Emergent Treatment of Acute Cholangitis and Acute Cholecystitis PDF

14 Emergent Treatment of Acute Cholangitis and Acute Cholecystitis Rakesh Navuluri, MD1 Matthew Hoyer, BS2 Murat Osman, BS3 Jonathan Fergus, MD1 1 Department of Radiology, The University of Chicago, Chicago, Illinois Address for correspondence...

14 Emergent Treatment of Acute Cholangitis and Acute Cholecystitis Rakesh Navuluri, MD1 Matthew Hoyer, BS2 Murat Osman, BS3 Jonathan Fergus, MD1 1 Department of Radiology, The University of Chicago, Chicago, Illinois Address for correspondence Rakesh Navuluri, MD, Department of 2 The Johns Hopkins University School of Medicine, Baltimore, Radiology, The University of Chicago, 5841 S. Maryland Avenue, Maryland MC 2026, Chicago, IL 60637 (e-mail: [email protected]). 3 George Washington University School of Medicine, Washington, District of Columbia Semin Intervent Radiol 2020;37:14–23 This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited. Abstract Acute pathology of the biliary tract including cholangitis and cholecystitis can lead to Keywords biliary sepsis if early decompression is not performed. This article provides an overview ► cholangitis of the presenting signs and symptoms and role of interventional radiology in the ► cholecystitis management of patients with acute cholangitis or acute cholecystitis. It is especially ► interventional important to understand the role of IR in the context of other treatment options radiology including medical management, endoscopy, and surgery. ► biliary drainage Interventional radiology plays an integral role in the man- Abdominal examination typically reveals voluntary and agement of patients with acute biliary conditions, including involuntary guarding, with a positive Murphy’s sign. Using acute cholecystitis and acute cholangitis. Percutaneous cholescintigraphy as the gold standard, a positive Murphy’s drainage of an obstructed biliary system can prevent biliary sign has been shown to have a sensitivity of 97% and a sepsis in patients who may not be candidates for traditional specificity of 48%.1 Laboratory findings may include leuko- first-line therapies including medical therapy and endosco- cytosis but do not commonly include elevated total serum py. Here, we review the pathophysiology, diagnosis, percu- bilirubin or alkaline phosphatase, which may be signs of taneous treatment, complications, outcomes, and alternate cholangitis or choledocholithiasis. treatment options of acute cholecystitis and cholangitis. Etiology Calculous cholecystitis comprises approximately 90% of Acute Cholecystitis cholecystitis cases and is thought to arise from gallstones Definition causing outflow obstruction of the gallbladder, resulting in Cholecystitis is inflammation of the gallbladder, most often gallbladder distention and wall edema, ultimately culminat- in the setting of outflow obstruction due to the presence of ing in ischemia and necrosis (referred to as gangrenous gallstones, which is referred to as calculous cholecystitis. cholecystitis) if left untreated.2 While the initial inflamma- Less commonly, the gallbladder may become inflamed in the tion is typically sterile, it is often followed by bacterial absence of gallstones, referred to as acalculous cholecystitis. superinfection. One study of patients with gallstone disease found that 46% of patients with acute cholecystitis had Symptoms positive gallbladder cultures, most commonly with bacteria The classic presentation of acute cholecystitis involves right such as Escherichia coli, Klebsiella, and Enterococcus.3 In cases upper quadrant abdominal pain, fever, nausea, and vomiting. of superinfection by gas-forming bacteria, gas may accumu- There may also be pain in the epigastrium or radiating to the late within the gallbladder wall or lumen, resulting in right shoulder or back. The pain is often severe and pro- emphysematous cholecystitis. If left untreated, acute calcu- longed in nature, and frequently follows fatty food ingestion. lous cholecystitis may progress to perforation, abscess Issue Theme Emergency IR; Guest Copyright © 2020 by Thieme Medical DOI https://doi.org/ Editors, Brian Funaki, MD and Charles E. Publishers, Inc., 333 Seventh Avenue, 10.1055/s-0039-3402016. Ray, Jr., MD, PhD, FSIR New York, NY 10001, USA. ISSN 0739-9529. Tel: +1(212) 760-0888.  