In the five years preceding 2022, 24 268 patients were admitted to UK hospitals with eating disorders and, although children and young people were the most affected, there was also a 79% increase in adults (Royal College of Psychologists (RCPsych), 2022a). This prompted the RCPsych to update its Management of Really Sick Patients with Anorexia Nervosa (MARSIPAN) recommendations to form the MEED guidelines (RCPsych), 2022b), a comprehensive guide to assessing and managing all forms of eating disorders.
Conditions such as avoidant, restrictive food intake disorder (ARFID) can be encountered on gastroenterology wards in patients with weight loss associated with dysmotilities, vomiting, gastroparesis and dyspepsia due to the avoidance of foods perceived as causing symptoms, such as as bloating, abdominal pain or discomfort, diarrhoea, constipation and vomiting (Murray et al, 2020). This highlights the growing frequency with which such patients are likely to be seen in various inpatient settings that do not have input from expert eating disorders services. MEED provides advice on risk assessment, safe refeeding and tube-feeding, and nutrition support teams (NSTs), nutrition specialist nurses and dietitians are ideally placed to ensure that this resource is used to optimise care through direct patient contact, developing policies and education.
MEED includes a detailed risk assessment that uses a flag system to alert clinicians to the impending threat to life from parameters that include weight, BMI, cardiovascular health, hydration status, muscular function, clinical sate, biochemistry, exercise and purging behaviours. Two or more red flags indicate a high risk, but it is imperative the assessment is carried out by nutritionally trained health professionals as clinical judgement is required for interpretation. For example, normal plasma levels of potassium, magnesium and phosphate in a patient who appears relatively well seem reassuring to an untrained clinician, but severely malnourished patients can be whole-body depleted of these electrolytes, despite their normal blood biochemistry, leading to the possibility of serious complications from inappropriate refeeding or electrolyte provision based solely on plasma levels (National Institute for Health and Clinical Excellence (NICE), 2017a).
Risk of refeeding syndrome is somewhat of a controversy because different guidelines have different criteria to determine it. The criteria set out in MEED are eating disorder-specific and have stricter criteria for determining high risk when compared with the more general criteria proposed by NICE (2017a): for example, a BMI of <13 kg/m2 is required in MEED as opposed to 16 kg/m2 in the NICE guideline. The reason for this is that eating disorder patients with malnutrition alone are likely to be at lower risk of refeeding syndrome than those with malnutrition and comorbidities that include sepsis, cancers or surgical complications. MEED provides a convincing rationale for aggressive refeeding of low-risk eating disorder patients, especially those in specialist eating disorders units (SEDUs). However, it seems likely that the majority of those admitted to acute hospitals will be at high risk, according to the criteria set out in both the MEED and NICE documents, warranting more cautious refeeding.
Pathophysiology of refeeding syndrome
A good knowledge of refeeding syndrome requires an understanding of the roles and distribution of the electrolytes potassium, magnesium, potassium and sodium, as well as the importance of cell membrane pumps in maintaining the optimal intracellular environment for good health. For example, magnesium is the most abundant cation (positively charged ion) in the body, with 98% found intracellularly, where it has a multitude of functions including energy metabolism and muscle contraction (Zacchia et al, 2016). The intracellular concentration of many electrolytes is maintained by cell membrane pumps, which are activated by insulin and require energy to function. In fact, up to around 40% of resting energy expenditure is accounted for by cell membrane pumping, highlighting how important they are to maintain optimal body function (O'Neill and Mikkelsen, 1987). A key cell membrane pump in refeeding syndrome is the sodium-potassium ATPase pump that pumps potassium into the cells and water and sodium out, requiring magnesium to function (Apell et al, 2017).
Due to the reduction in energy intake encountered in starvation and resultant decrease in circulating insulin, cell membrane pumps become significantly less active resulting in intracellular depletion of potassium, magnesium and phosphate, and a concomitant accumulation of water and sodium inside cells. The loss of intracellular potassium can maintain plasma levels in the normal range while whole body potassium becomes massively depleted, a principle that must be understood in order to effectively prescribe electrolyte replacement (NICE, 2017a; De Silva and Nightingale, 2020).
Upon providing energy as carbohydrate, cell membrane pumps are reactivated, with potassium and magnesium being pumped into the cell and water and sodium pumped out, leading to a potentially large deficit in circulating potassium and magnesium levels. The rising insulin levels also drive phosphate and glucose into cells where they are required for phosphorylation along with another easily depleted nutrient – thiamine (De Silva and Nightingale, 2020). The resulting hypokalaemia, hypomagnesaemia and hypophosphataemia can lead to arrhythmias (De Silva and Nightingale, 2020) among other symptoms, and have been cited as the cause of death in some refeeding cases, although these are incredibly rare (Matthews et al, 2018).
