The causes of hyponatraemia are shown in Table 8.1.

TABLE 8.1 Causes of hyponatraemia

Hyponatraemia is most commonly due to an excess of extracellular fluid (rather than sodium loss). This is often the result of excessive use of hypotonic intravenous fluids. Hyponatraemia may also result from the chronic use of some diuretic drugs; this is more commonly seen in the elderly. More rarely, hyponatraemia is associated with other forms of organ dysfunction, including renal dysfunction and hepatic cirrhosis (where it is seen in association with secondary hyperaldosteronism). Treatment is not usually necessary unless the serum sodium falls below 130 mmol/L. Serum sodium below 120 mmol/L may be associated with altered conscious level and fits. Symptoms are related as much to the speed of change in concentration as to the actual measured level.

Consider the underlying cause.

Change maintenance fluids to 0.9% saline.

Restrict total fluid intake. Allow the kidneys to clear excess fluid.

If oliguric, consider the need for renal replacement therapy to remove excess fluid.

Excessive antidiuretic hormone (ADH) secretion

This is a cause of dilutional hyponatraemia due to reduced free water clearance. It is most commonly seen as part of the syndrome of inappropriate ADH secretion (SIADH), which may accompany the neuroendocrine stress response to trauma, surgery and critical illness. Rarely, ectopic ADH secretion by tumours may produce a similar picture. Oliguria is accompanied by increased urine osmolality (>500 mosmol/L) and reduced plasma osmolality (<280 mosmol/L).

Restrict fluids.

Consider a trial of diuretic therapy.

Hyponatraemia due to sodium loss

Significant sodium depletion is associated with a reduction in extracellular fluid volume. This stimulates the release of aldosterone and causes the kidneys to retain salt and water and lose potassium. Urinary osmolality is raised and urinary sodium is low, less than 10 mmol/L (unless there is an intrinsic renal problem or use of diuretics).

Replace sodium and ECF with isotonic (0.9%) saline.

High serum sodium usually represents free water depletion. This is associated with a raised serum urea (without a significant corresponding rise in serum creatinine) and an increased serum osmolality (&290 mosmol/L). In critically ill patients, this situation can arise despite the apparent appearance of widespread oedema and ‘fluid overload’ as a result of fluid shifting between ‘compartments’.

Assess patient’s clinical volume status (tissue turgor, sunken eyes, CVP, etc.).

Review fluid balance regimen.

Give additional free water as 5% dextrose (e.g. 1 L over 6–12 h) or water via NG tube. Consider diluting enteral feeds with sterile water.

If additional fluid is contraindicated or undesirable, consider renal replacement therapy. This should be discussed with the nephrologists, on a case-by-case basis.

Hypernatraemia due to genuine sodium overload is uncommon. It is usually due to excess sodium chloride ingestion or administration, and is therefore accompanied by a high serum chloride and a hyperchloraemic acidosis. Management is essentially the same. Increase free water intake to allow the kidneys to excrete the additional solute load.

Causes of hypokalaemia are shown in Box 8.1.

Hypokalaemia is relatively common in the ICU. ECG changes include ST depression, flattening of the T wave and prominent U wave. If severe (<2 mmol/L), cardiac arrhythmias, including supraventricular and ventricular extrasystoles, tachycardias, atrial fibrillation, and ventricular fibrillation, may occur (Fig. 8.1).

Fig. 8.1 ECG changes associated with hypokalaemia.

Ensure adequate potassium concentration in maintenance fluids. The maximum safe concentration of potassium in peripheral fluid infusions is usually taken to be 60 mmol/L. In the intensive care unit where continuous monitoring is in place, a stronger potassium solution may be infused through a central line using a volumetric infusion pump or syringe driver

If additional potassium is required:

Do not give a rapid bolus injections of potassium, as there is a risk of sudden death.

Give 20 mmol of K⁺ in 20–40 mL of saline over 1 h via a central venous catheter using an infusion pump. Repeat as necessary.

Monitor the ECG during infusion.

In many patients, hypokalaemia is a reflection of a more widespread derangement of ionic homeostasis. It may be associated with an attempt to conserve magnesium in severe hypomagnesaemia. In this situation, correction of serum potassium is difficult and often transient until the hypomagnesaemia has also been corrected.

Causes of hyperkalaemia are shown in Box 8.2.

ECG changes include peaked T waves, broad QRS complexes and conduction defects (Fig. 8.2). Asystole may occur. Urgent treatment is usually required, although patients with long-term end-stage renal failure may be more tolerant of hyperkalaemia than the general intensive care patient population.

