Anorexia nervosa, re-feeding

syndrome and endocrine sequelaeMark Daly

Why this talk…..Traditionally eating disorders have been looked after by either gastro-enterologists or endocrinologists with the support of psychiatry

There are few conditions where such strong leadership is necessary in the best interests of the patient and may go counter to the instincts or wishes of members of staff

Anorexic woman from Wales to be force fed,

judge ordersA woman with "severe" anorexia who wanted to be allowed to die is to be force fed in her "best interests" by order of a High Court judge.

She was being looked after in a community hospital under a palliative care regime whose purpose was to allow her to die in comfort

Treatment - "does not merely entail bodily intrusion of the most intimate kind, but the overbearing of E's will in a way that she experiences as abusive".

A not unusual pathway of

care…..19 yr old girl, admitted BMI of 12

Intermittent institutionalised care since age 9 with Anorexia nervosa

Admitted because of recent further weight loss, minimal intake for 1 week

Agreed for a voluntary admission

Admission criteriaBased on recent change in the context of absolute BMI, physiological and functional parameters

Physical concernConcern Admit

BMI <14 <12

Wt loss (kg/week)

>0.5 >1

BP <90/70 <80/60

Postural drop >10 >20

Pulse <50 <40

Temp <35 <34

Muscular strength

Uses arms to stand

Can’t stand

WBC <4 <2

Hb <11 <9

Plts <130 <110

Physical concern(2)Concern Admit

NA+ <135 <130

K+ <3.5 <3.0

Mg2+ If depleted If depleted

Po4- If depleted If depleted

ECGqtc >450msec >450 or arrhythmia

ALT >45 >90

Bilirubin >20 >40

Alk phosp >110 >200

Albumin <35 <32

O/EWell presented

Gross cachexia

Hypotensive and bradycardic

Pre-pubertal

Initial investigations

Hb 11.0,WCC 2.0, Plts 78

Na+ 127, K+ 3.1, urea 1.8, creat 38, PO4- 0.75

ECG bradycardia, long QT

Initial planMedical

Initial assessmentNa+, K+, Urea, Creat, glucose, CRP

Mg2+, PO4-, Ca2+

Albumin, liver enzymes, INR

FBC, ferritin, folate, B12

FSH, LH Oest or testo

Thiamine 300mg daily, vit b complex strong 2 tabs od, multivit generic, sandophosp 2 tabs tds

Pabrinex

Initial planNutritional

5 kcal per kg stepping up over 5-7days to weight gain levels (+500kcal over estimates from Henry equation

(10kcal per kg if BMI>16)

Menu plans agreed with patient

Initial planBehavioural/other restrictions

Normal foods in preference to supplements

Bed rest/commode/wheelchair

Away from window, no fans

Restrictions according to Mental health status

Compliance essential

ProgressDay 3, non-compliance with feeding plan

Non-compliance with activity

Reviewed with psych

Formal section

Advised likely need to progress to NG feeding in absence of compliance and/or weight gain

Informed of need to search belongings

ProgressDay 5, intermittent compliance with feeding plan

Reviewed with psych

Razor blades and salt sachets removed

NG feeding under restraint, NG re-positioned/replaced 5 times first 24 hrs

Bolus feeds under restraint during periods of non-compliance

ProgressDay 8

Hypokalaemia and hypophosphataemia requiring IV replacement

Subsequent weight gain back to BMI 15

Established weight stability at BMI 15 on oral intake and basic mobility

Discharged to OP ED services

Anorexia nervosa

What is anorexia nervosa?Anorexia nervosa is defined as:

intense fear of weight gain

Weight consistently < 85th percentile for age and height (In women) three consecutive missed periods

Together with one of following: refusal to admit seriousness of weight loss undue influence of shape or weight on one’s

self-image disturbed experience in one’s shape or weight

DSM-IV-TR

Types of Anorexia

RestrictingWeight loss achieved by restricting calories

Following diets, fasting, and exercising to excess

• Purging– Weight loss

achieved by vomiting, laxatives, or diuretics

CausesAnorexia Nervosa patients tend to have

Low self-evaluation

Come from competitive, high-achieving, and protective families

Set perfectionist standards

Intensely concerned with how others perceive them

Fear falling short of expectations

Genetics

Culture

Idealize thinness

Have poor body image

Feel shame, depressed, and dissatisfied with their own bodies

SymptomsDramatic weight loss

Preoccupation with weight, food, calories, fat grams, and dieting

Refusal to eat certain foods, or whole categories of food (e.g. no carbohydrates)

Denial of hunger

Excessive, rigid exercise regimen

Withdrawal from usual friends and activities

Weight loss and dieting become primary concerns in life.