The sudden release of water and sodium into the circulation has been adequate to induce oedema in healthy volunteers upon refeeding (Kalm and Sembra, 2005; Korbonits et al, 2005). Sodium excretion more or less ceases in refeeding (Gozansky and Herman, 1971), partially due to insulin stimulating sodium reabsorption from the distal nephron, creating a high risk of fluid overload, which may be particularly harmful in patients with cardiac atrophy due to starvation (DeFronzo, 1981; De Silva and Nightingale, 2020). Heart failure and pulmonary oedema can develop, and the first clinical manifestations of refeeding syndrome can include increased respiratory rate and tachycardia (De Silva and Nightingale, 2020).
Perhaps too much emphasis has been placed on death as the main concern associated refeeding and, although this is a small possibility, problems due to fluid overload are much more likely to be encountered. These can be significant and have been summarised by Hanson (2021) (Table 1). It has been proposed that the marked oedema seen in kwashiorkor (severe malnutrition with ascites and bilateral swelling of the extremities) is not due to hypo-albuminaemia, but to severe intracellular potassium depletion, as potassium is required to exchange with sodium in cell membrane pumps (Jackson, 2015).
Table 1. Adverse effects of fluid overload on organ function
Safe refeeding in eating disorder patients
The goals of refeeding should be to build up energy intake as rapidly as possible while avoiding dangerous shifts in electrolytes and fluid overload. Experts such as the NST, dietitians and nutrition nurses are crucial to ensure appropriate energy provision, electrolyte supplementation and monitoring. Non-medical prescribers including dietitians and nutrition nurses can be invaluable in prescribing electrolytes, because junior doctors are usually trained to base electrolyte provision solely on plasma levels, which is not optimal in refeeding for the reasons already explained.
There has been extensive debate about the optimum level of energy provision on day 1 of feeding in high-risk patients, with criticism of the NICE recommendation of around 5-10 kcal/kg as being overly cautious (RCPsych, 2022b). However, it is likely that more emphasis should be placed on the rate of build-up and avoiding prolonged periods of low energy provision than the amount given on day 1. Although there is no hard evidence, it is possible to argue that excessive provision on day 1 can lead to a significant intracellular shift of electrolytes, such as potassium or phosphate, a large drop in plasma levels and a subsequent need to delay build-up of energy. MEED (RCPsych, 2022b) advocates a food-first approach to nutrition support and it may be unrealistic to assume that you can achieve precise levels of energy per kg when the meals are provided by a hospital catering department, even with input from a dietitian. This highlights the need for adequate electrolyte provision and careful monitoring. Failure to build feeds up to target quickly, and prolonged periods on low energy provision due to fear of refeeding problems, has been referred to as the underfeeding syndrome and has also been associated with deaths (RCPsych, 2022b).
Starting at 10 kcal/day allows compliance with both MEED (RCPsych, 2022b) and NICE (2017a) recommendations, and energy provision should be built up swiftly to meet or exceed target by day 4–7. In order to do this without precipitating significant drops in plasma electrolytes, prophylactic provision of 2-4 mmol/kg/day potassium, 0.2–0.4 mmol/kg/day magnesium and 0.3-0.6 mmol/kg/day of sodium is made unless plasma levels are high is recommended (NICE, 2017a). The easiest way to do this without excess fluid provision is to use oral preparations and suggested regimens for patients with normal renal function are presented in Table 2. Stanga et al (2008) recommended that >2 mmol/kg/day sodium and total fluid intake of approximately 20ml/kg/day are given during refeeding.
Table 2. Suggested prophylactic electrolyte provision for 30–40kg adult
|Electrolyte||Example preparation||Dose||Provision mmol|
|Effervescent potassium chloride||12 mmol tablet||2 tablets tds||72 mmol K|
|Potassium chloride||1 mmol/ml syrup||20 ml tds||60 mmol K|
|PO4||Phosphate Sandoz||1 tablet bd||36 mmol PO4|
|Mg-l-aspartate||Mg-l-aspartate10 mmol sachet||1 sachet bd||20 mmol Mg|
|Mg-glycerol phosphate||4 mmol tablets||2 tablets bd||16 mmol Mg|
K=potassium, Mg=magnesium, PO4=phosphate bd twice daily, tds=three times daily
For patients with a high BMI, ideal weight is preferable for estimating fluid and electrolyte requirements. This is because adipose tissue is relatively metabolically inactive and requires equivalent amounts of electrolytes to skeletal muscle. So, for example, patients with sarcopenic obesity are depleted of muscle, but can still weigh around 100 kg. Giving 2–4 mmol/kg of potassium per actual weight would effectively mean giving up to 400 mmol/kg, which would be practically impossible and potentially dangerous.
