Should my patient with below-knee venous thrombosis receive anticoagulation?

In contrast to proximal lower extremity deep venous thrombosis for which anticoagulation (AC) is standard therapy, whether below-knee deep venous thrombosis (BKDVT) (eg,  involving peroneal, soleus, tibial, or gastrocnemius veins) should routinely receive AC is a matter of debate because of lack of solid supportive evidence. 1-3

The American College of Chest Physicians (ACCP) recommends AC for patients with BKDVT who are severely symptomatic or have risk factors for extension of the thrombus but this recommendation is based on low-quality scientific evidence (grade 2C or “weak”).3 For other patients, surveillance ultrasound is recommended in 2 weeks to exclude clot propagation more proximally, and therefore the need for AC.  Of course, decision regarding AC should be made in the context of the patient’s risk of serious bleeding.

The following facts about BKDVT may help in therapeutic decision making:1

  • Most cases resolve spontaneously without AC
  • The incidence of propagation varies from 3%-32%
  • Embolization is unlikely in the absence of extension into proximal veins

Also remember that clot propagation usually occurs within 2 weeks of initial diagnosis. That’s why surveillance ultrasound is recommended during this period when watchful waiting is preferred.

References 

  1. Fleck D, Albadawi H, Wallace A, etal. Below-knee deep vein thrombosis (DVT): diagnostic and treatment patterns. Cariovasc Diagn Ther 2017;7(Suppl3):S134-39. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5778527/
  2. Olson EJ, Zander AL, Van Gent J-M, et al. Below-knee deep vein thrombosis: An opportunity to prevent pulmonary embolism? J Trauma Acute Care Surg 2014;77:459-63. https://www.ncbi.nlm.nih.gov/pubmed/25159251
  3. Kearon C, Akl EA, Comerota AJ, et al. Antithrombotic therapy for VTE disease. Antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. CHEST 2012;141 (Suppl):e419S-e494S. https://www.ncbi.nlm.nih.gov/pubmed/22315268

 

Should my patient with below-knee venous thrombosis receive anticoagulation?

Why isn’t my patient with congestive heart failure or end-stage liver disease losing weight despite being on diuretic therapy? Is the diuretic dose too low, or is the salt intake too high?

When a patient with congestive heart failure (CHF) or end-stage liver disease (ESLD) doesn’t respond as expected to diuretic therapy, measurement of urinary sodium (Na) can be helpful.

In low effective arterial blood volume states (eg, CHF and ESLD) aldosterone secretion is high, resulting in high urine potassium (K) and low urine Na concentrations. However, in the presence of diuretics, urinary Na excretion should rise.

Patients undergoing active diuresis are often restricted to a 2 g (88 mEq) Na intake/day, with ~10 mEq excreted via non-urinary sources (primarily stool), and ~ 78 mEq excreted in the urine to “break even” — that is, to maintain the same weight.

Although historically measured 1, a 24-hour urine Na and K collection is tedious, making spot urine Na/K ratio more attractive as a potential proxy.  Approximately 90% of patients who achieve a urinary Na/K ratio ≥1 will have a urinary Na excretion ≥78 mEq/day — that is to say, they are sensitive to the diuretic and will have a stable or decreasing weight at the current dose. 2,3

Urine Na/K may be interpreted as follows:

  • ≥1 and losing weight suggests effective diuretic dose, adherent to low Na diet
  • ≥1 and rising weight suggests effective diuretic dose, non-adherent to low Na diet
  • <1 and rising weight suggests ineffective diuretic dose

The “ideal” Na/K ratio as relates to responsiveness to diuretics has ranged from 1.0 to 2.5.4 In acutely decompensated heart failure patients on spironolactone, a K-sparing diuretic, Na/K ratio >2 at day 3 of hospitalization may be associated with improved outcome at 180 days. 5

Remember also that if the patient’s clinical syndrome is not correlating well with the ratio, it’s always a good idea to proceed to a 24-hour urine collection.