Emergent Treatment of Acute Cholangitis and Acute Cholecystitis Navuluri et al. 15 formation, or generalized peritonitis. Gallbladder perfora- likely caused by cystic duct obstruction due to edema and is tion has been shown to occur in up to 10% of acute cholecys- diagnostic of acute cholecystitis. titis cases, with mortality ranging between 12 and 16%.4 Contrast-enhanced computed tomography (CT) scans and Although acalculous cholecystitis is clinically indistin- magnetic resonance cholangiopancreatography (MRCP) may guishable from calculous cholecystitis, its etiology is quite be indicated to rule out alternative causes of abdominal pain different and often multifactorial. The pathogenesis of acalcu- or to evaluate for complications of cholecystitis. CT findings lous cholecystitis is thought to arise due to biliary stasis or may include gallbladder wall edema, pericholecystic strand- ischemia in the setting of serious illness, such as trauma, burn ing, and high-attenuation bile.11 Some gallstones may be injury, surgery, shock, sepsis, or total parenteral nutrition. isodense with bile, thereby decreasing the sensitivity of CT Gallbladder stasis leads to concentration of bile salts and for detecting gallstones. Overall, abdominal CT is sensitive gallbladder distention, eventually resulting in tissue necrosis. (94%) but not very specific (59%) for the diagnosis of acute Secondary infections are common and include similar enteric cholecystitis.12 Nevertheless, CT is often utilized to rule out pathogens to those implicated in calculous cholecystitis, serious complications such as perforation, emphysematous including E. coli, Klebsiella, and Enterococcus.5 Complications cholecystitis, or gallstone ileus in patients with signs of This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited. may occur in as many as 40% of cases and include perforation, sepsis, peritonitis, crepitus, or bowel obstruction. MRCP is gangrene, and empyema, with mortality ranging from 10 to useful in evaluating for concurrent choledocholithiasis but is 90% depending on the timing of the diagnosis.6 less sensitive than ultrasound in detecting gallbladder wall thickening. For this reason, it is often reserved for patients Diagnosis with acute cholecystitis and elevated liver transaminases or Initial laboratory investigation should rule out other causes of total bilirubin, or those with common bile duct dilation on abdominal pain as well as complications of acute cholecystitis ultrasound. and should thus include a complete blood count, serum lipase and amylase, and a complete metabolic panel including liver Management transaminases, albumin, bilirubin, and calcium. The Tokyo Guidelines, most recently updated in 2018, define While acute cholecystitis should be suspected in all cases of acute cholecystitis by severity.7 Grade I cases are mild patients with right upper quadrant or epigastric pain, fever, in severity and are managed by early laparoscopic cholecystec- and leukocytosis, the diagnostic criterion of the updated tomy in patients at low surgical risk, defined as the Charlson 2018 Tokyo Guidelines requires the presence of imaging comorbidity index (CCI)
5 and American Society of Anesthesi- findings characteristic of acute cholecystitis in addition to ologists physical status classification (ASA-PS)
2. In those at signs of local and systemic inflammation.7 Abdominal ultra- higher surgical risk, antibiotics and supportive care can be sound is the preferred initial imaging modality to assess for provided prior to surgery. Grade II and III cases involve severe both calculous and acalculous cholecystitis, especially in the local inflammation or organ dysfunction and require antibiotics acute setting. Key sonographic features of acute cholecystitis and supportive care prior to more definitive treatment. In include gallbladder wall thickening (>4–5 mm for calculous optimal surgical candidates (CCI
5 and ASA-PS
2 for grade cholecystitis and 3.5–4 mm for acalculous cholecystitis), a II cases, CCI
3 and ASA-PS
2 for grade III cases), early sonographic Murphy’s sign (inspiratory arrest during deep cholecystectomy remains the mainstay of therapy in these breathing while the gallbladder is being sonographed), and patients. However, many patients carry comorbid medical subserosal edema. Other findings may include intramural conditions and are at high risk for morbidity and mortality gas, echogenic bile or sludge, and hydrops. with surgical intervention. In these cases, placement of a A systematic review of 30 studies demonstrated that ultra- cholecystostomy tube decompresses and drains the inflamed sonography had a sensitivity of 88% and a specificity of 80% for gallbladder, and typically serves as a bridge to delayed laparo- the diagnosis of acute