INTRODUCTION

Sepsis is commonly seen in the emergency department and, if not identified and treated in a timely manner, can result in significant morbidity and mortality for patients. Sepsis is defined as life-threatening acute organ dysfunction secondary to infection.1 Although sepsis is a survivable diagnosis, one-third of patients die within the following year, and one-sixth will have persistent impairments. Every year over 19 million patients worldwide develop sepsis, with approximately 14 million surviving to discharge. According to the Centers for Disease Control and Prevention, nearly 270,000 Americans die from sepsis annually. One in three patients who die in the hospital have a diagnosis of sepsis. In 2011, it was estimated that healthcare costs secondary to sepsis were close to $20 billion dollars.2

One of the many consequences of sepsis includes acalculous cholecystitis: an inflammation of the gallbladder that occurs in the absence of a mechanical obstruction (i.e. gallstones). It accounts for 5-15% of cases of cholecystitis, with the more common cause being calculous cholecystitis.3,4 Acalculous cholecystitis is more likely to develop in the setting of other underlying conditions, such as sepsis, trauma, burns, surgery, strokes, and heart attacks, and is therefore usually reported in hospitalized intensive care patients.5 While reports of acalculous cholecystitis are numerous, few are able to determine the time frame for development since they lack initial negative imaging. Based on case reports, timeframes for development of acalculous cholecystitis range from days to weeks.6

The pathophysiology of acalculous cholecystitis remains unclear and appears to be multi-factorial. It is thought to occur as a result of gallbladder stasis and decreased motility. This condition leads to the formation of a biliary “sludge,” which is a calcium bilirubinate mixture with an increased level of unconjugated bilirubin. The accumulation of “sludge” increases the intraluminal pressure of the gallbladder, impacting the arterial, lymphatic, and venous flow to the organ, leaving it susceptible to necrosis and gangrene.7 Bile stasis also contributes to the colonization of bacteria leading to infection. These potential complications of infection, gangrene, and perforation can eventually lead to sepsis and shock.3 Most studies show that complications occur in 40% of cases of acalculous cholecystitis. Studies have also shown that complications of acalculous cholecystitis are more common than calculous cholecystitis.4 Hence, early recognition and treatment of this condition is imperative. CT scan and ultrasound are both very sensitive for the diagnosis of acalculous cholecystitis.8 Some studies have shown CT to have 100% sensitivity in identifying acalculous cholecystitis.9 We present a case of development of acalculous cholecystitis secondary to urosepsis within six hours of a normal CT of the abdomen and pelvis.

CASE REPORT

A 21-year-old previously healthy Caucasian female presented to the Emergency Department (ED) via Emergency Medical Services (EMS). Her family called EMS because she seemed increasingly lethargic and disoriented. On EMS arrival, she was confused, lethargic, and hyperthermic with an oral temperature of 106 degrees Fahrenheit. EMS was told that the patient had been febrile for an entire day.

On initial presentation to the ED, the patient seemed confused, combative, and unresponsive to questioning. Her insight and judgment were limited, and her speech was disorganized. As a result, history was primarily provided by a family member who was present. She was only able to state a limited history and review of systems. The patient had no pertinent past medical history, no surgical history, no tobacco history, consumed alcohol monthly, sexually active with her boyfriend with condoms and oral contraceptive pill for contraception, and no family history. Review of systems was limited secondary to the patient’s altered mental status.

On initial examination, her blood pressure was 101/74 mmHg, her heart rate was 175 beats per minute, her respiration rate was 18 breaths per minute, her rectal temperature was 106 degrees Fahrenheit, and her oxygen saturation was 98% on room air. She did appear to be in acute distress. She was combative and confused, attempting to pull out IVs.

