Resident Version

Hyperkalemia Module

Created by Bruce Horowitz, M.D.

Modified 9/07 by Dr. Wendy Gerstein

Objectives:

1) Recognize risk factors, causes and clinical presentation of hyperkalemia. 2) Recognize common complications of hyperkalemia. 3) Understand indications, time course of effect, and mechanisms of different treatments for hyperkalemia.

Reference:

Rose, BD, Post, TW, Clinical Physiology of Acid-Base and Electrolyte Disorders, 5th ed, McGraw-Hill, New York, 2001, pp. 383-396, 898-919. Case:

While on call during your medicine rotation, you are called by the lab to report of a cross- cover patient’s serum potassium of 6.5 mEq/L. You ask to have the test repeated.

What do you want to do now (before hanging up with the lab and before leaving the call room)?

What history do you want to obtain from the medical record?

More history: The patient is a 75 yo male with history of rheumatic heart disease, s/p mitral valvuloplasty and tricuspid annuloplasty in 2001 who was admitted from the ED ten days ago with increased dyspnea, lightheadedness and fatigue. He had no fever/chills, chest pain/pressure, URI symptoms, abdominal pain, diarrhea, or back pain. Has had some nausea with no vomiting. Pt had had dental extractions two weeks prior to admission. Antibiotics were given after, but not prior to the procedure. Home O2 is 2L/m via nasal prongs; pt currently on 4 L/m due to hypoxemia. He has no new complaints today.

Since admission, he has had a workup for infective endocarditis which has included an echocardiogram and blood cultures. Echocardiogram showed depressed EF (25%) and mitral regurgitation, pulmonary hypertension (PA syst 45 mm Hg), and severe mitral regurgitation, which is worse than the prior study (see below). The patient did have some urinary symptoms on admission (dysuria, foul smelling urine) and was found to have an Enterobacter Aerogenes UTI, which was initially treated with ciprofloxacin; however antibiotics were changed to vancomycin, ceftriaxone, rifampin and gentamicin for empiric coverage for infective endocarditis. On the day after admission, the patient underwent a cardiac catheterization which showed clean coronary arteries, moderate pulmonary HTN (58/23 mm Hg) and an increased wedge pressure (20-23 mm Hg).

3 days ago, one of the blood cultures from admission grew Streptococcus morbillorum, at which time the antibiotics were changed. Penicillin G 3 MU IV q 4 hours was added and gentamicin continued (ceftriaxone was discontinued. Since admission he has had an increase in creatinine from 1.7 to 2.3 today.

PAST MEDICAL HISTORY: rheumatic heart disease, mitral and tricuspid insufficiency, s/p Mitral valvuloplasty and tricuspid annuloplasty 5 years ago, CHF (nonischemic cardiomyopathy), hyperlipidemia, depression, BPH, recurrent UTI, anemia, renal insufficiency (creatinine pre-hospitalization, 1.7)

Echocardiograms: This hospitalization: normal LV wall thickness, LVEF 25-30%, impaired LV relaxation with regional wall motion abnormalities, which include posterior and inferior wall akinesis, and severe anterior and lateral wall hypokinesis. Left atrium is mildly dilated; PA pressure 40-45mmHg. Mitral Valve: severely thickened anterior leaflet and associated chordae, no mobility of posterior leaflet, severe mitral regurgitation. No change in trace TR, no AR, mild pulmonary valvular regurgitation.

Two years ago: LVEF 50-55%, mild posterior wall and inferior wall hypokinesis. Other findings similar to above.

Medications: penicillin g 3 million units IV Q4H, ciprofloxacin 250 mg po q12h, gentamicin 30 mg IV Q12H, nitropatch 0.3 mg/hr, hydralazine 30 mg Q8H, metoprolol 12.5mg po Q12H, ASA 81 mg daily, lovastatin 40 mg qpm, citalopram 40 mg daily, MVI, trazodone 25 mg hs prn, acetaminophen prn, ALOH/MGOH/SIMTH reg strength liquid 15ML PO TID prn, heparin 5000 units SC Q8HRS ALLERGIES: CODEINE

PHYSICAL EXAM: GEN: NAD, AOx3, pleasant VS: BP 104/54 P 80 RR 10 T 37 O2 94% 2L (nasal prongs) HEENT: head NC/AT; eyes PERRLA, EOMI; no conjunctival hemorrhage. NECK: supple, no lymphadenopathy, JVP about 8cm. Normal carotid upstroke. LUNGS: bibasilar crackles. HEART: RRR, IV/VI holosystolic murmur LLSB, radiates to axilla. No S3. ABD: soft, mild suprapubic tenderness, bowel sounds present, no masses or hepatosplenomegaly BACK: no CVAT EXT: 1+ pitting edema BLE; pulses 2+. No Osler's nodes or Janeway lesions.

