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Electrolyte disorders in the critically ill
INTENSIVE CARE
Electrolyte disorders in the critically ill
Learning objectives After reading this article, you should be able to C describe the multiple aetiologies of electrolyte abnormalities of the critically ill C list the signs and symptoms of the various electrolyte abnormalities C describe the appropriate management of electrolyte abnormalities, in particular the management of different types of dysnatraemia
Dinusha Thanippuli Arachchige Jason McClure
Abstract Electrolyte disorders are ubiquitous in the critically ill patient, and their identification and management are vital for the patient’s safe care. This article provides a guide to the aetiology, analysis and management of major electrolyte disorders in the critically ill.
Potassium readings may be falsely elevated in haemolysis (from damage to red cells during sample collection and transport and also from fragile leucocytes, e.g. in chronic lymphocytic leukaemia). Chloride ISEs are notoriously non-selective, and falsely increased results can be generated from the presence of bromide, iodine, thiocyanate, salicylate, bicarbonate and heparin, among others. There are also risks of samples being contaminated with intravenous fluids, total parenteral nutrition (TPN) and medications when taken from devices and veins containing these fluids, often generating bizarre and non-physiological electrolyte results.
Keywords Calcium; chloride; critically ill; dysnatraemia; electrolytes; fluid; magnesium; phosphate; potassium; sodium Royal College of Anaesthetists CPD Matrix: 1A01, 1A02, 2A05, 2C01, 3C00
Introduction Electrolyte disorders are ubiquitous in the critically ill, and safe patient care demands careful management of these. Abnormal serum electrolytes can be a marker of total body electrolyte deficit or excess, or movement between compartments, and may provide clues to the diagnosis, severity and even prognosis of illnesses. There is a paucity of high-level randomized controlled trial data on the topic, with management principles evolving from animal studies and physiological experiments on healthy individuals. However, these have been refined over the last 30 years from observational data and are likely to evolve further in the future.
Correction Many electrolyte disturbances can be ‘corrected’ by manipulating intake and output or by encouraging electrolyte movement between body compartments. This must be done with care e excessively rapid correction may cause injury or death via osmotic effects (e.g. with hyponatraemia) and electrochemical effects (e.g. potassium). Associated fluid shifts could cause organ dysfunctions of hypervolaemia (pulmonary oedema, heart failure, etc.) or hypovolaemia (renal injury, low cardiac output states). Care must also be taken to ensure the compatibility of electrolyte replacement with other medications and fluids if performed intravenously. Calcium, in particular, tends to form complexes with a multitude of medications and could cause dangerous emboli.
Measurement Electrolytes are mainly measured by ion-specific electrodes (ISEs) e based on potentiometric methods. The analysers used in central laboratories use indirect methods, involving the dilution of a serum or plasma sample prior to measurement. This enables very small sample volumes of serum/plasma to be analysed but requires an assumption to be made about the volume of solids in the serum/plasma e generally taken to be 7%. In contrast, point-of-care equipment uses the direct potentiometry of whole blood. The net effect is that laboratory tests are affected by the so-called ‘electrolyte exclusion effect’1 when the volume of solids is markedly different. This effect is most significant for sodium and is discussed later.
Specific electrolytes The normal values and effects of deficits and excesses of common electrolytes are listed in Table 1.
The cations Sodium Sodium is the primary extracellular cation and is a major contributor to serum osmolarity. Serum sodium levels are tightly regulated by thirst and the kidneys although the maintenance of plasma volume takes precedence over serum levels in hypovolaemic states. The relationship between plasma sodium and total body water is expressed in the simplified Edelman equation:
Dinusha Thanippuli Arachchige MBBS is an Intensive Care Registrar at Alfred Health, Melbourne, Australia. Conflicts of interest: none declared. Jason McClure MB ChB MRCP FRCA FCICM PGDip ENGINEERING is a Senior Intensivist at Alfred Health, Melbourne, Australia. Conflicts of interest: none declared.
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The normal physiologic ranges of the common electrolytes and effects of deficit or excess Electrolyte
Normal values (mmol/litre)
Effect of excess
Effect of deficit
Cation Sodium
136e145
Potassium
3.5e5.0
Cerebral haemorrhage and venous thrombosis, altered mental status, seizures and coma; cerebral oedema if corrected too quickly Peaked t-waves, widened QRS, ventricular arrhythmias, cardiac arrest; flaccid paralysis (especially in hyperkalaemic familial periodic paralysis)
Calcium
Total 2.10e2.60; Ionized 1.10e1.35
Neuromuscular excitability (e.g. hyperreflexia), altered mental status, lethargy, irritability, seizures and coma; demyelination syndromes if corrected too quickly Depressed ST segments, biphasic t-waves, prominent u-waves/tachyarrhythmias; hyponatraemia; muscle weakness, tetany and cramping, rhabdomyolysis, ileus, respiratory failure, polyuria with secondary polydipsia Tetany, diffuse encephalopathy, seizures, hyperreflexia, laryngospasm, dehydration secondary to hypercalcaemic, nephrogenic diabetes insipidus
Magnesium
0.6e1.2
Anion Chloride Phosphate
95e105 0.8e1.5
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) Prolonged PR interval, widened QRS, hyporeflexia, respiratory depression, cardiac arrest Possible acute renal impairment Symptoms of acute hypocalcaemia, acute tubular necrosis, ectopic calcification
Muscle weakness, tetany, hyperreflexia, seizures, cardiac arrhythmias; often associated with hypocalcaemia and hypokalaemia Unknown-/related to associated abnormality Below 0.32mmol/litre: respiratory muscle dysfunction, left shift of oxyhaemoglobin dissociation curve, myocardial dysfunction, arrhythmias, myopathy, encephalopathy, irritability, seizures, coma, rhabdomyolysis, haemolytic anaemia
Table 1
½Naserum ¼
½Nae þ ½Ke ; Total body water
sodium-rich medications is not uncommon. Excess hypotonic fluid losses often occur due to diarrhoea, vomiting or nasogastric losses and central or nephrogenic diabetes insipidus. These losses are often replaced with a comparatively hypertonic fluid such as 0.9% saline. Sustained hypernatraemia occurs when there is impaired renal excretion of the excess sodium, when access to free water is restricted or when the thirst mechanism is absent. There are rare cases of acute hypernatraemia (occurring over hours) in the community due to inadvertent and intentional salt intoxication; a 2017 systematic review by Campbell et al. identified 19 adult fatalities from this in the literature, with an average maximal sodium level of 206 mmol/litre. Mechanisms include shrinkage of brain cells, leading to shearing and haemorrhage, and cardiac QT prolongation and ventricular arrhythmias. Management e hypernatraemia raises serum osmolarity leading to fluid shifts from intracellular to extracellular compartments. Generally, this occurs over a number of days, allowing time for brain cells to react by upregulating transporters that accumulate organic osmolytes (including myo-inositol, taurine, glycerylphosphorylcholine and betaine), which protect
where the [Na]e and [K]e represent exchangeable (and thus osmotically active) ions of sodium and potassium in the body. Seventy per cent of the total body stores of sodium are exchangeable. Therefore, dysnatraemias need to be interpreted in the context of the patient’s volume status as well as serum and urinary osmolality. The concentration of exchangeable potassium plays a minor role, with low potassium states thought to drive sodium intracellularly and thus reduce serum levels. The expanded Edelman equation, which is beyond the scope of this chapter, incorporates additional variables. The prevalence of dysnatraemias in the intensive care unit (ICU) approaches 49%, and they are independent risk factors for increased mortality, leading to their incorporation into severityscoring systems such as APACHE II. Hypernatraemia: Aetiology e in the outpatient population, hypernatraemia is usually the result of water deficit relative to total body sodium. However, in the ICU population, excess total body sodium due to the administration of hypertonic fluid and
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starting point for suitable rates of water replenishment, while keeping in mind the limitation that this formula is based on the Edelman equation and considers the patient as a closed system, ignoring ongoing fluid losses (urinary, gastrointestinal, insensible, etc.). Subsequently, regular measurements of serum sodium levels and careful attention to urine output are required to avoid over- or under-correction. There is emerging literature2 suggesting faster correction than 0.6 mmol/litre/hour is not harmful in the adult population, but this has not made its way into practice guidelines. In particular, where the hypernatraemia has occurred over a period of hours, such as occurs with acute salt intoxication, rapid correction by 1 mmol/litre/hour improves prognosis without significant increase in risk of cerebral oedema.
