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Polymicrobial Sepsis Following Endoscopic Retrograde Cholangiopancreatography
GASTIIOENTEHOLOGY 69:507-510, \97f> Copyright@ 1975 hy The Williams & Wilkins Co.
Vol. nH, No.
~
Printed in U.S .A.
POLYMICROBIAL SEPSIS FOLLOWING ENDOSCOPIC RETROGRADE CHOLANGIOPANCREATOGRAPHY
c.
0.
ELSON,
M.D., K.
HATTOHI,
M.D.,
AND
M . 0.
BLACKSTONE,
M.D.
S ection of Gastroenterolo/iy , Department of Medicine , The University of Chicalio Pritzker School of Medicine, Chica/iO, Illinois
Cholangitis with polymicrobial sepsis followed endoscopic retrograde cholangiopancreatography in a patient without biliary tract obstruction. Inadequately disinfected endoscopy equipme1~t was strongly implicated as the source of infection. Results with a new method of disinfection using gluteraldehyde are given. Although endoscopic retrograde cholangiopancreatography (ERCP) is a firmly established diagnostic tool, septic complications continue to accompany its use . The risk of ERCP-related sepsis, although actually low, is nevertheless appreciable . In a recent review 1 and in other published series , 2 ' 7 there were 19 serious infections in 1942 patients, an incidence of 0.97 %. Bilbao et at. have just completed a survey of Olympus JF-B owners in the United States; in 8681 ERCP's , there were 97 (1.1 %) serious infectious complications (unpublished data). When jaundice is the indication for ERCP and extrahepatic obstruction is demonstrated, the incidence is higher. Vennes et at. 8 found an incidence of cholangitis of almost 15% of patients in whom extrahepatic obstruction was demonstrated. Filling a pancreatic pseudocyst carries with it an equal or greater likelihood of septic complications, although the precise incidence is as yet unknown. 9 • 1 0 In these cases it has been assumed that bowel flora has been introduced into a closed system or that bacteria already present were disseminated by the procedure. 1 Cholangitis with polymicrobial sepsis following an ERCP performed at the University of Chicago in a patient
without extrahepatic obstruction led us to examine our ERCP equipment as the source of infection and to consider its prevention through more effective instrument disinfection.
Case Report
A 54-year-old black woman with a 9-year history of ulcerative colitis was admitted to the hospital in May 1974. Her col it is had been largely inactive following a severe first allack and her only medication had been low doses of azulfidine as maintenance. Two months prior to admission she developed generalized urticaria and periorbital edema. She was seen by several physicians but the et iology remained obscure . One month before admission liver function tests were fi>und to be abnormal: SGOT 162 , SGPT 211 (normal fi>r both less than 35), bilirubin 0.7, alkaline phosphatase 99 (normal less than 45). There was no exposure to hepatitis or history of jaundice and the hepatitis-associated antigen was negative . Repeat tests done 1 month later were unchanged and she was admitted for liver biopsy which showed mild focal hepatitis but also portal fibrosis of a degree sufficient to raise the question of sclervsing cholangitis as an underlying process. Intravenous contrast studies of the biliary tract were not helpful. ERCP was performed by one of us (K.H.). The procedure was uneventful with biliary ducts, gallbladder, and main pancreatic duct all visualized. AlReceived February 24, 1975. Accept ed April 12, though the intrahepatic biliary tree was irregular and ectatic, there was no evidence of stric1975. Address requests for reprints to: C. 0 . Elson , M.D. , ture, stones, or carcinoma. Eighteen hours after the procedure the patient developed fever to Department of Medicine, The University of Chica go, 40°C, right upper quadrant pain, and tenderBox 400, 950 East 59th Street, Chicago, ness . Blood cultures were drawn 1 and subseIllinois 60637. 507
508
Vol. 69, No. 2
CASE REPORTS
quently grew Pseudomonas aeruginosa and Enterobacter aerogenes. She quickly responded to a course of antibiotic treatment. The cannula and endoscope used in the procedure were later cultured and the same organisms as were isolated from her blood were identified. The P. aeru{?inosa isolated from the patient's blood and from the endoscopy room were pyocin-typed 11 and found to be identical, indicating a nosocomial source of infection .
