Basic concepts of fluid and electrolyte therapy 2nd edition – Part 4
9 November 2023
BJS Academy is delighted to host the second edition of the textbook ‘basic concepts of fluid and electrolyte therapy’, by Lobo, Lewington and Allison.
The authors have kindly divided the book into four easily digestible sections, and then some multiple choice questions at the end. This is the fourth section.
Surgeons sometimes focus a little too much on the technical aspects of their work, but without a sound knowledge of fluid and electrolyte management, their efforts in the operating theatre may easily be undone.
All surgeons will benefit from reading this book and gaining an understanding of how best to optimise fluid management in their patients.
Director, BJS Academy
The authors have made every eﬀort to ensure that drug dosages in this book are in accordance with current recommendations and practice at the time of publication.
However, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions.
The ﬁrst edition of this book was published in 2013 with the aim of improving understanding and clinical practice in the ﬁeld of ﬂuid and electrolyte therapy. Studies at that time suggested that, even though ﬂuid and electrolyte preparations are the most commonly prescribed medications in hospitals, management of ﬂuid and electrolyte disorders was suboptimal, possibly due to inadequate teaching, causing avoidable morbidity and even mortality. It should not be forgotten that ﬂuid therapy, like other forms of treatment, has the capacity to do harm as well as good unless administered with care and based on sound knowledge.
A second edition was felt appropriate in the light of further advances in knowledge and practice over the last 9 years. We have updated the book, adding new chapters, ﬁgures, tables and ﬂow charts to help the reader. New chapters include Ageing and Fluid Balance, Chronic Kidney Disease, Fluid Overload and the De-escalation Phase, and Perioperative Fluid Therapy and Outcomes. We have also tried to maintain consistency with published national and international guidelines, where available. References have now been cited in the text. To limit the number of references, we have tried, as far as possible to cite important review articles from which original studies may be sourced. However, relevant original works have been referred to when appropriate. We have included multiple choice questions so that readers may test their knowledge after reading the book.
The subject of ﬂuid balance in paediatrics is not addressed and this book should be regarded as relevant to adults only. It is still not our intention to write a comprehensive textbook dealing with complex problems, but to provide a basic hand-book for students, nurses, trainee doctors and other health care professionals to help them to understand and solve some of the most common practical problems they face in day to day hospital practice. We hope that it will also stimulate them to pursue the subject in greater detail with further reading and practical experience. In diﬃcult cases, or where there is uncertainty, trainee health care professionals should never hesitate to ask for advice from senior and experienced colleagues.
Dileep N. Lobo
Andrew J. P. Lewington
Simon P. Allison
THE PATIENT WITH DIABETES MELLITUS
With better management of diabetes mellitus in recent years, admissions due to loss of control with or without ketosis are less frequent than in former times. Nonetheless, cases of decompensated diabetes with keto-acidosis (DKA) or hyperosmolar nonketotic (HONK) syndrome form an important part of every doctor’s experience of acute medicine109-112. Similarly, with the rising prevalence of diabetes, particularly type 2, the perioperative ﬂuid and metabolic management of diabetic patients has become increasingly important113-115.
Type 1 diabetes109,110: insulin secretion is impaired in most cases by >90%. This means that, with reduced or absent administration of insulin or with increased insulin demand due to intercurrent illness, not only does the blood glucose rise but control over fat and protein metabolism is lost, leading to ketoacidosis (β-hydroxybutyrate being the main keto-acid) and protein catabolism.
Type 2 diabetes111,112: This is associated initially with insulin resistance but only partial loss of secretion. At this stage, there is usually suﬃcient circulating insulin to prevent ketosis but not to control the blood glucose. Decompensation usually presents with HONK in which the blood glucose rises to higher levels than those seen in DKA (it only takes a fraction of the amount of insulin to control ketosis than it does to control blood glucose). With loss of insulin secretion over the years and with severe intercurrent illness, patients with type 2 diabetes can develop ketoacidosis, requiring insulin, even though they may be able to revert to tablet treatment afterwards.
DKA109,110 and HONK111 represent the two extremes of the spectrum of decompensated diabetes (Table 13.1), although intermediate cases are not infrequent, depending on the precipitating cause and the percentage loss of insulin secretion. In both situations, hyperglycaemia causes an osmotic diuresis with excessive urinary losses of salt, water, and potassium, leading to ECF and intravascular volume depletion and the risk of AKI.
With both types of decompensation, potassium is lost from cells due to catabolism of glycogen and protein. It is then excreted in the urine causing a deﬁcit, which only becomes apparent as hypokalaemia once the anabolic eﬀect of insulin treatment is felt. In severe cases the rate of K+ loss from cells, combined with AKI, can cause hyperkalaemia (>5.5 mmol/L) with the risk of cardiac arrest.
The presence of acidosis may present diagnostic problems. Although most patients with ketonuria and features of metabolic acidosis are suﬀering from ketoacidosis, this cannot always be assumed, particularly where there are other potential causes of acidosis, e.g. renal or circulatory failure. If large volumes of 0.9% saline have been used for resuscitation, a hyperchloraemic acidosis may be imposed on the underlying metabolic changes. For these reasons and to establish the diagnosis beyond doubt it is important to measure blood concentrations of lactate, chloride, and ketones. Arterial blood gas analysis should also be performed and the anion gap or the strong ion diﬀerence should be calculated.
The aims of treatment are similar in both DKA and HONK, although with diﬀerences of emphasis.
- Restore the circulation and the ECF deﬁcit by initially rapid ﬂuid infusion. This also has a beneﬁcial metabolic eﬀect by reducing the blood glucose, addressing circulatory failure and AKI, and reducing both acidosis and serum potassium concentration.
- Seek the underlying cause of the diabetic decompensation (e.g. sepsis) and treat it.
