My patient with sepsis and bacteremia has an extremely high serum Creatine kinase (CK) level. Can his infection be causing rhabdomyolysis?

 Absolutely! Although trauma, toxins, exertion, and medications are often listed as common causes of rhabdomyolysis, infectious etiologies should not be overlooked as they may account for 5% to 30% or more of rhabdomyolysis cases (1,2).

 

Rhabdomyolysis tends to be associated with a variety of infections, often severe, involving the respiratory tract, as well as urinary tract, heart and meninges, and may be caused by a long list of pathogens (1).  Among bacterial causes, Legionella sp. (“classic” pathogen associated with rhabdomyolysis), Streptococcus sp. (including S. pneumoniae), Salmonella sp, Staphylococcus aureus, Francisella tularensis have been cited frequently (3).  Some series have reported a preponderance of aerobic gram-negatives such as Klebsiella sp., Pseudomonas sp. and E. coli  (1,2).   Among viral etiologies, influenza virus, human immunodeficiency virus, and coxsackievirus are commonly cited (2,3).  Fungal and protozoal infections (eg, malaria) may also be associated with rhabdomyolysis (5).

 

So how might sepsis cause rhabdomyolysis? Several potential mechanisms have been implicated, including tissue hypoxemia due to sepsis, direct muscle invasion by pathogens (eg, S. aureus, streptococci, Salmonella sp.), toxin generation (eg, Legionella), cytokine-mediated muscle cell toxicity (eg, aerobic gram-negatives) as well as muscle ischemia due to shock (1,5).

 

Bonus Pearl: Did you know that among patients with HIV infection, infections are the most common cause (39%) of rhabdomyolysis (6)? 

 

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References

 

1. Kumar AA, Bhaskar E, Shantha GPS, et al. Rhabdomyolysis in community acquired bacterial sepsis—A retrospective cohort study. PLoS ONE 2009;e7182. Doi:10.1371/journa.pone.0007182. https://www.ncbi.nlm.nih.gov/pubmed/19787056.

2. Blanco JR, Zabaza M, Sacedo J, et al. Rhabdomyolysis of infectious and noninfectious causes. South Med J 2002;95:542-44. https://www.ncbi.nlm.nih.gov/pubmed/12005014

3. Singh U, Scheld WM. Infectious etiologies of rhabdomyolysis:three case reports and review. Clin Infect Dis 1996;22:642-9. https://www.ncbi.nlm.nih.gov/pubmed/8729203

4. Shih CC, Hii HP, Tsao CM, et al. Therapeutic effects of procainamide on endotoxin-induced rhabdomyolysis in rats. PLOS ONE 2016. Doi:10.1371/journal.pone.0150319. https://www.ncbi.nlm.nih.gov/pubmed/26918767

5. Khan FY. Rhabdomyolysis: a review of the literature. NJM 2009;67:272-83. http://www.njmonline.nl/getpdf.php?id=842

6. Koubar SH, Estrella MM, Warrier R, et al. Rhabdomyolysis in an HIV cohort: epidemiology, causes and outcomes. BMC Nephrology 2017;18:242. DOI 10.1186/s12882-017-0656-9. https://bmcnephrol.biomedcentral.com/track/pdf/10.1186/s12882-017-0656-9

My patient with sepsis and bacteremia has an extremely high serum Creatine kinase (CK) level. Can his infection be causing rhabdomyolysis?

Why is the bicuspid aortic valve of my middle age patient with endocarditis so heavily calcified?

Congenital bicuspid aortic valve (BAV) is a significant risk factor for valvular calcification, occurring about 20 years earlier than people with normal tricuspid aortic valve as they age. In fact, despite its prevalence of only 1-2% in the population, BAV may account for 50% of aortic valve stenosis (1).