Constant excuses to avoid mealtimes

Anxiety about gaining weight or being fat

EpidemiologyUK

1 in 250 females

1 in 2000 males

SMR 9.5

Mortality of 0.6% per year

Higher in those presenting after age 20

50 years of treatment outcomesComparison of outcomes 1950-1999 to gauge

whether any improvement over time.

119 studies conducted 1950-1999

5,590 patients, adolescents and adults

Follow-ups clustered into three time frames:

- fewer than 4 years after hospitalization;

- 4-10 years;

- more than 10 years after

Steinhausen HC. Am J Psychiatry. 2002.

Outcome measuresBroad outcome measures: death, recovery, improvement, chronicity.

Symptom normalization measures: weight, menstruation, eating behavior

Psychopathologies such as affective disorders, OCD, anxiety, substance abuse.

Steinhausen HC. Am J Psychiatry. 2002

Outcome of Anorexia Nervosa in 119 Patient Series by Duration of Follow-Up and Age at Onset.

A total of 577 patients had less than 4 years of follow-up, 2,132 had 4–10 years of follow-up, and 438 had more than 10 years of follow-up.

“The mortality rate was much lower in the group of younger patients than that in the group with a much wider age at onset of illness. The rates of recovery, improvement, and chronicity were more favorable in the group with the younger patients.”

Steinhausen HC. Am J Psychiatry. 2002

Outcome of Anorexia Nervosa in 119 Patient Series by Duration of Follow-Up and Time Period of Study.

A total of 577 patients had less than 4 years of follow-up, 2,132 had 4–10 years of follow-up, and 438 had more than 10 years of follow-up.

“Anorexia nervosa did not lose its relatively poor prognosis in the20th century.”

Steinhausen HC. Am J Psychiatry. 2002.

Re-feeding syndrome

First described in American Japanese POW

Precipitated cardiac failure

clinical features of refeeding syndromerhabdomyolysis, leucocyte dysfunction, respiratory failure, cardiac failure, hypotension, arrhythmias, seizures, coma, and sudden death

Driven by low serum phosphate (<0.5)

Re-feeding syndrome -

pathophysiologyinsulin is decreased due to a reduced oral carbohydrates.

fat and protein stores are catabolized

Intracellular loss of electrolytes, esp. phosphate.

intracellular phosphate stores can be depleted despite normal serum phosphate concentrations

a sudden shift from fat to carbohydrate metabolism -secretion of insulin increases -stimulates cellular uptake of phosphate,

usually occurs within four days of starting to feed again.

Phosphate is necessary for ATP from ADP and AMP

How do we manage it?

Risk is obvious

Degree of risk is not

Assume risk is reduced after 1 week of good intake AND weight gain

Often use telemetry – some centres use it continuously for all patients

ECG daily is essential

Exeter protocol(with thanks to Roderick

Warren)Assume high risk in all cases. Medical inpatients with anorexia nervosa who require inpatient feeding are almost always at high risk of refeeding syndrome.