them from osmotic dehydration. Following the correction of hypernatraemia, it may take several days for these accumulated solutes to disperse. Paediatric data demonstrate that too rapid a reduction in serum osmolarity may lead to cerebral oedema and irreversible neurological injury. The recommendation of correction by less than 0.6 mmol/litre/hour or 10e15 mmol/litre in a 24-hour period is based on this paediatric dataset. Hypotonic fluid such as free water or 0.45% saline in the lowest volume required is used. The water deficit to correct the serum sodium to 140mmol/litre can be calculated as follows: Water deficit in litres ¼ current body water in litres ½Naserum 1 ; 140 where the current body water is about 60% and 50% of lean body mass, in younger men and women, respectively, and somewhat less in older patients. This water deficit provides a
Hyponatraemia: Aetiology e historically, the causes of hyponatraemia have been classified according to patient volume state. As
Some causes of hyponatraemia Type Spurious
Biochemical features
Consider as causes
Normal or high serum osmolality
C C C
Polydypsias and impaired water excretion
Reduced serum osmolality Urine osmolality < serum osmolality, or urinary osmolality ¼<100 mOsm/kg
C C
C C
Low effective circulating volume
Urinary sodium ¼<30 mmol/l
C C C C C C C
Diuretic induced Endocrine causes
Urinary sodium >30 mmol/l
C C C C
Salt wasting
C C C
Syndromes of inappropriate antidiuresis
C
C
Hyperproteinaemia Hyperlipidaemia Hyperglycaemia Low dietary solute intake Primary polydipsia Psychogenic Exercise related Beer potomania Renal failure Heart failure Cirrhosis Nephrotic syndrome Diarrhoea and vomiting Third space losses Burns Remote diuretic use Thiazide diuretics Pituitary dysfunction Primary adrenal insufficiency Hypothyroidism Cerebral Renal Vomiting Syndrome of inappropriate antidiuresis (SIAD) Central Nephrogenic Reset osmostat
Table 2
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volume state is notoriously difficult to assess, approaches based on clinical history, assessment of serum/urine osmolality and urinary sodium levels, as shown in Table 2, may be more practical. Spurious, non-hypotonic hyponatraemia (or pseudohyponatraemia) remains an issue, particularly when indirect, dilutional biochemical testing is used in the setting of severe hyperprotenaemia, hyperlipidaemia and hyperglycaemia, and should be excluded by measuring the serum osmolality. Once spurious causes are excluded, the cause of true hyponatraemia should be identified. Reduced urine osmolality suggests causes of increased free water intake and reduced salt intake. These include primary polydipsias, beer potomania and other states of low solute intake. In elevated urinary osmolality, the urinary sodium helps distinguish causes of true intravascular depletion (such as heart failure, liver failure, nephrotic syndrome, gastrointestinal losses, third space losses and remote diuretic use) from causes of excessive sodium loss via renal or hormonally mediated pathways. Investigation of the latter pathways should include the measurement of cortisol levels (for primary or secondary adrenal insufficiency) and thyroid hormones (for hypothyroidism). A medication history must be taken; thiazide diuretics are a common cause of hyponatraemia. Syndrome of inappropriate antidiuresis (SIAD) should ideally be a diagnosis of exclusion. Clinical features e symptoms (Table 1) occur when sodium derangement is severe and/or occurs rapidly. Signs and symptoms relate predominantly to central nervous system (CNS) dysfunction and are not usually seen until serum sodium falls below 120 mmol/litre, although severity is also related to the speed of development. Acute hypotonic hyponatraemia (defined as occurring over <48 hours) poses the highest risk of cerebral oedema and tentorial herniation. Management e two principles guide the management of hyponatraemia. Firstly, emergency intervention with a bolus infusion of 3% hypertonic saline is warranted when there are severe symptoms of cerebral oedema, such as cardiorespiratory arrest, convulsions or unconsciousness. This is a medical emergency and usually occurs in severe hyponatraemia (serum sodium <120 mmol/litre). Moderately severe symptoms such as vomiting and a history of acute self-induced water intoxication may warrant the same. A 100e150 ml bolus of 3% saline should be administered over 10e20 minutes and repeated up to a total of 300 ml as required to correct the serum sodium by 4e6 mmol. As a second principle, care must be taken to avoid an excessively rapid rise in sodium when chronic hyponatraemia (>48 hours) is suspected to prevent osmotic demyelination syndrome (ODS). Sodium must not rise more than 10 mmol/litre in the first 24 hours and no more than 8 mmol/litre daily on each subsequent day (Box 1). The method for this slow correction varies with the cause of hyponatraemia, which should be identified and
treated. A slow infusion of hypertonic saline may be required for low salt intake states. A 0.9% saline solution is usually sufficient to correct serum sodium in mild hypovolemic hyponatraemia. In hypervolaemic hyponatraemia (e.g. syndrome of inappropriate antidiuresis), fluid restriction may be appropriate. Frusemide can be used to limit volume expansion. Vasopressin receptor antagonists can be used to increase free water loss. Urea can be administered as a medical food preparation and can increase serum sodium. There is a risk of an aquaresis when anti-diuretic hormone response is abolished during treatment of hypovolemic hyponatraemia with 0.9% saline. If inadvertent over-correction occurs from this or other causes, serum sodium may be safely lowered using desmopressin and/or hypotonic solutions to remain within target. Similar to formulae for fluid correction in hypernatraemia, formulae guiding the correction of hyponatraemia also consider the patient as a closed system. Regular measurements of serum sodium levels and careful attention to urine output are required to avoid over-correction. ODS is thought to be from direct injury to astrocytes and oligodendrocytes which have shed organic osmolytes in the setting of chronic hyponatraemia and thus rapidly lose water and acquire sodium and potassium when hyponatraemia is rapidly corrected. These changes in intracellular cation and volume states are thought to induce apoptosis of the astrocytes and oligodendrocytes, which are essential for the maintenance of myelin. The risk of ODS, including central pontine myelinolysis, is increased with rapid correction of hyponatraemia but may still occur following slow correction. ODS has been observed following eunatraemic hyperosmolar hyperglycaemia, suggesting a hypertonic insult as the underlying mechanism, leading to extracellular fluid shifts and cellular dysfunction and demyelination. Symptoms can range from reversible gait ataxias to spastic quadriparesis, pseudobulbar palsy and impaired consciousness with variable reversibility. Treatment is mainly supportive. Potassium Potassium is the primary intracellular cation, with only 2% located extracellularly. Total body potassium is regulated renally, with 90% of daily potassium loss occurring in the urine under the influence of aldosterone. In renal failure there is enhanced excretion through the bowel. Both renal losses and transmembrane potassium balance are influenced by factors such as medications and pH changes. The balance between extra- and intracellular potassium levels plays a major role in cellular electrophysiology. The Na/K adenosine triphosphate (ATPase) pump, present in almost all cell membranes, consumes energy to pump Naþ out of cells and Kþ into cells, thereby generating a potential difference across the cell membrane. This is particularly important in tissues of the nervous system and the heart. Due to this, electrocardiograms (ECGs) are often a useful tool in identifying potassium abnormalities. There is a U-shaped association of both low and high serum potassium concentrations with higher mortality rates in observational studies of multiple patient groups.
