IDA is diagnosed by haemoglobin less than the normal limit for the lab, MCV <76fl and ferritin <15ug/dl. Both microcytosis and hypochromia (MCH) are sensitive indicators of IDA. However they are also present in thalassaemia, sideroblastic anaemia and anaemia of chronic disease.

Ferritin is an acute phase reactant may be elevated, if concurrent inflammation is present. In such cases iron deficiency can be diagnosed by low serum iron and high TIBC or low transferrin saturation. In contrast anaemia of chronic disease has low serum iron and low TIBC with normal transferrin saturation.

How common is IDA?

IDA occurs in 2-5% of adult men and post-menopausal women in the developed world (responsible for 4-13% of GI referrals)

Discuss the causes of IDA?

IDA is often multifactorial

• Common causes- Aspirin/NSAID use, colonic cancer/polyp, gastric cancer, angiodysplasia, IBD, gastric ulcer.
• Uncommon- oesophagitis, oesophageal cancer, water melon stomach, intestinal telangiectasia, small bowel tumours, duodenal polyp, carcinoma of the ampulla of Vater, hookworm
• Malabsorption- Coeliac disease, gastrectomy (partial or total), gut resection or bypass, bacterial overgrowth, Whipple’s disease, lymphagiectasia.
• IDA is very common after either partial or total gastrectomy.
• In patients with recurrent IDA and normal OGD and colonoscopy results, H. pylori should be eradicated if present

Who should be investigated for IDA?

BSG recommends the following groups should be investigated with upper GI endoscopy and Colonoscopy/CT colonography:

• All postmenopausal women and all men with IDA
• All premenopausal women with IDA should be screened for coeliac disease, but other upper and lower GI investigation should be reserved for those aged 50 years or older, those with symptoms suggesting gastrointestinal disease, and those with a strong family history of colorectal cancer.
• Upper and lower GI investigation of IDA in postgastrectomy patients is recommended in those over 50 years of age
• In patients aged >50 or with marked anaemia or a signi?cant family history of colorectal carcinoma, lower GI investigation should still be considered even if coeliac disease is found.
• In patients with iron de?ciency without anaemia, endoscopic investigation rarely detects malignancy. Such investigation should be considered in patients aged >50 after discussing the risk and potential bene?t with them. Only postmenopausal women and men aged >50 years should have GI investigation of iron de?ciency without anaemia. All others should be treated empirically with oral iron replacement for 3 months and investigated if iron de?ciency recurs within the next 12 months.
• Age is the strongest predictor of pathology in patients with IDA, and thus GI investigation is recommended for asymptomatic premenopausal women with IDA aged 50 years or older
• If IDA develops in a patient with treated coeliac disease, upper and lower GI investigation is recommended in those aged >50 in the absence of another obvious cause.
• Colonic investigation in premenopausal women aged <50 years should be reserved for those with colonic symptoms, a strong family history (two affected ?rst-degree relatives or just one ?rst-degree relative affected before the age of 50 years), or persistent IDA after iron supplementation and correction of potential causes of losses (eg, menorrhagia, blood donation and poor diet)

Studies in patients referred to hospital for investigation of their IDA have shown that 5%-15% have a gastrointestinal cancer. However, age is the strongest predictor of pathology in patients with IDA.

Further, although it is convenient to use the term pre-menopausal, it is menstruation which influences the investigative pathway. It is probably wise to fully investigate those premenopausal women who have IDA but no menstruation (e.g. after hysterectomy).

A signi?cant family history of colorectal carcinoma should be sought, that is, one affected ?rst-degree relative <50 years old or two affected ?rst-degree relatives.

Discuss investigations for IDA?

• All patients with IDA should be checked for anti-endomysial antibodies or tissue transglutaminase.
• Urine testing for blood is important in the examination of patients with IDA as approximately 1% of patients with IDA will have renal tract malignancy. Further renal tract evaluation with ultrasound is recommended if haematuria is found, followed by intravenous urography and/or CT scan as necessary.
• Rectal examination is seldom contributory, and, in the absence of symptoms such as rectal bleeding and tenesmus, may be postponed until colonoscopy.
• All the groups mentioned above need OGD plus D2 biopsy (if coeliac antibodies are positive or not done and colonoscopy/CT colography. Colonoscopy has advantages over CT colography for investigation of the lower GI tract in IDA, but either is acceptable. Either is preferable to barium enema, which is useful if they are not available
• One or the other pathway only abandoned if gastric or colon cancer or coeliac disease diagnosed.  Investigation with OGD and colonoscopy/barium enema reveals a cause in 2/3 of the patients. It is reassuring to know that iron deficiency does not return in most patients in whom a cause for IDA is not found after upper GI endoscopy, small bowel biopsy and barium enema.
• Further direct visualisation of the small bowel is not necessary unless there are symptoms suggestive of small bowel disease, or if the haemoglobin cannot be restored or maintained with iron therapy .Wireless capsule endoscopy is the investigation of choice in such a scenario. If a small bowel lesion is identified, push or balloon enteroscopy can be used to treat the lesions. Many lesions detected by both enteroscopy and capsule endoscopy are within the reach of a gastroscope and repeat OGD should be considered prior to these procedures. Small bowel radiology is rarely of use unless the history is suggestive of Crohn’s disease.

Discuss iron replacement treatment?

• Oral replacement- This is achieved most simply and cheaply with ferrous sulphate 200 mg twice daily although ferrous gluconate and ferrous fumarate are as effective and may be better tolerated. A liquid preparation may be tolerated when tablets are not. Ascorbic acid enhances iron absorption and should be considered when response is poor.
• Parenteral replacement- should be used when there is intolerance to oral preparations or non-compliance.

Discuss the parenteral iron preparations?

• Intravenous iron sucrose is well tolerated Bolus IV iron sucrose (200mg iron) over 10minutes is licensed and more convenient than a two hour infusion.
• IV iron dextran can replenish iron and Hb levels in a single infusion, but serious reactions can occur (0.6-0.7%) and there have been fatalities associated with infusion. However, it can be given via IM route when venous access is problematic.
• Ferric carboxymaltose (Ferinject)- The principle advantage of ferinject is the abbreviated duration of infusion, without the need for a test dosed15 min compared with 6 h with Cosmofer (consisting of a 15 min test dose, 45 min observation, 4 h infusion, then 1 h observation). Although drug costs are higher, length of stay in a day-case or primary-care facility is reduced

IV iron sucrose and sodium ferric gluconate are rarely associated with severe allergic reactions and deaths, and are better tolerated than iron dextran even at high doses and thus are preferred.

How do you calculate the dose for parenteral iron therapy?

Dose in mg of iron= body weight in kg X (12-present Hb. X10) X 0.24

Add to this a depot of 500mg.

Link to calculate the iron dose

IV iron sucrose can be administered at 200mg weekly for five weeks. Alternatively, iron sucrose can be given at 500mg IV (in 250cc of NS) over four hours once weekly for two weeks.