cholecystitis. In the case of calculous scopic cholecystectomy. In poor surgical candidates, successful cholecystitis, ultrasonography was also shown to be useful in cholecystostomy tube placement may also serve as definitive the identification of gallstones, with a sensitivity and specificity therapy.13,14 of 84 and 99%, respectively.8 However, ultrasonography is less likely to identify stones or fragments under 3 mm.9 Gallbladder Preprocedure wall thickening is the most reliable sonographic feature of Coagulopathy and ascites are relative contraindications to acalculous cholecystitis but is not specific, as this may also be percutaneous cholecystostomy. In accordance with SIR Guide- the result of hypoalbuminemia, ascites, or sludge.10 lines for procedures with high risk of bleeding, coagulopathy As cholescintigraphy takes several hours to perform, it is should be corrected such that INR
1.5 to 1.8 and platelets not recommended in the acute setting. However, when the should be transfused for counts < 50,000/μL. Low-dose aspirin diagnosis remains uncertain, cholescintigraphy can help does not need to be withheld prior to the procedure. demonstrate patency of the cystic and common bile ducts. Preprocedural antibiotics should be administered within Morphine augments the entry of the radioactive tracer into 1 hour of the start of the procedure. Recommendations for the gallbladder by increasing the sphincter of Oddi pressure, antibiotics should cover common biliary organisms, including thereby increasing the pressure gradient for the movement extended-spectrum β-lactamase producing E. coli. Options of the tracer. Failure to visualize the gallbladder 30 minutes include a carbapenem, a fluoroquinolone, or ampicillin- following morphine augmentation or on delayed imaging is sulbactam.15 Seminars in Interventional Radiology Vol. 37 No. 1/2020 16 Emergent Treatment of Acute Cholangitis and Acute Cholecystitis Navuluri et al. As always, detailed history and physical examination should be obtained, and recent imaging studies should be reviewed. Common anatomic considerations include ascites, interposed bowel loops, and low diaphragmatic recess. In the case of significant ascites, paracentesis may be performed prior to continuing with the cholecystostomy. Procedure There are three important variables to consider when planning a cholecystostomy tube placement: imaging modality, route, and technique. Ultrasound guidance is quicker and less costly, and may also be performed at bedside. This can be particularly beneficial in intensive care unit (ICU) patients who are too ill to transport to interventional radiology. Doppler imaging also This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited. allows for real-time assessment of overlying abdominal wall vessels. However, we prefer to perform all ultrasound proce- dures in an angiography suite to allow for real time visualiza- tion of catheter and wire placement and also to perform cholangiography. CT guidance may be preferable if there is concern for overlying bowel or artifact from intraluminal gas. Fig. 1 Percutaneous transhepatic cholecystostomy access using a 21- Percutaneous cholecystostomy drains may be placed via gauge needle (arrow) (Seldinger technique) with ultrasound guidance. either a direct transperitoneal or a transhepatic approach route. Transhepatic placement allows for more catheter sup- port and stable positioning within the liver parenchyma. This is particularly important when treating an emphysematous gallbladder with a friable wall. Transhepatic placement also reduces the risk of bile leakage into the peritoneum should the drain become dislodged and may also permit faster maturation of catheter tract. On the other hand, puncture of the liver capsule and parenchyma potentially increases the risk of bleeding. Having noted these differences, a recent retrospec- tive observational study by Beland et al noted no difference in outcome between these two routes.16 In terms of procedural technique, drains may be placed either by Seldinger or trochar technique. The latter is preferred by some due to the theoretical risk of bile leakage and conse- quent bile peritonitis during the exchange of wires and cathe- ters involved when using the Seldinger technique. Additionally, trochar technique can be quicker as fewer steps are involved. Ultimately, the procedural technique and route chosen depend on the operator’s comfort level and preference. At our institution, the generally preferred method is transhe- Fig. 2 Retraction of cholecystostomy