 
Two potential mechanisms could account for the propensity of patients with BAV to develop valve calcification. First, genetic mutations that  account for some of the cases of BAV disease, may also be associated with valvular calcification (1). NOTCH1 mutation is one such candidate causing early developmental defect in the aortic valve, while later causing de-repression of calcium deposition (2). A mutation of the gene for endothelial nitric oxide synthase (eNOS) involved in preventing calcification in animal and tissue experiments may be another factor (3,4).

 
Besides genetic explanations, alteration in the mechanical force environments of the BAV itself likely plays an important part in the premature degeneration and calcification of the valve (1). Stenotic and skewed forward flow along with increased jet velocity may increase shear forces on the valve. The resultant inflammatory response and apoptosis could lead to a diseased valve, not unlike what may be seen with tricuspid aortic valve under similar circumstances (5). Perhaps more fascinating is the observation that fluid shear itself may influence bone morphogenetic protein expression, further contributing to valvular calcification (6).

 

Bonus Pearl: Did you know that the risk of infective endocarditis may be much higher (>20-fold) among patients with BAV compared to those with triscuspid aortic valve (7)?

 

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References
1. Yap CH, Saikrishanan N, Tamilselvan G, et al. The congenital bicuspid aortic valve can experience high-frequency unsteady shear stresses on its leaflet surface. Am J Physiol Heart Circ Physiol 2012; 303:H721-H731. doi:10.1152/ajpheart.00829.2011. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3468455/
2. Nigam V, Srivastava D. Notch 1 represses osteogenic pathways in aortic valve cells. J Mol Cell Cardiol 2009;47:828-34. https://www.ncbi.nlm.nih.gov/pubmed/19695258
3. Rajamannan NM, Subramanian M, Stock SR, et al. Atorvastatin inhibits calcification and enhances nitric oxide synthase production in the hypercholesterolaemic aortic valve disease. Heart 2005;91:806-10. https://www.ncbi.nlm.nih.gov/pubmed/15894785
4. Kennedy JA, Hua X, Mishra K, et al. Inhibition of calcifying nodule formation in cultured porcine aortic valve cells by nitric oxide donors. Eur J Pharmacol 2009;602:28-35. https://www.ncbi.nlm.nih.gov/pubmed/19056377
5. Wallby L, Janerot-Sjöberg B, Steffensen T, Broqvist M. T lymphocyte infiltration in non-rheumatic aortic stenosis: a comparative descriptive study between tricuspid and bicuspid aortic valves. Heart 88: 348–351, 2002. https://www.ncbi.nlm.nih.gov/pubmed/12231589
6. Sorescu GP, Song H, Tressel SL, et al. Bone morphogenic protein 4 produced in endothelial cells by oscillatory shear stress induces monocyte adhesion by stimulating reactive oxygen species production from a nox1-based NADPH oxidase. Circ Res 2004;84:773-79. https://www.ncbi.nlm.nih.gov/pubmed/15388638
7. Kiyota Y, Corte AD, Vieira VM, et al. Risk and outcomes of aortic valve endocarditis among patients with bicuspid and tricuspid aortic valves. Open Heart J 2017;4:e000545. Doi:10.1136/opnhrt-2016-000545. https://openheart.bmj.com/content/openhrt/4/1/openhrt-2016-000545.full.pdf

Why is the bicuspid aortic valve of my middle age patient with endocarditis so heavily calcified?

Is there a connection between trehalose, a natural sugar found in many foods, and Clostridioides difficile disease (CDD)?

There is experimental and epidemiological evidence that trehalose in the diet may enhance the virulence of the epidemic strains (eg. Ribotype 027) of C. difficile (1). 
Many of us may not be familiar with trehalose. It’s a disaccharide composed of 2 glucose molecules and found widely in nature, including bacteria, fungi (eg mushrooms, Brewer’s yeast), plants, insects, other invertebrates, but not vertebrates (2).

