Should I consider acute acalculous cholecystitis in my elderly ambulatory patient admitted with right upper quadrant pain?

Short answer: Yes! Although we usually associate acute acalculous cholecystitis (AAC) with critically ill patients (eg, with sepsis, trauma, shock, major burns) in ICUs, AAC is not as rare as we might think in ambulatory patients. In fact, a 7 year study of AAC involving multiple centers reported that AAC among outpatients was increasing in prevalence and accounted for 77% of all cases (1)!

Although the pathophysiology of ACC is not fully understood, bile stasis and ischemia of the gallbladder either due to microvascular or macrovascular pathology have been implicated as potential causes (2). One study found that 72% of outpatients who developed ACC had atherosclerotic disease associated with hypertension, coronary, peripheral or cerebral vascular disease, diabetes or congestive heart failure (1). Interestingly, in contrast to calculous cholecystitis, “multiple arterial occlusions” have been observed on pathological examination of the gallbladder in at least some patients with ACC and accordingly a name change to “acute ischemic cholecystitis” has been proposed (3).

AAC can also complicate acute mesenteric ischemia and may herald critical ischemia and mesenteric infarction (3). The fact that cystic artery is a terminal branch artery probably doesn’t help and leaves the gallbladder more vulnerable to ischemia when arterial blood flow is compromised irrespective of the cause (4).

Of course, besides vascular ischemia there are numerous other causes of ACC, including infectious (eg, viral hepatitis, cytomegalovirus, Epstein-Barr virus, Salmonella, brucellosis, malaria, Rickettsia and enteroviruses), as well as many non-infectious causes such as vasculitides and, more recently, check-point inhibitor toxicity (1,5-8).

Bonus Pearl: Did you know that in contrast to cholecystitis associated with gallstones (where females and 4th and 5th decade age groups predominate), ACC in ambulatory patients is generally more common among males and older age groups (mean age 65 y) (1)?


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1. Savoca PE, Longo WE, Zucker KA, et al. The increasing prevalence of acalculous cholecystitis in outpatients: Result of a 7-year study. Ann Surg 1990;211: 433-37.
2. Huffman JL, Schenker S. Acute acalculous cholecystitis: A review. Clin Gastroenterol Hepatol 2010;8:15-22.
3. Hakala T, Nuutinene PJO, Ruokonen ET, et al. Microangiopathy in acute acalculous cholecystitis Br J Surg 1997;84:1249-52.
4. Melo R, Pedro LM, Silvestre L, et al. Acute acalculous cholecystitis as a rare manifestation of chronic mesenteric ischemia. A case report. Int J Surg Case Rep 2016;25:207-11.
5. Aguilera-Alonso D, Median EVL, Del Rosal T, et al. Acalculous cholecystitis in a pediatric patient with Plasmodium falciparum infection: A case report and literature review. Ped Infect Dis J 2018;37: e43-e45.  
6. Kaya S, Eskazan AE, Ay N, et al. Acute acalculous cholecystitis due to viral hepatitis A. Case Rep Infect Dis 2013;Article ID 407182.
7. Simoes AS, Marinhas A, Coelho P, et al. Acalculous acute cholecystitis during the course of an enteroviral infection. BMJ Case Rep 2013;12.
8. Abu-Sbeih H, Tran CN, Ge PS, et al. Case series of cancer patients who developed cholecystitis related to immune checkpoint inhibitor treatment. J ImmunoTherapy of Cancer 2019;7:118.



Should I consider acute acalculous cholecystitis in my elderly ambulatory patient admitted with right upper quadrant pain?

What are the major changes in the definition of “sepsis” under the 3rd International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)?

Under Sepsis-3 [1], sepsis is defined as a “life-threatening organ dysfunction caused by a dysregulated host response to infection (suspected or confirmed)”. Systemic inflammatory response syndrome (SIRS) is no longer defined as part of the sepsis spectrum, and its criteria have been replaced by the Sequential Organ Failure Assessment (SOFA) with a change in score ≥2 (Table) having >10% in-hospital mortality. Septic shock is defined as hypotension requiring vasopressors to maintain a MAP ≥65 mm Hg and a lactate >2 mmol/L (18 mg/dL) despite adequate volume (>40% in-hospital mortality).

A bedside clinical tool “quickSOFA” (qSOFA), not meant to substitute for SOFA, is also proposed to identify patients primarily outside of the ICU who may be at high risk of adverse outcomes, based on the following criteria: systolic blood pressure ≤100 mmHg, respiratory rate ≥22/min, and altered mental status. A qSOFA score ≥2 is associated with poorer outcomes [1,2].

