Refeeding syndrome

Illness caused by the sudden feeding of a malnourished individual

Medical condition

Refeeding syndrome

Specialty| Gastroenterology
Risk factors|

* Starvation
* Very low weight
* Unintentional weight loss
* Low levels of potassium, phosphate, or magnesium before eating
* Alcohol use disorder
* Some types of medications[1]: 37–38

Refeeding syndrome (RFS) is a metabolic disturbance which occurs as a result of reinstitution of nutrition in people who are starved, severely malnourished, or metabolically stressed because of severe illness. When too much food or liquid nutrition supplement is eaten during the initial four to seven days following a malnutrition event, the production of glycogen, fat and protein in cells may cause low serum concentrations of potassium, magnesium and phosphate.[2][3] The electrolyte imbalance may cause neurologic, pulmonary, cardiac, neuromuscular, and hematologic symptoms—many of which, if severe enough, may result in death.

## Cause

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Any individual who has had a negligible nutrient intake for many consecutive days and/or is metabolically stressed from a critical illness or major surgery is at risk of refeeding syndrome. Refeeding syndrome usually occurs within four days of starting to re-feed. Patients can develop fluid and electrolyte imbalance, especially hypophosphatemia, along with neurologic, pulmonary, cardiac, neuromuscular, and hematologic complications.[citation needed]

During fasting, the body switches its main fuel source from carbohydrates to fat tissue fatty acids and it is contended that amino acids from protein sources such muscle as the main energy sources. This timing of protein use is contested: that at first the body practices autophagy to source amino acids rather than being simultaneously used with fat. That the body only uses protein as fuel source when all fat has been depleted. The spleen decreases its rate of red blood cell breakdown thus conserving red blood cells. Many intracellular minerals become severely depleted during this period, although serum levels remain normal. Importantly, insulin secretion is suppressed in this fasting state, and glucagon secretion is increased.[2]

During refeeding, insulin secretion resumes in response to increased blood sugar, resulting in increased glycogen, fat, and protein synthesis. Refeeding increases the basal metabolic rate. The process requires phosphates, magnesium and potassium which are already depleted, and the stores rapidly become used up. Formation of phosphorylated carbohydrate compounds in the liver and skeletal muscle depletes intracellular ATP and 2,3-diphosphoglycerate in red blood cells, leading to cellular dysfunction and inadequate oxygen delivery to the body's organs. Intracellular movement of electrolytes occurs along with a fall in the serum electrolytes, including phosphate and magnesium. Levels of serum glucose may rise, and B1 vitamin (thiamine) may fall. Abnormal heart rhythms are the most common cause of death from refeeding syndrome, with other significant risks including confusion, coma and convulsions and cardiac failure.[citation needed]

### Anorectics

[edit]

An anorectic or anorexic is a drug which reduces appetite, resulting in lower food consumption, leading to weight loss.[4]

Examples of anorectics includes stimulants like amphetamines, methylphenidate, and cocaine, along with opiates. Abusing them can lead to prolonged periods of inadequate calorie intake, mimicking anorexia nervosa. If someone misuses these substances and then starts eating normally again, they may be at increased risk of refeeding syndrome.

## Clinical situations

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The syndrome can occur at the beginning of treatment for eating disorders when patients have an increase in calorie intake and can be fatal. It can also occur when someone does not eat for several days at a time usually beginning after 4–5 days with no food. [5] It can also occur after the onset of a severe illness or major surgery. The shifting of electrolytes and fluid balance increases cardiac workload and heart rate. This can lead to acute heart failure. Oxygen consumption is increased which strains the respiratory system and can make weaning from ventilation more difficult.[citation needed]

## Diagnosis

[edit]

Refeeding syndrome can be fatal if not recognized and treated properly. The electrolyte disturbances of the refeeding syndrome can occur within the first few days of refeeding. Close monitoring of blood biochemistry is therefore necessary in the early refeeding period.[citation needed]

