acute acalculous cholecystitis ( aac ) is a well - recognized but still poorly understood entity . it is well - known to occur in very sick patients already admitted in intensive care unit ( icu ) , e.g. , after major trauma , burns , sepsis , major non - biliary surgery and after parenteral feeding , with high incidence of complications such as perforation and high mortality . other factors such as prolonged hyperalimentation , prolonged suctioning by nasogastric tube , positive pressure ventilatory support , numerous transfusions , use of vasoactive amines and use of morphine analgesia also have been implicated . the condition most likely results from a gradual increase in bile viscosity , due to prolonged stasis , that leads to a functional obstruction of the cystic duct . aac , if not managed effectively , tends to have a more fulminant course , frequently associated with gangrene , perforation , and empyema . unfortunately , both clinical and laboratory tests lack sensitivity and specificity for arriving at a diagnosis . after aac is clinically suspected , the next step is to diagnose and evaluate it . a hepatobiliary iminodiaceticacid ( hida ) scan is advised by the rome ii consensus group to be the next step in patient evaluation . the aim of our study was to determine the role of cholescintigraphy in management of patients diagnosed to have acalculous cholecystitis on usg abdomen . patients presenting to the out - patient department ( opd ) or referred from in - patient department or icu during the period between february 2008 and february 2010 were considered.patients with complaints of flatulent dyspepsia , vomiting , fever , upper abdominal pain and showing possibility of cholecystitis.usg abdomen findings suggestive of acalculous cholecystitis this added up to a total of 32 patients . patients presenting to the out - patient department ( opd ) or referred from in - patient department or icu during the period between february 2008 and february 2010 were considered . patients with complaints of flatulent dyspepsia , vomiting , fever , upper abdominal pain and showing possibility of cholecystitis . usg abdomen findings suggestive of acalculous cholecystitis this added up to a total of 32 patients . the criteria for labeling cholecystitis on usg abdomen were as per previous reports and studies . these were : gall bladder wall thickness > 4 mm in absence of ascites or hypoalbuminemia.pericholecystic fluid collection.sonographic murphy 's sign.gall bladder oedema with sonographic murphy 's sign and no underlying pathology such as ascites or hypoalbuminemia . gall bladder oedema with sonographic murphy 's sign and no underlying pathology such as ascites or hypoalbuminemia . patients were advised nil per orally for 4 hours ( h ) prior to the study . patients fasting for more than 12 h were fed with a standardized meal and were on fast for 4 - 5 h and then taken up for the study . there was a strict adherence to these criteria . this is because a recently ingested meal stimulates endogenous cholecystokinin production , which continues until the food has emptied from the upper small bowel . the rising serum cholecystokinin ( cck ) level causes gall bladder contraction , prevents radiotracer entry and may result in a false positive study for acute cholecystitis . on the other hand , fasting for long hours , causes collection of viscous bile and sludge in the gall bladder ( gb ) , thus preventing radiotracer entry and causing false positive results . technetium-99m(tc-99 m ) mebrofenin was administered intravenously ( a dose of 5 mci of tc-99 m mebrofenin was administered in patients with s. bilirubin < 2 mg / dl and increased up to 10 mci in patients with s. bilirubin > 10 mg / dl ) . the study was performed on multispect dual head gamma camera ( siemens , germany ) . serial static isotime * * images of the abdomen were acquired in anterior view , at different time intervals with the patient in supine position , up to delayed 4 h images , if the gall bladder was not visualized . in cases where gall bladder was visualized , pre- and post - fatty meal images were also acquired . fatty meal was formulated as humana fatty meal formula , 240 ml containing 20 g fats and 415 kcal . standardization of this fatty meal with gbef was done based on readings from ten normal volunteers . ( * * it was difficult to acquire dynamic 1 - 1.5 h. images for patients referred from the icu . studies were analyzed for hepatic uptake and excretion of tracer in to the biliary system , time to visualization of activity in small - bowel , time of visualization of gall bladder . endogenous cck secreted by the duodenal mucosa in response to fatty meal stimulus peaks during 20 - 30 min . the cck levels remain elevated until the meal has passed through the upper small - bowel and promptly return to baseline due to its rapid metabolism ( 2.5 min serum half - life ) . gall bladder contraction is initiated when the serum cck reaches a