Life Threatening Electrolyte Abnormalities

Dr. Chew Keng ShengProfessor/Emergency Physician,

Faculty of Medicine and Health Sciences,Universiti Malaysia Sarawak

1

Objectives1. Hyperkalemia

a. Basic science - potassium adaptation (feedforward control)b. Pseudohyperkalemiac. Clinical featuresd. Treatment

2. Hypokalemia3. Hyponatremia

a. Adjusting serum sodium according to glucose levelb. Formula for calculating sodium deficits - the caveatc. Goal and rate of correction

2

Hyperkalemia

3

The role of Aldosterone revisitedAldosterone stimulates renal K+ excretion only at supraphysiological levels, with little effect within the physiological range of K+

A kaliuretic reflex arising from receptors in the gut, portal vein or liver (?).

Rabinowitz, L. Aldosterone and potassium homeostasis. Kidney Int 49.6 (1996): 1738-1742.

4

Youn, J.H. and McDonough, A.A. "Recent advances in understanding integrative control of potassium homeostasis." Annual review of physiology 71 (2009): 381-401. 5

The ‘gut feeling’ is literally telling us that it is not easy to get hyperkalemia in a normal healthy individual!

Image source: pixabay.com

6

Potassium Adaptation Potassium Adaptation: enhanced efficiency of potassium excretion when potassium intake is increased

Hyperkalemia is a rare occurrence in normal individuals because of potassium adaptation

Youn, J.H. and McDonough, A.A. "Recent advances in understanding integrative control of potassium homeostasis." Annual review of physiology 71 (2009): 381-401.

7

What do we know

1. Increasing potassium intake alone is not a common cause of hyperkalemia unless it occurs acutely

2. Persistent hyperkalemia means impaired urinary potassium excretion (e.g. reduction in aldosterone secretion or responsiveness, acute or chronic kidney disease, etc)

3. Large release of potassium from the cells (increased tissue breakdown) causing a transient elevation

8

Pseudohyperkalemia

9

PseudohyperkalemiaTraumatic hemolysis from venipuncture (can be up to 20% of samples). Lab reports as “slightly hemolyzed”

Release from muscle cells distal to a tourniquet with fist clenching

Common in cases of leucocytosis (TWC > 50,000 - 100,000/mm3) or thrombocytosis (>500,000 - 1 million/mm3)

10

Effects of fist clenching

Don BR et al (1990): Both repeated fist clenching and isometric handgrip increased the plasma potassium level by as much as 1.6 mmol/l from the contracting arm.

Don, Burl R et al. "Pseudohyperkalemia caused by fist clenching during phlebotomy." New England Journal of Medicine 322.18 (1990): 1290-1292.

Solid circles represent patients, open circles represent controls

11

ThrombocytosisPotassium moves out of platelets after clotting has occurred. Therefore, serum potassium is normally higher than plasma potassium by 0.1 - 0.5 mmol/l

Graber et al (1988): N = 283 controls and 161 patients with reactive thrombocytosis.

Hyperkalemia noted in 34% of patients with a platelet count >500,000/mm3 vs 9% of patients with a platelet count less than 250,000/mm3

An increase of K+ level of 0.15 mmol/l for every increase of 100,000/mm3 in the platelet count. Graber, Mark et al. "Thrombocytosis elevates serum potassium." American Journal of Kidney Diseases 12.2

(1988): 116-120.12

LeucocytosisHigh white blood cell counts (>120,000/mm3) (e.g., due to chronic lymphocytic leukemia) causes pseudohyperkalemia due to cell fragility.

May be more prominent when blood is sampled in heparinized tubes Centrifugation of a heparinized tube causes in vitro cell destruction and release of potassium

Lee, Hong-Kee et al. "Pseudohyperkalemia—is serum or whole blood a better specimen type than plasma?." Clinica Chimica Acta 396.1 (2008): 95-96.

13

Exclude pseudohyperkalemia

Suspect when there no apparent cause for hyperkalemia in an asymptomatic patient

Look for wide variability in repeated measurements of K+ level

Attempt venipuncture without a tourniquet, repetitive fist clenching. If a tourniquet is required, release tourniquet after needle insertion. Then waiting for about one minute (or 2) before drawing the blood sample.