Safe rate of correction of hyponatraemia according to European Guidelines (2014) C C
10 mmol/litre in first 24 hours 8 mmol/litre daily on each subsequent day
Hyperkalaemia: Aetiology e hyperkalaemia most commonly occurs in setting of renal failure. For a broader list of causes, refer to Table 2.
Box 1
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Management e emergency management of hyperkalaemia involves stabilizing the myocardial membrane with calcium (gluconate or chloride), then shifting potassium intracellularly with insulin and glucose. Although protocols usually recommend a bolus of 10 U of insulin/25 g of dextrose, this may cause hypoglycaemia in certain patients, such as those with renal impairment or on CRRT. Beta agonists such as salbutamol (administered intravenously or inhaled) induce tachycardia and should be used with care in patients with cardiac disease. Sodium bicarbonate is no longer recommended due to a lack of efficacy but may be beneficial in patients with concurrent metabolic acidosis. Renal loss of potassium can be facilitated with loop and thiazide diuretics, while haemodialysis or filtration may be required in renal failure. Gastrointestinal potassiumbinding agents do not have a role acutely although they facilitate the longer-term lowering of potassium levels. The oldest of these, sodium polystyrene sulfonate, should be avoided in critically ill patients due to the risk of gastrointestinal side effects, such as colonic necrosis. Newer agents such as Patiromer (VeltassaÒ) and sodium zirconium cyclosilicate may have a more favourable sideeeffect profile.
Calcium Calcium is involved in numerous physiological processes, including neural transmission, muscular contraction and coagulation. Calcium levels are regulated by hormones acting on the intestine, bone and kidney. Although total serum calcium levels are frequently measured, ionized calcium is the physiologically active form and should be monitored directly as it is influenced by pH, lactate and bicarbonate levels. Calcium levels are affected by sepsis, blood transfusions, renal failure and renal replacement therapy, particularly when citrate anticoagulation is used. Rhabdomyolysis can precipitate the deposition of intracellular calcium, producing lowered ionized and total serum calcium levels. Management should follow specific protocols where applicable, e.g. during citrate-anticoagulated continuous renalreplacement therapy.
Hypokalaemia: Aetiology e often, the cause of hypokalaemia is obvious, as listed on Table 3. When the cause is less clear, measurement of urinary potassium excretion and assessment of acidebase status are helpful. A 24-hour urinary potassium excretion of >15 mmol, or a spot urinary potassium of >13 mmol/g creatinine, usually indicates inappropriate renal potassium loss. A metabolic acidosis in the presence of renal potassium wasting can suggest type 1 (distal) or type 2 (proximal) renal tubular acidosis. Metabolic alkalosis can cause intracellular shifts in potassium alongside insulin and beta agnoists. Management e the maintenance of potassium balance may be magnesium dependent. Magnesium levels should therefore also be measured, as combined deficiency is common and may precipitate cardiac arrhythmias. For correction, slow replacement
Hypercalcaemia: the symptoms of hypercalcaemia are classically taught as ‘painful bones, renal stones, abdominal groans and psychic moans’. Treatment of hypercalcaemia should be guided by the severity of symptoms and the urgency of correction. Intravenous rehydration with 0.9% saline provides both volume replacement and additional sodium to augment urinary co-excretion of sodium and calcium. Calcitonin is useful for treating severe hypercalcaemia as it has a relatively rapid onset of action and is usually well-tolerated. It reduces bone resorption but also has a mild calciuric effect. Bisphosphonates act by inhibiting osteoclast-mediated bone resorption and are 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
of potassium at 10e30 mmol/hour is usually recommended. In life-threatening arrhythmias, 2 mmol/minute for 10 minutes followed by 10 mmol over 5e10 minutes can be administered under continuous cardiac monitoring.
Causes of potassium disorders Hypokalaemia Decreased intake C Malnutrition C Alcoholism
Increased loss C Gastrointestinal Diarrhoea Vomiting Nasogastric losses C Renal Drugs: diuretics, steroids, amphotericin Excess mineralocorticoid activity (e.g. Conn’s syndrome) Renal tubular acidosis
Transcellular shift C Alkalosis C Drugs Insulin Beta-agonists
Decreased loss C Renal failure C Drugs: potassium sparing diuretics C Angiotensin converting enzyme inhibitors
Transcellular shifts C Acidosis C Tumour lysis syndrome C Rhabdomyolysis C Burns
Hyperkalaemia Increased intake C Oral or IV intake C Red cell transfusion
Table 3
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chloride’s role in acidebase physiology, where it is a major determinant of strong ion difference (SID) and thus hydrogen ion concentration. Chloride concentration should always be interpreted together with sodium as concurrent sodium and chloride derangement (hyperchloraemia with hypernatraemia) will not alter SID and therefore not affect the acidebase balance.
hypercalcaemia caused by endogenous overproduction of calcitriol (125-dihydroxyvitamin D). Diuretics such as frusemide should be avoided unless needed to correct excess fluid administration. Hypocalcaemia: Despite an observed association between hypocalcaemia and increased ICU morbidity and mortality, the correction of hypocalcaemia remains controversial. Hypocalcaemia will usually self-correct after a few days. Replacement does not improve the rate of normalization or mortality. Nonetheless, acute symptomatic hypocalcaemia may be treated with intravenous calcium gluconate 10% (10e20 ml) or calcium chloride 10% (5 ml) over 2 e3 minutes. If required, infusions of calcium gluconate or chloride can also be administered to maintain an ionized calcium level greater than 0.8 mmol/litre. Correction may be of particular benefit in improving clotting function. The identification and correction of co-existing magnesium, phosphate or vitamin D abnormalities are important as well.