However, NICE guidance (2006 – CG32) states that the risk is high if:• One of: BMI<16, weight loss >15% in last 3-6 months, little or no nutrition >10 days, low potassium/phosphate/magnesium levels prior to feeding.• Two of: BMI <18.5, weight loss >10% in last 3-6 months, little or no nutrition >5 days, history of alcohol abuse or use of insulin/chemotherapy/antacids/diuretics/(laxatives)

Exeter protocol

Bloods before feeding:

Sodium, potassium, urea, creatinine, glucose, CRP

Magnesium, phosphate, calcium

Albumin, liver enzymes, INR

FBC, ferritin, folate, B12

FSH, LH, oestradiol (females) or testosterone (males)

Thiamine: 300mg per dayVitamin B Complex (Strong): 2 tablets, once per day Multivitamins: generic, 1 tablet, once per day Phosphate-Sandoz: 2 tablets, three times daily

Exeter protocol

Daily bloods while risk of refeeding syndrome is high:

• Sodium, potassium, urea, creat, glucose, magnesium, phosphate, calcium

Bloods once-twice weekly when stable (after 3-4 days of sustained feeding and no electrolyte abnormalities):

Sodium, potassium, urea, creatinine, glucose

Magnesium, phosphate, calcium

Albumin, liver enzymes

FBC

Exeter protocol

Mild deficiency (3.0 – 3.5 mmol/L)

• Sando-K or equivalent, 4-8 tablets daily

Moderate-severe deficiency (<3.0 mmol/L)• Intravenous, using pre-prepared bags of 1 litre 0.9% saline with 40 mmol potassium chloride, given over at least 4 hours (but usually longer e.g. 12 hours).

Anorexic patients may be chronically hypokalaemic.

Exeter protocol

Mild deficiency (>0.5 mmol/L and not falling rapidly) • Phosphate-Sandoz 2 tablets, three times daily

Moderate-severe deficiency (<0.5 mmol/L, or higher but falling)• Intravenous, using pre-prepared bags of Phosphates Polyfusor, 500ml over 24 hours.

– monitor calcium. Will precipitate if co-infused with calcium – always avoid infusing magnesium or calcium through the same cannula.

– check levels after 24 hours.

IV phosphate. Various recommendations suggest 9, 12 or 18 mmol administered over 12 hours. However, the use of an entire Polyfusor bag (containing 50 mmol phosphate) has been shown to be a simple, effective and safe approach. Mild hyperphosphataemia is not uncommon (levels up to 1.57 mmol/L have been seen) – consider a smaller dose (e.g. 250 ml over 12 hours) for less severe hypophosphataemia.

Exeter protocol

Mild deficiency (>0.6 mmol/L) Magnesium glycerophosphate 2 tablets, twice daily.

May cause GI irritation/diarrhoea. Avoid with co-admin with phosphate

Moderate-severe deficiency (<0.6 mmol/L) IV magnesium sulphate, 20 mmol over 12 hours, or 40 mmol over 24 hours. Can be given faster in emergencies

Will precipitate if co-infused with phosphate – always used a separate cannula.

Magnesium levels may drop rapidly after correction - several days of IV replenishment may be required before they become stable.

Exeter protocol- calcium

rarely necessary. Correction of hypomagnesaemia may improve calcium levels. Administration of phosphate may lower calcium levels.

Asymptomatic mild-moderate deficiency

Calcichew, 1-3 tablets daily.

Do not administer at same time as phosphate – insoluble CaPO4 will form. Symptomatic or severe deficiency

• IV calcium chloride or calcium gluconate, 10 mmol over at least 10 min (but usually longer e.g. 1 hour).

Followed by infusion of 40 mmol over 24 hours.

Must be diluted before administration

A more unusual case….

Douglas

To GP, Feb 2010

Weight loss feeling tired

Recent junior Exeter chiefs player

Creat high at 110, glucose 2.1, Hb12.6, WCC 3.4

Subsequent fall in WCC, rise in ALT

DouglasFt4 12.3, cortisol 594, fsh 0.6, lh 0.4, PRL 208, testo 0.8

GH 15.1, IGF1 8.6

68kg BMI 20.9, prior weight 111kg 6 mths earlier

Clinically cachectic, lanugo hair, but post-pubertal

Admitted – psych confirmed significant AN

Weight regain to 76kg, BMI 23

Partial recovery of pancytopaenias, no recovery of gonadotrophins despite weight regain and 2 trials of testosterone cessation

Anorexia and fertility

Very little data in men for longer term

Testo crashes during acute illness

Seems to be less marked than in females

Partly an adaptive response

Many recovered anorexic patients go on to successful pregnancies

ConlcusionsBehaviourally challenging

Strong leadership

Need to be physiologically alert