(a) Describe the pharmacokinetic theory of a three compartment model in drug delivery.
Pharmacokinetic behaviour of many drugs can be described by three compartment model
Doesn’t describe anatomical boundaries or organs – it’s a theoretical construct
Drug enters central compartment (C1)
From here it is redistributed to peripheral compartments (C2, C3)
Simultaneously drug is eliminated via metabolism and excretion from central compartment
If theoretical volumes of the compartments are known and rates of movement then the drug concentration in the central compartment can be determined
(b) How does this correspond to the delivery of total intravenous anaesthesia (TIVA)?
Using three compartment model, the ‘BET’- (bolus, elimination, transfer) scheme was developed.
This dictated that to achieve TIVA three components are required
a bolus dose to fill the central compartment
constant final infusion rate- maintaining central compartment concentration by matching the elimination of a drug once redistribution is complete and drug concentrations in peripheral and central compartments are equal
an interim infusion rate- maintaining central compartment concentration by matching rates of transfer of the drug from central to peripheral compartments
(c) What is meant by the term “effect-site TCI”?
For many drugs central compartment is not their site of action.eg. Hypnotics act on the brain and it is the concentration at this ‘effect site’ not the plasma concentration that is responsible for anaesthetic effect.
Addition of the fourth effect site compartment to the three compartment model along with a rate constant for movement of drug into and out of the compartment allows the expected time course of a clinical effect to be modelled.
(d) What are the proposed benefits of TIVA over inhalational anaesthetic agents?
Reduced incidence of PONV
Reduced atmospheric pollution
Easily titrated anaesthetic with TCI
Safe in MH
Preservation of HPPV
Reduction in intracerebral pressure
Little evidence of organ toxicity
Separates provision of anaesthesia from ventilation- useful in shared airway cases
(e) What are the suggested disadvantages of TIVA?
Potential for equipment failure
Risk of awareness as no guiding figure like MAC
No monitoring of depth of anaesthesia
Risk of disconnection/venflon tissuing and anaesthetic is not delivered
Potential slow wake up
Frequent changes of syringes
(f) Describe the suitability of remifentanil as an agent or co-agent in TIVA.
Remifentanil is a mu receptor agonist, metabolised by non-specific esterases.
Metabolism is not affected by genetics, age or liver/renal failure
The context sensitive half-life is 3-5 mins and this makes it an ideal agent for infusion as onset and offset times are rapid regardless of the length of infusion.
Like other opioids synergism is shown between remifentanil and propofol.
Provides excellent intra-operative analgesia but post-operative hyperanalgesia has been demonstrated, therefore it is important that alternative analgesia is established before stopping remifentanil and wakening the patient.
Large boluses may cause chest wall rigidity