Hyperchloraemia: Aetiology e the administration of chloriderich fluids or TPN is one major cause of hyperchloraemia in the ICU. Other mechanisms include free water loss through diarrhoea, fever, burns and diabetes insipidus or increased renal chloride reabsorption in renal failure, renal tubular acidosis and medications such as acetazolamide. Despite an observed association between hyperchloraemia and increased morbidity and mortality, it is unclear whether hyperchloraemia contributes to, or is merely associated with, critical illness. Management e the use of balanced-salt solutions in place of normal saline reduces the risk of hyperchloraemic acidosis. However, interventional studies using balanced-salt solutions have failed to demonstrate any corresponding reduction in renal impairment or mortality. Correction of hyperchloraemic acidosis is possible with loop diuretics or sodium bicarbonate although the benefit is controversial.
Magnesium Magnesium is the second most abundant intracellular cation and is involved in neuroendocrine responses to stress, protein manufacture and mitochondrial function. It also modulates calcium channel function in the cardiovascular system. Serum magnesium levels are regulated by the reabsorption of urinary magnesium.
Hypochloraemia: Aetiology e hypochloraemia can occur through chloride loss (e.g. vomiting or diuretic therapy) or excess water gain (e.g. hypotonic fluid replacement, congestive heart failure and syndrome of inappropriate anti-diuretic hormone). Deficiencies in other electrolytes, including sodium, potassium and calcium, often coexist. Management e treatment is generally only required when hypochloraemia is a primary disorder rather than a compensatory mechanism. In hypovolaemia, replacement with sodium chloride is recommended.
Hypermagnesaemia: Aetiology e hypermagnesaemia is relatively less common in ICUs and is usually secondary to renal failure or excessive supplementation. It may lead to muscle weakness and is associated with a prolonged duration of ventilation. Management e patients in renal failure may require dialysis to lower serum magnesium. Patients with normal renal function should quickly return to normal serum levels when the source of excess magnesium is stopped due to its high renal clearance.
Phosphate Phosphate is an intracellular anion and is essential for numerous cellular functions, such as ATP production and neurohumoral signalling. Total body phosphate is regulated by gastrointestinal and renal mechanisms. Serum phosphate levels reflect a balance of intracellular and extracellular flux and may be influenced by physiological factors such as pH, catecholamine levels or carbohydrate metabolism. The significance of abnormal levels depends on the underlying cause and the presence of symptoms. Urinary phosphate measurement is particularly useful in determining the cause of the derangement.
Hypomagnesaemia: Aetiology e hypomagnesaemia in the ICU has a prevalence of up to 61% and is independently associated with increased mortality. As 99% of total body magnesium is stored intracellularly and in bone and therefore cannot be readily mobilized, even small losses may result in hypomagnesaemia. Management e hypomagnesaemia in high-risk or symptomatic patients should be corrected with intravenous magnesium sulphate (20e60 mmol/24 hours) to keep serum magnesium 1.0 e1.5 mmol/litre. A slow infusion is preferred due to the slow tissue redistribution and high renal clearance. Patients with mild deficits or ongoing losses may benefit from enteral supplementation although this is limited by the low bioavailability of magnesium.
Hyperphosphataemia: Aetiology e hyperphosphataemia occurs when either the phosphate load exceeds the kidneys’ maximal rate of excretion or when there is increased resorption of filtered phosphate in the proximal tubules. Tissue breakdown (e.g. rhabdomyolysis) or cellular shifts, as seen in lactic acidosis and ketoacidosis, can also lead to high serum levels. Oral phosphate bowel preparations have also been implicated in severe and sometimes fatal calcium and phosphate disturbances. Management e with normal renal function, hyperphosphataemia is self-correcting within 24 hours. Severe or
The anions Chloride Chloride is the body’s major extracellular anion. It is regulated by the kidneys, gut and skin. In health, over 99% of filtered chloride is reabsorbed in the distal tubule. With growing interest in Stewart’s approach to acidebase analysis, there is increasing recognition of
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symptomatic hyperphosphataemia in the setting of renal failure requires dialysis. Hypertonic glucose can be used to drive phosphate (and potassium) into cells.
Kardalas E, Paschou SA, Anagnostis P, Muscogiuri G, Siasos G, Vryonidou A. Hypokalemia: a clinical update. Endocr Connections 2018 Apr; 7: R135e46. Nguyen MK, Kurtz I. Role of potassium in hypokalemia-induced hyponatremia: lessons learned from the Edelman equation [Internet]. Clin Exp Nephrol 2004 Jun; 8: 98e102 [cited 2019 Oct 1]; Available from, http://link.springer.com/10.1007/s10157-0040281-3. Pfortmueller CA, Uehlinger D, von Haehling S, Schefold JC. Serum chloride levels in critical illnessdthe hidden story [Internet]. Intensive Care Med Exp 2018 Apr 13; 6 [cited 2019 Sep 29];. Available from, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5899079/. Spasovski G, Vanholder R, Allolio B, et al. Clinical practice guideline on diagnosis and treatment of hyponatraemia. Eur J Endocrinol 2014 Mar; 170: G1e47. Sterns RH. Treatment of severe hyponatremia. CJASN 2018 Apr 6; 13: 641e9. Ward FL, Tobe SW, Naimark DMJ. The role of desmopressin in the management of severe, hypovolemic hyponatremia: a singlecenter, comparative analysis. Can J Kidney Health Dis 2018 Jan; 5. 205435811876105.
Hypophosphataemia: Aetiology e hypophosphataemia may reflect a total body deficit due to excessive renal or gastrointestinal losses or reduced absorption. It may also be secondary to intracellular shifts. Although it may result from various conditions, such as sepsis and alkalosis, it is commonly seen in critically ill patients as a result of refeeding syndrome. Management e patients who are symptomatic or have severe hypophosphataemia (<0.32 mmol/litre) should have phosphate replaced intravenously at 5e20 mmol/hour, up to 100 mmol/ day, to keep serum phosphate levels greater than 0.8 mmol/litre. There is considerable controversy on the management of asymptomatic hypophosphataemia, which should be guided by the suspected cause (e.g. total body deficit versus transcellular shifts). Where possible, oral replacement is preferred over IV formulations to minimize the risk of overcorrection or precipitation of calcium phosphate complexes. A REFERENCES 1 Delanghe JR. Management of electrolyte disorders: also the method matters!. Acta Clin Belg 2019 Jan 2; 74: 2e6. 2 Chauhan K, Pattharanitima P, Patel N, et al. Rate of correction of hypernatremia and health outcomes in critically ill patients. Clin J Am Soc Nephrol 2019 May 7; 14: 656e63.