Since its approval by the FDA as a natural food additive in 2000, trehalose is increasingly used for its unique properties (including flavor enhancer and moisture stabilizer) in a variety of foods, including ice cream, pasta, ground beef, and sushi. Although in humans trehalose is enzymatically broken down to glucose by the brush borders of intestinal mucosa, intact trehalose is also found in the lower GI tract where C. difficile thrives.

 
In a series of intriguing experiments involving the interaction between trehulose and C. difficile published in Nature in 2018, Collins et al found that RT027 strain of C. difficile had acquired unique mechanisms to metabolize low concentrations of trehalose and that dietary trehalose increased its virulence associated with high mortality in a mouse model of infection even in the absence of antibiotic exposure. They further demonstrated that when human diet was simulated (eg, at concentrations suggested in ice cream), trehalose levels in the cecum of the mice were sufficient to induce production of the enzyme phosphotrehalase by the same strain in vitro by over 400X in the absence of antibiotics and by over 1000X in the presence of antibiotics. Similar results were found in the ileostomy fluid samples of 2 of 3 volunteers consuming normal diet (1). 

 
Equally fascinating is the epidemiological evidence that the timelines of trehalose adoption as a food additive in 2000, subsequent uptick in the number CDDs in the US, as well as the spread of RT027 strain in many countries seem to overlap (1).

 
These observations may at least partially explain the frequently severe nature of CDD during the past 2 decades as well why a significant proportion (up to a-third) of patient with CDD appear to have no recent exposure to antibiotics or hospitalization (3-5).  An epidemiological study examining the dietary habits of patients with CDD without apparent risk factors is in order. Stay tuned!

 
Bonus Pearl: Did you know that trehalose is classified as “generally regarded as safe” (GRAS)  natural food additive by the FDA and may be listed as “added sugar” or “natural flavor” on the food packaging?

 

References
1. Collins J, Robinson C, Danhof H, et al. Dietary trehalose enhances virulence of epidemic Clostridium difficile. Nature 2018;553;291-96. https://www.nature.com/articles/nature25178
2. Avonce N, Mendoza-Vargas A, Morett E, et al. Insights on the evolution of trehalose biosynthesis. BMC Evol Biol 2006;6:109. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1769515/
3. Wilcox MH, Mooney L, Bendall R, Settle CD et al. A case-control study of community-associated Clostridium difficile infection. J Antimicrob Chemother 2008;62:388-96. https://www.researchgate.net/publication/5419268_A_case-control_study_of_community-associated_Clostridium_difficile_infection
4. Severe Clostridium difficile-associated disease in populations previously at low risk. MMWR2005;54:1201-5. https://www.cdc.gov/mmwr/preview/mmwrhtml/mm5447a1.htm
5. Halvorson SAC, Cedfeldt AS, Hunter AJ. Fulminant, non-antibiotic associated Clostridium difficile colitis following Salmonella gastroenteritis. J Gen Intern Med 2010;26:95-7.

 

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Is there a connection between trehalose, a natural sugar found in many foods, and Clostridioides difficile disease (CDD)?

Is meropenem a good choice of antibiotic for treatment of my patient’s intraabdominal infection involving enterococci?

Although meropenem is a broad spectrum antibiotic that covers many gram-negative and gram-positive organisms as well as anaerobes, its activity against enterococci is generally poor and leaves much to be desired.

In a study of ampicillin-sensitive E. faecalis isolates from hospitalized patients, only 36% of isolates were considered susceptible (MIC≤4 mg/L); activity against E. faecium isolates was similarly poor.1 Several other studies have reported the suboptimal activity of meropenem against both E. faecalis and E. faecium, 2-4 with susceptibility rates as low as 8.6% depending on the MIC break point used.3

A popular textbook and a handbook on infectious diseases also do not recommend the use of meropenem for treatment of enterococcal infections. 5,6

Of interest, the package insert states that meropenem is indicated for complicated skin and soft tissue infections due to a variety of organisms, including E. faecalis (vancomycin-susceptible isolates only), but not for complicated intra-abdominal infections or meningitis due this organism.7

