World J. Surg. 16, 1 1 6 0 - 1 1 6 6 , 1992
World Journal of Surgery © 1992 by the Soci~t¢ lnternationale de Chirurgie
Acute Acalculous Cholecystitis Complicating Trauma: A Prospective Sonographic Study M. I m h o f , J. R a u n e s t , Ch. O h m a n n , and H . - D . R 6 h e r Department of General and Trauma Surgery, Heinrich-Heine-University, Diisseldorf, Federal Republic of Germany Acute acalculons eholecystitis (AAC) is a well known complication in severely traumatized patients. Existing data of AAC originate from retrospective analyses and episodic case reports. In a prospective study 45 polytranmatized patients admitted to our intensive care unit from January 1989 to June 1990 were clinically and sonographically screened for this condition at defined time intervals. Trauma scoring was performed according to the injury severity score and polytrauma score. AAC was defined as a combination of hydrops of the gallbladder, an increased wall thickness (>3.5 mm), and the demonstration of sludge. We were able to document this diagnostic triad in 8 (18%) of 45 patients. As a consequence early elective cholecystectomy was performed in 1 of the 8 patients. The remaining patients were treated conservatively. The incidence of AAC in severely traumatized patients is higher than figures so far published suggest. Ultrasound is a reliable method of early detection and follow-up of this complication.
Acute acalculous cholecystitis (AAC) is a well known complication in postoperative and particularly in severely traumatized intensive care patients. All that is known so far with regards to the incidence and clinical course of "stress"-cholecystitis is based on episodic case reports and retrospective analyses which, of course, omit subclinical forms of this condition. The incidence ranged between 0.5% and 4.2% [I--4] in severely traumatized patients. The first three authors, however, verified their cases exclusively by laparotomy. So cholecystitis is often diagnosed intra-operatively or post mortem by chance. Clinical and laboratory findings are often nonspecific or misleading. Tenderness, fever, tachycardia, leucocytosis, elevated erythrocyte sedimentation rate (ESR), bilirubin, alkaline phosphatase, gamma-glutamyl-transpeptidase (GGT) [4, 5] are not mandatory signs for acute cholecystitis. Right upper quadrant pain or the "sonographic Murphy sign" is rarely reliable in intensive care unit patients due to anesthetic and analgesic treatment. For this reason greater reliance is placed on ultrasound findings. In this prospective study we therefore expected a higher incidence of AAC in polytraumatized patients than previous data have revealed. An additional purpose was evaluation of early morphological changes of the gallbladder, investigating Reprint requests: Prof. Dr. H.-D. R6her, Department of General and Trauma Surgery, Heinrich-Heine-University, Moorenstr. 5, 4000 Dfisseidorf, Federal Republic of Germany.
etiological factors, the laparotomy rate, and the percentage of patients with spontaneous regression or mortality. Patients and Methods
All severely traumatized intensive care unit patients admitted from January 1989 to June 1990 were included in this study. Severe trauma was defined according to Schweiberer and coworkers [6] as simultaneous severe injury of 2 to 4 body cavities or regions, or severe multiple trauma of the locomotor system (spine, pelvis, 4 extremities). Patients after cholecystectomy or with primary injury of the gallbladder were excluded. Patients were also excluded if the period of observation was 3.5 mm, hydrops, sludge, sonolucent or double layer within the gallbladder wall (also called subserosal edema), and pericholecystic fluid collection (Table 1). According to the literature "stress"-cholecystitis is defined by the demonstration of a triad of increased thickness of the gallbladder wall, hydrops, and sludge [4, 9, 10]. The patient history, ultrasonographic findings, clinical course, laboratory values, therapy, and outcome were prospectively documented. For descriptive statistics of continuous variables the median and range were calculated. Qualitative variables were expressed as percentages. For the incidence of acute acalculous cholecystitis a 95% confidence interval was estimated. Statistical testing was performed with the chi-square test (qualitative variables) and the Mann-Whitney (Kniskal-Wallis) test (quantitative variables). Results The study population of 45 polytraumatized patients is shown in Table 2. Thirty-nine patients were primarily admitted to our department, 6 patients were transferred from other departments at the day of injury. Most patients were young males due to a high rate of motorcycle accidents. Furthermore, this explains a high rate of associated thoracic, head, and limb injury.
M. lmhof et al.: Acute Acalculous Cholecystitis
1161
Table 1. Major and minor sonographic criteria for the diagnosis of acute acalculous cholecystitis.
Table 2. Study population.
