LESLIE W. OTTINGER, M.D.
The clinical course and management of 40 patients who underFrom the General Surgical Services, went operation for acute cholecystitis developing as a postoperaMassachusetts General Hospital, tive complication were reviewed. Of note was the mortality of and the Department of Surgery, 47%, the high incidence of gangrene, perforation, empyema, Harvard Medical School, Boston, Massachusetts and cholangitis, and the atypical clinical presentation of acute cholecystitis under these conditions. Awareness of this possible complication, knowledge of its clinical features, and early surgical intervention are important facets of successful management. judged the primary cause of death and those in which it UTE CHOLECYSTITIS
following operations for
related disease was described by Glenn in 1947,2 though he found reference in the literature as early as 1844. Since that time, Glenn and several other authors have reported collected series of such cases.1'3-10 A relatively high mortality in our hospital for this complication, as compared to that described in these reports and that observed in patients in whom acute cholecystitis was the initial presenting complaint for hospitalization, has caused us to review our experience. Our overall mortality of 47%, observed during the last decade, presents a stark reminder that should oppration become necessary, cholecystitis in the postoperative period remains an exceedingly grave mishap. Material
Hospital records and autopsy findings of 40 patients who had surgery for acute cholecystitis and its associated complications developing in the convalescent phase of operations other than those on the biliary tree were reviewed. The antecedent operative procedures are listed in Table 1. There were 22 men and 18 women. Age distribution along with mortality is illustrated in Fig. 1. Mortality is for the hospitalization. The cases are further divided into those in which the biliary complication was Submitted for publication December 1, 1975. Reprint requests: Leslie W. Ottinger, M.D., 275 Charles Street, Boston, Massachusetts 02114.
was only a contributing factor. There were 10 patients in the first group and 9 in the second. Results In 36 patients, a detailed history was available. In 29, there was no history of disease of the biliary tree. In 3, a record of previous episodes suggesting cholecystitis was found. In 4 other patients, gallstones were known to exist. There had been a preceding postoperative complication prior to the development of cholecystitis in 2 of the survivors and in 8 of those who died. Twentynine of the 40 patients developed cholecystitis following their first operation of the admission whereas 11 had had two preceding surgical procedures. Time of onset of symptoms was distributed rather evenly over the first 14 postoperative days in 32 patients, developing within 48 hours in only 2. In the other 8, symptoms were noted first between the 15th and 50th days after the preceding operation. In only 4 did the resumption of oral intake of solid food seem to have precipitated the attack. In the others, no precipitating cause was apparent. Judging from material available in the records, delay in making the diagnosis did not appear to affect the outcome adversely. The average delay was 4.3 days in the survivors and 3.8 days in those who died. This probably reflects the tendency of complications such as gangrene or perforation of the gallbladder to develop rapidly rather than to occur as a delayed event. In patients who had only cholecystitis, the average delay was 3.9
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ACUTE CHOLECYSTITIS TABLE 1. Antecedent Operation
Hip reconstruction Colon resection Gastric resection Aortic resection Abdominal wall herniorraphy
Hemipelvectomy Peripheral vascular procedure Suture of liver laceration Splenorenal shunt Transthoracic suture of varices Ileal loop urinary diversion Radical hysterectomy Spinal fusion Splenectomy Miscellaneous procedures not involving a major body cavity
12 6 3 3 3
