Ketogenic DietDr Tan Pek

Yong

Case Illustration 1

• YJW, 14 year old, healthy girl• No known medical illness• Presented with refractory status epilepticus

for 1 month in the context of fever• All investigation including CSF sampling, MRI

brain was normal.• Diagnosis : FIRES

On admission to GICU:On Thiopentone, Propofol, Midazolam & multiple AED

Ketogenic Diet

After 1 week of Ketogenic diet

After 3 week of Ketogenic diet

After 6 week of Ketogenic diet (extubated !!)

Case Illustration 2

• NAD, 14 mths old girl• Presented with epileptic encephalopathy with

underlying GDD, central hypotonia and subtle dysmorphism.

• All genetic and IEM screening normal.• MRI brain show mild lost of white matter

(non-specific)

• EEG – epileptic encephalopathy

Ketogenic Diet

• EEG – marked improvement after 2 – 3 wks of KD

Ketogenic Diet

What is Ketogenic diet?

• A therapeutic diet for epilepsy

• High fat, low protein and low carbohydrate diet, with calorie control

• The goal: alter the body’s fuel source from glucose to fat.

No Dextrose!

No Syrup medications!

A Story from

A Parent’s Prespective

• Sam, 9 years old• Diagnosed to have myoclonic epilepsy at age

of 5 but was able to control with AED• Had absence seizure since 7 which was very

difficult to control • Tried 11 antiepileptic drugs• Had 100-130 seizures per day

A Parent’s Prespective

• Sam couldn’t even cry without interruption: he would cry for 15 seconds; have a 15-second seizure; and then continue sobbing.

• Sam had trouble even watching a movie. “Dad, I think the DVD is scratched. When I was watching, it kept leaving words out.”

Ketogenic Diet

• Breakfast: eggs are mixed with heavy cream and served with bacon. • Lunch: full-fat Greek yogurt mixed with coconut oil. • Dinner:hot dogs, bacon, macadamia nuts and cheese.

• An average week, Sam consumes a quart and a third of heavy cream, nearly a stick and a half of butter, 13 teaspoons of coconut oil, 20 slices of bacon and 9 eggs.

• That is twice the fat content of a McDonald’s Happy Meal and about 25 percent more than the most fat-laden phase of the Atkins diet.

A Parent’s Prespective

• Time consuming to prepare keto meals– Doing all this once is fascinating. – But administering the diet for three meals and two

snacks a day, seven days a week for two years is relentless.

– There is no “Let’s just order pizza”, no matter how busy.

A Parent’s Prespective

• To deal with child’s craving for common snacks– Ice cream, pizza, candy, cake, cookies, tortilla chips

and soda and the list goes on......

A Parent’s Prespective

• Ultimately what makes the diet so stressful is that on top of all the gross recipes and weird mechanics, there is no margin for error.

• Every last drop counts and that is from food preparation till the child finish every bite of every meal.

• The penalty for cheating, at least in Sam’s case, is seizures. – took a piece of toast: lost seizure control for a week.

Does it work?

For Sam:• After 2 years on ketogenic diet• 75% reduction in seizure

43%

Effectiveness

• 20-25% – seizures were completely controlled• 30-40% - seizure frequency decreased by 50%• 25-30% - not effective

Ketogenic Diet

History

• Ancient Greece• Biblical times

• 1920’s at Johns Hopkins University School of Medicine.

• Popularity faded in the 40’s and 50’s when new anticonvulsant drugs were discovered

• Resurgence in 1990’s because of the TV movie based on Charlie Abrahams

• Charlie Foundation funded a 7-center study of the diet designed to allow these centers to treat the patients resulting from the anticipated publicity.

• The multicenter study was started in 1994 and presented to the American Epilepsy Society in 1996.

• This later lead to an exponential increase in number of publications on KD.

Who is it for?

• For children with poorly controlled seizures or failed to respond to AEDs.

• Emerging evidence: – Severe myoclonic epilepsy of infancy (Dravet syndrome)– Myoclonic astatic epilespy – Tuberous sclerosis complex– Infantile spasms – Uncontrolled absence seizures

• Metabolic disease: – Glucose Transporter 1 Deficiency syndrome Rx of choice– Pyruvate dehydrogenase (PDH) deficiency

Contraindication / Caution

Contraindicated, or caution should be exercised for those with:

• Fatty acid oxidation defects • Organic acidurias• Diagnosis of diabetes mellitus• Hypoglycaemia under investigation• Familial hyperlipidaemia• Severe gastro oesophageal reflux• Feeding difficulties or food refusual

How does it work?

