Description

Hyperkalaemia is defined as plasma potassium in excess of 5.5 mmol/L.¹

Potassium is the most abundant intracellular cation - 98% of it being located intracellularly. Hyperkalaemia has 4 broad causes:¹

• Renal causes, e.g. due to decreased excretion or drugs.
• Increased circulation of potassium - can be exogenous or endogenous.
• A shift from the intracellular to the extracellular space.
• Pseudohyperkalaemia.

Epidemiology

The time of greatest risk is at the extremes of life. Reported incidence in hospitals is 1-10%,¹ drugs being implicated in about 75% of cases. Men are more likely than women to get hyperkalaemia whilst women are more likely to experience hypokalaemia.

Causes¹

• Renal causes:
  • Acute renal failure
  • Chronic kidney disease
    • Normally all potassium that is ingested is absorbed and excretion is 90% renal and 10% alimentary.
    • Most excretion by the gut is via the colon and in chronic renal failure this can maintain a fairly normal blood level of potassium.
    • It seems likely that the elevated potassium levels in chronic kidney disease trigger the excretion of potassium via the colon.²
    • Patients with chronic renal failure must be careful of foods rich in potassium.
  • Hyperkalaemic renal tubular acidosis.
  • Mineralocorticoid deficiency.
  • Medicines that interfere with potassium excretion, e.g. amiloride, spironolactone.
  • Medicines that interfere with the renin-angiotensin axis, e.g. angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), non-steroidal anti-inflammatory drugs (NSAIDS), heparin.
  • Other drugs that can cause hyperkalaemia include - ciclosporin, tacrolimus, pentamidine, co-trimoxazole, ketoconazole, metyrapone,
  • Also, remember to ask about herbal remedies.³

  Drugs that inhibit the renal excretion of potassium can cause hyperkalaemia but they are most dangerous if used in combination or if renal function declines.

• Increased circulation of potassium:
  • Exogenous, e.g. potassium supplementation.
  • Endogenous, e.g. tumour lysis syndrome,⁴ rhabdomyolysis, trauma, burns.
    • Massive tissue damage leads to loss of potassium into the circulation.
    • In crush syndrome this may be accompanied by renal impairment.
    • Fresh water drowning is more swiftly fatal than salt water drowning because the fresh water enters the circulation from the lungs and osmotic pressure causes erythrocytes to swell and burst. The sudden release of potassium can stop the heart.
• A shift from the intracellular to the extracellular space:
  • Acidosis, e.g. diabetic ketoacidosis (DKA).
  • Medications, e.g. digoxin toxicity, suxamethonium, beta blockade.
• Pseudohyperkalaemia:
  Hyperkalaemia is uncommon but serious. The diagnosis is based on a laboratory report and, especially if the result is unexpected, before initiating treatment, it is necessary to consider the possibility that the result may be spurious. There are a number of possible explanations for unexpectedly high results:^5,6
  • Prolonged tourniquet time.
  • There may have been difficulty collecting the sample.
  • The fist may have been clenched.
  • Test tube haemolysis, e.g. blood may have been squirted through a needle into the bottle or shaking the tube.
  • Use of the wrong anticoagulant, especially potassium EDTA.
  • Excessive cooling of specimen (in cold winter months, potassium in specimens from GP surgeries tends to be higher than in the summer).⁶
  • Length of storage of the specimen.
  • Marked leukocytosis and thrombocytosis.
  • Sample from limb receiving IV fluids containing potassium.

If there is doubt about the validity of the result, repeat it.

Special caveats

Dehydration:

• Dehydration in a patient taking drugs that may cause hyperkalaemia can reduce renal output and lead to a dangerous increase in potassium levels.
• Even in sickle cell trait, strenuous exertion, especially in the unfit and dehydrated, can precipitate sickling, haemolysis and sudden death from hyperkalaemia.⁷

• Diabetics pose particular problems as they may have impaired renal function, be on ACE inhibitors, and a healthy diet for diabetics tends to be low in sodium and high in potassium.⁸ Managing patients with diabetes and congestive heart failure is a difficult balance but the heart failure must be treated aggressively with ACE inhibitors and the new betablockers.⁹
• Potassium is often raised in DKA (prior to treatment). Insulin pushes both glucose and potassium into cells and potassium levels must be monitored during treatment. Glucagon impairs the intracellular shift of potassium.