Discuss follow up of IDA?

Once normal, the Hb concentration and red cell indices should be monitored at intervals. We suggest 3 monthly for 1 year, then after a further year, and again if symptoms of anaemia develop after that.

Ref

1. British Society of Gastroenterology Guidelines for the Management of Iron Deficiency Anaemia (2011)

?

Is measurement of waist circumference important?
Health risks of obesity are independently associated with abdominal fat measured by waist circumference. Thus, health risks are increased with increased waist circumference.

Why treat obesity?

• Co-morbidities
• Life style
• Improved survival

Obesity is associated with multiple co-morbidities

• Endocrine- Diabetes
• Cardiovascular- hypertension, hyperlipidemia, coronary & cerebral vascular disease
• Gynaecology- infertility and menstrual irregularities
• Orthopaedic- arthralgia, low back pain
• Dermatology- fungal infections
• Pulmonary- sleep apnea, asthma, pulmonary hypertension, hypoventilation
• GI- GORD, cholelithiasis, fatty liver/liver dysfunction
• Socio economic- discrimination
• Psychological- depression
• Increased risk of cancers

What is the health risks associated with obesity?
Obesity is second only to smoking as the leading cause of preventable death in the US.
More than 110,000 deaths/year in the US are associated with obesity.

Are any tests needed before treating obesity?

No single laboratory test is indicated for all patients with obesity. The specific evaluations will depend on presentation of symptoms, risk factors, and index of suspicion.

• Screen for co-morbidities- so check blood glucose, and lipids. Check for hypertension, obstructive sleep apnea and gall stone disease (USS abdomen)
• Endocrine diseases rarely cause obesity.
• Nonetheless, hypothyroidism, Cushing’s syndrome, hypothalamic tumors, and damage to the hypothalamus as a consequence of radiation, infection or trauma have all been associated with weight gain. These should be considered when indicated by patient history.
• Certain medications can contribute to obesity- steroids, antidepressants, sulphonylureas etc. Drug-induced effects should be suspected when the weight gain coincides with the initiation of the drug.

How do you treat obesity?
Treatment of obesity consists of several therapeutic options

• Life style changes- decrease energy intake and increase physical activity.
• This should be a component of all other therapies.
• Pharmacotherapy
• Bariatric surgery

What are the principles of weight loss programme?

• Based on balanced healthy diet
• Regular physical activity
• Weight loss of 0.5-1 kg a week
• Aim to lose 5-10% of body weight

Programme that do not meet these criteria are unlikely to help people maintain a healthy weight in the long term.

Waist should be measured at the Midpoint between the lowest rib and the iliac crest (WHO) at the end of expiration

How do you decide on the level of intervention?

The level of intervention should be based as follows

NB- Comorbidities include T2DM, hypertension, cardiovascular disease, osteoarthritis, dyslipidaemia and sleep apnoea.

Discuss life style changes?

• Physical activity
• At least 30 minutes of moderate-intensity physical activity on 5 or more days a week. The activity can be in one session or several lasting 10 minutes or more.
• Diet
  • 600 kcal/day deficit diet (that is, they contain 600 kcal less than the person needs to stay the same weight) are recommended for sustainable weight loss.
  • Low-calorie diets (1000–1600 kcal/day) may be considered, but are less likely to be nutritionally complete.
  • Very-low-calorie diets (less than 1000 kcal/day) may be used for a maximum of 12 weeks continuously, or intermittently with a low-calorie diet (for example for 2–4 days a week), by people who are obese and have reached a plateau in weight loss.

Discuss Pharmacological interventions?
Drug treatment should be considered for patients who have not reached their target
weight loss or have reached a plateau on life style changes. Drug treatment is not
generally recommended for children younger than 12 years.

• Orlistat (Xenical)
  • Mechanism- Peripheral lipase inhibitor; causes fat malabsorption.
  • Side effects- Fatty stool, Urgency, possible vitamin malabsorption
  • Mean weight loss- 2.9 kg (2.3-3.4)
  • Standard prescription dose of 120 mg three times daily before meals
  • The co prescribing of Orlistat with other weight loss drugs is not recommended.
• Sibutramine (Meridia in the U.S. and Canada, Reductil in Europe)
  • It is a SNRI (serotonin & norepinephrine reuptake inhibitor). It induces satiety
  • Side effects- Insomnia, Dry mouth, Nausea, Constipation, Increased blood pressure & heart rate. Pulse & blood pressure should be specifically monitored.
  • Mean weight loss- 4.6 kg (3.8-5.4)
  • 10 mg once daily (usually in the morning), if this proves insufficient the dose may be increased to 15 mg daily after 4 weeks.
  • Contra indication. Patients with uncontrolled hypertension, IHD, arrhythmias, congestive heart failure, stroke or transient ischemic attacks, seizure disorder, or severe kidney or liver disease.
  • Co prescribing of Sibutramine with other wt loss drugs is not recommended.
• Rimonabant (Acomplia, withdrawn from UK)
  • Selective cannabinoid-1 receptor (CB1) blocker. Blocking CB1 receptors reduces over activity of the endocannabinoid system (ECS). This contributes to the regulation of energy homeostasis and improves lipid profile, components of the metabolic syndrome, and glucose uptake.
  • Mean weight loss- 4.6 kg (4.3-5.0)
  • Side effects-  Nausea, Dizziness, Diarrhea, Insomnia, Depression

How do you decide which pharmacological intervention to use?
Sibutramine may be preferred in patients having difficulty controlling portion sizes due to hunger or not feeling full. It may also be useful in gastrointestinal conditions such as irritable bowel syndrome that would make it difficult to take orlistat.
Orlistat may be useful in patients needing additional motivation to adhere to a fat-modified diet

How long can you continue the drugs?

Discontinue if no response after 3 months (wt loss of at least 5%)
The medication may be continued if weight is lost within 6 months and is maintained after the initial weight loss phase. It can be continued as long as the patient continues to maintain weight loss and there are no significant adverse effects.

When would you recommend bariatric surgery?
Bariatric surgery is recommended as a treatment option for people with obesity if
all of the following criteria are fulfilled:

• They have a BMI of 40 kg/m² or more, or between 35 kg/m² and 40 kg/m² and
• other significant co morbid diseases (like t2dm or hypertension) that could be
• improved if they lost wt.
• All appropriate non-surgical measures have been tried but have failed to
• achieve or maintain adequate, clinically beneficial weight loss for at least 6 m
• The person has been receiving or will receive intensive management in a Specialist obesity service
• The person is generally fit for anaesthesia and surgery
• The person commits to the need for long-term follow-up.

Remember

• Bariatric surgery is also recommended as a first-line option (instead of lifestyle
• interventions or drug treatment) for adults with a BMI of more than 50 kg/m² in whom surgical intervention is considered appropriate.
• Surgery should be undertaken only after a comprehensive preoperative assessment of any psychological or clinical factors that may affect adherence to
• post operative care requirements, such as changes to diet.

