Fluid and electrolyte therapy

Published on 27/02/2015 by admin

Last modified 22/04/2025

Print this page

This article have been viewed 2783 times

Chapter 85 Fluid and electrolyte therapy

The management of patients’ fluid and electrolyte status requires an understanding of body fluid compartments as well as an understanding of water and electrolyte metabolism. These principles will be considered along with the commonly encountered fluid and electrolyte disturbances. Recent evidence for the use of fluid therapy in a number of common clinical scenarios will also be presented.

FLUID COMPARTMENTS (Table 85.1, Figure 85.1)

TOTAL BODY WATER

In humans, water contributes approximately 60% of body weight, with organs varying in water content (Table 85.2). The variation of the percentage of total body weight as water, between individuals, is largely governed by the amount of adipose tissue. The average water content as a percentage of total body weight is 60% for males and 50% for females. Total body water as a percentage of total body weight decreases with age, due to a progressive loss of muscle mass, causing bone and connective tissue to assume a greater percentage of total body weight¹^–³ (Table 85.3).

Table 85.1 Body fluid compartments

Fluid compartment	Volume (ml/kg)	% Total body weight
Plasma volume	45	4.5
Blood volume	75	7.5
Interstitial volume	200	20
Extracellular fluid volume	250	25
Intracellular fluid volume	350	35
Total body fluid volume	600	60

Figure 85.1 Body fluid compartments.

Table 85.2 Water content of various tissues

Tissue	% Water content
Brain	84
Kidney	83
Skeletal muscle	76
Skin	72
Liver	68
Bone	22
Adipose tissue	10

Table 85.3 Water content as a percentage of total body weight

Age (years)	Males (%)	Females (%)
10–15	60	57
15–40	60	50
40–60	55	47
> 60	50	45

Total body water is commonly divided into two volumes, the extracellular fluid (ECF) volume and the intracellular fluid (ICF) volume.² Sodium balance regulates the ECF volume, whereas water balance regulates the ICF volume. Sodium excretion is normally regulated by various hormonal and physical ECF volume sensors, whereas water balance is normally regulated by hypothalamic osmolar sensors.⁴

EXTRACELLULAR FLUID

ECF is defined as all body water external to the cell, and is commonly subdivided into plasma and interstitial fluid volumes. The ECF is normally 40% of total body water and 25% of total body weight. With acute or chronic illness, ICF volume is reduced, and ECF volume is increased and may even exceed the ICF volume. The ECF volume can be divided into the plasma volume, the extracellular fluid volume, and the interstitial volume.

INTRACELLULAR FLUID

ICF is defined as all the body water within cells and, unlike the ECF compartment, is an inhomogeneous, multicompartmental entity, with different pH and ionic composition depending upon the organ or tissue being considered. The ICF volume is often determined by inference from the difference in measurements of the total body water and ECF spaces. This estimation suffers from the inaccuracies inherent in both ECF and total body water measurements. In general, the ICF is considered to be 60% of total body water and 35% of total body weight.

TRANSCELLULAR FLUID

Fluids in this compartment have a common characteristic of being formed by transport activity of cells. The fluid is extracellular in nature and will be considered as part of the interstitial volume. It may vary from 1 to 10 l, with larger volumes occurring in diseased states (e.g. bowel obstruction or cirrhosis with ascites), and is formed at the expense of the remaining interstitial and plasma volumes.

WATER METABOLISM

Water balance is maintained by altering the intake and excretion of water. Intake is controlled by thirst, whereas excretion is controlled by the renal action of antidiuretic hormone (ADH). In health, plasma osmolalities of about 280 mOsm/kg suppress plasma ADH to concentrations low enough to permit maximum urinary dilution.⁵ Above this value, an increase in ECF tonicity of about 1–2% or a decrease in total body water of 1–2 l, causes the posterior pituitary to release ADH, which acts upon the distal nephron to increase water reabsorption. Maximum plasma ADH concentrations are reached at an osmolality of 295 mOsm/kg.⁵ The osmotic stimulation also changes thirst sensation and, in the conscious ambulant individual, initiates water repletion (drinking), which is more important in preventing dehydration than ADH secretion and action. Thus, in health, the upper limit of the body osmolality (and therefore serum sodium) is determined by the osmotic threshold for thirst, whereas the lower limit is determined by the osmotic threshold for ADH release.⁶

