982
11. 12.
13.
14.
cations of endoscopic retrograde cholangiopancreatography: Gastroenterology 69:303, 1975 Low DE, MICFIKIER AB, KENNEDY IK, STIVER HG: Infectious complications of endoscopic retrograde cholangiopancreatography: a prospective assessment. Arch Intern Med 140:1076, 1980 PARKER HW, GEENEN IE, BJORK H, STEWART ET: A prospective analysis of fever and bacteremia following ERCP. Gastrointest Endosc 25:102, 1979 ELSON CO, HATTORI K, BLACKSTONE MO: Polymicrobial sepsis following ERCP. Gastroenterology 69:507, 1975 MARTIN TR, SILVIS SE, VENNES 1A: The reduction of septic complications following ERCP in obstructed patients (abstract). Clin Res 24:566A, 1976 GREENE WH, MOODY M, HARTLEY R, EFFMAN E, AISNER J, YOUNG VM, WIERNIK PH: Esophagoscopy as a source of Pseudomonas aeruginosa sepsis in patients with acute leukemia: the need for sterilization of endoscopes. Gastroenterology 67:912, 1974 FLEMMA RJ, FLINT LM, OSTERHOUT S, SHINGLETON WW: Bacteriologic studies of biliary tract infection. Ann Surg 166:563, 1967 BICKMAN DE: Route of flow and micropathology resulting from retrograde intrabiliary injection of Indian ink and ferritin in experimental animals. Gastroenterology 67:234, 1974 MARTIN TR, GEENEN lE, RASKIN lB, ET AL: The reduction of septic complications following ERCP in obstructed patients (abstract). Gastrointest Endosc 25:43, 1979 SILVIS SE, VENNES lA, ROHRMANN CA: Endoscopic pancreatography in the evaluation of patients with suspected pancreatic pseudocyst. Am J Gastroenterology 61:452, 1974
by enterokinase. Secretin testing can be performed at the time of routine ERCP or in conjunction with upper gastrointestinal endoscopy. The IDST is not time consuming and can be performed by anyone with adequate ERCP experience. When performed in conjunction with ERCP, it is probably best to do the study prior to contrast injection, since the effects of pancreatic duct opacification on pancreatic secretion are unknown, Unfortunately, when the IDST and ERCP are done in this sequence, there is efflux of contrast material from the pancreatic duct immediately after cannula withdrawal; this is a result of active pancreatic secretion.
METHODOLOGY Preparation for the IDST is the same as for ERCP with the exception that the patient is not given antispasmodics, ganglionic blocking agents,12 or glucagon,! since these compounds significantly reduce secretory flow rates, enzyme secretion, and concentration. Diazepam itself does not appear to affect these parameters. 12 After proper orientation of the duodenoscope to the papilla, secretin (1 unit/kg of body wt) is administered intravenously as a bolus without prior skin testing. Flow of PPJ begins within 30 to 60 sec and reaches peak levels in several minutes. The pancreatic juice secreted during the first few minutes should not be used for diagnostic studies, since it represents primarily "washout" of duct contents. This fluid is high in protein and low in bicarbonate (HC0 3-). From 5 to 10 min after injection, peak secretory flow rates (PSFR) are stable, but protein secretion may vary slightly. To avoid any minute to minute changes in protein con199