The National Institute for Health and Clinical Excellence identifies the following criteria for individuals at high risk for refeeding syndrome:[6]

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[6]

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[6]

## Treatment

[edit]

In critically ill patients admitted to an intensive care unit, if phosphate drops to below 0.65 mmol/L (2.0 mg/dL) from a previously normal level within three days of starting enteral or parenteral nutrition, caloric intake should be reduced to 480 kcals per day for at least two days while electrolytes are replaced.[3] Daily doses of NADH/CoQ10/Thiamine, Vitamin B complex (strong) and a multivitamin and mineral preparation are strongly recommended. Blood biochemistry should be monitored regularly until it is stable. Although clinical trials are lacking in patients other than those admitted to intensive care, it is commonly recommended that energy intake should remain lower than that normally required for the first 3–5 days of treatment of refeeding syndrome for all patients.[1]: 1.4.8

## History

[edit]

In his 5th century BC work "On Fleshes" (De Carnibus), Hippocrates writes, "if a person goes seven days without eating or drinking anything, in this period most die; but there are some who survive that time but still die, and others are persuaded not to starve themselves to death but to eat and drink: however, the cavity no longer admits anything because the jejunum (nêstis) has grown together in that many days, and these people too die." Although Hippocrates misidentifies the cause of death, this passage likely represents an early description of refeeding syndrome.[7] The Roman historian Flavius Josephus writing in the 1st century AD described classic symptoms of the syndrome among survivors of the siege of Jerusalem. He described the death of those who overindulged in food after the famine, whereas those who ate at a more restrained pace survived.[8] The Shincho Koki chronicle also describes a similar outcome when starved soldiers were fed after the surrender at the siege of Tottori castle on October 25, 1581.[9]

There were numerous cases of refeeding syndrome in the Siege of Leningrad during World War II, with Soviet civilians trapped in the city having become malnourished due to the German blockade.[10]

A common error, repeated in multiple papers, is that "The syndrome was first described after World War II in Americans who, held by the Japanese as prisoners of war, had become malnourished during captivity and who were then released to the care of United States personnel in the Philippines."[11] However, closer inspection of the 1951 paper by Schnitker reveals the prisoners under study were not American POWs but Japanese soldiers who, already malnourished, surrendered in the Philippines during 1945, after the war was over.[citation needed]

Refeeding syndrome has also been documented among survivors of the Ebensee concentration camp upon their liberation by the United States Army in May 1945. After liberation, the inmates were fed rich soup; the stomachs of a few presumably could not handle the sudden caloric intake and digestion, and they died.[12][13]

It is difficult to ascertain when the syndrome was first discovered and named, but it is likely the associated electrolyte disturbances were identified perhaps in Holland, the Netherlands during the so-called Hunger Winter, spanning the closing months of World War II.[14]

## See also

[edit]

* Minnesota Starvation Experiment
* F-100 and F-75

## References

[edit]

