total intravenous anaesthesia cme presentation

total intravenous anaesthesia presentation cme topic

1. TIVA By: Nabilah Athirah binti Mohd Sazali Supervisor: Dr Lakshmi

2. TERMINOLOGY IN PK Volume of distribution: the apparent volume in which the drug is distributed. Vd = dose/ concentration of the drug Clearance: represent the volume of plasma from which the drug is eliminated per unit time to account for its elimination from the body Context sensitive half time: Time required for blood or plasma concentration of a drug to decrease by 50% after the discontinuation of drug administration The elimination half-life is the amount of time required for 50% of the drug to be removed from the blood during the terminal elimination phase. 

3. INTRODUCTION Technique of general anaesthesia using a combination of agents given solely by the intravenous route and in the absence of all inhalational agents including nitrous oxide. Poor understanding of the pharmacokinetics TIVA practice has contribute to accidental anaesthetic awareness There is no defined ‘ideal’ TIVA technique, but coadministration of propofol and remifentanil approach this goal Advantages: reduced incidence of post-operative nausea and vomiting, reduced atmospheric pollution, more predictable and rapid recovery, greater haemodynamic stability, preservation of hypoxic pulmonary vasoconstriction, reduction in intracerebral pressure and reduced risk of organ toxicity.

4. WHEN TO CONSIDER tiva

5. INDICATION OF TIVA

6. ADVANTAGES VS DISADVANTES advantages disadvantages faster/ cleaner recovery - disconnected IV access  awareness Less PONV - extra equipment/ training/ setup Less contamination from greenhouse gases - recovery can be slow in long operation No risk of malignant hyperthermia - All concentrations whether it be plasma or effect site are estimates made by the pump programme

7. CHOICE OF DRUGS Fast onset & offset time (recovery ) What are those drugs?? And why?? Propofol Why??? Large volume of distribution High clearence

8. Fentanyl Remifentanil Sulfentanil Alfentanil Rapid onset  greater lipid solubiity Shorter duration of action  rapid redistribution BUT Why not suitable for TIVA???  Vd ?? Elimination Effect site equilibration: 6.8 min The longer duration of infusion  longer CSHT Potency: similar to fentanyl *ester linkage  render brief action & lack of accumulation Small Vd , rapid clearance & rapid metabolism  less accumulation then other opioids  CSHT independent of infusion duration Rapid effect site equilibration ( 1.1 min) Potency: 5 – 10 x > fentanyl High lipid solubility Larger Vd > alfentanil CSHT < alfentanil after continuous infusion up to 8H However, slow redistribution  terminal half life is prolonged 15 -20H Alfentanil is analogue of fentanyl More rapid onset > fentanyl/ sulfentanil Duration of action: of fentanyl Elimination Vd ?? Rapid effect site equilibration (1.4 min) Fentanyl Remifentanil Sulfentanil Alfentanil Potency: similar to fentanyl *ester linkage  render brief action & lack of accumulation Small Vd , rapid clearance & rapid metabolism  less accumulation then other opioids  CSHT independent of infusion duration Rapid effect site equilibration ( 1.1 min) Potency: 5 – 10 x > fentanyl High lipid solubility Larger Vd > alfentanil CSHT < alfentanil after continuous infusion up to 8H However, slow redistribution  terminal half life is prolonged 15 -20H

9. CONTEXT SENSITIVE HALF TIME (CSHT)

10. Why propofol is used in combination with remifentanil? Propofol and remifentanil  synergism

11. THEN, WHAT IS TCI??? TIVA TCI TIVA is Total Intravenous Anaesthetic , no volatile anaesthetic gases such as sevoflurane and desflurane. While it can be given using a TCI pump this is not necessary and it can be given through a simple mls /hour pump or even bolused by hand. TCI or Target Controlled Infusion on the other hand, is giving an intravenous anaesthetic using a specialised microprocessor controlled syringe driver. With a TCI pump the anaesthetist enters the patient’s details, selects the target concentration (plasma or effect-site) and the pump calculates the appropriate infusion rate

12. METHOD OF DELIVERING TIVA Repeated single bolus doses can be used to maintain drug’s effect BUT the plasma concentration will be fluctuating  give rise to peaks and troughs  toxic and subtherapeutic effects Another approach would be to simply run a constant infusion of drug

13. Can we just give normal fixed infusion?? A fixed infusion rate may cause rising, declining or stable concentrations, depending on prior administration rate and duration of infusion, leading to a risk of under- or overdosage  AWARENESS Ex: On starting a propofol infusion at a fixed rate without an initial bolus, concentrations rise very slowly  reach near steady-state conditions after several hours On starting a propofol infusion at a fixed rate without an initial bolus, concentrations rise very slowly and only reach near steady-state conditions after several hours

14. TARGET- CONTROLLED INFUSION TCI: A target controlled infusion is an infusion controlled in such manner as to attempt to achieve a user defined drug concentration in a body compartment of interest or tissue of interest. A TCI pump contains a microprocessor programmed with pharmacokinetic models for relevant drugs. The user selects the drug and pharmacokinetic model to be used by that TCI pump and inputs the patient characteristics (covariates) such as body weight and age, and the target plasma or ‘brain’ (effect-site) concentration, with the pump determining the initial bolus and subsequent infusion rates.

