Objectives

This resource is designed to be a practical aid to guide the use of TIVA in clinical practice.
TIVA should be delivered via a Target Controlled Infusion (TCI) using a pharmacological model. Anaesthetist selects drug and pharmacokinetic model, then inputs patient characteristics, and target ‘plasma’ or ‘brain’ (effect-site) concentration. The pump then determines the initial bolus and infusion rate.

Scope

Commonly Used Models

Marsh model: Propofol 1% targeting plasma concentration (Cp)

  • Smaller bolus dose but overall larger mass of drug administered

  • With plasma targeting there is a lag time before for effect site concentration (Ce)

    to equilibrate, therefore lag in induction/changing depth of anaesthesia

  • Calculates plasma concentration and volume of all compartments based on

    weight only (need to programme the pump with age but this is not used in the

    calculations) CAUTIONS:

  • Limit for weight (150kg)

  • There is a lag time between Cp and Ce

  • Will only be programmed if patient over 16

 

Schnider model: Propofol 1% targeting effect site (Ce)

      • “Over-pressures” blood concentration to produce gradient that results in faster

        rise in effect-site level. This mimics an IV induction.

      • Requires gender, age, height, and total body weight for programming. Pump

        calculates lean body mass and calculates doses and infusion rates accordingly

      • Larger bolus dose used than the Marsh model but overall lower mass of drug

        delivered (may be beneficial in haemodynamically compromised patients or

        frail)

      • Suitable in the elderly who have a lower lean body mass CAUTIONS:

• BMI limit of < 35 kg.m-2 for females or < 42 kg.m-2 for males. For patients over

this, consider using maximum allowable weight for patient’s height

Suggested doses

Suggested Doses

There is no plasma or effect-site concentration that is appropriate for all patients and clinical correlation of the individual patient’s response is recommended during induction and maintenance of anaesthesia
Note: up to 30% higher/lower doses may be needed based on individual variation/surgical factors.

Clinical circumstances

Suggested effect site concentration

Notes

Rapid Induction of anaesthesia 4 – 6 μg.ml-1Beware of hypotension; may need higher concentrations in young unpremedicated patients
Slower induction of anaesthesia1 - 3 μg.ml-1Repeated 0.5– 1.0 μg.ml-1 incremental increases in the target concentration
Maintenance of anaesthesia3 – 6 μg.ml-1 May need to be higher if surgery very stimulating
Maintenance of anaesthesia with concurrent opioid use2.5 – 4 μg.ml-1

Dose reduction due to synergistic interaction of drugs, dose reduction of propofol requirements by approx 50%

Rapid sequence inductionHigh

Titrate down following LOC

Concentration on waking

1 - 2 μg.ml-1

Can be variable, use Ce on induction as a guide only

Remifentanil concentration when used with propofol2 – 6 ng.ml-1

Equivalent to manual infusion rates of

-approximately of 0.08–0.25 μg.kg-1 .min1-1

​

Induction of anaesthesia

2 methods:

1)  If a relatively rapid induction of anaesthesia is required, initial plasma (Marsh model) or effect-site (Schnider model) propofol target concentrations increased rapidly

2)  “Low to high induction technique”: A slower induction of anaesthesia may be achieved by setting a lower initial target propofol concentration and making repeated incremental increases in the target concentration

On induction:
• Note the effect site concentration when there is a loss of response to speech, and a loss of movement in

response to noxious stimuli (NMBD given after this point). Loss of response to noxious stimuli can be used as a guide to approximate concentration for maintenance of anaesthesia

Maintenance of anaesthesia

  • At knife to skin: particular attention should be paid to ensure adequate depth of anaesthesia using clinical parameters

  • The effect site/plasma concentration of propofol should be titrated to clinical effect

  • Stimulating surgery may need increased propofol Ce/Cp

At the end of a case

  • Towards the end of the case, as the intensity of surgical stimulus reduces, the target concentration can be gradually reduced

  • Do not decrease effect site concentration of propofol <2 μg.ml-1 until end of procedure