Clinical characteristic Major criteria
Minor criteria
Wall thickness >3.5 mm Hydrops
Double layer Pericholecystic fluid collection
Sludge
Patients, total Male Age, median, (range) (yrs) Period of observation, median, (range) (days) Total number of ultrasonographic examinations Injury pattern Thorax Head Lower limb Upper limb Pelvis Abdomen Spine Soft tissue Trauma score, median, (range) ISS PTS Mortality
45 37 29 (4---8I) 32 (8-97) 946 30 30 23 12 17 15 9 5
Sonomorphological changes of the gallbladder were detected in 36 of 45 patients (Fig. 1). Sludge was the most frequent sonographic finding. It was present in 26 patients. Thickening of the gallbladder wall >3.5 mm was observed in 17 patients. Equally, 17 patients showed hydrops of the gallbladder. Suspected minor criteria were double layer of the gallbladder wall (10 of 45 patients) and pericholecystic fluid collection (25 of 45 patients). We were able to demonstrate the diagnostic triad of acalculous cholecystitis in 8 (18%) men (95% confidence interval: 8%-32%) with a median age of 26 years (range 17-67 years). There were no differences in polytrauma scores compared to the 37 patients without the diagnostic triad. First sonographic changes were already seen at the first day of admission. The triad was detected on average at day 11. In 1 patient we were able to demonstrate it at the 3rd day. One patient underwent cholecystectomy with a histological confirmation. The diagnosis of acute cholecystitis was not confirmed histologically in another patient who did not fulfill all criteria of the triad but was operated because of septic temperatures. There were no deaths related to stress cholecystitis (Table 3). Clinical course and laboratory findings did not help in the diagnosis of acute acalculous cholecystitis. During the intensive care unit (ICU) stay the majority of patients with and without the diagnostic triad had temperatures >38°C, increased bilirubin, alkaline phosphatase, and GGT. Leucocytosis was seen in all 8 patients with acalculous cholecystitis and in 34 patients without this condition. Right upper quadrant pain and the so called "sonographic Murphy sign" were no valid diagnostic criteria in fact of ventilated and sedated patients. Nevertheless right upper quadrant pain was seen in 5 of 8 patients with, and 16 of 37 patients without, the triad (Table 4). A significant relationship between the number of blood transfusions and the incidence of acute acalculous cholecystitis could be found (p < 0.05). Higher morphine dosage was also observed in patients with the diagnostic triad, however the differences were statistically not significant (p < 0.08) (Table 5).
Despite several studies, the etiology and pathogenesis of acalculous cholecystitis are not yet completely understood. Obviously there are multiple pathophysiological mechanisms. Long-time bed rest with fasting during total parenteral nutrition probably reduces gallbladder motility. Increasing bile concentration following multiple blood transfusion, resorption of hematomas, and dehydration with subsequent stasis and possible bacterial contamination results in irritation of the gallbladder mucosa [1, 4, 12]. Decreased blood supply due to shock, sepsis, high sympathetic tone, toxins, arteriosclerosis, or high intraluminal pressure leads to wall necrosis [3, 5, 12-14, 16-21]. Bauer [22] speculated about a histamininduced stress-reaction in the development of post-traumatic choI'ecystitis. The true cause of acalculous cholecystitis may be multifactorial with several concomitant factors leading to the development of disease. A high morphine dose and multiple blood transfusion in the 8 patients with the diagnostic triad of acalculous cholecystitis were statistically significant prognostic factors (p < 0.05) (Table 5).
Discussion
Diagnosis
History
Diagnostic imaging procedures in patients with acute acalculous cholecystitis were evaluated retrospectively by Mirvis and associates [23J. Sonography and computed tomography scan (CT) were both highly sensitive (92% and 100%, respectively) and specific (96% and 100%, respectively). Hepatobiliary scintigraphy was compromised by frequent false-positive results which gave a specificity of only 38%. Ultrasound-guided gallbladder aspiration with bile culture revealed no effect in diagnosing acute cholecystitis (13 of 21 bile cultures were sterile, results were not available in time, gram-stained smears and bile cultures suffered from low sensitivity) [24]. Because ultrasound is relatively inexpensive and can be performed at the bedside, it
The first reported case of acute cholecystitis following an Unrelated operation was described by Duncan [11] in 1844 as a Complication of a femoral hernial repair. Sporadic and collected eases were described after this [12, 13], all seeking a common basis for this complication. Acute acalculous cholecystitis is now well recognized as a separate entity, differing from the acute stone-related cholecystitis. The disorder can follow any form of surgery, but it is most commonly encountered after trauma and abdominal surgery [13]. No stones are present in the gallbladder in about 5% to 10% of patients with primary acute
28 (17-45) 28 (10-53) 5
ISS: Injury severity score; PTS: Polytrauma score.
cholecystitis [14], as compared to 22% to 90% in acute postoperative cholecystitis [i 1, 14, t5].
Etiology
1162
World J. Surg. Vol. 16, No. 6, Nov./Dec. 1992 Table 4. Clinical and laboratory findings in patients with and without acute acalculous cholecystitis.
Hydrops
Triad present
Sludge
Parameter
yes (n = 8)
no (n = 37)
p value
Right upper quadrant pain Leucocytosis > 12,000 mm 3 Temperature >38°C Bilirubin >24/~mol/l Alk. Phos. > 190 U/I GTT >28 U/1
5 8 8 7 7 6
16 34 36 25 30 31
n.s. n.s. n.s. n.s. n.s. n.s.
n.s.: Not significant; Alk. phos.: Alkaline phosphatase; GGT: Gamma-glutamyl-transpeptidase. W a l l t h i c k n e s s > 3.5 m m
Fig. 1. Sonomorphological changes of the gallbladder concerning major criteria.
