In my critically ill patient with infection, is capillary refill time greater than 2 seconds indicative of septic shock?

The data on the performance of capillary refill time (CRT) in adults is quite limited and what’s available does not suggest that the commonly cited 2 seconds cutoff is useful in assessing peripheral perfusion in critically ill adults1,2.

For example, a large study involving 1000 healthy adults reported that 45% of participants had a CRT > 2 seconds3.  Age also affects CRT with its 95 percentile upper limits reaching 4.5 seconds among healthy adults >60 y old3

Among patients with septic shock, a baseline median CRT of 5 seconds has been reported.  Values <5.0 seconds within 6 hours of treatment of septic shock has also been highly associated with successful resuscitation even before normalization of lactate levels4.

For these reasons, if CRT is used as a measure of peripheral perfusion in critically ill adults, a cut off of 5 seconds, not 2 seconds, may be more appropriate. But just like many other diagnostic tests, CRT should never be interpreted in isolation from other clinical parameters. 

References

  1. Lima A, Bakker J. Clinical Assessment of peripheral circulation. Critical Care 2015:21: 226-31. https://www.ncbi.nlm.nih.gov/pubmed/25827585  
  2. Lewin J, Maconochie I. Capillary refill time in adults. Emerg Med J 2008;25:325-6. https://www.ncbi.nlm.nih.gov/pubmed/18499809
  3. Anderson B, Kelly AM, Kerr D, et al. Impact of patient and environmental factors on capillary refill time in adults. Am J Emerg Med 2008;26:62-65. https://www.ncbi.nlm.nih.gov/pubmed/18082783
  4. Hernandez G, Pedreros C, Veas E, et al. Evolution of peripheral vs metabolic perfusion parameters during septic shock resuscitation. A clinical-physiologic study. J Crit Care 2012;27:283-288.  https://www.ncbi.nlm.nih.gov/pubmed/21798706
In my critically ill patient with infection, is capillary refill time greater than 2 seconds indicative of septic shock?

Do most patients with mycotic aneurysms have endocarditis?

No! In fact, the great majority of patients who develop mycotic aneurysm (MAs) in the postantibiotic era have no evidence of endocarditis1-3.

MAs are thought to be related to microbial arteritis due to blood stream infection of any source with implantation of circulating pathogen (usually bacterial) in atherosclerotic, diseased, or traumatized aortic intima. Plus, MAs may develop due to an adjacent infectious process (eg, vertebral osteomyelitis), either through direct extension or via lymphatic vessels, pathogen seeding of vasa vasorum, or infection of a pre-existing aneurysm1,2.  All these factors may occur in the absence of endocarditis.

Many of your patients may be at risk of MA such as those with advanced age or history of diagnostic or therapeutic arterial catheterization, illicit intravascular drug use, hemodialysis and depressed host immunity1-3..  Staphylococcus aureus, Salmonella sp, S. epidermidis and Streptococcus sp are common culprits in descending order1-3.

So think of MA in your patient with recent blood stream infection,  particularly due to S. aureus or Salmonella sp, in the setting of persistent signs of infection  with or without evidence of endocarditis.

Final Fun Fact: Did you know that the term “mycotic aneurysm” is a misnomer, having been first introduced by Sir William Osler to describe aneurysms of the aortic arch in a patient with (you guessed it) bacterial not fungal endocarditis?

References:

  1. Gomes MN, Choyke PL, Wallace RB. Infected aortic aneurysms: A changing entity. Ann Surg 1992;215:435-42. https://www.ncbi.nlm.nih.gov/pubmed/1616380
  2. Muller BT, Wegener OR, Grabitz K, et al. Mycotic aneurysms of the thoracic and abdominal aorta and iliac arteries: Experience with anatomic and extra-anatomic repair in 33 cases. J Vasc Surg 2001;33:106-13. https://www.ncbi.nlm.nih.gov/pubmed/11137930
  3. Mukherjee JT, Nautiyal A, Labib SB. Mycotic aneurysms of the ascending aorta. Tex Heart Inst J 2012;39:692-5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3461658/
Do most patients with mycotic aneurysms have endocarditis?

Should male patients with suspected urinary tract infection routinely undergo a prostate exam?

Yes! That’s because any urinary tract infection (UTI) in men has the potential for prostatic involvement1 —-as high as 83% by one report2.  

To make the matters more confusing, patients with acute bacterial prostatitis (ABP) often present with symptoms just like those of UTI such as urinary frequency, dysuria, malaise, fever, and myalgias3.  In the elderly, atypical presentation is not uncommon (eg, confusion, incontinence, fall)4.  Under these circumstances, bacteriuria and pyuria may also be related to ABP and the prostate exam should be an important part of your evaluation.

