Cardiac

Cardiovascular compromise occurs early in AN in up to 87% of patients. It is the most common cause of death after suicide and is seen in proportion to nutritional deprivation.9 Malnutrition causes cellular changes within the cardiac muscle, leading to structural, functional or electrocardiological complications. Significant cellular changes include reduced protein synthesis, mitochondrial swelling, activation of calcium-dependent proteinases, reduced glycogen, oedema and myofibrillar atrophy.10

Cardiac muscle becomes hypotrophic leading to reduced cardiac output, preload and left ventricular function. Ejection fraction is often preserved.11 Reduction in cardiac muscle mass can cause mitral valve prolapse in 33–62% of patients. This is often asymptomatic, but sudden death is a known complication of this abnormality.12 13

Cardiac rhythm disturbances are common. The majority of patients develop a sinus bradycardia as an adaptation to the hypometabolic state. A tachycardia is therefore concerning. There is marked heart rate variability, possibly due to autonomic change. QT prolongation, seen in up to 15% of patients, has been associated with ventricular arrhythmias and death. Other ECG changes are common and include prolonged PR interval, first-degree heart block, prolonged QTc, ST segment changes, left shift of the QRS axis and diminished QRS amplitude. These are often related to underlying structural or electrolyte abnormalities and should be investigated at the time of presentation. Any reversible cause should be corrected.9 14,–,16 Blood sugar monitoring is important as hypoglycaemia can induce high blood catecholamine levels and potentially cause myocardial damage or arrhythmias.17

Orthostatic changes occur in 60–80% of patients, increasing their risk of syncope.18 Other cardiac complications include hypotension, peripheral oedema, pericardial effusions and congestive cardiac failure.19 In its mild form, peripheral oedema is simply dependent, but in severely malnourished patients, it can progress to hypovolaemia and circulatory collapse.9

Most cardiac complications improve with re-feeding.14 Due to their frequency and potential severity, close monitoring of heart rate, ECG, blood pressure and orthostatic changes is mandatory. Particular care should be taken in patients with prolonged QTc to avoid exacerbating the condition. Exercise should be avoided in severely compromised patients until cardiac function has normalised.16

Renal, fluid and electrolytes

Renal, electrolyte and volume disturbances occur in approximately 70% of patients. In extreme cases, renal failure can occur.9 20 Glomerular filtration rate falls, reducing the concentrating capacity of the kidneys. Blood urea rises but creatinine is low as a consequence of low muscle mass. Electrolyte abnormalities include hypocalcaemia, hyponatraemia, hypokalaemia, hypomagnesaemia and hypophosphataemia. The effects of these abnormalities are shown in table 3. Hypomagnesaemia is associated with hypocalcaemia and hypokalaemia, which may not resolve unless magnesium is concurrently replaced.9

There is an increased risk of renal stones and acid–base disturbances, which can adversely affect both enzyme and metabolic systems.4 A persistent hypovolaemic state can also lead to disturbances of the renin–angiotensin–aldosterone pathway and relative hyperaldosteronism. Vasopressin release can be erratic leading to neurogenic diabetes insipidus.8

Gastrointestinal

Restricting food intake and purging can damage the gastrointestinal tract. There is a 16% rate of oesophagitis and commencement of appropriate medication, such as proton pump inhibitors, is advised. Mallory-Weis and Boerhaave's tears can occur after excessive vomiting. Superior mesenteric artery syndrome, pancreatitis, impaired gastric motility, liver enzyme abnormalities, constipation and ileus have all been reported. Large bowel abnormalities may occur, often with a similar clinical presentation to inflammatory bowel disease, particularly with inappropriate use of laxatives.2 9 21

Dental pathology is common with increased risk of caries and acid erosion, particularly in cases of purging. Erythema of the pharynx and enlarged salivary glands (mainly parotid) may be seen. Regular dental reviews are recommended.2 9 18

Respiratory

Respiratory complications are uncommon until late in the disease, when patients may need critical care. Pulmonary function tests often show reduced pulmonary volumes early in the disease, but this is rarely of any clinical significance.4

Neurological

Neurological changes include apathy, poor concentration, muscle weakness, pain, cramps and myopathy. Patients who are immobile for prolonged periods may be at risk of further muscle wasting and nerve compression.

