Refeeding syndrome, an undiagnosed and forgotten potentially fatal condition

Abstract

Refeeding syndrome (RFS) has been well described but is also a frequently forgotten and undiagnosed complication in clinical practice, which, if untreated, may lead to death. Patients who are more prone to developing RFS are those with at least one of the following conditions: BMI <16 kg/m², a recent unintentional weight loss >15%, very little nutritional intake for >10 days, and/or low plasma concentrations of potassium, phosphate or magnesium before feeding; and those with at least two of the following conditions: BMI <18.5 kg/m², a recent weight loss >10%, very little nutritional intake for >5 day, and/or a history of alcohol abuse or drug use, including insulin, chemotherapy or diuretics. We report here a patient who, after undergoing intestinal resection (short gut syndrome), presented diarrhoea, weight loss and protein–energy malnutrition. After nutritional assessment, the nutritional support team decided to feed the patient by the parenteral route. After 16 h of parenteral nutrition, the patient developed supraventricular tachycardia, hypomagnesaemia and hypocalcaemia, and RFS was diagnosed and managed. After intestinal adaptation, the patient is currently able to maintain his nutritional status with nutrition therapy by the oral route.

BACKGROUND

Refeeding syndrome (RFS) was first reported during World War II, when starved occupants of Leningrad and prisoners of war were refed and developed oedema, dyspnoea and heart failure, often leading to death.¹ Although RFS has been well described, it is also a frequently overlooked and undiagnosed complication in clinical practice.^2–5 It is considered to be a potentially fatal condition that occurs in patients with starvation due to any cause, including anorexia nervosa, diarrhoea, vomiting and alcoholism, and after operations.⁶

CASE PRESENTATION

A 51-year-old man presented with acute abdominal pain initially characterised as cramping pain, followed by a continuous dull pain. He became unstable and was admitted for an urgent open laparotomy. Acute mesenteric ischaemia was diagnosed and intestinal resection was performed, with about 70 cm of small bowel being left and immediately reconnected to caecum. As he had been admitted to a hospital without the support of a nutritional team, he was fed by the enteral route, with some complications related to nutritional therapy soon becoming apparent, such as diarrhoea (up to 14 times daily) and weight loss (>5% of body weight). Because of these clinical complications, 20 days after surgery he was referred to the Division of Clinical Nutrition of the Ribeirão Preto School of Medicine for clinical evaluation. On admission, physical examination showed faded mucosa, scaling skin, atrophic lingual papillae, glossitis and depressive oedema. Laboratory examinations showed hypoalbuminaemia, anaemia, hypocalcaemia and hypomagnesaemia (table 1). As the patient had short gut syndrome and was losing weight, with severe diarrhoea, our institutional support team decided to introduce a central venous line via the subclavian vein and parenteral nutrition was prescribed. Because he was at risk for RFS we decided to offer about 50% of his energy requirements (table 2).

Table 1.

Patient’s anthropometric measurements and clinical–laboratory parameters on admission

	Patient	Reference value
Weight (kg)	56
Height (cm)	170.5
Body mass index (kg/m2)	19.3
Basal energy expenditure: Harris–Benedict (kcal)	1.339
Total energy expenditure: Harris–Benedict ×1.2 (kcal)	1607
Albumin (g/l)	24	35–48
Potassium (mmol/l)	3.5	3.5–5.0
Magnesium (mEq/l)	1.16	1.6–2.5
Phosphate (mg/dl)	2.4	2.5–5.6
Ionised calcium (mmol/l)	0.98	1.14–1.29

Table 2.

Composition of the parenteral nutrition delivered to the patient

Nutrient	Amount delivered
Amino acids, 10%	50 g
Glucose, 50%	112.5 g
Lipids, 20%	20 g
Twice-distilled water	180 ml
Total energy (kcal)	830
Non-protein energy (kcal)	630
Glucose infusion rate (mg/kg per min)	1.4
Potassium	50 mEq
Sodium	64 mEq
Calcium	15 mEq
Phosphate	20 mEq
Magnesium	12 mEq
Thiamine	3 mg
Riboflavin	3.6 mg
Niacin	40 mg
Pyridoxine	4 mg
Folate	400 μg
Biotin	60 μg
Pantothenic acid	15 mg
Cyanocobalamin	5 μg
Vitamin C	100 mg
Vitamin A	3300 IU
Vitamin D	200 IU
Vitamin E	10 mg
Zinc	5 mg
Copper	1.6 mg
Chromium	20 μg
Manganese	800 μg

Sixteen hours after the beginning of nutritional support, the patient developed sinus tachycardia (fig 1) without haemodynamic instability, associated with hypocalcaemia (ionised calcium: 1.02 mmol/l), hypomagnesaemia (1.08 mEq/l) and hyperlactataemia (3.3 mmol/l, normal range: 0.9–1.7 mmol/l). We decided to withdraw parenteral nutrition until cardiac rhythm could be controlled.

Figure 1.

Chest electrocardiogram (derivation D II, 25 mm/s) showing sinus tachycardia (approximately 200–250 bpm), probably secondary to electrolyte disturbances due refeeding syndrome.