tube 4 weeks after initial patic/Seldinger (►Fig. 1). We leave an 8.5-Fr drain to bulb placement via transperitoneal route, with extravasation of contrast suction after the gallbladder has been manually decom- into the peritoneum (white arrows). Note also the tortuous course of the catheter (black arrow) as a result of gallbladder decompression. pressed. However, we occasionally use the trochar technique This ultimately resulted in loss of access and necessitated placement in a dilated gallbladder via a transperitoneal route for ease and of a new cholecystostomy tube. simplicity. We recommend using a smaller catheter (6 or 7 Fr) in these cases, as larger catheters can be more difficult to trochar into the gallbladder lumen. It is worth mentioning that because the gallbladder will eventually decompress, subsequent drain retraction can Postprocedure occur (►Fig. 2). This can lead to leakage of bile and peritonitis Drains are routinely exchanged every 4 to 6 weeks until defini- if not recognized early. Subsequent exchange of transper- tive treatment with surgery. In the case of acalculous cholecys- itoneal drains can also become more challenging for this titis, drains may be removed once there is clinical resolution of same reason, unlike with transhepatic drains. inflammation, and fluoroscopic confirmation of cystic duct patency and maturation of the catheter tract. In our experience, Complications tract maturation requires at least 4 to 6 weeks, though periods of The overall complication rate for percutaneous cholecystos- 2 to 3 weeks have been reported in the literature. tomy has been reported between 2 and 16%.17,18 Major Seminars in Interventional Radiology Vol. 37 No. 1/2020  Emergent Treatment of Acute Cholangitis and Acute Cholecystitis Navuluri et al. 17 complications include sepsis, significant bleeding, and bile incidence of biliary injury during cholecystectomy may be leak with resulting peritonitis. Sepsis may occur after slightly higher following percutaneous cholecystostomy instrumentation of an infected biliary system, but signs of (1.6%) compared with surgeries without preceding chole- systemic infection are usually present prior to the procedure. cystostomy (0.08–1.1%), a complication associated with sig- Despite this, sepsis attributable to percutaneous cholecys- nificant morbidity and mortality.24 tostomy has been reported to be 0.9%.17 Bile peritonitis is a rare but serious complication that may occur due to over- Alternative Procedures distention of the gallbladder with contrast or due to tube While the standard definitive treatment of acute cholecystitis retraction with the presence of a side hole outside the remains to be cholecystectomy, patients who are poor surgical gallbladder lumen, resulting in intraperitoneal bile leak. candidates due to either high-risk comorbidities or poor Other rare complications described in the literature include performance status require other noninvasive options as pneumothorax, bowel injury, and abscess formation.19 either a temporary measure for interval cholecystectomy or Minor complications include tube dislodgement and bile for permanent, long-term treatment. Several alternative, min- leak. Tube dislodgement is the most common minor complica- imally invasive procedures have been elucidated in the litera- This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited. tion of percutaneous cholecystostomy, with reported frequen- ture, including endoscopic transpapillary gallbladder drainage cies between 4 and 15%.20 Dislodgement can be due to a (ETGBD) with cystic duct stenting (ETGBS) and endoscopic collapsed gallbladder or can be caused by the simple movement ultrasound-guided gallbladder drainage (EUSGBD). These of the liver and gallbladder during normal respiration. Tube alternative procedures have been proposed as an option for retention can be promoted using locking catheters and by certain high-risk patients with acute cholecystitis including coiling as much tubing as possible within the gallbladder at those with coagulopathy, large-volume abdominal ascites, or the time of placement. Bile leak may be due to ascites, which can other comorbidities that may preclude percutaneous drain be managed by paracentesis or placement of a side hole outside placement. the gallbladder lumen. Further management can be attempted Endoscopic gallbladder drainage has recently been pro- via catheter upsizing or placement of a colostomy bag around posed as a method to drain the gallbladder in high-risk the tube. In the setting of leakage due to catheter