Perforation of the Gallbladder: A Frequently Mismanaged Condition Joel Roslyn, MD, Los Angeles, California Ronald W. Busuttil, MD, PhD, Los Angeles, California
The first report of perforation of the gallbladder was published by Duncan in 1844 [I]. For the next ninety years sporadic mention appeared in the literature dealing with this fatal condition. It was not until 1934 that Neimeier [2] presented his classic description of acute perforation of the gallbladder and reviewed his experience with this complication of acute cholecystitis. He concluded that although a relatively rare condition, it “. . . demands eternal vigilance in the delayed treatment of acute cholecystitis. The mortality is extremely high. . . (and) it would appear from our series that prompt recognition and treatment might lower this considerably.” Despite his recommendation, forty-five years later this disease continues to present a dilemma in early diagnosis and carries significant morbidity and mortality. The reasons for the typical delayed recognition are many, but as summarized by Isch, Finnerman, and Nahrwold [3] in 1971, they can be narrowed down to the fact that the’clinical manifestations of gallbladder perforation are similar to those of acute cholecystitis without perforation. The purposes of the present study are to: (1) review the cases of gallbladder perforation at UCLA Hospital; (2) based on our series and a collective review of the literature, establish a set of criteria to identify the type of patient who is at high risk for gallbladder perforation; (3) detail an appropriate course of clinical diagnosis and management; and (4) present a unified concept of the pathogenesis of perforation of the gallbladder. Materials and Methods
A retrospective analysis was conducted of all patients seen at UCLA Hosnital during the years between 1955and From the Department of Surgery, UCLA School of Medicine, Los Angeles, California. Reprint requests should be addressed to Ronald W. Busuttil. MD, Department of Surgery, UCLA School of Medicine, Los Angeles, California 90024.
Volume 137,
March1979
1977who were diagnosed as having gallbladder perforation. This represented a total of seventeen patients, five of whom were diagnosed at the time of autopsy. By using a modification of Neimeier’s original classification, three categories of patients were established (Table I): type 1, those having acute, free perforation with bilestained peritoneal fluid; type 2, those who had subacute perforation with pericholecystic or right upper quadrant abscess; and type 3, those suffering chronic perforation with formation of either cholecystoenteric or cholecystocutaneous fistula. Results Age and Sex. There were eleven men and six women in this study whose average age was sixtythree years (sixty-one years for men and sixty-seven years for women). The male group included a thirty-two year old and a forty-eight year old, both of whom had severe systemic disease requiring long-term, high dose steroid therapy. Pathology. Six patients (35 per cent) had type 1 perforation, eight (47 per cent) had type 2, and three (18 per cent) had type 3. In thirteen patients, cholelithiasis was documented at the time of surgery or at autopsy. Available information is insufficient to identify the exact anatomic location of the perforation. Although twelve patients had pathologic evidence of chronic cholecystitis, a clinical history of chronic cholecystitis was elicited in only four patients. Thus, 70 per cent of those with gallbladder perforation had a pathologic diagnosis of chronic gallbladder disease, but only 27 per cent had a clinical diagnosis. Associated Systemic Diseases. Seven patients showed evidence of atherosclerotic cardiovascular disease, four of whom had documented myocardial infarctions in the past. Six patients had nonbiliary tract malignancies, and two were receiving long-term, high dose steroid therapy for rheumatoid arthritis
307
Roslyn and Busuttil
TABLE I
Age (yr)/ Sex
UCLA Series of Gallbladder Perforations Time from Onset
History Type of of Chronic Perfor- Choleation cvstitis
Optiration
Diagnosis and Operation
48/M
1
No
1 day
77/F
1
Yes
20 days
4 days
32/M 46/F 67/F 80/F 42/M 72/M
1 1 1 2 2 2
No Yes No No No No
60 4 3 5 2 12
days days days days days days
1 day 3 days 1 day 3 days 1 day 4 days
61/M 61/M 74/M 67/M 76/M 70/M 67/F
2 2 2 3 1 2 2
No Yes No Yes No No No
7 30 27 11
days days days mo’
4 days 30 days 25 days 6mo
72/M 67/F
3 3
No Yes
4 hr
Systemic Diseases
Postoperative Comolications
Rheumatoid arthritis; steroids; SBE None Systemic lupus erythematosis None None ASHD; AODM None ASHD; COPD; carcinoma, bladder None None ASHD; carcinoma, bladder ASHD ASHD, carcinoma, tongue Carcinoma, prostate ASHD; hypertension, carcinoma, rectum Carcinoma, nose ASHD
Atelectasis; sepsis: diabetes; perforated DU Atrial fibrillation; acute renal failure; coma Poor wound healing None None Atelectasis Pleural effusion CVA Seroma None None Seroma
Postoperative Hospital Stav
Survival
19 days
Died
23 days
Died
28 12 9 22 16 16
days days days days days days
Survived Survived Survived Survived Survived Survived
15 9 12 10
days days days days
Survived Survived Survived Survived Autbpsy Autopsy Autopsy Autopsy Autopsy
Chronic cholecystocutaneous fistula. Note: SBE = subacute bacterial endocarditis; ASHD = atherosclerotic heart disease; AODM = adult onset diabetes mellitus; COPD = chronic obstructive pulmonary disease; DU = duodenal ulcer; CVA = cerebrovascular accident. l
TABLE II
Incidence of Positive Physical Signs in Patients with Gallbladder Perforation
Clinical Findings Temperature > 36’C Pulse > lOO/minute Right upper quadrant tenderness Right upper quadrant mass Right upper quadrant rebound Diffuse tenderness
No. of Patients 6 6 9 6 4 2
(46%) (35%) (52%) (35%) (23%) (12%)
and systemic lupus erythematosis. Only one patient had proven diabetes mellitus. More than 50 per cent of the patients in this series had been admitted to the hospital for reasons related to their primary systemic disease. Symptoms. The average length of time between onset of symptoms precipitating surgery and the acute procedure was 16.5 days. The most common complaints were abdominal pain (13 patients, 77 per cent), nausea (7 patients, 41 per cent), fever (6 patients, 35 per cent), anorexia (6 patients, 35 per cent), vomiting (5 patients, 29 per cent), and back pain (3 patients, 17 per cent). Clinical and Laboratory Findings. Eight patients were febrile and had clinical evidence of infection. On