14

Clinical Features

15

Clinical FeaturesVague symptoms, may be overshadowed by primary illnesses that precipitate the hyperkalemia

Most serious manifestations - muscle weakness or paralysis, cardiac conduction abnormalities, and cardiac arrhythmias

Usually occur when the serum potassium concentration is ≥7.0 mmol/l

Absence of symptoms do not rule out hyperkalemia

16

Muscle WeaknessMuscle weakness may mimic Guillain-Barré syndrome - ascending muscle weakness that begins with the legs and progresses to the trunk and arms

Sphincter tone and cranial nerve function are typically intact

Symptoms resolve with correction of the hyperkalemia.

17

ECG Manifestations

ECG manifestations depends on:● the absolute se K+ level

● the rate of increase

Alfonzo, Annette VM et al. "Potassium disorders—clinical spectrum and emergency management." Resuscitation 70.1 (2006): 10-25.

Note:progression and severity of ECG changes do not correlate well with the serum potassium concentration

18

ECG ManifestationsIn a retrospective review of 90 hypokalemic patients by Montague et al (2008), although the probability of ECG abnormalities increased with increasing serum potassium, but the ECG was insensitive for the diagnosis of hyperkalemia.

Szerlip et al (1986) reported 2 cases of severe hyperkalemia >9.0 mmol/l with no expected ECG manifestations

Szerlip, Harold M, James Weiss, and Irwin Singer. "Profound hyperkalemia without electrocardiographic manifestations." American Journal of Kidney Diseases 7.6 (1986): 461-465.

Montague, Brian T, Jason R Ouellette, and Gregory K Buller. "Retrospective review of the frequency of ECG changes in hyperkalemia." Clinical Journal of the American Society of Nephrology 3.2 (2008):

324-330.

19

ECG ManifestationsSeen commonly when se K+ >5.5 mmol/l

Earliest ECG manifestation is narrow-based, peaked T waves (vs broad-based T waves in myocardial infarction or intracranial lesions)

Best seen leads II, III, V2 - V4

Only 22% of patients Parham, Walter A et al. "Hyperkalemia revisited." Texas Heart Institute Journal 33.1 (2006).

Image Graphic 80441 Version 5.0 from UptoDate

20

As the hyperkalemia gets more severe, there is progressive lengthening of the PR interval and QRS duration

When se K+ level reaches 8 - 9 mmol/l, SA node may stimulate the ventricles directly without evidence of atrial activity. This is because the SA node is less susceptible to the effects of hyperkalemia; the absence of P wave and widened QRS mimics ventricular tachycardia

When se K+ reaches 10 mmol/l, the progressively widened QRS merges with T wave producing sine wave

Parham, Walter A et al. "Hyperkalemia revisited." Texas Heart Institute Journal 33.1 (2006).

ECG Manifestations

21

Management in Emergency Department

22

Calcium Hyperkalemia-induced depolarization of the resting membrane potential leads to inactivation of sodium channels and decreased membrane excitability

Calcium restores the gap between resting membrane potential to the threshold potential

Effect seen within 1 min, last 30 - 60 minutes

Calcium gluconate vs calcium chloride

Solid line - normal action potentialDotted line- hyperkalemic effect

Parham, Walter A et al. "Hyperkalemia revisited." Texas Heart Institute Journal 33.1 (2006).23

InsulinInsulin works by stimulating Na-K-ATPase pump to drive potassium into the cells

Independent of its effect on glucose.

Glucose administration is to prevent hypoglycemia (not always necessary if se glucose >13 mmol/l)

Glucose without insulin may cause paradoxical effect by increasing plasma osmolality, drawing water and K+ out of cells

Alfonzo, Annette VM et al. "Potassium disorders—clinical spectrum and emergency management." Resuscitation 70.1 (2006): 10-25.

24

InsulinEffect begins in 10 to 20 min, peaks at 30 to 60 minutes, and lasts for 4 - 6 hours

Reduce potassium by 0.6 - 1.0 mmol/l

Renal failure patients maybe resistant to the glucose-lowering effect of insulin, but the hypokalemic effect of insulin is still intact because Na-K-ATPase activity can still be enhanced

Alvestrand, A et al. "Insulin-mediated potassium uptake is normal in uremic and healthy subjects." American Journal of Physiology-Endocrinology and Metabolism 246.2 (1984): E174-E180.

25

SalbutamolA beta-2 agonist drives potassium into the cells by increasing the activity of the Na-K-ATPase pump

Lowers se K+ level by 0.6 - 1.0 mmol/l

Nebulized form requires much higher dose than dose for asthma (10 - 20 mg vs 2.5 - 5 mg for asthma)

Effect begins in 10 to 20 min, peaks at 30 to 60 minutes, and lasts for 4 - 6 hours

Alfonzo, Annette VM et al. "Potassium disorders—clinical spectrum and emergency management." Resuscitation 70.1 (2006): 10-25.

