Some groups of malnourished patients at particular risk of developing the refeeding syndrome Low nutrient intake Increased nutrient losses/decreased nutrient absorption Unintentional weight loss
Clinical effects of Starvation Resting Energy Expenditure fall by about 25-35% by 3 weeks. Serum albumin concentrations remain normal. Serum prealbumin falls. Death occurs when body fat is depleted. Obese persons can withstand prolonged starvation.
Thiamine Deficiency Thiamine deficiency occurs due to increased cellular utilisation of thiamine in response to carbohydrate refeeding and is associated with the precipitation of Wernicke’s encephalopathy, and the potential development of Korsakov syndrome with its attendant lifelong neuropsychiatric disability.
In 1981, Weinsier and Krumdieck4 published a paper that outlined dramatic and rapidly evolving refeeding syndrome in 2 chronically malnourished patients who received aggressive dextrose-based TPN. Emphasis was placed by these authors on the hypophosphatemia (reported nadirs of 0.4 and 0.7 mg/dL) that developed in these 2 patients. This paper has been used extensively by nutrition support educators to emphasize the importance of recognizing patients at risk for refeeding syndrome and to approach the feeding of such patients with due caution. Patients who are typically at increased risk of refeeding syndrome are those who are extremely malnourished at the time of refeeding.
Cause of Oedema: The pathogenesis of refeeding oedema is complex. In general, two basic mechanisms are involved in oedema formation, namely: an alteration in capillary haemodynamics that favours the movement of fluid from the vascular space into the interstitium, and the retention of sodium and water by the kidneys During refeeding, there is increased secretion of insulin and it has been proposed that insulin release can result in significant oedema (Kalambokis GN, Tsatsoulis AA, Tsianos EV. The edematogenic properties of insulin. Am J Kidney Dis 2004; 44:575-90.) Insulin can promote sodium and potassium reabsorption in the diluting segment of the distal nephron and this effect is largely attributed to hypokalaemia(3,4). The role of glucagon has also been implicated - increased levels of glucagons during starvation exhibit a natriuretic effect(5), whereas decreased levels during refeeding enhances anti-natriuresis in the distal tubule
Weinsierand Krumdieck's cases hearkened back more to the World War II descriptions of refeeding complications, with the spotlight on the cardiovascular and pulmonary manifestations. Investigators during and immediately following World War II had not fully recognized the importance of hypophosphatemia in refeeding complications; this recognition largely emerged after the introduction of TPN in the late 1960s and 1970s, and Weinsier and Krumdieck's reports also emphasized this aspect of the syndrome.
Validation Hayek and Eisenberg 5 studied 25 patients receiving postoperative enteral feedings in the surgical intensive care unit. Within 2 to 5 days after initiation of enteral feedings (600 to 1200 kcal/d initially increased based on patient tolerance), serum phosphorus levels decreased from 2.4 to 4.8 mg/dL to 0.5 to 1.2 mg/dL(normal range 0.85-1.40 mmol/l) . It was concluded that highly stressed patients may have higher requirements for phosphorus than the amount present in standard isotonic enteral feedings. Note that this study focused on refeedinghypophosphatemia rather than the larger constellation of manifestations of refeeding syndrome.
In most casesThe phosphorus nadir tended to occur within the first week of initiating refeeding. Also, it had been noted in the older literature that cardiovascular complications were more likely to occur during the first week of refeeding as well whereas neurologic complications tended to occur a bit later
Complication Cardiovascular ( usually happens during the first week ), Respiratory, Haematological, Hepatic and Neuromuscular systems leading to clinical complications and even death ( usually happens in later stages)
Severe hypophosphataemia is a prime feature, and usually this is what alerts the clinician. The other facets to the metabolic disorder include thiamine and other vitamin deficiencies, hypokalaemia, hypomagnesaemia, as well as glucose and fluid balance abnormalities (Crook et al, 2001). The severe hypophosphataemia may present with rhabdomyolysis and cardiomyopathy. It may cause epilepsy, delirium and paraesthesia (Knochel, 1981). Haemolysis and platelet dysfunction are rare complications that usually follow severe hypophosphatemia (Jacob & Amsden, 1971; Knochel, 1981), although in the two cases we described haemolytic anaemia followed moderate reduction of phosphate levels. The exact mechanism is unknown but probably is due to increased rigidity of membranes (Jacob & Amsden, 1971) and metabolic acidosis induced by reduced levels of ATP (Knochel, 1981). Hypokalaemia may be associated with the development of cardiac arrhythmias, hypotension, and cardiac arrest. It may also cause ileus, weakness, paralysis, delirium and rhabdomyolysis. Hypomagnesaemia when severe may cause potentially fatal cardiac arrhythmias as well as neuromuscular symptoms, ataxia, epilepsy and delirium. Fluid intolerance in refeeding syndrome may result in cardiac failure, dehydration or fluid overload, hypotension, pre-renal failure and sudden death. Abnormal glucose and lipid metabolism can potentially trigger hyperglycaemia and hypercapnic respiratory failure (Crook et al, 2001).
Some complication of Carbohydrate overfeeding Hyperglycemia. In extreme cases, this could lead to: Osmotic diuresis, Dehydration, and Hyperosmolar nonketotic coma
Details for complications : In the classic form of refeeding syndrome, carbohydrate overfeeding of a chronically malnourished patient often led to hyperglycemia. In extreme cases, this could lead to osmotic diuresis, dehydration, and hyperosmolarnonketotic coma. Both of Weinsier and Krumdieck's case patients exhibited extreme hyperglycemia, one to a maximum of about 700 mg/dL and the other to about 1200 mg/dL. With what we now know about the downside of hyperglycemia in hospitalized patients, and particularly intensive care patients, this complication of refeeding syndrome is to be avoided.