TABLE
1. Cultures of equipment and room usin{? the
conventional method of disinfection Culture result
Culture of
ERCP cannula" Olympus JFB biopsy channel"
Olympus JFB-2 biopsy channel
Methods Multiple cultures were taken of the endoscopy room sink, counters, and walls with sterile swabs. A few milliliters of water were collected from the wash bottles. The endoscope was cultured after routine alcohol disinfection (according to manufacturer's instruction) by Hushing the suction channel with sterile water and collecting the effluent. The cannulae were cultured in a similar manner. All specimens were sent to the hospital's microbiology laboratory where they were handled by routine bacteriological methods. The method of disinfection was then changed from alcohol to 2% gluteraldehyde as proposed by Axon et a!. 12 The gl uteraldehyde was allowed to remain in the suction channel and wash bottle for 10 min. These were then thoroughly f1ushed with sterile water. If the instrument was not to be immediately used, the various ports were covered with sterile gauze before storage. The cannulae were individually wrapped and then sterilized with ethylene oxide. Cultures were taken immediately before and after an ERCP.
Results Bacteriology of endoscopic equipment after alcohol disinfection. The results shown in table 1 are very similar to those of Axon et a!. , 12 in that Pseudomonas and other enterobacteriaceae were found f1uorishing in the endoscopy equipment despite the standard disinfection procedure of soap, water, and 70% alcohol. Bacteriology of the ERCP equipment after gluteraldehyde disinfection. The results of this method are summarized in table 2. Evident from this bacteriology data is the fact that in the main, only mouth f1ora is cultured. The more virulent pathogens found in the inadequately disinfected equipment were seldom found in these cultures.
Wash bottles (2) Sink counter and drain, endoscopy room Dimethylsilicone Walls, cabinets, drawers of endoscopy room
P. aeruginosa E . cloacae P. aeruginosa E. aerogenes C. freundii Kl. pneumoniae P. aeruginosa K. pneumoniae E. coli E . aerogenes P. aeruginosa A. hemolyticans P. aeruginosa No growth Few bacillus species
"Used in present case.
2. Cultures of 10 consecutive cases ut iliz in/i the gluteraldehyde m ethod of disinfection
TABLE
Time culture ta ken
Site of iso late
Culture result
(10) No g-rowth (10) No growth
Pre-ERCP
Cannula Suction channel
Post-ERCP
(10) a-Hemolytic Suction streptococci channel (6) Nonhemolytic streptococci (4) Candida albicans (3) Enterococ cus (3) Diphtheroids (2) E . coli (2) N. pharyn,;eus (1) 11-Hemolytic streptococci (1) Micrococcus (1) Staph epidermidis (1) P. aeruginosa (1) Anerobic cocci ( 1) C. freundii (1) S. auretls (I) E . aerogenes
Discussion The role of the endoscopic equipment as a source of ERCP-related septic complications has not been emphasized. In an often cited fatal case of necrotizing pancreatitis
August 1975
!)09
CASE REPORTS
following ERCP in a patient with a pancreatic pseudocyst in which Escherichia coli, enterococci, and Proteus were cultured from peritoneal fluid at surgery, Ammann et a!. 9 dismiss the possibility of the injection of instrument bacteria into the pancreatic pseudocyst by asserting that their equipment was cleaned with the soap and alcohol (70%). While there is no evidence that bacteria are introduced into the duct systems by cannulation with great regularity, we do provide evidence that this is a definite possibility and cannot be dismissed out of hand , especially if the conventional method of disinfection has been employed. Cotton, in his review of ERCP in 1972, 1 found 10 cases out of 879 ERCP's reported to that time, in which severe febrile reactions, cholangitis, or septicemia occurred. He concluded that it was not clear if infection is introduced by the cannula no longer sterile after passing through the endoscopic channel and the duodenum, or from the dissemination of bacteria already within the biliary system, although he favored the latter proposition. Vennes et a!. 8 indicated a 15% incidence of cholangitis within 36 hr of visualizing the biliary system in patients with extrahepatic obstruction. Surgery was recommended within 24 hr of demonstrating an obstructed