308
TABLE III
Incidence of Abnormal Chemical Determination in Patients With Gallbladder Perforation Clinical Findings and Laboratorv Data
No. of Patients
WBC > 10,000 Bilirubin abnormal Alkaline Phosphatase abnormal SGOT abnormal SGPT abnormal OCG abnormal IVC abnormal Ultrasound abnormal
10 7 5 4 4 5 4 2
(83%) (77%) (71%) (50%) (66%) (100%) (100%) (100%)
Note: WBC = white blood cell count; SGOT = serum glutamic oxalacetic transaminase; SGPT = serum glutamic pyruvic transaminase; OCG = oral cholecystogram; IVC = intravenous cholangiogram.
examination there were right upper quadrant findings in twelve patients (70 per cent). Laboratory data were not available on all patients, but test results indicated elevated liver function in more than 67 per cent. Only seven in the series underwent radiographic evaluation, but findings were abnormal in all of them. (Tables II and III.) Microbiology. Positive cultures were obtained from eleven patients (taken from bile, peritoneal
The Amerlcan Journal of Surgery
Gallbladder
fluid, or abscess cavity). The most common organism was Escherichia coli, found in eight patients, four of whom had pure E coli, three of whom had both E coli and Klebsiella, and one of whom had E coli as well as Bacteroides fragilis. Staphylococcus aureus was found in a patient with a chronic cholecystocutaneous fistula. Treatment. Of the twelve patients who underwent cholecystectomy, the average interval between preoperative diagnosis of abdominal pathology and operation was 6.8 days. While a preoperative diagnosis of biliary tract disease was made in the majority of patients, in only 20 per cent was gallbladder perforation diagnosed. Vigorous fluid replacement, nasogastric decompression, and in most cases, broad spectrum antibiotics, comprised the preoperative treatment. Results. The length of hospitalization averaged 16 days. More than 58 per cent of the patients suffered some type of postoperative complication ranging from atelectasis to perforapd duodenal ulcer. (Table IV.) There were two deaths (16.7 per cent), both surgical emergencies. Comments
Gallbladder perforation is not as rare as once thought; the present incidence is said to be between 3 and 10 per cent of acute cholecystitis cases. In our series, as well as in others (Table V), there has been an alarmingly high complication rate. Pines and Rabinovitch [4] in 1954 reported an overall mortality of 17.7 per cent due to gallbladder perforations, a figure comparable to that in our series (16.7 per cent). Riesenfeld [5], reporting on sixth-one patients with gallbladder perforation in 1969, indicated an overall mortality of 21 per cent, as compared to 3 per cent in 259 patients who were operated on for acute cholecystitis without perforation [5]. He concluded, as did others, that the increased morbidity and mortality stem chiefly from the delay in diagnosis and a lack of urgency on the part of the physician. Our data support this hypothesis, and we therefore believe that the most effective means of facilitating early and appropriate management is immediate identification of patients who are at high risk of gallbladder perforation. Isch, Finnerman, and Nahrwold [3] observed that most patients with gallbladder perforation have abdominal complaints and findings similar to those patients who have acute cholecystitis without perforation, and that based on these criteria alone, differential diagnosis can be difficult. On the basis of our experience and reports in the literature, we conclude that patients at high risk of gallbladder perforation can be identified by examining such
voltm~~ 137, March 1979
TABLE IV
Perforation
Complications Following Gallbladder Perforation Complications
No. of Patients
Seroma Atelectasis Gastrointestinal bleeding Cardiovascular accident Pleural effusion Poor wound healing Acute renal failure Atrial fibrillation Perforated duodenal ulcer Sepsis Pancreatic insufficiency
2 2 2 1 1 1 1 1 1 1 1
factors as age, sex, previous clinical history, and of paramount importance, associated systemic diseases. Acute cholecystitis is classically described as affecting obese, middle aged, premenopausal women. ‘However, our study shows that patients with gallbladder perforation tend to be older (63 years) and are more frequently male (65 per cent). Isch, Finnerman, and Nahrwold [3] and Williams and Scobie [6] all published similar findings. (Table V.) It should be noted that two of our three patients younger than sixty years (both men) fell into a special category: they had been receiving chronic steroids, and one was undergoing immunosuppressive therapy. Thus, it appears that gallbladder perforation tends to occur primarily in elderly males, yet it occurs occasionally in younger males when certain conditions are present. Inasmuch as no critical analyses of the importance of associated diseases have been published by other authors, it is difficult to draw conclusions based solely on two patients. Nevertheless, the data in this series suggest that perforation is more likely to occur in younger persons if their immune system is compromised. Various authors have suggested that perforation occurs in the setting of acute cholecystitis. Although this is probably true, patients with perforation tend to have underlying chronic disease with superimposed acute cholecystitis. Williams and Scobie [6] stated that fourteen of nineteen patients with gallbladder perforation had either a history indicative of gallbladder disease or a previous diagnosis of chronic cholecystitis. However, a history compatible with chronic cholecystitis is not always elicited, as in our series in which only 27 per cent of patients claimed to have biliary tract disease, yet 70 per cent had pathologic evidence of chronic cholecystitis. The historic abscence of chronic cholecystitis should therefore not preclude the diagnosis of gallbladder
309
62.5
147
Total
Note:.RUCl = right upper quadrant.