26

Combined salbutamol + insulin-glucose?Allon & Copkney (1990):

● insulin with glucose alone: reduced 0.65 +/- 0.09 mmol/l● salbutamol alone: reduced 0.66 +/- 0.12 mmol/liter● combined regimen: reduced 1.21 +/- 0.19 mmol/l;● (p < 0.02)

Alfonzo, Annette VM et al. Potassium disorders—clinical spectrum and emergency management. Resuscitation 70.1 (2006): 10-25.

Allon, Michael, and Charles Copkney. Albuterol and insulin for treatment of hyperkalemia in hemodialysis patients. Kidney international 38.5 (1990): 869-872.

27

Sodium bicarbonateMore of historical interest

For persistent metabolic acidosis.

In a study by Blumberg et al (1992) on 12 dialysis patients (se K+ of 5.25 - 8.15 mmol/l) received IV bicarbonate over a 6-hour period. No change of potassium level noted during first 4 hours. Only at four and six hours did a moderate decline to 5.44 mmol/l (p<0.05) and to 5.30 mmol/l (p<0.01) noted respectively. In 3 patients, no or minimal change noted even after 6 hours

Blumberg, Alfred, Peter Weidmann, and Paolo Ferrari. Effect of prolonged bicarbonate administration on plasma potassium in terminal renal failure." Kidney international 41.2 (1992): 369-374.

28

Hypokalemia

29

IntroductionGenerally, se K+ decreases by 0.3 mmol/l for every 100 mmol reduction in total body potassium

Muscle weakness usually does not occur at se K+ level >2.5 mmol/l unless it develops acutely.

Many hypokalemic patients are also deficient in magnesium. Magnesium is important for potassium update and for maintenance of intracellular K+ level, particularly in the myocardium

Alfonzo, Annette VM et al. Potassium disorders—clinical spectrum and emergency management. Resuscitation 70.1 (2006): 10-25.

30

A note on hypomagnesemia● Can be subtle, commoner than expected - 12% in hospitalized patients (Agus

1999), 65% in ICU patients (Tong & Rude, 2005)● Neuromuscular - tremor, tetany, convulsions, weakness, delirium, and coma,

etc● Cardiovascular - widened QRS and peak, tall T waves, then widened PR

interval and ventricular arrhythmias with severe cases● Accompanying hypocalcemia, hypoparathyroidism, hypokalemia

31

Tong, G.M, and Rude, R.K.. Magnesium deficiency in critical illness. Journal of Int Care Med 20.1 (2005): 3-17.

Agus, Zalman S. Hypomagnesemia.Journal of the American Society of Nephrology 10.7 (1999): 1616-1622.

Treatment of hypokalemia2 g KCl in 200 ml over 2 hours or 1 g KCl in 100 ml over 1 hour

[1 g KCl = 13 mmol/l of potassium]

Rates as high as 40 mmol/hour may be required for life-threatening patients

Advising patient just to increase intake of potassium-rich foods, such as oranges and bananas may not be effective enough because dietary potassium is predominantly in the form of potassium phosphate or potassium citrate which results in the retention of only 40% as much potassium as KCl.

Image source: https://www.flickr.com/photos/codex41/9725166177 32

Hyponatremia

33

Classification1. Hypertonic hyponatremia

a. Hyperglycemiai. osmotic shift of water from ICF to ECFii. Need to do correction

2. Isotonic hyponatremiaa. Hyperlipidemia - Pseudohyponatremia

i. Relatively larger relative proportion of plasma volume occupied by excess lipids

3. Hypotonic hyponatremiaa. Hypervolemicb. Euvolemicc. Hypovolemic

Verbalis JG et al. Diagnosis, evaluation, and treatment of hyponatremia: expert panel recommendations. Am J Med. 2013;126(10 Suppl 1):S1-42.34

Adjusting se sodium level due to glucose levelHigh glucose load causes osmotic shift - pulls water out of the cells

Se sodium fall by about 1.6 mmol/l for each 5.5 mmol/L increase in se glucose concentration (Katz 1973)

Se sodium fall by about 2.4 mmol/l for each 5.5 mmol/L increase in se glucose concentration (Hillier et al, 1999)

Katz MA. Hyperglycemia-induced hyponatremia--calculation of expected serum sodium depression. N Engl J Med. 1973;289(16):843-4.

