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Drug dosing for the patient living with obesity

In this section you can learn how to adjust the dosing of common drugs used during anaesthesia when dealing with obese patients.

Drug dosing in the obese

  • Dependent on the properties of the drug
  • Fat-soluble drugs
    • Larger volume of distribution (more adipose tissue)
    • Accumulate in the peripheral compartments
    • Especially in the context of long infusions
  • Water-soluble drugs
    • Relatively smaller increases in the volume of distribution
    • Dosing recommendations should reflect body composition changes in the obese that are relevant for each specific drug
  • Paucity of information available on drug adjustments available
  • Society of Bariatric Anaesthesia Guidelines provides recommendations on drug dosing and what size descriptor to use
  • To add to the confusion the size descriptor required to predict the initial or loading dose may not be the same as that required to predict the maintenance dose

Size descriptor: Total Body Weight (TBW)

  • Most commonly used for drug dosing
  • Inaccurate as volumes and clearances do not increase proportionally with body weight in a linear manner.
    • Clearance of a drug increases in a non-linear manner with weight
    • This increases the risk of overdose
  • Allometric models using TBW have been successfully used to describe size-related non-linear changes in clearance, volumes and drug half-life
  • Allometry is the study of changes in the characteristics in relation to body size
  • The use of allometric scaling to determine pharmacokinetic parameters in obese individuals from data obtained from non-obese is sparse
  • TCI pumps are not available worldwide and a simpler method is required for manual TIVA

Size descriptor: Ideal body weight (IBW)

  • This is probably the best way to derive a “normal” body weight.
  • Can be derived using the BMI equation when the patient’s height is known and the ideal BMI is used

Size descriptor: Lean body weight (LBW)

  • LBW is the difference between TBW and fat mass
  • Having adipose tissue is normal so this will under predict weight
  • In non-obese this is usually 70% – 90% of TBW.
  • In obese this ratio is altered due to excess fat
  • James equation used in the Schnider and Minto model to calculate LBW leads to a paradoxical decrease in severe obesity – 70kg 175cm LBW= 56.5 kg – 280kg 175cm = -20 kg (negative value!)

Size descriptor: Fat-free mass (FFM)

  • Alternative to LBW but also underpredicts weight
  • Obese patients, if mobile, often have a lot of muscle
  • Predicted from sex, height and body weight.
  • Formula developed in adults but has been described for children as young as three years

Size descriptor: Adjusted Body Weight (ABW)

  • Practical and simple
  • ABW = IBW + Correction Factor X (TBW- IBW)
  • Correction Factor (CF) based on the physical properties of the drug – Fat-soluble drugs require a higher CF (CF = 0.4) – Fat-insoluble drugs can be assigned a CF of 0

Propofol:

  • High lipid solubility
  • High volume of distribution
  • Rapid clearance
  • Allometric models using TBW are more accurate than alternatives
    • Eleveld: uses allometry and TBW to scale volumes and clearances
    • Derived from 30 previously published studies
    • Appropriate for use in the general population
    • NONMEM (NONlinear Mixed Effects Modeling)
    • Anaesthetic drugs were explored as co-variates
    • The predictive performance was measured across young children, adults, elderly, high BMI individuals and in simulated TCI applications
  • Population-based models
    • Cortinez used data from only morbidly obese patients (BMI >35 kg.m−2)
      • Linear scaling of all parameters using TBW because it is designed specifically for the obese
    • Marsh and Schnider models are available in open TCI pumps but perform poorly in patients living with obesity
      • High BMI patients were not included in the population studies from which the models were derived – Lean body weight formulae in TCI pumps are inconsistent at extremes of size – Some practitioners target a lower plasma effect-site concentration using the TCI pump to circumvent this problem – We recommend inputting ABW and a correction factor of 0.4 in morbidly obese patients and using the Marsh model
  • TCI in obese children is more uncertain than in adults
  • The allometric TBW relationships included in the Eleveld models should be expected to perform better than the linear TBW relationships present in the Kataria model
  • Manual propofol infusion
    • ABW (suggested correction factor of 0.4) can be used instead of TBW and proceed with the usual formula Bristol manual infusion regime is an example which purports to produce a blood propofol concentration of 3 μg.ml−1
      • Loading dose of 1 mg/kg followed by an immediate infusion of
      • 10 mg/kg/hour for 10 minutes
      • 8 mg/kg/hour for the next 10 minutes
      • 6 mg/kg/hour thereafter
    • TBW to achieve propofol effect-site concentrations within 3 to 4 μg.ml−1 in a typical obese patient
      • Loading dose of 1.5 mg/kg followed by an immediate infusion of
      • 120 mcg/kg/minute for 10 minutes
      • 100 mcg/kg/minute for the next 10 minutes
      • 80 mcg/kg/minute thereafter

Remifentanil

  • Low lipid solubility
  • Low volume of distribution
  • Rapid clearance (metabolised by plasma esterases) which is organ independent
  • An infusion based on IBW and adjusted according to clinical response is a good option to administer remifentanil in obese patients
  • As BMI increases infusion rates in mcg/kg/minutes decrease in order to maintain the same plasma concentration
  • Remifentanil infusions based on TBW in obese subjects results in supra-therapeutic plasma concentrations and increases the risk of adverse side effects
  • Population based TCI infusion
    • Minto model did not incorporate obese individuals in their study population
    • Parameters: V1, V2, & clearance, are scaled with LBW
    • LBW is calculated with the same equation that is used by Schnider for propofol and is not appropriate for the morbidly obese (James equation)
    • Decreasing clearance for the morbidly obese
    • The use of the Minto model with ABW (CF = 0.4) results in slightly higher infusion rates than those predicted by the Kim model (PK model for remifentanil dosing calculations in adult obese patients)

Dexmedetomidine

  • Popular adjunct in TIVA
  • Lowers opioid and anaesthesia requirements
  • Relatively low lipid solubility, volume of distribution and clearance in comparison to propofol
  • If TBW is used infusions produce higher concentrations of the drug in obese compared to non-obese patients
  • Overestimates increases in volumes and clearances
  • Lower infusion rates should be used for mcg/kg/hr intra-operative maintenance
  • Base your infusion on IBW

Ketamine

  • Use ideal body weight for dosing

Muscle relaxants

  • Polar & hydrophilic drugs
    • Limited distribution in excess body fat
    • Obese patients can have a lot of muscle
  • SOBA guidelines recommend
    • LBW for non-depolarising muscle relaxants
      • However, we think this may underdose in obese patients who are mobile as they have more muscle than calculated from LBW
    • TBW for depolarising muscle relaxants (Suxamethonium)
      • Increase in pseudocholinesterase & extracellular fluid
  • Based on individual PK studies the following recommendations have been made
    • Atracurium (Varin et al)
      • Dose calculated on TBW
      • No difference in elimination half-life, volume of distribution at steady state and total clearance in obese vs non obese
      • No difference between the 2 groups in the time of recovery from neuromuscular blockade despite higher concentration in obese patients
    • Vecuronium (Schwartz et al)
      • Dose calculated on IBW
      • No difference in elimination half-life, volume of distribution at steady state and total clearance in obese vs non obese
    • Rocuronium (Puhringe et al)
      • Infusion rates decreased
      • Volume of distribution at steady state and clearance is decreased with longer elimination half life in obese vs non obese
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Introduction to Using Total Intravenous Anaesthesia (TIVA)

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