duct. He concluded that the etiology of the cholangitis was obscure. From the experience with this case and the culture results obtained, it would seem that introduction of instrument flora into the pancreas and biliary system is as likely a source of infection as dissemination of bacteria already present, and that some of the reported cases of cholangitis almost certainly have been the result of introduced bacteria. Although the point is made that septic complications occur only in the face of obstruction, 1 ' 2 with instrument bacteria this need not be so, as is clearly demonstrated by our case. The work of Bockman in an ex perimental model using retrograde bile duct injections of ferritin and Indi a Ink, under varying press ures, showed lightand electron-microscopic evidence of hepa tocyte disruption and escape of these mate-
rials into the sinusoids and the spaces of Disse . 1 3 This might be even more than a theoretical consideration in a pati ent with liver disease after an injection of bacteria laden contrast material. That the incidence of sepsis is as low as it is may have to do with effective filtering by the normal liver. A compromised, cirrhotic liver or one with even less severe disease such as in the patient we des cribe , may account for a siRDificant reduction in the hepa tic reticu loendothelial clearing of bacteria and a higher risk of sp read of bacte ria introduced by retrograde injection. As there is the potential hazard of introducing mouth bacterial nora into the biliary or pancreatic duct syste ms even art cr gluteraldehyde disinfection, the addition of an antibiotic to the contrast material as already instituted by some workers 14 may be required especially in the debilitated, poor risk patient in whom sepsis or emergent surgery would be disastrous. The use of antibiotics alone without an effective disinfection procedure will ultimately result in the emergence of antibiotic-resistant bacteria in the equipment. Whatever the ultimate role of antibiotics in the contrast material, it appears that a clear indication now exists for those employing ERCP for the diagnosis of hepatobiliary and pancreatic disorders to be cognizant of the septic potential of the equipment itself' and to take the appropriate steps to ensure its effective disinfection . REF'EHENCES 1. Cotto n PH: Cannulation oft he papilla of Vater by endosco py and retrograde chola ngiopa ncrcat ography (ERCP). Gul l:l:!O I 4- 1021i, 197:,! 2. Gaisford WD: Proceedings: endosco pi c cannula tion of the papilla of Vater. Arch Surg 108:519- 525, 197 4 3. Nebel OT, Fornes MF': Endoscopic pancreatocholang iography. Am ,) Dig Dis IR: 1042 - IOiiO, 197:1 4. Kasugai T, Kuno N, Kizu M: Endoscopic pancrealoc holangiography wilh spec ial reference lo manometric method. Med .J Aust 2:717 - 7'2.fl , 197:l 5. Gregg ,JA: Cannulation of the ampulla of Valer. Am ,J Gaslroenterol GO: 142- lli(), 197:l 6. Dickinson PH, Belsito AA , Cramer GG: DiagnosLic va lu e of e ndoscop ic c holnngio pancrea tography. ,JAMA 22fl:944-~J4R, I H?:l
510
CASE REPORTS
7. Silvis SE, Rohrmann CA, Vennes JA: Diagnostic criteria for the evaluation of the endoscopic pancreatogram. Gastrointest Enclose 20:51-55, 1973 8. Vennes JA, Jacobson JR, Silvis SE: Endoscopic cholangiography. for biliary system diagnosis. Ann Intern Med 80:61-64, 1974 9. Ammann RW, Deyhle P , Butikofer E: Fatal necrotizing pancreatitis after peroral cholangiopancreatography . Gastroenterology 64:320-323, 1973 10. Belsito AA, Cramer GG, Dickinson PB: Delayed ductal drainage: an endoscopic pancreatographic sign of carcinoma of the head of the pancreas. Am J Roentgenol Radium Ther Nucl Med 19:109- 114,
Vol. 69, No. 2
1973 11. Kocka FE, Harris JO: Pyocin typing: a method of categorizing Pseudomonas aeruginosa . Trans Ill State Acad Sci 66:15- 20, 1973 12. Axon ATR, Cotton PB, Phillips I, et al: Disinfection of gastrointestinal fibre endoscopes. Lancet 1:656- 658, 1974 13. Bockman DE: Route of tlow and micropathology resulting from retrograde intrabiliary injection of india ink and ferrritin in experimental animals. Gastroenterology 67: 324-332, 1974 14. Kasugai T, Kuno N, Kizu M: Manometric endoscopic retrograde pancreatocholangiography. Am J Dig Dis 19:485- 502, 1974
Vol. nH, No.
