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)?

 

If you liked this post, download the app and sign up under MENU to catch future pearls straight into your inbox, all for free! 

 

References
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. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1358029/pdf/annsurg00170-0061.pdf
2. Huffman JL, Schenker S. Acute acalculous cholecystitis: A review. Clin Gastroenterol Hepatol 2010;8:15-22. https://www.cghjournal.org/article/S1542-3565(09)00880-5/pdf
3. Hakala T, Nuutinene PJO, Ruokonen ET, et al. Microangiopathy in acute acalculous cholecystitis Br J Surg 1997;84:1249-52. https://bjssjournals.onlinelibrary.wiley.com/doi/abs/10.1046/j.1365-2168.1997.02775.x?sid=nlm%3Apubmed
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. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4941110/
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. https://journals.lww.com/pidj/pages/articleviewer.aspx?year=2018&issue=02000&article=00020&type=Fulltext  
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. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3784234/pdf/CRIM.ID2013-407182.pdf
7. Simoes AS, Marinhas A, Coelho P, et al. Acalculous acute cholecystitis during the course of an enteroviral infection. BMJ Case Rep 2013;12. https://casereports.bmj.com/content/12/4/e228306
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. https://jitc.biomedcentral.com/articles/10.1186/s40425-019-0604-2

 

 

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

Why is my patient with diabetic ketoacidosis (DKA) and hypovolemia hypertensive?

Although we may expect patients with DKA to present with hypotension due to hypovolemia, many patients with DKA may actually be hypertensive. This finding is particularly intriguing because hyperinsulinemia, not insulinopenia as found in DKA, has been associated with hypertension. 1,2

Though not proven, potential explanations for hypertension in DKA include elevated serum levels of catecholamines, pro-inflammatory cytokines, renin, angiotension II and aldosterone.3-5 Hyperosmolality may also lead to the release of antidiuretic hormone (ADH) which increases blood pressure via V2 receptors.  Another possibility is that the high insulin levels associated with the treatment of DKA suppress the catecholamine-stimulated production of vasodilative eicosanoids (eg, prostaglandins) by adipose tissue. 1 It’s possible that in any given patient, 1 or more of these mechanisms may be enough to override the potential hypotensive effect of insulin deficiency in DKA.

We should note that reports of frequent hypertension in DKA have primarily involved pediatric patients. A 2011 study found that 82% of pediatric patients with DKA had hypertension during the first 6 hours of admission with no patient having hypotension.3  

On the other extreme, refractory hypotension without obvious cause (eg, sepsis, acute adrenal insufficiency, cardiogenic causes) has also been reported in DKA.5Because insulin inhibits the production of vasodilative prostaglandins (eg, PGI2 and PGE2), severe insulin deficiency in DKA can also contribute to hypotension along with volume depletion. 

Potential genetic polymorphism in the synthesis and metabolism of prostaglandins may at least partially explain the varied blood pressure response and whether a patient with DKA presents with hypertension or hypotension. 5  

The author would like to acknowledge the valuable contribution of Lloyd Axelrod MD, Massachusetts General Hospital, to this post.

If you liked this post, sign up under MENU and catch future pearls right into your inbox!

References

  1. Axelrod L. Insulin, prostaglandins, and the pathogenesis of hypertension. Diabetes 1991;40:1223-1227. https://diabetes.diabetesjournals.org/content/40/10/1223 
  2. Chatzipantelli K, Head C, Megerman J, et al. The relationship between plasma insulin level, prostaglandin productin by adipose tissue and blood pressure in normal rats and rats with diabetes mellitus and diabetic ketoacidosis. Metabolism 1996;45:691-98. https://www.sciencedirect.com/science/article/abs/pii/S002604959690133X 
  3. Deeter KH, Roberts JS, Bradford H, et al. Hypertension despite dehydration during severe pediatric diabetic ketoacidosis. Pediatr Diabetes 2011;12:295-301. https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1399-5448.2010.00695.x 
  4. Ferris JB, O’Hare JA, Kelleher CM, et al. Diabetic control and the renin-angiotensin system, catecholamines and blood pressure. Hypertension 1985 7(Suppl II):II-58-II-63. https://www.ahajournals.org/doi/abs/10.1161/01.HYP.7.6_Pt_2.II58  
  5. Singh D, Cantu M, Marx MHM, et al. Diabetic ketoacidosis and fluid refractory hypotension. Clin Pediatrics 2016;55:182-84. https://journals.sagepub.com/doi/abs/10.1177/0009922815584549?journalCode=cpja 

 

Why is my patient with diabetic ketoacidosis (DKA) and hypovolemia hypertensive?