days; in those with gangrenous cholecystitis, 3.6 days; and in those with perforation, 2.5 days. The white blood count was normal in 4 patients, between 10,000 and 14,000 per cubic millimeter in 8, between 14,000 and 20,000 in 10, over 20,000 in 10, and not recorded in 8. The serum bilirubin was normal in 8 patients, between 1 and 5 mg% in 17, over 5 mg% in 10, and not recorded in 5. In the 6 patients who were found to have common duct stones, serum bilirubin was between 1 and 2 mg% in 3, between 2 and 3 mg% in 2, and 12 mg% in 1. Serum bilirubin was not, therefore, a useful test in separating those patients with common duct stones from those in whom none was present. Alkaline phosphatase was normal in but one patient and markedly elevated in 13. Included in this second group were 3 ofthe 6 patients with common duct stones. Thus, a high serum bilirubin and alkaline phosphatase were, in most instances, related to intrahepatic rather than extrahepatic factors, suggesting the seriousness of the preceding illnesses. In 22 of the 40 patients, an unexplained fever was the first evidence of cholecystitis. In only 11, pain located in the epigastric or right upper quadrant was the symptom to provide the first clue. In the remaining patients, the presenting abnormality was abdominal distension in 3, jaundice in 2, and vomiting in 2. That only about 25% presented in the typical fashion for acute cholecystitis with pain and upper gastrointestinal complaints is an important point. In almost all cases, the development of tenderness in the right upper quadrant led to the correct diagnosis, and delay in its appearance was usually the reason for not suspecting cholecystitis earlier as the cause of fever or pain. In 3 patients, gangrenous cholecystitis was not suspected until it was noted at laparotomy. A palpable mass was presented in about 50% of the patients at the time of operation. Operative findings are shown in Table 2. Whereas only 15 patients had cholecystitis alone, 25 had an additional complication of gangrene, perforation, empyema, or cholangitis. In 14 patients (35%), there were no stones in
163 either the' gallbladder or the common duct. In 7 of these patients (50%), there was either gangrene or perforation of the gallbladder. In the 26 patients with cholelithiasis, 18 (69%) had a complication of cholecystitis. Common duct stones were present in 6 patients of the series (15%). Cholecystectomy was performed in 17 cases, cholecystostomy in 12, and cholecystectomy and common duct exploration in 11. In 4 of the 11 patients, common duct stones were found. Two other patients with choledocholithiasis were managed with choledochostomy alone. Both patients died, but in neither case could a more extensive operative procedure have achieved a better outcome. Transduodenal sphincterotomy was performed in two cases of common duct exploration, once upon the indication of an impacted stone and once for cholecystitis and acute pancreatitis with small common duct stones. Though mortality was higher following cholecystostomy than cholecystectomy, it was not the result of employing the lesser operation. Seventeen patients had a complication of their biliary procedures. Complications seen in more than one were wound infections, upper gastrointestinal bleeding, pulmonary emboli, pneumonia, and acute renal shutdown. Intraoperative culture results were found for 22 patients. These showed no growth in 8. Of the positive cultures, 9 showed nonhemolytic streptococci with one of several gram-negative rods. In the other 5, E. coli, Staphlococcus aureus, alpha hemolytic streptococcus, and Klebsiella singly or in combination were isolated. In only two instances could the organism be related to an earlier infection occurring elsewhere. Overall mortality was 47%. In 27%, the death could be directly attributed to the biliary complication. In the others, it was but a further complication in a patient who could not reasonably have been expected to recover even without it. Fig. 1 relates mortality to age.
( CHOLECYSTITIS )
.QZ 3 -~AG
FIG. 1. Incidence and Mortality of Postoperative Cholecystitis by Age.