What are the principles of bariatric surgery?
Two main principles exist in combination or alone: restriction and malabsorption.
Purely restrictive operations limit the amount of solid food that can be consumed.

Vertical banded Gastroplasty (VBG)	Lap Band	Roux en Y gastric bypass
Purely restrictive operation	Purely restrictive operation	Restrictive plus malabsorption
Front of the stomach is stapled to the back in a vertical manner. The end of the pouch is restricted with either a polyprolene band or silastic ring.	No stapling. An adjustable band is placed below the OG junction to create a small pouch.	Induce weight loss by causing malabsorption of calories, inducing a dumping syndrome and altering appetite through alterations in GI peptides. Similar to VBG, a small pouch is created by either stapling or transecting the proximal stomach.  The pouch is then connected to and empties into a Roux-en-Y limb of jejunum.
Good results have been found with these operations; however, they are less effective in the long-term then bypass operations. Over time dilation of the pouch occurs and patients can adapt.	Advantages of Lap band and VBG- 50% excess weight loss at 1 year Minimal nutritional complications Disadv- poorly sustained weight loss at 10 or more years.	60% of excess weight lost in year 1 Maintains a weight loss of 50% for 25 years Rapid resolution of metabolic syndrome Improvement in obesity-related complications Disadv- severe dumping syndrome – rapid rush of liquid/soft high caloric food “dumping” into limb of small intestine….discomfort, nausea, bloating, diarrhea, weakness
Minimal risk of nutritional deficiencies	Minimal risk of nutritional deficiencies	High risk of nutritional deficiencies

NB- Biliopancreatic diversion with or without duodenal switch is another restrictive plus malabsorptive surgery. This is technically demanding and rarely performed.

Discuss post-operative complications of bariatric surgery? (Steinbrook R. NEJM 2004)

Combined Gastric Restriction & Malabsorption Operative Risks: (vs. cholecystectomy)
Perioperative Mortality        1-2%    vs. 0.2-0.8%
Early Complications            10%     vs. 2.9%
Late Complications             20%    vs. 1-2%

How do you monitor postoperatively?
There is a risk of nutritional deficiencies with malabsorptive operations.
Vitamin deficiencies- Thiamine, B12, folate, fat soluble vitamins, vitamin C
Minerals- Iron, calcium, zinc, selenium, copper
Deficiencies of protein and albumin could occur too.

There is lack of guidance regarding follow up and monitoring. However, it is suggested that;
FBC, urea and electrolytes, Ca, Mg, PO4, Glucose, LFTs, Ferritin, Vitamin B12, Folate, selenium, zinc, copper and fat soluble vitamins should be monitored at least 2-3 times a year
Bone mineral density should also be monitored
Lifelong supplementation of multivitamin tablets (including Lap band patients)

Ref

1. NICE guidance
2. Further reading (Archived copy at WebCite)

A diagnosis of anorexia requires four diagnostic criteria as defined in the DSM-IV:

• Refusal to maintain weight within a normal range for height and age (more than 15 percent below ideal body weight)
• Intense fear of weight gain, even though underweight
• Severe body image disturbance in which body image is the predominant measure of self-worth with denial of the seriousness of the illness
• In post menarche females, absence of the menstrual cycle, or amenorrhea (greater than three cycles).

There are two distinctive subtypes of anorexia: restricting; and binge eating/purging.
Who gets it?

90% of affected persons are female; most develop the disease after puberty but before age 25 years.

How can it be diagnosed?

The SCOFF questionnaire is a simple screening tool. The original study describing SCOFF reported that a “yes” to two or more questions was associated with a sensitivity and specificity of 100 and 87.5 percent for the diagnosis of an eating disorder.

• Do you make yourself Sick because you feel uncomfortably full?
• Do you worry you have lost Control over how much you eat?
• Have you recently lost more than one stone (14 pounds or 6.35 kg) in a three month period?
• Do you believe yourself to be Fat when others say you are too thin?

Would you say that Food dominates your life?

When do these patients need hospital admission?

The APA (American Psychiatric Association) criteria for hospitalization:

• Medical instability [significant bradycardia <40, hypotension <90/60, metabolic abnormality: glucose or electrolytes (K <3), dehydration, or evidence of organ compromise]
• Suicidal with high lethality plan or attempt.
• Weight <85 percent normal body weight or rapid decline with food refusal despite outpatient or partial hospitalization treatment
• Co-morbid psychiatric conditions
• Poorly motivated patient needing assistance to eat or cooperative only in a highly structured environment.

What are the Royal college of Psychiatrist guidelines for referral for primary care?

• Mild anorexia- BMI >17 and no additional co-morbidity. Monitor for 8 weeks and consider referral, if failure to respond
• Moderate anorexia- BMI 15-17 and no evidence of system failure- routine referral to eating disorders unit
• Severe anorexia- BMI <15, rapid weight loss, evidence of system failure- urgent referral to eating disorders unit

http://www.rcpsych.ac.uk/pdf/pcProtocol.pdf (Archived copy at WebCite)

Discuss the investigations for anorexia nervosa?

FBC, U&E, Ca, Mg, PO4, TSH, ESR, TTG, LFTs
Raised amylase of salivary source is common in anorexia.

Discuss the treatment?

• The most difficult part of management is engaging the patient with their treatment. A characteristic of people with anorexia nervosa is that they don’t accept that anything is wrong.
• It’s useful to involve the family in treatment plans, particularly with younger patients. Helping relatives to understand that anorexia is an illness may avoid confrontation.
• Inpatient nutritional treatment-
  • Correct fluid and electrolyte imbalance
  • Monitor for refeeding syndrome.
  • A weight gain of 0.5–1.0 kg per week is generally recommended for inpatients.
  • The use of oral thiamin supplements is recommended for in-patients and outpatients undergoing rapid weight gain. Parenteral B and C vitamins should be given before starting enteral feeding for at least the first 3 days of refeeding.
• Patients with anorexia nervosa are at risk for osteopenia. Treatment includes daily supplementation with 1200 to 1500 mg of elemental calcium plus vitamin D.  Estrogen/progestin replacement may be appropriate in selected women. Bisphosphonates such are not recommended for use in patients with anorexia in the APA guidelines
• Avoid drugs that prolong the QTc interval on the ECG; for example, antipsychotics, tricyclic antidepressants, macrolide antibiotics, and some antihistamines. In patients with anorexia nervosa at risk of cardiac complications, these drugs may compromise cardiac functioning.

Can compulsory treatment be used?
Compulsory treatment should be a last resort. The Mental Health Act can be used. The clinicians should still negotiate treatment options with patients who are receiving compulsory treatment.

What’s the long term prognosis?

One review found that approximately 50 percent of patients have good outcomes as defined by return of menses and weight gain, 25 percent have intermediate outcomes with some weight regain and some relapse, and 25 percent have a poor outcome.
Most deaths result from suicide or direct medical complications.