Why was the myocardial infarction in my postop patient silent?

Myocardial infarction (MI) in postop patients is in fact usually silent (1,2) but what is less clear is how myocardial ischemia can occur without any symptoms.

Although use of analgesics and narcotics postop may dampen or mask chest pain or other symptoms associated with MI, other factors are also likely to play an important role, such as decreased sensitivity to painful stimuli, autonomic neuropathy (eg, in diabetes mellitus), and higher pain threshold among some patients (3).

Additional factors associated with silent MIs include cerebral cortical dysfunction since frontal cortical activation appears to be necessary to experience cardiac pain. Mental stress is also a frequent trigger for asymptomatic myocardial ischemia, infarction and sudden cardiac death (4).  High levels of beta-endorphin, an endogenous opiate, may also play a role (5).

 
Perhaps the most intriguing explanation for lack of symptoms is the observation that the levels of anti-inflammatory cytokines (interleukin-4 and -10)—which block pain transmission pathways and increase the threshold for nerve activation—seem to be increased in patients with silent myocardial ischemia (6).  Even more relevant to our postop patient is the finding that interleukin-10 production increases during and after major abdominal surgery and correlates with the amount of intraoperative blood loss (7). 

No wonder MIs in postop patients are often silent!

References
1. Devereaux PJ, Xavier D, Pogue J, et al. Characteristics nd short-term prognosis of perioperative myocardial infarction in patients undergoing noncardiac surgery: a cohort study. Ann Intern Med 2011;154:523-8. https://annals.org/aim/article-abstract/746934/characteristics-short-term-prognosis-perioperative-myocardial-infarction-patients-undergoing-noncardiac 
2. Badner NH, Knill RL, Brown JE, et al. Myocardial infarction after noncardiac surgery. Anesthesiology 1998;88:572-78. http://anesthesiology.pubs.asahq.org/article.aspx?articleid=1948483
3. Ahmed AH, Shankar KJ, Eftekhari H, et al. Silent myocardial ischemia:current perspectives and future directions. Exp Clin Cardiol 2007;12:189-96. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2359606/ 
4. Gullette EC, Blumenthal JA, Babyak M, et al. Effects of mental stress on myocardial ischemia during daily life. JAMA 1997;277:1521-6. https://jama.jamanetwork.com/journals/jama/articlepdf/416233/jama_277_19_029.pdf
5. Hikita H, Kurita A, Takase B, et al. Re-examination of the roles of beta-endorphin and cardiac autonomic function in exercise-induced silent myocardial ischemia. Ann Noninvasive Electrocardiol 1997;2:319-25. https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1542-474X.1997.tb00195.x
6. Mazzone A, Cusa C, Mazzucchelli I, et al. Increased production of inflammatory cytokines in patients with silent myocardial ischemia. J Am Coll Cardiol 2001;38:1895-901. https://www.ncbi.nlm.nih.gov/pubmed/11738291
7. Kato M, Honda I, Suzuki H, et al. Interleukin-10 production during and after upper abdominal surgery. J Clin Anesth 1998;10:184-8. https://www.ncbi.nlm.nih.gov/pubmed/9603586 

If you liked this post, sign up under MENU and catch future pearls straight into your mailbox! 

Why was the myocardial infarction in my postop patient silent?

My patient is admitted with diabetic ketoacidosis (DKA) and is testing positive for cocaine. Can cocaine cause DKA?

Cocaine use has been generally linked to DKA but whether it’s through its antagonizing effect on insulin action or more indirectly through its association with non-compliance with insulin, or both, is not totally clear.