Increase in osmolality caused by permeant solutes (e.g. urea) does not stimulate ADH release. ADH may also be released in response to hypovolaemia and hypotension, via stimulation of low and high pressure baroreceptors. ADH release is extremely marked when more than 30% of the intravascular volume is lost. ADH may also be stimulated by pain and nausea, which are thought to act through the baroreceptor pathways.⁴ ADH release may also be stimulated by a variety of pharmacological agents (Table 85.4). Renal response to ADH depends upon an intact distal nephron and collecting duct, and a hypertonic medullary interstitium. The capacity to conserve or excrete water also depends upon the osmolar load presented to the distal nephron.⁴

Table 85.4 Drugs affecting ADH secretion

Stimulate	Inhibit
Nicotine	Ethanol
Narcotics	Narcotic antagonists
Vincristine	Phenytoin
Barbiturates
Cyclophosphamide
Chlorpropamide
Clofibrate
Carbamazepine
Amitriptylline

WATER REQUIREMENTS

Water is needed to eliminate the daily solute load, and to replace daily insensible fluid loss (Table 85.5). With a normal daily excretion of 600 mOsm solute, maximal and minimal secretions of ADH will cause urine osmolality to vary from 1200 to 30 mOsm/kg respectively, and the urine output to vary from 500 ml to 20 l/day respectively. Skin and lung water losses vary, and may range from 500 ml to 8 l/day depending on physical activity, ambient temperature and humidity.

Table 85.5 Daily fluid balance (for a 70-kg man at rest in a temperate climate)

DISORDERS OF OSMOLALITY

ELECTROLYTES

Chemical compounds in solution may either:

• Remain intact (i.e. undissociated), in which case they are called non-electrolytes (e.g. glucose, urea)

• Dissociate to form ions, in which case they are called electrolytes. Ions carry an electrical charge (e.g. Na⁺, Cl⁻). Ions with a positive charge are attracted to a negative electrode or cathode, and hence are called ‘cations’. Conversely, ions with a negative charge travel towards a positive electrode or anode and are called ‘anions’. Each body water compartment contains electrolytes with different composition and concentration (Table 85.6)

Table 85.6 Electrolyte composition of body fluid compartments

SODIUM

Sodium is the principal cation of the ECF and accounts for 86% of the ECF osmolality. In a 70-kg man, total body sodium content is 4000 mmol (58 mmol/kg) and is divided into a number of compartments (Table 85.7). ECF concentration of sodium varies between 134 and 146 mmol/l. The intracellular sodium concentration varies between different tissues, and ranges from 3 to 20 mmol/l.

Table 85.7 The sodium compartments in a 70-kg man

	Total (mmol)	(mmol/kg)
Total body sodium	4000	58
Non-exchangeable bone sodium	1200	17
Exchangeable sodium	2800	40
Intracellular sodium	250	3
Extracellular sodium	2400	35
Exchangeable bone sodium	150	2

The standard Western society dietary sodium intake is about 150 mmol/day, but the daily intake of sodium varies widely, with urinary losses ranging from < 1 to > 240 mmol/day.⁷ Sodium balance is influenced by renal hormonal and ECF physical characteristics. The complete renal adjustment to an altered sodium load usually requires 3–4 days before balance is restored.

HYPONATRAEMIA

Hyponatraemia is defined as a serum sodium less than 135 mmol/l and may be classified as isotonic, hypertonic or hypotonic, depending upon the measured serum osmolality (Table 85.8).

Table 85.8 Common causes of hyponatraemia

Isotonic hyponatraemia

Plasma normally contains 93% water and 7% solids (5.5% proteins, 1% salts and 0.5% lipids). If the solid phase is elevated significantly (e.g. in hyperlipidaemia or hyperproteinaemia), any device which dilutes a specific amount of plasma for analysis will give falsely lower values for all measured compounds. This effect produces ‘factitious hyponatraemia’ and is associated with a normal measured serum osmolality.⁸ Measurement of plasma sodium by an ion-selective electrode is not affected by the volume of plasma ‘solids’ and therefore ‘pseudohyponatraemia’ will not occur with this method.⁸

