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Sepsis in the management of complicated biliary disorders
Sepsis in the Management of Complicated Bi I iary Disorders John M. Holman, Jr, MD, Salt Lake City, Utah Layton F. Rikkers, MD, Salt Lake City, Utah Frank G. Moody, MD, Salt Lake City, Utah
Even with today’s sophisticated
diagnostic and sur-
gical techniques, sepsis frequently complicates the management of patients with chronic biliary obstruction. The high incidence of biliary bacteremia and wound sepsis in patients undergoing biliary surgery is well documented [l--3]. However, most. studies include mainly patients with calculous biliary to determine disease [4,5]. 0 ur study was undertaken the frequency of sepsis in a select high risk group of patients with obstructing lesions of the proximal extrahepatic biliary tract. Patient Population Twenty-five patients with complex lesions of the proximal biliary tree were studied in the 6 year interval from 1972 to 1978 (Table I). Patients with periampullary tumors, metastatic tumors of the hepatoduodenal ligament, and obstruction of the extrahepatic biliary tree by calculi were specifically excluded. The largest group consisted of 11 patients with benign strictures (44 per cent), including 1 patient with sclerosing cholangitis. These strictures occurred either high in the common bile duct or in the common hepatic duct. The two patients with Caroli’s disease had multiple intrahepatic saccular dilatations with intervening narrowed ductular connections. The two choledochal cysts involved the common bile duct. All groups covered a wide age range, but patients with carcinoma were the oldest and those with congenital obstruction the youngest. The sex distribution was nearly equal in patients with benign and malignant strictures, whereas congenital biliary obstruction was more common in women. The clinical characteristics of the patients are shown in Table II. Ninety per cent presented with evidence of cholestasis as indicated by elevated levels of serum alkaline phosphatase and bilirubin. The complex of fever, jaundice, and abdominal pain, suggesting cholangitis, was more From the Department of Surgery, University of Utah Medical Center, Salt Lake City, Utah. Reprint requests should be addressed to John M. Holman. Jr, MD, Department of Surgery, University of Utah Medical Center, 50 North Medical Drive, Salt Lake~City, Utah 84132. Presented at the 31st Annual Meeting of the Southwestern Surgical Congress, Las Vegas, Nevada, April 23-26. 1979.
Volume 138, December 1979
frequent in patients with benign stricture (21 per cent) than in patients with malignant stricture (0 per cent), but the difference was not statistically significant (p >O.l). Weight loss was five times more common in patients with biliary carcinoma than in those with benign lesions. The majority of patients (84 per cent) had had biliary surgery previously. All of the patients with benign stricture had had cholecystectomy, three with concurrent and four with subsequent common duct exploration. Dilation and repair of the stricture had been attempted earlier in one patient. The patients with congenital obstruction had had a variety of T tube and cystoenteric procedures. Four of the patients with biliary carcinoma had not previously been operated on whereas three had had biopsy of the tumor and T tube drainage. Sixty-eight per cent of the patients underwent one or more diagnostic procedures. Twelve had percutaneous transhepatic cholangiography, 13 had endoscopic retrograde cholangiopancreatography, and 3 had percutaneous liver biopsy. Prophylactic antibiotics were administered before 88 per cent of the procedures had been performed. The most common biliary drainage procedures that we performed initially were biliary enteric anastomoses. Hepaticojejunostomy was constructed in five patients with benign biliary strictures, in two patients with congenitally obstructed bile ducts, and in two patients with bile duct carcinoma. Choledochojejunostomy was used in four patients with benign strictures, in two with congenital obstruction, and in one with biliary carcinoma, The single patient with sclerosing cholangitis underwent cholecystojejunostomy. Roux-Y limbs were always used for biliary-jejunal anstomoses. Steats were not used (74 per cent) when a mucosa-to-mucosa anastomosis could be achieved. Stents, when placed, were left for a minimum of 6 months and changed whenever signs of obstruction developed. T tube drainage alone was used in one patient with benign stricture and in one with congenital biliary obstruction. Transhepatic drainage tubes were placed in four patients with bile duct carcinoma when the proximal extent of the tumor precluded resection. Tumor resection was accomplished in one patient. Bile cultures were always taken at surgery and postoperatively from drainage tubes when sepsis was suspected.
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Holman et al
-TABLE I
Patient Population
Diagnosis
No. of Patients
Benign biliary stricture Common bile duct Common hepatic duct Sclerosing cholangitis Congenital biliary obstruction Caroli’s disease Choledochal cyst Megacholedochus Biliary atresia Bile duct carcinoma Left hepatic duct Bifurcation of the hepatic ducts Common bile duct
11
Total
25
l
Mean f
Mean age (yr)” 57f
11
cholangitis, or both developed for a mean postoperative follow-up period of 24 months. Two patients were lost to follow-up study after their initial hospitalization.
Sex (M/F) 516.
Results
6 4 1 7
35f
18
Thirty-nine septic episodes complicated the postoperative course of 18 patients (72 per cent). Eight patients had multiple occurrences. Shock was associated with sepsis in six patients (33 per cent). Septic shock resulted in death in only one patient. Table III shows the relation between postoperative septic events and diagnosis. Sepsis occurred more commonly in patients with biliary carcinoma (86 per cent) and in those with congenital obstruction (86 per cent) than in those with benign stricture (54 per cent). In addition, sepsis was more frequently associated with shock in patients with carcinoma. Fiftyfour per cent of patients with biliary carcinoma had received prophylactic antibiotic coverage when cholangitis developed, including four patients (31 per
215
2 3 1 1 68 f 9
7
314
1 4 2 54f
18
10115
1 standard deviation.
