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Electrolyte disorders in the critically ill

Rochelle Barron 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 the different forms of dysnatraemia.

Electrolyte disturbance is almost ubiquitous in the critically ill. Competent analysis and management are crucial in providing quality intensive care, as evaluation may provide an aid to the diagnosis, a marker of disease severity and recovery, while specic electrolyte derangement may require specic management. While many electrolyte abnormalities can be managed by simply increasing intake to reverse decits and reducing intake and encouraging loss for excess levels, generalizing this approach is oversimplistic. Disturbed serum levels do not always reect the total body stores of the electrolyte but may reect a pathological process that requires specic denitive treatment. While established recipes for electrolyte replacement to correct abnormalities serve as a starting point, these cannot replace repeated clinical examination, and sequential measurement of the electrolytes. In this paper we provide a review of and a guide to the aetiology, analysis and management of the major electrolytes in the critically ill.

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

uid; magnesium; phosphate; potassium; sodium

Electrolyte disturbance is almost ubiquitous in the critically ill. Competent analysis and management of these multiple, and often repeated deviations from the population norms are crucial to providing quality intensive care. They represent:  aids to the diagnosis of the nature of the illness  markers of the disease severity and of recovery  specic electrolyte derangement that indicates body decit or excess of the disease requiring specic management. Many electrolyte abnormalities can be managed simply; decits by increasing intake and excess by reduction of intake and occasionally encouraging loss. However generalizing this approach to all electrolyte and metabolic abnormalities are over-simplistic. Concepts fundamental to understanding electrolyte disorders are:  The serum (or plasma) levels do not reect the total body stores of the electrolyte, for example potassium, a principally intracellular ion, is in total decit in diabetic ketoacidosis (DKA), yet serum levels are higher than normal. Simplistic interpretation would not identify the overall body decit that requires ongoing replacement.
Rochelle Barron MBChB is a Registrar in Anaesthesia and Intensive Care Medicine at Hawkes Bay Hospital, Hastings, New Zealand. Conicts of interest: none declared. Ross Freebairn MBChB FANZCA FCICM is a Medical Director of Intensive Care Services, Hawkes Bay Hospital, Hastings, New Zealand. Conicts of interest: none declared.

 The electrolyte abnormality reects an underlying pathologic process that may require denitive treatment. Many Ferraris are red, and Ferraris go fast. The observation that red cars go faster may be true, but repainting in racing red does not attain a higher velocity. Critically ill patients suffer electrolyte abnormalities, and critically ill patients often die. Correction does not necessarily improve (and may worsen) outcome and may simply mask the problem.  Correction to normality may not be necessary to improve the patient. (Green cars may also go fast.)  Established recipes for electrolyte replacement to correct abnormalities serve as a starting point, but cannot replace repeated clinical examination, and sequential measurement of the electrolytes.  All electrolytes are strong ions or weak acids and electrolyte abnormalities may alter the acidebase status and vice versa. Contribution of various electrolytes to the hydronium ion concentration or pH can be assessed with blood gas data.

Specic electrolytes
The effects of decit and excess of the common electrolytes are listed in Table 1.

Thirst, vasopressin, and the kidneys control serum levels of the major extracellular cation, sodium. The presence of either hyper- or hyponatraemia (dysnatraemias) in the intensive care unit (ICU) have a prevalence approaching 30% and are an independent risk factor for poor prognosis on admission or during ICU stay. Not surprisingly, dysnatraemias are incorporated into ICU scoring systems such as APACHE II. Sodium has osmotic and electrostatic activity so measured serum hypo- or hypernatraemia should be assessed in correlation with the patients volume status and serum and urinary osmolality to determine likely cause and appropriate method of correction. Hypernatraemia Aetiology: classical teaching in the outpatient population states hypernatraemia is rarely caused by excess sodium gain and is usually the result of water decit relative to total body sodium. In ICU, excess total sodium due to iatrogenic loading of hypertonic uid is not uncommon. Multiple factors promote renal losses of hypotonic uid in critically ill patients, which are then replaced with relatively hypertonic uid. Examples of losses include central or nephrogenic diabetes insipidus, sustained diarrhoea, vomiting or large nasogastric losses, and excessive sweating. Sustained



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The normal physiologic ranges of the common electrolytes and effects of decit or excess
Electrolyte Cations Sodium Normal values mmol/litre 136e145 Effect of excess Cerebral vascular rupture, haemorrhage death Effect of decit 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




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



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 AV or BB block) and skeletal (pain, arthralgia) Tetany and arrhythmias, atrial dysrhythmias, reduced cardiac output and death

Muscle weakness, decreased reexes, hypotension bradycardia somnolence coma. Where causes include gastrointestinal disorders (malabsorbtion, diarrhoea, NG 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