 

References

  1. Runyon B. Refractory Ascites. Semin Liver Dis. Semin Liver Dis. 1993 Nov;13(4):343-51. https://www.ncbi.nlm.nih.gov/pubmed/8303315
  2. Stiehm AJ, Mendler MH, Runyon BA. Detection of diuretic-resistance or diuretic-sensitivity by spot urine Na/K ratios in 729 specimens from cirrhotics with ascites: approximately 90 percent accuracy as compared to 24-hr urine Na excretion (abstract). Hepatology 2002; 36: 222A.
  3. da Silva OM, Thiele GB, Fayad L. et al. Comparative study of spot urine Na/K ratio and 24-hour urine sodium in natriuresis evaluation of cirrhotic patients with ascites. GE J Port Gastroenterol 2014;21:15-20 https://pdfs.semanticscholar.org/4dc3/4d18d202c6fa2b30a1f6563baab80d877921.pdf
  4. El-Bokl M, Senousy, B, El-Karmouty K, Mohammed I, Mohammed S, Shabana S, Shelby H. Spot urinary sodium for assessing dietary sodium restriction in cirrhotic ascites. World J Gastroenterol 2009; 15:3631. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2721236/
  5. Ferreira JP, Girerd N, Medeiros PB, et al. Spot urine sodium excretion as prognostic marker in acutely decompensated heart failure: the spironolactone effect. Clin Res Cardiol 2016;105:489-507. https://www.ncbi.nlm.nih.gov/pubmed/26615605

 

Contributed by Alyssa Castillo, MD, with valuable input from Sawalla Guseh, MD, both from Mass General Hospital, Boston, MA.

Why isn’t my patient with congestive heart failure or end-stage liver disease losing weight despite being on diuretic therapy? Is the diuretic dose too low, or is the salt intake too high?

How much blood is needed in the GI tract to cause melena?

Melena, characterized by black tarry stools, can occur with as little as 50 cc of blood in the stomach. How do we know this? We need to go back to clinical experiments involving oral administration of citrated blood in human subjects back in 1930’s and 40’s. 1-3 One study was performed on a group of “health medical students” who drank their own blood!3

Melena suggests an upper GI bleeding source where there is more time for enzymatic breakdown to transform blood to melena. Although gastric acid may also contribute to its formation, it does not appear to be a pre-requisite to melena as blood inserted into the small bowel or cecum can also produce melenic stools if it stays there long enough. Melena is dependent primarily on the length of transit time of blood in the GI tract, such that very rapid movement of 1 liter of blood from upper GI tract may lead to bright red blood per rectum, not melena, within 4 hours.2,4

Don’t get melena confused with other causes of dark stools such as oral iron supplementation and bismuth-containing medications (eg, Peptobismol®). In addition to its tarry texture, melena also has a characteristic pungent odor.

References

  1. Schiff L, Stevens R, Shaprio N, et al. Observations on the oral administration of citrated blood in man. Am J Med Sci 1942;203:409-12.
  2. Srygley FD, Gerardo CJ, Tran T, et al. Does this patient have a severe upper gastrointestinal bleed. JAMA 2012;307:1072-79. https://jamanetwork.com/journals/jama/article-abstract/1105075?redirect=true
  3. Daniel WA, Egan S. The quantity of blood required to produce a tarry stool. JAMA 1939;113:2232.
  4. Wilson ID. Hematemesis, melena, and hematochezia. In: Walker HK, Hall WD, Hurst JW, eds. Clinical Methods: The history, physical, and laboratory examinations. 3rd edition. Boston: Butterworths:1990. Chapter 85. Available from: https://www.ncbi.nlm.nih.gov/books/NBK411/

 

Contributed in part by Brad Lander, MD, Mass General Hospital, Boston, MA.

How much blood is needed in the GI tract to cause melena?

My patient with pyelonephritis has positive blood cultures for E. coli? Should I order repeat blood cultures to make sure the bacteremia is clearing?

Although a common practice, follow-up blood cultures (FUBCs) may not be necessary in otherwise clinically stable or improving patients with aerobic gram-negative bacteremia. This is probably due to the often-transient nature of gram-negative bloodstream infections  and less propensity of these organisms to cause intravascular infections (eg, endocarditis) compared to gram-positives. 1

A 2017 study addressing the value of FUBCs in gram-negative bacteremia found that repeat positive blood cultures were uncommon with positive results not associated with mortality or higher ICU admissions. 1 Specifically, 17 FUBCs had to be drawn to yield 1 positive result.  Although the numbers of positive FUBCs were too low for in-depth analysis, it was concluded that FUBCs added little value in the management of gram-negative bacteremias.