Brain CT and MRI scans have demonstrated enlarged cerebrospinal fluid spaces with volume deficits in grey and white matter suggesting a degree of cerebral atrophy. The magnitude of these changes generally correlates with the degree of malnutrition. Although white matter changes are reversible with nutritional rehabilitation, grey matter volume deficits and blood flow disturbances can persist despite weight restoration.8

Haematological

The most common haematological changes are to white blood cells. Although overall white cell count is usually within the normal range, patients have lower counts than healthy matched controls and may develop neutropaenia and lymphopaenia. This may be associated with a 15-fold increase in relative risk of infection. Granulocyte activity, cell-mediated immunity and complement activity may be reduced. Correlations have been suggested between severity of AN and infection risk.22 23

Anaemia is seen in 9–36% of patients and is generally normocytic. Thrombocytopenia is usually mild with few patients showing signs of purpura on admission. Haematological abnormalities can be associated with concurrent bone marrow changes. Pancytopaenia may occur in severe cases. All these changes are associated with a low BMI and are reversible with weight gain.23

Other complications

Patients can develop significant pressure areas as reduced adipose, poor-quality dry skin, reduced healing capacity and prolonged immobility take effect. Stress fractures may occur.24 Good-quality nursing care is of extreme importance in preventing such complications. Rarely vitamin deficiencies may lead to patients showing signs of pellagra (niacin deficiency) or scurvy (Vitamin C deficiency).9 Other reported effects include impaired temperature homeostasis with a lack of shivering, vasodilatation and vasoconstriction that may reflect a hypothalamic disturbance.9

In the longer term, consideration should be given to the consequences of malnutrition, eg, endocrine disturbance (delayed/arrested puberty and secondary amenorrhoea) and bone health (osteopenia and osteoporosis). There is no evidence to support the use of bisphosphonates and oestrogen therapy should be avoided as it can precipitate premature fusion of epiphyses.25

Re-feeding

Oral feeding is the preferred route for re-feeding. If this does not achieve the desired calorific intake, nasogastric feeding may be appropriate. A continuous infusion may be better tolerated than bolus feeds. Enteral feeding reduces the risk of bacterial translocation, line infections and metabolic disturbance seen with parenteral nutrition, the use of which should be limited to when no alternative is available.2 4 15 26

A multidisciplinary approach towards feeding is essential. Type, mode of administration, supervision and approach to non-compliance should be defined in advance. Consideration should be given to restriction of caffeine, excess fluid and salt, as well as the potential for concealment or disposal of calories. Weight should be regularly measured and patients monitored for signs of purging. Excessive exercise should be discouraged. If there is doubt regarding fluid intake, specific gravity of urine can be measured to ensure patients are not taking excessive fluids.4

The body adapts to low calorie intake by reducing basal metabolic rate. Resting energy expenditure falls and initial calorific requirements are low. These increase dramatically as rehabilitation occurs. There is debate about how fast weight gain should occur. Suggested target weight gain ranges from 0.5 to 1 kg per week. Independent of the type of nutritional rehabilitation, a balanced diet should be provided including 45–65% carbohydrates, 10–35% proteins and 20–35% fats. Calcium intake should be 1200–1500 mg per day. Patients should take a daily multivitamin and iron supplement.2 7 15

During the period of nutritional stabilisation, patients may show suicidal or depressive ideation as specific weights are reached or they notice changes in their body shape. Acne, breast pain, bloating, fluid retention, delayed gut motility and constipation can all occur. These can be distressing for patients who were previously pathologically in control of their own body. Psychiatric input is important during this period.