Hypertonic hyponatraemia

In patients who have hypertonicity due to increased amounts of impermeant solutes (e.g. glucose, mannitol, glycerol or sorbitol), a shift of water from the ICF to the ECF occurs to provide osmotic equilibration, thus diluting the ECF sodium. Such resultant hyponatraemia is often associated with an increased measured osmolality. For example, in the presence of hyperglycaemia, for every 3 mmol/l rise in glucose, the serum sodium decreases by 1 mmol/l.⁹

Hypotonic hyponatraemia

Hyponatraemia is almost always caused by an excess of total body water, due to excessive hypotonic or water-generating i.v. fluids (e.g. 1.5% glycine, 0.45% saline or 5% glucose) or excessive ingestion of water, particularly in the presence of high circulating ADH concentrations. It may rarely be caused by loss of exchangeable sodium or potassium. In the latter circumstances, a loss of approximately 40 mmol of sodium or potassium, without a change in total body water content, is required to lower the serum sodium by 1 mmol/l. As hyponatraemia may be associated with an alteration in both total body water and total body sodium, the ECF may be increased (hypervolaemia), decreased (hypovolaemia) or exhibit no change (isovolaemia).⁵

In health, a fluid intake up to 15–20 l may be tolerated before water is retained and hyponatraemia occurs. In psychogenic polydipsia, if the water intake exceeds the renal capacity to form dilute urine, water retention and hyponatraemia will occur. With this disorder, the plasma osmolality exceeds urine osmolality. In circumstances where ADH is increased (e.g. hypovolaemia, hypotension, pain or nausea), or where renal response to ADH is altered (i.e. in renal, hepatic, pituitary, adrenal or thyroid failure), water retention occurs with lower intakes of fluid.

Transurethral resection of prostate (TURP) syndrome

Clinical features

The TURP syndrome consists of hyponatraemia, cardiovascular disturbances (hypertension, hypotension, bradycardia), an altered state of consciousness (agitation, confusion, nausea, vomiting, myoclonic and generalised seizures) and, when using glycine solutions, transient visual disturbances of blurred vision, blindness and fixed dilated pupils, following TURP. It has also been described following endometrial ablation.¹⁰ It may occurwithin 15 minutes or be delayed for up to 24 hours postoperatively,¹¹ and is usually caused by an excess absorption of the irrigating fluid which contains 1.5% glycine with an osmolality of 200 mosm/kg. Hyponatraemic syndromes have also been described when irrigating solutions containing 3% mannitol or 3% sorbitol have been used. Symptomatology usually occurs when > 1 l of 1.5% glycine or > 2–3 l of 3% mannitol or sorbitol are absorbed.¹²

The excess absorption of irrigating fluid causes an increase in total body water (which is often associated with only a small decrease in plasma osmolality), hyponatraemia (as glycine, sorbitol or mannitol reduces the sodium component of ECF osmolality) and an increase in the osmolar gap.^12,¹³ When glycine is used, other features include hyperglycinaemia (up to 20 mmol/l; normal plasma glycine concentrations range from 0.15 to 0.3 mmol/l), hyperserinaemia (as serine is a major metabolite of glycine), hyperammonaemia (following deamination of glycine and serine), metabolic acidosis and hypocalcaemia (due to the glycine metabolites glyoxylic acid and oxalate). Because glycine is an inhibitory neurotransmitter, and as it passes freely into the intracellular compartment when glycine solutions are used, hyperglycinaemia may be more important in the pathophysiology of this disorder than a reduction in body fluid osmolality and cerebral oedema.¹⁴

Treatment

Treatment is largely supportive with the management of any reduction in plasma osmolality being based on the measured plasma osmolality and not the plasma sodium. If the measured osmolality is > 260 mOsm/kg and mild neurological abnormalities exist, and if the patient is haemodynamically stable with normal renal function, close observation and reassurance (e.g. the visual disturbances are reversible and will last for less than 24 hours) are usually all that is needed. If the patient is hypotensive and bradycardic with severe and unresolving neurological abnormalities, haemodialysis may be warranted. Hypertonic saline is only used if the measured osmolality is < 260 mOsm/kg and severe non-visual neurological abnormalities exist.¹⁵

Syndrome of inappropriate ADH secretion (SIADH)

This syndrome is a form of hyponatraemia in which there is an increased concentration of ADH inappropriate to any osmotic or volume stimuli that normally affect ADH secretion.¹⁶ Diagnostic criteria and common causes are listed in Tables 85.9 and 85.10, respectively.

