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Manual and Total Controlled Infusions

Total intravenous anaesthesia can be administered by manual or target-controlled infusions (TCI). TCI is preferable but we will discuss both methods

Total intravenous anaesthesia with propofol

  • Propofol is a fast onset, short-acting intravenous anaesthetic
  • Favourable pharmacokinetic properties allow accurate titration
  • Suitable for both induction and maintenance of anaesthesia
  • Propofol has a narrow therapeutic index (like most anaesthetics) which means it needs to be carefully administered
    • Underdosing will result in patient movement or awakening with possible recall
    • Overdosing can cause hypotension and respiratory depression
    • There is also evidence that excessive anaesthesia is bad for the brain – this applies to all anaesthetics
  • Induction and maintenance of anaesthesia with propofol requires a bolus followed by a variable infusion to maintain an appropriate plasma level of propofol
  • As there is significant interindividual variability in response to anaesthetics, titration is very important
    • Propofol TCI has a marked advantage over other anaesthetics in this regard
    • In adults, the plasma level (Cp) of propofol associated with sedation ranges from 0.5 – 2 mcg/ml and 1.5 – 3.5 mcg/ml for unconsciousness (anaesthesia)
    • Most studies suggest the median dose for anaesthesia is around 2.7 mcg/ml in healthy patients
    • Older and frailer patients may require significantly less
    • Propofol is NOT an analgesic and it is very important to use a powerful analgesic adjunct for surgical anaesthesia (e.g. remifentanil, alfentanil, regional block)
    • You only need to give enough propofol to produce loss of consciousness
    • Analgesia will be provided by your adjunct
    • If you only use propofol to produce surgical anaesthesia, you will require very large (excessive) doses which is not good for the patient
  • Titration is the key to the safe delivery of intravenous anaesthesia

Manual Infusion

  • This is called a time-variant system because the response to the same input varies with time
  • Induction and maintenance of anaesthesia with propofol involves a loading dose followed by a variable infusion which needs to be adjusted according to the depth of anaesthesia required
  • This is difficult, less accurate and less suitable for drugs with a narrow therapeutic range. Therefore, the use of processed EEG monitoring is advised
  • When deepening of anaesthesia is required, a bolus dose with an increase in infusion rate is needed to raise the Cp
  • Bristol manual infusion regime is an example which purports to produce a blood propofol concentration of 3 mcg/ml
    • 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

Target controlled infusion (TCI)

  • Computers and high-precision “smart” pumps have facilitated the development of target-controlled infusions (TCI) and these are readily available in most countries – except the USA! (Prof G Kenny says NIH = Not Invented Here)
  • Complex pharmacokinetic models with multiple covariates are used. These represent diverse patient populations and incorporate features such as effect-site modelling to describe the time course of the pharmacodynamic effect in the brain
  • These devices are similar in concept to using a vaporiser with inhalational drugs
    • You select a blood concentration in the same way as you would choose a vapour %
  • They are time-invariant as the response to a change of target will be the same irrespective of the time at which the target is changed
  • TCI systems are pre-programmed with pharmacokinetic data for a patient population
  • The system determines the dose required to achieve and maintain a given blood or effect-site concentration based on a 3 compartment model, and will continuously adjust this
  • The anaesthetist can then focus on the expected effect of the drug and the timing of the effect rather than the complex calculations required to produce it
  • They are more accurate, less labour intensive and more intuitive and simple to use
  • Recent models, such as the Eleveld, incorporate allometric scaling where adjustments are made for patient height, weight, sex and age

Developing TCI models

  • Both non-population and population-based approaches can be used

Two-stage approach (traditional non-population methods)

  • Small numbers of subjects intensively studied
  • Sequential sample collection following bolus or infusion and the data is then used to construct a poly-exponential curve fitted to drug concentration vs. time
  • Derived parameters from a group of subjects are averaged to create simple estimates of mean parameter values in that population
  • TCI systems work the reverse way by using the PK model to calculate a drug dose
  • Propofol models
    • Marsh
    • Schnider
    • Eleveld
    • Paedfusor
    • Kataria
  • Remifentanil model
    • Minto
  • Alfentanil
    • Scott
    • Maitre

Population pharmacokinetic methods

  • These are based on a larger number of subjects
  • Separately estimates fixed and random components
  • Data is analysed as a population but patient individual identity is retained
  • Parameters can be incorporated that influence PK, e.g. weight, age, sex
  • The Eleveld Model is the latest example and has received favourable reviews

Open TCI systems

  • TCI was initially restricted to proprietary drug preparations and pumps e.g. Diprifusor but these are rarely used now.
  • Open TCI systems are smart pumps incorporating drug libraries with a choice of PK infusion models and a choice of drugs
  • These systems allow non-tagged syringes containing generic drugs to be used
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Introduction to Using Total Intravenous Anaesthesia (TIVA)

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