TREATMENT

After treatment with intravenous amiodarone, the patient’s tachycardia was controlled. He was found to have Wolf–Parkinson–White syndrome that might have contributed to the development of arrhythmia.

All electrolyte disturbances were corrected and thiamine was supplemented (100 mg per day) before restarting nutritional support. The patient started to receive about 40% of his energy requirements and after 4 days he was able to receive his full energy requirements without any metabolic complication.

OUTCOME AND FOLLOW-UP

One month later, the patient was discharged and continued to receive parenteral nutrition for 6 months due to short gut syndrome. After intestinal adaptation, he is able to maintain nutritional status with nutrition therapy by the oral route.

DISCUSSION

RFS can be defined as the potentially fatal shifts in fluids and electrolytes that may occur in malnourished patients receiving artificial refeeding (whether orally, enterally or parenterally).^2,7 These shifts result from hormonal and metabolic changes and may cause serious clinical complications. The hallmark biochemical feature of RFS is hypophosphataemia. However, the syndrome is complex and may also feature an abnormal sodium and fluid balance; changes in glucose, protein and fat metabolism; thiamine deficiency; hypokalaemia; and hypomagnesaemia.^5,6

Mechanisms of RFS can be explained by metabolic complications related to the refeeding process. Patients who are submitted to long starvation periods or who are in catabolic states often develop protein, fat, electrolyte, mineral and vitamin depletion as well as water and salt intolerance. A too rapid refeeding, particularly with carbohydrates, may precipitate a number of metabolic and pathophysiological complications, which may adversely affect the cardiac, respiratory, haematological, hepatic and neuromuscular systems, leading to clinical complications and even death.⁵ When we start the refeeding process we promote an anabolic stimulus as we offer nutrients, mainly in the form of carbohydrate. A glucose load stimulates insulin release, causing increased cellular uptake of glucose, phosphate, potassium, magnesium and water, and protein synthesis. This cellular uptake of electrolytes is responsible for the reduction of blood concentrations of phosphate, potassium and magnesium. Decreased levels of such important minerals can lead to altered myocardial function, cardiac arrhythmias, haemolytic anaemia, liver dysfunction, neuromuscular abnormalities, acute respiratory failure, gastrointestinal and renal disorders, and death.^6–8

To prevent RFS, some steps should be followed, including awareness of the condition and close monitoring of patients at risk, particular regarding their vital functions, fluid balance and plasma electrolytes, such as phosphate and magnesium.^8,9 Serum phosphate, magnesium, calcium, potassium, urea and creatinine concentrations should be measured before feeding and the measurements should be repeated daily for at least 4 days after feeding is started.⁹

Some authors’ suggestions are to refeed slowly and to build up the macronutrient content of the feed over several days (some of them suggest beginning with 25–50% of the energy requirement, 20 kcal/kg per day, or not to exceed 1000 kcal).^2,3,8–10 Although we followed this guideline and started nutritional support with 50% of energy requirements, the patient reported here developed RSF, which means that nutritional therapy should be tailored to individual needs. So far, there is no consensus regarding the prevention of RFS and no guidelines are available. Most recommendations are made by experts in clinical nutrition.⁷

To prevent electrolyte imbalance, some experts suggest to anticipate the additional requirements, particularly of phosphate, potassium, magnesium^7–9 and thiamine,⁵ and to minimise salt intake, unless the patient is salt depleted.^5,7 Fluid intake should also be minimised to that required to replace any deficit or to allow normal renal function.^5,7,9

Although there is no consensus, some authors recommend correcting vitamin and trace-element deficiencies as well as supplementing them, specifically thiamine, which should be given at least 30 min before feeding because it is required for carbohydrate metabolism and its deficiency may be related to metabolic acidosis and may predispose to heart failure.

The patient reported here received the recommend daily allowance (RDA) of vitamins and trace elements. Before 2005, most of the parenteral multivitamin preparations offered about 3 mg of thiamine, which might be insufficient for malnourished patients or for patients at nutritional risk. Today, parenteral multivitamin requirements have been modified, with some of the vitamins being increased in relation to the RDA reference (eg, thiamine from 3 to 6 mg, folic acid from 400 to 600 μg, and ascorbic acid from 100 to 200 mg). Thiamine deficiency may have been one of the mechanisms explaining the RFS of the patient reported here because RFS was no longer present when the patient received thiamine supplementation (100 mg/day).

In summary, RFS may be frequent in clinical practice, mainly among critical ill and malnourished patients. Physicians, dieticians, nurses and the nutritional support team should be ready to prevent, recognise, diagnose and treat RFS. Aggressive refeeding should be avoided to prevent this clinical condition that may lead to death, and all patients at risk of developing RFS should be submitted to clinical and laboratory monitoring.

LEARNING POINTS

• RFS is a potentially fatal condition caused by rapid initiation of refeeding after a period of undernutrition.

• Awareness of RFS and identification of patients at risk is crucial as the condition is preventable and the metabolic complications are avoidable.

• Nutritional support should be started with caution and slowly.

• Serum electrolytes should be monitored daily during the first week of refeeding, mainly in patients at risk, and all electrolyte deficiencies should first be corrected before total parenteral nutrition is commenced.