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

Table 1

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: chronically, the brain can compensate by retaining other solutes to restore cell volume, although the hypertonic state remains. It takes several days for these accumulated solutes to disperse when correction commences. If large volumes of hypotonic uid are delivered rapidly, the resultant cerebral oedema can precipitate 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 using hypotonic uid e for example pure water, 5% dextrose, or 0.45% saline at the lowest volume required to correct the hypertonicity. Hyponatraemia Aetiology: hyponatraemia can occur in the setting of low, normal or high total body water as outlined in Table 2 and can be associated with variable tonicity and osmolality depending on

the presence of other solutes. Differentiating the cause of hyponatraemia usually requires a few simple investigations combined with a clinical examination, including estimation of uid status and serum and urine osmolality. In hyperglycaemia for example, the excess osmotic load holds water in the extracellular space, causing a translocational hyponatraemia that is hyperosmolar and hypertonic. Hypervolaemic hyponatraemia is most often related to impaired ability of the kidneys to excrete water, and hypovolaemic hyponatraemia due to renal or extrarenal sodium plus water loss. Cerebral salt-wasting (CSW), or renal salt-wasting (RSW), previously a misrepresentation of the syndrome of inappropriate secretion of antidiuretic hormone (SIADH), is now accepted as a distinct entity. RSW is essentially extracellular volume depletion due to a renal sodium transport abnormality when other causes have been excluded. RSW and SIADH have similar laboratory ndings, but are distinguished by extracellular uid volume. The goal of treatment is uid repletion in RSW and uid restriction in SIADH.



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Potential causes of the different types of hyponatremia

Fluid state in hyponatraemia Hypovolaemic Diarrhoea/vomiting Diuretics Osmotic diuresis Aldosterone deciency Third spaces losses e burns, pancreatitis SIADH Stress response: postop, pneumonia Head injury Positive pressure ventilation Hypothyroidism Cortisol deciency Congestive cardiac failure Cirrhosis Nephrotic syndrome Renal failure

Recommended maximum rate of correction of hyponatraemia

6e8 mmol/litre in 24 hours 12e14 mmol/litre in 48 hours 14e16 mmol/litre in 72 hours Table 3



SIADH, syndrome of inappropriate secretion of antidiuretic hormone.

Table 2

Clinical features (see Table 1) are seen in situations where sodium derangement (both hyper and hypo) is severe and/or occurs rapidly, and predominantly produce central nervous system dysfunction. Symptoms are usually absent until the serum sodium falls to <125 mmol/litre but severity is related also to speed of development. Acute hypotonic hyponatraemia is most dangerous as entry of water into brain cells causes oedema and risk of tentorial herniation. The categories of hyponatraemia are shown in Table 2. Management: convulsions, unconsciousness, self-induced water intoxication, and hyponatraemia associated with intracranial pathology are medical emergencies that demand prompt and denitive intervention with hypertonic saline. The aim is a rapid rise in serum sodium of about 3e7 mmol/litre or return serum sodium to approximately 120 mmol/litre and is best achieved with bolus infusions of concentrated saline. If strong saline is unavailable, or if there is concern regarding uid overload, furosemide can be used to limit volume expansion. Ongoing correction above 120 mmol/litre should proceed at the slower recommended rate. Vasopressin receptor antagonists are another therapeutic option. Priority should then be given to identifying and correcting the underlying cause, for example ceasing any medications that promote uid loss. Signicant morbidity and mortality may result from sodium derangement or its hasty correction. A severe neurologic complication osmotic demyelination (including central pontine myelinolysis (CPM)), can follow resolving hyponatraemia. The incidence and precipitating factors remain poorly dened. While hyperkalaemia and precipitous correction of sodium (>10 mmol/ litre in 24 hours, 18 mmol/litre in 48 hours, and 20 mmol/litre in 72 hours) may increase the risk, slow correction does not always avoid the complication. A guideline is listed in Table 3. Eunatraemic hyperosmolar hyperglycaemia can also precipitate CPM, suggesting that a hypertonic insult may be the mechanism.

CPM can vary in severity from an isolated gait ataxia that improves signicantly despite an initial concerning 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 and ignore the variable ongoing uid losses. Studies using these formulae report a wide discrepancy in serum sodium change and must be used only as an initial estimate of need. A cornerstone of management is serial measurements of serum sodium, initially 2e4 hourly to avoid correction error. Fluid restriction may be appropriate in some mild hypervolaemic cases, and isotonic saline is usually sufcient to correct mild hypovolaemic hyponatraemias. Hyponatraemia with heart failure in any volume state carries a poor prognosis, and often does not respond to hypertonic uid therapy. Correction of the hyponatraemia is more successful with vasopressin antagonists, but evidence of improved long-term outcomes is lacking. If inadvertent rapid correction of hyponatraemia occurs, carefully re-lowering the serum sodium may be preferred using concurrent administration of desmopressin and 5% dextrose in water.