~
Printed in U.S .A.
POLYMICROBIAL SEPSIS FOLLOWING ENDOSCOPIC RETROGRADE CHOLANGIOPANCREATOGRAPHY
c.
0.
ELSON,
M.D., K.
HATTOHI,
M.D.,
AND
M . 0.
BLACKSTONE,
M.D.
S ection of Gastroenterolo/iy , Department of Medicine , The University of Chicalio Pritzker School of Medicine, Chica/iO, Illinois
Cholangitis with polymicrobial sepsis followed endoscopic retrograde cholangiopancreatography in a patient without biliary tract obstruction. Inadequately disinfected endoscopy equipme1~t was strongly implicated as the source of infection. Results with a new method of disinfection using gluteraldehyde are given. Although endoscopic retrograde cholangiopancreatography (ERCP) is a firmly established diagnostic tool, septic complications continue to accompany its use . The risk of ERCP-related sepsis, although actually low, is nevertheless appreciable . In a recent review 1 and in other published series , 2 ' 7 there were 19 serious infections in 1942 patients, an incidence of 0.97 %. Bilbao et at. have just completed a survey of Olympus JF-B owners in the United States; in 8681 ERCP's , there were 97 (1.1 %) serious infectious complications (unpublished data). When jaundice is the indication for ERCP and extrahepatic obstruction is demonstrated, the incidence is higher. Vennes et at. 8 found an incidence of cholangitis of almost 15% of patients in whom extrahepatic obstruction was demonstrated. Filling a pancreatic pseudocyst carries with it an equal or greater likelihood of septic complications, although the precise incidence is as yet unknown. 9 • 1 0 In these cases it has been assumed that bowel flora has been introduced into a closed system or that bacteria already present were disseminated by the procedure. 1 Cholangitis with polymicrobial sepsis following an ERCP performed at the University of Chicago in a patient
without extrahepatic obstruction led us to examine our ERCP equipment as the source of infection and to consider its prevention through more effective instrument disinfection.
Case Report
A 54-year-old black woman with a 9-year history of ulcerative colitis was admitted to the hospital in May 1974. Her col it is had been largely inactive following a severe first allack and her only medication had been low doses of azulfidine as maintenance. Two months prior to admission she developed generalized urticaria and periorbital edema. She was seen by several physicians but the et iology remained obscure . One month before admission liver function tests were fi>und to be abnormal: SGOT 162 , SGPT 211 (normal fi>r both less than 35), bilirubin 0.7, alkaline phosphatase 99 (normal less than 45). There was no exposure to hepatitis or history of jaundice and the hepatitis-associated antigen was negative . Repeat tests done 1 month later were unchanged and she was admitted for liver biopsy which showed mild focal hepatitis but also portal fibrosis of a degree sufficient to raise the question of sclervsing cholangitis as an underlying process. Intravenous contrast studies of the biliary tract were not helpful. ERCP was performed by one of us (K.H.). The procedure was uneventful with biliary ducts, gallbladder, and main pancreatic duct all visualized. AlReceived February 24, 1975. Accept ed April 12, though the intrahepatic biliary tree was irregular and ectatic, there was no evidence of stric1975. Address requests for reprints to: C. 0 . Elson , M.D. , ture, stones, or carcinoma. Eighteen hours after the procedure the patient developed fever to Department of Medicine, The University of Chica go, 40°C, right upper quadrant pain, and tenderBox 400, 950 East 59th Street, Chicago, ness . Blood cultures were drawn 1 and subseIllinois 60637. 507
508
Vol. 69, No. 2
CASE REPORTS
quently grew Pseudomonas aeruginosa and Enterobacter aerogenes. She quickly responded to a course of antibiotic treatment. The cannula and endoscope used in the procedure were later cultured and the same organisms as were isolated from her blood were identified. The P. aeru{?inosa isolated from the patient's blood and from the endoscopy room were pyocin-typed 11 and found to be identical, indicating a nosocomial source of infection .