In contrast, FUBCs are recommended in the following situations: 1-3

  • Staphylocccus aureus bacteremia given the propensity of this organism to cause intravascular (eg, endocarditis) and metastatic infections.
  • Presumed or documented endocarditis or intravascular device infections (eg, intravenous catheters and pacemakers) to document timely clearance of bacteremia
  • Infections involving organisms that may be difficult to clear such as fungemia or multi-drug resistant pathogens.

As with many things in medicine, clinical context is important before ordering tests and blood cultures are no different. The urge to order FUBCs should also be balanced with the possibility of having to deal with  contaminants. 

References

  1. Canzoneri CN, Akhavan BJ, Tosur Z et al. Follow-up blood cultures in gram-negative bacteremia: Are they needed? Clin Infect Dis 2017;65:1776-9. https://www.ncbi.nlm.nih.gov/pubmed/29020307
  2. Tabriz MS, Riederer K, Baran J, et al. Repeating blood cultures during hospital stay: Practice pattern at a teaching hospital and a proposal for guidelines. Clin Microbiol Infect 2004;10:624-27. https://onlinelibrary.wiley.com/doi/full/10.1111/j.1469-0691.2004.00893.x
  3. Mylotte JM, Tayara A. Blood cultures: Clinical aspects and controversies. Eur J Clin Microbiol Infect Dis 200;19:157-63. https://www.ncbi.nlm.nih.gov/pubmed/10795587

 

 

My patient with pyelonephritis has positive blood cultures for E. coli? Should I order repeat blood cultures to make sure the bacteremia is clearing?

Should my patient with compensated heart failure be placed on a sodium-restricted diet?

Although sodium restriction is routinely recommended for patients with heart failure (HF), the data is often conflicting with a number of studies suggesting that it may be harmful in some HF patient. 

Two randomized trials (by the same group) involving patients with compensated HF recently discharged from the hospital reported that “less restricted” sodium diet (2.8 gm/d) along with fluid restriction (1 liter/d) and high-dose furosemide (at least 125-250 mg furosemide bid) was associated with less rates of readmissions and improved levels of brain natriuretic peptide, aldosterone and plasma renin activity when compared to patients on more restricted sodium diet (1.8 gm/d).1,2

Analysis of data from the multihospital HF Adherence and Retention Trial enrolling New York Heart Association functional class II/III HF patients found that sodium restriction (<2.5 gm/d) was associated with significantly higher risk of death or HF hospitalization but only in patients not on an angiotension converting enzyme inhibitor or angiotensin receptor blocker.3

In normal subjects who are not sodium deprived, excess sodium intake has been shown to cause expansion of intravascular volume without increasing total body water.4 Thus, sodium restriction combined with diuretics may reduce intravascular volume and renal perfusion, further stimulating the renin-angiotensin-aldosterone system and fluid retention.5

Now that’s interesting! Did you know that the 2013 American College of Cardiology Foundation/American Heart Association guidelines downgraded the recommendation for sodium restriction to Class IIa (reasonable) with Level of Evidence:C? 6

 

References

  1. Paterna S, Gaspare P, Fasullo S, et al. Normal-sodium diet compared with low-sodium diet in compensated congestive heart failure: is sodium an old enemy or a new friend? Clin Sci 2008;114:221-230. https://www.ncbi.nlm.nih.gov/pubmed/17688420
  2. Paterna S, Parrinello G, Cannizzaro S, et al. Medium term effects of different dosage of diuretic, sodium, and fluid administration on neurohormonal and clinical outcome in patients with recently compensated heart failure. Am J Cardiol 2009;103:93-102. https://www.ncbi.nlm.nih.gov/pubmed/19101237
  3. Doukky R, Avery E, Mangla A, et al.Impact of dietary sodium restriction on heart failure outcomes. J Am Coll Cariol HF 2016;4:24-35. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4705447/
  4. Heer M, Baisch F, Kropp J et al. High dietary sodium chloride consumption may not induce body fluid retention in humans. Am J Physiol Renal Physiol 2000;278:F585-F595. https://www.ncbi.nlm.nih.gov/pubmed/10751219
  5. Rothberg MB, Sivalingam SK. The new heart failure diet: less salt restriction, more micronutrients. J Gen Intern Med 25;1136-7. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2955483/
  6. Yancy CW, Jessup M, Bozkurt B, et al. 2013 CCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2013;62:e147-239. https://www.ncbi.nlm.nih.gov/pubmed/23741058
Should my patient with compensated heart failure be placed on a sodium-restricted diet?