Hillier TA, Abbott RD, Barrett EJ. Hyponatremia: evaluating the correction factor for hyperglycemia. Am J Med. 1999;106(4):399-403.

35

36

Assuming se sodium falls 2.0* mmol/l for every 5.5 mmol/l (equivalent of 100 mg/dl)

Corrected serum sodium = Measured serum sodium + [se glucose - 5.5 mmol/l] * (2.0/5.5)

*1.6 mmol/l (Katz 1973), 2.4 mmol/l (Hillier et al, 1999)

37

Formula for predicting sodium deficits

Sodium deficit

= (Desired se sodium - measured se sodium) * Total body water

= (Desired se sodium - measured se sodium) * 0.5ϕ * body weightNote:ϕ some would take 0.6

In 3% NaCl, sodium concentration is approx 500 mmol/l or 1 ml = 0.5 mmol/l [1 g NaCl = 17 mmol/l]

Therefore, every 1 ml per kg body weight of 3% NACl increases se sodium by 1 mmol/l

Caveat:

38

Formulas may not accurately predict the magnitude of change in serum sodium.

In a series of 62 patients with a baseline se sodium of 112 mmol/l given hypertonic saline (Mohmand et al, 2007), 74% had an increase in se sodium higher than what was expected.

Reasons:Correction of hyponatremia using hypertonic saline removes the hypovolemic stimulus of ADH release (unless it is in SIADH)

Mohmand, Hashim K et al. Hypertonic saline for hyponatremia: risk of inadvertent overcorrection. Clinical Journal of the American Society of Nephrology 2.6 (2007): 1110-1117.

Goal of therapy● A 4- to 6-mmol/L increase in serum is sufficient to reverse the most serious

manifestations of acute hyponatremia (Sterns et al, 2010)● In emergency therapy, the goal is to rapidly increase the serum sodium by 4

to 6 mmol/L over a period of 6 hours (Sterns et al, 2010)

Sterns RH, Nigwekar SU, Hix JK. The treatment of hyponatremia. Semin Nephrol. 2009;29(3):282-99.

Sterns RH, Hix JK, Silver S. Treating profound hyponatremia: a strategy for controlled correction. Am J Kidney Dis. 2010;56(4):774-9.

39

Indications for emergency therapy● Patients with severe symptoms due to hyponatremia, such as seizures or

obtundation.● Patients with symptomatic acute hyponatremia, even if symptoms are mild. ● Patients with hyperacute hyponatremia due to self-induced water intoxication,

even if asymptomatic during initial evaluation (risk of cerebral edema due to osmotically driven water across blood-brain barrier).

● Symptomatic patients who have either acute postoperative hyponatremia or hyponatremia associated with intracranial pathology.

Verbalis JG, Goldsmith SR, Greenberg A, Korzelius C, Schrier RW, Sterns RH, et al. Diagnosis, evaluation, and treatment of hyponatremia: expert panel recommendations. Am J Med. 2013;126(10 Suppl 1):S1-42.

40

Rate of correction● Risk of osmotic demyelination syndrome (ODS) in severe hyponatremia -

when serum sodium concentration was increased > 10 to 12 mmol/L within 24 hours or more than 18 mmol/l within 48 hours (Sterns 1987; Karp & Laureno, 1993)

● Keep the rate of increase below 8 mmol/l over 24 hours (Sterns et al, 2009; Sterns et al, 2010)

Sterns RH. Severe symptomatic hyponatremia: treatment and outcome. A study of 64 cases. Ann Intern Med. 1987;107(5):656-64.

Karp BI, Laureno R. Pontine and extrapontine myelinolysis: a neurologic disorder following rapid correction of hyponatremia. Medicine (Baltimore). 1993;72(6):359-73.

Sterns RH, Hix JK, Silver S. Treatment of hyponatremia. Curr Opin Nephrol Hypertens. 2010;19(5):493-8.41

“six a day makes sense for safety; so six in six hours for severe sx’s and stop”

42

43

Conclusion1. Hyperkalemia - calcium, insulin, salbutamol are useful (insulin + salbutamol

has synergistic effect)2. If nebulized salbutamol is used, it is 3 times the normal dose used in asthma. 3. Cranial nerve involvement is not common in hyperkalemia4. Hyponatremia - remember that it may be higher than expected in the

presence of hyperglycemia5. formula may be used as a guide, but beware that the rise in sodium may be

higher than expected due to diuresis 6. More important is to know the goal: six a day makes sense, so six in six in

severe sxs and stop

44