Fluids and insulin
- In the absence of shock or oliguria, give 1-2 litres of crystalloid (see below) in the ﬁrst 2 hours, then 1 litre over the next 4 hours and 4 litres over the next 24 hours. In severe cases, administration should be faster initially, aiming to correct half the ﬂuid deﬁcit within the ﬁrst 6 hours and the remainder over the ensuing 24 hours. With HONK the ﬂuid deﬁcits are larger (Table 13.1)
- After the ﬁrst litre of ﬂuid add KCl 20-40 mmol to each subsequent litre of ﬂuid infused, depending on the changes in serum K+ with treatment.
- To avoid precipitating cerebral oedema, the eﬀective serum osmolality should not be reduced at a rate greater than 3 mOsm/kg/h. This is particularly important in cases involving children or the elderly and in the treatment of HONK.
- When the blood glucose has fallen to 14 mmol/L, change to a hypotonic (e.g. 0.45% saline in 5% dextrose) glucose-containing solution adjusted according to the insulin-induced changes in blood glucose and the serum sodium and osmolality.
- Treat acidosis with ﬂuid infusion, insulin, and, in severe cases (pH <7.0), with bicarbonate
- If serum potassium concentration exceeds 5.5 mmol/L, this will usually respond to infusion of ﬂuid and insulin. However, in patients with AKI or higher potassium concentrations, adopt the regimen recommended in Chapter 10.
- Reduce blood glucose and ketones with insulin infusion. It may take up to 48 hours to clear ketones if DKA is severe. Add 50 U soluble short-acting insulin to 50 ml 0.9% saline in a syringe driver and administer intravenously at 6 U/h, adjusting subsequently to lower the blood glucose at a rate no faster than 4 mmol/L/h.
- Monitor blood glucose, urinary ketones, acid-base status, serum potassium, sodium, chloride and, if appropriate, osmolality, every hour or two initially. Watch particularly for a fall in serum potassium and correct this with increased potassium input to maintain serum K+ in the range of 3.3-4.5 mmol/L. Monitor clinical status, vital signs, kidney function and urine output.
Traditionally, 0.9% saline has been used for resuscitation, followed by 0.45% saline in 5% dextrose and KCl as the volume deﬁcit nears restoration. Recent studies suggest that using a balanced electrolyte solution avoids the hyperchloraemic acidosis associated with administration of 0.9% saline although there is currently no evidence concerning its clinical advantage in this situation.
Hypotonic solutions pose a risk of too rapid a fall in osmolality unless the plasma sodium and osmolality are monitored carefully and the infusion rate controlled accordingly. It should be remembered that glucose acts like Na+ as an ECF osmotic agent, so that as the blood glucose falls with insulin treatment, water passes from the ECF to the ICF, thereby raising the ECF sodium concentration by 1.6 mmol/L for every 5.6 mmol/L fall in blood glucose. It is common, therefore, particularly in HONK, to see the plasma Na+ rise with treatment, necessitating a switch to a more hypotonic solution. It is at this point that switching from 0.9% to 0.45% saline may be useful gradually to reduce the plasma Na+ to normal.
Although there is a phosphate deﬁcit in decompensated diabetes, and phosphate concentration falls with treatment, phosphate supplementation has not been shown to be beneﬁcial.
SURGERY IN THE PATIENT WITH DIABETES
This section gives only a very brief outline of the subject. For more complete advice, the reader is urged to consult recently published guidelines113-115.
Perioperative glucose control
For short procedures, involving missing no more than one meal, particularly in patients with Type 2 diabetes, the normal treatment may be delayed until postoperatively, with hourly monitoring of blood glucose and treatment of diabetes with insulin if blood glucose rises above 12.0 mmol/L.
Those expected to miss more than 1 meal, particularly patients with Type 1 diabetes should receive variable rate insulin infusion (VRII) to maintain blood glucose within the range 4-12 mmol/L as shown by hourly monitoring. Insulin should be administered in 0.45% saline in 5% glucose and KCl 20-40 mmol/L (depending on the presence of hypokalaemia) via a syringe pump, starting approximately 6 hours preoperatively and continuing postoperatively until normal oral intake is established.
Perioperative ﬂuid and electrolyte management
The principles are the same as those we have outlined for the patient without diabetes. In the patient with Type 1 diabetes, however, in order to avoid ketosis, it is useful to have a constant rate of infusion of a crystalloid containing 5% glucose with appropriate VRII cover. This can be achieved using 0.45% saline with 5% dextrose and 20 or even 40 mmol KCl/L, depending on the serum potassium concentration. Alternatively, if a multi electrolyte-containing solution is preferred, use Plasma-Lyte 56 Maintenance if available (see Chapter 6).
DISORDERS OF SODIUM, POTASSIUM, CALCIUM, MAGNESIUM AND PHOSPHATE
It is impossible to give a detailed account of all aspects of these electrolytes in a brief chapter such as this. We have, therefore, conﬁned ourselves to a short summary of some common aspects. For more detailed treatment of the subject the reader is referred to excellent review articles and books10,55,116-119.
The total body sodium is 3000-4000 mmol (69-92 g), of which only 60% is exchangeable, the remainder being locked mainly in bone. The required daily intake in health to maintain balance is about 1 mmol/kg body weight. Short-term changes in the serum sodium concentration are usually due to changes in water balance, although, in some cases, changes in salt balance may contribute. This reﬂects the fact that salt balance relates mainly to maintenance of volume, whereas water balance is more concerned with osmolality. Hyponatraemia and hypernatraemia, resulting from excess or deﬁcit of water, may occur in the presence of positive, negative or zero salt balance. The serum sodium concentration on its own, therefore, cannot be used to diagnose the state of sodium balance, although if change in water balance is known from serial weighing, then the day-to-day balance of sodium can be inferred from the change in serum sodium concentration over the same period (see Chapter 5).
In severe cases with serum sodium <120 mmol/L, there is a risk of developing cerebral oedema and brain damage, particularly in children and the elderly. Conversely, too rapid correction of severe hyponatraemia may also cause neurological damage (osmotic demyelination). It is advised that hyponatraemia be corrected at a rate not exceeding 8-10 mmol/L/day.
In the diﬀerential diagnosis of hyponatraemia, pseudo-hyponatraemia should be excluded. Milky serum due to severe hyperlipidaemia, may cause the serum sodium concentration to be falsely low since the lipid expands ECF volume but contains no sodium.
