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Dr. Savas Totonidis

Course : 6 Year : 2009 Language : English Country : Nepal City : Kathmandu Weight : 557 kb Related text : No

Basic Pharmacokinetics Yes I know this is very boring.

Please Mummy, Make Him Stop!!

Compartment Modelling

One Compartment Model Loading Dose


x Target Level

V1 (Plasma)


Maintenance Infusion

Concentration x Clearance

3 Compartment Model

So what happens when we give a single bolus dose of a drug?

TIVA - Aims

1. BOLUS Dose to reach initial target and induce patient: 2. Maintenance Infusion to keep patient asleep by replacing:

of drug Redistribution of drug

What Determines Offset Time of a Drug Infusion?

Elimination Half Life and Clearance values of a drug are not useful in helping to determine the offset of effect of a drug infusion.

Context Sensitive Half Time (Hughes et al 1992 ) is more important:

Context Sensitive refers to length of infusion. The drugs we want for TIVA ideally would be context INSENSITIVE.

CSHT - Hypnotics


CSHT - Opioids



Ketamine/Midazolam TIVA combination has been shown to be very effective


et al 2003 , European Academy of Anaesthesiology


TIVA equivalent to Halothane/N20 anaesthesia in intraoperative stability and postoperative recovery profile

PROPOFOL Manual Infusion

The ONLY way to do it in the USA as TCI models are not approved for use. ONE RECIPE THAT WORKS The Roberts Method

Bolus 1 mg/kg propofol 2. Start infusion at 10 mg/kg/hr for first 10 minutes 3. Decrease to 8 mg/kg/hr for next 10 minutes 4. Infuse at 6 mg/kg/hr until the end of the case

PROPOFOL Manual Infusion

Is this Accurate?

Accurate Enough Asleep Levels reached quickly

Has been used clinically for years.


PROPOFOL Target Controlled Infusion ( TCI )

A TARGET CONTROLLED infusion is one where the user attempts to achieve a target level of drug in the tissue of interest.

Computer models in pumps allow this to be achieved rapidly and accurately.

Tissue of Interest plasma or effect site.

PROPOFOL - Pharmacokinetic Models

Several models exist: (Marsh, Schnider, Kataria models) Differences between the models include:

Differing values for kinetic and dynamic variables Covariates adjusted for ( age, weight, sex )

All have their advantages and disadvantages. Just pick one model and get to know it well. Marsh model is the most popular.
Entering the patients WEIGHT is the most important variable.

But what about really fat people?

Marsh model gives 180kg patient three times as much propofol as a 60 kg patient Inappropriate. Schnider model uses Lean Body Mass according to height. BUT a 180 kg patient will receive less propofol than a 120 kg patient Inappropriate. So what should I do?


My Suggestion enter weight up to a BMI of 35 for females and 42 for males


Initial Target Level to aim for:

6-8 mcg/ml in healthy patients Decrease in the elderly or unwell Alter as appropriate throughout the case
Current Time

Effect Site Level

Time Until Wake Up

Target Concentrati on Time Scale


The target level ( pharmaco kinetics ) is much less variable between patients than the PHARMACODYNAMIC response to propofol.

Adjust target level according to response of patient.


Ultra short acting opioid. Manual Infusion very popular as plasma levels rise very quickly:

0.25 mcg/kg/min initially Titrate within range 0.03 0.5 mcg/kg/min during case Wears off within 10 minutes regardless of length of infusion

Pharmacodynamic response HIGHLY VARIABLE Hypotension and bradycardia can be a problem. Patients almost always need mechanical ventilation.


