Thanks to everyone who contributed to the discussions about Ellen an 18 year old female who had weight loss.
This week’s question setter & expert was Dr Phil Smith, Gastroenterology SpR & BSG Trainees Section Chair, Whipps Cross Hospital, London.
Information available at the start of the week:
Ellen Baxter an 18-year-old female law student, presents to outpatient clinic with her mother with 2-year history of weight loss, amenorrhoea, and occasional ‘diarrhoea’
History reveals no red flag symptoms, other than gradual weight loss and increasing exercise over the last 2 years, with a previous history of laxative abuse as a teenager. She admits she still takes laxatives regularly, as she feels constipated, although she has watery diarrhoea intermittently. She admits she regularly ‘skips’ meals. She has not menstruated for at least 2 years.
On examination, she was anxious and her mood is guarded in affect. Her Body Mass Index (BMI) is 12 kg/m2, appeared dry and malnourished with widespread lanugo hair. There is some mild peripheral oedema. She is bradycardiac (Pulse 40 bpm), but there were no other external examination findings. PR examination shows solid stool in the rectum.
Initial blood tests showed a low potassium (2.9 mmol/L), low phosphate (0.65 mmol/L), low random glucose (3.5 mmol/L), borderline-low albumin (33 g/dL), with liver function tests showing a mild transaminitis.
Question 1: What is your differential diagnosis?
A. Coeliac Disease
B. Inflammatory Bowel Disease
C. Anorexia Nervosa
D. GI Malignancy
E. Bile Salt Malabsorption
CORRECT ANSWER: C
Q2. What is your initial management?
Q3. She is at high risk of re-feeding syndrome, but what factors determine whether a patient is high risk of re-feeding syndrome?
Q4. What is the mechanism of re-feeding syndrome?
Q5. What are the pathological and metabolic consequences of re-feeding syndrome?
- Patient’s with a very low BMI and anorexia nervosa are at high risk of re-feeding syndrome on reintroduction of food and calories
- It is crucial to identify those patients at high risk of re-feeding syndrome before the introduction of food and calorific administration
- Re-feeding syndrome is a severe metabolic syndrome characterised by multiple electrolyte disturbances – as well as major alterations in fluid balance
A number of journal papers are referenced in the expert commentary, which are the best source of further information related to this case. The papers also help provide additional information and discussion surrounding such patients and their clinical management.
For further information visit:
Dr Phil Smith, Gastroenterology Registrar, says:
This a very important topic to discuss and be aware of given the severe, life-threatening consequences if the patient is not managed appropriately and by a specialist multi-disciplinary team. The patient clearly has anorexia nervosa and is at high risk of re-feeding syndrome, a metabolic syndrome.
This patient clearly has a diagnosis of anorexia nervosa with an extremely low BMI. This is consistent with the history of laxative abuse, excess exercise and admission by the patient that she restricts her calorie intake. The diarrhoea described appears to be overflow diarrhoea associated with chronic laxative abuse. She has secondary amenorrhoea due to her low BMI. The differential diagnosis is limited given the findings, but in the absence of key components in the history (laxative abuse, calorie restriction) and more definite history of chronic diarrhoea, the presence of anaemia, one may consider excluding organic causes such as coeliac disease and inflammatory bowel disease, or other causes of malabsorption. There are no ‘red’ flag symptoms (including rapid weight loss, night sweats, ‘B symptoms’ (consistent with a haematological malignancy) or any other GI symptoms such as dysphagia, PR bleeding). There is no history of previous GI surgery (such as a right hemicolectomy) leading to diarrhoea via bile salt malabsorption – furthermore you would not expect any of the other features seen in this patient with this condition.
Given this patient has an extremely low BMI, electrolyte disturbance and evidence of fluid imbalance (peripheral oedema), it is clear this patient needs admission to hospital and inpatient management by a multi-disciplinary team (Nutrition team, nurses, dieticians, psychiatric team) whilst her fluid, electrolyte and nutritional status is closely monitored and corrected (see Mehanna et al, 2008 BMJ, page 1495). Using the MUST (Malnutrition Universal Screening Tool) (Stroud et al, 2003, Gut) she is categorised as a patient that is high risk of malnutrition.