Standard aerobic and anaerobic culture techniques were applied. Patients were evaluated throughout the postoperative period for evidence of cholangitis or septic shock. Cholangitis was defined as pain and tenderness in the right upper abdominal quadrant, a fever greater than 38T orally, a white blood cell count greater than lO,OOO/mm3, and the absence of an intraabdominal abscess. Septic shock was attributed to biliary obstruction only when all other possible etiologic factors were eliminated by appropriate diagnostic measures. Shock was characterized by fever. greater than 3872 orally, hypotension, and evidence of decreased tissue perfusion such as oliguria of less than 30 mm/hour or mental confusion, or both. Patients were seen at 1 to 6 month intervals or more of recurrent
cent) who manifested the infection Moreover, 31 per cent of these septic another surgical procedure to relieve and control the sepsis. No episodes
of septic shock occurred in patients with congenital biliary obstruction, and secondary surgical procedures were required in only 15 per cent of these patients. Septic complications developed in 54 per cent of patients with benign stricture, including the one patient who died. This patient had had T tube drainage of the common bile duct and transduodenal ampullary sphincter dilatation performed elsewhere. A biliary and duodenal fistula and subsequent septic shock
frequently
when evidence
biliary obstruction,
TABLE II
Patient History, Presenting Physical Findings, and Laboratory Values*
History of: Jaundice Pruritus Abdominal pain Fever Weight loss Duration of symptoms (wk) Presenting physical findings Jaundice Abdominal mass Ascites Temperature >101.5’F Presenting laboratory values White blood cell count >10,000/mm3 Protime >2 set, prolonged Bilirubin >1.5 mg/lOO ml Serum glutamic oxaloacetic transaminase >45 Ill/liter Lactic dehydrogenase >225 IU/liter Alkaline phosphatase >115 Ill/liter
as septic shock. events required the obstruction
Benign Stricture
Congenital Obstruction
Bile Duct Carcinoma
All Patients
64 27 64 45 18 l-8
57 28 100 43 14 12-24
100 57 57 28 86 20-32
72 36 72 40 36 l-32
45 36 9 18
28 >o >o 43
100 43 >o >o
56 28 4 20
27 18 55 82 36 82
43 28 57 71 43 86
14 43 100 100 71 100
28 28 68 84 48 88
* Figures represent percentage of patients.
810
The American Journalof Surgery
Sepsis
TABLE III
Postoperative
Patients Total
Benign stricture Congenital obstruction Bile duct carcinoma
11 7 7
Total
25
Disorders
by Diagnosis*
Sepsis
Lesion
and Biliary
Sepsis
Total
Shock
6 (54) 6 (86) 6 (86)
13 13 13
2 (15)Q 0 (0) 4 (31)
18 (72)
39
6 (15)
Septic Episodes Antibiotics+
Secondary Proceduret
3 (23) 1 (8) 7 (54)
2 (15) 2 (15) 4 (31)
11 (28)
8 (21)
* Numbers in parentheses indicate percentages. + Refers to patients receiving antibiotics at the onset of sepsis. r Refers to patients who required a secondary surgical procedure for the resolution of sepsis, Q One mortality.
developed. Autopsy revealed acute tubular necrosis, acute pancreatitis, and a pancreatic abscess. Blood, bile, and pancreatic abscess cultures all grew Pseuodomonas, enterococcus, and Escherichia coli. Table IV shows the relation between septic events and operative procedure. There was no significant difference in the incidence of postoperative sepsis among the various surgical procedures performed. However, sepsis was more common after nonstented anastomoses (86 per cent) than after stented anastomoses (40 per cent) (p <0.05). In addition, septic shock occurred only after nonstented biliary-enteric
TABLE IV
anastomoses (17 per cent). Tube drainage alone resulted in a 67 per cent incidence of sepsis. Table V describes the 42 diagnostic procedures performed and the resultant septic complications. Seventeen per cent of all procedures were followed by cholangitis or septic shock. Shock developed after percutaneous transhepatic cholangiography in two patients, both of whom had received prophylactic antibiotic therapy. Subsequent drainage was required to resolve the sepsis in these patients. Sixty per cent of bile cultures grew E coli, the most commonly found organism. In decreasing order of
Postoperative Sepsis by Operative Procedure* Septic Episodes Patients
Procedure
Total
Seps.
Total
Shock
Antibiotics+
Secondary Procedure*
Hepaticojejunostomy Choledochojejunostomy§ Tube drainage only
9 10 6
7 (78) 7 (70) 4 (67)
13 15 11
2 (15) 2 (13) 2 (18)”
2 (15) 4 (26) 5 (45)
4 (31) 4 (26) 2 (18)
Total
25
18 (72)
39
6 (15)
11 (28)
8 (21)
* Numbers in parentheses indicate percentages. r Refers to patients receiving antibiotics at the onset of sepsis. 1 Refers to patients who required a secondary surgical procedure for the resolution of sepsis. 5 Includes one cholecystojejunostomy (in a patient with sclerosing cholangitis). 1 One mortality.