Similarly, hyperglycaemia expands ECF volume by its osmotic action and, as the blood glucose falls with treatment of decompensated diabetes (see Chapter 13), water passes from the ECF to the ICF and the sodium concentration rises. Conversely, serum sodium concentration falls by 1.6 mmol/L for every 5.6 mmol/L rise in plasma glucose. In cases of hyperglycaemia, therefore, the serum sodium concentration should be corrected upwards appropriately. It is the corrected value that should guide ﬂuid replacement.
Some clinical causes of hyponatraemia are listed below:
- Positive water and salt balance: This often occurs as a result of infusions of hypotonic ﬂuid postoperatively, following trauma, or during acute illness, when the metabolic response to injury prevents excretion of any salt and/or water excess and impairs the ability of the kidney to correct a low serum osmolality by increasing free water clearance (see Chapter 1). In this situation there is usually a positive sodium balance, but a proportionally greater positive water balance. Urinary sodium concentrations are usually low since, during the salt and water retention phase of injury, the normal physiological relationship between sodium balance and urinary sodium is lost. Treatment consists mainly of stopping or reducing intravenous ﬂuids until normal ﬂuid balance is regained.
- Positive water and normal or slightly negative salt balance. This occurs with the syndrome of inappropriate ADH secretion (SIADH), classically associated with small cell carcinoma of the lung, but is also caused by a number of other conditions. With water retention in SIADH, the serum sodium is diluted, but the urinary sodium is normal or high, as the kidneys respond to the slight hypervolaemia and the associated reduction in aldosterone secretion. This condition is often over-diagnosed and should not be confused with the far more common response to injury described above in which the urinary sodium is usually low. SIADH can be treated with water restriction, supplemented in some cases with thiazide diuretics.
- Normal water balance and negative salt balance. This classically occurs in Addison’s disease with its loss of both mineralocorticoid and glucocorticoid secretion and clinical features of weakness, weight loss, pigmentation and hypotension. Hyponatraemia occurs not only due to renal salt loss, but also due to the impaired ability of the kidney to correct osmolality; ﬁrstly because salt loss causes ECF hypovolaemia, which stimulates ADH secretion, and secondly because glucocorticoids have a permissive role in the distal tubule, allowing urinary dilution. In their absence, free water clearance is impaired, the basis for the old Kepler water load test for the condition. Nowadays diagnosis is made simply by measuring serum cortisol concentrations and their response to Synacthen (the short Synacthen test).
- Water excess and negative sodium balance. This occurs when salt losses from the gastrointestinal tract or the kidneys (diuretics or tubular disease) are combined with excess water or hypotonic ﬂuid intake by mouth or other routes. The sodium depletion causes hypovolaemia, which, in turn, stimulates not only the renin angiotensin aldosterone system (RAAS) but also ADH secretion, thereby impairing free water clearance and any osmolar correction.
- Diuretics. Diuretics may cause problems, especially among older adults, in whom hyponatraemia is not uncommon. The taking of regular thiazide or loop diuretics in a ﬁxed dose may result in negative sodium and potassium balance, particularly during periods of reduced intake due to intercurrent illness. Combined with normal or elevated water intake, this results in both hyponatraemia and sodium deﬁcit. These cause mental confusion and, due to a diminished ECF, fainting and falls. To prevent this problem, it has been our practice to teach patients to adjust their diuretic dose according to daily weight (reﬂecting ﬂuid balance). If weight is unchanged or lost during the previous 24 hours the dose is omitted. Conversely a gain in weight warrants a normal or increased dose. Patients soon learn to titrate their own diuretic dose in this way.
- Sick cell syndrome. In severe catabolic illness e.g. burns120, septicaemia, etc., cell membrane function may be impaired and the sodium pump aﬀected so that intracellular sodium concentrations rise and those in the ECF fall despite considerable positive sodium balance3. This has been called the ‘sick cell syndrome’. With improved tissue perfusion and oxygenation and correction of underlying sepsis this may resolve. In the past, insulin, glucose and potassium have also been used with eﬀect. With improved care of patients with severe injury and critical illness, the sick cell syndrome has become less common.
- Hypernatraemia. The most common cause is net loss of hypotonic ﬂuid from the gastrointestinal tract, e.g. from vomiting and diarrhoea so that, in relation to plasma, proportionately more water is lost than sodium, even though sodium balance is also negative. A similar eﬀect occurs with renal losses due to the osmotic diuresis associated with uncontrolled diabetes. Large ﬂuid losses from sweat (hypotonic ﬂuid with a sodium concentration of around 50 mmol/L), e.g. in the tropics, cause similar changes. The rare primary hyperaldosteronism also causes mild hypernatraemia. Treatment is with hypotonic ﬂuids orally, enterally or intravenously with frequent monitoring of serum biochemistry. Oral water may be suﬃcient in mild cases. In the presence of diarrhoea, oral rehydration solutions may be appropriate. Severe cases should be treated cautiously with hypotonic intravenous ﬂuids (e.g. 5% dextrose, 0.18% saline in 4% dextrose) taking care to avoid too rapid reduction in plasma sodium or osmolality, which can precipitate cerebral oedema. Correction should be achieved slowly over 48 hours, at a rate no greater than 2 mmol/L/h.
Chloride is the main anion of the ECF at a concentration of 95-105 mmol/L. Unfortunately, because most clinical chemistry laboratories do not report the serum chloride concentration as part of routine biochemical screening, abnormal states such as hyperchloraemic acidosis have sometimes gone undetected. As a consequence, metabolic acidosis due to chloride excess has not infrequently been mistaken for other causes of acidosis, leading to inappropriate treatment. We, therefore, advise that serum chloride should always be measured in the presence of a metabolic acidosis or whenever large volumes of saline have been administered. It is important to remember that while the concentration of sodium in 0.9% saline is 10% higher than that in plasma, the concentration of chloride is 50% higher. The commonest cause of hypochloraemic alkalosis is loss of gastric juice (with its high HCl content) by vomiting or gastric aspiration. This is the main indication for giving 0.9% saline rather than a balanced electrolyte solution.