• Hypoparathyroidism,
• Vitamin D deficiency
• Magnesium deficiency
• Malabsorption (ass with Vit D and Mg deficiency)
• Hyperphosphatemia due to renal failure or tumour lysis.

Discuss the diagnosis?

Serum calcium levels corrected for albumin level

Discuss the clinical features?

• Tetany can occur when serum calcium falls below 1.8-1.9 mmol/l. It may be mild (perioral numbness, paresthesias of hand and feet, muscle cramps) or severe (carpopedal spasm, laryngospasm, focal or generalised seizures)
• Hypocalcaemia can cause dementia and psychological symptoms (anxiety and depression) in adults
• Hypocalcaemia can cause papilloedema

Discuss the treatment?

Mild asymptomatic hypocalcaemia
Increase dietary calcium intake (unless the patient has hyperphosphatemia).

Symptomatic hypocalcaemia

• IV Calcium- The most appropriate treatment (unless low Mg) is IV calcium. 10 ml of 10% Calcium gluconate (2.25 mmol of elemental calcium) or 10mls of 10% calcium chloride (6.75 mmol of elemental calcium). The calcium should be given slowly over 10-20 minutes to avoid the risk of serious cardiac dysfunction. Such infusions raise the serum calcium concentration for 2-3 hours, and therefore should be followed by a slow infusion of calcium. The optimum dose should be 1.25mmol per hour for a 50 kg man. The calcium should be diluted in dextrose and water or saline. Calcium gluconate is preferred to calcium chloride because it is less likely to cause tissue necrosis if extravasated.
• Oral calcium- Intravenous calcium should be continued until the patient is receiving an effective regimen of oral calcium and vitamin D. Calcitriol,( in a dose of 0.25 to 0.5 µg/day), is  preferred in patients with severe acute hypocalcemia because of its rapid onset of action (hours).
• Magnesium- Hypomagnesemia is a common cause of hypocalcemia, both by inducing resistance to PTH and by diminishing its secretion. Thus, an alternative approach, if the serum magnesium concentration is not known (or is low), and if renal function is normal (so that excess magnesium can be excreted), is to administer magnesium. Two grams (4ml of 50%) of magnesium sulfate should be infused as a 10 percent solution over 10 minutes, followed by 1 gram in 100 mL of fluid per hour.

Chronic hypocalcaemia associated with hypoparathyroidism.

1.5-2 g of elemental calcium should be given orally (Calcium carbonate-250mg of elemental Ca/650 mg tablet)
Vitamin D should be added if there is insufficient response (50,000 units/day of vitamin D or its equivalent as calcitriol).

B12 absorption depend on 5 factors-

• Dietary intake
• Acid-pepsin in the stomach to liberate B12 from binding to proteins
• Pancreatic proteases to free B12 from binding to R factors
• Secretion of intrinsic factor (IF) by the gastric parietal cells
• Ileum

Discuss the causes of B12 deficiency?

• Dietary deficiency- strict vegans
• Stomach- pernicious anaemia, gastritis, gastrectomy
• Small bowel- malabsorption, ileal disease/resection, blind loops
• Pancreatic insufficiency
• Drugs blocking absorption- metformin, PPI

Discuss the causes of folate deficiency?

• Poor diet
• Malabsorption
• Drugs- methotrexate, trimethoprim, phenytoin
• Increased demand- pregnancy, haemolysis

Discuss the diagnosis?

Serum B12 and folate
The serum folate concentration is a reflection of short-term folate balance. One hospital meal can normalize the serum folate in patients who are folate deficient. The red cell folate concentration is a more reliable indicator of tissue folate adequacy.  However, it is not entirely without its own problems of interpretation. Thus, the less expensive serum folate concentration should be obtained as an initial screening test.

Discuss the treatment?

Folic acid deficiency
Oral folic acid is 1 to 5 mg/day orally for 1-3 months until complete hematologic recovery occurs. The oral route is sufficient even in those with malabsorption. Vitamin B12 deficiency must be ruled out, and treated if present, before giving folic acid to a patient with megaloblastic anemia, since administration of folic acid may worsen neurologic complications of untreated vitamin B12 deficiency.

Vitamin B12 deficiency

IM 1 mg alternate days for 2 weeks and then 3 monthly

Preop and postop nutrition- EN is recommended if it is anticipated that the pt will be unable to eat for more than 7 days peri-operatively. American Society for Parenteral and
Enteral Nutrition guidelines (ASPEN) recommend postoperative nutritional support for patients who cannot meet their caloric requirements within 7–10 days.

When is preoperative EN indicated?

Patients with severe nutritional risk benefit from nutritional support for 10–14 days prior to major surgery even if surgery has to be delayed.
Severe nutritional risk refers to at least one:

• Weight loss 10–15% within 6 months
• BMI less than 18.5 kg/m2
• Subjective Global Assessment Grade C
• Serum albumin 30 g/l (with no evidence of hepatic or renal dysfunction)

Is there any role of immunonutrition?

Pts undergoing major cancer surgery of the neck and abdomen as well as after severe trauma benefit from the use of ONS (3X250 ml) enriched with immune modulating substrates (arginine, omega-3 fatty acids and nucleotides).  Wherever possible these should be started 5-7 days before surgery and continued postoperatively for 5–7 days after uncomplicated surgery. It   reduces postoperative morbidity and length of stay. Undernourished patients, in particular, appear to benefit

What is the role of early post op (<24hrs) normal food intake or EN after GI surgery?

Early introduction of normal food intake or enteral feeding is recommended after GI surgery. When anastomosis of the proximal gastrointestinal tract has been performed, EN can be delivered via a tube whose tip is placed distal to the anastomosis.

How should patients be tube fed after surgery?

Use of naso-jejunal tube/jejunostomy is recommended for all candidates for TF undergoing major abdominal surgery. TF should be initiated within 24h after surgery.
TF should start with a low flow rate (e.g. 10—max. 20 ml/h) due to limited intestinal tolerance. It may take 5–7 days to reach the target intake and this is not considered
harmful.

What are the energy and substrate requirements for parenteral nutrition in the perioperative period?

• Energy- 25kcal/kg ideal body weight. Severe stress- 30kcal/kg IBW
• Protein-1.5g/kg IBW
• Protein: fat: CHO caloric ratio- 20:30:50%
• The optimal PN regimen for critically ill surgical pts should probably include supplemental glutamine and n-3 fatty acids.
• The standard lipid emulsion is soybean based rich in n-6 PUFA.  n-6 PUFA tend to have a pro-inflammatory effect. In contrast, n-3 PUFAs have an anti-inflammatory effect and have been shown to blunt the physiological response to endotoxins. Thus increasing dose of n-3 PUFAs has been shown to reduce ICU and overall hospital stay following major abdominal surgery. Thus mixtures of LCT and MCT are used as also LCT emulsion with olive/fish oil.
• Glutamine has a major role as a substrate for the immune system and for the small bowel. Postoperative PN supplemented with glutamine dipeptide (20-40g/24h) has been shown to reduce infection rate and hospital stay. Glutamine is unstable in solution and not very soluble, so glutamine peptides have been constructed with glycine and alanine.