In our patient with intraabdominal infection,  we may consider piperacillin-tazobactam instead.  Piperacillin-tazobactam is a broad spectrum antibiotic with excellent coverage against anaerobes and ampicillin-susceptible E. faecalis.1,8  

 

References

  1. Endtz HP, van Dijk WC, Verbrugh HA, et al. Comparative in-vitro activity of meropenem against selected pathogens from hospitalized patients in the Netherlands. J Antimicrob Chemother 1997;39:149-56. https://www.ncbi.nlm.nih.gov/pubmed/9069534
  2. Pfaller MA, Jones RN. A review of the in vitro activity of meropenem and comparative antimicrobial agents tested against 30,254 aerobic and anaerobic pathogens isolated world wide. Diag Microbiol Infect Dis 1997;28:157-63. https://www.ncbi.nlm.nih.gov/pubmed/9327242
  3. Hallgren A, Abednazari H, Ekdahl C, et al. Antimicrobial susceptibility patterns of enterococci in intensive care units in Sweden evaluated by different MIC breakpoint systems. J Antimicrob Chemother 2001;48:53-62. https://www.ncbi.nlm.nih.gov/pubmed/11418512
  4. Hoban DJ, Jones RN, Yamane N, et al. In vitro activity of three carbapenem antibiotics comparative studies with biapenem (L-627), imipenem, and meropenem against aerobic pathogens isolated worldwide. Diag Microbiol Infect Dis 993;17:299-305.https://www.ncbi.nlm.nih.gov/pubmed/8112045
  5. Chambers HF. Carbapenem and monobactams. In Mandell GL et al. eds. Principles and practice of infectious diseases. 2010, pp 341-45.
  6. Cunha CB, Cunha BA. Antibiotic essentials. 2017, pp 689-91.
  7. Meropenem.http://online.lexi.com/lco/action/doc/retrieve/docid/patch_f/7253?searchUrl=%2Flco%2Faction%2Fsearch%3Fq%3Dmeropenem%26t%3Dname
  8. Perry CM, Markham A. Piperacillin/tazobactam. Drugs 1999;57:805-43. https://link.springer.com/article/10.2165%2F00003495-199957050-00017

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Is meropenem a good choice of antibiotic for treatment of my patient’s intraabdominal infection involving enterococci?

My postop patient now has fever with atelectasis on her chest X-ray one day after surgery. Does atelectasis cause fever?

Although fever and atelectasis often coexist during the early postop period, there is no evidence that atelectasis causes fever.

A 2011 systematic analysis of 8 published studies found that all but 1 study failed to find a significant association between postop fever and atelectasis.A 1988 study reported a significant association between postop fever during the first 48 h and atelectasis on day 4 postop, but not each postop day.2  Even in this study, however, fever as a predictor of atelectasis performed poorly with a sensitivity of 26%, specificity of 75% and accuracy of 43%.

In another study involving postop cardiac surgery patients, despite a fall in the incidence of fever from day 0 to day 2, the incidence of atelectasis based on serial chest X-rays actually  increased. 3

Experimental studies in dogs and cats in the 1960s also support the lack of a causative relationship between atelectasis and fever. 4,5 Although fever was observed within 12 hrs of placement of cotton plugs in the left main bronchus of these animals, almost all animals also developed pneumonia distal to the plug.  Antibiotic treatment was associated with resolution of fever but not atelectasis.

