Y08. Pharmacopeia: Gastrointestinal Pharmacology

Overview of parental nutrition

• Parental nutrition is the delivery of nutrients into venous circulation (peripherally or centrally) instead of the enteral route → it can be used to supplement nutrient delivery via enteral route, or supplement nutrient delivery in its entirety (total parental nutrition)
• It is prepared by sterile technique → typically a 3L bag of hyperosmolar solution (containing glucose, amino acids, lipids, H2O, electrolytes, vitamins and trace elements)
• It can only be administered by CVC due to its ↑ tonicity (Nb. issues with irritation and thrombosis if given via PIVC) → infused over 24 hrs
• It also requires multidisciplinary team involvement

Indications for parental nutrition

• Indicated for those unable to ingest or digest nutrients or to absorb them from GI tract for a prolonged period of time (> 3-4 days) → includes those who have:
• A failed trial of enteral feeding
• Contraindications to enteral nutrition:
  • GI obstruction
  • Upper GI strictures and fistulae (Eg. enterocutaneous fistulae)
  • Severe pancreatitis
  • Prolonged ileus (Eg. major abdominal surgery where feeding not anticipated for days, paralytic ileus)
  • Inflammatory conditions (Eg. IBD or mucositis due to chemotherapy)
  • Short gut syndromes (Eg. major SB resection)

Daily nutritional requirements for parental nutrition

BUT these vary according to:

• Physiological factors:
  • Age, gender, body size
  • Pregnancy
  • Activity level
  • Hydration status
• Pathological factors
  • Burns and sepsis → ↑ protein and caloric intake
  • Renal failure → ↓ volume, protein and electrolyte (esp K+) content
  • CCF → fluid reduction
  • Hepatic failure → ↓ a.a/protein content to prevent encephalopathy
  • Respiratory failure → ↓ glucose to minimise CO2 production

Components of parental nutrition

• (1) Energy source → glucose:lipid mixture (60:40 or 50:50)
  • Glucose (as 50% dextrose)
    • Used as an energy substrate → provides 50% of daily caloric needs
    • Glucose has ↓ energy density → 3.4 kcal/g only (cf. 4 kcal/g for carbohydrates) → 50% dextrose needs to be given (1 L = 940 kcal) → BUT this is hypertonic (1900 mosm/L) and requires delivery via CVC
    • Insulin can be given to aid glucose utilisation (esp in stressed patients)
    • Need to avoid excess glucose delivery → risk of ↑ BGL, lipogenesis (liver disease), ↑ MR and ↑ CO2 production (delayed ventilatory wean)
  • Lipid (as 10% or 20% intralipid)
    • Used as (i) an energy substrate (provides 30-40% daily caloric needs), and (ii) provision of essential FAs (vital for cell membranes and PG synthesis)
    • ↑ energy density cf. glucose → 1.1 kcal/mL (10%) and 2 kcal/mL (20%) → thus 1000 kcal can be achieved by 500 mL of 20% or 1L of 10%
    • Can be infused separately (Ie. not mixed with glucose/a.a. solution) → can be given 1x/week BUT usually given daily to aid caloric delivery in the smallest volume of solution –
• Nitrogen-source (as symthamin 17)
  • Used for (i) tissue protein synthesis (Eg. enzymes) and (ii) caloric needs
  • Includes > 50% essential a.a.’s (isoleucine, leucine, valine, lysine, methionine, phenylalanine, threonine, tryptophane) and > 25% branched chain a.a
  • Nb. A.a. are all L-isomers (as the body cannot use D-isomers)
• H2O → to maintain body H2O balance and replace losses (Eg. dehydration, bleeding)
• Electrolytes (Na+ /K+ /Cl- /PO4 3-/Mg2+, Ca2+) → to maintain and replace losses
• Vitamin/trace elements → vital to enzyme systems and metabolic pathways in body
  • Vitamin solutions – both H2O and fat-soluble vitamins (esp folic, thiamine, vitamin K)
  • Trace elements (Zn, Fe, Cu, Mn, Co, Se, I, Cr, Mb)