TABLE V
Sepsis After Diagnostic Procedures’ Septic Episodes Patients
Procedure
Total
Sepsis
Total
Shock
Antibioticsf
Secondary Procedure1
ERCP PTC Liver biopsy Tube manipulation@
13 12 3 14
; (16) 1 (33) 4 (28)
0 2 1 4
0 2 (100) 0 0
0 2 (100) l(lO0) 1 (25)
0 2 (loo! 0 0
Total
42
7 (17)
7
2 (28)
4 (56)
2 (28)
Numbers in parentheses indicate percentages. 7 Refers to patients receiving antibiotics at the onset of sepsis. i Refers to patients who required a secondary surgical procedure for the resolution of sepsis. 5 Changing the tube over guidewire or bile reinfusions. ERCP = endoscopic retrograde cholangiopancreatography; PTC = percutaneous transhepatic l
Volume 138, December 1979
cholangiography.
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Holman et al
frequency the following organisms were also found: enterococci (38 per cent), Pseudomonas (34 per cent), Klebsiella (30 per cent), enterobacter (17 per cent), and Proteus (13 per cent). Anaerobes were grown in only 7 per cent of cultures (Clostridium perfringens, 5 per cent; bacteroides species, 2 per cent). Comments
Biliary sepsis was a frequent complication in the management of our patients. At least one septic episode occurred in 72 per cent of the patients, shock developed in 25 per cent, and, overall, 44 per cent of the patients in whom sepsis developed required a second surgical procedure to relieve recurrent biliary obstruction. In the remaining patients cholangitis, presumably secondary to bile sludging, was resolved by antibiotics, irrigation of bile drainage catheters, or both. Sepsis was common in all three groups: those with benign stricture, congenital obstructing lesions, and biliary carcinoma. Similar results have been reported previously. Warren and Jefferson [6], in an extensive review of 987 patients with benign biliary stricture, found that sepsis accounted for 21 per cent of the morbidity and 9 per cent of the mortality in their series. Also, the frequency of septic complications increased with successive attempts at stricture repair. Flanigan [7] reported that cholangitis and its consequences were the leading cause of death in patients with both operated and unoperated choledochal cysts. Thirty of 60 patients with biliary carcinoma (50 per cent) reported on by Longmire et al [8] experienced biliary sepsis at some point in their course: Although chronic and recurrent biliary obstruction is probably the most important cause of . sepsis in the majority of these patients, immunologic factors may also play a role, especially in patients with carcinoma. Although not investigated in our study, depression of the reticuloendothelial system and other aspects of the immune response may have contributed to the increased incidence and severity of septic episodes observed in our patients with biliary carcinoma. The general type of surgical procedure performed had little influence on the incidence of postoperative sepsis. However, patients with stented biliary-enteric anastomoses had significantly less cholangitis than those without stems. Although most biliary surgeons prefer to stent an anastomosis when a mucosa-tomucosa anastomosis is impossible to achieve, both methods have been associated with a fairly high,incidence of postoperative sepsis. Stefanini [9] and Lane et al [IO] found that septic sequelae developed in 22 and 33 per cent, respectively, of patients with-
812
out stents, and 60 per cent required further surgery. In the series of Wexler and Smith [1I], 18 per cent of stented anastomoses failed, and all patients required corrective surgery. In the series of Cameron et al [12], postoperative sepsis developed in 20 per cent of patients who received long-term transhepatic stems for benign biliary stricture. Surgical management of malignant strictures usually includes the placement of a stent through an unresectable tumor to provide biliary drainage. Transhepatic t.ube [ 22]‘and T t,ube drainage [8] of biliary carcinoma has resulted in septic complications in 25 and 50 per cent of patients, respectively. In contrast, in one series postoperative sepsis developed in 42 per cent of patients with biliary carcinoma managed by hepaticojejunostomy without stents, resulting in death in all affected patients [13]. Seventeen per cent of the invasive diagnostic procedures performed in our patients were followed by sepsis. Fifty per cent of these septic complications were in patients with malignant strictures. In large series, sepsis occurring after diagnostic procedures of the liver and biliary tract is infrequent and is more common in patients with benign obstruction. Elias et al [14] found a 4.6 per cent incidence of cholangitis after percutaneous transhepatic cholangiography. As Dodd [15] reported, these infections may be overwhelming and uncontrollable. Both of our patients in whom sepsis developed after percutaneous transhepatic ‘cholangiography (16 per cent) were given antibiotics before the procedure, and both required surgery for control of sepsis. LoIndice et al [ 261 reported a 0.3 per cent incidence of cholangitis in 979 patients undergoing percutaneous liver biopsy. Only two other cases of sepsis after liver biopsy had been reported at the time of their report. Bilbao et al [17] found an 0.8 per cent incidence of sepsis in a collected review of 10,000 cases of endoscopic retrograde cholangiopancreatography. Although uncommon, sepsis was the most common cause of death in that study. Although prophylactic antibiotic coverage is mandatory before any manipulation of the obstructed biliary tract, it does not guarantee protection against sepsis. Twenty-eight per cent of the septic episodes in .’ this study occurred while the patients were on prophylactic antibiotics therapy. Throughout the course of the study multiple antibiotic regimens were used. Our present policy is to prophylactically administer cefamandole, a newly introduced cephalosporin that is highly concentrated in bile and has a broad gram-negative spectrum, to patients who are about to undergo surgery or invasive diagnostic procedures of the obstructed biliary tract