Admission: CBC normal WBC, platelets, hematocrit 41%; Trop [-] x3; Chem: BUN/Creat 31/1.7 (GFR 42), K 4.7, Na/Cl/CO2/Ca/Mg/phos/glc: normal

Today: K 6.5; BUN/Creat 33/2.2 (GFR 33); Na/Cl/Ca/Mg/glucose: normal; Po4 4.7

UA: nitrite +, mod LCE, 102 wbc, 18 rbc; CXR mild pulm edema

EKG: Sinus bradycardia, normal intervals. T waves show peaking especially apparent in V2 and V3, which is not present on admission tracing

What risk factors or possible etiologies does this patient have for hyperkalemia?

What do you want to do next (acutely)?

What changes could be made for long term? Outline for discussion:

I. Normal potassium equilibrium

A. Determined by potassium intake, the distribution of potassium between the cells and the extracellular fluid, and urinary potassium excretion

1. Most dietary potassium is excreted in the urine

2. Potassium is secreted by the principal cells in the cortical collecting tubule. This potassium secretion is primarily stimulated by three factors:

a) Increased serum [K+]

b) Increased plasma aldosterone

c) Increased delivery of Na+ and water to the distal secretory site

II.Causes of Hyperkalemia

A. Cellular: Increased potassium release or decreased uptake

1. Pseudohyperkalemia: occurring after the sample is drawn

a) Results from mechanical trauma during venipuncture (hemolysis)

b) Caution in the case of severe intravascular hemolysis, in which represents true hyperkalemia

2. Metabolic acidosis

a) Results from an attempt to buffer H+

b) K+ moves extracellularly to maintain electroneutrality

3. Insulin deficiency, hyperglycemia, and hyperosmolality

a) Insulin promotes K moving intracellularly in conjunction with glucose.

(1) Elevated plasma osmolality results in K movement out of cells.

4. Tissue Breakdown

a) Results in release of intracellular K+ into extracellular space

b) Examples include trauma, rhabdomyolysis, and tumor lysis syndrome

5. Beta-adrenergic blockers

a) Interferes with the beta-2-adrenergic facilitation of potassium uptake by the cells

6. Intense exercise

7. Drugs

a) Digitalis: dose-dependent inhibition of the Na-K-ATPase pump

b) Succinylcholine (in patients with burns, extensive trauma, or neuromuscular disease).

c) Drugs that activate ATP-dependent K+ channels in cell membranes: diazoxide, minoxidil and several volatile anesthetics (i.e. isoflurane).

B. Decreased urinary excretion

1. Hypoaldosteronism: Any cause of decreased aldosterone release or effect

a) Hyporeninemic hypoaldosteronism

b) Drugs such as potassium sparing diuretics (triampterene), heparin, cyclosporine and pentamidine, and cyclosporine.

c) Since a high [K+] directly stimulates renal tubular K secretion, hyperkalemia is rare with normal renal function.

2. Renal failure

a) K excretion is maintained as long as aldosterone effect and distal renal blood flow are maintained

b) Hyperkalemia occurs in patients with renal insufficiency in the setting of oliguria, impaired aldosterone function, or additional insults (high K diet, tissue breakdown, other medications, fasting).

3. Effective circulating volume depletion

a) Examples include CHF, cirrhosis. Causes of hyperkalemia may be multifactorial in these cases (drugs, renal insufficiency).

4. Hyperkalemic (type 1) RTA a) Impaired Na+ reabsorption in the cortical collecting tubule is the primary defect.

b) Normally, reabsorption of Na+ produces H+ and K+ secretion.

c) In type I RTA, Na transport is inhibited, which reduces H+ and K+ secretion, and result is metabolic acidosis and hyperkalemia.

d) Type 1 RTA is most often seen with urinary tract obstruction or sickle cell disease.

III. Presentation

A. Very few symptoms or signs unless [K+] > 7.0 or rapid rise in [K+]

B. Patients may display symptoms from an underlying cause, for example diabetes causing polyuria and polydipsia.

C. Severe muscle weakness or paralysis

1. This is caused by impaired neuromuscular transmission and depolarization. Potassium gradient, which is required for muscle depolarization, is decreased.

D. Cardiac conduction abnormality

1. ECG changes begin with a tall peaked T wave with shortened QT interval

2. This is followed by progressive lengthening of the PR interval and QRS duration. P-wave may disappear, QRS widens which may result in ‘sine-wave’ and ultimately ventricular fibrillation or ‘flat line’

3. Other conduction disturbances may occur, including RBBB, LBBB, bifascicular block, and high degree AV block

4. ECG may change rapidly and varies between patients. This is in part related to calcium and sodium levels, pH, as well as rapidity of change in K+. It is important to monitory the ECG in patients with hyperkalemia.