50%
50%
65%
63
17
Present series
35%
57%
43%
57
48%
23
Abu-Dalu and Urea [ 71
M 41%
Sex
40%
52%
59%
F
60%
61.6
T$
69
19
Williams and Scobie [6]
[31
lsch et al
27
61
Riesenfeld
151
Pa&ts
No.
47%
48%
32%
68%
35%
16%
48%
28 %
44 %
33%
2
1
Types
Collective Series of Gallbladder Perforation
Series
TABLE V
20%
18%
16%
19%
28%
3
Abdominal pain 86 % Vomiting 60 % Nausea 69 % Anorexia 42%
Abdominal pain 100% Vomiting 61 % Nausea 78 % Anorexia 39 % Abdominal pain 76% Nausea 4 1% Vomiting 29 % Anorexia 35 %
Nausea 89 % Vomiting 89 % Abdominal pain 82 % Anorexia 52%
Symptoms
Tenderness 72% Mass 35 % Temp 51%
Tenderness 52% Mass 35 % Temp 46 %
Tenderness 85% Mass 41% Temp 56 % Tenderness 79% Mass 30 %
RUQ Examination
76%
76%
48%
89%
74%
95%
Cholelithiasis
47%
27%
57%
74%
30%
History of Chronic Cholecystitis
Cholecystectomy 86%; cholecystostomy 7.5%
Cholecystectomy 100%: cholecystostomy 0
4% .
Cholecystectomy 87%; cholecystostomy
Cholecystostomy 8.3%; cholecvstectomy 91.7%. Cholecystectomy 64%: cholecystostomy 18%
Operations
15%
16.7%
0
23%
21.3%
Mortality
Gallbladder Perforation
perforation in an otherwise appropriate clinical setting. Another significant factor in identifying the high risk patient is the presence of severe systemic disease. Williams and Scobie [6] reported that 21 per cent of their patients with perforation had associated atherosclerotic heart disease, and Abu-Dalu and Urea [7] observed a 25 per cent incidence of diabetes mellitus among their patients. In our group, nearly 65 per cent had a severe systemic disease: atherosclerosis (41 per cent); malignancy (35.3 per cent); rheumatoid arthritis (5.8 per cent); or systemic lupus erythematosis (5.8 per cent). These data suggest an association between severe systemic disease and an increased propensity for the development of gallbladder perforation in patients who have chronic gallbladder disease. Gallbladder perforation is not a disease of the young healthy person with acute cholecystitis; rather, it appears to occur in two distinct clinical settings. The first group comprises elderly patients with atherosclerotic heart disease and presumed diffuse atherosclerotic changes. Isch, Finnerman, and Nahrwold [3] and Abu-Dalu and Urea [7] recognized that when the site of perforation could be identified, the fundus was the most common location. Anatomically, this corresponds to the gallbladder area that is least vascularized, implying that vascular changes and ischemia are crucial factors in the pathogenesis of perforation. In elderly patients with atherosclerotic visceral vessels and intermittent chronic low cardiac output, ischemia of the gallbladder wall could occur, thus predisposing them to eventual ischemic necrosis and perforation, The second group includes those patients, both young and old, who are immunosuppressed, either secondary to widespread malignancy or owing to drug therapy. They have impaired host defense mechanisms and are unable to contain a normally nonlethal infection such as cholecystitis, and are thus at great risk of the development of virulent infection and perforation. In this series, both patients receiving steroids had type 1 free perforations. Although it is difficult to extrapolate data from the recent literature on these concepts of vascular changes and immunosuppression relative to gallbladder perforation, we believe that these are key factors, and when present in the setting of chronic cholecystitis, the patient is in serious jeopardy of gallbladder perforation developing. Awareness of these clinical groupings forms the basis for early recognition and treatment of gallbladder perforation. When either of these settings is present in a patient with right upper quadrant symptoms and findings, the clinician should suspect
Volume 137, March 1979
*
HDI,
f
Figure 1. Proposed unified concept of pathogenesis of gallbladder perforation.