So if it’s not atelectasis, what’s the explanation for early postop fever? The great majority of postop fevers during the first 4 days postop are unlikely to be related to infections. Instead, a more plausible explanation is the inflammatory response to the tissue injury as a result of the surgery itself causing release of cytokines (eg, interleukin-1 and -6 and tumor necrosis factor) associated with fever. 6

References

  1. Mavros MN, Velmahos GC, Falagas ME. Atelectasis as a cause of postoperative fever. Where is the clinical evidence? CHEST 2011;140:418-24. https://www.ncbi.nlm.nih.gov/pubmed/21527508
  2. Roberts J, Barnes W, Pennock M, et al. Diagnostic accuracy of fever as a measure of postoperative pulmonary complications. Heart Lung 1988;17:166-70. https://www.ncbi.nlm.nih.gov/pubmed/3350683
  3. Engoren M. Lack of association between atelectasis and fever. CHEST 1995;107:81-84. https://www.ncbi.nlm.nih.gov/pubmed/7813318
  4. Lansing AM, Jamieson WG. Mechanisms of fever in pulmonary atelectasis. Arch Surg 1963;87:168-174. https://jamanetwork.com/journals/jamasurgery/fullarticle/561080
  5. Jamieson WG, Lansing AM. Bacteriological studies in pulmonary atelectasis. Arch Surg 1963;87:1062-66. https://www.ncbi.nlm.nih.gov/pubmed/14063816
  6. Narayan M, Medinilla SP. Fever in the postoperative patient. Emerg Med Clin Nam 2013;31:1045-58. https://www.ncbi.nlm.nih.gov/pubmed/24176478 

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My postop patient now has fever with atelectasis on her chest X-ray one day after surgery. Does atelectasis cause fever?

My patient with brain tumor suffered a myocardial infarction (MI) just before having a diagnostic brain surgery. Could the tumor have placed him at higher risk of a coronary event?

Yes! Arterial thromboembolism—just as venous thromboembolism— is more common in patients with cancer.

In a large 2017 epidemiologic study involving patients 66 years of age or older, the 6-month cumulative incidence of MI was nearly 3-fold higher in newly-diagnosed cancer patients compared to controls, with the excess risk resolving by 1 year. 1 These findings were similar to a previous report involving patients with newly-diagnosed cancer, although in that study the overall coronary heart disease risk remained slightly elevated even after 10 years. 2

In addition, the incidence of coronary events and unstable ischemic heart disease during the 2 year period prior to the diagnosis of cancer is 2-fold higher among cancer patients suggesting that ischemic heart disease may be precipitated by occult cancer. 3

The association of cancer and thromboembolic coronary events may be explained through several mechanisms, including development of a prothrombotic or hypercoagulable state through acute phase reactants, abnormal fibrinolytic activity and increased activation of platelets which are also significantly involved in the pathophysiology of acute coronary syndrome (ACS). 4 Coronary artery embolism from cancer-related marantic endocarditis may also occur.5

More specific to our case, primary brain tumors may be associated with a hypercoagulable state through expression of potent procoagulants such as tissue factor and tissue factor containing microparticles, with a subset producing carbon monoxide, another procoagulant. 6

So our patient’s MI prior to his surgery for brain tumor diagnosis might have been more than a pure coincidence!

Bonus Pearl: Did you know that cancer-related prothrombotic state, also known as  “Trousseau’s syndrome” was first described in 1865 by Armand Trousseau, a French physician who diagnosed the same in himself and died of gastric cancer with thrombotic complications just 2 years later? 7,8