The American Journal of Surgery
Sepsis and Biliary Disorders
for the first time. However, in previously operated patients who are at a particularly high risk of developing biliary sepsis, the prophylactic combination of gentamicin and clindamycin is preferred. Summary
Postoperative sepsis developed in 72 per cent of 25 patients with noncalculous proximal biliary tract obstruction. Six episodes of shock and one death resulted. Twenty-eight per cent of septic events occurred despite the administration of prophylactic antibiotics. The incidence of septic complications was similar regardless of the biliary drainage procedure used. Despite the advent of broad spectrum antibiotics and improved surgical techniques for biliary decompression, sepsis remains a serious and frequent complication in patients with chronic bile duct obstruction. References 1. Keighley MRB, Lister DM, Jacobs SI, Giles GR: Hazards of surgical treatment due to micro-organisms in the bile. Surgery 75: 578, 1974. 2. Mason GR: Bacteriology and antibiotic selection in biliary tract surgery. Arch Surg 97: 533, 1968. 3. Chetlin SH, Elliot DW: Biliary bacteremia. Arch Surg 102: 303, 1971. 4. Keighley MRB: Identification of the presence and type of biliary microflora by immediate gram stain. Surgery 81: 469, 1977. 5. Fukunaga FH: Gallbladder bacteriology, histology, and gallstones Arch Surg 106: 169, 1973. 6. Warren KW, Jefferson MF: Prevention and repair of strictures of the extrahepatic bile ducts. Surg C/in North Am 53: 1169, 1973. 7. Flanigan DP: Biliary cysts. Ann Surg 182: 635, 1978. 8. Longmire WP, McArthur MS, Bastounis EA, Hiatt J: Carcinoma of the extrahepatic biliary tract. Ann Surg 17B: 333. 1973. 9. Stefanini P: Roux-en-Y hepaticojejunostomies: a reappraisal of its indications and results. Ann Surg 181: 213,1973. 10. Lane CE, Sawyers JL, Riddell DH, Scott HW: Long-term,results of Roux-en-Y hepaticojejunostomies. Ann SurQ 177: 714, 1973. 11. Wexler MJ, Smith R: Jejunal mucosal graft. Am J Surg 129: 204, 1975. 12. Cameron JL, Gayler BW, Zuidema GD: The use of silastic transhepatic stents in benign and malignant biliary strictures. Ann Surg 188: 552, 1978. 13. Ragins H, Diamond A, Meng C: lntrahepatic cholangiojejunostomy in the management of malignant biliary obstruction. Surg Gynecol Obsfet 136: 27, 1973. 14. Elias E, Hamlyn AN, Jain S, Long RG, Summerfield JA, Dick R, et al: Proceedings: a randomized trial of percutaneous transhepatic cholangiography with the Chiba needle versus endoscopic retrograde cholangiography for bile duct visualization in jaundice. Gestroenferology 71: 439, 1976.
Volume 138, December 1979
15. Dodd GD: Percutaneous transhepatic cholangiography. Surg C/in North Am 47: 1095, 1967. 16. Lolndice T, Buhac I, Balint J: Septicemia as a complication of percutaneous liver biopsy. Gastroenterology 72: 949, 1977. 17. Bilbao MK, Dotter CT, Lee TG, Katon RM: Complications of endoscopic retrograde cholangiopancreatography (ERCP). Gastroenterology 70: 314, 1976.
Discussion J. Gary Maxwell (Salt Lake City, UT): Dr. Holman, what is the mechanism by which biliary obstruction leads to sepsis? For instance, if the right hepatic duct is completely ligated in the presence of sterile bile, will it. become infected? Conversely, if the same right hepatic duct is partially ligated, will it eventually become infected? Why is there this difference, if it exists, between complete and partial obstruction? You indicate that sepsis occurred more frequently with mucosa-to-mucosa anastomosis in which the diameter of the anastomosis was large and no stent was used. I would not have predicted that result and wonder if you have an explanation in terms of other variables. Finally, does decompression with a needle placed percutaneously before definitive surgery make that operation or the preoperative period safer with regard to septic episodes?
Do you recommend
it as a preparatory
measure?
John Holman (closing): Dr. Maxwell, the question of partial versus total obstruction has been answered in reports by Longmire and others who found that a totally occluded bile duct does not become septic; in fact, the liver lobe behind that duct atrophies. The reason a partially obstructed duct becomes septic is that with the reflux of bowel contents up through the Roux-Y limb or choledochoduodenostomy into the biliary tree and with stasis behind a partially obstructed anastomosis, proliferation of bacteria occurs with subsequent cholangitis. We had more infection in our patients with nonstented larger anastomoses because this group contained more patients with congenital obstruction, Caroli’s disease, and choledochal cysts in whom saccular dilatations of the biliary tree allowed for stasis of bile contents. Then, with reflux of bowel contents up through the Roux-Y limb, the mechanism just mentioned, the infection occurs. Also, this group contained a high percentage of patients with bile duct carcinoma in whom, although the initial anastomosis may have been adequate, the progressive nature of the neoplasm eventually obstructed the internal drainage in several patients. The question of preoperative decompression of the bile ducts in these patients has been answered in reports by other investigators. We recommend preoperative decompression of the biliary system through a skinny needle, if available.