15. Principles of TCI Pharmacokinetics model is a mathematical model that predicts the plasma concentration of a drug after administration by infusion/ bolus The data are derived from measuring plasma concentration measurement after a bolus or infusion in a group of volunteer

16. Principles of TCI

17. Principles of TCI Goal: Achieving a steady plasma concentration as to achieve the desire effect To achieve a steady state, it is necessary to administer:- BOLUS: to fill the central compartment and provide rapid induction of anaesthesia ELIMINATION: is a constant rate infusion to replace the drug lost through elimination from the central compartment. TRANSFER: interim infusion rate maintaining central compartment concentration by matching the rates of transfer of drug from central to peripheral compartment. When the target concentration has been reached the infusion rate decreases Eventually, when the steady state is achieved, the infusion rate will match the clearance of the drug

18. GOAL in TIVA

19. Selection of appropriate pharmacokinetics model

20. Marsh VS Schnider Marsh model Schnider model The use of a weight-proportional pharmacokinetic model, (Marsh model), means that all the volumes and clearances of a multi-compartment model are proportional to only the weight of the patient. doubling of the weight has the same effect on the infusion rates as a doubling of the targeted concentration. estimated plasma concentrations after a given bolus are proportional to the patient's weight use in non-elderly adults who are of a normal body habitus. In the elderly, the Marsh model will typically display a wide variability. Uses age and lean body mass as co-variates it may be a safer model to use when administering propofol to both elderly and overweight patients. Schnider’s model for effect site targeting there is less plasma overshoot and better cardiovascular stability in compromised or elderly patients. will estimate that the same peak plasma concentration is achieved for all patients, irrespective of their age, height, or weight

21. In paeditric age group… The following two paediatric TCI models are commonly used: Paedfusor : suitable for ages 1 to 16 years and weight 5 to 61 kg Kataria : suitable for ages 3 to 16 years and weight 15 to 61 kg paediatric TCI models work on plasma site concentration prediction (Cp) rather than effect site concentration prediction (Ce)

22. PLASMA VS EFFECT-SITE TARGETING Early TCI systems were designed to achieve a user-defined plasma ‘target concentration’. It soon became apparent that there was hysteresis in the relationship between plasma concentration and clinical effect , caused by the temporal delay in equilibration between plasma concentrations and the concentration at the sites of action within the central nervous system rate of plasma/effect-site equilibration depends on factors that determine the rate of drug delivery to the effect-site (such as cardiac output and cerebral blood flow) and pharmacological properties that determine the rate of drug transfer across the blood–brain barrier (lipid solubility, degree of ionization, etc ). The time course of plasma/effect-site equilibration can be mathematically described by a first-order rate constant typically referred to as the k eo .

23. Effect site targeting Principal effect of anaesthetics intravenous agents are sedative & hypnotic The site at which the drug exert these effect is the brain, termed as effect site. Unfortunately, not feasible to measure brain concentration (effect site) TCI system manipulates the plasma concentration to achieve the effect-site concentration as rapidly as possible.

24. TCI system briefly increases the plasma concentration to an optimal level above the target effect-site concentration before temporarily stopping the infusion to allow the plasma concentration to decrease to the level of the target effect-site concentration.

25. How to administer??

26. Dose adjustment during maintanence of TIVA

27. CONSIDERATION IN SPECIAL GROUP Young children have an increased central compartment size and volume of distribution  larger induction bolus doses & higher initial infusion rates  reduced in maintenance Challenge: delayed emergence from anaesthesia immaturity of hepatic enzyme systems also results in slower metabolism  requiring lower maintenance infusion rates For induction: suggest to use lean body weight For maintenance: suggest to use total body weight Smaller central volume of distribution, decreased clearance and increased receptor sensitivity to drug Lose consciousness at a lower blood concentration

28. Remifentanil when used in target controlled infusion: a) Is ideal for use in prolonged infusion due to its short elimination half life. b) Does not offer postoperative analgesia. c) Shows synergism when used in combination with propofol. d) Its pharmacokinetics is not altered by patient age. e) Can be safely used as a sole anaesthetic agent for short surgical procedures.