References

  1. Navi BB, Reinder AS, Kamel H, et al. Risk of arterial thromboembolism in patients with cancer. JACC 2017;70:926-38. https://www.ncbi.nlm.nih.gov/pubmed/28818202
  2. Zoller B, Ji Jianguang, Sundquist J, et al. Risk of coronary heart disease in patients with cancer: A nationwide follow-up study from Sweden. Eur J Cancer 2012;48:121-128. https://www.ncbi.nlm.nih.gov/pubmed/22023886
  3. Naschitz JE, Yeshurun D, Abrahamson J, et al. Ischemic heart disease precipitated by occult cancer. Cancer 1992;69:2712-20. https://www.ncbi.nlm.nih.gov/pubmed/1571902
  4. Lee EC, Cameron SJ. Cancer and thrombotic risk: the platelet paradigm. Frontiers in Cardiovascular Medicine 2017;4:1-6. https://www.ncbi.nlm.nih.gov/pubmed/29164134
  5. Lee V, Gilbert JD, Byard RW. Marantic endocarditis-A not so benign entity. Journal of Forensic and Legal Medicine 2012;19:312-15. https://www.ncbi.nlm.nih.gov/pubmed/22847046
  6. Nielsen VG, Lemole GM, Matika RW, et al. Brain tumors enhance plasmatic coagulation: the role of hemeoxygenase-1. Anesth Analg 2014;118919-24. https://www.ncbi.nlm.nih.gov/pubmed/24413553
  7. Thalin C, Blomgren B, Mobarrez F, et al. Trousseau’s syndrome, a previously unrecognized condition in acute ischemic stroke associated with myocardial injury. Journal of Investigative Medicine High Impact Case Reports.2014. DOI:10.1177/2324709614539283. https://www.ncbi.nlm.nih.gov/pubmed/26425612
  8. Samuels MA, King MA, Balis U. CPC, Case 31-2002. N Engl J Med 2002;347:1187-94. https://www.nejm.org/doi/pdf/10.1056/NEJMcpc020117?articleTools=true

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My patient with brain tumor suffered a myocardial infarction (MI) just before having a diagnostic brain surgery. Could the tumor have placed him at higher risk of a coronary event?

My middle-aged patient with a history of mediastinal irradiation for Hodgkin’s lymphoma in his 20s now has moderate aortic regurgitation. Could his valvular disease be related to the radiation he received over 20 years ago?

Absolutely! Mediastinal irradiation is associated with several cardiac complications, including coronary artery disease, pericarditis, systolic or diastolic dysfunction and valvular disease. Valvular disease may occur in 2-37% of patients after mediastinal irradiation, is dose-dependent, and generally does not manifest until 10-20 years after the radiation exposure.1 Since mediastinal irradiation is common in young adults diagnosed with Hodgkin’s lymphoma, these complications may be seen in early middle-age or later.

Valvular retraction is usually the first radiation-induced valvular change, and most commonly leads to mitral and aortic valve regurgitation.2 This retraction tends to occur within 10 years of the radiation therapy, followed by fibrosis and calcification of the valves after 20 years.

Although the pathophysiology of radiation-induced valvular disease is not entirely understood, activation of fibrogenic growth factors (eg, tissue growth factor β1 and myofibroblasts) which promote the synthesis of collagen has been postulated.1 Additionally, irradiation of aortic interstitial cells has been shown to cause transformation to an osteogenic phenotype that produces bone morphogenic protein 2, osteopontin and alkaline phosphatase, all important factors in bone formation and possibly valvular calcification.3

Since radiation-induced heart disease is the most common cause of non-malignant morbidity and mortality in patients who have undergone mediastinal irradiation, some have recommended screening of asymptomatic patients for valvular disease every 5 years by echocardiography beginning 10 years after radiation therapy. 2  If an abnormality is found, the screening frequency should increase to every 2-3  years,  if the valvular abnormality is mild, or annually if the abnormality is moderate. For severe valvular abnormalities, the patients should be considered for valve replacement.

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References

    1. Gujral DM, Lloyd G, Bhattacharyya S. Radiation-induced valvular heart disease. Heart 2016;102:269–276. https://heart.bmj.com/content/heartjnl/102/4/269.full.pdf
    2. Cuomo JR, Sharma GK, Conger PD, Weintraub NL. Novel concepts in radiation-induced cardiovascular disease. World J Cardiol. 2016; 8 (9):504-519. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5039353/
    3. Nadlonek NA, Weyant MJ, Yu JA, et al. Radiation induces osteogenesis in human aortic valve interstitial cells. J Thorac Cardiovasc Surg 2012;144:1466–70. doi:10.1016/j.jtcvs.2012.08.041 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3665422/

Contributed by Rachel Wallwork, MD, Mass General Hospital, Boston, MA

 

My middle-aged patient with a history of mediastinal irradiation for Hodgkin’s lymphoma in his 20s now has moderate aortic regurgitation. Could his valvular disease be related to the radiation he received over 20 years ago?