Chloride excess can also result in renal vasoconstriction, reduced renal blood ﬂow and decreased glomerular ﬁltration rate, leading to decreased urinary sodium and water excretion, and tissue oedema55,56,121. However, it has been suggested that adverse eﬀects only occur when the serum chloride concentration exceeds 108 mmol/L122.
The total body potassium is between 3000 and 3500 mmol (66-82 g) and is contained largely in the intracellular space where it is the chief cation at a concentration of 120-145 mmol/L, balancing the negative charges on proteins and other non-diﬀusible anions. Only a very small proportion is in the ECF, where its concentration lies crucially in the narrow range of 3.5-5.3 mmol/L. The balance of potassium across the cell membrane is maintained by the sodium pump combined with the Gibbs-Donnan equilibrium as described in Chapter 1. The normal daily requirements are 1 mmol/kg body weight. The following points are of clinical importance:
- Hyperkalaemia: the serum potassium concentration rises with renal failure and catabolic states, e.g. the response to injury. During the ﬂow phase of injury, as glycogen and protein are broken down, potassium linked to them is released from the cells into the ECF. Conversely, during the convalescent or anabolic phase of injury, the cells take up potassium again as glycogen and protein are resynthesised, causing a fall in ECF potassium concentration. Serum potassium concentrations also rise in response to internal haemorrhage or tissue damage, e.g. muscle necrosis, as potassium is released from dead or dying cells. If AKI and a catabolic state are combined, serum potassium concentrations rise rapidly to dangerous levels, usually accompanied by a metabolic acidosis. A rise in concentration above 6.0 mmol/L risks cardiac arrest and any increase above 5.5 mmol/L necessitates urgent treatment. With ﬂuid depletion and pre-renal AKI, intravenous ﬂuids may be suﬃcient, but additional treatment includes bicarbonate as well as insulin and glucose, both of which drive potassium back into the cells, but only temporarily (4-6 hours). This is a useful emergency measure which may need repeating. Calcium gluconate also helps to stabilize the heart. If these measures fail or oliguria persists, then calcium resonium rectally or renal replacement therapy should be carried out without delay. (see Chapter 10).
ECG monitoring in hyperkalaemia
While the ECG ﬁndings in hyperkalaemia can usually be correlated with the serum potassium concentration, potentially life-threatening arrhythmias can occur without warning.
- Mild (5.5 – 6.5 mmol/L)
- Tall ‘tented’ T waves (seen across the precordial leads) (Fig. 14.1) Prolonged PR segment
- Moderate (6.5 – 7.5 mmol/L)
- Decreased or ‘ﬂattened’ P wave
Prolonged QRS complex
- Severe (>7.5 mmol/L)
- Progressive widening of the QRS complex Axial deviation and bundle branch blocks
The progressively widened QRS eventually merges with the T wave, forming a sine wave pattern. Ventricular ﬁbrillation or asystole may follow.
Hypokalaemia: a fall in serum concentrations below 3.5 mmol/L nearly always reﬂects potassium deﬁciency and is usually accompanied by alkalosis because of the interchange of K+, Na+, and H+ in the distal tubule but, with renal tubular defects and laxative abuse, acidosis may be present. Although the relationship between the degree of hypokalaemia and the total potassium deﬁcit is not a precise one, in general it takes a loss of 200-400 mmol to reduce the serum potassium concentration from 4.0 to 3.0 mmol/L and a further loss of the same amount to reduce it to 2.0 mmol/L.
Symptoms include muscle weakness and, in more severe cases, as serum potassium falls below 2.5 mmol/L, paralysis and cardiac arrhythmias. The most common causes of hypokalaemia are gastrointestinal ﬂuid loss and diuretic therapy. It should also be remembered that patients with diabetic keto-acidosis may have a deﬁcit in excess of 400 mmol even though at presentation the serum potassium concentration may be high due to catabolism, acidosis and pre-renal AKI from ﬂuid loss. As the acidosis is corrected and insulin is given, potassium moves rapidly back into the cells and serum potassium concentrations plunge to dangerous levels unless adequate potassium replacement is given (see Chapter 13). A similar phenomenon is seen with the refeeding syndrome (see Chapter 15).
Immediate treatment of hypokalaemia should be aimed at raising the serum potassium concentration to a safe level above 3.0 mmol/L rather than correcting the whole deﬁcit, which can then be done more slowly over the next few days. With mild hypokalaemia (3-3.4 mmol/L), oral supplements at an initial dose of 60-80 mmol/day should be tried, although many patients ﬁnd oral supplements diﬃcult to tolerate. Potassium chloride is preferred in order to provide chloride to correct any accompanying alkalosis. The more easily tolerated eﬀervescent potassium preparations provide undesirable bicarbonate in the presence of alkalosis, although these may be helpful in the presence of the less severe acidosis.
In the presence of alkalosis, the distal tubules continue to excrete potassium in exchange for H+ even in the face of a potassium deﬁcit. In long-term diuretic therapy, a potassium-sparing diuretic or spironolactone should be added to prevent recurrence. In more severe cases, i.e. serum potassium <3.0 mmol/L, it is usually necessary to give KCl in saline intravenously. This also provides extra chloride to correct alkalosis. The use of dextrose as a vehicle risks lowering serum K+ still further as it stimulates insulin secretion and a combination of insulin and glucose drives potassium into the cell. In general, intravenous KCl should not be given faster than 10-20 mmol/h, although higher rates may need to be given to patients with severe hypokalaemia causing paralysis and arrhythmias. Rates as high as 40-100 mmol/h have been given under these circumstances but this should only be done via a central line under high dependency supervision with ECG and biochemical monitoring.
ECG monitoring in hypokalaemia
Typical ECG changes in mild hypokalaemia include ﬂattening and inversion of T waves. In more severe hypokalemia there is prolongation of the Q-T interval, a visible U wave and mild ST depression (Fig. 14.2). The QU interval may also be prolonged. Severe hypokalemia can cause arrhythmias such as ventricular tachycardia.