813
Even with today’s sophisticated
diagnostic and sur-
gical techniques, sepsis frequently complicates the management of patients with chronic biliary obstruction. The high incidence of biliary bacteremia and wound sepsis in patients undergoing biliary surgery is well documented [l--3]. However, most. studies include mainly patients with calculous biliary to determine disease [4,5]. 0 ur study was undertaken the frequency of sepsis in a select high risk group of patients with obstructing lesions of the proximal extrahepatic biliary tract. Patient Population Twenty-five patients with complex lesions of the proximal biliary tree were studied in the 6 year interval from 1972 to 1978 (Table I). Patients with periampullary tumors, metastatic tumors of the hepatoduodenal ligament, and obstruction of the extrahepatic biliary tree by calculi were specifically excluded. The largest group consisted of 11 patients with benign strictures (44 per cent), including 1 patient with sclerosing cholangitis. These strictures occurred either high in the common bile duct or in the common hepatic duct. The two patients with Caroli’s disease had multiple intrahepatic saccular dilatations with intervening narrowed ductular connections. The two choledochal cysts involved the common bile duct. All groups covered a wide age range, but patients with carcinoma were the oldest and those with congenital obstruction the youngest. The sex distribution was nearly equal in patients with benign and malignant strictures, whereas congenital biliary obstruction was more common in women. The clinical characteristics of the patients are shown in Table II. Ninety per cent presented with evidence of cholestasis as indicated by elevated levels of serum alkaline phosphatase and bilirubin. The complex of fever, jaundice, and abdominal pain, suggesting cholangitis, was more From the Department of Surgery, University of Utah Medical Center, Salt Lake City, Utah. Reprint requests should be addressed to John M. Holman. Jr, MD, Department of Surgery, University of Utah Medical Center, 50 North Medical Drive, Salt Lake~City, Utah 84132. Presented at the 31st Annual Meeting of the Southwestern Surgical Congress, Las Vegas, Nevada, April 23-26. 1979.
Volume 138, December 1979
frequent in patients with benign stricture (21 per cent) than in patients with malignant stricture (0 per cent), but the difference was not statistically significant (p >O.l). Weight loss was five times more common in patients with biliary carcinoma than in those with benign lesions. The majority of patients (84 per cent) had had biliary surgery previously. All of the patients with benign stricture had had cholecystectomy, three with concurrent and four with subsequent common duct exploration. Dilation and repair of the stricture had been attempted earlier in one patient. The patients with congenital obstruction had had a variety of T tube and cystoenteric procedures. Four of the patients with biliary carcinoma had not previously been operated on whereas three had had biopsy of the tumor and T tube drainage. Sixty-eight per cent of the patients underwent one or more diagnostic procedures. Twelve had percutaneous transhepatic cholangiography, 13 had endoscopic retrograde cholangiopancreatography, and 3 had percutaneous liver biopsy. Prophylactic antibiotics were administered before 88 per cent of the procedures had been performed. The most common biliary drainage procedures that we performed initially were biliary enteric anastomoses. Hepaticojejunostomy was constructed in five patients with benign biliary strictures, in two patients with congenitally obstructed bile ducts, and in two patients with bile duct carcinoma. Choledochojejunostomy was used in four patients with benign strictures, in two with congenital obstruction, and in one with biliary carcinoma, The single patient with sclerosing cholangitis underwent cholecystojejunostomy. Roux-Y limbs were always used for biliary-jejunal anstomoses. Steats were not used (74 per cent) when a mucosa-to-mucosa anastomosis could be achieved. Stents, when placed, were left for a minimum of 6 months and changed whenever signs of obstruction developed. T tube drainage alone was used in one patient with benign stricture and in one with congenital biliary obstruction. Transhepatic drainage tubes were placed in four patients with bile duct carcinoma when the proximal extent of the tumor precluded resection. Tumor resection was accomplished in one patient. Bile cultures were always taken at surgery and postoperatively from drainage tubes when sepsis was suspected.
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Holman et al
-TABLE I
Patient Population
Diagnosis
No. of Patients
Benign biliary stricture Common bile duct Common hepatic duct Sclerosing cholangitis Congenital biliary obstruction Caroli’s disease Choledochal cyst Megacholedochus Biliary atresia Bile duct carcinoma Left hepatic duct Bifurcation of the hepatic ducts Common bile duct
11
Total
25
l
Mean f
Mean age (yr)” 57f
11
cholangitis, or both developed for a mean postoperative follow-up period of 24 months. Two patients were lost to follow-up study after their initial hospitalization.
Sex (M/F) 516.
Results
6 4 1 7
35f
18
Thirty-nine septic episodes complicated the postoperative course of 18 patients (72 per cent). Eight patients had multiple occurrences. Shock was associated with sepsis in six patients (33 per cent). Septic shock resulted in death in only one patient. Table III shows the relation between postoperative septic events and diagnosis. Sepsis occurred more commonly in patients with biliary carcinoma (86 per cent) and in those with congenital obstruction (86 per cent) than in those with benign stricture (54 per cent). In addition, sepsis was more frequently associated with shock in patients with carcinoma. Fiftyfour per cent of patients with biliary carcinoma had received prophylactic antibiotic coverage when cholangitis developed, including four patients (31 per
215
2 3 1 1 68 f 9
7
314
1 4 2 54f
18
10115
1 standard deviation.