Fig. 8.2 ECG changes in hyperkalaemia.

Treatment to reduce risk of immediate arrhythmia

10 mL of 10% calcium chloride as a slow i.v. bolus will help to stabilize cardiac muscle.

In the presence of metabolic acidosis, give 50 mL 8.4% bicarbonate.

Treatment to lower serum potassium:

Nebulized salbutamol 2.5 mg, repeated as necessary.

50 mL of 8.4% bicarbonate, particularly in the presence of metabolic acidosis.

20% dextrose infusion plus 10 units of short-acting insulin i.v. (e.g. Actrapid).

Oral/rectal calcium resonium (chelating agent).

Consider the need for urgent renal replacement therapy.

Hypocalcaemia is common on the ICU. Typical causes are shown in Box 8.3.

Hypocalcaemia causes depressed cardiac function, loss of vasomotor tone, muscle weakness, paraesthesia and tetany.

Give 10 mL of 10% calcium chloride as slow i.v. bolus (into central vein, as it is a sclerosant).

Repeat as necessary or consider slow infusion.

In hypocalcaemia secondary to phosphate accumulation, there are risks of calcium phosphate deposition in tissues with overzealous calcium administration. Seek specialist advice.

This occurs less commonly, and is generally due to an underlying disease process. Typical causes are listed in Box 8.4.

Symptoms include GI disturbance, confusion and polyuria. Treatment is by rehydration and the use of calcium-binding agents.

Give 0.9% saline to rehydrate the patient. Check plasma osmolality is within the normal range (280–290 mosmol/L).

A forced diuresis may be used to aid excretion. Furosemide (frusemide) is administered and the urine output replaced with alternating 0.9% saline and 5% dextrose.

Calcitonin reduces the rate of calcium and phosphate release from the bones. It is useful in patients with hypercalcaemia associated with malignancy, and generally reduces the calcium level within 2 h.

Bisphosphonates (e.g. disodium etidronate) also reduce release of calcium from bones but generally take a few days to achieve maximum effect.

Corticosteroids may be helpful in hypercalcaemia associated with sarcoidosis and malignancy.

This is common in the ICU. It is usually multifactorial, resulting from reduced intake (particularly in patients receiving TPN), redistribution and increased losses (especially patients on renal replacement therapy). Hypophosphataemia causes muscle weakness, which may lead to heart failure or difficulty in weaning from artificial ventilation. It also contributes to failure of many metabolic processes and, if severe, results in depressed conscious level and seizures. It has also been associated with insulin resistance.

It is debatable at what level replacement is required. In most cases, as the patient’s overall condition improves, phosphate balance returns. Patients whose levels are below 0.8 mmol/L, particularly if symptomatic, may benefit from additional phosphate either in feeds or intravenously.

Use sodium phosphate or potassium phosphate depending upon requirements.

Give 30–60 mmol phosphate diluted in 100–500 mL 5% dextrose over 24 h.

Hyperphosphataemia is caused by excessive intake or decreased excretion (e.g. renal failure). Maintain adequate hydration with 5% dextrose. If severe, consider the need for renal replacement therapy. Phosphate is effectively removed by continuous RRT techniques, with haemodialysis and haemodiafiltration performing better than simple filtration techniques.

Magnesium is the second most common intracellular cation and as such, serum levels are a poor guide to the need for replacement. Serum magnesium is frequently depleted in critical illness. Common causes of hypomagnesaemia are shown in Box 8.5.

Hypomagnesaemia is usually asymptomatic, but can give rise to muscle weakness and cardiac arrhythmias (hypomagnesaemia exacerbates the effects of hypokalaemia, see above.). The treatment is by magnesium supplementation.

Give 10 mmol magnesium sulphate i.v. over 30 min.

If severe can be followed by 50–100 mmol over 24 h.

This is less common and generally results from excessive administration, particularly in the presence of renal failure. Consciousness level may be reduced. Cardiac conduction may be impaired with prolongation of the PR interval and broadening of the QRS complexes. At extreme levels, this may result in cardiac arrest.

10 mL calcium chloride i.v. will temporarily improve cardiac conduction.

Consider the need for urgent haemofiltration or haemodialysis.

Low serum albumin is common in critically ill patients. Common causes of hypoalbuminaemia are shown in Box 8.6.

Low albumin concentration is generally a marker of disease severity rather than a problem in its own right. There is no benefit in giving albumin solely to raise the albumin concentration. Concentrations will recover as the patient’s condition improves, and synthesis of albumin by the liver increases while capillary leak is reduced. Ensure adequate nutrition in order to encourage protein synthesis and treat the underlying condition.