Table 3. Description of patients with and without acute acalculous cholecystitis. Triad present Parameter
yes (n = 8)
no (n = 37)
p value
Male Age, median, (range) (yrs) Scoring, median, (range) ISS PTS Day of occurrence, median (range) First signs Traid Cholecystectomy Death
8 26 (17--67)
28 29 (4-81)
n.s. n.s.
28 (21--41) 26 (23-52)
26 (11--45) 29 (10-53)
n.s. n.s.
2 (0--16)a 1 5
n.s. n.s. n.s.
3 (0-6) 11 (3-29) 1 0
First signs seen in 26 patients. n.s.: Not significant; ISS: Injury severity score; PTS: Polytrauma score.
should be regarded as a satisfactory first line diagnostic screening procedure. Ultrasound offers several advantages over other methods of examination. The system is portable, noninvasive, and serial examinations are easily obtained. The presence of sutures, drains, orthopedic or life-support devices usually do not cause any problems [25]. The use of CT scan as an initial diagnostic procedure seems reasonable in transportable patients, especially when other disease (e.g., thoracic, cerebral) are suspected [13].
Definition In a comparison of ultrasound and postoperative measurements of the gallbladder some authors found a gallbladder wall measuring >3.5 mm to be a reliable independent diagnostic criterion for cholecystitis with a sensitivity >98% [25-28]. Several ultrasonic studies have reported gallbladder wall thickening in patients with various nonbiliary conditions, including alcoholic liver disease, ascites, portal venous hypertension, hypoalbuminemia, hepatitis, chronic heart failure, and renal insufficiency without intrinsic gallbladder disease [4, 19, 28-30]. The diagnosis of acute cholecystitis should be made with caution when based on only one criterion. This has led to the definition of
various major and minor criteria for an abnormal gallbladder. Although there is no clearcut agreement about the value of any single criterion, most studies have indicated that the sensitivity of major criteria for acute cholecystitis is 81% to 86%, and the specificity is 94% to 98%. Inclusion of any minor criterion increases the sensitivity of ultrasound to 90% to 98% but reduces the specificity to as low as 70%. The sensitivity for acalculous cholecystitis may also be somewhat lower [31]. A diagnostic accuracy index, corrected for chance, was statistically and clinically more relevant with 3 as the minimum number of criteria for the ultrasonic diagnosis of acute cholecystitis [32]. If very restrictive criteria are applied to the diagnosis of acute cholecystitis (for example, the presence of both major and minor criteria), the sensitivity of ultrasound may decrease to 70% to 76% [33-37]. A definition problem is caused by different options in the literature regarding the classification of criteria as major or minor.
Clinical and Laboratory Findings Virtually every series of patients with acalculous cholecystitis has documented that the majority of patients present with right upper quadrant pain, fever, and leucocytosis. H o w e v e r , these findings may be masked in postoperative or post-traumatic patients who are intubated, neurologically impaired, or heavily sedated. The diagnosis may thus be difficult and contribute to the diagnostic and therapeutic delay. In our series clinical and laboratory findings were not significantly different in the groups with or without the diagnostic triad (Table 4).
Treatment Over the past centuries therapeutic strategies of post-traumatic or postoperative acute acalculous cholecystitis ranged from surgical cholecystostomy to obligate cholecystectomy, from ultrasound guided percutaneous transhepatic cholecystostomy with optional secondary elective cholecystectomy to conservative treatment (Table 6). Surgical cholecystostomy has been advocated if a patient with acute cholecystitis is considered to be too ill to survive cholecystectomy. Whereas cholecystostomy is technically " e a s i e r " to perform than cholecystectomy it is associated with mortality rates up to 40% and complication rates up to 20% [38, 39]. The lack of diagnostic accuracy, particularly the lack of reliable diagnostic methods, contributes to the delay in diagnosis and treatment and leads to high mortality rates. In H o w a r d ' s retrospective review over 25 years
M. Imhof et al.: Acute Aealculous Cholecystitis
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Table 5. Possible etiological factors inducing acute acalculous cholecystitis. Factor
No. of sonographic criteria
p value
Patients Blood transfusion units, median, (range) Morphin-dose (mg/day), median, (range)
3 (n=8) 32 (7-119)
2 (n=9) 20 (8--73)
15.1 (8.8-19.8)
14.4 (0.1-18)
1 (n = 18) 12 (2-100) 7.2 (1.6-24.3)
0 (n = 10) 6 (1-21)