threshold that is considerably lower than the peak cck . simultaneously , cck relaxes sphincter of oddi , allowing bile to empty in to small - bowel . hence , in patients where in the gall bladder was visualized , gall bladder ejection fraction ( gbef ) 30 min post fatty meal was calculated . gbef was calculated by the following formula : scintigraphic criteria for interpretation as acalculous cholecystitis non - visualization of gall bladderif gall bladder was visualized , gbef < 40% non - visualization of gall bladder if gall bladder was visualized , gbef < 40% the following patients were taken up for surgery : patients who showed hepatic uptake and excretion of radiopharmaceutical through the common bile duct , however , without visualization of gall bladder until the delayed 4 h image.patient with gbef < 40% , if they gave an informed consent for surgery . patients who showed hepatic uptake and excretion of radiopharmaceutical through the common bile duct , however , without visualization of gall bladder until the delayed 4 h image . patient with gbef > 40% and those with gbef < 40% but did not consent for surgery , were taken in to the conservative management arm . patients were followed - up in the opd for 3 months post - commencement of treatment ( medical / surgical ) . they were assessed for the presence of symptoms , and if so , whether there was an improvement or worsening of symptoms . in addition , post - operative patients were assessed for surgery related symptoms / complications and wound healing . in patients with either non - visualized gallbladder or gbef < 40% , the odds ratio for the different modes of management was calculated . patients presenting to the out - patient department ( opd ) or referred from in - patient department or icu during the period between february 2008 and february 2010 were considered.patients with complaints of flatulent dyspepsia , vomiting , fever , upper abdominal pain and showing possibility of cholecystitis.usg abdomen findings suggestive of acalculous cholecystitis this added up to a total of 32 patients . patients presenting to the out - patient department ( opd ) or referred from in - patient department or icu during the period between february 2008 and february 2010 were considered . patients with complaints of flatulent dyspepsia , vomiting , fever , upper abdominal pain and showing possibility of cholecystitis . usg abdomen findings suggestive of acalculous cholecystitis this added up to a total of 32 patients . the criteria for labeling cholecystitis on usg abdomen were as per previous reports and studies . these were : gall bladder wall thickness > 4 mm in absence of ascites or hypoalbuminemia.pericholecystic fluid collection.sonographic murphy 's sign.gall bladder oedema with sonographic murphy 's sign and no underlying pathology such as ascites or hypoalbuminemia . gall bladder oedema with sonographic murphy 's sign and no underlying pathology such as ascites or hypoalbuminemia . patients were advised nil per orally for 4 hours ( h ) prior to the study . patients fasting for more than 12 h were fed with a standardized meal and were on fast for 4 - 5 h and then taken up for the study . this is because a recently ingested meal stimulates endogenous cholecystokinin production , which continues until the food has emptied from the upper small bowel . the rising serum cholecystokinin ( cck ) level causes gall bladder contraction , prevents radiotracer entry and may result in a false positive study for acute cholecystitis . on the other hand , fasting for long hours , causes collection of viscous bile and sludge in the gall bladder ( gb ) , thus preventing radiotracer entry and causing false positive results . technetium-99m(tc-99 m ) mebrofenin was administered intravenously ( a dose of 5 mci of tc-99 m mebrofenin was administered in patients with s. bilirubin < 2 mg / dl and increased up to 10 mci in patients with s. bilirubin > 10 mg / dl ) . the study was performed on multispect dual head gamma camera ( siemens , germany ) . serial static isotime * * images of the abdomen were acquired in anterior view , at different time intervals with the patient in supine position , up to delayed 4 h images , if the gall bladder was not visualized . in cases where gall bladder was visualized , pre- and post - fatty meal images were also acquired . fatty meal was formulated as humana fatty meal formula , 240 ml containing 20 g fats and 415 kcal . standardization of this fatty meal with gbef was done based on readings from ten normal volunteers . ( * * it was difficult to acquire dynamic 1 - 1.5 h. images for patients referred from the icu . studies were analyzed for hepatic uptake and excretion of tracer in to the biliary system , time to visualization of activity in small - bowel , time of visualization of gall bladder . endogenous cck secreted by the duodenal mucosa in response to fatty meal stimulus peaks during 20 - 30 min . the cck levels remain elevated