Remember to take into account the electrolyte content of oral nutritional supplements, dietary sources and tube feeds when prescribing. Additional electrolytes can usually be stopped after 10 days (NICE, 2017a) or when feeding has been fully established and plasma levels are stable. Monitor adjusted calcium carefully when giving phosphate because it can induce a reduction in plasma levels. When using oral preparations with eating disorder patients, their intake should be supervised to ensure that the patient takes them and does not vomit.
Urea and electrolytes, magnesium, phosphate and adjusted calcium should be monitored once or twice daily during refeeding (NICE, 2017a; RCPsych, 2022b). Giving prophylactic electrolytes should allow energy provision to be increased if modest drops in potassium, magnesium and phosphate are encountered. However, feed rates may need to be reduced if the patient has severely low levels of potassium (<2.5 mmol/L), phosphate (<0.4 mmol/L) or magnesium (<0.4 mmol/L). The need for intravenous (IV) replacement should therefore be considered.
Intravenous electrolyte replacement
Although IV magnesium can be given to a target of 0.2 mmol/kg in relatively small fluid volumes, potassium and phosphate can pose problems in this respect. With 10 mmol phosphate/100 ml, the Polyfusor is possibly the best option for infusing 0.3-0.6 mmol/kg without excess fluid, however it does contain moderate amounts of sodium (16 mmol/100 ml). It is therefore recommended that, wherever possible, patients requiring IV potassium or phosphate are transferred to a high-dependency unit or similar for administration of concentrated electrolytes.
Although MEED (RCPsych, 2022b) advocates correction of electrolyte abnormalities according to local policies, caution should be taken with this approach in the case of potassium because it is common to recommend giving 20-40 mmol of potassium in 1000 ml 0.9% saline for levels <2.5 mmol/L. This would result in administering >4-5 times the requirement of sodium and chloride, excess fluid and only 0.5-1 mmol/kg potassium for a 40 kg patient. Since hyperchloraemia constricts renal arteries and lowers glomerular filtration rate (Li et al, 2016), the resulting circulatory overload would be of immense concern in a patient with cardiac atrophy and possible ECG changes. Hyperchloraemia also depletes potassium from cells, potentially increasing the intracellular deficit (Li et al, 2016).
Contrary to some local policies, 5% glucose is probably a superior IV diluent, as the fluid load is easily excreted (Lobo et al, 2001), and should be recommended as long as the energy from glucose and the risk of hyponatraemia are taken into account. If a central line is in place, 40 mmol of potassium can be given in 500 ml 5% dextrose. However, in patients with high gastrointestinal losses such as those due to vomiting or laxative abuse, 0.9% sodium chloride may be preferable (NICE, 2017b).
Thiamine and micronutrients
Thiamine (vitamin B1) is a water-soluble vitamin that is rapidly depleted: this is because the body only has the capacity to store enough to last a maximum of 18 days with poor intake (Osiezagha et al, 2013). It plays a vital role in carbohydrate metabolism, predominantly in the Krebs cycle, where it is a co-factor for the enzyme pyruvate dehydrogenase (Osiezagha et al, 2013). Failure to give adequate thiamine during refeeding can lead to incomplete carbohydrate metabolism and a build-up of lactic acid, with the resulting acidosis causing a possible increase in excretion of key electrolytes such as potassium, magnesium and phosphate (De Silva and Nightingale, 2020). Synthesis of the active form of thiamine pyrophosphate requires magnesium which provides another good reason with prophylactic provision of the electrolyte (Osiezagha et al, 2013).
Thiamine has a number of crucial roles in the central nervous system (CNS), including synthesis and regulation of neurotransmitters such as dopamine, acetyl choline and gama-amino butyric acid, as well as myelin production (Osiezagha et al, 2013). Deficiency in highly metabolically active parts of the brain can cause nerve cell death and the development of Wernicke's encephalopathy (WE) (Osiezagha et al, 2013). The symptoms of WE include confusion, confabulation and ataxia, and the failure to treat them with high-dose parenteral thiamine can result in permanent brain injury. Patients with untreated WE can develop Korsakoff 's psychosis, which includes disorientation and short-term memory less (Stanga et al, 2008).