3.5 mm) et de la pr6sence de sludge. Cette triade a 6t6 retrouv6e chez 8 des 45 patients (18%). Une chol6cystectomie pr6coce a 6t6 d6cid6e chez un de ces patients, alors que les 7 autres ont 6t6 trait6s m6dicalement. L'incidence de C A L chez le polytraumatis6
M. Imhof et al.: Acute Acalcuious Cholecystitis
grave est sfirement plus 616vre qu'il n'est classique de le dire. L'rchographie est une mrthode fiable pour la dgtection prgcoce et pour suivre cette complication post-traumatique. Resumen
La colelitiasis acalculosa (CAA) es una reconocida complicaci6n en pacientes con trauma severo. E1 conocimiento sobre la CAA emana de an,'tlisis retrospectivos y de reportes esporfidicos de casos individuales. En un estudio prospectivo se investig6 esta entidad por medio de examenes clinicos y sonogrfificos seriados en 45 pacientes politraumatizados que ingresaron a nuestra unidad de cuidado intensivo entre el 1° de enero de 1989 y el 30 de junio de 1990. La severidad del trauma fue determinada mediante el ISS (Injury-Severity-Score) y el PTS (Polytrauma-Score). La CAA fue definida como la combinaci6n de hidrops de la vesicula biliar, aumento del aspesor de la pared (>3.5 mm) y la demonstraci6n de barro biliar. Esta traida diagn6stica pudo ser documentada en 8 de 45 pacientes (= 18%). Consecuentemente, se preactic6 colecistectomia precoz electiva en i de 8 pacientes con la traida diagn6stica de CAA; el resto de los casos fue tratado en forma conservadora. La incidencia de CAA es mils alta de lo que sugieren las estadfsticas publicadas. La ultrasonografia constituye un mrtodo confiable de detecci6n precoz y de seguimiento de esta complicaci6n. References
1. Lindberg, E.F., Grinnan, G.L.G., Smith, L.: Acalcutous cholecystiffs in Viet Nam casualities. Ann. Surg. 171:152, 1970 2. Lorgeron, P., Parmentier, G., Katz, A.: L'abdomen du polytraumatise. J. Chir. 120:85, 1983 3. Rfiedi, T., Frutiger, A., Leutenegger, A.: "Steinlose" nekrotisierende Cholezystitis beim Polytrauma. Helv. Chir. Acta 52:131, 1985 4. Waydhas, C., Sepp-Lukas, L., Nast-Kolb, D., Pfeifer, K.J., Schweiberer, L.: Cholezystitis nach Polytrauma. Unfallchirurg 91:10, 1988 5. Johnson, L.B.: The importance of early diagnosis of acute acalculous cholecystitis. Surg. Gynecol. Obstet. 164:197, 1987 6. Schweiberer, L., Nast-Kolb, D., Duswald, K.H.: Das Polytrauma--Behandlung nach dem diagnostischen und therapeutischen Stufenplan. Unfallchirurg 90:529, 1987 7. Baker, S.P., O'Neill, B.O., Haddon, W., Long, W.B.: The injury severity score: A method for describing patients with multiple injuries and evaluating emergency care. J. Trauma 14:187, 1974 8. Oestern, H.J., Tscherne, H., Sturm, J., Nerlich, M.: Klassifizierung der Verletzungsschwere. Unfallchirurg 88:465, 1985 9. Meissner, K., Meiser, G., Schwaiger, E.: Reaktive steinfreie Cholezystistis: blande und asymptomatische Vertaufsform Zur Dunkelziffer einer klassischen Stresserkrankung. Langenbecks Arch. Chir. 374:46, 1989 t0. Rouby, J.J.: Acute acalculous cholecystitis: An increasing entity in critically ill patients. In Proceedings of the 4th World Congress on Intensive and Critical Care Medicine, Jerusalem. 1985, p. 243 11. Duncan, J.: Femoral hernia: Gangrene of gallbladder; extravasation of bile; peritonitis; death. North. J. Med. 2:151, 1844 12. Du Priest, R.W., Khaneja, S.C., Cowley, R.A.: Acute cholecystitis complicating trauma. Ann. Surg. 189:84, 1979 13. Glenn, F.: Acute acalculous cholecystitis. Ann. Surg. 189:458, 1979 14. Howard, J.M., Milford, M.T., de Bakey, M.E.: The significance of the sympathetic nervous system in acute cholecystitis. Surgery 32: 251, 1952 15. Inoue, T., Mishima, Y.: Postoperative acute cholecystitis: A collective review of 494 cases in Japan. Jpn. J. Surg. •8:35, 1988 16. Flament, J.B., Palot, J.P., Delattre, J.F., Rives, J.: Les cholecystites aigues postoperatoires. Chirurgie 112:115, 1986
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17. Freising, S.: Nekrotisierende Cholecystitis beim Polytrauma. Unfallheilkunde 86:83, 1983 18. Orlando, R., Gleason, E., Drezner, A.D.: Acute acalculous cholecystitis in the critically ill patients. Am. J. Surg. 145:472, 1983 19. Rice, J., Williams, H.C., Flint, L.M., Richardson, J.D.: Posttraumatic acalculous cholecystitis. South. Med. J. 73:14, 1980 20. Johnson, E.E., Hedley-Whyte, J.: Continuous positive pressure ventilation in choledochoduodenal flow resistance. J. Appl. Physiol. 