A retrospective study found cocaine users to account for 14% of all DKA admissions.1 Cocaine users were also less likely than controls to have an intercurrent illness identified as a precipitant for DKA, and more likely to have missed taking insulin prior to admission. Another study also reported active cocaine use to be associated with DKA, but found its effect to be independent of non-compliance. 2

Yet another retrospective study limited to patients admitted with hyperglycemia, found no significant association between active cocaine use and development of hyperglycemic crisis.

There are reasons to believe that cocaine may contribute to DKA. Cocaine has been proposed as a possible precipitant of DKA due to its ability to potentially enhance counterregulatory mechanisms designed to antagonize the effect of insulin by increasing catecholamine and cortisol levels. 1,3

So next time you have a patient with DKA, consider cocaine as a possible precipitant, particularly when the cause of DKA is unclear.

 

References

  1. Warner EA, Greene GS, Buchsbaum MS et al. Diabetic ketoacidosis associated with cocaine use. Arch Intern Med 1998; 158:1799-802. https://www.ncbi.nlm.nih.gov/pubmed/9738609
  2. Nyenwe E, Loganathan R, Blum S, et al. Active use of cocaine: An independent risk factor for recurrent diabetic ketoacidosis in a city hospital. Endocr Pract 2007;13:22-29. https://www.ncbi.nlm.nih.gov/pubmed/17360297
  3. Modzelewski KL, Rybin DV, Weinberg JM, et al. Active cocaine use does not increase the likelihood of hyperglycemic crisis. J Clin Transl Endocrinol 2017;9:1-7 http://www.jctejournal.com/article/S2214-6237(16)30056-4/pdf

 

Contributed in part by Quin L Sievers, Medical Student, Harvard Medical School

My patient is admitted with diabetic ketoacidosis (DKA) and is testing positive for cocaine. Can cocaine cause DKA?

My diabetic patient complains of acute blurred vision past few days since her blood glucoses have been out of control. How does high blood glucose affect the vision acutely?

“Vision loss or blurriness” is one of the most common manifestations of acute hyperglycemia in diabetic patients and is due to the osmotic swelling of the lens resulting in changes in its characteristics and the inability to properly focus an image.1

Since glucose acts as a solute, an increase in the concentration of glucose causes a rise in osmotic forces and movement of fluid into the lens, resulting in transient myopia. Interestingly, the increase in the fluid in the lens causes a change in its refractory index which is associated with focusing an image at a different length; it does not affect  its curvature or position. 

Baseline vision should be eventually restored by correcting glucose levels.2 Also remember that rapid correction of hyperglycemia may make the lens swelling worse, causing increased visual disturbances.3  

Fun fact: Did you know that chronic hyperglycemia is associated with cataract formation due to excess conversion of glucose to sorbitol in the lens? 4

References

  1. Bron A.J, Sparrow J, Brown N, Harding J, Blakytny, R. The Lens in Diabetes. Eye 1993; 7: 260-75 https://www.nature.com/articles/eye199360.pdf
  2. Huntjens B. O’Donnell C. Refractive error changes in Diabetes Mellitus. Optometry in Practice 2006; 7:103-114. http://openaccess.city.ac.uk/6185/3/Refractive_Error_Changes_in_DM_FINAL.pdf
  3. Sychev YV, Zepeda EM, Lam DL. Bilateral cateract formation via acute spontaneous fracture of the lens following treatment of hyperglycemic hyperosmolar syndrome: Case report. Am J Ophthalmol 2017;7:66-69. https://www.ncbi.nlm.nih.gov/pubmed/29260081
  4. Pollreisz A, Ursula SE. Diabetic Cataract—Pathogenesis, Epidemiology and Treatment. Journal of Ophthalmology 2010; vol. 2010, Article ID 608751. https://www.hindawi.com/journals/joph/2010/608751

 

Contributed by Felicia Hsu, Medical Student, Harvard Medical School

My diabetic patient complains of acute blurred vision past few days since her blood glucoses have been out of control. How does high blood glucose affect the vision acutely?