There are 33,000 mmol (1300 g) in the body, 99% being in bone and only 1% being freely exchangeable. The normal serum concentration is 2.2-2.6 mmol/L, all except 0.8-1.24 mmol/L being bound to protein, chieﬂy albumin. With falls in serum albumin due to illness and dilution with intravenous ﬂuids, the measured serum Ca2+ should be corrected upwards by 0.02 mmol/L for every 1 g/L fall in serum albumin between 40 and 25 g/L. Calcium plays a vital role, not only in bone, but also in neural conductivity, muscular conduction and many other physiological and metabolic processes.
Calcium absorption, excretion and serum concentration are governed by parathyroid hormone, calcitonin, and Vitamin D. Under normal circumstances 240 mmol/day of calcium are ﬁltered by the kidney, with all but 2-10 mmol being reabsorbed. Although some vitamin D is derived from food, most is formed in the skin under the inﬂuence of sunlight. It is then hydroxylated in the liver and subsequently the kidney to its most active form 1,25(OH)2D3.
Four common aspects of calcium disorders deserve a mention here:
- Osteomalacia: This is due to Vitamin D deﬁciency caused by lack of exposure to sunlight, malnutrition, some gastrointestinal diseases which cause fat malabsorption, and CKD causing reduced levels of 1,25(OH)2D3. It is characterised by typical radiological changes in bone, low serum calcium, raised serum phosphate, elevated alkaline phosphatase and parathormone, and low blood vitamin D concentrations. Treatment is with 0.25-1 μg of 1α hydroxycholecalciferol daily and, in some cases, calcium supplements.
- Osteoporosis: This involves not only thinning of bone calcium but also of its protein matrix. Its causes are multifactorial but include ageing, the menopause, immobility, calcium deﬁciency and hypogonadism. It is diagnosed radiologically and by bone density measurement. It may be reduced by sex hormone replacement, calcium and vitamin D supplements, and exercise, and treated by bisphosphonates.
- Hypercalcaemia: Any elevation of serum calcium concentration should be investigated thoroughly. Although, in severe cases it may be important to reduce very high levels of calcium as soon as possible, the main challenge to the doctor is to distinguish early between malignant causes, e.g. myeloma, secondary malignancy in bone, or parathormone secreting tumours, and more easily curable ‘benign’ causes such as hyperparathyroidism, vitamin D intoxication and sarcoidosis. Primary hyperparathyroidism and functional parathyroid tumours are associated with elevated parathormone concentrations whereas these are suppressed in secondary malignancy from non-parathormone secreting tumours.
- Mild hypercalcaemia, i.e. <3.0 mmol/L is usually asymptomatic, is often due to hyperparathyroidism, and may require no active intervention other than monitoring. More severe hypercalcaemia, i.e. ≥3.0 mmol/L is usually symptomatic in proportion to the magnitude and rapidity of rise in the serum calcium concentration. Symptoms include polyuria (due to inhibition of ADH action on the renal tubule), weakness, depression, drowsiness, lethargy, and even coma. It also causes constipation, nausea, vomiting, anorexia and peptic ulcer. Prolonged hypercalcaemia may also result in renal stones and nephrocalcinosis causing CKD. Fluid loss from polyuria may cause pre-renal AKI and a further rise in serum calcium concentration. Treatment depends on the severity of the condition, but consists ﬁrstly of intravenous saline or a calcium-free balanced crystalloid such as Plasma-Lyte 148, which may of itself be suﬃcient to reduce the serum calcium concentration. A loop diuretic may be added and, in severe cases, a bisphosphonate given in at least 500 ml of ﬂuid over 4 hours to avoid nephrotoxicity. Etidronate, 7.5 mg/kg can be given daily in this fashion for 3-7 days with careful monitoring of the serum calcium to avoid overshoot hypocalcaemia. Description of the use of other drugs, long-term treatment, and the indications for surgery may be found in appropriate reference works.
- Hypocalcaemia: This is usually caused by vitamin D deﬁciency or hypoparathyroidism, but there are other causes such as CKD and acute pancreatitis. It can also be secondary to hypomagnesaemia, which inhibits parathormone secretion; so in all cases of hypocalcaemia, the serum magnesium should also be measured. Falsely low concentrations of total serum calcium due to hypoalbuminaemia should be excluded (see above). Symptoms include neuromuscular irritability causing paraesthesiae, tetany and convulsions. A prolonged QT interval on the ECG may progress to ventricular ﬁbrillation or heart block. Treatment depends on its severity and cause, but may involve vitamin D replacement in the form of 1-α cholecalciferol and/or calcium supplements by the oral or intravenous routes. Symptomatic hypocalcaemia should be treated urgently with infusion of 3.75 mmol/kg of elemental calcium (in the form of calcium gluconate) over 4–6 h which will raise the total serum calcium concentration by 0.5–0.75 mmol/L.
This is distributed mainly in bone (500-600 mmol, 12-14.5 g) and the ICF (500-850 mmol). Only 12-20 mmol are in the ECF at any given time, at a concentration of 0.8-1.2 mmol/L. It is an important component of many enzyme systems and helps maintain cell membrane stability. The following facts are important to remember.
- Magnesium, like calcium, is bound to albumin and a low serum concentration should be interpreted in the light of the prevailing albumin concentration.
- Magnesium concentration in gastrointestinal ﬂuid varies according to the distance along the intestine. In the proximal small bowel ﬂuid it is only present at 1 mmol/L, whereas in the distal small bowel it rises to higher concentrations. Signiﬁcant hypomagnesaemia is, therefore, more likely to occur from chronic diarrhoea or from distal stomas or ﬁstulae rather than from more proximal gastrointestinal losses. Gastrointestinal losses are the most common cause of hypomagnesaemia in clinical practice.
- Hypomagnesaemia causes blood parathormone concentrations to fall, resulting in secondary hypocalcaemia. In all cases of hypocalcaemia, therefore, the serum magnesium concentration should be measured. Replacement of magnesium deﬁcits restores parathormone secretion and hence calcium concentrations to normal73.