39:937, t975 21. Glenn, F., Becker, C.G.: Acute acalculous cholecystitis. Ann. Surg. 195:131, 1982 22. Bauer, H.: Die Gallenblase als Stressorgan. Chirurg 55:828, 1984 23. Mirvis, S.E., Vainright, J.R., Nelson, A.W.: The diagnosis of acute acalculous cholecystitis: A comparison of sonography, scintigraphy and CT. A.J.R. 147:1171, 1986 24. Mc Gahan, J.P., Lindfors, K.K.: Acute cholecystitis: Diagnostic accuracy of percutaneous aspiration of the gallbladder. Radiology 167:669, 1988 25. Deitch, E.A., Engel, J.M.: Acute acalculous cholecystitis: Ultrasonic diagnosis. Am. J. Surg. 142:290, 1981 26. Marchal, G., Crolla, D., Baert, A.L.: Gallbladder wall thickening: A new sign of gallbladder disease visualized by gray scale cholecystosonography. J. Clin. Ultrasound 6:177, 1978 27. Marchal, G., Casaer, M., Baert, A.L.: Gallbladder wall sonolucency in acute cholecystitis. Radiology 133:429, 1979 28. Wegener, M., B6rsch, G., Schneider, J.: Gallbladder wall thickening: A frequent finding in various nonbiliary disorders--A prospective ultrasonographic study. J. Clin. Ultrasound •5:307, 1987 29. Fiske, C.E., Laing, F.C., Brown, T.W.: Ultrasonographic evidence of gallbladderwall thickening in association with hypoalbuminaemia. Radiology 135:713, 1980 30. Kelbel, C., Brrner, N., Weilemann, L.S.: Die sonographische Gallenblasenwand-verdickung und ihre diagnostische Bedeutung bei intensivpflichtigen Patienten. Ultraschall 9:106, 1988 31. Shuman, W.P., Rogers, J.V., Rudd, T.G., Mack, L.A., Plumley, T., Larson, E.B.: Low sensitivity of sonography and cholescintigraphy in acalculous cholecystitis. A.J.R. 142:531, 1984 32. Martinez, A., Bona, X., Velasco, M., Martin, J.: Diagnostic accuracy of ultrasound in acute cholecystitis. Gastrointest. Radiol. ••:334, 1986 33. Raghavendra, B.N., Feiner, H.D., Subramanyan, B.R.: Acute cholecystitis: Sonographic-pathologic analysis. A.J.R. 137:327, 1981 34. Freitas, J.E., Mirkes, S.H., Fink-Bennett, D.M., Bree, R.L.: Suspected acute cholecystitis: Comparison of hepatobiliary scintigraphy versus ultrasonography. Clin. Nucl. Med. 7:364, 1982 35. Fink-Bennett, D., Freitas, J.E., Ripley, S.D., Bree, R.L.: The sensitivity of hepatobiliary imaging and real-time ultrasonography in the detection of acute cholecystitis. Arch. Surg. 120:904, 1985 36. Becker, C.D., Burckhardt, B., Terrier, F.: Ultrasound in postoperative acalculous cholecystitis. Gastrointest. Radiol. ••:47, 1986 37. Herlin, P., Ericsson, M., Holmin, T., J6nsson, P.E.: Acute acalculous cholecystitis following trauma. Br. J. Surg. 69:475, 1982 38. Skillings, J.C., Kumai, C., Hinshaw, J.R.: Cholecystostomy: A place in modern biliary surgery? Am. J. Surg. 139:865, 1980 39. Glenn, F., Mc Sherry, C.K.: Calculous biliary tract disease. Curr. Probl. Surg. 1, 1975 40. Howard, R.J.: Acute acalculous cholecystitis. Am. J. Surg. 141: 194, 1981 41. Eggermont, A.M., Lameris, J.S. Jeekel, J.: Ultrasound guided percutaneous transhepatic cholecystostomy for acute acalculous cholecystitis. Arch. Surg. t20:1354, 1985 42. Lohela, P., Soiva, M., Suramo, I., Taavitsainen, M., Holopainen, O.: Ultrasonic guidance for percutaneous puncture and drainage in acute cholecystitis. Acta Radiol. 27:543, 1986 43. Mc Gaban, J.P., Lindfors, K.K.: Percutaneous chotecystectomy: An alternative to surgical choecystostomy for acute cholecystitis? Radiology 173:481, 1989 44. Berger, H., Pratschke, E., Arbogast, H., Stabler, A.: Percutaneous cholecystostomy in acute acalculous cholecystitis. Hepato-gastroenterol. 36:346, 1989 45. Berger, H., Forst, H., Nattermann, U., Pratschke, E.: Perkutane Cholezystostomie in der Behandlung der akuten Cholezystitis des Risikopatienten. Fortschr. R6ntgenstr. 150:694, 1989
World Journal of Surgery © 1992 by the Soci~t¢ lnternationale de Chirurgie
Acute Acalculous Cholecystitis Complicating Trauma: A Prospective Sonographic Study M. I m h o f , J. R a u n e s t , Ch. O h m a n n , and H . - D . R 6 h e r Department of General and Trauma Surgery, Heinrich-Heine-University, Diisseldorf, Federal Republic of Germany Acute acalculons eholecystitis (AAC) is a well known complication in severely traumatized patients. Existing data of AAC originate from retrospective analyses and episodic case reports. In a prospective study 45 polytranmatized patients admitted to our intensive care unit from January 1989 to June 1990 were clinically and sonographically screened for this condition at defined time intervals. Trauma scoring was performed according to the injury severity score and polytrauma score. AAC was defined as a combination of hydrops of the gallbladder, an increased wall thickness (>3.5 mm), and the demonstration of sludge. We were able to document this diagnostic triad in 8 (18%) of 45 patients. As a consequence early elective cholecystectomy was performed in 1 of the 8 patients. The remaining patients were treated conservatively. The incidence of AAC in severely traumatized patients is higher than figures so far published suggest. Ultrasound is a reliable method of early detection and follow-up of this complication.