gallbladder perforation. There are no data available to determine the time of perforation. Although the optimal means of preventing perforation is to perform earlier surgery on patients with acute cholecystitis, this is not feasible in all cases, and thus, the physician must keep a high index of suspicion and be willing to act accordingly if poor results are to be minimized. In situations in which a high risk patient had right upper quadrant findings, we would recommend a vigorous and expedient diagnostic and therapeutic regimen. After careful examination and routine blood tests, including liver function tests, vigorous hydration, nasogastric decompression, and appropriate antibiotic coverage should be instituted. Since the offending organism in most cases is a gram-negative coliform, ampicillin or a cephalosporin in combination with an aminoglycoside would be appropriate. At this point, if the patient is stable and shows no evidence of sepsis, diagnostic testing should be performed. This should include intravenous cholangiography and abdominal ultrasound. Once preoperative stabilization and diagnostic testing has been performed (in most cases this can be done in 12 hours), we would then recommend early operative intervention. All of our patients underwent cholecystectomy, but cholecystostomy may be indicated in a critically ill patient and can be accomplished using local anesthesia. We maintain that if the prescribed protocol is adhered to in the appropriate clinical setting of those patients-at high risk for gallbladder perforation, the inordinately high morbidity and mortality associated with this syndrome can be satisfactorily lowered. Why do gallbladders perforate? The exact cause and pathogenesis remain to be elucidated. It would seem that, as Glenn and Moore [I] wrote in 1942, “. . . this process is closely associated with circulatory changes and infection.” In the elderly male cardiac patient with presumed diffuse vascular disease, the
311
Roslyn
and Busuttil
prime factor is probably hypoperfusion leading to ischemia and eventual ischemic necrosis. Ischemia and local tissue hypoxia lead to cellular dysfunction and breakdown. This impaired function superimposed upon chronic inflammation and irritation secondary to cholelithiasis provides a potential for severe infection with resulting gangrene and perforation. In the immunosuppressed patient, a minimal amount of inflammation can lead to overwhelming infection with edema, venous congestion, arterial insufficiency, and ultimately, gangrenous perforation. Usually vascular disease and immune deficiency may play separate roles in the evolution of perforation. (Figure 1.) A patient with perforation and systemic lupus erythematosis may represent a clinical situation in which both of these mechanisms are operative, because ischemia and immunosuppression are present on the basis of vasculitis and steroid therapy, respectively. The exact cause of gallbladder perforation remains unclear, but it would seem that this disease is a separate entity from acute cholecystitis. As such, it has its own set of predisposing circumstances and, thus, should have specific guidelines for diagnosis and therapy.
The majority of patients were elderly men (mean age, 61 years) and women (mean age, 67 years) with significant atherosclerotic cardiovascular disease or underlying malignancy. Another important subset of patients consisted of young men who were receiving long-term steroid or immunosuppressive therapy for collagen vascular disease. Almost all of the patients with gallbladder perforation were subjected to an inordinate delay in diagnosis and surgical intervention (6.8 days), and this was responsible for a significant complication rate of 58 per cent as well as an extended postoperative hospitalization time (16 days). The mortality for the entire series was 17 per cent. The successful management of gallbladder perforation is based on early recognition of the patients who are at high risk for this condition. Preoperative diagnostic and therapeutic measures can usually be performed within 12 hours and should include ultrasonography or intravenous cholangiography, fluid resuscitation, nasogastric decompression, and broad spectrum antibiotic administration. A successful outcome in these patients, however, can be achieved only with operative intervention.
Summary
References
Gallbladder perforation is a lethal complication of cholecystitis, a relatively common disease, and has a mortality of 15 to 20 per cent. At UCLA Hospital seventeen patients with perforation of the gallbladder were evaluated and compared with patients who had previously been reported in the English literature. The purpose of this report was to: (1) establish a set of criteria to identify the patient who is at high risk for gallbladder perforation; (2) detail an appropriate course of diagnostic and therapeutic management; and (3) propose a unified concept of the pathogenesis of gallbladder perforation.
1.
312
2.
3. 4.
5. 6. 7. 8.
Glenn F, Moore SW: Gangrene and perforation of the wall of the gallbladder. Arch Surg 44: 677, 1942. Neimeier OW: Acute free perforation of the gallbladder. Ann Surg 99: 922, 1934. lsch J, Finnerman J, Nahrwold D: Perforation of the gallbladder. Am J Gastroenterol55: 45 1, 197 1. Pines B, Rabinovitch J: Perforation of gallbladder in acute cholecystitis. Ann Surg 140: 170, 1954. Riesenfeld G: Perforation of the gallbladder. Int Surg 52: 216, 1969. Williams N, Scobie T: Perforation of the gallbladder. Can Med Assoc J 115: 1223, 1976. Abu-Dalu J, Urea I: Acute cholecystitis with perforation into the peritoneal cavity. Arch Surg 102: 108, 1971. Berkowitz R, Rappaport N, Coodley E, Matsumoto T: Gallbladder perforation into the lesser sac. Int Surg 61: 229, 1976.