WE may manifest during refeeding when the remaining stores of thiamine are used up in carbohydrate metabolism throughout the body, leading to a deficiency in the CNS, and there are documented cases of permanent brain injuries arising from the infusion of parenteral nutrition without vitamins (Stanga et al, 2008).
To prevent problems in most patients it should be adequate to treat them with 300 mg/day of oral thiamine (NICE, 2017a). Because the patient may have deficiencies of other micronutrients, it is recommended that vitamin B compound strong, and balanced multivitamin and mineral tablets, are given in the first 10 days of refeeding (NICE, 2017a). Patients deemed at very high risk of refeeding, those with malabsorption problems or a history of high alcohol intake should be given high-dose parenteral thiamine. Pabrinex 1 pair of ampoules once daily for 3–5 days should be adequate for prophylaxis in most eating disorder patients; however, those with a history of high alcohol intake may require two pairs of ampoules three times a day until feeding is established and there are no symptoms of WE (Turner, 2017).
Experts in nutrition are also required to safely interpret other aspects of biochemistry and observation charts in eating disorder patients who are being fed on general wards because they are at increased risk of infection, but may not show classic signs of sepsis such pyrexia and raised C-reactive protein (CRP) levels (Robinson et al, 2011; Webb et al, 2011). For example, a low serum albumin may be attributed to malnutrition, however it is a very poor nutritional marker and does not drop as the result to starvation alone (Klein, 1990; Soeters et al, 2019).
Hypo-albuminaemia is not found in uncomplicated anorexia nervosa and is most likely to be a sign of occult sepsis requiring broad-spectrum antibiotics (Krantz et al, 2005). Similarly, the combination of hypothermia, hypoglycaemia and low BMI has been termed the ‘deadly triad’ and also indicates infection that requires prompt antimicrobial therapy (Jackson 2005; Robinson et al, 2011).
Artificial nutrition support
The MEED guidance (RCPsych, 2022b) explains that nasogastric feeding can be considered as a short-term measure in certain circumstances where oral nutrition support is unsuccessful and the patient consents to placement of a tube. It may be used where malnutrition poses a threat to life, but it presents increased risks on general wards, and dietitians and nutrition nurses may be required to develop protocols and educate staff on its use.
Continuous nasogastric feeding may be appropriate in metabolically unstable patients at very high risk of refeeding problems, but daytime bolus feeding has the advantage of presenting less opportunities for the feed to be tampered with (RCPsych, 2022b).
Although it is legal to feed under restraint in eating disorder patients at risk of death in the UK, this can be undertaken only with input from expert psychiatric professionals. The use of nasal retention devices with nasogastric tubes on general wards is not recommended because they are designed to reduce the possibility of accidental displacement only and can lead to significant nasal septum damage if forcibly removed (RCPsych, 2022b).
Gastrotomy tubes are generally not recommended, but nasojejunal feeding could be considered in patients with ARFID associated with gastrointestinal dysmotility. Such patients can also be referred for parenteral nutrition but, again, this is only likely to be appropriate as a short-term measure under the supervision of the NST, because long-term use in this group of patients is usually associated with harm, such as line sepsis and liver dysfunction (Nightingale et al, 2020).
Patients with eating disorders are increasingly likely to be encountered on general hospital wards which may not have the expertise to safely manage them. This demonstrates a clear role for experts such as NSTs, nutrition nurses and dietitians to ensure delivery of high-quality care through implementation of the MEED guidelines.
- There has been a 79% increase in the number of adults admitted to UK hospitals with eating disorders in the past 5 years
- Many of these patients will be at high risk of refeeding syndrome, requiring expert management to avoid dangerous electrolyte in balances and fluid overload
- Prophylactic replacement of electrolytes with oral preparations can allow rapid build-up of feeding, while reducing need for intravenous electrolyte provision, which carries a high risk of fluid, sodium and chloride overload
- Nasogastric feeding can be used in eating disorders where oral intake is insufficient, but special protocols may need to be developed to carry it out safely on general wards
CPD reflective questions
- Why should you be concerned about a low serum albumin in severely malnourished patients with eating disorders, and what would be the likely treatment?
- What are the risks associated with giving 40 mmol of potassium in 1000 ml 0.9% sodium chloride intravenously to a 40 kg eating disorders patient?
- What would a raised respiratory rate and increased heart rate suggest in a patient being refed?