Acute acalculous cholecystitis (AAC) is a well known complication in postoperative and particularly in severely traumatized intensive care patients. All that is known so far with regards to the incidence and clinical course of "stress"-cholecystitis is based on episodic case reports and retrospective analyses which, of course, omit subclinical forms of this condition. The incidence ranged between 0.5% and 4.2% [I--4] in severely traumatized patients. The first three authors, however, verified their cases exclusively by laparotomy. So cholecystitis is often diagnosed intra-operatively or post mortem by chance. Clinical and laboratory findings are often nonspecific or misleading. Tenderness, fever, tachycardia, leucocytosis, elevated erythrocyte sedimentation rate (ESR), bilirubin, alkaline phosphatase, gamma-glutamyl-transpeptidase (GGT) [4, 5] are not mandatory signs for acute cholecystitis. Right upper quadrant pain or the "sonographic Murphy sign" is rarely reliable in intensive care unit patients due to anesthetic and analgesic treatment. For this reason greater reliance is placed on ultrasound findings. In this prospective study we therefore expected a higher incidence of AAC in polytraumatized patients than previous data have revealed. An additional purpose was evaluation of early morphological changes of the gallbladder, investigating Reprint requests: Prof. Dr. H.-D. R6her, Department of General and Trauma Surgery, Heinrich-Heine-University, Moorenstr. 5, 4000 Dfisseidorf, Federal Republic of Germany.
etiological factors, the laparotomy rate, and the percentage of patients with spontaneous regression or mortality. Patients and Methods
All severely traumatized intensive care unit patients admitted from January 1989 to June 1990 were included in this study. Severe trauma was defined according to Schweiberer and coworkers [6] as simultaneous severe injury of 2 to 4 body cavities or regions, or severe multiple trauma of the locomotor system (spine, pelvis, 4 extremities). Patients after cholecystectomy or with primary injury of the gallbladder were excluded. Patients were also excluded if the period of observation was 3.5 mm, hydrops, sludge, sonolucent or double layer within the gallbladder wall (also called subserosal edema), and pericholecystic fluid collection (Table 1). According to the literature "stress"-cholecystitis is defined by the demonstration of a triad of increased thickness of the gallbladder wall, hydrops, and sludge [4, 9, 10]. The patient history, ultrasonographic findings, clinical course, laboratory values, therapy, and outcome were prospectively documented. For descriptive statistics of continuous variables the median and range were calculated. Qualitative variables were expressed as percentages. For the incidence of acute acalculous cholecystitis a 95% confidence interval was estimated. Statistical testing was performed with the chi-square test (qualitative variables) and the Mann-Whitney (Kniskal-Wallis) test (quantitative variables). Results The study population of 45 polytraumatized patients is shown in Table 2. Thirty-nine patients were primarily admitted to our department, 6 patients were transferred from other departments at the day of injury. Most patients were young males due to a high rate of motorcycle accidents. Furthermore, this explains a high rate of associated thoracic, head, and limb injury.
M. lmhof et al.: Acute Acalculous Cholecystitis
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Table 1. Major and minor sonographic criteria for the diagnosis of acute acalculous cholecystitis.
Table 2. Study population.
Clinical characteristic Major criteria
Minor criteria
Wall thickness >3.5 mm Hydrops
Double layer Pericholecystic fluid collection
Sludge
Patients, total Male Age, median, (range) (yrs) Period of observation, median, (range) (days) Total number of ultrasonographic examinations Injury pattern Thorax Head Lower limb Upper limb Pelvis Abdomen Spine Soft tissue Trauma score, median, (range) ISS PTS Mortality
45 37 29 (4---8I) 32 (8-97) 946 30 30 23 12 17 15 9 5
Sonomorphological changes of the gallbladder were detected in 36 of 45 patients (Fig. 1). Sludge was the most frequent sonographic finding. It was present in 26 patients. Thickening of the gallbladder wall >3.5 mm was observed in 17 patients. Equally, 17 patients showed hydrops of the gallbladder. Suspected minor criteria were double layer of the gallbladder wall (10 of 45 patients) and pericholecystic fluid collection (25 of 45 patients). We were able to demonstrate the diagnostic triad of acalculous cholecystitis in 8 (18%) men (95% confidence interval: 8%-32%) with a median age of 26 years (range 17-67 years). There were no differences in polytrauma scores compared to the 37 patients without the diagnostic triad. First sonographic changes were already seen at the first day of admission. The triad was detected on average at day 11. In 1 patient we were able to demonstrate it at the 3rd day. One patient underwent cholecystectomy with a histological confirmation. The diagnosis of acute cholecystitis was not confirmed histologically in another patient who did not fulfill all criteria of the triad but was operated because of septic temperatures. There were no deaths related to stress cholecystitis (Table 3). Clinical course and laboratory findings did not help in the diagnosis of acute acalculous cholecystitis. During the intensive care unit (ICU) stay the majority of patients with and without the diagnostic triad had temperatures >38°C, increased bilirubin, alkaline phosphatase, and GGT. Leucocytosis was seen in all 8 patients with acalculous cholecystitis and in 34 patients without this condition. Right upper quadrant pain and the so called "sonographic Murphy sign" were no valid diagnostic criteria in fact of ventilated and sedated patients. Nevertheless right upper quadrant pain was seen in 5 of 8 patients with, and 16 of 37 patients without, the triad (Table 4). A significant relationship between the number of blood transfusions and the incidence of acute acalculous cholecystitis could be found (p < 0.05). Higher morphine dosage was also observed in patients with the diagnostic triad, however the differences were statistically not significant (p < 0.08) (Table 5).