Prevention There are several ways to prevent and control the refeeding syndrome:
Protocols for repletion of hypophosphatemia have been refined since the early reports of refeeding syndrome in recipients of nutrition support. An intravenous phosphorus repletion regimen proposed by Vannattaet al7 became popularized at about the same time as the refeeding syndrome reports from Weinsier and Krumdieck. This regimen used 9 mmol of potassium phosphate infused continuously every 12 hours for patients with severe hypophosphatemia, A more aggressive phosphorus repletion regimen was proposed by Kingston and Al-Siba'i .8 In this approach, 0.5 mmol/kg of phosphorus was recommended for serum phosphorus less than 0.5 mg/dL and 0.25 mmol/kg for serum phosphorus between 0.5 and 1 mg/dL.
********* Significant serum electrolyte abnormalities should be corrected prior to beginning nutrition support. Provision of supplemental potassium, magnesium,and phosphorus beyond amounts normally anticipated to be required for maintenance may be prudent in patients at risk for refeeding syndrome. Research to determine optimal electrolyte repletion regimens for obese patients would be useful as these patients have typically been excluded from, for example, the phosphate repletion studies mentioned earlier. Serum electrolytes should be monitored daily during the firstweek of refeeding in at-risk patients. Supplemental thiamine in amounts higher than found in most multivitamin preparations is also sometimes recommended for the first several days of refeeding of at-risk patients.
************ Another study recommends that Regardless of the rout (oral, total parenteral nutrition or enteral delivery) clinicians should initiate feeding at 50% or less the patient's energy goal, and advance gradually, as tolerated in order to avoid cardiac overload and rapid electrolyte shift. for the first day, patients should be hydrated slowly and their electrolytes corrected. A small amount of intravenous glucose can be give to spare protein mobilization ( in the range of 150 g glucose (500 calories) per day. With at least 10 mmol of phosphate, and about 30-40 mmol of potassium, depending on renal function. For the energy goal, there is no absolute method to calculate the amount of calorie required, but in general, it should be based on the patient’s current, not ideal body weight. We use the Harris-bendict formula and multiply it by 1.3 if the patents is lethargic and in bed, or by 1.5 if the patients is ambulatory. To replete protein stores, we give 1.2-1.5 g/kg of protein based on the IBW.13 To prevent hypophosphatemia, 10-20 mmol of phosphorus/1000 Kcal of carbohydrate should be given.
Protein Some sources suggest giving 1.2-1.5 g/kg/day and others suggest giving 1.5-2 g/kg/day High CHO intake exacerbates the refeeding syndrome. Low protein High energy diet causes fat gain but not lean tissue. High protein diet can reduce nitrogen loss even if energy deficient. Exercising is important to regain muscle mass. For Calculating Energy, use Actual weight. For Calculating Protein, use Ideal weight.17
Case report14 European Journal of Clinical Nutrition (2008) 62, 687–694; doi:10.1038/sj.ejcn.1602854; published online 15 August 2007
27-year-old asylum seeker, with no previous medical history, went on hunger strike over a period of 4 months, refusing all nourishment apart from tea and coffee with sugar. At this time, he was admitted to hospital and, over the subsequent 2 weeks, lost a further 10 kg in weight to 49 kg, (BMI 14.7 kg/m2). He became progressively weaker, more inactive and apathetic. At this point, he was treated by enteral and parenteral nutrition with a total intake of 1600 kcal/day. He was also given a daily infusion of 500 ml 0.9% saline with 20 mmol KCl and vitamins and trace elements according to the dietary reference intakes (DRI)
After 3 days,his condition had deteriorated. He had gained 5 kg in weight, due to salt and water retention, and developed hypokalaemia 2.8 mmol/l, normal range: 3.5–4.7 mmol/l, hypomagnesaemia 0.49 mmol/l, normal range: 0.7–1.0 mmol/l and hypophosphataemia 0.05 mmol/l, normal range: 0.74–1.55 mmol/l. He showed neurological symptoms and signs with vertigo and vertical nystagmus. Artificial nutritional support was discontinued; a single dose of thiamine 200 mg was given intravenously and potassium phosphate 40 mmol was infused daily for 3 days. He also received a single i.v. dose of magnesium sulphate 20 mmol.
After 3 dayshis electrolyte and mineral concentrations had risen into the normal range (K+ 4.2 mmol/l, Mg2+ 0.77 mmol/l and PO42- 1.16 mmol/l). Three days later,oral nutrition (1600 kcal/day) was started and micronutrients were given i.v. according to the DRI After 37 days,his vertigo resolved. His mood and physical strength gradually improved and He wasdischarged after 57days in hospital with a weight of 64.4 kg (gain of 15.4 kg) and a BMI of 19.2 kg/m2. Unfortunately, the vertical nystagmus continued, preventing him from reading or watching television.
Cont. case report Key notes:15 This case illustrates the vulnerability of patients with extreme weight loss and a very low BMI to the refeeding syndrome. The rapid falls in potassium, magnesium and phosphate within 24–48 h without adequate supplements were typical, although his main neurological sequelae were due mainly to Wernicke's encephalopathy from acute thiamine deficiency. Thiamine is not stored in appreciable amounts, so that any acceleration of carbohydrate metabolism—for which it is a cofactor—may precipitate acute deficiency. In such cases, this should always be anticipated by giving prophylactic thiamine at a dose of 200–300 mg i.v. daily, with the first dose being given 30 min before refeeding. The incidence of some form of the refeeding syndrome in severely malnourished patients started on artificial feeding is approximately 50% , with half of these developing the syndrome within 3 days of starting treatment