Acknowledgements The authors gratefully acknowledge the contribution of Drs Ross Freebairn and Sing Chee Tan to the previous version of this article in 2017.
FURTHER READING Hansen B-A, Bruserud Ø. Hypomagnesemia in critically ill patients. J Intensive Care 2018 Dec; 6: 21.
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Electrolyte disorders in the critically ill
Learning objectives After reading this article, you should be able to C describe the multiple aetiologies of electrolyte abnormalities of the critically ill C list the signs and symptoms of the various electrolyte abnormalities C describe the appropriate management of electrolyte abnormalities, in particular the management of different types of dysnatraemia
Dinusha Thanippuli Arachchige Jason McClure
Abstract Electrolyte disorders are ubiquitous in the critically ill patient, and their identification and management are vital for the patient’s safe care. This article provides a guide to the aetiology, analysis and management of major electrolyte disorders in the critically ill.
Potassium readings may be falsely elevated in haemolysis (from damage to red cells during sample collection and transport and also from fragile leucocytes, e.g. in chronic lymphocytic leukaemia). Chloride ISEs are notoriously non-selective, and falsely increased results can be generated from the presence of bromide, iodine, thiocyanate, salicylate, bicarbonate and heparin, among others. There are also risks of samples being contaminated with intravenous fluids, total parenteral nutrition (TPN) and medications when taken from devices and veins containing these fluids, often generating bizarre and non-physiological electrolyte results.
Keywords Calcium; chloride; critically ill; dysnatraemia; electrolytes; fluid; magnesium; phosphate; potassium; sodium Royal College of Anaesthetists CPD Matrix: 1A01, 1A02, 2A05, 2C01, 3C00
Introduction Electrolyte disorders are ubiquitous in the critically ill, and safe patient care demands careful management of these. Abnormal serum electrolytes can be a marker of total body electrolyte deficit or excess, or movement between compartments, and may provide clues to the diagnosis, severity and even prognosis of illnesses. There is a paucity of high-level randomized controlled trial data on the topic, with management principles evolving from animal studies and physiological experiments on healthy individuals. However, these have been refined over the last 30 years from observational data and are likely to evolve further in the future.
Correction Many electrolyte disturbances can be ‘corrected’ by manipulating intake and output or by encouraging electrolyte movement between body compartments. This must be done with care e excessively rapid correction may cause injury or death via osmotic effects (e.g. with hyponatraemia) and electrochemical effects (e.g. potassium). Associated fluid shifts could cause organ dysfunctions of hypervolaemia (pulmonary oedema, heart failure, etc.) or hypovolaemia (renal injury, low cardiac output states). Care must also be taken to ensure the compatibility of electrolyte replacement with other medications and fluids if performed intravenously. Calcium, in particular, tends to form complexes with a multitude of medications and could cause dangerous emboli.
Measurement Electrolytes are mainly measured by ion-specific electrodes (ISEs) e based on potentiometric methods. The analysers used in central laboratories use indirect methods, involving the dilution of a serum or plasma sample prior to measurement. This enables very small sample volumes of serum/plasma to be analysed but requires an assumption to be made about the volume of solids in the serum/plasma e generally taken to be 7%. In contrast, point-of-care equipment uses the direct potentiometry of whole blood. The net effect is that laboratory tests are affected by the so-called ‘electrolyte exclusion effect’1 when the volume of solids is markedly different. This effect is most significant for sodium and is discussed later.
Specific electrolytes The normal values and effects of deficits and excesses of common electrolytes are listed in Table 1.
The cations Sodium Sodium is the primary extracellular cation and is a major contributor to serum osmolarity. Serum sodium levels are tightly regulated by thirst and the kidneys although the maintenance of plasma volume takes precedence over serum levels in hypovolaemic states. The relationship between plasma sodium and total body water is expressed in the simplified Edelman equation:
Dinusha Thanippuli Arachchige MBBS is an Intensive Care Registrar at Alfred Health, Melbourne, Australia. Conflicts of interest: none declared. Jason McClure MB ChB MRCP FRCA FCICM PGDip ENGINEERING is a Senior Intensivist at Alfred Health, Melbourne, Australia. Conflicts of interest: none declared.
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The normal physiologic ranges of the common electrolytes and effects of deficit or excess Electrolyte
Normal values (mmol/litre)
Effect of excess
Effect of deficit
Cation Sodium
136e145
Potassium
3.5e5.0
Cerebral haemorrhage and venous thrombosis, altered mental status, seizures and coma; cerebral oedema if corrected too quickly Peaked t-waves, widened QRS, ventricular arrhythmias, cardiac arrest; flaccid paralysis (especially in hyperkalaemic familial periodic paralysis)
Calcium
Total 2.10e2.60; Ionized 1.10e1.35
Neuromuscular excitability (e.g. hyperreflexia), altered mental status, lethargy, irritability, seizures and coma; demyelination syndromes if corrected too quickly Depressed ST segments, biphasic t-waves, prominent u-waves/tachyarrhythmias; hyponatraemia; muscle weakness, tetany and cramping, rhabdomyolysis, ileus, respiratory failure, polyuria with secondary polydipsia Tetany, diffuse encephalopathy, seizures, hyperreflexia, laryngospasm, dehydration secondary to hypercalcaemic, nephrogenic diabetes insipidus
Magnesium
0.6e1.2
Anion Chloride Phosphate
95e105 0.8e1.5
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) Prolonged PR interval, widened QRS, hyporeflexia, respiratory depression, cardiac arrest Possible acute renal impairment Symptoms of acute hypocalcaemia, acute tubular necrosis, ectopic calcification
Muscle weakness, tetany, hyperreflexia, seizures, cardiac arrhythmias; often associated with hypocalcaemia and hypokalaemia Unknown-/related to associated abnormality Below 0.32mmol/litre: respiratory muscle dysfunction, left shift of oxyhaemoglobin dissociation curve, myocardial dysfunction, arrhythmias, myopathy, encephalopathy, irritability, seizures, coma, rhabdomyolysis, haemolytic anaemia
Table 1
½Naserum ¼
½Nae þ ½Ke ; Total body water
sodium-rich medications is not uncommon. Excess hypotonic fluid losses often occur due to diarrhoea, vomiting or nasogastric losses and central or nephrogenic diabetes insipidus. These losses are often replaced with a comparatively hypertonic fluid such as 0.9% saline. Sustained hypernatraemia occurs when there is impaired renal excretion of the excess sodium, when access to free water is restricted or when the thirst mechanism is absent. There are rare cases of acute hypernatraemia (occurring over hours) in the community due to inadvertent and intentional salt intoxication; a 2017 systematic review by Campbell et al. identified 19 adult fatalities from this in the literature, with an average maximal sodium level of 206 mmol/litre. Mechanisms include shrinkage of brain cells, leading to shearing and haemorrhage, and cardiac QT prolongation and ventricular arrhythmias. Management e hypernatraemia raises serum osmolarity leading to fluid shifts from intracellular to extracellular compartments. Generally, this occurs over a number of days, allowing time for brain cells to react by upregulating transporters that accumulate organic osmolytes (including myo-inositol, taurine, glycerylphosphorylcholine and betaine), which protect