Standard aerobic and anaerobic culture techniques were applied. Patients were evaluated throughout the postoperative period for evidence of cholangitis or septic shock. Cholangitis was defined as pain and tenderness in the right upper abdominal quadrant, a fever greater than 38T orally, a white blood cell count greater than lO,OOO/mm3, and the absence of an intraabdominal abscess. Septic shock was attributed to biliary obstruction only when all other possible etiologic factors were eliminated by appropriate diagnostic measures. Shock was characterized by fever. greater than 3872 orally, hypotension, and evidence of decreased tissue perfusion such as oliguria of less than 30 mm/hour or mental confusion, or both. Patients were seen at 1 to 6 month intervals or more of recurrent
cent) who manifested the infection Moreover, 31 per cent of these septic another surgical procedure to relieve and control the sepsis. No episodes
of septic shock occurred in patients with congenital biliary obstruction, and secondary surgical procedures were required in only 15 per cent of these patients. Septic complications developed in 54 per cent of patients with benign stricture, including the one patient who died. This patient had had T tube drainage of the common bile duct and transduodenal ampullary sphincter dilatation performed elsewhere. A biliary and duodenal fistula and subsequent septic shock
frequently
when evidence
biliary obstruction,
TABLE II
Patient History, Presenting Physical Findings, and Laboratory Values*
History of: Jaundice Pruritus Abdominal pain Fever Weight loss Duration of symptoms (wk) Presenting physical findings Jaundice Abdominal mass Ascites Temperature >101.5’F Presenting laboratory values White blood cell count >10,000/mm3 Protime >2 set, prolonged Bilirubin >1.5 mg/lOO ml Serum glutamic oxaloacetic transaminase >45 Ill/liter Lactic dehydrogenase >225 IU/liter Alkaline phosphatase >115 Ill/liter
as septic shock. events required the obstruction
Benign Stricture
Congenital Obstruction
Bile Duct Carcinoma
All Patients
64 27 64 45 18 l-8
57 28 100 43 14 12-24
100 57 57 28 86 20-32
72 36 72 40 36 l-32
45 36 9 18
28 >o >o 43
100 43 >o >o
56 28 4 20
27 18 55 82 36 82
43 28 57 71 43 86
14 43 100 100 71 100
28 28 68 84 48 88
* Figures represent percentage of patients.
810
The American Journalof Surgery
Sepsis
TABLE III
Postoperative
Patients Total
Benign stricture Congenital obstruction Bile duct carcinoma
11 7 7
Total
25
Disorders
by Diagnosis*
Sepsis
Lesion
and Biliary
Sepsis
Total
Shock
6 (54) 6 (86) 6 (86)
13 13 13
2 (15)Q 0 (0) 4 (31)
18 (72)
39
6 (15)
Septic Episodes Antibiotics+
Secondary Proceduret
3 (23) 1 (8) 7 (54)
2 (15) 2 (15) 4 (31)
11 (28)
8 (21)
* Numbers in parentheses indicate percentages. + Refers to patients receiving antibiotics at the onset of sepsis. r Refers to patients who required a secondary surgical procedure for the resolution of sepsis, Q One mortality.
developed. Autopsy revealed acute tubular necrosis, acute pancreatitis, and a pancreatic abscess. Blood, bile, and pancreatic abscess cultures all grew Pseuodomonas, enterococcus, and Escherichia coli. Table IV shows the relation between septic events and operative procedure. There was no significant difference in the incidence of postoperative sepsis among the various surgical procedures performed. However, sepsis was more common after nonstented anastomoses (86 per cent) than after stented anastomoses (40 per cent) (p <0.05). In addition, septic shock occurred only after nonstented biliary-enteric
TABLE IV
anastomoses (17 per cent). Tube drainage alone resulted in a 67 per cent incidence of sepsis. Table V describes the 42 diagnostic procedures performed and the resultant septic complications. Seventeen per cent of all procedures were followed by cholangitis or septic shock. Shock developed after percutaneous transhepatic cholangiography in two patients, both of whom had received prophylactic antibiotic therapy. Subsequent drainage was required to resolve the sepsis in these patients. Sixty per cent of bile cultures grew E coli, the most commonly found organism. In decreasing order of
Postoperative Sepsis by Operative Procedure* Septic Episodes Patients
Procedure
Total
Seps.
Total
Shock
Antibiotics+
Secondary Procedure*
Hepaticojejunostomy Choledochojejunostomy§ Tube drainage only
9 10 6
7 (78) 7 (70) 4 (67)
13 15 11
2 (15) 2 (13) 2 (18)”
2 (15) 4 (26) 5 (45)
4 (31) 4 (26) 2 (18)
Total
25
18 (72)
39
6 (15)
11 (28)
8 (21)
* Numbers in parentheses indicate percentages. r Refers to patients receiving antibiotics at the onset of sepsis. 1 Refers to patients who required a secondary surgical procedure for the resolution of sepsis. 5 Includes one cholecystojejunostomy (in a patient with sclerosing cholangitis). 1 One mortality.