Lactate measurements are increasingly available from blood gas analysers. There is considerable argument as to their value. Lactate levels >2 mmol/L are abnormal. There are two situations in which lactic acidosis may occur.

Type A

This is the commonest type of metabolic acidosis seen in the ICU and is due to inadequate delivery of oxygen to the tissue. This may occur, for example, as a result of cardiorespiratory arrest or from inadequate tissue perfusion, as seen in shock states. Inadequate oxygen delivery leads to anaerobic metabolism and the accumulation of lactate. It is not uncommon, however, for patients with severe shock and acidosis to have a normal lactate.

Restore adequate oxygen delivery and tissue perfusion.

Give bicarbonate as above if necessary.

Consider the need for renal replacement therapy. If already on RRT using lactate buffered replacement/dialysis fluid, consider changing to bicarbonate buffered solutions. Seek senior advice.

Lactate levels usually return to normal with adequate resuscitation. Failure to do so implies either a failure of resuscitation or critically ischaemic or dead tissue. Look for hidden areas of ischaemic tissues, e.g. ischaemic bowel.

Where lactic acidosis is sustained and refractory to treatment, the prognosis is poor.

Type B

This is uncommon, and is due to the accumulation of lactate without evidence of tissue hypoxia. It may be precipitated by drugs, ingestion of ethylene glycol or methanol, liver failure and some rare hereditary disorders, including disorders of mitochondrial function.

Treat the underlying condition if possible. The acidosis should be corrected. This may be possible simply by removing the underlying precipitating cause, but may require vigorous resuscitation.

Infusion of bicarbonate solution (potentially in large volumes) may be necessary as part of the initial resuscitation.

Renal replacement therapy may be necessary, and should be considered early. (See Methanol/ethylene glycol poisoning, p. 240.)

Elevated serum chloride levels, for example following resuscitation with large volumes of normal saline, produce a corresponding decrease in bicarbonate levels (in order to maintain anion balance) and hyperchloraemic acidosis. This usually resolves without the need for treatment as the chloride levels correct (see choice of fluids, p. 49).

This is a metabolic acidosis arising from renal tubular dysfunction, in which there is excess loss of bicarbonate through the kidneys, with a corresponding increased serum chloride (normal anion gap). This may present as a feature of renal disease, or may result as a side-effect from drugs (e.g. amphotericin). If you suspect renal tubular acidosis, test the urine pH. A systemic acidosis accompanied by a non acid urine (pH > 6) is highly suggestive. Type 1 (distal convoluted tubule) and type 2 (proximal convoluted tubule) are associated with hypokalaemia. Type 4 results from hypoaldosteronism or aldosterone resistance, and is associated with hyperkalaemia and metabolic acidosis. (Type 3 is no longer recognized.)

Hypoglycaemia can be defined as a blood glucose <3 mmol/L. It occurs most commonly as a consequence of insulin or oral hypoglycaemic therapy in diabetic patients, but may also be associated with some disease states. Typical causes are shown in Box 8.8.

Clinical signs of hypoglycaemia include confusion, sweating, tachycardia and seizures, leading if untreated to coma and brain damage. Such signs may be masked or absent in the critically ill or sedated patient, so great care and regular glucose monitoring are required in patients receiving insulin infusions. It should be appreciated that at present there is no clinically available real time technique for monitoring blood glucose, and plasma glucose concentrations can fall to dangerously low levels very quickly after the administration of insulin. This means that there is a real chance of missing hypoglycaemia between intermittent (e.g. hourly) glucose measurements.

Consider the cause. Reduce or discontinue hypoglycaemic agents as appropriate.

Give 50 mL of IV 20% dextrose and repeat as necessary. Boluses of 50% dextrose have been associated with significant disturbances of osmolality, and are best avoided.

Commence infusion of 10–20% dextrose (with potassium) as necessary to maintain blood sugar.

(See Hepatic failure, p. 176.)

This is common in the critically ill, and may result from pre-existing diabetes or glucose intolerance. The effects of critical illness, the associated stress response and the effects of drugs such as exogenous catecholamines and steroids can all lead to glucose intolerance. This may be further compounded by the use of high glucose loads in TPN. Consequently, hyperglycaemia is common and frequently requires the use of insulin infusions to control the blood sugar, even in the non-diabetic patient.

Start a sliding scale insulin infusion.

Monitor potassium – insulin drives K⁺ into cells.

