INTENSIVE CARE

Electrolyte disorders in the critically ill

Raja Palepu Ross Freebairn

Learning objectives
After reading this article readers should be able to: C recognize the multiple aetiologies of electrolyte abnormalities of the critically ill C identify the signs and symptoms of the various electrolyte abnormalities C prescribe appropriate management of abnormalities, in particular the management of different types of dysnatraemia

Abstract
Electrolyte disorders are extremely common in the critically ill patient. Competent analysis and management of these is essential in providing quality intensive care. This article provides a review of and guide to aetiology, analysis, and management of the major electrolytes in the critically ill.

Keywords Calcium; chloride; critically ill; dysnatraemia; electrolytes;

uid; magnesium; phosphate; potassium; sodium Royal College of Anaesthetists CPD Matrix: 1A01, 1A02, 2A05, 2C01, 3C00

 Established recipes for electrolyte replacement to correct abnormalities serve as a starting point, but cannot replace repeated clinical examination and serial measurement of electrolytes.  All electrolytes are strong ions or weak acids and electrolyte disturbances may alter the acidebase status and viceversa. This can be assessed with blood gas data.

Specic electrolytes Introduction

Electrolyte disorders are extremely common in the critically ill patient. Competent analysis and management of these is essential in providing quality intensive care. Electrolyte disorders represent:  aids to the diagnosis of the nature of the illness  markers of disease severity and prognosis  indications of total body decit or excess requiring specic management. Many electrolyte disturbances can be managed simply; decits by increasing intake and excess by reducing intake or encouraging loss but generalizing this approach to all electrolyte and metabolic disturbances is over-simplistic. Fundamental concepts in understanding electrolyte disorders include the following.  Serum (or plasma) levels do not always reect total body stores of the electrolyte. For example potassium, a principally intracellular ion, is in a total body decit in diabetic ketoacidosis (DKA) yet serum levels are elevated. Simplistic interpretation would not identify the total body decit requiring ongoing replacement.  An electrolyte abnormality reects an underlying pathological process that may require denitive treatment.  Correction of a specic electrolyte abnormality may not improve a patients condition, and may even worsen their outcome, or mask the problem. The normal values and effects of decit and excess of common electrolytes are listed in Table 1.

Sodium
Thirst, vasopressin, and the kidneys control serum levels of the major extracellular cation, sodium. The prevalence of dysnatraemias in the intensive care unit (ICU) approaches 30%. They are an independent risk factor for poor prognosis on admission and during ICU stay and, not surprisingly, are incorporated into severity scoring systems such as APACHE II. Sodium has osmotic and electrostatic activity so measured hypo- or hypernatraemia needs to be assessed in correlation with the patients volume status and serum and urinary osmolality to determine the likely cause and appropriate method of correction. Hypernatraemia Aetiology: in the outpatient population hypernatraemia is rarely caused by excess sodium gain, and is usually the result of water decit relative to total body sodium. In the ICU population however, excess total body sodium due to iatrogenic loading of hypertonic uid is not uncommon. Multiple factors lead to renal loss of hypotonic uid in critically ill patients, which may then be replaced with a comparatively hypertonic uid such as 0.9% saline. Examples of hypotonic uid loss include sustained diarrhoea, vomiting or nasogastric losses, excessive sweating and central or nephrogenic diabetes insipidus. Sustained hypernatraemia can only occur when access to free water is restricted or when the thirst mechanism is absent e a common situation in ICU. Management: as sodium is the major extracellular cation, in hypernatraemia there will be a uid shift from intracellular to extracellular. The brain compensates to this by retaining other solutes to restore cell volume, although the hypertonic state remains. When correction commences it takes several days for

Raja Palepu MB ChB is a Registrar in Anaesthesia and Intensive Care Medicine at Hawkes Bay Hospital, Hastings, New Zealand. Conicts of interest: none declared. Ross Freebairn MB ChB FANZCA FCICM FRCPE is a Consultant Intensive Care Physician at Hawkes Bay Hospital, Hastings, New Zealand and Adjunct Associate Professor, Chinese University of Hong Kong, Hong Kong, China. Conicts of interest: none declared.