Despite several studies, the etiology and pathogenesis of acalculous cholecystitis are not yet completely understood. Obviously there are multiple pathophysiological mechanisms. Long-time bed rest with fasting during total parenteral nutrition probably reduces gallbladder motility. Increasing bile concentration following multiple blood transfusion, resorption of hematomas, and dehydration with subsequent stasis and possible bacterial contamination results in irritation of the gallbladder mucosa [1, 4, 12]. Decreased blood supply due to shock, sepsis, high sympathetic tone, toxins, arteriosclerosis, or high intraluminal pressure leads to wall necrosis [3, 5, 12-14, 16-21]. Bauer [22] speculated about a histamininduced stress-reaction in the development of post-traumatic choI'ecystitis. The true cause of acalculous cholecystitis may be multifactorial with several concomitant factors leading to the development of disease. A high morphine dose and multiple blood transfusion in the 8 patients with the diagnostic triad of acalculous cholecystitis were statistically significant prognostic factors (p < 0.05) (Table 5).
Discussion
Diagnosis
History
Diagnostic imaging procedures in patients with acute acalculous cholecystitis were evaluated retrospectively by Mirvis and associates [23J. Sonography and computed tomography scan (CT) were both highly sensitive (92% and 100%, respectively) and specific (96% and 100%, respectively). Hepatobiliary scintigraphy was compromised by frequent false-positive results which gave a specificity of only 38%. Ultrasound-guided gallbladder aspiration with bile culture revealed no effect in diagnosing acute cholecystitis (13 of 21 bile cultures were sterile, results were not available in time, gram-stained smears and bile cultures suffered from low sensitivity) [24]. Because ultrasound is relatively inexpensive and can be performed at the bedside, it
The first reported case of acute cholecystitis following an Unrelated operation was described by Duncan [11] in 1844 as a Complication of a femoral hernial repair. Sporadic and collected eases were described after this [12, 13], all seeking a common basis for this complication. Acute acalculous cholecystitis is now well recognized as a separate entity, differing from the acute stone-related cholecystitis. The disorder can follow any form of surgery, but it is most commonly encountered after trauma and abdominal surgery [13]. No stones are present in the gallbladder in about 5% to 10% of patients with primary acute
28 (17-45) 28 (10-53) 5
ISS: Injury severity score; PTS: Polytrauma score.
cholecystitis [14], as compared to 22% to 90% in acute postoperative cholecystitis [i 1, 14, t5].
Etiology
1162
World J. Surg. Vol. 16, No. 6, Nov./Dec. 1992 Table 4. Clinical and laboratory findings in patients with and without acute acalculous cholecystitis.
Hydrops
Triad present
Sludge
Parameter
yes (n = 8)
no (n = 37)
p value
Right upper quadrant pain Leucocytosis > 12,000 mm 3 Temperature >38°C Bilirubin >24/~mol/l Alk. Phos. > 190 U/I GTT >28 U/1
5 8 8 7 7 6
16 34 36 25 30 31
n.s. n.s. n.s. n.s. n.s. n.s.
n.s.: Not significant; Alk. phos.: Alkaline phosphatase; GGT: Gamma-glutamyl-transpeptidase. W a l l t h i c k n e s s > 3.5 m m
Fig. 1. Sonomorphological changes of the gallbladder concerning major criteria.
Table 3. Description of patients with and without acute acalculous cholecystitis. Triad present Parameter
yes (n = 8)
no (n = 37)
p value
Male Age, median, (range) (yrs) Scoring, median, (range) ISS PTS Day of occurrence, median (range) First signs Traid Cholecystectomy Death
8 26 (17--67)
28 29 (4-81)
n.s. n.s.
28 (21--41) 26 (23-52)
26 (11--45) 29 (10-53)
n.s. n.s.
2 (0--16)a 1 5
n.s. n.s. n.s.
3 (0-6) 11 (3-29) 1 0
First signs seen in 26 patients. n.s.: Not significant; ISS: Injury severity score; PTS: Polytrauma score.
should be regarded as a satisfactory first line diagnostic screening procedure. Ultrasound offers several advantages over other methods of examination. The system is portable, noninvasive, and serial examinations are easily obtained. The presence of sutures, drains, orthopedic or life-support devices usually do not cause any problems [25]. The use of CT scan as an initial diagnostic procedure seems reasonable in transportable patients, especially when other disease (e.g., thoracic, cerebral) are suspected [13].