Potassium is predominantly intracellular and is the bodys major cation. Only 2% is normally in the serum. In health, 90% of daily potassium loss is by renal excretion regulated by aldosterone. In renal failure enhanced potassium excretion occurs through 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 can be affected by medications, pH changes and osmolarity. Increased popularity of the renineangiotensinealdosterone axis medications may inuence prevalence of potassium derangements. Causes for hypo- and hyperkalaemia are listed in Table 4. Management Hyperkalaemia: emergency hyperkalaemia management is to stabilize myocardial membrane with calcium (gluconate or chloride), then an insulin/glucose or a sodium bicarbonate infusion to shift potassium intracellularly. Diuretics (loop or thiazide) cause a potassium loss. Haemodialysis or ltration may be required in cases of renal failure. Hypokalaemia: slow sequential replacement of 10e30 mmol/ hour is usually indicated for low potassium. Uptake and maintenance of intracellular potassium may be magnesium dependent. As combined deciency is common and potentiates cardiac arrhythmia, concurrent potassium and magnesium replacement are recommended.



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Causes of potassium disorders

Hypokalaemia Decreased intake Malnutrition Alcoholism

Increased loss Gastrointestinal - Diarrhoea/vomiting - NG loss Renal Drugs Diuretics, steroids, amphotericin Aldosterone and cortisol excess Renal tubular acidosisl

Transcellular shift Alkalosis Drugs - Insulin/glucose - b2 agonists

Hyperkalaemia Increased Intake Oral or intravenous Stored red blood cells transfused

Decreased loss Renal failure Drugs: Potassium sparing diuretics Angiotensin-converting enzyme inhibitors

Transcellular shifts Acidosis Tumour lysis syndrome Rhabdomyolysis Burns

Table 4

The usual maximum recommended intravenous dose is 30 mmol/hour. Administration of 2 mmol/minute for 10 minutes followed by 10 mmol over 5e10 minutes under close monitoring may be required for unstable life-threatening arrhythmias.

Chloride, the bodys major anion, has a normal serum level of 95e105 mmol/litre and is regulated via the kidneys, gut and skin. In healthy subjects >99% of ltered chloride is reabsorbed in the distal tubule. Hyperchloraemia Aetiology: hyperchloraemia is common in ICU patients, and with renewed interest in Stewarts hypothesis of acidebase physiology, hyperchloraemic acidosis has become increasingly recognized after uid resuscitation with 0.9% NaCl. Why giving the same chloride load elevates some patients chloride levels profoundly while sparing others is unclear. Altered renal handling of chloride or intrato extracellular shift as part of an inammatory process are possible explanations. Similarly, whether hyperchloraemic acidosis is associated with, or contributes to, altered outcomes including mortality in ICU patients remains unresolved. Independent of chloride loading, hyperchloraemia is observed in early acute renal failure, some forms of chronic renal failure and in rare congenital forms of renal tubular acidosis. Management: treatment of hyperchloraemia and subsequent outcomes is yet to be studied. Loop diuretics are capable of reducing serum chloride with little effect on serum sodium. Treatment of chronic hyperchloraemic acidosis with sodium bicarbonate may be appropriate. Hypochloraemia Aetiology: hypochloraemia often occurs with dehydration but can occur after net water gain. Hyponatraemia, hypokalaemia,

hypocalcaemia and hypoalbuminaemia often coexist. Hypochloraemic alkalosis has been historically well described in hyperemesis, cystic brosis, and in Bartters and Gitelmans syndromes e rare inherited disorders characterized by hypokalaemia, hyperreninaemic hyperaldosteronism, and a decrease in the fractional chloride reabsorption. Hypochloraemia is a complication in critically ill and postoperative patients with high chloride loss from throughout the gastrointestinal tract. Renal loss of chloride is a common cause of hypochloraemic alkalosis. While diuretics enjoy common usage in ICU, the incidence of diuretic-induced alkalosis is unclear. Hypochloraemic alkalosis has been observed as a compensatory mechanism during chronic hypercapnia and has been suggested as a compensatory mechanism in lactic acidosis and diabetic ketoacidosis. Management: treatment of hypochloraemia if it is a primary disorder (i.e. not a compensatory mechanism) in the hypovolaemic patient should be achieved by administration of sodium or potassium chloride.