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Normal physiologic ranges of the common electrolytes and effects of decit or excess
Electrolyte Cations Sodium Normal values (mmol/litre) Effect of excess Effect of decit

136e145

Cerebral vascular rupture, haemorrhage death

Potassium

3.5e5.0

Peaked t-waves, can proceed to widened QRS, heart block, bradycardia, cardiac arrest, muscle weakness, paraesthesia, loss of tendon reexes, ileus, constipation, and palpitations Neurological (headache, fatigue, apathy, confusion), gastrointestinal (pain, constipation, vomiting), renal (polyuria, nephrolithiasis, renal failure) cardiovascular (arrhythmias, short QT interval and atrioventricular or bundle branch block) and skeletal (pain, arthralgia) Tetany and arrhythmias, atrial dysrhythmias, reduced cardiac output and death

Calcium

Total 2.10e2.60, ionized: 1.10e1.35

Headache, lethargy, irritability, spasticity, seizures and coma, demyelination syndromes if corrected too quickly Depressed ST segments, biphasic t-waves, prominent u-waves / tachyarrhythmias. Muscle weakness, paraesthesia, loss of tendon reexes, ileus, constipation, and palpitations Tetany, paraesthesia, mental changes, areexia, decrease in cardiac output with hypotension, dehydration via hypercalcaemic nephrogenic diabetes insipidus

Magnesium

0.6e1.2

Muscle weakness, decreased reexes, hypotension bradycardia somnolence coma. Where causes include gastrointestinal disorders (malabsorption, diarrhoea, nasogastric losses, pancreatitis, and short bowel), endocrine disorders, renal losses and drugs Unknown-/related to associated abnormality Below 0.32 mmol/litre respiratory muscle dysfunction, left shift of oxyhaemoglobin dissociation curve, myocardial dysfunction, arrhythmias, muscle weakness, insulin resistance, neuropathy, seizures, coma, haemolytic anaemia Copper deciency resulting in bone marrow abnormalities

Anions Chloride Phosphate

95e105 0.8e1.5

Unknown-/related to associated abnormality Symptoms of acute hypocalcaemia, acute tubular necrosis, ectopic calcication

Zinc

10.7e22.9 mmol/litre (serum) 13.8e22.9 mmol/litre (plasma)

Sparse hair, easily pluckable hair, alteration of taste; reddish dermatitis around nose, mouth and groin; hair loss, poor wound healing

these accumulated solutes to disperse. If large volumes of hypotonic uid are delivered rapidly, the resultant cerebral oedema can lead to irreversible brain damage. For this reason, correction by less than 0.6 mmol/litre/hour or 10e15 mmol/litre in a 24-hour period is recommended. Hypotonic uid such as pure water, 5% dextrose, or 0.45% saline in the lowest volume required to correct the hypertonicty should be used. Hyponatraemia Aetiology: hyponatraemia can occur in the setting of low, normal, or high total body water as outlined in Table 2. It can also occur in variable states of tonicity and osmolality depending on the presence of other solutes. For example, in hyperglycaemia the excess osmotic load of glucose holds water in the extracellular space, causing a hyponatraemia that is hyperosmolar and hypertonic. Differentiating the cause of hyponatraemia requires clinical examination of uid status along with simple investigations to assess serum and urine sodium and osmolality.

Hypervolaemic hyponatraemia is most often related to impaired water excretion by the kidneys. Hypovolaemic hyponatraemia is most often due to renal or extrarenal concurrent sodium and water loss. Clinical features: (Table 1) are seen when sodium derangement (hyper or hypo) is severe and/or occurs rapidly. Signs and symptoms relate predominantly to central nervous system (CNS) dysfunction. These are not usually seen until serum sodium falls below 125 mmol/litre but severity is also related to the speed of development. Acute hypotonic hyponatraemia is most dangerous as the entry of water into brain cells results in cerebral oedema and risk of tentorial herniation. Management: in mild hypovolaemic hyponatraemia isotonic saline (0.9% saline) is usually sufcient to correct serum sodium. In mild hypervolaemic cases uid restriction may be appropriate. Convulsions, unconsciousness, self-induced water intoxication, and hyponatraemia associated with intracranial pathology are medical emergencies that demand prompt and denitive

