By James Waterson, RN, M.Med.Ed. MHE. Becton Dickinson. Medical Affairs Manager, Middle East & Africa
In simple terms Target-Controlled Infusion (TCI) means that instead of setting a dose-rate on the pump, the pump is programmed to target a required plasma concentration or effect-site concentration. A TCI pump automatically calculates how much drug is needed during induction and maintenance to maintain the desired effect-site or plasma concentration.
A TCI algorithm (the ‘target’ and plan on which the pump relies to deliver appropriate induction and maintenance rates to maintain anaesthesia without overdosing the patient) is based on pharmacokinetic (PK) and pharmodynamic (PD) models and on Absorption, Distribution, Metabolism, and Excretion of medications by the body.
For example, the effect-site concentration of Propofol required to produce loss of consciousness is about 3 to 6 mcg/ml, depending on the patients’ demographics. Patients waking from anaesthesia generally have a blood concentration of around
1- 2 mcg/ml, although this is dependent on other drugs given during anaesthesia.
Adequate analgesia with Remifentanil is generally achieved with 3-6 ng/ml. A Remifentanil infusion of 0.25-0.5 mcg/kg/ min in an ‘average’ man – 70 kg, 170 cm, 40 years old – produces a blood concentration of around 6ng/ml after 25 minutes.
PK models are based on body compartments
Conventionally the body compartment that the drug is injected into is V1 (plasma/blood), the next compartment is the ‘vessel-rich’ or ‘fast re-distribution’ compartment and is characterized as V2 (heart, liver, etc.). The final compartment, which is anatomically ‘vessel-poor’ and ‘slow’ in terms of re-distribution, is V3 (fatty tissue).
Drug distribution and the metabolism/ elimination of each drug in each compartment is also part of each TCI model, as is the pharmacodynamics of the time taken between the plasma and effect-site effect.
Computer simulations and mathematical modelling of infusion schemes based on the above theories of compartments and clear- ances give models for both Target Plasma Concentration (Cpt) and Target Effect Concentration (Cet) and these can be incorporated into specialist infusion pumps.
The Marsh model for Propofol requires only age and weight to be programmed in the pump. The Schnider model is an alternative model for Propofol and has advantages in elderly patients as it is based on a lean body mass (LBM) calculation for each patient. Elderly patients receive a lower induction and maintenance dose, which can assist with hemodynamic stability.
The Remifentanil Minto model uses age, height, gender and weight, and determines LBM for its calculations.
TCI pumps deliver the infusion at a constantly altering rate, but it is useful to think of this one infusion as being a mean average of three continually calculated infusion rates: a constant rate to replace drug elimination and two exponentially decreasing infusions to match drug removed from central compartments to other peripheral compartments of distribution.
Key features of an ideal TCI infusion system or pump are:
- Critical information such as decrement time, current Cet or Cpt and respective targets, current dose rate and concentration and type of agent being infused can be displayed at the same time on one screen.
- Patient parameters used during the setting-up of infusions appear on one screen to avoid the need for shuttling through multiple screens to check vital information.
- An Induction Time adjustable from seconds to minutes to allow for a gentle induction for patients with cardiovascular conditions or established hypotension.
Obese patients have previously presented a problem for ‘classic’ TCI, and the physiological differences between paediatrics and adults had required separate models for children.
Now, however, we have the Eleveld model for both Propofol and Remifentanil, and the Kim-Obara-Egan Remifentanil model which are much more universal and can potentially allow TCI in age ranges from 6 months to 99 years of age, and from
2.5 to 215 kg.
TCI, with its emphasis on evidence-based anaesthesia, and new near universal patient models seems primed to change our approach to the management of all patients receiving sedatives and analgesic agents.