• Glucose → Fat (as the primary fuel source)• Ketone bodies – the acidic products formed

from excessive breakdown of fat. • The brain uses the ketones as fuel.• No one knows why this works!

Before starting KD

• Initial assessment by Paediatric Neurologist experienced in KD

• Types of Seizures– Frequency and type of seizures must be documented for

one month prior to commencing the ketogenic diet and throughout the course of the diet.

– The neurologist will review medications before the diet is commenced, changing syrup medications to tablet form, due to their high sugar content.

Before starting KD

Education and commitment by parents

Areas covered include:• Aims of the diet,• How the diet works,• The advantages and disadvantages of the diet,• How the diet is calculated,• Examples of the types of meals a child would eat on the diet,• Duration of diet,• Admission process and• Ongoing management at home• Cost of KD

Family Expectation

• How long to know its effect?• How long to go on with KD?• Seizure reduction?• What about AED reduction?• What about improvement in cognition?

Be Realistic!

Initiating KD

• Hospitalization to induce ketosis• Under the supervision of Paeds Neurologist

and trained dietician• Blood sugar and ketone levels monitored• Baseline Ix:– FBC / RP / LFT / FLP / Ufeme

Initiating KD

• Start with ketogenic formula, encourage to drink more water

• If ketosis is being established and the ketogenic

formula tolerated, food is introduced after a 48 hour period until the calculated ratio and energy level is reached.

• The dietitian calculates all energy requirements and grades the fat ratio up slowly.

Calculation of KD

• The ketogenic ratio – 4:1• Calculate the # of calories needed a day

(based on RDAs)

• Fortunately leave it to the DIETICIAN!!!

Ketogenic Ratio

• Ratio of fat to protein plus carbohydrate in the diet. (by weight, not calories)

• The ratio determines how "ketogenic" the diet is - the higher the ratio, the more ketogenic (ie stronger) the diet.

• Typical ketogenic diets are operated in the range from 2:1 to 5:1.

• By comparison, a normal everyday diet has a ketogenic ratio in the range 1:2 to 1:3.

Sample Meals• Meal 1:

– melted butter– heavy whipping cream– chicken– apple– sugar free Jell-O

• Meal 2:– Hot dog slices w/ sugar-free catsup– Asparagus w/ butter– Chopped lettuce w/ mayo– Sugar-free vanilla cream popsicle

Variations of the Diet

• MCT oil– MCT oil is more "ketogenic", it is possible to increase the

levels of carbohydrate and protein, and still achieve the basic objective of the diet which is the body going into ketosis.

– The increase in carbohydrates and protein enables a wider range of foods within the diet, so it looks more like a “normal‟ diet.

• More and more studies show that there is no difference in efficacy on both diet as long as calculations are correct.

Variations of the Diet

• Modified Atkins diet– No fluid or calorie restriction.– Fats are strongly encouraged, but no restrictions on

proteins. – Foods are not weighed and measured, but carbohydrate

counts are monitored.– Foods can be eaten more freely in restaurants and outside

the home, and families can do it as well. – “Modified" = allow for less carbohydrates than traditional

Atkins (10-20g/day) and more strongly encourages fat intake.

Supplementation

• Calcium & Vitamins • Adequate fluids• ± carnitine• ± laxatives

Maintenance of the Diet

• All medications are continued• Constant calculations!• BE VERY PRECISE!• Watch for cheating!– Special toothpaste– No added seasonings

Problems that may arise

• Low blood sugar• Lethargy• Nausea• Vomiting• Elevated cholesterol

• Kidney stones• Constipation • Weight loss or gain• Dehydration• Cheating

Side Effects• Metabolic

– Hyperuricemia (2%–26%)– Hypocalcemia (2%)– Hypomagnesemia (5%)– Decreased amino acid levels and acidosis (2%–5%)

• Gastrointestinal symptoms– vomiting, constipation, diarrhea, and abdominal pain occur in 12%–50% of children

• Carnitine • Hypercholesterolemia (14%–59%)• Renal calculi (3%–7%)

– Stone composition includes uric acid (50% of stones), calcium oxalate, calcium phosphate, and mixed calcium/uric acid stones.