Definition In a comparison of ultrasound and postoperative measurements of the gallbladder some authors found a gallbladder wall measuring >3.5 mm to be a reliable independent diagnostic criterion for cholecystitis with a sensitivity >98% [25-28]. Several ultrasonic studies have reported gallbladder wall thickening in patients with various nonbiliary conditions, including alcoholic liver disease, ascites, portal venous hypertension, hypoalbuminemia, hepatitis, chronic heart failure, and renal insufficiency without intrinsic gallbladder disease [4, 19, 28-30]. The diagnosis of acute cholecystitis should be made with caution when based on only one criterion. This has led to the definition of
various major and minor criteria for an abnormal gallbladder. Although there is no clearcut agreement about the value of any single criterion, most studies have indicated that the sensitivity of major criteria for acute cholecystitis is 81% to 86%, and the specificity is 94% to 98%. Inclusion of any minor criterion increases the sensitivity of ultrasound to 90% to 98% but reduces the specificity to as low as 70%. The sensitivity for acalculous cholecystitis may also be somewhat lower [31]. A diagnostic accuracy index, corrected for chance, was statistically and clinically more relevant with 3 as the minimum number of criteria for the ultrasonic diagnosis of acute cholecystitis [32]. If very restrictive criteria are applied to the diagnosis of acute cholecystitis (for example, the presence of both major and minor criteria), the sensitivity of ultrasound may decrease to 70% to 76% [33-37]. A definition problem is caused by different options in the literature regarding the classification of criteria as major or minor.
Clinical and Laboratory Findings Virtually every series of patients with acalculous cholecystitis has documented that the majority of patients present with right upper quadrant pain, fever, and leucocytosis. H o w e v e r , these findings may be masked in postoperative or post-traumatic patients who are intubated, neurologically impaired, or heavily sedated. The diagnosis may thus be difficult and contribute to the diagnostic and therapeutic delay. In our series clinical and laboratory findings were not significantly different in the groups with or without the diagnostic triad (Table 4).
Treatment Over the past centuries therapeutic strategies of post-traumatic or postoperative acute acalculous cholecystitis ranged from surgical cholecystostomy to obligate cholecystectomy, from ultrasound guided percutaneous transhepatic cholecystostomy with optional secondary elective cholecystectomy to conservative treatment (Table 6). Surgical cholecystostomy has been advocated if a patient with acute cholecystitis is considered to be too ill to survive cholecystectomy. Whereas cholecystostomy is technically " e a s i e r " to perform than cholecystectomy it is associated with mortality rates up to 40% and complication rates up to 20% [38, 39]. The lack of diagnostic accuracy, particularly the lack of reliable diagnostic methods, contributes to the delay in diagnosis and treatment and leads to high mortality rates. In H o w a r d ' s retrospective review over 25 years
M. Imhof et al.: Acute Aealculous Cholecystitis
1163
Table 5. Possible etiological factors inducing acute acalculous cholecystitis. Factor
No. of sonographic criteria
p value
Patients Blood transfusion units, median, (range) Morphin-dose (mg/day), median, (range)
3 (n=8) 32 (7-119)
2 (n=9) 20 (8--73)
15.1 (8.8-19.8)
14.4 (0.1-18)
1 (n = 18) 12 (2-100) 7.2 (1.6-24.3)
0 (n = 10) 6 (1-21)
3.5 mm) et de la pr6sence de sludge. Cette triade a 6t6 retrouv6e chez 8 des 45 patients (18%). Une chol6cystectomie pr6coce a 6t6 d6cid6e chez un de ces patients, alors que les 7 autres ont 6t6 trait6s m6dicalement. L'incidence de C A L chez le polytraumatis6
M. Imhof et al.: Acute Acalcuious Cholecystitis
grave est sfirement plus 616vre qu'il n'est classique de le dire. L'rchographie est une mrthode fiable pour la dgtection prgcoce et pour suivre cette complication post-traumatique. Resumen
La colelitiasis acalculosa (CAA) es una reconocida complicaci6n en pacientes con trauma severo. E1 conocimiento sobre la CAA emana de an,'tlisis retrospectivos y de reportes esporfidicos de casos individuales. En un estudio prospectivo se investig6 esta entidad por medio de examenes clinicos y sonogrfificos seriados en 45 pacientes politraumatizados que ingresaron a nuestra unidad de cuidado intensivo entre el 1° de enero de 1989 y el 30 de junio de 1990. La severidad del trauma fue determinada mediante el ISS (Injury-Severity-Score) y el PTS (Polytrauma-Score). La CAA fue definida como la combinaci6n de hidrops de la vesicula biliar, aumento del aspesor de la pared (>3.5 mm) y la demonstraci6n de barro biliar. Esta traida diagn6stica pudo ser documentada en 8 de 45 pacientes (= 18%). Consecuentemente, se preactic6 colecistectomia precoz electiva en i de 8 pacientes con la traida diagn6stica de CAA; el resto de los casos fue tratado en forma conservadora. La incidencia de CAA es mils alta de lo que sugieren las estadfsticas publicadas. La ultrasonografia constituye un mrtodo confiable de detecci6n precoz y de seguimiento de esta complicaci6n. References
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