Re-feeding syndrome

First described at the end of the Second World War, RFS is a potentially lethal combination of fluid and electrolyte shifts. It occurs acutely in severely malnourished individuals when feeding is re-started. The key biochemical abnormality is hypophosphataemia, but other derangements include hypokalaemia, hypomagnesaemia, acute thiamine deficiency, salt and water retention and hypoglycaemia. Re-feeding of grossly malnourished individuals can cause fatal diarrhoea, heart failure, coma and convulsions.12 15

Prolonged starvation causes protein breakdown with loss of skeletal and cardiac muscle mass. This is associated with loss of phosphate (the most abundant intracellular anion), potassium (which electrically balances negatively charged protein molecules) and water. The serum levels of phosphate and potassium may remain normal but the body as a whole may be depleted of these ions. When the malnourished patient receives a carbohydrate load, the body switches from catabolism to anabolism. This leads to a large increase in intracellular requirements for phosphate and causes hypophosphataemia. Phosphate is needed in many intracellular enzyme systems and to make adenosine triphosphate, 2,3-diphosphoglycerate and creatine phosphokinase. Requirements for potassium and thiamine also increase (Fig 1).

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Figure 1

Re-feeding syndrome diagram.

The development of RFS must be anticipated and prophylactic treatment given. The key features to identify are

1. Salt and water retention, fluid overload and cardiac failure. Even in cases that do not progress to RFS, oedema can be seen within a few days of re-feeding due to fluid imbalance.

2. Electrolyte imbalances.

3. Muscle weakness (due to depletion of myocyte ATP and possible sarcolemmal failure with rhabdomyolysis).

4. Diarrhoea.

5. Respiratory compromise (due to muscle weakness and diaphragmatic atrophy).

6. Delirium, hallucinations and decreased consciousness level.

7. Encephalopathy and seizures.

Delirium has been reported in the second week of re-feeding and may continue for several weeks, unaffected by correcting phosphate.27 Deficiency of thiamine can lead to Wernicke's encephalopathy, which may be irreversible. Re-feeding has also been linked with liver damage. There may be an increase in liver enzymes consistent with fatty infiltration, nutritional hepatitis or hypoperfusion.21

Re-feeding is central to the treatment of AN. Although many different feeding regimens have been suggested, randomised controlled trials have not shown any to be superior at avoiding the problems of RFS. Bearing this in mind, the following factors should be considered.

First, calorie intake should initially be kept low, at approximately the current level of intake and increases should be undertaken regularly but in a timely fashion with guidance from a dietitian. There is a temptation to give a very low calorie intake to avoid RFS but underfeeding can worsen symptoms as much as overfeeding can precipitate RFS.

Second, particular care should be taken regarding fluid and electrolyte balance. Serum electrolytes should be measured before re-feeding, six hours after commencing intake and then daily. Supplemental electrolytes may be required prophylactically, particularly phosphate, and these should be replaced in a timely fashion.7 Fluid balance should be closely monitored, particularly with regard to renal function. Fluid restriction may be appropriate in some patients but only after discussion with specialist teams.

Finally, vitamin supplements should be prescribed in the form of a multivitamin and thiamine preparation.3

Although the guidance shown in table 2 may be helpful in identifying high-risk patients, assessing the risk of RFS accurately is difficult. Incidence increases as BMI decreases and if weight loss is rapid. The greatest period of risk is within the first week of re-commencing nutrition. Observations and monitoring should therefore be continued until the patient shows signs of biochemical and cardiovascular stability.28 It is hard to set firm criteria because of normal variability of BMI, physiology and behaviour in patients of different ages.

Drug therapy in malnutrition

In malnutrition, care must be taken when prescribing medications.25 Particular consideration should be given to:

1. Drug absorption – if given orally is the drug being absorbed?

2. Low albumin and effect on drug binding – dose reductions may be required when drugs are highly protein bound.

3. Effect of abnormal electrolytes and malnutrition on drug function.

4. Drug metabolism – enzyme function, how is the drug metabolised? This can be affected by pH and electrolyte balance.

5. Renal and liver function – drug excretion and metabolism. Drug doses may need to be reduced to take account for this, especially antibiotics.