Table 85.9 Criteria for the diagnosis of syndrome of inappropriate antidiuretic hormone (SIADH)

Hypotonic hyponatraemia

Urine osmolality greater than plasma osmolality

Urine sodium excretion greater than 20 mmol/l

Normal renal, hepatic, cardiac, pituitary, adrenal and thyroid function

Absence of hypotension, hypovolaemia, oedema and drugs affecting ADH secretion

Correction by water restriction

Table 85.10 Aetiologies of syndrome of inappropriate antidiuretic hormone (SIADH)

Clinical features

While cerebral manifestations are usually absent when the sodium concentration exceeds 125 mmol/l, progressive symptomatology of headache, nausea, confusion, disorientation, coma and seizures are often observed when plasma sodium is below 120 mmol/l.¹⁷

Treatment

Initial treatment should be fluid restriction with close monitoring of serum sodium. If serum sodium concentration is not increasing with fluid restriction, judicious administration of sodium as intravenous normal or hypertonic saline may be required. As the true duration and rapidity of onset of hyponatraemia is often unclear, the presence and severity of symptoms may be used as the trigger for active correction of hyponatraemia.¹⁷ The evidence base available to guide therapy is limited and there is consequently no consensus on the optimum rate at which to correct the serum sodium concentration. The major concern is to avoid neurological damage from untreated seizures or cerebral oedema and from myelinolysis.¹⁷ In the absence of good evidence, recommended rates at which to increase the sodium concentration vary from 0.5 to 2 mmol/l per hour. Unless the treating clinician feels that more rapid correction is indicated, it seems prudent to correct the serum sodium concentration at a slower rather than a faster rate.

Cerebral salt wasting

Cerebral salt wasting (CSW) is a syndrome occurring in patients with a cerebral lesion and an excess renal loss of sodium and chloride.¹⁸ The exact aetiology of the syndrome remains unclear. Although hyponatraemia is not necessary for the diagnosis, the syndrome is commonly associated with hyponatraemia.¹⁹ The diagnosis of CSW is suspected in patients with a cerebral lesion, such assubarachnoid haemorrhage, traumatic brain injury or a cerebral tumour, when there is an elevated urine output, with elevated urinary sodium in the absence of a physiological cause for increased sodium excretion.¹⁹ The syndrome can be differentiated from the SIADH, as patients with CSW will have evidence of ECF depletion (e.g. negative fluid balance, tachycardia, increased haematocrit, increased urea, low central venous pressure) as opposed to the SIADH where ECF volume will be normal or slightly expanded.²⁰ Treatment of patients involves exclusion of other causes of hyponatraemia and increased urine output, replacement of sodium and fluid losses, and possibly fludrocortisone.²¹

Hypertonic saline

Hypertonic saline, most commonly as 3% saline, is used as a therapy for patients with symptomatic hyponatraemia. Due to the osmolarity (1000 mosm/l) of 3% saline, it must be given through a central line, and care must be taken to avoid the known complications of its use. Complications reported with hypertonic saline therapy include congestive cardiac failure and central pontine and extrapontine myelinolysis (osmotic demyelination syndrome).^22,²³ Careful haemodynamic and electrolyte monitoring throughout saline administration is required. There is still no uniform agreement that osmotic demyelination is produced by a rapid correction of hyponatraemia.

While hypertonic saline has been proposed as a therapy for raised intracranial pressure in a number of clinical settings,²⁴ its use remains controversial.²⁵ In a recent methodologically sound (adequate allocation concealment, blinded and using intention to treat analysis) randomised clinical trial, which included 229 patients with severe traumatic brain injury, resuscitation with 250 ml of 7.5% saline was not associated with improved mortality or functional outcomes compared to Hartmann’s solution.²⁶

Vasopressin receptor antagonists

V₂ receptor antagonists, such as lixivaptan, tolvaptan and OPC-31260, have recently been developed. These agents come from a novel class of non-peptide agents that bind to V₂ receptors in the distal tubule of the kidney and prevent vasopressin-mediated aquaporin mobilisation, and thus promote an aquaresis.²⁷ These agents have been trialled as therapeutic options for the treatment of hyponatraemia in a number of clinical settings including hyponatraemia associated with cardiac failure, cirrhosis and SIADH.^27,²⁸ At present the role of V₂ receptor antagonists in the management of hyponatraemia in the critically ill remains uncertain.