- Overt symptoms of hypomagnesaemia, with neuromuscular irritability, convulsions, and arrhythmias are not usually apparent until the serum magnesium concentration falls below 0.4 mmol/L, although with milder degrees of hypomagnesaemia patients may experience improved well-being with adequate replacement, suggesting that even mild hypomagnesaemia may cause sub-clinical symptoms.
- In mild cases of hypomagnesaemia, oral replacement may be suﬃcient, using magnesium oxide or glycerophosphate. However, magnesium salts are not well absorbed, and in more severe cases it may be necessary to give as much as 160 mmol of magnesium sulphate intravenously in saline over 48 hours to restore normal concentrations. In patients undergoing intravenous feeding for gastrointestinal failure, daily requirements are 8-12 mmol (see Chapter 15). An alternative method of replacement, which we have found extremely eﬀective in restoring and maintaining magnesium concentrations, as well as replacing salt and water losses, is to give magnesium sulphate in 0.9% saline subcutaneously (hypodermoclysis) at a concentration of 6-12 mmol/L in up to 2 litres over 4-6 hours every day73. This is particularly useful in the short bowel syndrome or inﬂammatory bowel disease and can be readily administered at home by patients or their carers.
This is an important constituent of food, the normal intake being 8.5-15 mmol/day (800-1400 mg). Most is in the ICF, and the normal serum concentration lies between 0.8 and 1.5 mmol/L. Severe hypophosphataemia (<0.32 mmol/L) such as may occur acutely in the refeeding syndrome (see Chapter 15) or chronically in diseases of bone and mineral metabolism, risks symptoms of myopathy, dysphagia, ileus, respiratory failure, impaired cardiac contractility and encephalopathy. Severe cases may necessitate cautious intravenous administration of 300-500 ml of Phosphate Polyfusor (Fresenius Kabi, 100 mmol PO42-, 19 mmol K+ and 162 mmol Na+/L) or 30-50 mmol of PO42- in 1 litre 0.9% saline over 6-12 hours with frequent monitoring of serum phosphate and other electrolyte concentrations. Excessive or too rapid intravenous administration risks precipitating acute hypocalcaemia and deposition of calcium in soft tissues. Less severe cases can be treated orally with 1 g/day phosphate (e.g. Phosphate-Sandoz) replacement.
Refeeding syndrome is an important condition of insidious onset, which may be lethal or cause serious morbidity123-126. All patients suﬀering from weight loss or a period of starvation are potentially liable to develop this condition if given large amounts of nutrients, particularly carbohydrate, too rapidly. This is true whether the nutrients are administered orally, enterally or intravenously. The greater the degree of malnutrition or length of starvation, the greater the risk. Even dextrose containing solutions may precipitate it, if they are administered in large amounts over long periods.
The condition has several components, which may occur separately or in combination. These are hypokalaemia, hypophosphataemia, hypomagnesaemia, oedema, and acute thiamine deﬁciency causing irreversible brain damage from Wernicke’s encephalopathy. It is important to identify patients at risk and take prophylactic measures, rather than waiting until the condition has developed and then trying to treat it.
HYPOKALAEMIA <3.5 mmol/L: (normal range 3.5-5.3 mmol/L)
Potassium reserves may already be reduced in patients suﬀering from malnutrition, but carbohydrate administration in any patient stimulates insulin secretion and drives potassium from the ECF to the ICF where it is linked to glycogen. Similarly, protein synthesis obliges the cellular uptake of potassium. Particularly in those with diminished potassium reserves, refeeding may precipitate a suﬃcient degree of hypokalaemia to cause muscle weakness and/or cardiac arrhythmias. Any patient at risk or who is receiving dextrose containing solutions for prolonged periods should be receiving potassium supplements and having their serum potassium concentrations measured at the outset and monitored daily.
HYPOPHOSPHATAEMIA <0.7 mmol/L: (normal range 0.8-1.5 mmol/L)
Exactly the same considerations apply as for hypokalaemia. Since glucose taken up by cells undergoes phosphorylation, carbohydrate administration may precipitate hypophosphataemia. This has been reported in patients receiving intravenous dextrose solutions for several days and can result in decreased respiratory, cardiovascular and neuromuscular function. Symptoms include paraesthesiae, muscular weakness and confusion, sometimes progressing to convulsions and coma. The daily requirement for phosphate is about 20 mmol and prevention of hypophosphataemia can usually be achieved by giving 10 mmol of phosphate for every 1000 kcal that the patient receives. Remember 1 litre of 5% dextrose contains 50 g of carbohydrate with an approximate energy value of 200 kcal.
SALT AND WATER BALANCE
Malnutrition, like the response to injury, is associated with a reduced capacity to excrete a salt and water load. Malnourished patients are, therefore, at risk of developing oedema (famine oedema) from salt and water retention during refeeding. The intake of salt and water in such patients should, therefore, be restricted to that which maintains zero balance. This should be monitored by daily weighing and serum biochemistry. In a small thin patient for example, water intake for maintenance may be as little as 1 litre per day. Initial sodium intake may also need to be reduced below the normal requirements of 1 mmol/kg/day. On the other hand, any deﬁcit in salt and water balance should be corrected carefully.
Severely malnourished patients as well as those who consume alcohol in excess are particularly liable to this complication as they already have low thiamine reserves. Since thiamine is a cofactor in carbohydrate metabolism, refeeding may precipitate symptoms of thiamine deﬁciency including confusion, cerebellar signs with nystagmus, and peripheral neuropathy (Wernicke’s encephalopathy). As these changes are irreversible once established, identiﬁcation of patients at risk and provision of prophylactic treatment are vital. Prevention may be achieved by giving 200 mg of thiamine intravenously prior to refeeding, followed by 300 mg daily by mouth or 100 mg intravenously. Thiamine deﬁciency may also present as wet beri-beri with heart failure.