occlusion, patients with acute cholecystitis after failing conventional routine tube exchange is advised. measures such as percutaneous transhepatic gallbladder drainage/aspiration (PTGBA/D) or in patients with end-stage Outcomes liver disease due to advanced cancer or those awaiting liver Technical success in percutaneous cholecystostomy place- transplantation. This method is generally performed through ment is 95% or higher.18 Failures are most frequently due to endoscopic retrograde cholangiopancreatography (ERCP) in issues with access, often in the setting of wall calcification, either a transpapillary or transmural approach, whereby stone impaction, or a decompressed gallbladder. selective bile duct cannulation is achieved and a wire is Clinical success varies greatly based on disease severity negotiated into the cystic duct or gallbladder through which and overall treatment plan. In a study of 5,329 patients with a double-pigtail stent or nasocholecystic drain is deployed grade III acute cholecystitis in Japan and Taiwan, the lowest crossing the ampulla with the proximal and distal pigtails in mortality (0.79%) was achieved in patients who underwent the gallbladder and duodenum, respectively. Reported adverse initial percutaneous cholecystostomy followed by cholecys- events include pancreatitis, biliary perforation, and rarely tectomy, while the highest mortality (13.5%) was seen in stent migration and cholangitis. Technical success can be those who underwent cholecystostomy without subsequent affected by not only technical skill but also aberrant biliary cholecystectomy. These results most likely reflect the poor anatomy or degree of inflammation.25 Thus, a high degree of health status of the latter group, which likely precludes them technical expertise is needed to successfully perform this from receiving definitive surgical treatment. Nonetheless, procedure. these findings have been supported by other studies in the Endoscopic ultrasound-guided gallbladder drainage (EUS- literature.21,22 A recent randomized, multicenter clinical GBD) is a technique whereby the gallbladder is punctured from trial in the Netherlands compared treatment with laparo- the body or antrum of the stomach or duodenal bulb under scopic cholecystectomy to percutaneous cholecystostomy in direct EUS visualization. This is achieved by inserting a guide- high-risk patients with acute calculous cholecystitis.23 This wire through the gallbladder and dilating the formed tract trial demonstrated similar overall mortality between the through which a double pigtail plastic, self-expandable metal, two treatment groups. However, the major complication or lumen-apposing metal stent (LAMS) is placed. LAMS has rate, including recurrent biliary disease and reintervention, been reported to allow for better tissue apposition and lower was lower in those who received cholecystectomy (12 vs. the rate of stent migration. Due to its larger diameter, it is also 65%). Furthermore, healthcare costs were reduced by more associated with improved patency and allows for easier stone than 30% in the surgical group. These studies suggest that extraction. Certain considerations should be appreciated while laparoscopic cholecystectomy is the preferred treat- while planning EUS-GBD to ensure long-term patency of ment option in the sickest patients, percutaneous cholecys- stents. For example, transduodenal access through EUS-GBD tostomy may benefit select patients who would benefit from may interfere with subsequent cholecystectomy in cases of cholecystectomy by providing them with additional time for interval EUS-GBD while transgastric EUS-GBD may be more their condition to improve prior to surgery. Of note, the prone to stent dislocation or migration due to gastric motility. Seminars in Interventional Radiology Vol. 37 No. 1/2020 18 Emergent Treatment of Acute Cholangitis and Acute Cholecystitis Navuluri et al. Given the nature of the procedure, abdominal pain which may but a low sensitivity for diagnosis cholangitis. Of the three reflect pneumoperitoneum, biliary peritonitis, or stent migra- symptoms, pain and fever are more common features than tion should be assessed. jaundice. Reynold’s pentad, coined in 1959, is composed of A recent meta-analysis by Luk et al comparing 206 and Charcot’s triad plus altered mental state and septic shock. 