The American Journal ot Surgery
The first report of perforation of the gallbladder was published by Duncan in 1844 [I]. For the next ninety years sporadic mention appeared in the literature dealing with this fatal condition. It was not until 1934 that Neimeier [2] presented his classic description of acute perforation of the gallbladder and reviewed his experience with this complication of acute cholecystitis. He concluded that although a relatively rare condition, it “. . . demands eternal vigilance in the delayed treatment of acute cholecystitis. The mortality is extremely high. . . (and) it would appear from our series that prompt recognition and treatment might lower this considerably.” Despite his recommendation, forty-five years later this disease continues to present a dilemma in early diagnosis and carries significant morbidity and mortality. The reasons for the typical delayed recognition are many, but as summarized by Isch, Finnerman, and Nahrwold [3] in 1971, they can be narrowed down to the fact that the’clinical manifestations of gallbladder perforation are similar to those of acute cholecystitis without perforation. The purposes of the present study are to: (1) review the cases of gallbladder perforation at UCLA Hospital; (2) based on our series and a collective review of the literature, establish a set of criteria to identify the type of patient who is at high risk for gallbladder perforation; (3) detail an appropriate course of clinical diagnosis and management; and (4) present a unified concept of the pathogenesis of perforation of the gallbladder. Materials and Methods
A retrospective analysis was conducted of all patients seen at UCLA Hosnital during the years between 1955and From the Department of Surgery, UCLA School of Medicine, Los Angeles, California. Reprint requests should be addressed to Ronald W. Busuttil. MD, Department of Surgery, UCLA School of Medicine, Los Angeles, California 90024.
Volume 137,
March1979
1977who were diagnosed as having gallbladder perforation. This represented a total of seventeen patients, five of whom were diagnosed at the time of autopsy. By using a modification of Neimeier’s original classification, three categories of patients were established (Table I): type 1, those having acute, free perforation with bilestained peritoneal fluid; type 2, those who had subacute perforation with pericholecystic or right upper quadrant abscess; and type 3, those suffering chronic perforation with formation of either cholecystoenteric or cholecystocutaneous fistula. Results Age and Sex. There were eleven men and six women in this study whose average age was sixtythree years (sixty-one years for men and sixty-seven years for women). The male group included a thirty-two year old and a forty-eight year old, both of whom had severe systemic disease requiring long-term, high dose steroid therapy. Pathology. Six patients (35 per cent) had type 1 perforation, eight (47 per cent) had type 2, and three (18 per cent) had type 3. In thirteen patients, cholelithiasis was documented at the time of surgery or at autopsy. Available information is insufficient to identify the exact anatomic location of the perforation. Although twelve patients had pathologic evidence of chronic cholecystitis, a clinical history of chronic cholecystitis was elicited in only four patients. Thus, 70 per cent of those with gallbladder perforation had a pathologic diagnosis of chronic gallbladder disease, but only 27 per cent had a clinical diagnosis. Associated Systemic Diseases. Seven patients showed evidence of atherosclerotic cardiovascular disease, four of whom had documented myocardial infarctions in the past. Six patients had nonbiliary tract malignancies, and two were receiving long-term, high dose steroid therapy for rheumatoid arthritis
307
Roslyn and Busuttil
TABLE I
Age (yr)/ Sex
UCLA Series of Gallbladder Perforations Time from Onset
History Type of of Chronic Perfor- Choleation cvstitis
Optiration
Diagnosis and Operation
48/M
1
No
1 day
77/F
1
Yes
20 days
4 days
32/M 46/F 67/F 80/F 42/M 72/M
1 1 1 2 2 2
No Yes No No No No
60 4 3 5 2 12
days days days days days days
1 day 3 days 1 day 3 days 1 day 4 days
61/M 61/M 74/M 67/M 76/M 70/M 67/F
2 2 2 3 1 2 2
No Yes No Yes No No No
7 30 27 11
days days days mo’
4 days 30 days 25 days 6mo
72/M 67/F
3 3
No Yes
4 hr
Systemic Diseases
Postoperative Comolications
Rheumatoid arthritis; steroids; SBE None Systemic lupus erythematosis None None ASHD; AODM None ASHD; COPD; carcinoma, bladder None None ASHD; carcinoma, bladder ASHD ASHD, carcinoma, tongue Carcinoma, prostate ASHD; hypertension, carcinoma, rectum Carcinoma, nose ASHD
Atelectasis; sepsis: diabetes; perforated DU Atrial fibrillation; acute renal failure; coma Poor wound healing None None Atelectasis Pleural effusion CVA Seroma None None Seroma
Postoperative Hospital Stav
Survival
19 days
Died
23 days
Died
28 12 9 22 16 16
days days days days days days
Survived Survived Survived Survived Survived Survived
15 9 12 10
days days days days
Survived Survived Survived Survived Autbpsy Autopsy Autopsy Autopsy Autopsy
Chronic cholecystocutaneous fistula. Note: SBE = subacute bacterial endocarditis; ASHD = atherosclerotic heart disease; AODM = adult onset diabetes mellitus; COPD = chronic obstructive pulmonary disease; DU = duodenal ulcer; CVA = cerebrovascular accident. l
TABLE II
Incidence of Positive Physical Signs in Patients with Gallbladder Perforation
Clinical Findings Temperature > 36’C Pulse > lOO/minute Right upper quadrant tenderness Right upper quadrant mass Right upper quadrant rebound Diffuse tenderness
No. of Patients 6 6 9 6 4 2
(46%) (35%) (52%) (35%) (23%) (12%)
and systemic lupus erythematosis. Only one patient had proven diabetes mellitus. More than 50 per cent of the patients in this series had been admitted to the hospital for reasons related to their primary systemic disease. Symptoms. The average length of time between onset of symptoms precipitating surgery and the acute procedure was 16.5 days. The most common complaints were abdominal pain (13 patients, 77 per cent), nausea (7 patients, 41 per cent), fever (6 patients, 35 per cent), anorexia (6 patients, 35 per cent), vomiting (5 patients, 29 per cent), and back pain (3 patients, 17 per cent). Clinical and Laboratory Findings. Eight patients were febrile and had clinical evidence of infection. On