TABLE
1. Cultures of equipment and room usin{? the
conventional method of disinfection Culture result
Culture of
ERCP cannula" Olympus JFB biopsy channel"
Olympus JFB-2 biopsy channel
Methods Multiple cultures were taken of the endoscopy room sink, counters, and walls with sterile swabs. A few milliliters of water were collected from the wash bottles. The endoscope was cultured after routine alcohol disinfection (according to manufacturer's instruction) by Hushing the suction channel with sterile water and collecting the effluent. The cannulae were cultured in a similar manner. All specimens were sent to the hospital's microbiology laboratory where they were handled by routine bacteriological methods. The method of disinfection was then changed from alcohol to 2% gluteraldehyde as proposed by Axon et a!. 12 The gl uteraldehyde was allowed to remain in the suction channel and wash bottle for 10 min. These were then thoroughly f1ushed with sterile water. If the instrument was not to be immediately used, the various ports were covered with sterile gauze before storage. The cannulae were individually wrapped and then sterilized with ethylene oxide. Cultures were taken immediately before and after an ERCP.
Results Bacteriology of endoscopic equipment after alcohol disinfection. The results shown in table 1 are very similar to those of Axon et a!. , 12 in that Pseudomonas and other enterobacteriaceae were found f1uorishing in the endoscopy equipment despite the standard disinfection procedure of soap, water, and 70% alcohol. Bacteriology of the ERCP equipment after gluteraldehyde disinfection. The results of this method are summarized in table 2. Evident from this bacteriology data is the fact that in the main, only mouth f1ora is cultured. The more virulent pathogens found in the inadequately disinfected equipment were seldom found in these cultures.
Wash bottles (2) Sink counter and drain, endoscopy room Dimethylsilicone Walls, cabinets, drawers of endoscopy room
P. aeruginosa E . cloacae P. aeruginosa E. aerogenes C. freundii Kl. pneumoniae P. aeruginosa K. pneumoniae E. coli E . aerogenes P. aeruginosa A. hemolyticans P. aeruginosa No growth Few bacillus species
"Used in present case.
2. Cultures of 10 consecutive cases ut iliz in/i the gluteraldehyde m ethod of disinfection
TABLE
Time culture ta ken
Site of iso late
Culture result
(10) No g-rowth (10) No growth
Pre-ERCP
Cannula Suction channel
Post-ERCP
(10) a-Hemolytic Suction streptococci channel (6) Nonhemolytic streptococci (4) Candida albicans (3) Enterococ cus (3) Diphtheroids (2) E . coli (2) N. pharyn,;eus (1) 11-Hemolytic streptococci (1) Micrococcus (1) Staph epidermidis (1) P. aeruginosa (1) Anerobic cocci ( 1) C. freundii (1) S. auretls (I) E . aerogenes
Discussion The role of the endoscopic equipment as a source of ERCP-related septic complications has not been emphasized. In an often cited fatal case of necrotizing pancreatitis
August 1975
!)09
CASE REPORTS
following ERCP in a patient with a pancreatic pseudocyst in which Escherichia coli, enterococci, and Proteus were cultured from peritoneal fluid at surgery, Ammann et a!. 9 dismiss the possibility of the injection of instrument bacteria into the pancreatic pseudocyst by asserting that their equipment was cleaned with the soap and alcohol (70%). While there is no evidence that bacteria are introduced into the duct systems by cannulation with great regularity, we do provide evidence that this is a definite possibility and cannot be dismissed out of hand , especially if the conventional method of disinfection has been employed. Cotton, in his review of ERCP in 1972, 1 found 10 cases out of 879 ERCP's reported to that time, in which severe febrile reactions, cholangitis, or septicemia occurred. He concluded that it was not clear if infection is introduced by the cannula no longer sterile after passing through the endoscopic channel and the duodenum, or from the dissemination of bacteria already within the biliary system, although he favored the latter proposition. Vennes et a!. 8 indicated a 15% incidence of cholangitis within 36 hr of visualizing the biliary system in patients with extrahepatic obstruction. Surgery was recommended within 24 hr of demonstrating an