HYPERNATRAEMIA

Hypernatraemia, defined as a serum sodium greater than 145 mmol/l, is always associated with hyperosmolality and may be caused by excessive administration of sodium salts (bicarbonate or chloride), water depletion or excess sodium and loss of water (Table 85.11).

Table 85.11 Causes of hypernatraemia

Excessive ingestion of sodium salts is rare but intravenous infusion of large volumes of sodium-containing fluids is common in the management of hospitalised patients. Hypernatraemia often occurs in the recovery phase of acute illness when spontaneous diuresis or diuretic therapy results in more rapid clearance of free water than sodium. Pure water depletion is uncommon, unless water restriction is applied to a patient who is unconscious or unable to obtain or ingest water, as the thirst response normally corrects water depletion. If it occurs, the serum sodium concentration increases, in association with loss of both ECF and ICF.

Clinical features

Hypernatraemia usually produces symptoms if the serum sodium exceeds 155–160 mmol/l (i.e. osmolality > 330 mOsm/kg). The clinical features include increased temperature, restlessness, irritability, drowsiness, lethargy, confusion and coma.²⁹ Convulsions are uncommon. The diminished ECF volume may reduce cardiac output, thereby reducing renal perfusion, leading to pre-renal renal failure.

Treatment

For pure water depletion, this consists of water administration. If i.v. fluid is required, 5% glucose or hypotonic saline solutions (0.45% saline) are often used, as sterile water infusion causes haemolysis. In rare cases, i.v. sterile water may be used, by administering through a central venous catheter.³⁰ Since rapid rehydration may give riseto cerebral oedema, the change in serum sodium should be no greater than 0.5 mmol/l per hour.²⁹

POTASSIUM

Potassium is the principal intracellular cation and accordingly (along with its anion) fulfils the role of the ICF osmotic provider. It also plays a major role in the functioning of excitable tissues (e.g. muscle and nerve). As the cell membrane is 20-fold more permeable to potassium than sodium ions, potassium is largely responsible for the resting membrane potential. Potassium also influences carbohydrate metabolism and glycogen and protein synthesis.

Total body potassium is 45–50 mmol/kg in the male (3500 mmol/70 kg) and 35–40 mmol/kg (2500 mmol/65 kg) in the female; 95% of the total body potassium is exchangeable. As ECF potassium ranges from 3.1 to 4.2 mmol/l, the total ECF potassium ranges from 55 to 70 mmol. About 90% of the total body potassium is intracellular: 8% resides in bone, 2% in ECF water and 70% in skeletal muscle. With increasing age (and decreasing muscle mass), total body potassium decreases.

FACTORS AFFECTING POTASSIUM METABOLISM

The potassium content of cells is regulated by a cell wall pump-leak mechanism. Cellular uptake is by the Na⁺/K⁺ pump which is driven by Na⁺/K⁺ ATPase. Movement of potassium out of the cell is governed by passive forces (i.e. cell membrane permeability and chemical and electrical gradients to the potassium ion).

Acidosis promotes a shift of potassium from the ICF to the ECF, whereas alkalosis promotes the reverse shift. Hyperkalaemia stimulates insulin release, which promotes a shift of potassium from the ECF to the ICF, an effect independent of the movement of glucose. β₂-adrenergic agonists promote cellular uptake of potassium by a cyclic AMP-dependent activation of the Na⁺/K⁺ pump, whereas α-adrenergic agonists cause a shift of potassium from the ICF to the ECF.³¹ Aldosterone increases the renal excretion of potassium; glucocorticoids are also kaliuretic, an effect which may be independent of the mineralocorticoid receptor.

Normally, mechanisms to reduce the ECF potassium concentration (by increasing renal excretion and shifting potassium from the ECF to the ICF) are very effective. However, mechanisms to retain potassium in the presence of potassium depletion are less efficient, particularly when compared to those of sodium conservation. Even with severe potassium depletion, urinary loss of potassium continues at a rate of 10–20 mmol/day. Metabolic alkalosis also enhances renal potassium loss, by encouraging distal nephron Na⁺/K⁺, rather than Na⁺/K⁺ exchange.