Patient was found to have profound electrolyte abnormalities, anemia, thrombocytopenia, an elevated lactic acid, and a non-anion-gap metabolic acidosis. (Table 1) COVID-19 swab was negative. Computed tomography of the head without contrast displayed no acute intracranial process. Computed tomography of the abdomen and pelvis with intravenous contrast was indicated for suprapubic pain which displayed mildly distended bowel loops suggestive of ileus. Since meningitis remained high on the differential, two grams of ceftriaxone and 20 milligrams per kilogram (mg/Kg) of vancomycin and 30mL/kg of lactated ringers were given.

Table 1.Lab values
Result Value Reference Range
Basic Metabolic Panel
Sodium 134 mEq/L 136-144 mEq/L
Potassium 1.8 mEq/L 3.7-5.2 mEq/L
Chloride 115 mmol/L 96-106 mmol/L
CO2 10 mmol/L 23-29mmol/L
Creatinine 1.37 mg/dL 0.8-1.2mg/dL
Calcium 4.1 mg/dL 8.5-10.2 mg/dL
Complete Blood Count
Red Blood Cells 2.87 x1012/L 3.93-5.22x x1012/L
Hemoglobin 8.4 g/dL 11.2-15.7g/dL
Hematocrit 25.1% 34.1-44.9%
Platelet 80 x109/L 182-369 x109/L
White Blood Cell 8.9 x109/L 3.98-10.04 x109/L
Hepatic Function Panel
Serum Albumin 1.3 g/dL 3.5-5.0 g/dL
Total Protein 3.1 g/dL 6.3-8.2 g/dL
Total Bilirubin 2.3 mg/dL 0.2-1.3 mg/dL
Direct Bilirubin 0.9 mg/dL 0.0-0.3 mg/dL
Alkaline Phosphatase <20 U/L 38-126U/L
Urinalysis
Urine Total Protein 70 mg/dL NEGATIVE
Urine Ketones Trace NEGATIVE
Leukocytes 500/mm3 NEGATIVE
Appearance Ex. Turbid CLEAR
Urine Color Dark-Yellow YELLOW
Red Blood Cell 6-10 per HPF NONE SEEN
White Blood Cell >100 per HPF NONE SEEN
Bacteria Moderate NONE SEEN
Hyaline Casts NONE SEEN NONE SEEN
Granular Casts NONE SEEN NONE SEEN
Other Lab Results
C-reactive Protein 133.3 mg/L <10mg/L
Lactic Acid 3.4 mmol/L <2 mmol/L
Magnesium 0.6 mEq/L 1.7-2.2 mEq/L
TSH 0.161 μU/mL 0.5-5 μU/mL

The patient’s tampon was removed which had bloody discharge on it. A speculum exam revealed that there were no abnormalities with the vagina. With toxic shock syndrome now on the differential, clindamycin was given for toxin suppression. A lumbar puncture was performed and displayed clear cerebrospinal fluid. Given the significance of her vital sign abnormalities, the electrolyte derangements, and her confusion, other diagnoses were considered such as sympathomimetic toxicity, anticholinergic toxicity, medication reaction such as serotonin syndrome, and neuroleptic malignant syndrome. The patient had no home medications. Mother and boyfriend adamantly denied any drug abuse history. Eventual urine drug screen was negative for cocaine, amphetamines, and PCP.

At this point, the patient was still severely altered, tachycardic, and hypotensive. A norepinephrine infusion was started, and the patient was admitted to the intensive care unit (ICU) with the initial impression of septic shock, altered mental status, tachycardia, and urinary tract infection. The patient continued to have ill symptoms such as fever, sweats, and fatigue. On re-examination in the ICU, the patient’s mentation improved, and she began to localize pain to the right upper-quadrant of the abdomen. Her blood pressure was 93/68 mmHg, heart rate was 120 beats per minute, 35 respirations per minute, her temperature was 101.9 degrees Fahrenheit, and her oxygen saturation was 100%.