Although the sensitivity of prostate tenderness on digital rectal exam varies widely for ABP (9%-100%), a painful exam should raise suspicion for ABP, and by itself may be an independent predictor for clinical and bacteriologic failure of therapy1. Along with tenderness, fluctuance of prostate, particularly in the setting of voiding difficulties and longer duration of symptoms, may also suggest the presence of prostatic abscess5,6

But be gentle when performing a prostate exam and don’t massage it because you could potentially cause bacteremia and worsening of sepsis!1,7

References

  1. Etienne M, Chavanet P, Sibert L, et al. Acute bacterial prostatitis: heterogeneity in diagnostic criteria and management. Retrospective multicentric analysis of 371 patients diagnosed with acute prostatitis. BMC Infectious Diseases 2008;8:12. https://bmcinfectdis.biomedcentral.com/track/pdf/10.1186/1471-2334-8-12?site=bmcinfectdis.biomedcentral.com
  2. Ulleryd P, Zackrisson B, Aus G, et al. Prostatic involvement in men with febrile urinary tract infection as measured by serum prostate-specific antigen and transrectal ultrasonography. BJU Int 1999;84:470-4. http://onlinelibrary.wiley.com/doi/10.1046/j.1464-410x.1999.00164.x/pdf
  3. Krieger JN, Nyberg L, Nickel JC. NIH consensus definition and classification. JAMA 1999;282:236-37. http://jamanetwork.com/journals/jama/article-abstract/1030245
  4. Harper M, Fowlis. Management of urinary tract infections in men. Trends in Urology Gynaecology & Sexual Health. January/February 2007. http://onlinelibrary.wiley.com/doi/10.1002/tre.8/pdf
  5. Lee DS, Choe HS, Kim HY, et al. Acute bacterial prostatitis and abscess formation. BMC Urology 2016;16:38. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4936164/
  6. Oliveira P, Andrade JA, Porto HC, et al. Diagnosis and treatment of prostatic abscess. International Braz J Urol 2003;29: 30-34. http://www.scielo.br/pdf/ibju/v29n1/v29n1a06.pdf
  7. Lipsky BA, Byren I, Hoey CT. Treatment of bacterial prostatitis. Clin Infect Dis 2010; 50:1641-52. https://oup.silverchair-cdn.com/oup/backfile/Content_public/Journal/cid/50/12/10.1086/652861/2/50-12-1641.pdf?Expires=1501276981&Signature=X5SLG2Pq5IpbsjDigES70~Nk6g5onrPwhrFClIAFIvdFiEyCsc1~2aWN9LpR~56DlGqxjmZuIX33JtOn-tURGG0puEwnulZDEDXFjFt6fXucSgtKMDOmGXSKoMvgtPZe86nduJMNDuaifEZXITpDXjSLXAJXVamJ-bbSUMEqSysnCCMxZx~5MaAb6WEikqG5Vi~Xnp58fXABG7BJS~ZFRn2~BTlVEEvmIIDDaY5cJjgUcN7SNOhs0rOS71WzlNtlXSqnXffZEdFSJ~iDcbyRL-wh-9OZqZ2fwojdk8Be89DsKJg8rIh8dlLc5O7v92yL~cZ6iieiP8xTGOU-21tVeA__&Key-Pair-Id=APKAIUCZBIA4LVPAVW3Q
Should male patients with suspected urinary tract infection routinely undergo a prostate exam?

Why are patients with cirrhosis and upper gastrointestinal bleed routinely treated with antibiotics?

Cirrhotic patients with upper gastrointestinal bleed (UGIB) are at high risk of bacterial infections: 22% during the first 48 h after admission, 35-66% within 2 weeks of initial bleeding1. Antibiotic prophylaxis has been shown to reduce short term mortality, bacterial infections, early rebleeding and volume of blood transfused1-4.

But what is the exact connection between UGIB and bacterial infections in cirrhosis? One hypothesis is that UGIB sets up the host for bacterial infection via translocation (eg, due to hypovolemia), procedures necessary in the management of bleeding (eg endoscopy, sclerotherapy, IV access), and aspiration pneumonia. More intriguing is the reverse hypothesis—that is the bacterial infection serves as a trigger for UGIB.  Several lines of evidence support this view1,2.

  • Cirrhotic patients admitted for non-UGIB-related conditions may be 4x more likely to develop UGIB during their hospitalization in the presence of bacterial infection on admission4
  • Infections predispose to early variceal rebleeding
  • Infection/endotoxemia increase portal pressure, and impair liver function and coagulation
  • Commonly cited risk factors for variceal bleeding (eg, hepatic venous pressure gradient, liver function, size of varices) do not readily explain why bleeding occurs unpredictably and why despite daily increases in portal pressure (eg, following daily meals and exercises), UGIB is relatively infrequent.