until the meal has passed through the upper small - bowel and promptly return to baseline due to its rapid metabolism ( 2.5 min serum half - life ) . gall bladder contraction is initiated when the serum cck reaches a threshold that is considerably lower than the peak cck . simultaneously , cck relaxes sphincter of oddi , allowing bile to empty in to small - bowel . hence , in patients where in the gall bladder was visualized , gall bladder ejection fraction ( gbef ) 30 min post fatty meal was calculated . gbef was calculated by the following formula : scintigraphic criteria for interpretation as acalculous cholecystitis non - visualization of gall bladderif gall bladder was visualized , gbef < 40% non - visualization of gall bladder if gall bladder was visualized , gbef < 40% the following patients were taken up for surgery : patients who showed hepatic uptake and excretion of radiopharmaceutical through the common bile duct , however , without visualization of gall bladder until the delayed 4 h image.patient with gbef < 40% , if they gave an informed consent for surgery . patients who showed hepatic uptake and excretion of radiopharmaceutical through the common bile duct , however , without visualization of gall bladder until the delayed 4 h image . patient with gbef > 40% and those with gbef < 40% but did not consent for surgery , were taken in to the conservative management arm . patients were followed - up in the opd for 3 months post - commencement of treatment ( medical / surgical ) . they were assessed for the presence of symptoms , and if so , whether there was an improvement or worsening of symptoms . in addition , post - operative patients were assessed for surgery related symptoms / complications and wound healing . in patients with either non - visualized gallbladder or gbef < 40% , the odds ratio for the different modes of management was calculated . the findings of cholescintigraphy [ figure 1 ] were as follows:(i)non - visualization of gb [ figure 2 ]  7 ( 21.87%).(ii)gbef < 40% [ figure 3 ]  4 ( 12.5%).(iii)gbef > 40% [ figure 4] 20 ( 62.5%).(iv)rim sign  6 ( 18.75%).(v)duodenogastric reflux  4 ( 12.5%).of the patients suspected to have cholecystitis clinically , 32 patients had usg abdomen findings suggestive of acalculous cholecystitis.twenty six of the 32 patients had positive sonographic murphy 's sign . out of these 26 , 10 were having ef < 40% or non - visualization of gall bladder.all patients who had pericholecystic fluid collection were having non - visualization of gall bladder on cholescintigraphy . one of these patients had finding of gangrenous gall bladder per operatively [ figure 5].gbef of < 40% or non - visualization of gall bladder were considered as indicators of better post - operative outcome as suggested by many investigators.surgical option was given to patients falling in these two categories . however , as some of these patients denied surgery , they were shifted to control arm and managed conservatively . of the 11 patients in this category , six underwent cholecystectomy [ figure 6 ] and 5 were medically managed as per patient 's decision . these patients were followed for 3 months and evaluated for symptom relief . of the surgically treated patients , however , 83.33% of the surgically treated group showed improvement as against 40% of the medically treated group [ figure 7 , 8].twenty - one patients had gbef > 40% and were managed medically and followed - up . of the medically managed patients , 19 patients hence , in this group , the percentage of patients having symptomatic improvement was 90.47% [ figure 2].the odds ratio was found to be 7.4 with a confidence interval of 0.46 - 122.70 . the findings of cholescintigraphy [ figure 1 ] were as follows : ( i)non - visualization of gb [ figure 2 ]  7 ( 21.87%).(ii)gbef < 40% [ figure 3 ]  4 ( 12.5%).(iii)gbef > 40% [ figure 4] 20 ( 62.5%).(iv)rim sign  6 ( 18.75%).(v)duodenogastric reflux  4 ( 12.5% ) . non - visualization of gb [ figure 2 ]  7 ( 21.87% ) . gbef < 40% [ figure 3 ]  4 ( 12.5% ) . suspected to have cholecystitis clinically , 32 patients had usg abdomen findings suggestive of acalculous cholecystitis . out of these 26 , 10 were having ef < 40% or non - visualization of gall bladder . all patients who had pericholecystic fluid collection were having non - visualization of gall bladder on cholescintigraphy . one of these patients had finding of gangrenous gall bladder per operatively [ figure 5 ] . gbef of < 40% or non - visualization of gall bladder were considered as indicators of better post - operative outcome as suggested by many investigators . however , as some of these patients denied surgery , they were shifted to control arm and managed conservatively . of the 11 patients in this category , six underwent cholecystectomy [ figure 6 ] and 5 were medically managed as per patient 's decision . these patients were followed for 3 months and evaluated for symptom relief . of the surgically treated