Refeeding Syndrome

In my 2-week attachment at the surgical ward, I came across quite a few Total Parenteral Nutrittion (TPN) cases. The calories required by patient is calculated based on 20 kcal/kg then titrate up by 5 kcal/kg. The reason for this is to prevent refeeding syndrome.


Refeeding syndrome is the potentially fatal shift in fluids and electrolytes that may occur in malnourished patients receiving artificial feeding (enterally or parenterally). It was first described inFar East prisoners of ward in WWII. Eating again after prolonged period of starvation seemed to precipitate cardiac failure.

Prolonged Fasting
Muscles & other tissues: decrease use of ketone bodies, use fatty acids as main energy source

Increase in blood levels of ketone bodies stimulate the brain to use ketone bodies (instead of glucose) as its main energy source

Liver decreases rate of gluconeogenesis, thus preserving muscle protein

Several intracellular minerals become severely depleted during the period of prolonged starvation. However, serum concentrations of these minerals (including phosphate) may remain normal because they are mainly in the intracellular compartment.

Refeeding
Sudden shift from fat to carbohydrate metabolism occurs and secretion of insulin increases

Insulin stimulates glycogen, fat & protein synthesis, which require minerals such as phosphate (Po4) & Magnesium (Mg) and cofactors such as thiamine.

Insulin stimulates the absorption of K into the cells through Na-K-ATPase symporter, which also transports glucose into the cells.

Mg and PO4 are also taken up into the cells, water follows by osmosis.

These result in a decrease in the serum levels of PO4, Mg, K, all of which are already depleted.

This phenomenon usually occurs within 4 days of starting to feed again.


How can refeeding syndrome be prevented?
Identify patients with high risk of developing refeeding syndrome, and the management that follows suit is illustrated in the figure below.

Patients with high risk of developing refeeding syndrome-
1. Patients with 1 or more of the following:

• BMI <16>
• Unintentional weight loss > 15% in the past 3-6 months
• Little or no nutritional intake for > 10 days
• Low levels of K, Mg, or PO4 before feeding

2. Patients with 2 or more of the following:

• BMI > 18 kg/m2
• Unintentional weight loss > 10% in the past 3-6 months
• Little or no nutritional intake for > 5 days
  
• History of alcohol misuse or drugs, including insulin, antacids, chemotherapy or diuretics

The NICE guidelines recommend that refeeding should start at a maximum of 0.021 MJ/kg/day (10 kcal/kg/day), with cardiac monitoring due to the risk of cardiac arrhythmias.



References
1. Hearing SD. Refeeding syndrome is underdiagnosed and undertreated, but treatable. BMJ 2004; 328 (7445): 908-909. Available from: URL: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC390152/

2. Mehanna HS, Moledina J and Travis J. Refeeding syndrome: what it is, and how to prevent adn treat it. BMJ 2008; 336: 1495-1498. Available from: URL: http://www.bmj.com/cgi/content/full/336/7659/1495

Antibiotics Use in MRSA

An ICU patient was undergoing continuous veno-venous haemodiafiltration and had line-related bacteraemia. She has MRSA currently and was put on IV linezolid. IV Vancomycin was deemed not suitable as patient was on it for 2 months (previous admission) and showed no clinical response. Interestingly, blood culture showed sensitivity to vancomycin, rifampicin, fusidic acid, and clindamycin.


The issue raised by one pharmacist was, is linezolid a substitute for vancomycin (when patient does not response to it) in bacteraemia? She pointed out that while linezolid is efficacious when vancomycin fails in pneumonia, linezolid is not indicated for bacteraemia.


The most appropriate (antibiotic) treatment [can include removal of source, i.e. the line] is beyond the scope of this post as we did not follow up the case personally and thus do not have a full picture of her condition. However, the ICU case presentation prompted me to read up on antibiotics use in MRSA and I would like to share the findings here.


Community-acquired MRSA (CA-MRSA)- acquired by persons who have not been recently (within the past year) hospitalised or had a medical procedure (e.g. dialysis, surgery, catheters)

Hospital-acquired MRSA (HA-MRSA)-acquired by persons who have had frequent or recent contact with hospitals or healthcare facilities (e.g. nursing homes, dialysis centres) withint the previous year, have recently undergone an invasive medical precodure, or are immunocompromised.

A very good comparison between CA-MRSA and HA-MRSA (in the aspects of areas affected, modes of transmission, treatment & management, prevention) is available at a glance HERE.

Some other points of interest:
The treatment of choice for cutaneous abscesses caused by S aureus, irrespective of antibiotic susceptibility, is incision and drainage.


Vancomycin: still considered the first-line treatment for hospitalised patients with invasive S. aureus infection.

Microbiologic treatment failure may occur with vancomycin even if there is no increase in the minimal inhibitory concentration (MIC) on susceptibility testing. S. aureus isolates with low-level (so-called intermediate) resistance to vancomycin (MIC, >2 µg per milliliter) as well as those with high-level resistance (MIC, >16 µg per milliliter) have been described. <--Perhaps an explanation to patient's lack of response to vancomycin?

Also, nephrotoxicity is associated with high doses needed to attain the recommended vancomycin trough concentrations of 15—20 μg/mL.


Linezolid is FDA-approved for the treatment of complicated skin infections and hospital-acquired pneumonia due to MRSA in adults.

However, linezolid is expensive and has the potential for substantial toxicity, including myelosuppression, peripheral neuropathy, optic neuritis, and lactic acidosis.

Parenteral linezolid lacks bactericidal activity, which some experts believe is important in treating intravascular infection, a common feature of invasive disease. One of the selling points by the drug company is that linezolid is also available in oral form [Tab linezolid 600 mg is available in the blue book] so patient can be converted to the oral form upon discharge. However, this situation is more applicable in overseas (discharged while disease is almost resolved as they have healthcare system which includes home visits); in the government hospitals here, patients will be managed in the hospital until they are fully recovered.


Rifampicin or fusidic acid could be used as adjunctively with another active drug or together; neither agent should be used alone because resistance is likely to emerge during single-drug therapy.

Watch out for potential drug-drug interactions in patient on this regimen as rifampicin is a potent inducer of drug-metabolizing enzymes.


Tigecycline, a parenteral glycylcycline–minocycline derivative, was also recently approved by the Food and Drug Administration (FDA) for the treatment of skin and soft-tissue infections caused by MRSA.

A fixed combination of the streptogramins quinupristin and dalfopristin was licensed by the FDA for the treatment of skin and soft-tissue infections caused by MRSA. Its use has been limited by the potential for drug–drug interactions and by side effects (including arthralgias, myalgias, and gastrointestinal toxic effects).


References:

1. Deleo FR et al. Community associated methicillin-resistant Staphylococcus aureus. The Lancet, 2010 March 5. Available from: URL: http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2809%2961999-1/fulltext?_eventId=login
2. Daum RS. Skin and soft-tissue infections caused by methicillin-resistant Staphylococcus aureus. New Engl J med 2007; 357: 380-390. Available on: URL: http://content.nejm.org/cgi/content/full/357/4/380
3. Strategies for Clinical Management of MRSA in the Community: Summary of an Experts’ Meeting Convened by the Centers for Disease Control and Prevention.2006 March. Available from: URL: http://www.cdc.gov/ncidod/dhqp/pdf/ar/CAMRSA_ExpMtgStrategies.pdf