where the [Na]e and [K]e represent exchangeable (and thus osmotically active) ions of sodium and potassium in the body. Seventy per cent of the total body stores of sodium are exchangeable. Therefore, dysnatraemias need to be interpreted in the context of the patient’s volume status as well as serum and urinary osmolality. The concentration of exchangeable potassium plays a minor role, with low potassium states thought to drive sodium intracellularly and thus reduce serum levels. The expanded Edelman equation, which is beyond the scope of this chapter, incorporates additional variables. The prevalence of dysnatraemias in the intensive care unit (ICU) approaches 49%, and they are independent risk factors for increased mortality, leading to their incorporation into severityscoring systems such as APACHE II. Hypernatraemia: Aetiology e in the outpatient population, hypernatraemia is usually the result of water deficit relative to total body sodium. However, in the ICU population, excess total body sodium due to the administration of hypertonic fluid and
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starting point for suitable rates of water replenishment, while keeping in mind the limitation that this formula is based on the Edelman equation and considers the patient as a closed system, ignoring ongoing fluid losses (urinary, gastrointestinal, insensible, etc.). Subsequently, regular measurements of serum sodium levels and careful attention to urine output are required to avoid over- or under-correction. There is emerging literature2 suggesting faster correction than 0.6 mmol/litre/hour is not harmful in the adult population, but this has not made its way into practice guidelines. In particular, where the hypernatraemia has occurred over a period of hours, such as occurs with acute salt intoxication, rapid correction by 1 mmol/litre/hour improves prognosis without significant increase in risk of cerebral oedema.
them from osmotic dehydration. Following the correction of hypernatraemia, it may take several days for these accumulated solutes to disperse. Paediatric data demonstrate that too rapid a reduction in serum osmolarity may lead to cerebral oedema and irreversible neurological injury. The recommendation of correction by less than 0.6 mmol/litre/hour or 10e15 mmol/litre in a 24-hour period is based on this paediatric dataset. Hypotonic fluid such as free water or 0.45% saline in the lowest volume required is used. The water deficit to correct the serum sodium to 140mmol/litre can be calculated as follows: Water deficit in litres ¼ current body water in litres ½Naserum 1 ; 140 where the current body water is about 60% and 50% of lean body mass, in younger men and women, respectively, and somewhat less in older patients. This water deficit provides a
Hyponatraemia: Aetiology e historically, the causes of hyponatraemia have been classified according to patient volume state. As
Some causes of hyponatraemia Type Spurious
Biochemical features
Consider as causes
Normal or high serum osmolality
C C C
Polydypsias and impaired water excretion
Reduced serum osmolality Urine osmolality < serum osmolality, or urinary osmolality ¼<100 mOsm/kg
C C
C C
Low effective circulating volume
Urinary sodium ¼<30 mmol/l
C C C C C C C
Diuretic induced Endocrine causes
Urinary sodium >30 mmol/l
C C C C
Salt wasting
C C C
Syndromes of inappropriate antidiuresis
C
C
Hyperproteinaemia Hyperlipidaemia Hyperglycaemia Low dietary solute intake Primary polydipsia Psychogenic Exercise related Beer potomania Renal failure Heart failure Cirrhosis Nephrotic syndrome Diarrhoea and vomiting Third space losses Burns Remote diuretic use Thiazide diuretics Pituitary dysfunction Primary adrenal insufficiency Hypothyroidism Cerebral Renal Vomiting Syndrome of inappropriate antidiuresis (SIAD) Central Nephrogenic Reset osmostat
Table 2
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volume state is notoriously difficult to assess, approaches based on clinical history, assessment of serum/urine osmolality and urinary sodium levels, as shown in Table 2, may be more practical. Spurious, non-hypotonic hyponatraemia (or pseudohyponatraemia) remains an issue, particularly when indirect, dilutional biochemical testing is used in the setting of severe hyperprotenaemia, hyperlipidaemia and hyperglycaemia, and should be excluded by measuring the serum osmolality. Once spurious causes are excluded, the cause of true hyponatraemia should be identified. Reduced urine osmolality suggests causes of increased free water intake and reduced salt intake. These include primary polydipsias, beer potomania and other states of low solute intake. In elevated urinary osmolality, the urinary sodium helps distinguish causes of true intravascular depletion (such as heart failure, liver failure, nephrotic syndrome, gastrointestinal losses, third space losses and remote diuretic use) from causes of excessive sodium loss via renal or hormonally mediated pathways. Investigation of the latter pathways should include the measurement of cortisol levels (for primary or secondary adrenal insufficiency) and thyroid hormones (for hypothyroidism). A medication history must be taken; thiazide diuretics are a common cause of hyponatraemia. Syndrome of inappropriate antidiuresis (SIAD) should ideally be a diagnosis of exclusion. Clinical features e symptoms (Table 1) occur when sodium derangement is severe and/or occurs rapidly. Signs and symptoms relate predominantly to central nervous system (CNS) dysfunction and are not usually seen until serum sodium falls below 120 mmol/litre, although severity is also related to the speed of development. Acute hypotonic hyponatraemia (defined as occurring over <48 hours) poses the highest risk of cerebral oedema and tentorial herniation. Management e two principles guide the management of hyponatraemia. Firstly, emergency intervention with a bolus infusion of 3% hypertonic saline is warranted when there are severe symptoms of cerebral oedema, such as cardiorespiratory arrest, convulsions or unconsciousness. This is a medical emergency and usually occurs in severe hyponatraemia (serum sodium <120 mmol/litre). Moderately severe symptoms such as vomiting and a history of acute self-induced water intoxication may warrant the same. A 100e150 ml bolus of 3% saline should be administered over 10e20 minutes and repeated up to a total of 300 ml as required to correct the serum sodium by 4e6 mmol. As a second principle, care must be taken to avoid an excessively rapid rise in sodium when chronic hyponatraemia (>48 hours) is suspected to prevent osmotic demyelination syndrome (ODS). Sodium must not rise more than 10 mmol/litre in the first 24 hours and no more than 8 mmol/litre daily on each subsequent day (Box 1). The method for this slow correction varies with the cause of hyponatraemia, which should be identified and