– They typically do not require diet discontinuation and lithotripsy is only rarely necessary.

– Polycitra K appears to help prevent stone formation

Side Effects

• There is conflicting data on the effect of the KD on growth in children. – One retrospective review of linear growth found that 86% of children on the

diet had slowed growth.– A prospective study of 237 children found that the while older children grew

“almost normally”; younger children grew poorly. – There does not appear to be a difference between diets used despite the

greater protein content of the MCT diet.

• Cardiac abnormalities (rare)– cardiomyopathy and prolonged QT interval

Long Term Side Effects

• > 2 years on KD– higher risk of bone fractures, kidney stones, and

decreased growth, but dyslipidemia was not identified

• Periodic dual energy x-ray absorptiometry (DEXA) screening for bone health recommended.

• The long-term effects of this high-fat diet on the cardiovascular system remain to be determined.

Advantages & Disadvantages

• It works for many children!

• Frequently medications are greatly decreased or discontinued.

• VERY STRICT!• Long duration• Stunted Growth?• Heart Problems?

Discontinuation

• Unsuccessful: consider stopping after 3 months• Sussessful: consider stopping after 2 years

• Longer diet durations are necessary for GLUT-1 and PDHD.

• Before discontinuation in seizure-free children, a routine EEG and review of clinical data should be performed to counsel families regarding recurrence risk, which is 20% overall.

• Children with an epileptiform EEG, abnormal MRI, and tuberous sclerosis complex are at higher risk.

Trouble Shooting

Hypoglycaemia

• Treating hypoglycaemia using rapidly absorbed carbohydrate– 100ml of NON DIET Coca Cola®– 55ml of Lucozade®, Energy Original– 100ml of pure fruit juice– 2tsp of sugar, ordinary jam, honey or syrup– 10g (two level teaspoons) Dextrose powder in 100ml water.

• If the response to the above treatment is inadequate, more can be administered after 10-15 minutes.

• For patients with reduced consciousness level or/and seizures– Give 5 -10ml/kg 10% dextrose intravenously

GI Illness

Vomiting or Diarrhoea• Check blood glucose levels two- to four-hourly if children are

unwell, especially if nil by mouth (note that if the child is ketotic, blood sugar may be low but still acceptable, ie > 2.5 mmol/L.)

• Test urine for ketones every time child passes urine.

• Rehydrate with low carbohydrate clear fluids if tolerated orally.• If IV fluids are required use normal saline (0.9% NaCl)

• Reflo < 3mmol/L - 2.5% or 5% dextrose/saline solution to maintain Reflo between 3 and 4 mmol/l.

NBM

• The high fat diet regimen of the ketogenic diet (70-90% of calories) forces the body into a dietary induced ketosis. The acidosis that occurs when the diet is first initiated corrects itself with days and is not sustained.

• The literature on ketogenic diet and general anaesthetic is scarce, with very little consensus on management.

• The most comprehensive study undertaken so far suggests that carbohydrate-free solutions are safe and blood glucose remains stable throughout surgical procedures up to 1.5 hours.

• Current advice suggest therefore monitoring blood pH in procedures > three hours and administering IV bicarbonate where necessary.

PICU Admission• Intravenous fluids: use normal saline (0.9% NaCl) or Ringers lactate, unless blood

glucose levels are low (< 3 mmol/l).• If low then give dextrose / saline solutions (2.5% or 5%), aim to maintain blood glucose

between 3 and 4 mmol/l.• Monitor for hypoglycaemia and metabolic acidosis: blood glucose levels and blood gas

one- to two- hourly as appropriate.• Investigations should also include measurement of ketones (urine or blood), excessive

ketosis and acidosis may require treatment with iv bicarbonate• A base excess of -10 indicates significant metabolic acidosis and should be half corrected

over four hours with intravenous bicarbonate.– If acidosis is explained by excess ketosis, dextrose containing maintenance fluids (2.5% or 5 %

dextrose) would be appropriate.– If acidosis is not completely explained by excess ketosis ie high blood lactate this could be

discussed with the Metabolic team (choice of maintenance fluids (normal saline/saline).• Medication: must be in lowest carbohydrate form. • Enteral feeding: please contact dietitians

Thank You