  • Infusion can usually be stopped when dressings are being applied

  • When stopping remifentanil, ensure longer acting opioid is given

  • Flush cannula to ensure dead space does not have residual drug in it

Safety checklist prior to starting any TIVA Case

  • Ensure PK pump available and is/are charged/plugged into mains

  • Use correct giving set with a Luer-lock connector at each end, an antisyphon valve on the drug delivery

    line(s) and an anti-reflux valve on any fluid administration line, and minimal dead space distal to the point of

    agent and/or i.v. fluid mixing (see diagram)

  • Ensure IV access is visible and well secured

  • Always set up with IV fluids

  • Set up EEG monitoring/BIS if being used (advised if patient is paralysed)

  • Place syringe containing drug to be infused in the pump with correct syringe type and size

  • Ensure correct low and high infusion pressure alarms set

  • Programme the pump: Select the drug (ensuring correct drug dilutions), patient details, and pharmacokinetic

    model to be used

  • Any patient considerations to make? What is the plan if the pump fails?

Troubleshooting and special considerations

1) Pump failure/loss of IV access: 3 options

Option 1: Default to volatile based anaesthetic – this is the safest option providing no absolute contraindication to volatile use. Do not delay this if problem not immediately solvable.

If there is an absolute contraindication to volatile, consider:

Option 2: Re-start pump in manual mode using mls/hr. If steady state was reached, and the mls/hr being delivered was recorded at a given target concentration, this may be used as an estimate (usually between 30 and 50mls/hr).

−1 −1 The Bristol model guideline may also be used: 10 mg.kg .hr−1

Option 3: Restart pump in TCI mode. This is not a safe option as device will be naïve to the drug already present at the effect-site.

2) How to deepen anaesthesia quickly

• Anticipate when deep plane of anaesthesia may be needed, e.g. knife to skin, increase the target concentration rapidly to over pressure, followed by down titration.

3)  Switching from volatile anaesthetic to TIVA

• Key is to avoid awareness as volatile concentration falls and propofol concentration rises. Increase propofol Cp/Ce incrementally as end tidal volatile concentration falls and observe clinical parameters

4) Obese patients

  • Schnider model only accepts a BMI <35kg.m-2 for females or <42kg.m-2 for males. Marsh model will accept higher weight (up to 150kg)

  • Both models should be used with caution in obese patients (may get a relative overdose of propofol as actual body weight used for calculations, where central compartment is a lot smaller than peripheral compartments)

  • For obese patients, consider using formula ‘actual body weight – 20%’ for more accurate compartment calculation

5) Older patients/ASA 3 – 5/haemodynamically compromised patients

• Recommended to use incremental increases in target concentration to avoid over use. 6) Paediatrics

  • Works on predicted plasma concentration (Cp).

  • Paedfusor model: Uses age and weight as covariates; can be used between 5 and 61 kg, and 1–16 yr of age.

  • Kataria can be used from 3 to 16 yr of age and works with a minimum weight of 15 kg

  • Teenage children weighing >61kg can be managed using the Marsh model

References

1) Guidelines for the safe practice of total intravenous anaesthesia (TIVA) (2018)
Joint Guidelines from the Association of Anaesthetists and the Society for IntravenousAnaesthesiahttps://www.aagbi.org/sites/default/files/total%20intravenous%20guideline_0.pdf

2)  The Society for Intravenous Anaesthesia https://siva.ac.uk/

3)  Principles of total intravenous anaesthesia: basic pharmacokinetics and model descriptions. Al-Rifai, Z et al.

BJA Education , Volume 16 , Issue 3 , 92 – 97

4)  Principles of total intravenous anaesthesia: practical aspects of using total intravenous anaesthesia. Al-Rifai, Z

et al. BJA Education , Volume 16 , Issue 8 , 276 – 280

  1. 5)  For use of TIVA in Paediatrics:

https://www.wfsahq.org/components/com_virtual_library/media/0e97e5586360871fc0a53c2f51c157ec- atow-392-00-01.pdf