treated. A slow infusion of hypertonic saline may be required for low salt intake states. A 0.9% saline solution is usually sufficient to correct serum sodium in mild hypovolemic hyponatraemia. In hypervolaemic hyponatraemia (e.g. syndrome of inappropriate antidiuresis), fluid restriction may be appropriate. Frusemide can be used to limit volume expansion. Vasopressin receptor antagonists can be used to increase free water loss. Urea can be administered as a medical food preparation and can increase serum sodium. There is a risk of an aquaresis when anti-diuretic hormone response is abolished during treatment of hypovolemic hyponatraemia with 0.9% saline. If inadvertent over-correction occurs from this or other causes, serum sodium may be safely lowered using desmopressin and/or hypotonic solutions to remain within target. Similar to formulae for fluid correction in hypernatraemia, formulae guiding the correction of hyponatraemia also consider the patient as a closed system. Regular measurements of serum sodium levels and careful attention to urine output are required to avoid over-correction. ODS is thought to be from direct injury to astrocytes and oligodendrocytes which have shed organic osmolytes in the setting of chronic hyponatraemia and thus rapidly lose water and acquire sodium and potassium when hyponatraemia is rapidly corrected. These changes in intracellular cation and volume states are thought to induce apoptosis of the astrocytes and oligodendrocytes, which are essential for the maintenance of myelin. The risk of ODS, including central pontine myelinolysis, is increased with rapid correction of hyponatraemia but may still occur following slow correction. ODS has been observed following eunatraemic hyperosmolar hyperglycaemia, suggesting a hypertonic insult as the underlying mechanism, leading to extracellular fluid shifts and cellular dysfunction and demyelination. Symptoms can range from reversible gait ataxias to spastic quadriparesis, pseudobulbar palsy and impaired consciousness with variable reversibility. Treatment is mainly supportive. Potassium Potassium is the primary intracellular cation, with only 2% located extracellularly. Total body potassium is regulated renally, with 90% of daily potassium loss occurring in the urine under the influence of aldosterone. In renal failure there is enhanced excretion through the bowel. Both renal losses and transmembrane potassium balance are influenced by factors such as medications and pH changes. The balance between extra- and intracellular potassium levels plays a major role in cellular electrophysiology. The Na/K adenosine triphosphate (ATPase) pump, present in almost all cell membranes, consumes energy to pump Naþ out of cells and Kþ into cells, thereby generating a potential difference across the cell membrane. This is particularly important in tissues of the nervous system and the heart. Due to this, electrocardiograms (ECGs) are often a useful tool in identifying potassium abnormalities. There is a U-shaped association of both low and high serum potassium concentrations with higher mortality rates in observational studies of multiple patient groups.
Safe rate of correction of hyponatraemia according to European Guidelines (2014) C C
10 mmol/litre in first 24 hours 8 mmol/litre daily on each subsequent day
Hyperkalaemia: Aetiology e hyperkalaemia most commonly occurs in setting of renal failure. For a broader list of causes, refer to Table 2.
Box 1
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Management e emergency management of hyperkalaemia involves stabilizing the myocardial membrane with calcium (gluconate or chloride), then shifting potassium intracellularly with insulin and glucose. Although protocols usually recommend a bolus of 10 U of insulin/25 g of dextrose, this may cause hypoglycaemia in certain patients, such as those with renal impairment or on CRRT. Beta agonists such as salbutamol (administered intravenously or inhaled) induce tachycardia and should be used with care in patients with cardiac disease. Sodium bicarbonate is no longer recommended due to a lack of efficacy but may be beneficial in patients with concurrent metabolic acidosis. Renal loss of potassium can be facilitated with loop and thiazide diuretics, while haemodialysis or filtration may be required in renal failure. Gastrointestinal potassiumbinding agents do not have a role acutely although they facilitate the longer-term lowering of potassium levels. The oldest of these, sodium polystyrene sulfonate, should be avoided in critically ill patients due to the risk of gastrointestinal side effects, such as colonic necrosis. Newer agents such as Patiromer (VeltassaÒ) and sodium zirconium cyclosilicate may have a more favourable sideeeffect profile.
Calcium Calcium is involved in numerous physiological processes, including neural transmission, muscular contraction and coagulation. Calcium levels are regulated by hormones acting on the intestine, bone and kidney. Although total serum calcium levels are frequently measured, ionized calcium is the physiologically active form and should be monitored directly as it is influenced by pH, lactate and bicarbonate levels. Calcium levels are affected by sepsis, blood transfusions, renal failure and renal replacement therapy, particularly when citrate anticoagulation is used. Rhabdomyolysis can precipitate the deposition of intracellular calcium, producing lowered ionized and total serum calcium levels. Management should follow specific protocols where applicable, e.g. during citrate-anticoagulated continuous renalreplacement therapy.
Hypokalaemia: Aetiology e often, the cause of hypokalaemia is obvious, as listed on Table 3. When the cause is less clear, measurement of urinary potassium excretion and assessment of acidebase status are helpful. A 24-hour urinary potassium excretion of >15 mmol, or a spot urinary potassium of >13 mmol/g creatinine, usually indicates inappropriate renal potassium loss. A metabolic acidosis in the presence of renal potassium wasting can suggest type 1 (distal) or type 2 (proximal) renal tubular acidosis. Metabolic alkalosis can cause intracellular shifts in potassium alongside insulin and beta agnoists. Management e the maintenance of potassium balance may be magnesium dependent. Magnesium levels should therefore also be measured, as combined deficiency is common and may precipitate cardiac arrhythmias. For correction, slow replacement
Hypercalcaemia: the symptoms of hypercalcaemia are classically taught as ‘painful bones, renal stones, abdominal groans and psychic moans’. Treatment of hypercalcaemia should be guided by the severity of symptoms and the urgency of correction. Intravenous rehydration with 0.9% saline provides both volume replacement and additional sodium to augment urinary co-excretion of sodium and calcium. Calcitonin is useful for treating severe hypercalcaemia as it has a relatively rapid onset of action and is usually well-tolerated. It reduces bone resorption but also has a mild calciuric effect. Bisphosphonates act by inhibiting osteoclast-mediated bone resorption and are 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
of potassium at 10e30 mmol/hour is usually recommended. In life-threatening arrhythmias, 2 mmol/minute for 10 minutes followed by 10 mmol over 5e10 minutes can be administered under continuous cardiac monitoring.