HYPOKALAEMIA

Hypokalaemia is defined as a serum potassium of less than 3.5 mmol/l (or plasma potassium less than 3.0 mmol/l). It may be due to decreased oral intake, increased renal or gastrointestinal loss, or movement of potassium from the ECF to the ICF (Table 85.12).

Table 85.12 Causes of hypokalaemia

Clinical features

These include weakness, hypotonicity, depression, constipation, ileus, ventilatory failure, ventricular tachycardias (characteristically torsades de pointes), atrial tachycardias, and even coma.³² With prolonged and severe potassium deficiency, rhabdomyolysis and thirst and polyuria, due to the development of renal diabetes insipidus, may occur. The ECG changes are relatively non-specific, and include prolongation of the PR interval, T-wave inversion and prominent U-waves.

Treatment

Intravenous or oral potassium chloride will correct hypokalaemia, particularly if it is associated with metabolic alkalosis. If the patient has renal tubular acidosis and hypokalaemia, potassium acetate or citrate may be preferred to potassium chloride. Intravenous administration of potassium should normally not exceed 40 mmol/hour, and plasma potassium should be monitored at 1–4-hourly intervals.³³ In patients with acute myocardial infarction and hypokalaemia, some recommend i.v. potassium to maintain the serum potassium at 4.0 mmol/l.³⁴ The plasma concentration should be monitored closely.

HYPERKALAEMIA

Hyperkalaemia is defined as a serum potassium greater than 5.0 mmol/l or plasma potassium greater than 4.5 mmol/l. It may be artifactual (from sampling errors such as in vitro haemolysis); true hyperkalaemia may be due to excessive intake, severe tissue damage, decreased excretion or body fluid compartment shift (Table 85.13).

Table 85.13 Causes of hyperkalaemia

Clinical features

These include tingling, paraesthesia, weakness, flaccid paralysis, hypotension and bradycardia. The characteristic ECG effects include peaking of the T-waves, flattening of the P-wave, prolongation of the PR interval (until sinus arrest with nodal rhythm occurs), widening of the QRS complex, and the development of a deep S-wave. Finally, a sine wave ECG pattern which deteriorates to asystole may occur at serum potassium levels of 7 mmol/l or greater.

Treatment

This is directed at the underlying cause, and may include dialysis. Rapid management of life-threatening hyperkalaemia may be achieved by:³⁵

• Calcium chloride 5–10 ml i.v. of 10% (3.4–6.8 mmol, which is used to reduce the cardiac effects of hyperkalaemia)

• Sodium bicarbonate, 50–100 mmol i.v.

• Glucose, 50 g i.v. with 20 units of soluble insulin

• Oral and rectal resonium A, 50 g

• Diuresis with furosemide, 40–80 mg i.v.

CALCIUM

Almost all (99%) of the body calcium (30 mmol or 1000 g or 1.5% body weight) is present in bone. A small but significant quantity of ionised calcium exists in the ECF, and is important for many cellular activities, including secretion, neuromuscular impulse formation, contractile functions and clotting. Normal daily intake of calcium is 15–20 mmol, although only 40% is absorbed. The average daily urinary loss is 2.5–7.5 mmol. The total ECF calcium of 40 mmol (2.20–2.55 mmol/l) exists in three forms: 40% (1.0 mmol/l) is bound to protein (largely albumin), 47% is ionised (1.15 mmol/l) and 13% is complexed (0.3 mmol/l) with citrate, sulphate and phosphate. The ionised form is the physiologically important form, and may be acutely reduced in alkalosis which causes a greater amount of the serum calcium to be bound to protein.³⁶ While the serum ionised calcium can be measured, total serum calcium is usually measured, which can vary with the serum albumin concentrations. A correction factor can be used to offset the effect of serum albumin on serum calcium. This is 0.02 mmol/l for every 1 g/l increase in serum albumin (up to a value of 40 g/l), added to the measured calcium concentration. For example, if measured serum calcium is 1.82 mmol/l, and serum albumin is 25 g/l, corrected serum calcium = 1.82 + [(40–25) × 0.02] mmol/l = 2.12 mmol/l. It has been suggested that ionised calcium, where available, is a better indicator of calcium status in the critically ill.³⁷