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Potential causes of the different types of hyponatraemia

Hypovolaemia Diarrhoea/vomiting Diuretics Osmotic diuresis Aldosterone deciency Third space losses e burns, pancreatitis Cerebral/renal salt wasting SIADH Stress response: postoperative pneumonia Head injury Positive pressure ventilation Hypothyroidism Cortisol deciency Congestive cardiac failure Cirrhosis Nephrotic syndrome Renal failure

Euvolaemia

Hypervolaemia

The incidence and precipitating factors of CPM remain poorly dened. Hyperkalaemia and rapid correction of hyponatraemia may increase risk, but CPM may still occur following slow correction. CPM has also been observed to occur after eunatraemic hyperosmolar hyperglycaemia, suggesting that a hypertonic insult may by the mechanism, in which free water leaves brain cells leading to cellular dysfunction and demyelination. Animal studies into drugs that may prevent or reduce the risk of CPM after correction of hyponatraemia have been promising. CPM can vary in severity from isolated gait ataxias that improve signicantly post-presentation, through to spastic quadriparesis, pseudobulbar palsy, and impairment in consciousness with variable reversibility. Formulae guiding the correction of dysnatraemias generally consider the patient as a closed system, ignoring the variable ongoing uid losses. Studies using these formulae report a wide discrepancy in serum sodium change and should therefore only be used as an initial estimate of need. A cornerstone of management is serial measurement of serum sodium, initially 2e4hourly, to avoid correction error. If inadvertent over correction of hyponatraemia occurs, carefully re-lowering the serum sodium may be preferred using desmopressin and 5% dextrose in water.

SIADH, syndrome of inappropriate anti-diuretic hormone secretion.

Potassium
Potassium is predominantly intracellular and is the bodys major cation. Only 2% is normally in serum. In health, 90% of daily potassium loss is by renal excretion regulated by aldosterone. In renal failure there is enhanced excretion though the bowel. Intracellular potassium concentrations are dependent on active uptake by the Na/K adenosine triphosphate (ATP-ase) pump, and passive leak along electrochemical gradient. Both of these are affected by medications, pH changes and osmolarity. Increased popularity of the renineangiotensinealdosterone axis medications may inuence prevalence of potassium derangements. Causes of hypo- and hyperkalaemia are listed in Table 3. Management Hyperkalaemia: emergency hyperkalaemia management is to stabilize myocardial membrane with calcium (gluconate or chloride), then shift potassium intracellularly with either an insulin/glucose or bicarbonate infusion. Loop and thiazide diuretics can assist potassium loss. Haemodialysis or ltration may be required in renal failure. Hypokalaemia: slow replacement of 10e30 mmol/hour is usually recommended. Uptake and maintenance of intracellular potassium may be magnesium dependent and this should also be measured when replacing potassium. Combined deciency is common and may potentiate cardiac arrhythmia. The usual maximum recommended intravenous dose is 30 mmol/hour. In unstable life-threatening arrhythmias 2 mmol/ minute for 10 minutes, followed by 10 mmol over 5e10 minutes can be administered under close cardiac monitoring.

Table 2

intervention with hypertonic saline. The aim is a rapid rise in serum sodium of about 3e7 mmol/litre or return a serum sodium to approximately 120 mmol/litre. This is best achieved with bolus infusions of concentrated saline. If strong saline is unavailable, or there is concern regarding uid overload, frusemide can be used to limit volume expansion. Vasopressin receptor antagonists, which act to increase free water loss, are another treatment option. Ongoing correction above 120 mmol/litre should proceed at the slower correction rate outlined in Box 1. Priority should then be given to identifying and treating the underlying cause, for example stopping any medications which promote uid loss. There is signicant morbidity and mortality associated with dysnatraemias and/or their rapid correction. Severe neurological derangement can occur following correction of hyponatraemia. Osmotic demyelination syndrome, including central pontine myelinolysis (CPM) is perhaps the most dangerous and wellknown complication.