O1TINGER TABLE 2. Operative Findings
Cholecystitis Gangrene Perforation Empyema Cholangitis Total
Cholelithiasis and Choldocholithiasis
6 7 6 1 0
2 0 0 1 3
7 5 2 0 0
12 8 2 3
Average age in survivors was 56 years and in those who died, 67 years. Table 3 does the same for the various complications of the episodes. Of the 13 patients with performation, empyema, or cholangitis, only 2 recovered. The cause of death in almost every case in which it was attributed to the biliary complication was sepsis: hepatic and intra-abdominal abscesses in 5 patients, cholangitis with its complications in 2 despite adequate drainage of the common duct, and metastatic abscesses in 1. Acute renal shutdown and the complications of pulmonary infections accounted for the others. In an effort to discover possible etiologic factors, the patients were somewhat arbitrarily divided into two groups, one with a course that paralleled the usual one for cholecystitis and one that followed a more virulent course. Reasons for inclusion in the second group included a rapid progression to complications and extensive and severe involvement of the gallbladder. There were 7 patients in the first group and 27 in the second, excluding the 6 with common duct stones. There were no significant differences between the two groups with reference to age, sex, presence or absence of stones, and the use of meriperidine, morphine, coumadin, and antibiotics before the attack of cholecystitis. Discussion In several ways, cholecystitis that develops following an unrelated surgical procedure differs from that which is the primary presentation. The patients are older, there is a greater proportion of men, the acalculus incidence is higher, the presentation is somewhat different, and the mortality is significantly higher. These differences sugTABLE 3. Complications with Related Mortality
Cholecystitis Gangrene Perforation Empyema Cholangitis
4 4 7 2 2
36% 33% 88%
8 1 0 1
Surg. * August 1976
gest that in at least a portion of the patients the pathologic process may be different. Resting on what is known of the pathophysiology of acute cholecystitis in other settings, several mechanisms for postoperative cholecystitis have been advanced. Bile stasis leading to concentration and inspissation of the contents of the gallbladder and obstruction to outflow, either from stones or from inspissated contents of the gallbladder, are the common elements. Factors often present in the postoperative patient and known to contribute to the stasis are fasting, anesthesia, dehydration, fever, and narcotics for the relief of pain. Some patients had gangrene of the entire gallbladder and bile-stained fluid in the peritoneal cavity. This may mean that under some circumstances, concentration and other changes in gallbladder contents lead to necrosis of the structure and thus may be one factor that is not operative in the usual care of cholecystitis. The coincidence of these attacks with the resumption of oral feedings was pointed out by Glenn.2 This was confirmed by Levin but not by Lindberg and his associates,7'8 and in most of our cases, it could not be shown to be a factor. It is thought that in these patients, contraction of the gallbladder obstructed by thick inspissated bile or stones leads to a sequence of changes which result in cholecystitis. This is an important concept as it does open for consideration the only apparent avenues for prevention of the complication. Lindberg and associates reported acalcus cholecystitis in 12 war casualties between the ages of 19 and 30.8 These patients had had multiple operations and blood transfusions. A heavy pigment load secondary to transfused blood was cited as a possible contributing factor. It was also shown that in 6 of their 9 patients with positive bile cultures, the same organisms were present in infected wounds or in the blood stream. These authors suggested that, under postoperative conditions, the gallbladder may become a target for blood-borne bacteria. In two of our patients, this was a possible mechanism for cholecystitis. Among the other contributing factors that have been proposed are sympathetic stimulation leading to spasm, ischemia, and mural damage and states of decreased perfusion leading to hypoxia of the gallbladder. It seems likely that multiple factors including gallstones are involved. Not all need be present. These rather than new etiologic factors probably account for the postoperative cholecystitis. The high mortality is apparently the result of the greater incidence of gangrene and other complications and the contributory burdens of increased age, the preceding illness, and operations. The finding that more than 60% of the cases were complicated by gangrene, perforation, empyema, or cholangitis differs from our experience with cholecystitis