6. Drugs that affect QTc – long QTc is common in AN patients. Drugs that prolong QTc may lead to fatal arrhythmias.

7. Increased adverse reactions to certain medications in malnutrition.

1. Adverse reactions to monoamine-oxidase inihibitor (MAOI)and tricyclic antidepressants are more pronounced in malnutrition.

2. Bupropion should be avoided due to increased seizure risk in patients with eating disorders.

3. High risk of dependence on benzodiazepines – avoid where possible.

Capacity and consent

In some cases, young people may have become so unwell that they present to hospital ‘peri-arrest’. In emergency situations, current General Medical Councilguidance allows life-saving resuscitation, even when the patient's consent to treatment is uncertain.29

Once initial resuscitation has occurred, a patient in a critical care setting may express a wish not to be treated either verbally or non-verbally. If these actions put the patient's life at risk (eg, self-removal of central venous or arterial catheters), action must be taken to provide emergency stabilisation. Following this, a stepwise approach guided by the principles of good medical practice should be followed.30

The first priority is to establish the best interests of patients by listening to their concerns and thoughts around treatment. It is important to attempt to gain basic cooperation and make an assessment of patients' capacity and competence. If patients are younger than 18 years of age and competent, they can consent to treatment. However, even if patients are deemed competent, they cannot refuse treatment. Parents of a child younger than 18 can consent to treatment on behalf of their child. In most cases, communication between the clinical team, young person and family should result in a decision acceptable to all. Despite best efforts, this is not always possible. There are likely to be barriers to competence in a young person suffering from AN and the burden on parents to consent to treatment against the wishes of their child, can be difficult.

When neither young person nor parent will consent, there are three options available to the clinical team. The first utilises the principle of best interests to allow emergency treatment if needed. Alternative options are to use the mental health act31 or to apply for a court ruling under the terms of the Children's Act 1989.32 In the case of a young person in a critical care setting, it is probably more appropriate to apply to the courts, as treatment will focus on medical management. GMC guidance is to seek legal advice if competent young persons and/or their parents refuse to consent to treatment felt to be in the patients' best interests by the clinical team.30

Coercion and restraint

Coercion can include use of legal interventions, parental consent overruling the young person's wishes and techniques, such as rewards or withholding privileges.

While use of coercion can be controversial, there is general consensus to support its use in at-risk patients. There is debate about whether to use coercion in patients who retain capacity.33 The use of legal coercion tends to be associated with a high health risk (low BMI/increased risk of RFS), higher complexity condition (eg, other psychiatric co-morbidities) and a high number of previous admissions.34 There is evidence to suggest that young people who have had legally coerced treatment as opposed to voluntary treatment, have a higher mortality rate.35

The Mental Capacity Act36 has useful advice regarding use of restraint, however, it cannot be legally applied to people younger than 16 years. Under the terms of the Act, restraint is allowed only if the person using it reasonably believes it is necessary to prevent harm. The restraint must be proportionate to the likelihood and seriousness of the harm. These are useful guiding principles, to help decide if the use of restraint is appropriate. If deemed appropriate, it is sensible to seek legal advice and to discuss the use of restraint in the court application for treatment.

Parental involvement and collaboration

Dealing with complex family dynamics and history is beyond the scope of this article. An awareness of interfamily dynamics and potential effects on the patient are vital.37 It is important to include the family in the care of the patient while ensuring confidentiality and dignity are respected. This is especially important if there have been disagreements between the clinical team and the patient/family around treatment decisions or if the courts have been involved. As the team moves away from the resuscitation phase towards long-term rehabilitation, ongoing cooperation with the young person and parents is vital. Medical staff should guard against being pulled in to family conflict, and keep the patient at the heart of any decisions.

Collusion and manipulation

The desire for control and the ability to manipulate family, friends, teachers and clinicians is a well-recognised trait of AN.38 This can be challenging for medical, nursing and allied health professionals working with young people. In the critical care setting, there may be several specialists involved in the management of the patient. It is helpful to identify a lead professional and provide clear rules for nursing and medical staff, so that consistent messages are given. It is just as important to establish boundaries with the parents as the patient.