289 EUS-GBD and PT-GBD patients, respectively, found However, it is present in only 3.5 to 5.1% of patients.30–32 similar rates of technical and clinical success between the Patients typically present with leukocytosis as well as labo- two procedures.26 ratory evidence of cholestasis including elevated direct biliru- bin, alkaline phosphatase, and GGT. Of these three markers, alkaline phosphatase is the most consistently elevated.33 Alka- Acute Cholangitis line phosphatase is also useful to monitor posttreatment, as it Acute cholangitis is the result of obstruction and subsequent has a relatively quicker recovery pattern after decompression infection of biliary ductal system. When frank pus is present and is thus a more accurate indicator of adequate drainage. One within the biliary system, this is referred to as acute suppu- promising laboratory marker currently being studied is procal- rative cholangitis. citonin. There is evidence that it is a more accurate marker of This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited. severe disease and can better indicate need for emergent Etiology decompression.34 Obstruction can be due to various etiologies with choledocho- The Tokyo Guidelines, originally published in 2007 and lithiasis accounting for nearly two-thirds of cases. Stones within subsequently revised in 2013 and 2018, were created to the gallbladder neck or cystic duct can also compress the more definitely delineate the diagnostic criteria, grading, and common bile duct (Mirizzi syndrome). Other causes include management of acute cholangitis. Diagnostic criteria are malignant obstruction (24%), benign biliary strictures (4%), based on clinical or laboratory evidence of systemic inflam- sclerosing cholangitis (3%), or even Lemmel’s syndrome in mation, cholestasis, and findings on imaging. A study of the which a duodenal diverticulum compresses the ductal opening TG13 criteria allowed for accurate diagnosis in 90% of cases.35 into the duodenum. The Tokyo Guidelines also score the severity of disease from Bacterial infection of bile most commonly results from grade I to III based on age and the presence of leukocytosis, ascending migration of pathogens from gastrointestinal fever, hyperbilirubinemia, and hypoalbuminemia. Patients tract.27 Decreased biliary flow secondary to obstruction allows with grade I disease meet none of the aforementioned ascent of bacteria from duodenum—also referred to as ascend- criteria, while grade III is defined by the presence of organ ing cholangitis. The higher positive bile duct culture rates in dysfunction. The guidelines go even further and provide a partial obstruction compared with complete obstruction is management flowchart which recommends early drainage consistent with this pathophysiology.28 Infection can also be in grade II disease, and urgent decompression grade III iatrogenic in nature following endoluminal or percutaneous disease. A secondary benefit to treating patients with early instrumentation. The presence of a biliary stent itself increases biliary drainage, regardless of severity of disease, is shorter risk of bacteremia. For this reason, routine exchange every hospital stays.36 3 months is recommended. Bacterial translocation from the portal venous or lymphatic system is also a possible, though Imaging less likely, mechanism. The goal of imaging is to determine not only the presence of The most common pathogen in cholangitis is E. coli. In the obstruction but also the cause and level of obstruction. case of cholangitis associated with indwelling stents, Entero- Additionally, it is important to identify complications such coccus is more commonly seen. Other pathogens include as abscess, portal vein thrombosis, suppurative cholangitis, Klebsiella and Pseudomonas aeruginosa.29 and biliary peritonitis. If left untreated, obstruction and infection of the biliary Ultrasound can be used to identify gallbladder stones and tract may lead to biliary sepsis, systemic inflammatory ductal dilatation. The normal diameter of the common bile response syndrome (SIRS), and even death. As intraductal duct varies based on age and a history of prior surgery. If pressure increases with production of bile in the setting of there is no history of cholecystectomy, a normal CBD meas- obstruction, there is disruption of junctions between hepatic ures 6 to 8 mm. The intrahepatic bile ducts should not exceed cellular architecture which, in turn, leads to bacteria entering 2 mm in diameter or 40% of the caliber of the accompanying the bloodstream. Bile secreted at pressures of 12 to 15 cm portal vein branch. Even in experienced hands, ultrasound H2O and normal extrahepatic biliary ductal pressure is 10 to has poor sensitivity in detecting CBD stones (