The Case

A patient with a history of T6 paraplegia due to a motor vehicle accident was brought to the emergency department due to delirium. He was found to be hypotensive and febrile. Laboratory tests revealed a high white blood cell count and mild elevation of his bilirubin and liver enzymes. His physical examination was unremarkable, but given the laboratory findings, the emergency physician was concerned for hepatitis or cholecystitis (inflammation of the gallbladder due to obstructing gallstones) as the cause of his hypotension. A stat CT scan of the abdomen and pelvis was performed that showed a mildly thickened gallbladder wall but no definitive evidence of gallstones, acute cholecystitis, or liver findings. The patient was admitted to the intensive care unit (ICU) with a provisional diagnosis of septic shock. He was empirically treated with broad-spectrum antibiotics and intravenous fluids.

The patient's delirium and hypotension improved and he defervesced. However, results of blood and urine cultures were negative, and no clear source of infection was found. His bilirubin and liver enzymes remained elevated. He was transferred to the ward on hospital day 2. Shortly after arriving on the ward, he had a low-grade fever. The hospitalist who received the patient on the ward examined the patient and realized his diagnosis was still unclear. She noted the CT findings of a thickened gallbladder wall and decided to obtain another CT scan. Results showed that the patient had a 6 cm abscess adjacent to the liver, likely arising from an acutely inflamed gallbladder that had perforated. A surgical consultation was immediately obtained, and the patient underwent an urgent open cholecystectomy and drainage of the abscess. He remained hospitalized for several more days, but he was ultimately discharged home in good condition.

On reviewing the case, the surgeon thought that the patient had in fact presented with acute cholecystitis and that surgery consultation should have been obtained earlier. The ICU physician expressed surprise when the surgeon brought this up with him, as the patient did not have any abdominal symptoms during his stay in the ICU.

The Commentary

by Zara Cooper, MD, MSc

Acute cholecystitis, a constellation of right upper quadrant pain, leukocytosis, and fever caused by gallbladder inflammation, is among the most common causes for inpatient surgical admission.¹ Approximately 90% of patients with cholecystitis have gallstones.² Most are silent; however, approximately 10% of patients with symptomatic gallstones will go on to have acute cholecystitis.^3,4 The remaining patients with acute cholecystitis have acalculous cholecystitis, which is due to necrosis and inflammation of the gallbladder secondary to gallbladder ischemia, bile stasis, and subsequent infection. Patients with acalculous cholecystitis are more likely to present with perforation, gallbladder emphysema, and abscess. Bile stasis may also lead to jaundice.

As this case demonstrates, acalculous cholecystitis can be a vexing diagnosis to make because it tends to occur in critically or chronically ill patients who have confounding symptoms and diagnoses. Therefore, patients may present with shock of unknown etiology, and the first hint of gallbladder disease may be seen on a CT scan obtained to evaluate abdominal pain. Diagnosing an acute abdomen in patients with spinal cord injury is particularly challenging because such patients usually do not present with classic signs of pain and peritonitis (rigidity, guarding, rebound).⁵ Clinicians who are not mindful of the prevalence and risk factors for acalculous cholecystitis may be misled by the absence of gallstones on CT or ultrasound. Early diagnosis is critical in acalculous cholecystitis, since approximately 40% of patients progress to gangrene, perforation, and emphysema of the gallbladder wall.⁶ Early intervention by either surgery or percutaneous drainage (if the patient is too sick to tolerate surgery) is associated with better outcomes. Nonetheless, mortality is quite high because the presence of acalculous cholecystitis is usually a marker of overall illness severity.