Recommended maximum rates of correction of hyponatraemia

C C C

6e8 mmol/litre in 24 hours 12e14 mmol/litre in 48 hours 14e16 mmol/litre in 72 hours

Chloride
Chloride is the bodys major extracellular anion. It is regulated via the kidneys, gut and skin. In health over 99% of ltered

Box 1

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Causes of potassium disorders

Hypokalaemia Decreased intake Malnutrition Alcoholism Increased loss Transcellular shift

of hyperchloraemia and the subsequent outcomes of this are yet to be studied in published clinical trials. Hypochloraemia Aetiology: hypochloraemia can occur through chloride loss, as seen in vomiting and other gastric loss, diuretic therapy, and chronic respiratory acidosis, or in excess water gain, such as in hypotonic uid replacement, congestive heart failure, and syndrome of inappropriate anti-diuretic hormone (SIADH). Deciencies in other electrolytes including sodium, potassium, calcium, and in albumin often co-exist. Management: treatment is generally only given when hypochloraemia is a primary disorder rather than a compensatory mechanism. In the hypovolaemic patient replacement with sodium or potassium chloride is recommended.

Gastrointestinal Alkalosis C Diarrhoea/ Drugs C vomiting Insulin/glucose C C Nasogastric loss b2 agonists Renal Drugs Diuretics, steroids, amphotericin Aldosterone and cortisol excess Renal tubular acidosis Decreased loss Renal failure Drugs: Potassium sparing diuretics Angiotensin-converting enzyme inhibitors Transcellular shifts Acidosis Tumour lysis syndrome Rhabdomyolysis Burns

Hyperkalaemia Increased intake Oral or IV Stored RBCs transfused

Calcium
Calcium is an intracellular messenger and cell function regulator. It is tightly controlled by hormones acting on calcium transporters in the intestine, bone, and kidney. As pH, lactate, and bicarbonate inuence ionized calcium levels, direct measurement of ionized calcium is the gold standard. Calculated correction of total serum calcium provides a poor alternative to ionized calcium in ICU. Aetiology Calcium disturbance is common in the ICU setting. Causes are multifactorial, inuenced by sepsis, blood transfusions, renal failure, and renal replacement therapy, particularly when citrate anticoagulation is used. Rhabdomyolysis can precipitate deposition of intracellular calcium producing lowered extracellular ionized and total serum calcium levels. Management Management should follow specic protocols where applicable, for example during continuous renal replacement therapy. Hypercalcaemia: hypercalcaemia leads to dehydration via hypercalcaemic nephrogenic diabetes insipidus. Intravenous rehydration with 0.9% saline provides both volume replacement and additional sodium to interrupt the resorption of sodium and calcium. Frusemide can be used to promote calcium excretion but should only be used in uid replete patients. Bisphosphonates are commonly used in the oncology setting and act by inhibiting osteoclast mediated bone resorption. Given as a single intravenous infusion, results are seen in 24e48 hours and the therapeutic effect may last for several weeks. Glucocorticoids are only useful in cases of hypercalcaemia caused by endogenous overproduction of calcitriol (125-dihydroxyvitamin D.) Hypocalcaemia: early identication and correction of co-existing magnesium, phosphate or vitamin D abnormality are important. Prolonged critical illness is associated with vitamin D deciency that is poorly responsive to replacement. Acute symptomatic hypocalcaemia is treated with intravenous calcium gluconate 10% 10 ml or calcium chloride 10% 5 ml (3.4 mmol) over 2e3 minutes. In the presence of ongoing symptoms, 1e5 ml/hour of