Of the commonly used drugs for benign prostatic hypertrophy (BPH), which ones may be the least likely to cause hypotension in my hospitalized patient with borderline systolic blood pressures?

5-alpha-reductase inhibitors (RIs) (eg, finasteride and dutasteride) are less likely to cause hypotension than alpha-1-adrenergic antagonists (AAs) (eg, tamsulosin, doxazocin, terazocin, and alfuzocin), the other major class of drugs commonly used for treatment of signs and symptoms of benign prostatic hypertrophy (BPH).

A Cochrane systematic review found that finasteride, an RI, has a lower risk of postural hypotension compared to doxazosin, an AA. 1 In fact, there’s no solid evidence that RIs exacerbate hypotension on their own. 2,3 Unfortunately, RIs take longer to achieve benefit because they work by reducing prostate size over time, while AAs work much faster by reducing prostate smooth muscle tone.4 So, while it’s reasonable to choose an RI over an AA in our patient with soft pressures, it’s also reasonable to expect it won’t work quite as well during his hospital stay and you may still be forced to choose an AA.  

Among AAs, tamsulosin is the least likely to be associated with hypotension when compared to others in the same class (eg, doxazocin and terazocin) which are also sometimes used for treatment of hypertension. Thus, tamsulosin may be the best choice for patients at risk of  hypotension.5 However, even tamsulosin is not totally safe in this regard, especially in the first 4 weeks after starting or re-starting treatment when its risk of hospital admission for hypotension is about double that of RIs.6

Bonus pearl: Did you know that prazocin was the first promising selective AA investigated for BPH but likely because of its availability in generic form and the general notion at the time that medical therapy of BPH would not be widely accepted by urologists, larger randomized-controlled trials were never pursued!7

References

  1. Tacklind J, Fink HA, MacDonald R, et al. Finasteride for benign prostatic hyperplasia. Cochrane Database of Systematic Reviews, 2010 Oct 6. https://www.ncbi.nlm.nih.gov/pubmed/20927745
  2. Finasteride prescribing information: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/020180s037lbl.pdf
  3. Dutasteride prescribing information: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/021319s014lbl.pdf
  4. Rigatti P, Brausi M, Scarpa RM, et al. A comparison of the efficacy and tolerability of tamsulosin and finasteride in patients with lower urinary tract symptoms suggestive of benign prostatic hyperplasia. Prostate Cancer and Prostatic Diseases 2003; 6:315–323. https://www.ncbi.nlm.nih.gov/pubmed/14663474
  5. Tewari A and Narayan P. Alpha-adrenergic blocking drugs in the management of benign prostatic hyperplasia: interactions with antihypertensive therapy. Urology 1999 Mar;53:14-20. https://www.ncbi.nlm.nih.gov/pubmed/10094096
  6. Bird ST, Delaney JAC, Brophy JM, et al. Tamsulosin treatment for benign prostatic hyperplasia and risk of severe hypotension in men aged 40-85 years in the United States: risk window analyses using between and within patient methodology. BMJ 2013; 347 :f6320. https://www.ncbi.nlm.nih.gov/pubmed/24192967
  7. Lepor H. Alpha blockers for the treatment of benign prostatic hyperplasia. Rev Urol 2007;9:181-90.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2213889/

Contributed by Nick Bodnar, Harvard medical student, Boston, MA.

 

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Of the commonly used drugs for benign prostatic hypertrophy (BPH), which ones may be the least likely to cause hypotension in my hospitalized patient with borderline systolic blood pressures?

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 

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Why was the myocardial infarction in my postop patient silent?