Although CT scan is frequently obtained to elucidate sources of intrabdominal infection, it is not a definitive test for cholecystitis. Due to its portability, low cost, reproducibility, and adequate sensitivity and specificity, ultrasound is usually the first-line test to diagnose cholecystitis. However, a recent prospective study of patients who underwent cholecystectomy for acute cholecystitis showed that CT was significantly more sensitive than ultrasound (92% versus 79% ) for diagnosis.⁷ Positive CT scan findings include gallbladder distention and wall thickening, as well as pericholecystic fat and fluid, but these findings are nonspecific. The most common nonspecific finding on CT scan is gallbladder wall thickening (as in this case), which may also be present in hepatitis or conditions associated with hypervolemia such as heart failure and renal disease 

Ultrasound is particularly useful for detecting gallstones, but it may have in fact been misleading in this case if acalculous disease was not in the clinician's differential diagnosis. Cholescintigraphy (HIDA scan) is the most accurate imaging modality, with 96% sensitivity and 90% specificity.⁸ In this case, where the differential diagnosis was broad due to a nonspecific clinical exam, a CT scan was reasonable as a first step to evaluate abdominal pain. However, findings of a mildly thickened gallbladder wall increased the posttest possibility of biliary disease and should have prompted additional imaging for acute cholecystitis. Because of the absence of stones on the CT, a HIDA was a reasonable next step to rule out acalculous cholecystitis. Moreover, elevated bilirubin in a patient with sepsis raises the possibility of cholangitis due to common duct obstruction which would also warrant further workup with an ultrasound or MRI. Cholangitis would prompt an emergent ERCP [endoscopic retrograde cholangiopancreatography].

Definitive treatment for acute cholecystitis is cholecystectomy, and surgery should occur during the index hospitalization unless the patient is a prohibitive risk.⁹ In a large Canadian study of more than 25,000 patients admitted with a first episode of acute cholecystitis, among those discharged without cholecystectomy, 19% had a gallstone-related event within 12 weeks, of which 30% were for gallstone-related complications including pancreatitis or biliary obstruction.¹⁰ Moreover, delay in surgery for greater than 48 hours is associated with longer length of stay, higher risk of conversion to an open procedure, greater complication risk, and increased cost.^11-13 Therefore, surgeons should be engaged early in the clinical decision-making process. Patients at high risk for surgery may be offered percutaneous gallbladder drainage instead. In this case, the patient was sent to the next phase of care without a clear diagnosis. Earlier surgical involvement could have prevented diagnostic delay. Acute care surgery services—which include in-hospital coverage by surgeons who treat trauma, emergency general surgery, and critical care—are associated with less time to surgery and shorter length of stay for patients with biliary disease.^14,15 Patients with acute cholecystitis admitted to surgical rather than medical services have less time to surgery and shorter hospital stays.¹⁶ Together, these findings support triggers for early surgical involvement when acute cholecystitis is suspected. 

Sepsis is among the most common sources of diagnostic error in the emergency setting, with atypical presentation being the most common contributory factor.¹⁷ Moreover, gallbladder disease is the most common missed diagnosis in patients with acute abdominal pain.¹⁸ Miscalibration, or confidence in inaccurate clinical decisions, contributes to diagnostic errors and likely played a role in this case in which, despite abnormal CT findings, the ICU physician did not pursue additional testing or request surgical consultation.¹⁹ Direct feedback and standardized approaches to reporting diagnostic errors can provide an important feedback loop to improve patient safety.²⁰

Take-Home Points

• Clinicians should have a high index of suspicion for acute acalculous cholecystitis in critically and chronically ill patients with sepsis of unknown etiology.
• Because CT scan is sensitive but not specific for acute acalculous cholecystitis, cholescintigraphy (HIDA scan) should be used to definitively rule out the diagnosis.
• Cholecystectomy is the definitive treatment for cholecystitis, so surgeons should be involved early in cases where the diagnosis is suspected.
• Abdominal pain and sepsis are among the most common reasons for diagnostic error in the emergency department.
• Systematic approaches for error reporting and reducing miscalibration errors can improve patient safety.
• Triggers or pathways that prompt early surgical consultation when acute cholecystitis is suspected expedite treatment and have potential to achieve earlier surgical treatment, shorter length of stay, and lower costs.

Zara Cooper, MD, MSc
Associate Professor of Surgery
Harvard Medical School
Boston, MA

References

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