Monitoring of parental nutrition

• Needed to assess for (i) progress of nutritional state and (ii) complications of therapy
• Involves:
  • Clinical r/v (Eg. fluid balance, weight, nutritional assessment, infections)
  • Frequent ward glucose testing (until BGL stabilises)
  • Investigations → daily EUC, CMP, BGL; weekly FBC, LFT (incl albumin), Coags, Lipid studies, and plasma/urine osmolality

Complications of parental nutrition

• Catheter-related (MOST common) → PTX, chylothorax, embolism (air/thrombus), infection, Etc.
• Fluid/electrolyte disturbances
  • Fluid overload or hyperosmolar dehydration
  • Electrolyte disturbances
  • Normal AG metabolic acidosis (due to ↑ Cl- content)
• Metabolic disturbances
  • Hyperglycaemia (initially) → delay in ↑ endogenous insulin (thus supplemental insulin required)
  • Rebound hypoglycaemia (with abrupt cessation of TPN) → due to ↑ levels of endogenous insulin
  • Metabolic bone disease
• Others:
  • Immune suppression (due to fat component)
  • Liver disease → initially deranged LFTs → later fatty liver/steatohepatitis
  • ↑ PaCO2 (due to excessive glucose metabolism)

Bianca

2021A 04: 59% of candidates passed this question.
The pharmacology of enteral and parenteral nutrition is a level 1 topic in the first part syllabus. The TPN dose in terms of daily calorie and other nutritional requirements were key expectations in first part of the question. A detailed list of all macro and micronutrients was required under TPN composition. Expected information about macronutrients were their forms in the TPN solution (e.g., carbohydrate in the form of glucose, protein in the form amino acids), their relative calorie contributions and their essential components (e.g., the names of the essential amino acids). Identification of potential variability in composition and dose based on specific patient factors scored extra marks. Side effects included metabolic derangements (refeeding syndrome, over or under-feeding, hyperglycaemia, hyperlipemia), biochemical disturbances (fluid and electrolyte imbalances), organ injury (liver, pancreas) and vascular access related complications. Limited breadth and depth of information as well as incorrect facts were prevalent in the answers that scored lower marks.

Enteral feeding in critically ill

• Primary goal to alter course and outcome of critical illness
• Major goals determined by following principles:
  • Catabolism > anabolism. Calorie consumption reduced with better management of critical illness
  • Carbohydrates preferred as fat mobilization impaired
  • Protein: mitigate breakdown of muscle protein into AA
  • Recovery phase: Anabolism>catabolism. Nutritional support provides substrate for anabolic state

Dose

• Mainly observational evidence and clinical experience
• Adjustments can be made based upon an estimate of individuals’s Resting Energy Expenditure (REE) or their body weight
• Adjustment based on body weight, variations based on age, using equations or indirect calorimetry
• Indirect calorimetry
  • better than REE equations
  • not routinely accessible, not adequately tested
• Predictive equations significant inaccuracy
• Dosing weight is hence routinely based on body weight / BMI with specific adjustments

Dosing weight

• Estimate current or pre-admission dry body weight
• Choose appropriate body weight based on BMI from which to calculate caloric and protein intake
  • Underweight (BMI <18.5 kg/m2): current weight as initial dosing weight. Ideal body weight could lead to excess initial calories and induce refeeding syndrome
  • Normal weight (BMI 18.5-24.9 kg/m2): current weight as dosing weight
  • Overweight (BMI 24.9-29.9 kg/m2): current weight as dosing weight
  • Obese (BMI >= 20 kg/m2): Adjusted body weight
• Ideal Body Weight (Devine formula):
  • IBW (men) = 50 kg + 2.3 kg x (height, in – 60)
  • IBW (women) = 45.5 kg + 2.3 kg x  (height, in – 60)
• Adjusted Body Weight
  • AdjBW = IBW + (0.4 * [Actual weight – IBW])
    • or AdjBW = 1.1 x IBW

DAILY NUTRITIONAL REQUIREMENTS

BUT these vary according to:

• Physiological factors:
  • Age, gender, body size
  • Pregnancy
  • Activity level
  • Hydration status
• Pathological factors
  • Burns and sepsis → ↑ protein and caloric intake
  • Renal failure → ↓ volume, protein and electrolyte (esp K+) content
  • CCF → fluid reduction
  • Hepatic failure → ↓ a.a/protein content to prevent encephalopathy
  • Respiratory failure → ↓ glucose to minimise CO2 production

• Calories
  • Fewer calories in the first week of critical illness: approx 8-10 kcal/kg/day
  • 25-30 kcal/kg/day in stable patient
  • upto 35 kcal/kg/day if weight gain is desired in stable patient and in a lower inflammatory state
  • 25kcal/kg/day or less if extubation is imminent
• Protein
  • Mild-mod Critical illness: 0.8-1.2 g/kg/day
  • Severe Critical Illness: 1.2-1.5kg/day
  • Severe burns: upto 2g/kg/day

Composition

FORMULATIONS:

• Common differences between formulas include osmolarity, caloric density, and amount of protein per calorie, as well as electrolyte, vitamin, and mineral content.
• Most are formulated to provide 100 percent of recommended daily vitamin and mineral dose when a minimum of approximately 1000 or more kilocalories are delivered per day.

STANDARD

• Isotonic to serum
• Caloric density of approximately 1 kcal/mL
• Lactose-free
• Intact (nonhydrolyzed) protein content of about 40 g/1000 mL (40 g/1000 kcal)
• Nonprotein calorie to nitrogen ratio of approximately 130
• Mixture of simple and complex carbohydrates
• Long-chain fatty acids (although some are now including medium-chain and omega-3 fats)
• Essential vitamins, minerals, and micronutrients (usually RDA provided in ~ 1000ml of feed)

OTHERS

• CONCENTRATED
  • useful in fluid restriction
  • mildly hyperosmolar
  • caloric density of 1.2,1.5 or 2.0 kcal/ml
  • no mortality or morbidity benefit
• PREDIGESTED
  • protein hydrolyzed to short-chain peptides, less complex carbohydrates
  • reduced total fat, increased MCT or altered TGs
  • weakly supported by data
  • Potential benefit in: Thoracic duct leak/chylothorax, digestive defects/malabsorbtion syndromes, failure to tolerate standard EN
  • Caloric density of 1 or 1.5 kcal/ml

COMPOSITION

• CARBOHYDRATE/FAT
  • Standard 49-53% / 29-30%
  • Other (not recommended for routine EN):
  • Low carb/high fat 28-40%/40-55%
  • high carb/low fat 85%/15%
• PROTEIN
  • High protein EN (1.2-2g/kg/day) – improved mortality
  • Acute/chronic renal disease: Low-protein EN not recommended for routine use. Renal formulas only if difficult to manage volume and electrolytes
  • Standard feeds for patients on CRRT
• Peptides – unlikely to be beneficial
• Omega-3 fatty acids and antioxidants, glutamine, probiotics/prebiotics – unlikely to be beneficial, and may be harmful
• Fiber
  • no benefit in diarrhoea prevention.
  • Mixed fibre feeds may help in persistent diarrhoea
  • avoid in pressors/ reduced mobility due to bezoars
• Vitamins and trace elements
  • included in feed upto RDA amounts
  • Routine supplementation usually not necessary. Definitely donot provide more than RDA

Side Effects

2022B 06: 60% of candidates passed this question.
Generally, most candidates had a reasonable approach to structuring their answers using the headings provided in the question. To score well candidates were required to outline a method of dosing (per body weight, variations based on age, using equations or indirect calorimetry) and describe the composition in terms of the macronutrient daily requirements and energy content as well as other included components (micronutrients). Very few candidates discussed the variations in formulations beyond concentration change nor the reasons for such variations in sufficient detail. Candidates that did not score well were often lacking in detail or missing sections such as side effects or significant elements of the composition. No marks were awarded for content related to the presence of delivery tubes, administration details (e.g. definitions of gastric tolerance, trophic feeding, commencement rate) or for details that related specifically to parenteral nutrition.