 

References

  1. Thalheimer U, Triantos CK, Samonakis DN, et al. Infection, coagulation, and variceal bleeding in cirrhosis. Gut 2005;54:556-63. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1774431
  2. Goulis J. Bacterial infection in the pathogenesis of variceal bleeding. Is there any role for antibiotic prophylaxis in the cirrhotic patient. Ann Gastroenterol 2001;14:205-11. http://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=4&ved=0ahUKEwjNh-rhlpLVAhXGdD4KHSurANcQFgg4MAM&url=http%3A%2F%2Fwww.annalsgastro.gr%2Findex.php%2Fannalsgastro%2Farticle%2Fdownload%2F80%2F71&usg=AFQjCNHJfAyYAjuNXpwsWGrVuyuxxgJYKg
  3. Soares-Weiser K, Brezis, Tur-Kaspa R, et al. Antibiotic prophylaxis of bacterial infections in cirrhotic inpatients: a meta-analysis of randomized controlled trials. Scand J Gastroenterol 2003;38:193-200. http://www.tandfonline.com/doi/abs/10.1080/00365520310000690
  4. Anastasioua J, Williams R. When to use antibiotics in the cirrhotic patient? The evidence base. Ann Gastroenterol. 2013; 26(2): 128–131. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3959942
  5. Benavides J, Fernandez N, Colombato L, et al. Further evidence linking bacterial infection and upper G.I. bleeding in cirrhosis. Results from a large multicentric prospective survey in Argentina. J Hepatol 2003;38 (suppl 2):A176. http://www.journal-of-hepatology.eu/article/S0168-8278(03)80592-5/abstract
Why are patients with cirrhosis and upper gastrointestinal bleed routinely treated with antibiotics?

How well does procalcitonin distinguish bacterial from viral causes of community-acquired pneumonia in hospitalized patients?

Not extremely well! Although a recent multicenter prospective study in adult hospitalized patients reported that the median procalcitonin (PCT) concentration was significantly lower for community-acquired pneumonia (CAP) caused by viral pathogens ( 0.09 u/ml vs atypical bacteria [0.2 ug/ml] and typical bacteria [2.5 ug/ml]),  PCT was <0.1 ug/ml and <0.25 ug/ml  in 12.4% and 23.1% of typical bacterial cases, respectively1

This means that we could potentially miss about a quarter of CAP cases due to typical bacterial causes if we use the <0.25 ug/ml threshold (<0.20 is ug/ml has been used to exclude sepsis2). For these reasons and based on the results from another study3, no threshold for PCT can reliably distinguish bacterial from viral etiologies of CAP4.  Clinical context is essential in interpreting PCT levels! Also go to a related pearl on this site5.

Can PCT distinguish Legionella from other atypical bacterial causes of CAP (eg, caused by Mycoplasma or Chlamydophila)? The answer is “maybe”! Legionella was associated with higher PCT levels compared to  Mycoplasma and Chlamydophila in one study1, but not in another3.

References

  1. Self WH, Balk RA, Grijalva CG, et al. Procalcitonin as a marker of etiology in adults hospitalized with community-acquired pneumonia. Clin Infect Dis 2017;65:183-90. https://www.ncbi.nlm.nih.gov/pubmed/28407054
  2. Meisner M. Update on procalcitonin measurements. Ann Lab Med 2014;34:263-73.
  3. Krüger S, Ewig S, Papassotiriou J, et al. Inflammatory parameters predict etiologic patterns but do not allow for individual prediction of etiology in patients with CAP-Results from the German competence network CAPNETZ. Resp Res 2009;10:65. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2714042/pdf/1465-9921-10-65.pdf
  4. Bergin SP, Tsalik EL. Procalcitonin: the right answer but to which question? Clin Infect Dis 2017; 65:191-93. https://academic.oup.com/cid/article-abstract/65/2/191/3605416/Procalcitonin-The-Right-Answer-but-to-Which?redirectedFrom=fulltext
  5. https://pearls4peers.com/2017/07/01/should-i-order-serum-procalcitonin-on-my-patient-with-suspected-infection
How well does procalcitonin distinguish bacterial from viral causes of community-acquired pneumonia in hospitalized patients?

Should I order serum procalcitonin on my patient with suspected infection?

 

Two things to ask before you order procalcitonin (PCT): 1. Will it impact patient management?; and 2. If so, will the result be available in a timely manner ie, within hours not days?