HYPOMAGNESAEMIA, mild 0.5-0.6 mmol/L, severe <0.4 mmol/L: (normal range 0.8-1.2 mmol/L) Magnesium, being involved in the formation of adenosine triphosphate (ATP) is taken up by cells during refeeding. Deﬁciency can cause muscle weakness, cardiac arrhythmias, and hypocalcaemia by reducing parathormone levels. It is not necessary in most cases to give prophylaxis unless there is prior magnesium deﬁciency, e.g. in short bowel syndrome. Monitoring magnesium concentrations in patients at risk and giving supplements if concentrations fall below 0.7 mmol/L is usually suﬃcient. Daily requirements are 0.2 mmol/kg/d intravenously or 0.4 mmol/kg/d orally. If magnesium concentrations fall below 0.5 mmol/L then give 24 mmol Mg2+ as MgSO4 intravenously over 24 hours.
It is important to be aware that the refeeding of patients suﬀering from weight loss or starvation can precipitate dangerous metabolic changes including hypokalaemia, hypophosphataemia, hypomagnesaemia, acute thiamine deﬁciency with Wernicke’s encephalopathy and oedema secondary to salt and water retention. The risks of developing refeeding syndrome can be avoided by appropriate monitoring and prophylactic supplementation with potassium, phosphate, magnesium and thiamine, and avoidance of salt and water overload.
PERIOPERATIVE FLUID THERAPY AND OUTCOMES
Although intravenous ﬂuids are the most frequently used “drug” in elective surgical practice, their prescription is often left to the most junior members of the surgical team who may have little knowledge of or training in the subject127-129. Perioperative ﬂuid therapy has a major bearing on surgical outcome. Great care is needed in the prescription of ﬂuids administered in the pre-, intra- and postoperative periods if complications and adverse outcomes are to be avoided130.
There is a relatively narrow margin of safety in perioperative ﬂuid therapy and either too much or too little can have a negative eﬀect on physiological processes and clinical outcome52,66,131 (Fig. 16.1). The goal of perioperative intravenous volume therapy should be to maintain tissue perfusion and cellular oxygen delivery, while at the same time keeping the patient in as near zero ﬂuid and electrolyte balance as possible.
Patients should reach the anaesthetic room in a state as close to euvolaemia as possible with any preoperative ﬂuid and electrolyte imbalance having been corrected. Pre-existing comorbidities must be considered when assessing ﬂuid status. Prolonged periods of preoperative fasting cause patients to reach the anaesthetic room in a state of ﬂuid depletion, which may be further compounded by unnecessary bowel preparation. Current anaesthetic recommendations that allow patients to eat for up to 6 h and drink clear ﬂuids up to 2 h prior to the induction of anaesthesia help to prevent preoperative ﬂuid depletion without increasing aspiration-related complications132. In those instances when mechanical bowel preparation is indicated, patients may lose up to 2 L of total body water as a consequence133, and ﬂuid and electrolyte derangements may occur even if patients are permitted oral ﬂuids. Some of these patients, therefore, may require appropriate intravenous ﬂuid therapy to compensate for these deﬁcits134. It has recently been shown that withholding oral ﬂuids for prolonged periods prior to the in- duction of anaesthesia can result in intraoperative hypotension and adverse events135.
On the other hand, the practice of prescribing volumes of salt containing ﬂuids in excess of requirements during the preoperative period causes salt and water overload which also has adverse eﬀects on surgical outcome.
The aim of intraoperative intravenous ﬂuid therapy is to maintain intravascular volume, cardiac output and tissue perfusion whilst avoiding salt and water overload. Most patients require crystalloids (see Chapters 6 and 7) at a rate of 1-4 ml/kg/h to maintain homeostasis77. However, some patients develop intravascular volume deﬁcits which require correction by administration of goal-directed boluses of intravenous solutions (usually a colloid). Goal directed ﬂuid therapy (GDFT) is aimed at maintaining intravascular normovolaemia guided by changes in stroke volume as measured by a minimally invasive cardiac output monitor to optimize the position of each patient on his/her individual Frank–Starling curve136,137. In addition to the background crystalloid infusion, ﬂuid boluses (200-250 ml) should be given to treat any objective evidence of hypovolaemia (>10% fall in stroke volume) in order to optimise intravascular volume and cardiac output138. A recent meta-analysis that included 23 studies with 2099 patients has shown that GDFT was associated with a signiﬁcant reduction in morbidity, hospital length of stay, intensive care length of stay, and time to passage of faeces139. However, when patients were managed within enhanced recovery after surgery (ERAS) pathways, with optimal perioperative care and avoidance of postoperative ﬂuid overload, the only signiﬁcant reductions were in intensive care length of stay and time to passage of faeces. Hence, within ERAS programmes, it may not be necessary to oﬀer all patients GDFT140, which should be reserved for high-risk patients or for patients undergoing high risk procedures77.
For most patients undergoing elective surgery intravenous ﬂuid therapy is usually unnecessary beyond the day of operation, except for those undergoing upper gastrointestinal and pancreatic procedures. With these exceptions, patients should be encouraged to drink as soon as they are awake and free of nausea after the operation. An oral diet can usually be started on the morning after surgery141,142. When adequate oral ﬂuid intake is tolerated, intravenous ﬂuid administration should be discontinued and be restarted only if required to maintain ﬂuid and electrolyte balance. If intravenous ﬂuids are required, then in the absence of ongoing losses, only maintenance ﬂuids should be given at a rate of 25-30 ml/kg/day with no more than 70-100 mmol sodium/day, along with potassium supplements (up to 1 mmol/kg/day)130. As long as this volume is not exceeded, hyponatraemia is very unlikely to occur despite the provision of hypotonic solutions57,143. Any ongoing losses (e.g. vomiting or high stoma losses) should be replaced on a like for like basis, in addition to maintenance requirements. After ensuring the patient is normovolaemic, hypotensive patients receiving epidural analgesia should be treated with vasopressors rather than indiscriminate ﬂuid boluses144,145. Fluid deﬁcit or overload of as little as 2.5 L9 can cause adverse eﬀects in the form of increased postoperative complications, prolonged hospital stay and higher costs due to increased utilisation of resources66,146,147.