308
TABLE III
Incidence of Abnormal Chemical Determination in Patients With Gallbladder Perforation Clinical Findings and Laboratorv Data
No. of Patients
WBC > 10,000 Bilirubin abnormal Alkaline Phosphatase abnormal SGOT abnormal SGPT abnormal OCG abnormal IVC abnormal Ultrasound abnormal
10 7 5 4 4 5 4 2
(83%) (77%) (71%) (50%) (66%) (100%) (100%) (100%)
Note: WBC = white blood cell count; SGOT = serum glutamic oxalacetic transaminase; SGPT = serum glutamic pyruvic transaminase; OCG = oral cholecystogram; IVC = intravenous cholangiogram.
examination there were right upper quadrant findings in twelve patients (70 per cent). Laboratory data were not available on all patients, but test results indicated elevated liver function in more than 67 per cent. Only seven in the series underwent radiographic evaluation, but findings were abnormal in all of them. (Tables II and III.) Microbiology. Positive cultures were obtained from eleven patients (taken from bile, peritoneal
The Amerlcan Journal of Surgery
Gallbladder
fluid, or abscess cavity). The most common organism was Escherichia coli, found in eight patients, four of whom had pure E coli, three of whom had both E coli and Klebsiella, and one of whom had E coli as well as Bacteroides fragilis. Staphylococcus aureus was found in a patient with a chronic cholecystocutaneous fistula. Treatment. Of the twelve patients who underwent cholecystectomy, the average interval between preoperative diagnosis of abdominal pathology and operation was 6.8 days. While a preoperative diagnosis of biliary tract disease was made in the majority of patients, in only 20 per cent was gallbladder perforation diagnosed. Vigorous fluid replacement, nasogastric decompression, and in most cases, broad spectrum antibiotics, comprised the preoperative treatment. Results. The length of hospitalization averaged 16 days. More than 58 per cent of the patients suffered some type of postoperative complication ranging from atelectasis to perforapd duodenal ulcer. (Table IV.) There were two deaths (16.7 per cent), both surgical emergencies. Comments
Gallbladder perforation is not as rare as once thought; the present incidence is said to be between 3 and 10 per cent of acute cholecystitis cases. In our series, as well as in others (Table V), there has been an alarmingly high complication rate. Pines and Rabinovitch [4] in 1954 reported an overall mortality of 17.7 per cent due to gallbladder perforations, a figure comparable to that in our series (16.7 per cent). Riesenfeld [5], reporting on sixth-one patients with gallbladder perforation in 1969, indicated an overall mortality of 21 per cent, as compared to 3 per cent in 259 patients who were operated on for acute cholecystitis without perforation [5]. He concluded, as did others, that the increased morbidity and mortality stem chiefly from the delay in diagnosis and a lack of urgency on the part of the physician. Our data support this hypothesis, and we therefore believe that the most effective means of facilitating early and appropriate management is immediate identification of patients who are at high risk of gallbladder perforation. Isch, Finnerman, and Nahrwold [3] observed that most patients with gallbladder perforation have abdominal complaints and findings similar to those patients who have acute cholecystitis without perforation, and that based on these criteria alone, differential diagnosis can be difficult. On the basis of our experience and reports in the literature, we conclude that patients at high risk of gallbladder perforation can be identified by examining such
voltm~~ 137, March 1979
TABLE IV
Perforation
Complications Following Gallbladder Perforation Complications
No. of Patients
Seroma Atelectasis Gastrointestinal bleeding Cardiovascular accident Pleural effusion Poor wound healing Acute renal failure Atrial fibrillation Perforated duodenal ulcer Sepsis Pancreatic insufficiency
2 2 2 1 1 1 1 1 1 1 1
factors as age, sex, previous clinical history, and of paramount importance, associated systemic diseases. Acute cholecystitis is classically described as affecting obese, middle aged, premenopausal women. ‘However, our study shows that patients with gallbladder perforation tend to be older (63 years) and are more frequently male (65 per cent). Isch, Finnerman, and Nahrwold [3] and Williams and Scobie [6] all published similar findings. (Table V.) It should be noted that two of our three patients younger than sixty years (both men) fell into a special category: they had been receiving chronic steroids, and one was undergoing immunosuppressive therapy. Thus, it appears that gallbladder perforation tends to occur primarily in elderly males, yet it occurs occasionally in younger males when certain conditions are present. Inasmuch as no critical analyses of the importance of associated diseases have been published by other authors, it is difficult to draw conclusions based solely on two patients. Nevertheless, the data in this series suggest that perforation is more likely to occur in younger persons if their immune system is compromised. Various authors have suggested that perforation occurs in the setting of acute cholecystitis. Although this is probably true, patients with perforation tend to have underlying chronic disease with superimposed acute cholecystitis. Williams and Scobie [6] stated that fourteen of nineteen patients with gallbladder perforation had either a history indicative of gallbladder disease or a previous diagnosis of chronic cholecystitis. However, a history compatible with chronic cholecystitis is not always elicited, as in our series in which only 27 per cent of patients claimed to have biliary tract disease, yet 70 per cent had pathologic evidence of chronic cholecystitis. The historic abscence of chronic cholecystitis should therefore not preclude the diagnosis of gallbladder
309
62.5
147
Total
Note:.RUCl = right upper quadrant.