Presentation

Symptoms

Symptoms are nonspecific and include weakness and fatigue. Occasionally, a patient presents with muscular paralysis or shortness of breath. They also may complain of palpitations or chest pain.

Signs

• There is little abnormality except occasional bradycardia due to heart block or tachypnoea from respiratory muscle weakness.
• Muscle weakness and flaccid paralysis.
• Depressed or absent tendon reflexes.
• Physical examination is unlikely to suggest the diagnosis, except if severe bradycardia is present or if muscles are tender as well as weak, suggesting rhabdomyolysis.

Investigations

Blood tests

• Any unexpected result should be repeated. If blood has been left standing a long time or shaken vigorously, damage to erythrocytes will result in potassium loss from cells and a spurious result. Check urea, other electrolytes and creatinine too.
• Check 24 hours urine volume and electrolytes.
• Full blood count - looking for normocytic, normochromic anaemia (which may suggest acute haemolysis), thrombocytosis and/or leukocytosis.
• Capillary blood glucose and plasma glucose.
• If the patient takes digoxin, check blood levels.
• Arterial blood gas - looking for a metabolic acidosis (will also give a potassium level which can be compared to the lab result).

Electrocardiogram

Serum potassium will monitor the extracellular concentration but the best way to assess the intracellular situation is an electrocardiogram (ECG) and, in severe cases, continuous monitoring is required. In hyperkalaemia the ECG may show:

• Peaked T waves - can be difficult to determine.
• Prolongation of the PR interval.
• Widening of the QRS.
• Reduced or loss of the P wave.
• AV dissociation.
• Sine wave pattern.
• Asystole.
• In patients with heart disease and abnormal baseline ECG, bradycardia may be the only new ECG abnormality.

Management

The aggression of treatment will depend upon the level of potassium, the rate of rise and ECG abnormalities.
The GAIN guidelines on treating hyperkalaemia provide an easy to follow protocol:¹

1. Is this true hyperkalaemia? Any doubt warrants an urgent repeat (getting an ABG can provide an almost instant result).
2. Determine severity of hyperkalaemia:

   Mild	5.5-6.0 mmol/L (this level is common and well tolerated in CKD)
   Moderate	6.1-6.9 mmol/L
   Severe	≥7.0 mmol/L or if any ECG changes or symptoms* at any level of potassium >5.5 mmol/L (especially if associated with hypoxia)

   *Symptoms here include muscle weakness, flaccid paralysis, palpitations and paraesthesias.
   

   Potassium ≥7.0 mmol/L, or any rise in potassium associated with ECG changes or symptoms, need to be urgently treated.

3. Get a 12-lead ECG and look for changes as above. But remember the following:
   • ECG may be normal even in severe hyperkalaemia.
   • The absence of ECG changes does not mean no need for treatment.
   • Presence of ECG changes means need for urgent treatment.
4. Try to determine why hyperkalaemia has occurred:
   • Take a full history and full medication history.
   • Is there a past medical history of renal failure?
   • Check medication and fluid prescription chart.
   • Examine as above and also look for presence of bladder distension.
5. Reduce potassium:
   
   Stop further potassium accumulation:
   • Stop any potassium supplements or drugs that conserve potassium.
   • Consider stopping digoxin and betablockers as these may prevent buffering of intracellular potassium and reduce effectiveness of insulin-glucose.¹
   • Decrease high intake of potassium in the diet.
   Protect cardiac membrane:
   • Give 10 ml 10% calcium gluconate (calcium chloride is an alternative ideally given via central access) which will improve ECG changes within 1-3 minutes, but this effect only has a transient effect 30-60 minutes.
   • If no improvement then give 10 ml every 10 minutes till ECG normalises (may need up to 50 ml).
   • In patients who are taking digoxin give calcium gluconate in an infusion (add to 100 ml glucose 5%) and run over 20 minutes (otherwise can precipitate myocardial digoxin toxicity).
   Shift potassium into cells:
   • Insulin-glucose IV - usually 10 units of Actrapid® are added to 50 ml of glucose 50% and infused over 30 minutes.
   • Capillary blood glucose needs to be checked before, during and after.
   • GAIN guidance uses a "hyperkalaemia kit" where the insulin is added to a Minijet® of glucose and given as a bolus over 5 minutes.
   • Potassium will decrease (0.6-1.0 mmol/L) in 15 minutes and lasts 60 minutes.
   • Check potassium 30 minutes afterwards and if there is a good response check U&E 2 hours later.
   • Also give 10 mg nebulised salbutamol - this reduces potassium (0.5-1.0 mmol/L) in 15-30 minutes and lasts 2 hours.
   • Sodium bicarbonate is not recommended as the risks outweigh the benefits.
   Remove potassium from body:
   • Calcium polystyrene sulphonate resin (Calcium Resonium®) with regular lactulose will remove potassium via the GI tract.
   • Each gram removes 1 mmol/L of potassium but onset is slow, taking over 2 hours.
   • Haemodialysis will also remove potassium from the body (see below).