1. ^ a b "Evidence — Nutrition support for adults: oral nutrition support, enteral tube feeding and parenteral nutrition — Guidance". National Institute for Health and Care Excellence (NICE). 22 February 2006 [Updated 4 August 2017]. Web page with link to full guideline CG32.
2. ^ a b Mehanna HM, Moledina J, Travis J (June 2008). "Refeeding syndrome: what it is, and how to prevent and treat it". BMJ. 336 (7659): 1495–8. doi:10.1136/bmj.a301. PMC 2440847. PMID 18583681.
3. ^ a b Doig, GS; Simpson, F; Heighes; Bellomo, R; Chesher, D; Caterson, ID; Reade, MC; Harrigan, PWJ (2015-12-01). "Restricted versus continued standard caloric intake during the management of refeeding syndrome in critically ill adults: a randomised, parallel-group, multicentre, single-blind controlled trial". The Lancet Respiratory Medicine. 3 (12): 943–952. doi:10.1016/S2213-2600(15)00418-X. ISSN 2213-2619. PMID 26597128.
4. ^ Lemke, Thomas L.; Williams, David A., eds. (2012). "Anorexiants as Pharmacologic Agents in the Management of Obesity". Foye's Medicinal Chemistry. Lippincott Williams & Wilkins. pp. 1451–6. ISBN 978-1-60913-345-0.
5. ^ Webb GJ, Smith K, Thursby-Pelham F, Smith T, Stroud MA, Da Silva AN (2011). "Complications of emergency refeeding in anorexia nervosa: case series and review". Acute Medicine. 10 (2): 69–76. doi:10.52964/AMJA.0470. PMID 22041604.
6. ^ a b c Butt, Ifrah; Ulloa, Nicolas; Surapaneni, Balarama K.; Kasmin, Franklin; Butt, Ifrah; Ulloa, Nicolas; Surapaneni, Balarama K.; Kasmin, Franklin (17 July 2019). "Refeeding Syndrome and Non-Alcoholic Wernicke's Encephalopathy in a Middle-aged Male Initially Presenting with Gallstone Pancreatitis: A Clinical Challenge". Cureus. 11 (7): e5156. doi:10.7759/cureus.5156. ISSN 2168-8184. PMC 6750637. PMID 31538039. This article incorporates text from this source, which is available under the CC BY 3.0 license.
7. ^ Hippocrates of Kos. De Carnibus. 5th century BCE.
8. ^ The Wars of the Jews by Flavius Josephus. October 2001. p. book V, chapter XIII, paragraph 4. Retrieved 2018-05-22 - via www.gutenberg.org.
9. ^ "Researchers play detective to track earliest case of medical malady | The Asahi Shimbun: Breaking News, Japan News and Analysis". The Asahi Shimbun. Retrieved 2024-01-31.
10. ^ Juliana Machado; et al. (March 5, 2009). "Refeeding syndrome, an undiagnosed and forgotten potentially fatal condition". BMJ Case Reports. 2009: bcr07.2008.0521. doi:10.1136/bcr.07.2008.0521. PMC 3028379. PMID 21686764.
11. ^ Schnitker MA, Mattman PE, Bliss TL (1951). "A clinical study of malnutrition in Japanese prisoners of war". Annals of Internal Medicine. 35 (1): 69–96. doi:10.7326/0003-4819-35-1-69. PMID 14847450.
12. ^ Persinger, Robert B. "Remembering Ebensee 1945 Robert B. Persinger, May 6th 2005". Memorial Ebensee. Archived from the original on 7 October 2011.
13. ^ Nawyn, Kathleen J. "The Liberation of the Ebensee Concentration Camp, May 1945". history.army.mil. U.S. Army Center of Military History. Retrieved 1 October 2018.
14. ^ Burger, GCE; BSandstead, HR; Drummond, J (1945). "Starvation in Western Holland: 1945". The Lancet. 246 (6366): 282–83. doi:10.1016/s0140-6736(45)90738-0.

## Bibliography

[edit]