My middle age patient complains of night sweats for several months, but she has had no weight loss and does not appear ill. What could I be missing?

Night sweats (NS) is a common patient complaint, affecting about a third of hospitalized patients on medical wards1.  Despite its long list of potential causes, direct relationship between the often- cited conditions and NS is usually unclear2, its cause may remain elusive In about a third to half of cases in the primary care setting, and its prognosis, at least in those >65 y of age, does not appear to be unfavorable 2,3.

Selected commonly and less frequently cited conditions associated with NS are listed (Table)2-9.  Although tuberculosis is one of the first conditions we think of when faced with a patient with NS, it should be emphasized that NS is not common in this disease (unless advanced) and is rare among hospitalized patients as a cause of their NS1,9.

In one of the larger study of adult patients seen in primary care setting, 23% reported pure NS and an additional 18% reported night and day sweats5; the prevalence of NS in both men and women was highest in 41-55 y age group. In multivariate analyses, factors associated with pure NS in women were hot flashes and panic attacks; in men, sleep disorders. 

Table. Selected causes of night sweats

Commonly cited Less frequently cited
Neoplastic/hematologic (eg, lymphoma, leukemia, myelofibrosis)

Infections (eg, HIV, tuberculosis, endocarditis)

Endocrine (eg, ovarian failure, hyperthyroidism, orchiectomy, carcinoid tumor, diabetes mellitus [nocturnal hypoglycemia], pheochromocytoma)

Rheumatologic (eg, giant cell arteritis)

Gastroesophageal reflux disease

B-12 deficiency

Pulmonary embolism

Drugs (eg, anti-depressants, SSRIs, donepezil [Aricept], tacatuzumab)

Sleep disturbances (eg, obstructive sleep apnea)

Panic attacks/anxiety disorder

Obesity

Hemachromatosis

Diabetes insipidus

References

  1. Lea MJ, Aber RC, Descriptive epidemiology of night sweats upon admission to a university hospital. South Med J 1985;78:1065-67.
  2. Mold JW, Holtzclaw BJ, McCarthy L. Night sweats: A systematic review of the literature. J Am Board Fam Med 2012; 25-878-893.
  3. Mold JW, Lawler F. The prognostic implications of night sweats in two cohorts of older patients. J Am Board Fam Med 2010;23:97-103.
  4. Mold JW, Holtzclaw BJ. Selective serotonin reuptake inhibitors and night sweats in a primary care population. Drugs-Real World Outcomes 2015;2:29-33.
  5. Mold JW, Mathew MK, Belgore S, et al. Prevalence of night sweats in primary care patients: An OKPRN and TAFP-Net collaborative study. J Fam Pract 2002; 31:452-56.
  6. Feher A, Muhsin SA, Maw AM. Night sweats as a prominent symptom of a patient presenting with pulmonary embolism. Case reports in Pulmonology 2015. http://dx.doi.org/10.1155/2015/841272
  7. Rehman HU. Vitamin B12 deficiency causing night sweats. Scottish Med J 2014;59:e8-11.
  8. Murday HK, Rusli FD, Blandy C, et al. Night sweats: it may be hemochromatosis. Climacteric 2016;19:406-8.
  9. Fred HL. Night sweats. Hosp Pract 1993 (Aug 15):88.
My middle age patient complains of night sweats for several months, but she has had no weight loss and does not appear ill. What could I be missing?

Is diabetes mellitus (DM) an independent risk factor for venous thromboembolism (VTE)?

Although DM was originally thought to be an independent risk factor for DM1,2, more recent data suggest otherwise.

A population-based study involving residents of Olmsted County, Minnesota, calculated the incidence of VTE among patients with DM over a 25-year period and found it to be higher than that of controls .   However, in the same study, after controlling for hospitalization for major surgery or medical illness and nursing home confinement, no association between DM and VTE was found2  .  

A recent systematic review and meta-analysis of case-control and cohort studies involving over 1 million patients found no significant association between DM and VTE when controlled for common risk factors (eg, obesity, sedentary life style, smoking, hypertension, or dyslipidemia)3.  The authors concluded that DM and its complications are not independent risk factors for incident VTE.  