Resistant hyperkalaemia

• May need to give further glucose and IV insulin and/or IV calcium.
• The use of intravenous diuretics, e.g. furosemide is more contentious. But this would be a good choice if other comorbidities are present, e.g. CCF.
• If, despite repeated glucose and IV insulin infusions, potassium remains too high then the case should be discussed with renal physicians.
• Sodium bicarbonate may be useful in the setting of resistant hyperkalaemia with acidosis. However, it can be dangerous and thus is best used after discussion with renal specialists and is best avoided in DKA.
• Haemodialysis may be required but is invasive.

Prognosis

In a study of patients in hospital, hyperkalaemia was an independent risk factor for death.¹⁰ 1.4% of 29,000 patients developed hyperkalaemia, with an overall mortality of 14.3%. The risk increased as potassium levels rose. 28% with serum potassium level above 7 mmol/L died, compared with 9% of those with a level less than 6.5 mmol/L. In 7 of 58 deaths, it was directly attributed to hyperkalaemia. Most fatal cases were complicated by renal failure but patients who died of hyperkalaemia had normal potassium levels within 36 hours before death.

Prevention

Much dangerous hyperkalaemia is iatrogenic. If patients take 2 drugs that reduce potassium excretion, check U&E if they develop diarrhoea or vomiting. Beware of NSAIDs with these drugs. In patients with renal impairment, the ACE inhibitors and angiotensin-II receptor antagonists are very effective and reduce blood pressure and possible albumin loss but they must be used with care to prevent hyperkalaemia. Whether the newer angiotensin-II receptor antagonists are any safer than the ACE inhibitors is still unknown.¹¹

Document references

1. Guidelines for the treatment of hyperkalaemia in adults, Guidelines and Audit Implementation Network (Dec 2008)
2. Gennari FJ, Segal AS; Hyperkalemia: An adaptive response in chronic renal insufficiency.; Kidney Int. 2002 Jul;62(1):1-9. [abstract]
3. Isnard Bagnis C, Deray G, Baumelou A, et al; Herbs and the kidney.; Am J Kidney Dis. 2004 Jul;44(1):1-11. [abstract]
4. Kalemkerian GP, Darwish B, Varterasian ML; Tumor lysis syndrome in small cell carcinoma and other solid tumors.; Am J Med. 1997 Nov;103(5):363-7. [abstract]
5. Smellie WS; Spurious hyperkalaemia. BMJ. 2007 Mar 31;334(7595):693-5.
6. Johnston JD, Hawthorne SW; How to minimise factitious hyperkalaemia in blood samples from general practice. BMJ. 1997 Apr 19;314(7088):1200-1.
7. Kerle KK, Nishimura KD; Exertional collapse and sudden death associated with sickle cell trait.; Am Fam Physician. 1996 Jul;54(1):237-40. [abstract]
8. Jarman PR, Kehely AM, Mather HM; Hyperkalaemia in diabetes: prevalence and associations.; Postgrad Med J. 1995 Sep;71(839):551-2. [abstract]
9. Fonarow GC; Managing the patient with diabetes mellitus and heart failure: issues and considerations.; Am J Med. 2004 Mar 8;116 Suppl 5A:76S-88S. [abstract]
10. Paice B, Gray JM, McBride D, et al; Hyperkalaemia in patients in hospital.; Br Med J (Clin Res Ed). 1983 Apr 9;286(6372):1189-92. [abstract]
11. Shusterman N; Risk-benefit assessment of angiotensin II receptor antagonists.; Expert Opin Drug Saf. 2002 Jul;1(2):137-52. [abstract]

Internet and further reading

• Lederer E et al; Hyperkalemia, eMedicine, Mar 2010

Acknowledgements