TABLE V
Sepsis After Diagnostic Procedures’ Septic Episodes Patients
Procedure
Total
Sepsis
Total
Shock
Antibioticsf
Secondary Procedure1
ERCP PTC Liver biopsy Tube manipulation@
13 12 3 14
; (16) 1 (33) 4 (28)
0 2 1 4
0 2 (100) 0 0
0 2 (100) l(lO0) 1 (25)
0 2 (loo! 0 0
Total
42
7 (17)
7
2 (28)
4 (56)
2 (28)
Numbers in parentheses indicate percentages. 7 Refers to patients receiving antibiotics at the onset of sepsis. i Refers to patients who required a secondary surgical procedure for the resolution of sepsis. 5 Changing the tube over guidewire or bile reinfusions. ERCP = endoscopic retrograde cholangiopancreatography; PTC = percutaneous transhepatic l
Volume 138, December 1979
cholangiography.
811
Holman et al
frequency the following organisms were also found: enterococci (38 per cent), Pseudomonas (34 per cent), Klebsiella (30 per cent), enterobacter (17 per cent), and Proteus (13 per cent). Anaerobes were grown in only 7 per cent of cultures (Clostridium perfringens, 5 per cent; bacteroides species, 2 per cent). Comments
Biliary sepsis was a frequent complication in the management of our patients. At least one septic episode occurred in 72 per cent of the patients, shock developed in 25 per cent, and, overall, 44 per cent of the patients in whom sepsis developed required a second surgical procedure to relieve recurrent biliary obstruction. In the remaining patients cholangitis, presumably secondary to bile sludging, was resolved by antibiotics, irrigation of bile drainage catheters, or both. Sepsis was common in all three groups: those with benign stricture, congenital obstructing lesions, and biliary carcinoma. Similar results have been reported previously. Warren and Jefferson [6], in an extensive review of 987 patients with benign biliary stricture, found that sepsis accounted for 21 per cent of the morbidity and 9 per cent of the mortality in their series. Also, the frequency of septic complications increased with successive attempts at stricture repair. Flanigan [7] reported that cholangitis and its consequences were the leading cause of death in patients with both operated and unoperated choledochal cysts. Thirty of 60 patients with biliary carcinoma (50 per cent) reported on by Longmire et al [8] experienced biliary sepsis at some point in their course: Although chronic and recurrent biliary obstruction is probably the most important cause of . sepsis in the majority of these patients, immunologic factors may also play a role, especially in patients with carcinoma. Although not investigated in our study, depression of the reticuloendothelial system and other aspects of the immune response may have contributed to the increased incidence and severity of septic episodes observed in our patients with biliary carcinoma. The general type of surgical procedure performed had little influence on the incidence of postoperative sepsis. However, patients with stented biliary-enteric anastomoses had significantly less cholangitis than those without stems. Although most biliary surgeons prefer to stent an anastomosis when a mucosa-tomucosa anastomosis is impossible to achieve, both methods have been associated with a fairly high,incidence of postoperative sepsis. Stefanini [9] and Lane et al [IO] found that septic sequelae developed in 22 and 33 per cent, respectively, of patients with-
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out stents, and 60 per cent required further surgery. In the series of Wexler and Smith [1I], 18 per cent of stented anastomoses failed, and all patients required corrective surgery. In the series of Cameron et al [12], postoperative sepsis developed in 20 per cent of patients who received long-term transhepatic stems for benign biliary stricture. Surgical management of malignant strictures usually includes the placement of a stent through an unresectable tumor to provide biliary drainage. Transhepatic t.ube [ 22]‘and T t,ube drainage [8] of biliary carcinoma has resulted in septic complications in 25 and 50 per cent of patients, respectively. In contrast, in one series postoperative sepsis developed in 42 per cent of patients with biliary carcinoma managed by hepaticojejunostomy without stents, resulting in death in all affected patients [13]. Seventeen per cent of the invasive diagnostic procedures performed in our patients were followed by sepsis. Fifty per cent of these septic complications were in patients with malignant strictures. In large series, sepsis occurring after diagnostic procedures of the liver and biliary tract is infrequent and is more common in patients with benign obstruction. Elias et al [14] found a 4.6 per cent incidence of cholangitis after percutaneous transhepatic cholangiography. As Dodd [15] reported, these infections may be overwhelming and uncontrollable. Both of our patients in whom sepsis developed after percutaneous transhepatic ‘cholangiography (16 per cent) were given antibiotics before the procedure, and both required surgery for control of sepsis. LoIndice et al [ 261 reported a 0.3 per cent incidence of cholangitis in 979 patients undergoing percutaneous liver biopsy. Only two other cases of sepsis after liver biopsy had been reported at the time of their report. Bilbao et al [17] found an 0.8 per cent incidence of sepsis in a collected review of 10,000 cases of endoscopic retrograde cholangiopancreatography. Although uncommon, sepsis was the most common cause of death in that study. Although prophylactic antibiotic coverage is mandatory before any manipulation of the obstructed biliary tract, it does not guarantee protection against sepsis. Twenty-eight per cent of the septic episodes in .’ this study occurred while the patients were on prophylactic antibiotics therapy. Throughout the course of the study multiple antibiotic regimens were used. Our present policy is to prophylactically administer cefamandole, a newly introduced cephalosporin that is highly concentrated in bile and has a broad gram-negative spectrum, to patients who are about to undergo surgery or invasive diagnostic procedures of the obstructed biliary tract