HYPOCALCAEMIA

Common causes of hypocalcaemia include hypoparathyroidism and pseudohypoparathyroidism, septic shock, acute pancreatitis and rhabdomyolysis.³⁸ Clinical features of a reduced serum ionised calcium include tetany, cramps, mental changes and decrease in cardiac output. Symptomatic hypocalcaemia should be treated with i.v. calcium, either as calcium chloride or calcium gluconate. It should be remembered that 1 ml of calcium chloride has three times as much elemental calcium as 1 ml of calcium gluconate, and so the former is the preferred formulation in acute situations. Calcium should be administered via a central vein when practical due to the risk of tissue damage if extravasated.³⁸

HYPERCALCAEMIA

The clinical features of hypercalcaemia include nausea, vomiting, pancreatitis, polyuria, polydipsia, muscular weakness, mental disturbance and ectopic calcification. Some of the common causes of hypercalcaemia include endocrine diseases such as hyperparathyroidism and thyrotoxicosis, renal failure, malignancy, thiazide diuretics and prolonged immobilisation.³⁸

Severe hypercalcaemia (> 3.3 mmol/l) or more moderate symptomatic hypercalcaemia will require specific therapy. A cause for the elevated calcium concentration should be sought, and specific treatment may be warranted. General measures include restoration of intravascular volume with normal saline, followed by the use of a loop diuretic such as furosemide to promote calcium excretion. The use of bisphosphonates, such as pamidronate (30–90 mg by i.v. infusion), is recommended for severe cases.³⁹ Other therapies to consider include steroids, calcitonin and mithramycin.

MAGNESIUM

Magnesium is primarily an intracellular ion which acts as a metallo-coenzyme in numerous phosphate transfer reactions. It has a critical role in the transfer, storage and utilisation of energy.

In humans, the total body magnesium content is 1000 mmol, and the plasma concentrations range from 0.70 to 0.95 mmol/l. The daily oral intake is 8–20 mmol (40% of which is absorbed) and the urinary loss, which is the major source of excretion of magnesium, varies from 2.5 to 8 mmol/day.⁴⁰

HYPOMAGNESAEMIA

Hypomagnesaemia is caused by decreased intake or increased loss (Table 85.14). Clinical features include neurological signs of confusion, irritability, delirium tremors, convulsions and tachyarrhythmias. Hypomagnesaemia is often associated with resistant hypokalaemia and hypocalcaemia. Treatment consists of i.v. magnesium sulphate as a bolus of 10 mmol, administered over 5 minutes, followed by 20–60 mmol/day.

Table 85.14 Causes of magnesium deficiency

HYPERMAGNESAEMIA

Hypermagnesaemia is often caused by excessive administration of magnesium salts or conventional doses of magnesium in the presence of renal failure. Clinical features include drowsiness, hyporeflexia and coma, vasodilatation and hypotension, and conduction defects of sinoatrial and atrioventricular nodal block and asystole may occur. Treatment is directed towards increasing excretion of the ion, which may require dialysis. Intravenous calcium chloride may be used for rapidly treating the cardiac conduction defects.⁴⁰

MAGNESIUM THERAPY

There are increasing reports of the use of magnesium as a therapy for a variety of conditions. A randomised control trial of over 10 000 women with pre-eclampsia demonstrated the efficacy of magnesium in the prevention of eclampsia,⁴¹ and it is also a recommended treatment for established eclampsia. It has been used to treat atrial fibrillation, to achieve both rate control and reversion to sinus rhythm in a number of settings, including post cardiac surgery, and in the emergency department.^42,⁴³ Magnesium, given either intravenously or nebulised, may be beneficial for patients with acute severe asthma.^44,⁴⁵ There are also preliminary trials to suggest that magnesium may prevent delayed cerebral ischaemia due to vasospasm in patients with subarachnoid haemorrhage.⁴⁶

PHOSPHATE

While most of the body phosphate exists in bone, 15% is found in the soft tissues as ATP, red blood cell 2,3-DPG, and other cellular structural proteins, including phospholipids, nucleic acids and phosphoproteins. Phosphate also acts as a cellular and urinary buffer.⁴⁰

HYPERPHOSPHATAEMIA

Hyperphosphataemia is usually caused by an increased intake or decreased excretion (Table 85.16). Clinical features include ectopic calcification of nephrocalcinosis, nephrolithiasis and band keratopathy. Treatment may require haemodialysis; otherwise oral aluminium hydroxide and even hypertonic glucose solutions to shift ECF phosphate into the ICF can be used.

