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?

What is the significance of hyponatremia in my patient with acute decompensated congestive heart failure (ADCHF)?

Hyponatremia, defined as a serum sodium <135 meq/L, is observed in ~20% of patients hospitalized with ADCHF, and is often dilutional, not “depletional” (ie, not associated with hypovolemia) in this condition1. In ADCHF, hyponatremia is primarily caused by the production of arginine vasopressin (AVP) (also known as anti-diuretic hormone, or ADH) as a result of decreased perfusion pressures in the aortic arch and renal afferent arterioles, and increased thirst due to the activation of the renin-angiotensin system.  Hyponatremia correlates with the severity of ADCHF and adverse clinical outcomes2.   

 A common approach to dilutional hyponatremia in ADCHF is fluid restriction. Other potential therapies include angiotension converting enzyme inhibitors (by increasing cardiac output and decreasing thirst), loop diuretics (by reducing water reabsorption in the renal distal tubule), and AVP antagonists (eg, tolvapatan, satavaptan)1,3.  Otherwise, in the absence of symptoms, no specific therapy is generally indicated for serum sodium levels ≥ 120mEq/L.

 

References 

  1. Verbrugge FH, Steels P, Grieten L, Nijst P, Tang WHW, Mullens W. Hyponatremia in acute decompensated heart failure: Depletion versus dilution. J Am Coll Cardiol 2015;65:480-92.
  2. Leier CV, Dei Cas L, Metra M. Clinical relevance and management of the major electrolyte abnormalities in congestive heart failure: hyponatremia, hypokalemia, and hypomagnesemia. Am Heart J. 1994;128:564. 
  3. Schrier RW, Gross P, Gheorghiade M, Berl T, Verbalis JG, Czerwiec FS, Orlandi C, SALT Investigators. Tolvaptan, a selective oral vasopressin V2-receptor antagonist, for hyponatremia. N Engl J Med. 2006;355:2099. 

 

Contributed by Ricardo Ortiz, Medical Student, Harvard Medical School

What is the significance of hyponatremia in my patient with acute decompensated congestive heart failure (ADCHF)?

My patient with chronic lymphocytic leukemia (CLL) and normal renal function has mysteriously developed a persistently severe hyperkalemia with a normal EKG without an apparent cause. What could I be missing?

Although the causes of hyperkalemia are legion, normal renal function and lack of compatible EKG findings may be a clue to pseudohyperkalemia (PH), which is commonly defined as a difference between serum and plasma [K+] > 0.4 mEq/L when the samples are obtained concurrently, remain at room temperature and are tested within an hour of collection1; plasma is obtained in heparinized tubes which prevent platelet aggregation, degranulation and Krelease. In the absence of visible hemolysis, PH may be related to the lysis of high number of WBCs (particularly when fragile as seen in CLL) or platelets. 

Early recognition of PH is important to avoid inappropriate treatment that may result in serious hypokalemia. Several factors in the technique by which blood is collected and processed may lead to PH, including prolonged tourniquet use, fist clenching, inappropriate needle diameter, excessive force with syringe draw, vacuum tubes, and inappropriate temperature or delayed processing of the specimen.

When PH is suspected, concurrent K+ measurement by conventional phlebotomy and by a blood gas specimen or a venous specimen by gentle aspiration via a butterfly needle into a non-vacuum tube is  recommended2.

 

References

  1. Avelar T. Reverse pseudohyperkalemia in a patient with chronic lymphocytic leukemia. Perm J 2014;18:e150-e152.
  2. Chan JS, Baker SL, Bernard AW. Pseudohyperkalemia without reported hemolysis in a patient with chronic lymphocytic leukaemia. BMJ Case Reports 2012;doi:10.1136/bcr.12.2011.5330
My patient with chronic lymphocytic leukemia (CLL) and normal renal function has mysteriously developed a persistently severe hyperkalemia with a normal EKG without an apparent cause. What could I be missing?

My hospitalized patient has developed hyperkalemia while on heparin prophylaxis. Can heparin really cause hyperkalemia and what is its mechanism?

Heparin is one of the most overlooked causes of hyperkalemia in hospitalized patients, occurring in 5-8% of treated patients, including those on thromboprophylaxis1.

The mechanism of heparin-induced hyperkalemia appears to be through suppression of aldosterone synthesis by inhibiting the function of the glomerulosa zone of the adrenal medulla2,3.  Such inhibitory action is usually of no consequence when renal function is normal and potassium excretion is not otherwise impaired.

The risk of heparin-induced hyperkalemia is increased in the elderly, those with preexisting diabetes mellitus or renal insufficiency, as well patients on concomitant use of certain drugs such as spironolactone, ACE inhibitors, NSAIDs, and trimethoprim2

Hyperkalemia is usually detected after at least 3-4 days of treatment with subcutaneous heparin, and usually resolves within a few days of  discontinuation of therapy1,2.  Fractionated heparin products such as enoxaparin may also be associated with hyperkalemia2 but the risk appears to be lower1.

Fludrocortisone has been used to normalize serum potassium in patients who  remain on heparin.4

References

  1. Potti A, Danielson B, Badreddine R, et al. Potassium homeostasis in patients receiving prophylactic enoxaparin therapy. J Thromb Haemost 2004;2:1208-9. http://onlinelibrary.wiley.com/doi/10.1111/j.1538-7836.2004.00791.x/pdf
  2. Thomas CM, Thomas J, Smeeton F, et al. Heparin-induced hyperkalemia. Diabetes Res Clin Pract 2008;80:e7-e8. https://www.ncbi.nlm.nih.gov/pubmed/18343525
  3.  Liu AA, Bui T, Nguyen HV, et al. Subcutaneous unfractionated heparin-induced hyperkalemia in an elderly patient. Australas J Ageing 2009;28:97. https://www.ncbi.nlm.nih.gov/pubmed/19566805
  4. Brown G. Fludrocortisone for heparin-induced hyperkalemia. CJHP 2011;64:463-4. https://www.cjhp-online.ca/index.php/cjhp/article/view/1091/1394
My hospitalized patient has developed hyperkalemia while on heparin prophylaxis. Can heparin really cause hyperkalemia and what is its mechanism?