The American Journal of Surgery
Sepsis and Biliary Disorders
for the first time. However, in previously operated patients who are at a particularly high risk of developing biliary sepsis, the prophylactic combination of gentamicin and clindamycin is preferred. Summary
Postoperative sepsis developed in 72 per cent of 25 patients with noncalculous proximal biliary tract obstruction. Six episodes of shock and one death resulted. Twenty-eight per cent of septic events occurred despite the administration of prophylactic antibiotics. The incidence of septic complications was similar regardless of the biliary drainage procedure used. Despite the advent of broad spectrum antibiotics and improved surgical techniques for biliary decompression, sepsis remains a serious and frequent complication in patients with chronic bile duct obstruction. References 1. Keighley MRB, Lister DM, Jacobs SI, Giles GR: Hazards of surgical treatment due to micro-organisms in the bile. Surgery 75: 578, 1974. 2. Mason GR: Bacteriology and antibiotic selection in biliary tract surgery. Arch Surg 97: 533, 1968. 3. Chetlin SH, Elliot DW: Biliary bacteremia. Arch Surg 102: 303, 1971. 4. Keighley MRB: Identification of the presence and type of biliary microflora by immediate gram stain. Surgery 81: 469, 1977. 5. Fukunaga FH: Gallbladder bacteriology, histology, and gallstones Arch Surg 106: 169, 1973. 6. Warren KW, Jefferson MF: Prevention and repair of strictures of the extrahepatic bile ducts. Surg C/in North Am 53: 1169, 1973. 7. Flanigan DP: Biliary cysts. Ann Surg 182: 635, 1978. 8. Longmire WP, McArthur MS, Bastounis EA, Hiatt J: Carcinoma of the extrahepatic biliary tract. Ann Surg 17B: 333. 1973. 9. Stefanini P: Roux-en-Y hepaticojejunostomies: a reappraisal of its indications and results. Ann Surg 181: 213,1973. 10. Lane CE, Sawyers JL, Riddell DH, Scott HW: Long-term,results of Roux-en-Y hepaticojejunostomies. Ann SurQ 177: 714, 1973. 11. Wexler MJ, Smith R: Jejunal mucosal graft. Am J Surg 129: 204, 1975. 12. Cameron JL, Gayler BW, Zuidema GD: The use of silastic transhepatic stents in benign and malignant biliary strictures. Ann Surg 188: 552, 1978. 13. Ragins H, Diamond A, Meng C: lntrahepatic cholangiojejunostomy in the management of malignant biliary obstruction. Surg Gynecol Obsfet 136: 27, 1973. 14. Elias E, Hamlyn AN, Jain S, Long RG, Summerfield JA, Dick R, et al: Proceedings: a randomized trial of percutaneous transhepatic cholangiography with the Chiba needle versus endoscopic retrograde cholangiography for bile duct visualization in jaundice. Gestroenferology 71: 439, 1976.
Volume 138, December 1979
15. Dodd GD: Percutaneous transhepatic cholangiography. Surg C/in North Am 47: 1095, 1967. 16. Lolndice T, Buhac I, Balint J: Septicemia as a complication of percutaneous liver biopsy. Gastroenterology 72: 949, 1977. 17. Bilbao MK, Dotter CT, Lee TG, Katon RM: Complications of endoscopic retrograde cholangiopancreatography (ERCP). Gastroenterology 70: 314, 1976.
Discussion J. Gary Maxwell (Salt Lake City, UT): Dr. Holman, what is the mechanism by which biliary obstruction leads to sepsis? For instance, if the right hepatic duct is completely ligated in the presence of sterile bile, will it. become infected? Conversely, if the same right hepatic duct is partially ligated, will it eventually become infected? Why is there this difference, if it exists, between complete and partial obstruction? You indicate that sepsis occurred more frequently with mucosa-to-mucosa anastomosis in which the diameter of the anastomosis was large and no stent was used. I would not have predicted that result and wonder if you have an explanation in terms of other variables. Finally, does decompression with a needle placed percutaneously before definitive surgery make that operation or the preoperative period safer with regard to septic episodes?
Do you recommend
it as a preparatory
measure?
John Holman (closing): Dr. Maxwell, the question of partial versus total obstruction has been answered in reports by Longmire and others who found that a totally occluded bile duct does not become septic; in fact, the liver lobe behind that duct atrophies. The reason a partially obstructed duct becomes septic is that with the reflux of bowel contents up through the Roux-Y limb or choledochoduodenostomy into the biliary tree and with stasis behind a partially obstructed anastomosis, proliferation of bacteria occurs with subsequent cholangitis. We had more infection in our patients with nonstented larger anastomoses because this group contained more patients with congenital obstruction, Caroli’s disease, and choledochal cysts in whom saccular dilatations of the biliary tree allowed for stasis of bile contents. Then, with reflux of bowel contents up through the Roux-Y limb, the mechanism just mentioned, the infection occurs. Also, this group contained a high percentage of patients with bile duct carcinoma in whom, although the initial anastomosis may have been adequate, the progressive nature of the neoplasm eventually obstructed the internal drainage in several patients. The question of preoperative decompression of the bile ducts in these patients has been answered in reports by other investigators. We recommend preoperative decompression of the biliary system through a skinny needle, if available.
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