Is weaning from PN necessary?

No. Traditionally PN has been tapered prior to discontinuation so as to prevent hypoglycaemia. However, it has been shown recently that even after prolonged PN the beta cells remain sensitive to changes in glucose level and thus hypoglycemia is unusual

Ref

1. ESPEN guidelines

• Nutritional status is one of the main factors determining outcome in ARF patients.
• ARF, especially in ICU seldom occurs as isolated organ failure but usually in the setting of MODS.
• Standard formulae are adequate for most patients.  Disease specific formulae for CRF may be justified in pts exclusively on EN or in hypercatabolic ICU patients
• Nutritional requirements (ESPEN 2006)
  • Non protein Energy- 20-30Kcal/kg/day (adjust for underweight or obese)
  • Carbohydrates 3-5 g/kg/day (max 7)
  • Fat- 0.8-1.2 (max 1.5)g/kg/day
  • Protein-
    • Conservative treatment- 0.6-0.8 (max 1) g/kg/day
    • Extracorporeal RRT- 1-1.5
    • RRT, hypercatabolic- upto 1.7 max
• Acutely ill patients with CRF on HD should be treated as ARF.

Discuss parenteral nutrition in acute renal failure?

• Energy and macronutrient requirements as above
• Loss of protein (0.2gm/kg/day) occurs in the pts undergoing dialysis.
• The enhanced requirements of water soluble vitamins induced by extracorporeal treatment should be met by supplementing multivitamin products. Experimental ARF is associated with an increase in plasma retinol. Although retinol intoxication has not been reported in ARF patients, signs of vitamin A toxicity should be carefully sought during supplementation. Similarly Vitamin C supplementation should not exceed 30-50mg/day, because inappropriate supplementation may result in secondary oxalosis. Selenium and thiamine levels should be monitored as depletion may occur despite supplementation.
• Restriction of electrolytes (Na, K, PO4 etc) is usually unnecessary on RRT.
• Standard formulae are adequate for the majority of patients. However,
• requirements can differ and have to be assessed individually. When there are
• electrolyte derangements, three-in-one formulae without electrolytes or customized formulae can be advantageous.

Discuss nutrition in chronic renal failure (stage III to V, treated conservatively)?

• Nutritional requirements
  • Calorie intake of 35Kcal/kg/day for stable CRF patients in the range of ideal body weight +/- 10% (adjust for underweight or obese)
  • Protein requirements 0.55-0.6 g/kg/day (2/3 high biological value-HBV)
  • Minerals (just a guide)
  • Phosphate-600-1000mg/day
  • K-1500-2000mg/day
  • Na- 1.8-2.5g/day
• Standard formulae can be used for short-term EN (< 5 days) but for EN for more than 5 days, disease-specific formulae (protein-restricted with reduced electrolyte content) should be used.

Discuss parenteral nutrition in chronic renal failure (stage III to V, treated conservatively)?

• Energy and minerals requirements as above
• Metabolic acidosis in uraemia is an important factor for the activation of protein catabolism. Alkalinization therapy is thus standard in the treatment of CKD patients.
• Loss of protein due to proteinuria exceeding 1 g/d should lead to compensatory additions to daily protein intake such as by the calculation of protein/AA intake needed based on ideal body weight (kg x 0.6 – 0.8 x proteinuria).
• The nutritional requirements of acutely ill CKD patients are dealt with as in ARF
• Standard PN mixtures should be used if PN is indicated. In patients receiving PN without any enteral supply, vitamins and trace elements should also be administered intravenously. If the patient needs PN for a period exceeding two weeks, accumulation of vitamin A and trace elements should be considered

Discuss nutrition in chronic renal failure (on maintenance HD)?

• Nutritional requirements
  • HD or CAPD- 35 Kcal/kg/day (for CAPD in pts <60- 30 Kcal/kg/day)
  • Protein intake-
    • HD- 1.2-1.4 (50% HBV)
    • CAPD- 1.2-1.5 (50% HBV)
  • Minerals (guide only)
  • Phosphate-800-1000mg/day
  • K-2000-2500mg/day
  • Na- 1.8-2.5g/day
  • Fluid- 1000+urine volume
• Due to dialysis-induced losses, water-soluble vitamins need to be supplied: folic acid (1mg/ day), pyridoxine (10–20 mg/day) and vitamin C (30–60mg /day). Vitamin D should be given according to serum calcium, phosphorus and parathyroid hormone levels.
• Thiamine should also be supplemented with a daily oral dose of 1-5 mg. Vitamin E may also be prescribed to patients at high cardiovascular risk at a daily dose of 800 IU of alpha-tocopherol. Routine haemodialysis does not induce significant trace-element losses. However, in depleted patients zinc (15 mg/day) and selenium (50–70mg/day) supplementation may be useful.
• Dialysis specific formulae should be used (high protein content of HBV, reduced electrolytes with high energy concentration)
• Due to an increased incidence of peritonitis, PEG/PEJ is contraindicated in adult CAPD patients but is standard in children
• Dialysis initially leads to improvement in nutritional indices. However, after this initial improvement, the time on dialysis becomes directly associated with a significant decline in all measured nutritional parameters because dialysis procedure is itself a catabolic event.

Discuss parenteral nutrition in chronic renal failure (on maintenance HD)?

• In acutely ill HD patients the requirements are the same as in ARF patients.
• Energy and macronutrients as above
• Phosphorus intake should be limited to 10-15 mg/kg/day. As phosphorus and protein are combined in nutrients with a ratio of 10-13 mg pho

• Conservative treatment- 0.6-0.8 (max 1) g/kg/day
• Extracorporeal RRT- 1-1.5
• RRT, hypercatabolic- upto 1.7 max

• sphorus/g protein, most HD patients who have an adequate protein intake will need phosphate binders to prevent an increase in serum phosphorus.
• Severe malnutrition is as defined as low BMI (<20), body weight loss more than 10% over 6 months, serum albumin less than 35 g/l and serum transthyretin less than 300 mg/l.
  • Severe malnutrition plus spontaneous intakes less than 20 kcal/kg/day or in stress conditions: both ONS and IDPN are generally unable to provide satisfactory nutritional supply and are not recommended; daily nutritional support is necessary and EN should be preferred to PN.
  • In patients exhibiting severe malnutrition, with spontaneous intakes more than 20 kcal/day: dietary counseling and ONS should be prescribed; IDPN is indicated in patients unable to comply with ONS; EN can be necessary when ONS or IDPN fail to improve nutritional status.
• IDPN- Intradialytic PN (IDPN) is a cyclic PN given (usually) three times weekly through the venous line of the dialysis circuit. The following technical rules have been proposed in order to ensure optimal tolerance:
  • IDPN should be infused at constant rate during a typical 4-hour dialysis session;
  • IDPN delivery should be progressively increased from 8 ml/kg/IDPN during the first week, to a maximum of 16 ml/kg/IDPN without exceeding 1000 ml/HD
  • IDPN should be associated with controlled ultrafiltration, volume for volume;
  • 75 mmol Na should be added per liter of IDPN solution in order to compensate Na losses due to ultrafiltration.
  • IDPN typically provides 800-1200 kcal three times weekly, in the form of glucose and fat emulsion and 30 to 60 g of protein. Standard amino acid solutions can be used for IDPN.
• Recommended longitudinal monitoring of nutritional status in maintenance dialysis patients: dietary interviews every 6 months; body mass index monthly; serum albumin and transthyretin, anthropometrics every 1-3 months as needed according to nutritional status.
• Alternative treatments for protein-energy wasting in dialysis may be needed when nutritional support is insufficient. The administration of nandrolone decanoate has been demonstrated to increase muscle mass. Exercise combined with IDPN, as compared with IDPN alone, has been shown to promote net muscle protein accretion. These data argue in favor of a multimodal treatment of malnutrition in dialysis, combining nutritional support, exercise and anabolic agents.