obstructed duct. He concluded that the etiology of the cholangitis was obscure. From the experience with this case and the culture results obtained, it would seem that introduction of instrument flora into the pancreas and biliary system is as likely a source of infection as dissemination of bacteria already present, and that some of the reported cases of cholangitis almost certainly have been the result of introduced bacteria. Although the point is made that septic complications occur only in the face of obstruction, 1 ' 2 with instrument bacteria this need not be so, as is clearly demonstrated by our case. The work of Bockman in an ex perimental model using retrograde bile duct injections of ferritin and Indi a Ink, under varying press ures, showed lightand electron-microscopic evidence of hepa tocyte disruption and escape of these mate-
rials into the sinusoids and the spaces of Disse . 1 3 This might be even more than a theoretical consideration in a pati ent with liver disease after an injection of bacteria laden contrast material. That the incidence of sepsis is as low as it is may have to do with effective filtering by the normal liver. A compromised, cirrhotic liver or one with even less severe disease such as in the patient we des cribe , may account for a siRDificant reduction in the hepa tic reticu loendothelial clearing of bacteria and a higher risk of sp read of bacte ria introduced by retrograde injection. As there is the potential hazard of introducing mouth bacterial nora into the biliary or pancreatic duct syste ms even art cr gluteraldehyde disinfection, the addition of an antibiotic to the contrast material as already instituted by some workers 14 may be required especially in the debilitated, poor risk patient in whom sepsis or emergent surgery would be disastrous. The use of antibiotics alone without an effective disinfection procedure will ultimately result in the emergence of antibiotic-resistant bacteria in the equipment. Whatever the ultimate role of antibiotics in the contrast material, it appears that a clear indication now exists for those employing ERCP for the diagnosis of hepatobiliary and pancreatic disorders to be cognizant of the septic potential of the equipment itself' and to take the appropriate steps to ensure its effective disinfection . REF'EHENCES 1. Cotto n PH: Cannulation oft he papilla of Vater by endosco py and retrograde chola ngiopa ncrcat ography (ERCP). Gul l:l:!O I 4- 1021i, 197:,! 2. Gaisford WD: Proceedings: endosco pi c cannula tion of the papilla of Vater. Arch Surg 108:519- 525, 197 4 3. Nebel OT, Fornes MF': Endoscopic pancreatocholang iography. Am ,) Dig Dis IR: 1042 - IOiiO, 197:1 4. Kasugai T, Kuno N, Kizu M: Endoscopic pancrealoc holangiography wilh spec ial reference lo manometric method. Med .J Aust 2:717 - 7'2.fl , 197:l 5. Gregg ,JA: Cannulation of the ampulla of Valer. Am ,J Gaslroenterol GO: 142- lli(), 197:l 6. Dickinson PH, Belsito AA , Cramer GG: DiagnosLic va lu e of e ndoscop ic c holnngio pancrea tography. ,JAMA 22fl:944-~J4R, I H?:l
510
CASE REPORTS
7. Silvis SE, Rohrmann CA, Vennes JA: Diagnostic criteria for the evaluation of the endoscopic pancreatogram. Gastrointest Enclose 20:51-55, 1973 8. Vennes JA, Jacobson JR, Silvis SE: Endoscopic cholangiography. for biliary system diagnosis. Ann Intern Med 80:61-64, 1974 9. Ammann RW, Deyhle P , Butikofer E: Fatal necrotizing pancreatitis after peroral cholangiopancreatography . Gastroenterology 64:320-323, 1973 10. Belsito AA, Cramer GG, Dickinson PB: Delayed ductal drainage: an endoscopic pancreatographic sign of carcinoma of the head of the pancreas. Am J Roentgenol Radium Ther Nucl Med 19:109- 114,
Vol. 69, No. 2
1973 11. Kocka FE, Harris JO: Pyocin typing: a method of categorizing Pseudomonas aeruginosa . Trans Ill State Acad Sci 66:15- 20, 1973 12. Axon ATR, Cotton PB, Phillips I, et al: Disinfection of gastrointestinal fibre endoscopes. Lancet 1:656- 658, 1974 13. Bockman DE: Route of tlow and micropathology resulting from retrograde intrabiliary injection of india ink and ferrritin in experimental animals. Gastroenterology 67: 324-332, 1974 14. Kasugai T, Kuno N, Kizu M: Manometric endoscopic retrograde pancreatocholangiography. Am J Dig Dis 19:485- 502, 1974