Remifentanil TIVA:

Model Adjusts infusion for age, sex, weight, and gender Leads to less variability in response amongst patient groups Start initially at 3 ng/ml Adjust during case to 1- 12 ng/ml

Propofol/Opioid Synergy

Modern Anaesthesia is always a 2 agent technique:

Anaesthesia Analgesia

Very difficult to produce anaesthesia with one drug alone. Propofol COMBINED with opioid has synergistic effects. Combination of the 2 drugs means much less of each drug is needed, leading to fewer side effects. Tailor the ratio of propofol to opioid to the patient

TIVA - Advantages

Decreased Post Operative Nausea and Vomiting Decreased exposure of staff and environment to anaesthetic gases

Patients wake up quicker Anaesthesia can be deepened or lightened quickly

Technique of choice for certain patient groups

TIVA - Disadvantages

Infusion Pumps Propofol/Remifentanil

Lack of suitable drugs Wider variety of clinical response at the same drug levels compared with anaesthetic gases

Unknown Anaesthetic Depth ( possibly increased awareness)


TIVA Useful For Thoracotomies

Decreased Hypoxic Pulmonary Vasoconstriction

TIVA - Useful For Neurosurgery

Anaesthesia can be rapidly deepened or lightened. Haemodynamic Stability. No increase in cerebral blood flow

TIVA Useful For. Jet Ventilation

Anaesthesia provided by TIVA Jet provides oxygen and ventilation.

Excellent for short stimulating procedures.

Much easier than using inhalational agents.

TIVA Useful For

Anaesthesia in the field ( military, trauma, transfers )

Sedation for Fibreoptic Bronchoscopy


TIVA Useful For Threatened Airway

Traditional Teaching Gas Induction Gently increasing TIVA offers a reliable alternative Ensures anaesthesia whilst trying to instrument the airway If obstruction occurs, turning off TIVA leads to faster wake up than inhalational gases. Now widely practised

Practical Aspects of TIVA How to make it work

Practical Aspects - Pumps

Do I really need to use a pump? Probably. The Drug Pump is now an extension of your anaesthetic machine. You must check it just as thoroughly before using:
Is your drug dilution correct? Is the syringe and plunger properly held in the clamp? Are your infusion units correct? Is the weight correct (for calculator pumps)? Has the dead space been taken out of the line? Have the batteries been checked? Has the pump been serviced regularly?

Practical Aspects - Pumps

Practical Aspects One Way Valve


Ensures delivery of drug to the patient and not back up the maintenance fluid.

Practical Aspects Minimise Dead Space

Ensure TIVA entry point is as close to the IV cannula as possible, otherwise changes in maintenance fluid rates can affect infused drug dose.

Even better is a dedicated TIVA set, where the entry point is at the cannula.

Practical Aspects Check IV Cannula

Keep IV cannula visible at all times if possible

Practical Aspects Drugs and Syringes

Always use the same concentration of drugs and the same syringe sizes.

This will minimise errors when calculating infusion rates.

Practical Aspects Should I use Nitrous Oxide?


Patient need less intravenous anaesthesia, with fewer side effects Provides analgesia Cheaper Some anaesthesia is being delivered even if IV cannula fails


Patients may feel sick Inappropriate for some surgery

My Recommendation:

Use N2O with TIVA when you are getting familiar with the technique

Practical Aspects - Should I paralyse the patient?

You cannot measure the patients plasma drug levels By paralysing the patient you take away one more sign of awareness I always use a BIS monitor If you dont have one, avoid paralysis if possible.

Take Home Messages

Some drugs are good for TIVA:

Propofol, ketamine, remifentanil

Some drugs are bad for TIVA:

Thiopentone, fentanyl

Combination of hypnotic + opioid means you have to give much less of each. Manual infusions are good, TCI models are better but not a lot better.
Even the best models are only accurate to +/- 20%

Take Home Messages

Even if you KNOW the plasma level of the drug, you cannot predict the patients RESPONSE. Some patients need more, some patients need less Easy TIVA = TIVA + Nitrous Oxide Much more important than knowing the intricacies of the pharmacokinetics and models is:

Be paranoid about your pump, IV cannula, dead space, one way valve, and syringes. Start at low dose and increase to desired effect USE YOUR CLINICAL JUDGEMENT