Discuss parenteral nutrition in CAPD?

• Energy requirements as above
• Therapy-associated losses of proteins during CAPD are higher than in HD. Protein losses are approximately 10 g/day and increases in peritonitis. Because peritoneal solutions with a high glucose content are used as standard in CAPD, this method is associated with a glucose uptake of 100 to 200 g/d which is further
• increased during peritonitis. Due to the increased glucose load, body weight may
• even increase in CAPD patients. The high glucose load is also responsible for
• induction or aggravation of diabetes, hypertriglyceridaemia and increased LDL and VLDL cholesterol.
• In patients exhibiting severe malnutrition, with spontaneous intakes more than 20 kcal/day: dietary counselling and ONS should be prescribed; IPPN may be considered in patients unable to comply with ONS; EN can be necessary when ONS are unable to improve nutritional status.
• In patients exhibiting severe malnutrition, with spontaneous intakes less than 20 kcal/day, or in stress conditions: daily nutritional support is necessary and EN should be preferred to PN; central venous PN is indicated when EN is impossible or insufficient (e.g. severe encapsulating peritonitis)
• The special form of PN unique to CAPD patients is Intraperitoneal Parenteral Nutrition (IPPN). IPPN is shown to improve nitrogen balance and nutritional parameters. IPPN mainly consists of the intraperitoneal administration of 1.1% amino acid-based solution. IPPN can be associated with hypokalaemia, hypophosphataemia and mild acidosis.  So close monitoring during this treatment is needed
• In acutely ill patients with CKD on CAPD the route for PN should be the same as in ARF patients. In these patients a combined use of PN (CHO and fat) and IPPD, using AA based PD solution can be suggested.
• In non-acutely ill malnourished CAPD patients, the preferred route is via the peritoneum.

Ref

1. ESPEN guidelines

• Mild acute Pancreatitis- EN is not indicated if the patient can eat normal food after 5-7 days
• Severe acute Pancreatitis (AP)
  • Early EN (asap especially in alcoholics) improves the course of acute pancreatitis
  • Continuous EN is recommended, if tolerated. TF is feasible in the majority of the patients with AP. However TF may need to be supplemented with parenteral feeding if the requirements cannot be met enterally
  • NJ feeding can be tried if gastric feeding is not tolerated
  • Try standard formulae first and if not tolerated peptide based formulae can be used.
  • Avoid overfeeding during the acute phase (CH 50%, Fat 30%, protein 1-1.5 gm/kg/day). TG should be monitored regularly. Values below 10–12 mmol/l are tolerated but serum lipid levels should ideally be kept within normal ranges.
• Chronic Pancreatitis
  • Pancreatic enzymes taken with meals with a normal fat content (30% of total energy intake) are the mainstay of treatment.
  • Whole protein ONS (with pancreatic enzymes) may be used if oral intake is insufficient.   Peptide-based ONS may be tried if whole protein ONS is not tolerated. However, the palatability of peptide supplements is low and compliance is poor.
  • If adequate weight gain cannot be achieved and steatorrhoea is persistent, then medium chain triglycerides (MCT) are useful due to lipase independent absorption of MCT. However MCTs have a lower energy density (8.3 kcal/g), are not very palatable, and may induce side effects such as abdominal pain, nausea and diarrhoea.
  • Jejunal EN with peptide or amino acid based formula (given overnight) is recommended if the patients cannot ingest sufficient calories.  For long-term therapy a percutaneous endoscopic gastrostomy (PEG) with a jejunal tube is probably best.

When is PN indicated in Acute Pancreatitis?

• PN is only required when EN is contraindicated (like persisting ileus, complex pancreatic fistulae or abdominal compartment syndrome).
• PN in pts with severe AP (who cannot be fed enterally) PN initiated within the first 24-48 h of hospital admission have an adverse impact on clinical outcomes. So PN should be delayed till after the period of the peak inflammatory response has passed.

How should PN be used in severe AP?

• Avoid overfeeding- maximum caloric intake should be 30 Kcal/kg/day. This should be reduced to 15-20 kcal/kg/day in case with SIRS or MODS and when the patient is at risk of refeeding syndrome.
• 50-70% of the total calories should come from glucose.  As in other critically ill patients, glucose oxidation reaches the maximal level at 4mg/kg/min (3-5 gm/kg/day). Exceeding this limit may cause lipogenesis, hypercapnia and hyperglycemia. Tight glucose control (4-6 mmol/l) with insulin therapy appears to be beneficial in critically ill patients.
• Protein- 1.2-1.5 g/kg/day.  This should be reduced to 1-1.2 g/kg/day in the case of hepatic or renal failure complicating AP.
• When PN is indicated, parenteral glutamine supplementation (dose > 0.2, usually 0.3-0.4g/kg) should be considered.
• Glutamine is the most abundant free amino acid in the body and plays a central role in many metabolic processes (interorgan transport of C and N2 skeletons, regulator of acid base balance). In AP, 3 RCT’s showed use of glutamine was associated with a trend towards reduction in overall complications and shorter hospital stay.
• Lipid emulsions- not more than 1g/kg/day. The use of IV lipids in AP is safe if hypertriglyceridaemia (HTG) is avoided. The lipid infusion should be discontinued if persistent (>72 hrs) HTG occurs (>12 mmol/l)

Discuss the relationship between hypertriglyceridemia and acute pancreatitis?

The relationship between HTG and AP is controversial because it is still unclear whether hyperlipidaemia is a cause or a consequence of AP or a combination of both. The latter seems more likely, since serum lipids normalize spontaneously within 48-72 hours when there is no continuing exogenous source of lipids.