patients , however , 83.33% of the surgically treated group showed improvement as against 40% of the medically treated group [ figure 7 , 8 ] . twenty - one patients had gbef > 40% and were managed medically and followed - up . of the medically managed patients , 19 patients hence , in this group , the percentage of patients having symptomatic improvement was 90.47% [ figure 2 ] . the odds ratio was found to be 7.4 with a confidence interval of 0.46 - 122.70 . findings of cholescintigraphy in various patients image of cholescintigraphy in patient with non - visualization of gallbladder image of cholescintigraphy in patient with gall bladder ejection fraction < 40% image of cholescintigraphy in patient with gall bladder ejection fraction > 40% gangrenous gall bladder intraoperative photograph in patient with non - visualization of gall bladder on cholescintigraphy specimen of empyematous gall bladder in patient with gall bladder ejection fraction < 40% on cholescintigraphy comparison of groups according to ejection fraction and management , on follow - up comparison of various treatment groups according to gall bladder ejection fraction in terms of symptomatic improvement on follow - up comparison of treatment groups in patients with gall bladder ejection fraction < 40% imaging studies have played an incremental role in the diagnosis and management of acute cholecystitis . overall sensitivity and specificity for hepatobilliary scintigraphy in the diagnosis of acute cholecystitis are 95 - 100% and 81 - 100% respectively , whereas the sensitivity and specificity of sonography is reported as 67 - 93% and 82 - 100% , respectively . the role of imaging studies in establishing the diagnosis and management of aac is less established . a 7 years review at yale university by savoca et al . showed an increasing prevalence of aac in out - patients with 77% patients developing aac while at home and 23% while hospitalized . our study showed 21 patients presenting to out - patients department with aac which is 65.62% . in - patients consisted 34.38% , out of which some investigators have developed the ultrasonographic scoring system to improve the accuracy in detecting aac in critically - ill . two points are given for distention of the gallbladder or thickening of the gallbladder wall , and one point each is given for striated thickening of the gallbladder wall , sludge , or pericholecystic fluid . the overall sensitivity of ultrasonography for detecting aac has been reported to range from 67% to 92% , with specificity for more than 90% . a cholescintigraphy scan has been advised by the rome ii consensus group to be the next step in patient evaluation . a cholescintigraphy scan can be done using cck infusion or fatty meal provocation if proper attention to meals and measurement sequence has been given . we used fatty meal provocation method as it is more cost - effective , more physiological and easily available . on the other hand , use of sincalide ( synthetic c - terminal octapeptide of cck ) is quicker , reliable and reproducible . group criteria , assessment of gall bladder emptying by cholescintigraphy is a decision making tool in the diagnosis of functional gall bladder disorders . they have suggested a limit of gbef > 40% to call it as normally functioning gallbladder . on the other hand , they also suggested that in presence of normal sonography findings and liver function tests ( lft)/pancreatic enzyme levels and a reduced gbef , cholecystectomy is recommended . there are three meta - analyses on the issue of predictive value of cholescintigraphy in symptomatic aac patients . yap et al . studied only symptomatic patients with abnormal and normal cholescintigraphy results who underwent surgery . while study by ponsky et al . and mahid et al . examined outcomes of patients with abnormal cholescintigraphy results who were medically treated compared with those who underwent surgery . these meta - analyses concluded that cholecystectomy is indicated in symptomatic patients with low ejection fraction on cholescintigraphy , however , without gallstones . our results were comparable to the odds ratio with confidence interval of the work done by mishkind et al . the percentage of patients having symptom relief after cholecystectomy , obtained in our study , is comparable to the results obtained in previous studies [ table 3 ] . patients with gbef > 40% who were managed medically were followed up after 3 months and revealed a symptom relief rate of 90.47% which is also comparable with previous studies . a small sample size was one of the limitations of the study . a larger number of patients need to be studied in order to draw statistically significant conclusions . also randomization of patients would have given more reliable results and conclusions . cholescintigraphy is a functional study that defines the underlying pathophysiology of the disease and the value of gbef directly correlates with gall bladder motility .