My patient just developed a fixed drug reaction from ibuprofen. What is the mechanism of this type of skin reaction?

Although its mechanism is not full elucidated, fixed drug eruption (FDE) is thought to result from the drug-induced cytotoxic activation of CD8+ memory T cells.1 ,2

In this context, the culprit medication behaves as a hapten that adheres to basal keratinocytes which in turn results in the recruitment of T cells and inflammation.  However, as the inflammation resolves, CD8+  effector-memory T cells remain in the area in question,  setting the stage for more rapid immunologic reaction when the drug is reintroduced.

Why a systemic drug triggers a reaction only at specific sites in the body is a fascinating question. Prior herpes simplex virus (HSV) infection (eg, on the lips or genitalia) may explain some cases.1 Interestingly, despite the absence of prior herpetic lesions, most patients with FDE are seropositive for HSV. Previously traumatized body sites (e.g. from burns or insect bites) may also create an immune microenvironment conducive to FDE.

The classic presentation of FDE is reappearance of a rash in the genitals, perianal areas, hands, and feet within 30 min to 8 hours of taking the culprit medication.3 Look specifically for NSAIDs, tetracyclines, sulfonamides, and aspirin on the patient’s drug list. 4

References

  1. Shiohara, T. Fixed drug eruption: Pathogenesis and diagnostic tests. Curr Opin Allergy Clin Immunol 2009; 9:316-21. https://www.ncbi.nlm.nih.gov/pubmed/19474709
  2. Butler, DF. Fixed Drug Eruptions. Medscape. http://emedicine.medscape.com/article/1336702-overview#a4. Accessed March 26, 2018.
  3. Korkij W, Soltani K. Fixed drug eruptions: A brief review. Arch Dermatol 1984;120:520. https://www.ncbi.nlm.nih.gov/pubmed/6231004
  4. Oakley, A. Fixed Drug Eruption. https://www.dermnetnz.org/topics/fixed-drug-eruption Accessed March 26, 2018.

 

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

My patient just developed a fixed drug reaction from ibuprofen. What is the mechanism of this type of skin reaction?

How accurate are peripheral thermometers for estimating body temperature in my patient with chills?

Though convenient, oral, tympanic membrane, axillary, and temporal artery thermometers (AKA “peripheral thermometers”) may not be highly accurate in measuring body temperature.

A 2015 systematic review and meta-analysis of the performance of peripheral thermometers involving 75 studies (mostly in adults) found that compared to central thermometers (eg, pulmonary artery, urinary bladder, rectal), peripheral thermometers had a low sensitivity (64%, 95% CI 55%-72%), but much better specificity (96%, 95% CI 93%-97%) for fever (most commonly defined as 37.8° C [100° F] or greater).1

In the same study, for oral electronic thermometers, sensitivity was 74% with a specificity of 86%. For temporal artery thermometers, sensitivities ranged from 26% to 91%, while specificities ranged from 67% to 100%. For tympanic membrane thermometers, sensitivities ranged from 23% to 87%, with a specificity of 57% to 99%.

A 2016 study involving adult emergency department patients reported the sensitivity of peripheral thermometers (vs rectal temperature 38 C [100.4] or higher) as follows: oral (37%), tympanic membrane (68%), and temporal artery (71%). Specificity for fever was >90% for all peripheral thermometers. 2

So, it looks like while we may be pretty comfortable with a diagnosis of “fever” when our patient with chills has a high temperature recorded by a peripheral thermometer, lack of fever alone by these devices should not veer us away from the possibility of systemic infection. When in doubt and if possible, check a rectal temperature.

References

  1. Niven DJ, Gaudet JE, Laupland KB. Accuracy of peripheral thermometers for estimating temperature: A systematic and meta-analysis. Ann Intern Med 2015;163:768-777. https://www.ncbi.nlm.nih.gov/pubmed/26571241
  2. Bijur PE, Shah PD, Esses D. Temperature measurement in the adult emergency department: oral tympanic membrane and temporal artery temperatures versus rectal temperature. Emerg Med J 2016;33:843-7. https://www.ncbi.nlm.nih.gov/pubmed/27334759

 

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How accurate are peripheral thermometers for estimating body temperature in my patient with chills?