Table 3

chloride is reabsorbed in the distal tubule. With increasing interest in Stewarts approach to acidebase analysis, chloride has become more important in understanding acid-base physiology. In Stewarts approach chloride is one of the major inuences on the strong ion difference (SID), and thus the hydrogen ion concentration. Chloride concentration should always be interpreted in relation to sodium, as concurrent sodium and chloride derangement (hyperchloraemia with hypernatraemia) will not alter the SID, and therefore not affect the acidebase balance. Hyperchloraemia Aetiology: a number of mechanisms can lead to hyperchloraemia in the ICU setting. Chloride loading, through administration of chloride-rich uids such as 0.9% saline, or in total parenteral nutrition (TPN) is one major mechanism. Other mechanisms include water loss through diarrhoea, fever, burns, renal losses, and diabetes insipidus or increased renal chloride reabsorption through early renal failure, renal tubular acidosis and medications such as acetazolamide. The signicance of hyperchloraemia in the ICU patient remains unclear. Animal studies have shown that in sepsis elevated serum chloride can contribute more to the total acid load than lactate. Hyperchloraemic acidosis has also been shown to be pro-inammatory and promote cytokine release in animals. It is still undecided whether hyperchloraemic acidosis contributes to, or is merely associated with critical illness. Management: loop diuretics are capable of reducing serum chloride without reducing sodium. Sodium bicarbonate can also be used in the correction of hyperchloraemic acidosis. Treatment

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10% calcium chloride should be administered with 4-hourly monitoring to keep ionized calcium greater than 0.8 mmol/litre. Hypocalcaemia usually normalizes after a few days in ICU. Although failure to normalize is associated with increased mortality, calcium replacement appears not to improve normalization or mortality.

tubules. Tissue breakdown (e.g. rhabdomyolysis) or cellular shift, as seen in lactic and ketoacidosis, can lead to excess phosphate load in the ICU setting. Oral phosphate bowel preparations have also been implicated in severe and sometime fatal electrolyte disturbances. Management: with normal renal function hyperphosphataemia is self-correcting within 24 hours. Severe or symptomatic hyperphosphataemia in the setting of renal failure requires dialysis. Hypertonic glucose can be used to drive phosphate (and potassium) into cells. Hypophosphataemia Aetiology: hypophosphataemia be due to total body depletion, as in renal wasting or large gastrointestinal losses, or compartment shift. It is seen postoperatively, particularly post-cardiac procedures, and in sepsis. Management: Phosphate should be replaced either orally or intravenously at 2e20 mmol/hour, up to 100 mmol/day to keep serum phosphate levels greater than 0.8 mmol/litre. A

Magnesium
Magnesium is a primarily intracellular ion that acts as a coenzyme in phosphate transfer reactions, and is also required for protein manufacture and mitochondrial function. Its role can be described as an intracellular calcium channel blocker. Serum magnesium undergoes diurnal variation. Routine regulation is controlled by variable reabsorption of urinary magnesium in the ascending loop. Hypermagnesaemia Aetiology: usually renal failure or grossly excess intake is required to elevate levels. Lithium poisoning, diabetic ketoacidosis and hypercatabolic states may alter levels. Management: patients in renal failure may require dialysis to lower serum magnesium. Patients with normal renal function should return to normal serum levels when the source of excess magnesium is stopped. Hypomagnesaemia Aetiology: hypomagnesaemia occurs frequently in hospitalized patients and has a higher prevalence in intensive care. Upper gastrointestinal secretions contain high concentrations of magnesium. As 99% of total body magnesium is stored intracellularly and in bone and cannot be readily mobilized, even small ongoing losses may results in low serum magnesium levels. Hypomagnesaemia on admission to ICU has been documented in 61% of patients and is associated with a doubling of mortality in patients with equivalent APACHE II scores. Management: hypomagnesaemia in high risk or symptomatic patients should be corrected with intravenous magnesium sulphate 10 mmol over 15 minutes and in repeated doses or infusion (20e60 mmol/24 hours) to keep serum magnesium 1.0 e1.5 mmol/litre.

Phosphate
Phosphate is an intracellular anion, and a vital part of the ATP pathway. It acts as a buffer and is also a component of several important cellular molecules. Normal clearance is predominantly renal. Urinary phosphate measurement is useful in determining the cause of derangement. Hyperphosphataemia Aetiology: hyperphosphataemia occurs when either the phosphate load exceeds the kidneys rate of ltration or when there is increased resorption of ltered phosphate in the proximal

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