Causes of potassium disorders Hypokalaemia Decreased intake C Malnutrition C Alcoholism
Increased loss C Gastrointestinal Diarrhoea Vomiting Nasogastric losses C Renal Drugs: diuretics, steroids, amphotericin Excess mineralocorticoid activity (e.g. Conn’s syndrome) Renal tubular acidosis
Transcellular shift C Alkalosis C Drugs Insulin Beta-agonists
Decreased loss C Renal failure C Drugs: potassium sparing diuretics C Angiotensin converting enzyme inhibitors
Transcellular shifts C Acidosis C Tumour lysis syndrome C Rhabdomyolysis C Burns
Hyperkalaemia Increased intake C Oral or IV intake C Red cell transfusion
Table 3
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chloride’s role in acidebase physiology, where it is a major determinant of strong ion difference (SID) and thus hydrogen ion concentration. Chloride concentration should always be interpreted together with sodium as concurrent sodium and chloride derangement (hyperchloraemia with hypernatraemia) will not alter SID and therefore not affect the acidebase balance.
hypercalcaemia caused by endogenous overproduction of calcitriol (125-dihydroxyvitamin D). Diuretics such as frusemide should be avoided unless needed to correct excess fluid administration. Hypocalcaemia: Despite an observed association between hypocalcaemia and increased ICU morbidity and mortality, the correction of hypocalcaemia remains controversial. Hypocalcaemia will usually self-correct after a few days. Replacement does not improve the rate of normalization or mortality. Nonetheless, acute symptomatic hypocalcaemia may be treated with intravenous calcium gluconate 10% (10e20 ml) or calcium chloride 10% (5 ml) over 2 e3 minutes. If required, infusions of calcium gluconate or chloride can also be administered to maintain an ionized calcium level greater than 0.8 mmol/litre. Correction may be of particular benefit in improving clotting function. The identification and correction of co-existing magnesium, phosphate or vitamin D abnormalities are important as well.
Hyperchloraemia: Aetiology e the administration of chloriderich fluids or TPN is one major cause of hyperchloraemia in the ICU. Other mechanisms include free water loss through diarrhoea, fever, burns and diabetes insipidus or increased renal chloride reabsorption in renal failure, renal tubular acidosis and medications such as acetazolamide. Despite an observed association between hyperchloraemia and increased morbidity and mortality, it is unclear whether hyperchloraemia contributes to, or is merely associated with, critical illness. Management e the use of balanced-salt solutions in place of normal saline reduces the risk of hyperchloraemic acidosis. However, interventional studies using balanced-salt solutions have failed to demonstrate any corresponding reduction in renal impairment or mortality. Correction of hyperchloraemic acidosis is possible with loop diuretics or sodium bicarbonate although the benefit is controversial.
Magnesium Magnesium is the second most abundant intracellular cation and is involved in neuroendocrine responses to stress, protein manufacture and mitochondrial function. It also modulates calcium channel function in the cardiovascular system. Serum magnesium levels are regulated by the reabsorption of urinary magnesium.
Hypochloraemia: Aetiology e hypochloraemia can occur through chloride loss (e.g. vomiting or diuretic therapy) or excess water gain (e.g. hypotonic fluid replacement, congestive heart failure and syndrome of inappropriate anti-diuretic hormone). Deficiencies in other electrolytes, including sodium, potassium and calcium, often coexist. Management e treatment is generally only required when hypochloraemia is a primary disorder rather than a compensatory mechanism. In hypovolaemia, replacement with sodium chloride is recommended.
Hypermagnesaemia: Aetiology e hypermagnesaemia is relatively less common in ICUs and is usually secondary to renal failure or excessive supplementation. It may lead to muscle weakness and is associated with a prolonged duration of ventilation. Management e patients in renal failure may require dialysis to lower serum magnesium. Patients with normal renal function should quickly return to normal serum levels when the source of excess magnesium is stopped due to its high renal clearance.
Phosphate Phosphate is an intracellular anion and is essential for numerous cellular functions, such as ATP production and neurohumoral signalling. Total body phosphate is regulated by gastrointestinal and renal mechanisms. Serum phosphate levels reflect a balance of intracellular and extracellular flux and may be influenced by physiological factors such as pH, catecholamine levels or carbohydrate metabolism. The significance of abnormal levels depends on the underlying cause and the presence of symptoms. Urinary phosphate measurement is particularly useful in determining the cause of the derangement.
Hypomagnesaemia: Aetiology e hypomagnesaemia in the ICU has a prevalence of up to 61% and is independently associated with increased mortality. As 99% of total body magnesium is stored intracellularly and in bone and therefore cannot be readily mobilized, even small losses may result in hypomagnesaemia. Management e hypomagnesaemia in high-risk or symptomatic patients should be corrected with intravenous magnesium sulphate (20e60 mmol/24 hours) to keep serum magnesium 1.0 e1.5 mmol/litre. A slow infusion is preferred due to the slow tissue redistribution and high renal clearance. Patients with mild deficits or ongoing losses may benefit from enteral supplementation although this is limited by the low bioavailability of magnesium.
Hyperphosphataemia: Aetiology e hyperphosphataemia occurs when either the phosphate load exceeds the kidneys’ maximal rate of excretion or when there is increased resorption of filtered phosphate in the proximal tubules. Tissue breakdown (e.g. rhabdomyolysis) or cellular shifts, as seen in lactic acidosis and ketoacidosis, can also lead to high serum levels. Oral phosphate bowel preparations have also been implicated in severe and sometimes fatal calcium and phosphate disturbances. Management e with normal renal function, hyperphosphataemia is self-correcting within 24 hours. Severe or
The anions Chloride Chloride is the body’s major extracellular anion. It is regulated by the kidneys, gut and skin. In health, over 99% of filtered chloride is reabsorbed in the distal tubule. With growing interest in Stewart’s approach to acidebase analysis, there is increasing recognition of
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symptomatic hyperphosphataemia in the setting of renal failure requires dialysis. Hypertonic glucose can be used to drive phosphate (and potassium) into cells.
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Hypophosphataemia: Aetiology e hypophosphataemia may reflect a total body deficit due to excessive renal or gastrointestinal losses or reduced absorption. It may also be secondary to intracellular shifts. Although it may result from various conditions, such as sepsis and alkalosis, it is commonly seen in critically ill patients as a result of refeeding syndrome. Management e patients who are symptomatic or have severe hypophosphataemia (<0.32 mmol/litre) should have phosphate replaced intravenously at 5e20 mmol/hour, up to 100 mmol/ day, to keep serum phosphate levels greater than 0.8 mmol/litre. There is considerable controversy on the management of asymptomatic hypophosphataemia, which should be guided by the suspected cause (e.g. total body deficit versus transcellular shifts). Where possible, oral replacement is preferred over IV formulations to minimize the risk of overcorrection or precipitation of calcium phosphate complexes. A REFERENCES 1 Delanghe JR. Management of electrolyte disorders: also the method matters!. Acta Clin Belg 2019 Jan 2; 74: 2e6. 2 Chauhan K, Pattharanitima P, Patel N, et al. Rate of correction of hypernatremia and health outcomes in critically ill patients. Clin J Am Soc Nephrol 2019 May 7; 14: 656e63.
Acknowledgements The authors gratefully acknowledge the contribution of Drs Ross Freebairn and Sing Chee Tan to the previous version of this article in 2017.
FURTHER READING Hansen B-A, Bruserud Ø. Hypomagnesemia in critically ill patients. J Intensive Care 2018 Dec; 6: 21.
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