Thus, it appears that much of the risk of DVT in DM may be related to its comorbidities and the need for hospitalization, surgery or nursing home stay.

References

  1. Petrauskiene V, Falk M, Waernbaum I, et al. The risk of venous thromboembolism is markedly elevated in patients with diabetes. Diabetologia 2005;48:1017-21. https://www.ncbi.nlm.nih.gov/pubmed/15778859
  2. Heit JA, Leibson CL, Ashrani AA, et al. Is diabetes mellitus an independent risk factor for venous thromboembolism? A population-based case-control study. Thromb Vasc Biol 2009; 29:1399-1405. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2735343/
  3. Gariani K, Mavrakanas T, Combescure C, et al. Is diabetes mellitus a risk factor for venous thromboembolism? A systematic review and meta-analysis of case-control and cohort studies. Eur J Intern Med 2016;28:52-58. https://www.ncbi.nlm.nih.gov/pubmed/26507303
Is diabetes mellitus (DM) an independent risk factor for venous thromboembolism (VTE)?

Should we treat asymptomatic candiduria?

This is a common scenario among our hospitalized patients with indwelling catheters, prior antibiotic therapy or diabetes mellitus who seem to have no clinical signs of infection. Fortunately, candidemia from urinary sources appears uncommon to rare, with up to nearly ½ of patients clearing their candiduria with removal of the indwelling catheter alone (1). The Infectious Diseases Society of America guidelines do not recommended treatment of asymptomatic candiduria unless the patient belongs to a group at high risk of dissemination, such as severely immunosuppressed or neutropenic patients, infants with low birth weight, and patients who will undergo urologic manipulation (2).  Supporting such recommendation is a retrospective long-term follow-up of patients with candiduria demonstrating no significant improvement in rates of recurrences of candiduria or candidemia with treatment (3).  Fluconazole is usually considered the first-line agent of choice when treatment is indicated.  

1. Kauffman CA. Candiduria. Clin Infect Dis 2005;41:S371-6.

2. Pappas PG, Kauffman CA, Andes D, et al. Clinical Practice Guidelines for the Management of Candidiasis: 2009 Update by the Infectious Diseases Society of America. Clin Infect Dis 2009; 48:503–35.

3. Revankar SG, Hasan MS, Revankar VS, et al. Long-term follow-up of patients with candiduria. Eur J Clin Microbiol Infect Dis 2011;30:137-140.

Should we treat asymptomatic candiduria?

Should we routinely use broad spectrum empiric antibiotic therapy in our diabetic patients with cellulitis of the lower extremities?

The short answer is “No”!

The myth that diabetics with acute bacterial skin and skin structure infections should be routinely placed on antibiotics against gram-positives as well as gram-negatives and/or anaerobes probably originates from the extrapolation of data revolving around the frequent polymicrobial nature of diabetic foot infections.  These infections often originate from chronic ulcers and are complicated by deep tissue infection or gangrene (1), which is often not the case in our diabetic patients with cellulitis alone.  

In a recent study of the microbiology of cellulitis or cutaneous abscess in hospitalized patients, Staphylococcus and Streptococcus sp. accounted for 90% of cultured organisms in  diabetic patients, not significantly different than that of non-diabetics (1).

These finding support national guidelines which do not recommend routine use of broader spectrum antibiotics in diabetics with cellulitis or cutaneous abscess (2).  

References

1. Jenkins TC, Knepper BC, Moore SJ, et al. Comparison of the microbiology and antibiotic treatment among diabetic and nondiabetic patients hospitalized for cellulitis or cutaneous abscess. J Hosp Med 2014;9:788-794. https://www.ncbi.nlm.nih.gov/pubmed/25266293

2. Stevens DL, Bisno AL, Chambers HF, et al. Practice guidelines for the diagnosis and management of skin and soft tissue infections. Clin Infect Dis 2014;59:e10-e52. https://www.ncbi.nlm.nih.gov/pubmed/24973422

Should we routinely use broad spectrum empiric antibiotic therapy in our diabetic patients with cellulitis of the lower extremities?