50%
50%
65%
63
17
Present series
35%
57%
43%
57
48%
23
Abu-Dalu and Urea [ 71
M 41%
Sex
40%
52%
59%
F
60%
61.6
T$
69
19
Williams and Scobie [6]
[31
lsch et al
27
61
Riesenfeld
151
Pa&ts
No.
47%
48%
32%
68%
35%
16%
48%
28 %
44 %
33%
2
1
Types
Collective Series of Gallbladder Perforation
Series
TABLE V
20%
18%
16%
19%
28%
3
Abdominal pain 86 % Vomiting 60 % Nausea 69 % Anorexia 42%
Abdominal pain 100% Vomiting 61 % Nausea 78 % Anorexia 39 % Abdominal pain 76% Nausea 4 1% Vomiting 29 % Anorexia 35 %
Nausea 89 % Vomiting 89 % Abdominal pain 82 % Anorexia 52%
Symptoms
Tenderness 72% Mass 35 % Temp 51%
Tenderness 52% Mass 35 % Temp 46 %
Tenderness 85% Mass 41% Temp 56 % Tenderness 79% Mass 30 %
RUQ Examination
76%
76%
48%
89%
74%
95%
Cholelithiasis
47%
27%
57%
74%
30%
History of Chronic Cholecystitis
Cholecystectomy 86%; cholecystostomy 7.5%
Cholecystectomy 100%: cholecystostomy 0
4% .
Cholecystectomy 87%; cholecystostomy
Cholecystostomy 8.3%; cholecvstectomy 91.7%. Cholecystectomy 64%: cholecystostomy 18%
Operations
15%
16.7%
0
23%
21.3%
Mortality
Gallbladder Perforation
perforation in an otherwise appropriate clinical setting. Another significant factor in identifying the high risk patient is the presence of severe systemic disease. Williams and Scobie [6] reported that 21 per cent of their patients with perforation had associated atherosclerotic heart disease, and Abu-Dalu and Urea [7] observed a 25 per cent incidence of diabetes mellitus among their patients. In our group, nearly 65 per cent had a severe systemic disease: atherosclerosis (41 per cent); malignancy (35.3 per cent); rheumatoid arthritis (5.8 per cent); or systemic lupus erythematosis (5.8 per cent). These data suggest an association between severe systemic disease and an increased propensity for the development of gallbladder perforation in patients who have chronic gallbladder disease. Gallbladder perforation is not a disease of the young healthy person with acute cholecystitis; rather, it appears to occur in two distinct clinical settings. The first group comprises elderly patients with atherosclerotic heart disease and presumed diffuse atherosclerotic changes. Isch, Finnerman, and Nahrwold [3] and Abu-Dalu and Urea [7] recognized that when the site of perforation could be identified, the fundus was the most common location. Anatomically, this corresponds to the gallbladder area that is least vascularized, implying that vascular changes and ischemia are crucial factors in the pathogenesis of perforation. In elderly patients with atherosclerotic visceral vessels and intermittent chronic low cardiac output, ischemia of the gallbladder wall could occur, thus predisposing them to eventual ischemic necrosis and perforation, The second group includes those patients, both young and old, who are immunosuppressed, either secondary to widespread malignancy or owing to drug therapy. They have impaired host defense mechanisms and are unable to contain a normally nonlethal infection such as cholecystitis, and are thus at great risk of the development of virulent infection and perforation. In this series, both patients receiving steroids had type 1 free perforations. Although it is difficult to extrapolate data from the recent literature on these concepts of vascular changes and immunosuppression relative to gallbladder perforation, we believe that these are key factors, and when present in the setting of chronic cholecystitis, the patient is in serious jeopardy of gallbladder perforation developing. Awareness of these clinical groupings forms the basis for early recognition and treatment of gallbladder perforation. When either of these settings is present in a patient with right upper quadrant symptoms and findings, the clinician should suspect
Volume 137, March 1979
*
HDI,
f
Figure 1. Proposed unified concept of pathogenesis of gallbladder perforation.