It may be impossible to achieve normal blood glucose levels in very sick patients. In this case, avoid peaks and troughs in glucose levels caused by repeated changes in insulin dosage. It was previously considered that perfect glucose control was not necessary in the critically ill, but recent evidence suggested that the outcome of critically ill patients, particularly those with sepsis, may be improved by tightly controlling blood glucose within the normal range (see Sepsis, p. 329). More recent analysis has suggested that such benefit is more questionable, and there is a very real risk of dangerous hypoglycaemia with more aggressive glucose control. Therefore, seek reasonable control aiming to get within the upper range of the normal limit within a few hours rather than minutes Brain injury is worsened in the presence of hyperglycaemia.

Absolute or relative deficiency of insulin leads to an imbalance between the hyperglycaemic effects of stress hormones and the hypoglycaemic effects of insulin. Increased hepatic glycogen breakdown and gluconeogenesis coupled with reduced cellular uptake of glucose results in hyperglycaemia. This in turn leads to polyuria, with loss of water, sodium and potassium. The hormonal changes also result in lipolysis with release of triglycerides and fatty acids, which are metabolized by the liver to ketones, which exacerbate the metabolic acidosis.

Similar to DKA above.

Give oxygen. Secure the airway and institute ventilation if necessary.

Invasive cardiovascular monitoring. NG tube. Urinary catheter.

If severely shocked, colloid bolus and inotropic support may be required.

Use 0.9% saline as rehydration fluid (0.45% saline in severe cases). Correct dehydration more slowly than in DKA, typically over 24–48 h. Rapid correction may be associated with cerebral oedema.

Insulin as in DKA but typically give lower doses, e.g. 3 units/h.

Monitor potassium and replace as necessary. Potassium requirements are usually less than for DKA because of the absence of significant acidosis.

Patients with diabetic hyperosmolar states are at high risk of deep vein thrombosis. You should play close attention to the prophylaxis of deep vein thrombosis. This should include all the usual measures, such as support stockings and the use of a low molecular weight heparin; early mobilization and physiotherapy.

Addison’s disease (primary adrenal cortical failure) is rare, but should be considered as a differential diagnosis in critically ill patients. It is easily missed due to the non-specific nature of signs and symptoms

The typical clinical features are increased pigmentation, weakness, abdominal pain (may be mistaken as a surgical acute abdomen), vomiting, diarrhoea and hypotension. Biochemical findings include hyponatraemia, hyperkalaemia, hypoglycaemia and hypercalcaemia. Aside from general support measures:

If possible perform a short Synacthen test (Synacthen is an ACTH analogue). Give Synacthen 0.25 mg i.m. Measure plasma cortisol before and 30 min after. Cortisol level should rise by 2–3 times the basal level.

Give steroid replacement therapy. Basal replacement doses hydrocortisone 20 mg a.m., 10 mg p.m. In stress states give larger doses, e.g. 100 mg 3 times daily.

Consider mineralocorticoid replacement, e.g. fludrocortisone 50–300 μg daily (only available as an enteral preparation).

Many patients will already be on long-term corticosteroids for management of various disease processes. The true significance of pituitary adrenal suppression by longer term steroid therapy is still debatable but most authorities recommend increasing doses of steroids during critical illness and major surgical interventions. Equivalent anti-inflammatory doses for a change from oral steroids to i.v. hydrocortisone are:

hydrocortisone 20 mg = prednisolone 5 mg

Whist primary adrenal failure is rare, it is increasingly recognized that critically ill patients may have inadequate levels of cortisol production for their needs. This can contribute to refractory shock. Low-dose steroid replacement may improve outcomes in these patients and there are a number of conflicting large clinical trials. At the time of writing there is little evidence for the routine use of steroids in this situation, but if the patient is deteriorating despite all other measures it is probably reasonable to assess the effects of low dose steroids.

Measure random cortisol or perform short Synacthen test (above).

Give low (physiological) replacement doses of hydrocortisone, e.g. 50 mg b.d.

High-dose steroid therapy has been trialled in shock states but studies tend to show it worsens outcomes. Likewise there is no benefit in traumatic acute brain injury. Steroids have been reported to improve outcomes in some other conditions (Box 8.9).

Thyroid function tests are often abnormal in the critically ill patient. Most sick patients will have results consistent with the so-called sick euthyroid syndrome. The pattern is low T3, low T4, and inappropriately low/normal TSH. This pattern persists until recovery occurs. The current consensus is that it does not reflect true clinical hypothyroidism so thyroid replacement therapy is not usually warranted. Seek expert advice if unclear.