• The diagnosis of hypertriglyceridaemia-associated pancreatitis is based on lipaemic serum, a serum
• TG level greater that 12 mmol/L and the presence of chylomicronaemia. The mechanism is poorly understood. Hydrolysis of TG in and around the pancreas by pancreatic lipase secreted by acinar cell leads to accumulation of free fatty acids in high concentrations. Free fatty acids cause activation of pancreatic pro-enzymes, proinflammatory cytokines and free radicals, thus initiating AP.
• Lipid emulsion should be avoided with PN in HTG associated pancreatitis. The goal is to maintain TG levels within a normal range.
• If the serum TG level cannot be maintained below 12 mmol/L, drug therapy is indicated. Plasma exchange has been used to lower lipid and pancreatic enzymes levels, and to improve the signs and symptoms of AP.
• Keeping blood TG levels < 4.6 mmol/L, in patients with previous HTG-associated AP can effectively prevent further episodes of pancreatitis

Ref

1. ESPEN guidelines

This is very difficult. BMI may be difficult to use because cachexia may be masked by edema. However in general the following BMI indicates malnutrition in liver disease patients:

• BMI <22 in patients without ascites
• BMI <23 in patients with mild ascites
• BMI <25 in patients with tense ascites

Mid arm muscle circumference (MAMC) and triceps skin fold thickness may also be used to diagnose malnutrition.

SGA (subjective global analysis) is very reliable and specific in detecting malnutrition. ESPEN recommends use of SGA and/or anthropometrics (BMI/MAMC/ triceps skin fold thickness) to diagnose malnutrition.

Discuss enteral nutrition in alcoholic hepatitis (AH)/ cirrhosis of liver?

• Undernourished patients have a poor prognosis
• ESPEN (2006) recommends a calorie intake of 35-40Kcal/kg/day (dry body weight) and a protein intake of 1.2-1.5 g/kg/day (dry body weight)
• Use ONS or TF, if oral intake is not sufficient. Whole protein formulae should be used. Use of BCAA enriched formulae should be reserved, if hepatic encephalopathy develops despite appropriate medical treatment.
• ESPEN supports the insertion of fine bore NG tubes in patients with oesophageal varices.
• PEG is associated with a higher risk of complications (due to ascites and varices) and should be avoided.
• In the study by Cabre E et al (Hepatology 2000) EN was found to be as effective as steroids in alcoholic hepatitis.

When do you consider PN in AH or cirrhosis?
PN should be considered when oral/enteral intake is insufficient.

What are the energy requirements?

• Energy intake- 1.3 X BMR
  • CHO- 50-60 % of non protein requirements
  • Protein 1.2 gm/kg/day (1.5 gm/kg/day if severely malnourished)
  • Lipids- 40-50% of non protein requirements
  • In patients with ascites ideal weight according to the height should be used.
• Vitamins and minerals should be administered daily from the beginning. Due to the high risk of Wernicke’s encephalopathy, vitamin B1 must be administered prior to starting i.v. glucose in alcoholic patients.
• Lipid should be provided using emulsions with a content of n-6 unsaturated fatty acids lower than in traditional pure soy bean oil emulsions (n-6:n-3 = 8:1). New fat emulsions have a lower content in n-6 unsaturated fatty acids due to the admixture of MCT and/or olive oil and/or fish oil rendering them less suppressive on leucocyte and immune function and less pro-inflammatory modulators.
• A standard solution should be given in encephalopathy stage I-II and a liver-adapted complete amino acid solution should be given in encephalopathy stage III-IV. Such solutions contain an increased amount of branched-chain amino acids and lower content of aromatic amino acids, methionine and tryptophan. BCAA solutions lead to an improvement in mental state, but no definite benefit on survival.
• Like in other conditions, the administration of micronutrients has no proven therapeutic effect apart from the prevention or correction of deficiency states. Supplementing zinc and vitamin A may indirectly improve food intake and nutritional state by improving dysgeusia. Zinc and selenium deficiency have been observed in alcoholic and non-alcoholic liver disease. An impressive association between HE and zinc deficiency has been described in case reports. However oral zinc supplementation does not have a therapeutic effect on HE.  In a pragmatic approach, liberal supplementation is recommended in the first two weeks of nutritional support, because the laboratory diagnosis of a specific trace element or vitamin deficiency may be more costly, and would delay provision.

Discuss nutrition in AH/Cirrhosis?

• The prevalence of protein energy malnutrition increases from 20 % in Child-Pugh class A to over 60 % in class C
• In patients with cirrhosis, overnight fasting can cause depletion of glycogen stores and lead to a metabolic condition similar to prolonged starvation. Thus it is recommended that patients who need fasting should be given glucose IV at a rate equal to the endogenous hepatic production (2-3gm/kg/day).
• Due to psychomotor dysfunction oral nutrition often is not sufficient even in encephalopathy stage I-II.  Tube feeding should be considered to ensure adequate nutrient provision. PN should be considered in patients with unprotected airways and advanced HE.
• In the early postoperative phase often there is a disturbance of glucose metabolism associated with insulin resistance. Hyperglycaemia In this situation should be managed by reducing glucose intake because higher insulin doses are unable to increase glucose oxidation.

Discuss nutrition in acute Liver failure?

• As in other critically ill patients artificial nutrition in acute LF is indicated when the patient is considered unlikely to resume normal oral nutrition within the next 5 to 7 days.
• In acute liver failure resting energy expenditure is increased 1.2- to 1.3-fold compared to healthy individuals. Whenever possible, the individual energy requirement should be measured by use of indirect calorimetry.
• Sufficient glucose provision (2 – 3 g/kg/day) is mandatory for the prophylaxis or treatment of hypoglycaemia
• Lipid (0.8 – 1.2 g/kg/day). Most centers use LCT/MCT emulsion
• Amino acid administration is not mandatory in hyperacute LF. In acute or subacute LF, however, amino acids (0.8–1.2 g/kg/day in PN) or protein (0.8 – 1.2 g/kg/day) in enteral nutrition) should be used in order to support protein synthesis.
• The use of amino acid infusion often was omitted for fear of aggravating existing hyperammonaemia and hyperaminoacidaemia causing brain oedema and encephalopathy especially in hyperacute liver failure.
• Adequate metabolic monitoring is necessary in order to adapt nutrient provision to substrate utilisation. Strict control of the plasma levels of glucose (target: 5 – 8 mmol/L), lactate (target: < 5.0 mmol/L), triglycerides (target: < 3.0 mmol/L) and ammonia (target: < 100 micromole/L) are necessary for this purpose.

NB- BCAA are essential amino acids leucine, isoleucine and valine. In cirrhosis there are reduced body stores of BCAA. This directly or indirectly influence brain ammonia levels.