gallbladder perforation. There are no data available to determine the time of perforation. Although the optimal means of preventing perforation is to perform earlier surgery on patients with acute cholecystitis, this is not feasible in all cases, and thus, the physician must keep a high index of suspicion and be willing to act accordingly if poor results are to be minimized. In situations in which a high risk patient had right upper quadrant findings, we would recommend a vigorous and expedient diagnostic and therapeutic regimen. After careful examination and routine blood tests, including liver function tests, vigorous hydration, nasogastric decompression, and appropriate antibiotic coverage should be instituted. Since the offending organism in most cases is a gram-negative coliform, ampicillin or a cephalosporin in combination with an aminoglycoside would be appropriate. At this point, if the patient is stable and shows no evidence of sepsis, diagnostic testing should be performed. This should include intravenous cholangiography and abdominal ultrasound. Once preoperative stabilization and diagnostic testing has been performed (in most cases this can be done in 12 hours), we would then recommend early operative intervention. All of our patients underwent cholecystectomy, but cholecystostomy may be indicated in a critically ill patient and can be accomplished using local anesthesia. We maintain that if the prescribed protocol is adhered to in the appropriate clinical setting of those patients-at high risk for gallbladder perforation, the inordinately high morbidity and mortality associated with this syndrome can be satisfactorily lowered. Why do gallbladders perforate? The exact cause and pathogenesis remain to be elucidated. It would seem that, as Glenn and Moore [I] wrote in 1942, “. . . this process is closely associated with circulatory changes and infection.” In the elderly male cardiac patient with presumed diffuse vascular disease, the
311
Roslyn
and Busuttil
prime factor is probably hypoperfusion leading to ischemia and eventual ischemic necrosis. Ischemia and local tissue hypoxia lead to cellular dysfunction and breakdown. This impaired function superimposed upon chronic inflammation and irritation secondary to cholelithiasis provides a potential for severe infection with resulting gangrene and perforation. In the immunosuppressed patient, a minimal amount of inflammation can lead to overwhelming infection with edema, venous congestion, arterial insufficiency, and ultimately, gangrenous perforation. Usually vascular disease and immune deficiency may play separate roles in the evolution of perforation. (Figure 1.) A patient with perforation and systemic lupus erythematosis may represent a clinical situation in which both of these mechanisms are operative, because ischemia and immunosuppression are present on the basis of vasculitis and steroid therapy, respectively. The exact cause of gallbladder perforation remains unclear, but it would seem that this disease is a separate entity from acute cholecystitis. As such, it has its own set of predisposing circumstances and, thus, should have specific guidelines for diagnosis and therapy.
The majority of patients were elderly men (mean age, 61 years) and women (mean age, 67 years) with significant atherosclerotic cardiovascular disease or underlying malignancy. Another important subset of patients consisted of young men who were receiving long-term steroid or immunosuppressive therapy for collagen vascular disease. Almost all of the patients with gallbladder perforation were subjected to an inordinate delay in diagnosis and surgical intervention (6.8 days), and this was responsible for a significant complication rate of 58 per cent as well as an extended postoperative hospitalization time (16 days). The mortality for the entire series was 17 per cent. The successful management of gallbladder perforation is based on early recognition of the patients who are at high risk for this condition. Preoperative diagnostic and therapeutic measures can usually be performed within 12 hours and should include ultrasonography or intravenous cholangiography, fluid resuscitation, nasogastric decompression, and broad spectrum antibiotic administration. A successful outcome in these patients, however, can be achieved only with operative intervention.
Summary
References
Gallbladder perforation is a lethal complication of cholecystitis, a relatively common disease, and has a mortality of 15 to 20 per cent. At UCLA Hospital seventeen patients with perforation of the gallbladder were evaluated and compared with patients who had previously been reported in the English literature. The purpose of this report was to: (1) establish a set of criteria to identify the patient who is at high risk for gallbladder perforation; (2) detail an appropriate course of diagnostic and therapeutic management; and (3) propose a unified concept of the pathogenesis of gallbladder perforation.
1.
312
2.
3. 4.
5. 6. 7. 8.
Glenn F, Moore SW: Gangrene and perforation of the wall of the gallbladder. Arch Surg 44: 677, 1942. Neimeier OW: Acute free perforation of the gallbladder. Ann Surg 99: 922, 1934. lsch J, Finnerman J, Nahrwold D: Perforation of the gallbladder. Am J Gastroenterol55: 45 1, 197 1. Pines B, Rabinovitch J: Perforation of gallbladder in acute cholecystitis. Ann Surg 140: 170, 1954. Riesenfeld G: Perforation of the gallbladder. Int Surg 52: 216, 1969. Williams N, Scobie T: Perforation of the gallbladder. Can Med Assoc J 115: 1223, 1976. Abu-Dalu J, Urea I: Acute cholecystitis with perforation into the peritoneal cavity. Arch Surg 102: 108, 1971. Berkowitz R, Rappaport N, Coodley E, Matsumoto T: Gallbladder perforation into the lesser sac. Int Surg 61: 229, 1976.
The American Journal ot Surgery