Hypothyroidism should be considered in the elderly patient presenting with hypothermia, coma or other non-specific illness. Treat with replacement therapy in the form of oral/parenteral T3 or thyroxine.

Uncontrolled hyperthyroidism is rarely seen. It should be considered in cases of AF, other dysrhythmias and metabolic disturbances. Hyperthyroidism may present in patients on ICU with other pathologies. Management includes antithyroid drugs, e.g. carbimazole, β-blockers and general supportive measures.

Core temperature measurements may be obtained from the tympanic membrane, nasopharynx, oesophagus, bladder and rectum, or from an indwelling vascular catheter. These reflect the patient’s true temperature more reliably than axillary, oral or peripheral temperature measurements. The core–peripheral temperature gradient gives an indication of the cardiovascular condition of the patient and the degree of peripheral vasoconstriction. A well-filled, well perfused patient has a core to peripheral temperature gradient of <2°C.

Hyperthermia is important as a marker for infection or other disease processes. Causes of hyperthermia are shown in Box 8.10.

The exact mechanisms that produce hyperthermia are not known but in many cases it can be viewed as a physiological response to critical illness rather than a significant part of the disease process. There is debate, therefore, about the need to treat a mildly raised temperature <39°C except in brain-injured patients, where increased temperature is associated with a worse outcome. (See Brain injury, p. 272 and Management of cardiac arrest, p. 109.)In general, however, measures such as regular paracetamol and tepid sponging for low-grade pyrexia may improve patient comfort.

Urgent treatment is required if core temperature exceeds 39°C. Prolonged core temperatures of >42°C are associated with cardiovascular collapse, rigors, seizures, brain injury, coagulopathy, multiple organ failure and death.

Ensure adequate hydration (increased insensible losses).

Give regular rectal paracetamol (ibuprofen is also effective if there are no contraindications to NSAIDs).

Institute passive cooling: wet drapes, ice packs, fans, and gastric, peritoneal or bladder lavage with cold fluids.

Consider sedation, intubation, ventilation and muscle relaxation to reduce metabolic rate.

If severe hyperpyrexia, consider an extracorporeal circuit to actively cool the patient. Seek senior advice.

Dantrolene is a muscle relaxant that works distal to the neuromuscular junction. It has an established role in malignant hyperpyrexia, and appears to work after Ecstasy ingestion. It has not been shown to be effective in other conditions; however, it has limited side-effects in ventilated patients so can be tried when other measures fail.

Dantrolene 1 mg/kg bolus repeated every 10 min up to 10 mg/kg. (See Malignant hyperpyrexia, p. 363.)

Hypothermia is defined as a core temperature below 35°C. To avoid missing hypothermia, you should always have a high index of suspicion and measure core temperature in at-risk patients. Common causes are given in Box 8.11.

Hypothermia is associated with a number of adverse effects. These include: arrhythmias, myocardial depression, vasoconstriction, coagulopathy, increased risk of wound infections and wound dehiscence, prolonged drug clearance, altered acid–base balance and prolonged ICU stay. In the surgical context, prevention is better than cure. The use of fluid warming devices, warming blankets and heated humidifiers perioperatively all help to reduce the risk.

In severely hypothermic patients from other causes:

Exclude other injuries, drug ingestions, head injury, myxoedema, pressure necrosis of limbs, compartment syndromes, rhabdomyolysis and renal failure (measure CK). Treat appropriately (see Trauma, p. 306).

Most patients respond to passive slow rewarming with a slow rise in core temperature of about 1°C per hour. Utilize a warm environment, hot-air warming blankets, and warm i.v. fluids for volume replacement.

For severely hypothermic patients, with a core temperature below 32°C, consider more active warming measures such as peritoneal lavage with warm fluids, instillation of warm fluids into the bladder, or partial (femoral–femoral) bypass with a heat exchanger.

Patients may develop dysrhythmias on rewarming, usually at around 31°C, and may need repeated cardioversion. It may, however, be difficult to restore sinus rhythm while the patient remains hypothermic. Occasionally under these circumstances profoundly hypothermic patients can be successfully warmed utilizing cardiopulmonary bypass.

In profoundly hypothermic patients it may be difficult to determine whether the patient has actually died. This follows cases of patients making a full recovery from prolonged circulatory arrest and deep hypothermia after cold water immersion. Therefore, resuscitation efforts should be continued until the patient approaches normothermia. Remember the maxim, ‘you can’t be dead until you’re warm and dead’. Seek senior advice.