However, it has not been unusual in the past for patients to receive in excess of 5 L water and 700 mmol sodium (and chloride)/day in the early postoperative period. Most of the retained ﬂuid after such infusions accumulates in the interstitial compartment, leading to oedema if overload exceeds 2-3 L. An excess of 0.9% saline in such cases causes hyperosmolar states, hyperchloraemic acidosis11,50,51,148-150, and decreased renal blood ﬂow and glomerular ﬁltration rate, which in turn exacerbates sodium retention55,56. Oedema impairs pulmonary gas exchange and tissue oxygenation leading to an increase in tissue pressure in organs such as the kidney which are surrounded by a non-expansible capsule. Microvascular perfusion is compromised, arterio-venous shunting increases and lymphatic drainage is reduced, leading to further oedema (Fig. 16.2). Hyperchloraemic acidosis, as a result of saline infusions has been shown to reduce gastric blood ﬂow and decrease gastric intramucosal pH in elderly surgical patients (see Chapter 2), and both respiratory and metabolic acidosis have been associated with impaired gastric motility. Fluid overload also causes splanchnic oedema resulting in increased abdominal pressure, ascites and even the abdominal compartment syndrome, which may lead to decreased mesenteric blood ﬂow and ileus, with delayed recovery of gastrointestinal function, an increase in gut permeability, intestinal failure and even anastomotic dehiscence (Fig. 16.3)151,152.
Fluid restriction resulting in ﬂuid deﬁcit can be as detrimental as ﬂuid excess by causing decreased venous return and cardiac output, diminished tissue perfusion and oxygen delivery and increased blood viscosity. It can also lead to an increase in the viscosity of pulmonary mucus and result in mucous plug formation and ateletactasis. Induction of anaesthesia in patients with a ﬂuid deﬁcit further reduces the
eﬀective circulatory volume by decreasing sympathetic tone. Inadequate ﬂuid resuscitation and decreased tissue perfusion can lead to gastrointestinal mucosal acidosis and poorer outcome.
A meta-analysis of patients undergoing major abdominal surgery has shown that patients managed in a state of near-zero ﬂuid and electrolyte balance had a 59% reduction in risk of developing complications when compared with patients managed in a state of ﬂuid imbalance (deﬁcit or excess). There was also a 3.4-day reduction in hospital stay in the near-zero ﬂuid balance group66.
A recent randomised clinical trial that studied intraoperative and day 1 postoperative ﬂuid therapy153, however, showed that a restrictive ﬂuid regimen was not associated with a higher rate of disability-free survival than a liberal ﬂuid regimen. In addition, there was a higher rate of AKI in patients who received a restrictive ﬂuid regimen. However, it should be highlighted that the authors did not record ﬂuid balance after day 1 and that weight gain was 0.3 kg in the restrictive group and 1.6 kg in the liberal group. This is below the 2.5 kg weight gain that is the threshold for producing oedema and complications9. In addition, there was no record of fasting, oral ﬂuids and food consumption. Hence, it may be concluded that a modestly liberal administration of balanced salt solutions does not create substantial ﬂuid retention and that it may be safer than a truly restrictive regimen.
BALANCED CRYSTALLOIDS vs. 0.9% SALINE
As described above, there is considerable evidence from physiological studies that large volumes of intravenous 0.9% saline cause hyperchloraemic acidosis, interstitial ﬂuid overload, impairment of renal blood ﬂow and glomerular ﬁltration with a consequent reduction in urinary water and sodium excretion51,55,56,121,150,154.
A large observational, propensity-matched study in patients undergoing surgery has suggested that 0.9% saline, because of its high chloride content, may be harmful, especially to the kidney when com- pared with a balanced crystalloid155. Another propensity-matched study has suggested that up to 22% of patients develop acute hyperchloraemia (>110 mmol/L) in the postoperative period and that this is associated with an increased risk of 30-day mortality and longer length of stay than those who do not develop hyperchloraemia156. However, as there are no large-scale randomised trials comparing 0.9% saline with balanced crystalloids in a surgical population, the current evidence cannot be regarded as high quality. In addition, a recent meta-analysis that was limited by imprecision and studies of a small sample size has shown that for unselected critically ill or perioperative adult patients there was no evidence of beneﬁt from low- versus high-chloride solutions157. However, because of the observed undesirable eﬀects of 0.9% saline, we suggest the use of more physiological balanced crystalloids, except where there is speciﬁc chloride deﬁciency.
MANAGEMENT OF POSTOPERATIVE OLIGURIA
Oliguria in the adult is usually deﬁned as a urine output <0.5 ml/kg/h, or <500 ml in 24 h (See Chapter 9). However, urine output and oliguria alone are not reliable indicators of intravascular volume deﬁcit in the ﬁrst 48 h after surgery as the postoperative metabolic response leads to salt and water retention158. Oliguria should be assessed carefully and should only be treated with additional intravenous ﬂuids if there is clear evidence of intravascular hypovolaemia (e.g. tachycardia, hypotension, sweating, confusion, decreased capillary return, etc.), as excessive ﬂuid administration has been associated with AKI88,159. If there are no clinical signs of intravascular hypovolaemia, it is useful to average urine output over the previous 4 hours rather than rely on a single hourly value, before reconsidering the need for additional ﬂuid. A conservative ﬂuid regimen does not appear to increase the risk of postoperative oliguria or AKI147,160-162. Unnecessary additional intravenous ﬂuids or diuretics do not improve renal function or protect against AKI159-161,163.
The algorithm in Fig. 16.4 outlines a practical approach to applying the above principles to ﬂuid provision in elective surgery.
Perioperative ﬂuid therapy has a major eﬀect on postoperative outcomes. If complications are to be avoided, patients should be managed in as near a state of “zero ﬂuid balance” as possible as both ﬂuid overload and deﬁcit can lead to complications. Accurate management of ﬂuid balance forms an important part of ERAS programmes, which have done so much to improve surgical outcome and shorten hospital stay. Moore and Shires164 wrote in 1967, “The objective of care is restoration to normal physiology and normal function of organs, with a normal blood volume, functional body water and electrolytes. This can never be achieved by inundation.” This recommendation has never been bettered.
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