So what do these new guidelines mean for clinicians? Under the new terminology, “sepsis” now refers only to what was previously considered severe sepsis with or without shock, and those who may need more aggressive therapy, closer monitoring and possible transfer to an ICU [1,2]. As the guidelines stress, however, failure to meet qSOFA or SOFA criteria should by no means lead to a deferral or delay in evaluation or treatment of infection deemed necessary by clinicians, and SIRS criteria may still be useful in identification of infection [1].

It remains to be seen whether limiting the definition of sepsis to only patients with associated organ dysfunction will translate into an overall earlier diagnosis and improved prognosis for this condition.

Using SIRS criteria (ie, 2 or more of the following, heart rate >90/min, respiratory rate >20/min  or PaC02 <32 mm Hg, temperature<36 C or >38 C, WBC <4,000 or >12,000 or bandemia >10%) in patients suspected of having a potentially serious infection still makes sense if the goal is to identify it “upstream” before organ dysfunction or shock sets in.  Stay tuned!


Table. Sequential (sepsis-related) organ failure assessment (SOFA) score (adapted from ref.1)____________________________________________________________________________________________________


Parameter                                0                      1                      2                      3                      4


Pa02/Fi02                           ≥400                 <400                <300                 <200*          <100*

Platelets (no./mL)           >150,000         <150,000         <100,000         <50,000       <20,000

Bilirubin (mg/dL)            <1.2                  1.2-1.9              2.0-5.9             6.0-11.9       >12.0

MAP (mm Hg) or VP      MAP≥70         MAP<70          DPA≤5           DPA 5.1-15        DPA>15

Glascow Coma Scale       15                    13-14            10-12                    6-9                 3-6

Creatinine (mg/dL)        <1.2                 1.2-1.9           2.0-3.4                  3.5-4.9        >5.0

OR U.O.  (mL/dL)                                                                                              <500                <200


MAP= mean arterial pressure, VP=vasopressor (includes agents other than dopamine), DPA=dopamine (in mcg/kg/min for ≥1 hour);U.O.= urine output

*With respiratory support


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  1. Singer MS, Deutschman CS, Seymour CW, et al; The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016;315[8]:801-810.  
  2. Jacob JA. New Sepsis Diagnostic Guidelines Shift Focus to Organ Dysfunction. JAMA. 2016;213[8]:739-740.


Contributed by Erik Kelly MD, Mass General Hospital, Boston, MA

What are the major changes in the definition of “sepsis” under the 3rd International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)?

Can syncope be related to acute pulmonary embolism in the absence of hemodynamic instability or right ventricular failure?

Although we often think of syncope caused by acute pulmonary embolism (APE) in the setting of submassive or massive APE and right ventricular failure or shock (1,2), less massive APE may potentially cause syncope as well by triggering a vaso-vagal reflex (3).

For sure, a significant association between submassive or massive APE and syncope has been reported (1,2).  More specifically, patients with syncope and APE may be more likely to have systolic blood pressure <90 mmHg, right ventricular dilation and right ventricular hypokinesis (1). Another study reported a higher rate of central embolism (83% vs 43%), right ventricular dysfunction (91% vs 68%) and troponin positivity (80% vs 39%), but not 30 day mortality (2).

In contrast, 1 study found that patients with syncope as a presenting symptom of APE did not show a more serious clinical picture (e.g. shock) than those without syncope (3), while another found EKG signs of acute right ventricle overload in only 25% of patients with syncope (4).  

So while massive APEs may be associated with syncope, they don’t seem to be a prerequisite for this condition.


1.  Omar HR, Mirsaeidi M, Weinstock MB, et al. Syncope on presentation is a surrogate for submassive and massive acute pulmonary embolism. Am J Emerg Med 2018;36:297-300.

2. Altinsoy B, Erboy F, Tanriverdi H, et al. Syncope as a presentation of acute pulmonary embolism. Ther Clin Risk Manag 2016;12:1023-28.

3. Castelli R, Tarsia P, Tantardini G et al. Syncope in patients with pulmonary embolism: comparison between patients with syncope as the presenting symptom of pulmonary embolism and patients with pulmonary embolism without syncope. Vascular Medicine 2003;8:257-261.

4. Miniati M, Cenci, Monti S, et al. Clinical presentation of acute pulmonary embolism: survey of 800 cases. PloS One 2012;7:e30891.

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Can syncope be related to acute pulmonary embolism in the absence of hemodynamic instability or right ventricular failure?