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under other circumstances and bears further scrutiny. It is probable that many less severe attacks of cholecystitis go unnoticed in the early postoperative period. Our own relatively high mortality as compared to that in other series does, in part, reflect the fact that we did not include nonoperated cases. Thus in 2 patients, the history documented signs and symptoms that were probably the result of cholecystitis following earlier operations, and in a third, surgery was performed electively after the attack subsided. Even in the patient who has had an operation involving neither the abdominal cavity nor its wall, gastrointestinal symptoms such as anorexia, distention, and cramps are not unusual in the convalescent phase, and mild attacks of cholecystitis are probably often missed. The group of patients represented in the series had symptoms and signs which extended beyond 24 hours after onset and in any series of cholecystitis, this group would be classified with the more severe attacks. One has the impression despite this that, in the postoperative period, cholecystitis carries an increased risk for complications. Cholecystitis in the postoperative period is a complication that for obvious reasons we have come to regard as exceedingly serious. Though delay in diagnosis may not lead to an increase in local complications, it clearly does magnify their systemic and secondary effects. Pain, so characteristic of the usual clinical presentation of cholecystitis, was not the earliest finding in 75% of the patients. Rather, fever is the abnormality most often noted initially, and because cholecystitis in the postoperative period is relatively rare, this diagnosis is not likely to head the list of possible causes of temperature elevation. Making the diagnosis rests almost exclusively on the findings on physical examination. Even when cholecystitis is suspected, failure to opacify the gallbladder by oral cholecystography does not confirm it even though it may increase the possibility. Parenthetically, opacification rather reliably excludes acute cholecystitis. Intravenous cholecystography may opacify the gallbladder even in the presence of cholecystitis and is not of help in establishing the diagnosis. Laboratory studies may likewise be helpful but are not confirmatory. The clinical diagnosis resides in repeated examination of the right upper abdomen for the development of a mass or for signs of local peritoneal irrita-
tion. There is no practical way to prevent the complication. Avoiding unnecessary fasting and narcotics may be helpful. While the presence of stones may increase the likelihood of an attack, preoperative studies undertaken routinely to discover their presence are not justified. A history of attacks of cholecystitis, particularly after previous operations, should be carefully sought. With such a history or the presence of gallstones in mind,
diagnosis of this postoperative complication would perhaps be more decisive. Though cholecystectomy is our preferred operation, if a lesser procedure is indicated by local findings or by the patient's condition, we do not hesitate to perform a cholecystostomy unless the entire gallbladder is necrotic. After cholecystostomy, which may be performed under local anesthesia, confirmation of drainage of the common duct by injection of radiopaque dye into the tube is usually indicated. Subsequent elective cholecystectomy is not always necessary.11 This experience with cases of acute cholecystitis following the treatment of unrelated disease has caused us to adopt the principle of operative intervention on diagnosis. Though it is probably possible to carry some patients through the episode for later elective surgery if stones be present, there is little merit in this approach. Virtually all of these patients have had symptoms of fever and leukocytosis persisting beyond 24 hours by the time the diagnosis is suspected. Under more usual circumstances, they would be subjected to immediate cholecystectomy because the chance of recovery without it would be minimal. Gangrene, perforation, and empyema are found early and frequently in these patients, and one should not delay operation pending definite clinical evidence of their presence. Only the earliest possible intervention can avoid their secondary septic complications. Whether or not one subscribes to the practice of immediate surgery for all patients who require hospitalization for cholecystitis, it is clearly the best course for the postoperative patient with acute chole-
cystitis. References 1. Bell, G. A. and Holubitsky, I. B.: Acute Cholecystitis Following Unrelated Surgery. Can. Med. Assoc. J. 101:94, 1969. 2. Glenn, F.: Acute Cholecystitis Following the Surgical Treatment of Unrelated Disease. Ann. Surg., 126:411, 1947. 3. Glenn, F. and Wantz, G. E.: Acute Cholecystitis Following Surgical Treatment of Unrelated Disease. Surg. Gynecol. Obstet., 102:145, 1956. 4. Howard, R. J. and Delaney, J. P.: Postoperative Cholecystitis. Dig. Dis., 17:213, 1972. 5. Knudson, R. J. and Zaber, W. F.: Acute Cholecystitis in the Postoperative Period. N. Engl. J. Med., 269:289, 1963. 6. Leon, W.: Acute Cholecystitis Following Unrelated Surgery. Am. Surg., 20:549, 1954. 7. Levin, M. N.: Acute Cholecystitis Following Surgery Unrelated to the Biliary Tract. JAMA, 177:644, 1961. 8. Lindberg, E. F., Grinnan, G. L. B. and Smith, L.: Acalculus Cholecystitis in Viet Nam Casualties. Ann. Surg., 171:152, 1970. 9. Schwegman, C. W. and DeMuth, W. E., Jr.: Acute Cholecystitis Following Operation for Unrelated Disease. Surg. Gynecol.
Obstet., 97:167, 1953. 10. Thompson, J. W., III, Ferris, D. 0. and Baggenstoss, A. H.: Acute Cholecystitis Complicating Operation for Other Disease. Ann. Surg., 155:489, 1962. 11. Welch, J. P. and Malt, R. A.: Outcome of Cholecystostomy. Surg. Gynecol. Obstet., 135:717, 1972.