E. Since complications correlate with chronicity (or rapidity) of hyperkalemia, history is important when considering management in individual patients.

IV. Treatment

A. Treatment is directed to three major mechanisms: antagonizing the membrane effects of potassium (stabilizing the membrane), intracellular movement of potassium, and eliminating total body K+ B. Calcium

1. Directly antagonizes the membrane actions of hyperkalemia. The mechanism is not well understood however likely has to with reversing sodium channels inhibition and membrane excitability.

2. IV Calcium therapy is indicated when significant electrocardiographic abnormalities are seen. The protective effect of calcium begins within minutes, but is short-lived.

3. Use caution in patients taking digoxin, as calcium can induce digoxin toxicity

C. Insulin and glucose

1. Drives potassium into cells through increased Na-K-ATPase pump activity in skeletal muscle. Insulin results in cotransport of glucose and potassium via this pump. Peak effect one hour.

D. Sodium bicarbonate

1. Raises pH which results in hydrogen ion release from the cells (as part of the buffering reaction), which causes potassium movement into the cells to maintain electroneutrality. This is more effective in patients with metabolic acidosis. Peak effect one hour.

E. Beta blockers

1. Beta agonists activate Na-K-ATPase activity which drives potassium into cells (similar mechanism to insulin). Effect within 30 minutes IV forms, 90 minutes with inhalation.

F. Cation exchange resin (Kayexalate®, sodium polystyrene sulfonate)

1. Takes up potassium in exchange for sodium in the gut

2. Side effects include

a) Edema due to sodium retention,

b) Diarrhea (or constipation if not given with sorbitol solution)

c) Intestinal necrosis in the case of decreased motility (postoperatively and/or from opiates)

3. Can be given orally or rectally.

(1) Enema can lower [K+] by 0.5-1 mEq/L; may repeat q2- 4h. 4. Low oral dose (5 - 10 gm BID to TID of Kayexalate ®) can be used in renal insufficiency for chronic mild hyperkalemia. Low dose is generally well tolerated (no nausea or constipation).

G. Hemodialysis

1. Used in limited settings:

a) When conservative measures have failed

b) Severe hyperkalemia

c) Marked tissue breakdown (when large amounts of potassium are released)

2. Patients may be dialyzed against a zero [K+] bath, which lowers plasma [K+] quickly.

a) Higher (3-4 mEq) potassium baths lower the plasma potassium concentration in a slower, safer manner. Board Review Question:

1) 54 yo male with h/o paranoid schizophrenia and hypertension presents with severe cellulitis of his left leg. It has been swollen, red and blistering for 1 week. He has been drinking a lot of fluids, but notes his urine is a different color. On exam vitals: T 36, p 89, bp 124/81, rr 12, nl O2 saturation. PE notable only for left leg with 4+ pitting edema to thigh, severe erythema/blistering with weeping lesions circumferentially around lower leg, tissue tense with palpation, but not particularly tender. Patient refused foley in ER, but nurse reports 400cc in urinal. Labs at presentation are as follows:

Wbc 11.7 with 84% neutrophils; hct 42, platelets 219 Na 124, K+ 5.8, CL 88, HCO3 16, BUN 106, Cr 11.1, measured osmolality 299 Phos 6.4, Mg 3.4, Ca 7.4 Alk Phos 138, AST 643, ALT 410, lactate .7 Urine sodium 36, urine creatinine 67 UA: yellow, clear Sp Gr 1.008, pH 5.0 Prot 30 Negative glucose, ketones, bilirubin, nitrites, leukocyte esterase, urobilinogen Large blood 1 RBC/hpf 4 WBC/hpf No casts seen

Based on the patient’s history, presentation, and lab findings as noted above, what is the most likely cause of the hyperkalemia and renal failure? (Be able to defend your choice.)

A) Acute tubular necrosis due to dehydration and low mean arterial pressure (pre-renal).

B) Post-streptococcal glomerulonephritis

C) Rhabdomyolysis

D) Toxin ingestion (such as methanol or ethylene glycol)

E) Post obstructive renal failure

Post Module Evaluation

Please place completed evaluation in an interdepartmental mail envelope and address to Dr. Wendy Gerstein, Department of Medicine, VAMC (111).

1) Topic of module:______

2) On a scale of 1-5, how effective was this module for learning this topic? ______(1= not effective at all, 5 = extremely effective)

3) Were there any obvious errors, confusing data, or omissions? Please list/comment below:

______

4) Was the attending involved in the teaching of this module? Yes/no (please circle).

5) Please provide any further comments/feedback about this module, or the inpatient curriculum in general:

6) Please circle one:

Attending Resident (R2/R3) Intern Medical student