Table 85.16 Causes of hyperphosphataemia

Rhabdomyolysis

Renal failure (acute or chronic)

Pseudohypoparathyroidism

Diphosphonate therapy

Excess i.v. administration

FLUID AND ELECTROLYTE REPLACEMENT THERAPY

GENERAL PRINCIPLES

In critical illness many of the body’s normal homeostatic mechanisms are deranged and basic life-preserving senses such as hunger and thirst may be abolished by disease processes or by treatments such as the use of sedation. As a result, the survival of critically ill patients depends on the administration of appropriate volumes of fluids, and appropriate quantities of electrolytes and nutrition by their medical and nursing attendants. Basal requirements for water, electrolytes and nutrients are discussed in Chapter 87. In addition to basal requirements, many critically ill patients have abnormal fluid and electrolyte losses that must be replaced; examples are discussed below.

GASTROINTESTINAL LOSSES

The daily volumes and composition of gastrointestinal tract (GIT) secretions in mmol/l are shown in Table 85.17. Clinical effects of fluid loss from the GIT are largely determined by the volume and composition of the fluid, and therapy is usually directed at replacing the losses. Gastric fluid loss (e.g. from vomiting and nasogastric suction) results in water, sodium, hydrogen ion, potassium and chloride depletion. Hence, metabolic alkalosis, hypokalaemia, hypotension and dehydration develop if the saline and potassium chloride losses are not correctly replaced.

Table 85.17 Daily volume and electrolyte composition of GIT secretions

Systemic hypotension is a common feature of acute critical illness and first-line treatment is usually the administration of intravenous resuscitation fluid. The fluids available to clinicians to maintain or expand intravascular volume are crystalloids, colloids and blood products; the properties of colloid solutions and blood products are discussed in Chapter 89.

Whether the choice of resuscitation fluid influences patients’ outcomes has been the subject of long-running debate. The debate has been fuelled by the conflicting and inconclusive results of a number of meta-analyses.⁴⁷^–⁵⁰ At present, the published data do not provide unequivocal support for either side of the debate. The only adequately powered trial to date, the Saline versus Albumin Fluid Evaluation Study, found that saline and albumin produced comparable outcomes in a heterogeneous population of adult patients.⁵¹ Whether specific fluids are beneficial or harmful in more highly selected subpopulations of critically ill patients is not yet clear. A number of investigator-initiated trials are currently underway and are expected to report their results in the next few years. These trials may provide clinicians with the data needed to make rational fluid choices.

REFERENCES

1 Edelman IS, Leibman J. Anatomy of body water and electrolytes. Am J Med. 1959;27:25-77.

2 Gamble J. Chemical Anatomy, Physiology and Pathology of Extracellular Fluid. Cambridge, MA: Harvard University Press, 1954.

3 Moore FD, Olesen KH, McMurray JD. Body Composition in Health and Disease. Philadelphia: WB Saunders, 1963.

4 Bie P. Osmoreceptors, vasopressin, and control of renal water excretion. Physiol Rev. 1980;60:961-1048.

5 Humes HD. Disorders of water metabolism. In: Kokko JP, Tannen RL, editors. Fluid and Electrolytes. Philadelphia: WB Saunders; 1986:118-149.

6 Phillips PJ. Water metabolism. Anaesth Intensive Care. 1977;5:295-304.

7 Intersalt Cooperative Research Group. Intersalt: an international study of electrolyte excretion and blood pressure. Results for 24 hour urinary sodium and potassium excretion. BMJ. 1988;297:319-328.

8 Weisberg LS. Pseudohyponatremia: a reappraisal. Am J Med. 1989;86:315-318.

9 Katz MA. Hyperglycemia-induced hyponatremia – calculation of expected serum sodium depression. N Engl J Med. 1973;289:843-844.

10 Arieff AI, Ayus JC. Endometrial ablation complicated by fatal hyponatremic encephalopathy. JAMA. 1993;270:1230-1232.

11 Gravenstein D. Transurethral resection of the prostate (TURP) syndrome: a review of the pathophysiology and management. Anesth Analg. 1997;84:438-446.