Whatever the result, PCT should always be interpreted in the context of the patient’s illness and other objective data. Not surprisingly then, as a “screening” test, PCT may be more useful in patients with low pre-test likelihood of having bacterial infection, not dissimilar to the use of D-dimer in patients with low pre-test probability of pulmonary embolism1.  

Several potential clinical uses of this biomarker have emerged in recent years,  including:1,2

  1. Helping decide when to initiate antibiotics in patients with upper acute respiratory tract infections and bronchitis. A normal or low PCT supports viral infection.
  2. Helping decide when to discontinue antibiotics (ie, when PCT normalizes) in community-acquired or ventilator-associated pneumonia.
  3. Helping monitor patient progress with an expected drop in PCT of about 50% per day (half-life ~ 24 hrs) with effective therapy.

Few caveats…

PCT may be unremarkable in about a third of patients with bacteremia (particularly caused by less virulent bacteria, including many gram-positives)3.  

PCT levels are lowered by high-flux membrane hemodialysis, so check a baseline level before, not after, hemodialysis4.

Lastly, despite its higher specificity for bacterial infections compared to other biomarkers such as C-reactive protein, PCT may be elevated in a variety of non-infectious conditions, including pancreatitis, burns, pulmonary edema or aspiration, mesenteric infarction (ischemic bowel), cardiogenic shock, and hypotension during surgery2.

 

References:

  1. Schuetz P, Muller B, Chirst-Crain M, et al. Procalcitonin to initiate or discontinue antibiotics in acute respiratory tract infections (review). Evid-Based Child Health (A Cochrane Review Journal) 2013;8:4;1297-137. http://onlinelibrary.wiley.com/doi/10.1002/ebch.1927/pdf
  2. Gilbert GN. Use of plasma procalcitonin levels as an adjunct to clinical microbiology. J Clin Microbiol 2010;48:2325-29. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2897488/pdf/0655-10.pdf
  3. Yan ST, Sun LC, Jia HB. Procalcitonin levels in bloodstream infections caused by different sources and species of bacteria. Am J Emerg Med 2017;35:779-83. https://www.ncbi.nlm.nih.gov/m/pubmed/27979420/#fft
  4. Grace E, Turner RM. Use of procalcitonin in patients with various degrees of chronic kidney disease including renal replacement therapy. Clin Infect Dis 2014;59:1761-7. https://www.ncbi.nlm.nih.gov/pubmed/25228701
Should I order serum procalcitonin on my patient with suspected infection?

What is the mechanism of anemia of chronic disease in my patient with rheumatoid arthritis?

Anemia of chronic disease (ACD)—or more aptly “anemia of inflammation”— is the second most common cause of anemia after iron deficiency and is associated with numerous acute or chronic conditions (eg, infection, cancer, autoimmune diseases, chronic organ rejection, and chronic kidney disease)1.

The hallmark of ACD is disturbances in iron homeostasis which result in increased uptake and retention of iron within cells of the reticuloendothelial system, with its attendant diversion of iron from the circulation and reduced availability for erythropoiesis1. More specifically, pathogens, cancer cells, or even the body’s own immune system stimulate CD3+ T cells and macrophages to produce a variety of cytokines, (eg, interferon-ɤ, TNF-α, IL-1, IL-6, and IL-10) which in turn increase iron storage within macrophages through induction of expression of ferritin, transferrin and divalent metal transporter 1.

In addition to increased macrophage storage of iron, ACD is also associated with IL-6-induced synthesis of hepcidin, a peptide secreted by the liver that decreases iron absorption from the duodenum and its release from macrophages2. TNF-α and interferon-ɤ also contribute to ACD by inhibiting the production of erythropoietin by the kidney.  Finally, the life span of RBCs is adversely impacted in AKD due to their reduced deformability and increased adherence to the endothelium in inflammatory states3.

Of interest, it is often postulated that by limiting access to iron through inflammation, the body hinders the growth of pathogens by depriving them of this important mineral2.

 

References

  1. Weiss, G and Goodnough, L. Anemia of chronic disease. N Engl J Med 2005; 352; 1011-23. http://www.med.unc.edu/medclerk/medselect/files/anemia2.pdf
  2. D’Angelo, G. Role of hepcidin in the pathophysiology and diagnosis of anemia. Blood Res 2013; 48(1): 10-15. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3624997/pdf/br-48-10.pdf                                                                                                                                  
  3. Straat M, van Bruggen R, de Korte D, et al. Red blood cell clearance in inflammation. Transfus Med Hemother 2012;39:353-60. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3678279/pdf/tmh-0039-0353.pdf

 

Contributed by Amir Hossein Ameri, Medical Student, Harvard Medical School

                     

What is the mechanism of anemia of chronic disease in my patient with rheumatoid arthritis?