* Shils, M.E., Shike, M., Ross, A.C., Caballero, B. & Cousins, R.J. (2006). Modern nutrition in health and disease, 10th ed. Lippincott, Williams & Wilkins. Baltimore, MD.
* Mahan, L.K. & Escott-Stump, S.E. (2004) Krause's Food, Nutrition, & Diet Therapy, 11th ed. Saunders, Philadelphia, PA.
* Hearing S (2004). "Refeeding syndrome: Is underdiagnosed and undertreated, but treatable". BMJ. 328 (7445): 908–9. doi:10.1136/bmj.328.7445.908. PMC 390152. PMID 15087326.
* Crook M, Hally V, Panteli J (2001). "The importance of the refeeding syndrome". Nutrition. 17 (7–8): 632–7. doi:10.1016/S0899-9007(01)00542-1. PMID 11448586.
* Lauts N (2005). "Management of the patient with refeeding syndrome". J Infus Nurs. 28 (5): 337–42. doi:10.1097/00129804-200509000-00007. PMID 16205500. S2CID 39877542.
* Kraft M, Btaiche I, Sacks G (2005). "Review of the refeeding syndrome" (PDF). Nutr Clin Pract. 20 (6): 625–33. doi:10.1177/0115426505020006625. hdl:2027.42/142310. PMID 16306300.
* "Evidence — Nutrition support for adults: oral nutrition support, enteral tube feeding and parenteral nutrition — Guidance". National Institute for Health and Care Excellence (NICE). 22 February 2006 [Updated 4 August 2017]. Web page with link to full guideline CG32.
* Mehanna, H. M., Moledina, J., & Travis, J. (2008). Refeeding syndrome: what it is, and how to prevent and treat it. BMJ (Clinical research ed.), 336(7659), 1495–1498. https://doi.org/10.1136/bmj.a301

## External links

[edit]

Classification|

* MeSH: D055677
* DiseasesDB: 11205
* SNOMED CT: 427698009

|

* v
* t
* e

Intensive care medicine

* Health science
* Medicine
* Medical specialities
* Respiratory therapy

General terms|

* Intensive care unit (ICU)
* Neonatal intensive care unit (NICU)
* Pediatric intensive care unit (PICU)
* Coronary care unit (CCU)
* Critical illness insurance
* Geriatric intensive-care unit

Conditions|

| Organ system failure|

Shock sequence
SIRS
Sepsis
Severe sepsis
Septic shock
Multiple organ dysfunction syndrome

Other shock
Cardiogenic shock
Distributive shock
Anaphylaxis
Obstructive shock
Neurogenic shock
Spinal shock
Vasodilatory shock

Organ failure
Acute renal failure
Acute respiratory distress syndrome
Acute liver failure
Respiratory failure
Multiple organ dysfunction syndrome

* Neonatal infection
* Polytrauma
* Coma

|

Complications|

* Critical illness polyneuropathy / myopathy
* Critical illness–related corticosteroid insufficiency
* Decubitus ulcers
* Fungemia
* Stress hyperglycemia
* Stress ulcer

Iatrogenesis|

* Methicillin-resistant Staphylococcus aureus
* Oxygen toxicity
* Refeeding syndrome
* Ventilator-associated lung injury
* Ventilator-associated pneumonia
* Dialytrauma

Diagnosis|

* Arterial blood gas
* Catheter
* Arterial line
* Central venous catheter
* Pulmonary artery catheter
* Blood cultures
* Screening cultures

Life-supporting treatments|

* Airway management and mechanical ventilation
* Tracheal intubation
* Cardiac devices
* Intra-aortic balloon pump
* Ventricular assist device
* Chest tube
* Kidney dialysis
* Early goal-directed therapy
* Induced coma
* Nutritional supplementation
* Enteral feeding
* Total parenteral nutrition
* Therapeutic hypothermia

Drugs|

* Analgesics
* Antibiotics
* Antithrombotics
* Inotropes
* Intravenous fluids
* Neuromuscular-blocking drugs
* Recombinant activated protein C
* Sedatives
* Stress ulcer prevention drugs
* Vasopressors

ICU scoring systems|

* APACHE II
* Glasgow Coma Scale
* PIM2
* SAPS II
* SAPS III
* SOFA

Physiology|

* Hemodynamics
* Hypotension
* Level of consciousness
* Acid–base imbalance
* Water-electrolyte imbalance

Organisations|

* Society of Critical Care Medicine
* Surviving Sepsis Campaign
* European Society of Paediatric and Neonatal Intensive Care

Related specialties|

* Anesthesiology
* Internal medicine
* Cardiology
* Neurology
* Pulmonology
* Pediatrics
* Surgery
* Traumatology

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