Ref

1. ESPEN guidelines

• Current literature strongly favours using enteral nutrition as the first line method for feeding ITU patients.
• Further there is no significant difference in the efficacy of gastric versus jejunal feeding in ITU patients.
• Use of prokinetics should be considered in patients intolerant to enteral feeding.
• Whole protein formulas are appropriate in most cases. There is no advantage of a peptide based formula.
• ESPEN (2006) guidelines favours early (<24hr) feeding of haemodynamically stable patients.
• EN is indicated in all patients who are not expected to be on full oral diet within 3 days
• During the acute phase of illness, provision of higher amounts of nutrients is associated with a less favourable outcome. Hence during the first 72-96 hours calorie intake in excess of 20-25 Kcal/kg/day (25-30 Kcal.kg/day for undernourished/chronic catabolic state patients) may be associated with less favorable outcome. During he recovery phase, aim to provide 25-Approve User Registration30 Kcal/kg/day.
• Indication of parenteral nutrition- only if pts are intolerant of EN or to provide supplemental PN if sufficient EN cannot be fed.
• Evidence for the use of glutamine- Glutamine should be added to EN in burned and trauma patients. Glutamine is a conditionally essential immunonutrient that is derived from muscle protein breakdown.
• Consider supplementation with omega-3-fatty acids, arginine and nucleotides (immune modulating formula) in elective upper GI patients, pts with mild sepsis (APACHE II <15), trauma and ARDS pts. However ICU patients with very severe illness and who do not tolerate more than 700 ml EN/day  should not receive a immune modulating formula

Parenteral nutrition in ICU

What is the indication for PN in ICU?

Patients who are not expected to be on oral nutrition within 3 days should receive PN if EN is contraindicated or if they do not tolerate EN. All patients who are not expected to be on a full oral diet within 3 days and who do not receive sufficient enteral nutrition for > 24h should receive complementary parenteral nutrition

What are the energy and substrate requirements?

• Energy requirements as above in EN section of ICU nutrition. Provide energy as close as possible to the measured energy expenditure to decrease negative energy balance
• The minimal requirements for glucose are about 2g/kg BW/day and they should not exceed 5-6 g/kg/day.
• Hyperglycemia should be avoided to prevent infectious complications. Tight glucose control (4.5-6.1 mmol/l) may lead to decreased mortality in surgical ICU patients. Whether a target below 8.3 mmol/L is equally effective and perhaps safer remains unknown
• IV lipids (LCT, MCT or mixed emulsions) can be administered safely at a rate of 0.7 up to 1.5 g/kg/d.
• Soybean oil-based lipid emulsions (LCT) high in linoleic acid are largely used in the ICU and remain the reference emulsion. LCT/MCT lipid emulsions show a clinical advantage to LCT alone but no improvement in survival.
• A balanced amino acids mixture should be infused at 1.3 – 1.5 g/kg ideal body weight/day in patients receiving adequate energy supply. In acute patients receiving hypocaloric feeding protein requirements were increased by about 25-30%.
• The amino acid solution should include 0.2 to 0.4 g/kgBW /day of glutamine (0.3 to 0.6 g/kg/day alanyl-glutamine).
• It is the most abundant free amino acid that under normal conditions is not an essential amino acid. However in the critically ill, its demand is increased for immune activity and repair.  A low plasma level is associated with a worse outcome. Various studies have shown reduced mortality or improved morbidity with reduced infections, improved glycaemic control or reductions in length of stay. Where the dipeptide cannot be incorporated within the PN feed it has been shown safe to administer through a peripheral line.
• Any prescription of PN includes 1 daily dose of multivitamins and 1 daily dose of trace elements. Parenteral feeding solutions (unlike enteral solutions) contain no trace elements or vitamins for stability reasons; this implies that they must be prescribed separately. However, clinicians very often forget to prescribe them, as they consider the PN bags to be analogue to the enteral complete feeding solutions.
• The micronutrients are invariably prescribed as “1 daily dose”, whatever the bodyweight or metabolic rate. When PN is prolonged, and if the patient remains critically ill, determination of plasma concentrations on monthly basis enables detection of gross deficiencies that should be supplied by the individual trace element: selenium and zinc are particularly at risk.

Some patients have specific substitution requirements that should be considered separately from PN requirements:

• Continuous renal replacement therapy causes a continuous loss in the effluent varying between 1-2  adult doses of selenium, zinc and thiamine per day that should be given in addition to basal requirements.
• Major burns cause large exudative Cu, Se and Zn losses
• In alcoholic patients- thiamine supplements (100-300 mg/day) are needed during the first 3 days in the ICU to prevent neurological side effects associated with PN glucose delivery.

There is no specific solution for these patients: it is therefore tempting to administer 2 or 3 vials of existing preparations to achieve an adequate dose. However this may cause toxicity.  A compromise solution may be the development of new basic multiple trace element preparation to which additional trace elements can be added for patients with increased trace element losses such as selenium and zinc

Are there any advantages of specific lipid formulations?

There are a number of different formulations of parenteral lipids:

• Soybean oil-based (e.g., Intralipid, Livolipid, etc); these are often referred to as long chain triglycerides (LCT)
• Mixtures (usually 50:50) of LCT and MCT e.g., Lipofundin
• Mixture (20:80) of LCT and olive oil (Clinoleic)
• Mixtures of lipids including fish oil (e.g. 30:30:25:15 mixture of LCT, MCT, olive oil and fish oil  (SMOFLipid); 40:50:10 mixture of LCT, MCT and fish oil (Lipoplus, also known as Lipidem)
• Fish oil for use as a supplement to be diluted with soybean oil (Omegaven).

Intravenous fish oil, providing eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) decreases the synthesis of inflammatory cytokines, when compared to LCT/MCT. A multicenter study showed that IV fish oil had favorable effects on survival, infection rate, antibiotic requirements and length of stay when administered in doses between 0.1 and 0.2 g/kg/day. The best effects were observed in abdominal sepsis.

Although there is a theoretical basis for the inclusion of fish oil as a component of a lipid mixture such as seen in SMOFLipid, there is very little direct evidence of the efficacy of such mixtures. LCT/MCT, olive oil and fish oil enriched emulsions show clinical advantages on Omega 6 fatty acids emulsions, except in terms of survival.

ESPEN currently recommends use of fish oil enriched lipid emulsions in abdominal sepsis and surgical patients requiring ICU.

Discuss lipid biochemistry?

• Fatty acids are classified as saturated (no double bonds in the chain) or unsaturated (one or more double bonds in the chain), with the latter sub classified as monounsaturated (one double bond in the chain) or polyunsaturated (two or more double bonds in the chain).
• According to the chain length, fatty acids are termed short chain (< 8 carbons), medium chain (8 to 14 carbons) or long chain (16 or more carbons).
• With regard to the position of the double bond within the fatty acid chain three families are typically distinguished: omega-9, omega-6 and omega-3 (sometimes referred to as n-9, n-6 and n-3).
• Many fatty acids can be synthesized within the human body but two fatty acids (linoleic acid and alpha-linolenic acid) cannot. These fatty acids are required to be supplied to humans and are referred to as essential fatty acids. The essential fatty acids are synthesized in plants and are found in high  amounts in plant oils (e.g. corn, sunflower, soybean). They can be further metabolized to longer  chain, more unsaturated fatty acids including arachidonic acid (omega-6), and eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) (both omega-3).
• Fish oil contains EPA and DHA. Olive oil contains the omega-9 monounsaturated fatty acid oleic acid.

Ref

1. ESPEN guidelines