Risk of re-feeding syndrome
She is high risk of re-feeding syndrome (Mehanna et al, 2008 BMJ; NICE Guidelines on Enteral Nutrition, 2006) based on the following criteria:
Either the patient has one or more of the following:
– Body mass index (kg/m2) <16
– Unintentional weight loss >15% in the past three to six months
– Little or no nutritional intake for >10 days
– Low levels of potassium, phosphate, or magnesium before feeding
Or the patient has two or more of the following:
– Body mass index <18.5
– Unintentional weight loss >10% in the past three to six months
– Little or no nutritional intake for >5 days
– History of alcohol misuse or drugs, including insulin, chemotherapy, antacids, or diuretics
The history of the individual patient would also indicate if a patient is at risk of re-feeding syndrome (Mehanna et al, 2008 BMJ; Hearing SD, 2008 BMJ)
– Patients with anorexia nervosa
– Patients with chronic alcoholism
– Oncology patients
– Post operative patients
– Elderly patients (comorbidities, decreased physiological reserve)
– Patients with uncontrolled diabetes mellitus (electrolyte depletion, diuresis)
– Patients with chronic malnutrition: Marasmus, prolonged fasting or low energy diet, morbid obesity with profound weight loss, high stress patient unfed for >7 days, malabsorptive syndrome (such as inflammatory bowel disease, chronic pancreatitis, cystic fibrosis, short bowel syndrome)
– Long term users of antacids (magnesium and aluminium salts bind phosphate)
– Long term users of diuretics (loss of electrolytes)
Mechanism of re-feeding syndrome
To understand the mechanism of re-feeding syndrome, you must first appreciate the metabolic changes in starvation. During prolonged fasting, hormonal and metabolic changes are aimed at preventing protein and muscle breakdown. Muscle and other tissues decrease their use of ketone bodies and use fatty acids as the main energy source. This results in an increase in blood levels of ketone bodies, stimulating the brain to switch from glucose to ketone bodies as its main energy source. The liver decreases its rate of gluconeogenesis, thus preserving muscle protein. During the period of prolonged starvation, several intracellular minerals become severely depleted. However, serum concentrations of these minerals (including phosphate) may remain normal. This is because these minerals are mainly in the intracellular compartment, which contracts during starvation (Mehanna et al, 2008 BMJ; Kohn et al, 2011 Curr Opin Pediatr).
During re-feeding syndrome, glycaemia leads to increased insulin and decreased secretion of glucagon. Insulin stimulates glycogen, fat, and protein synthesis. This process requires minerals such as phosphate and magnesium and cofactors such as thiamine. Insulin stimulates the absorption of potassium into the cells through the sodium-potassium ATPase symporter, which also transports glucose into the cells. Magnesium and phosphate are also taken up into the cells. Water follows by osmosis. These processes result in a decrease in the serum levels of phosphate, potassium, and magnesium, all of which are already depleted. The clinical features of the re-feeding syndrome occur as a result of the functional deficits of these electrolytes and the rapid change in basal metabolic rate (Mehanna et al, 2008 BMJ; Kohn et al, 2011 Curr Opin Pediatr).
The metabolic and pathophysiological consequences of re-feeding syndrome include:
Metabolic consequences include:
– Hypophosphataemia (key feature)
– Fluid and sodium balance abnormalities
Pathophysiological consequences include:
1) Cardiac failure/arrhythmias and cardiac arrest
2) Neuromuscular failure (paraesthesia, muscle weakness, seizures, tremors)
3) Respiratory failure (muscle weakness)
4) Renal failure
5) Hepatic failure
What you need to do as the junior Doctor caring for this patient
As a FY1 on the ward admitting Ellen from clinic you should:
- Complete history and examination and baseline observations (pulse, blood pressure including lying and standing blood pressures to look for postural drop, temperature, oxygen saturations, and blood glucose) and ensure nurses aware of the requirement for close observations
- Inform your seniors and the specialist nutrition team (if available) +/- dietician and nurses that there is a patient who is high risk of refeeding syndrome with a very low BMI. Inform inpatient psychiatric team.
- Perform a MUST score (this is not just the role of the nurses!) and document and outcome
- Check bloods FBC, U+E, LFTs, Albumin (not a good measure of malnutrition as a acute phase protein) – most importantly checking Magnesium, Potassium, Phosphate, and calcium
- NOTE: You do not have to correct any abnormal results prior to starting feeding, although most physicians do (i.e. if potassium is low, replace the potassium)
- ECG – perform a baseline ECG (to check for features associated with hypokalaemia such as ST depression and U waves, PR prolongation for example).
- Perform baseline CXR (patients are at risk of cardiac failure) +/- for NG Tube (NGT) placement/position confirmation in the event of NGT feeding being required
- Gain good intravenous access
- Give intravenous IV Thiamine and multivitamins (typically Pabrinex)
- After dietetics review, start refeeding (as per local guidelines) which is typically extremely slowly and increasing slowly as per specialist team/dietician directed guidance – an example guideline is in Mehanna et al, 2008 BMJ paper (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2440847/pdf/bmj-336-7659-cr-01495.pdf)
- Rehydrate slowly and carefully given risk of cardiac failure and fluid overload
- Daily bloods (including daily potassium, Magnesium, phosphate, calcium) as a minimum with correction of electrolytes. Continue to check bloods and amend treatment for 1-2 weeks or until electrolytes stable and patient on a stable feeding regimen
- Daily review and examination (even at weekend)