Calcium, an intracellular messenger and cell function regulator, 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 ionized calcium measurement is the gold standard. Calculated correction of total serum calcium provides a poor alternative in ICU. Aetiology Calcium disturbance is common, often multifactorial, inuenced by sepsis, prolonged elevation of inammatory cytokines, blood transfusions, renal failure and/or renal replacement therapy. Calcium and magnesium disturbances can arise in massive transfusions and on extracorporeal circuits when citrate anticoagulation is utilized. Rhabdomyolysis can precipitate



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deposition of intracellular calcium producing lowered extracellular ionized and total plasma calcium levels. Management Management should follow specic protocols where applicable, for example during continuous renal replacement therapy. Hypercalcaemia causes dehydration via hypercalcaemic nephrogenic diabetes insipidus. Intravenous 0.9% saline to replace volume and provide additional sodium required interrupts the resorption of both sodium and calcium. Furosemide given to promote calcium excretion 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 continue for several weeks. Glucocorticoids are only useful in cases of hypercalcaemia caused by endogenous overproduction of calcitriol (1,25-dihydroxyvitamin D). Hypocalcaemia: early identication and correction of coexisting 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 10% calcium chloride should be administered with 4-hourly monitoring to keep ionized calcium >0.8 mmol/litre.

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 hour) to keep serum magnesium 1.0e1.5 mmol/litre.

Phosphate, an intracellular anion, is an important component of the ATP pathway. It acts as a buffer and is a component of several important cellular molecules. Normal clearance is predominantly renal. Urinary phosphate measurement is useful in determining the cause of the derangement. Hyperphosphataemia Aetiology: hyperphosphatemia occurs when the phosphate load exceeds the kidneys rate of ltration and is often seen in marked tissue breakdown (e.g. rhabdomyolysis) or cellular shift in lactic or ketoacidosis. Oral phosphate bowel preparations have been implicated in severe and sometimes fatal electrolyte disturbances. Increased resorption of ltered phosphate in the proximal tubule can also raise levels. Management: with normal renal function, hyperphosphataemia is self-correcting within 24 hours. Severe or symptomatic hyperphosphataemia in the setting of renal failure requires dialysis although hypertonic glucose will drive phosphate (and potassium) into cells. Hypophosphataemia Aetiology: may be due to total body depletion (e.g. renal wasting or excessive gastrointestinal losses) or compartment shift. It is seen postoperatively (especially post-cardiac procedures) and in sepsis. Management: phosphate measurement is part of the assessment of the critically ill. Hypophosphataemia can be managed with oral or intravenous phosphate at 2e20 mmol/hour, up to 100 mmol a day to keep plasma level >0.8 mmol/litre. A

Magnesium is a primarily intracellular ion that acts as a co-enzyme in phosphate transfer reactions, and is also required for protein manufacture and mitochondrial functioning. Its role can be described as an intracellular calcium channel blocker. Serum magnesium undergoes diurnal variation, and routine regulation is controlled by variable reabsorption of urinary magnesium in the ascending loop. Hypermagnesaemia Aetiology: usually requires renal failure or grossly excess intake 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 is a frequent phenomenon in hospitalized patients and has a higher prevalence in intensive care. Upper gastrointestinal secretions contain high concentrations of magnesium and as 99% of total body magnesium is stored (predominantly in bone and in the intracellular compartment) and cannot be readily mobilized, even small ongoing losses may result in low serum magnesium levels. Hypomagnesaemia on admission to ICU has been documented in 61% of patients and is associated

FURTHER READING AND REFERENCES HJ, Madias NE. Hypernatremia. N Engl J Med 2000 May 18; 342: Adrogue 1493e9. Alfonzo AV, Isles C, Geddes C, Deighan C. Potassium disorderseclinical spectrum and emergency management. Resuscitation 2006 Jul; 70: 10e25. Baker SB, Worthley LI. The essentials of calcium, magnesium and phosphate metabolism: part I & II. Disorders. Crit Care Resusc 2002 Dec; 4: 307e15. 301e306. Handy JM, Soni N. Physiological effects of hyperchloraemia and acidosis. Br J Anaesth 2008 Aug; 101: 141e50. Hoorn EJ, Betjes MG, Weigel J, Zietse R. Hypernatraemia in critically ill patients: too little water and too much salt. Nephrol Dial Transplant 2008 May; 23: 1562e8. Lloyd P, Freebairn R. Using quantitative acidebase analysis in the ICU. Crit Care Resusc 2006 Mar; 8: 19e30.



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Nyirenda MJ, Tang JI, Padeld PL, Seckl JR. Hyperkalaemia. BMJ 2009; 339: b4114. Slomp J, van der Voort PH, Gerritsen RT, Berk JA, Bakker AJ. AlbuminAdjusted calcium is not suitable for diagnosis of hyper- and hypocalcemia in the critically ill. Crit Care Med 2003 May; 31: 1389e93.

Stelfox HT, Ahmed SB, Khandwala F, Zygun D, Shahpori R, Laupland K. The epidemiology of intensive care unit-acquired hyponatraemia and hypernatraemia in medical-surgical intensive care units. Crit Care 2008; 12: R162. Sterns RH, Nigwekar SU, Hix JK. The treatment of hyponatremia. Semin Nephrol 2009 May; 29: 282e99.



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