Right upper quadrant was evaluated via ultrasound which displayed gallbladder wall thickening and pericholecystic fluid consistent with cholecystitis. No gallstones were present. Patient underwent percutaneous cholecystostomy for drain placement. The patient’s mentation and right upper-quadrant pain were much improved post-drain placement. Her blood pressure was 100/64 mmHg, her heart rate was 118 beats per minute, her respiration rate was 28 breaths per minute, her temperature was 99.3 degrees Fahrenheit, and her oxygen saturation was 95% on room air.

The patient was discharged eight days after ED presentation with cefdinir. She was in an improved and stable condition. A follow-up appointment with general surgery was scheduled for one week after discharge. A cholecystectomy was scheduled for four-to-six weeks post-drain placement.

There was no diagnosis of acalculous cholecystitis in the ED. Additionally, the patient had a CT of the abdomen and pelvis with IV contrast with no gallbladder wall thickening and no pericholecystic fluid observed at that time.

DISCUSSION

Acalculous cholecystitis presents similarly to calculous cholecystitis, with right upper-quadrant pain and a positive Murphy’s sign. Other signs and symptoms, such as jaundice, fever, elevated white blood cell count, elevated bilirubin, and nausea may also be present.3 Otherwise, acalculous cholecystitis should be suspected in septic patients with unknown origin. When acalculous cholecystitis is suspected, the best imaging modality is ultrasound (US) due to its portability and speed.5 US can be used to visualize increased gallbladder wall thickness (over 3.5 mm), pericholecystic fluid, and biliary sludge, all of which may indicate acalculous cholecystitis.3,5 A CT scan of the abdomen and pelvis could also show similar findings with similar sensitivity. Another useful diagnostic test is a HIDA scan. A radionuclide is administered to visualize the gallbladder and examine its function. Cholecystokinin is administered to stimulate gallbladder contraction. If contraction and emptying are limited, this may be indicative of acalculous cholecystitis.5 It is important to acknowledge that our case report utilized two different imaging modalities, each with their own sensitivities and specificities, to document the progression of the disease and its impact on the clinical conclusion.

Treatment of acalculous cholecystitis involves surgical cholecystectomy or percutaneous drainage of the gallbladder.3,4,7 Historically, the definitive treatment was cholecystectomy.5 However, in an emergency situation, or in an unstable patient, percutaneous cholecystostomy provides immediate relief and is potentially lifesaving. Studies have shown that there is a low risk of recurrence of acalculous cholecystitis after drainage.4 Therefore, drainage may be a sufficient treatment unless gangrene or perforation has occurred. Acalculous cholecystitis has a mortality rate of 30% which is related to lethal complications such as perforation, gangrene, and emphysematous cholecystitis. Detection of acalculous cholecystitis is vital in preventing additional complications.

As in the patient presented in this aforementioned case, sepsis has a staggering impact on patient outcomes; it is crucial to recognize the signs of sepsis and initiate treatment immediately. Source control in sepsis requires identification of the source, followed by an intervention. While in the emergency department, this may be a challenging task as sources of sepsis can be difficult to uncover. The standard workup often includes a chest x-ray and a urinalysis, which can lead to a premature diagnosis of urinary tract infection or pneumonia.10 Having a systematic way to approach sources of sepsis can help physicians identify sources.1 It is important to know the epidemiology of one’s area and the most common causes of sepsis, which are intra-pulmonary and intra-abdominal infections.11 Identifying risk factors in patient history such as alcoholism, diabetes, recent surgical procedures, and foreign hardware is important. A thorough physical examination and obtaining directed imaging is likewise vital. The use of biomarkers can be helpful, but most experts agree that a trend is more important than a single observation in the case of procalcitonin.1

CONCLUSION

This case reinforces the importance of considering acalculous cholecystitis in patients who present with sepsis and then develop right upper-quadrant pain. A point-of-care ultrasound or repeat abdominal CT should be considered to rule out acalculous cholecystitis. While septic patients may commonly present with variable symptoms, the absence of right upper-quadrant pain or markedly elevated bilirubin does not rule out the rapid development of acalculous cholecystitis.