TIVA IN 21ST CENTURY

Dr. Mrs. Minnu M. PanditraoConsultant

Dept. Anesthesiology & ICU

Rand memeorial HospitalFreeport, Bahamas

DEFINITION:It is a form of balanced anaesthesia where the anaesthetic state is achieved with the help of intravenous administration of a combination of hypnotic & analgesic drugs without the use of inhalational anaesthetic agents including N2O

HISTORY:

Christopher Wren 1657 Alexander Wood 1853 Pierre Cyprien Ore 1874 (Chloral Hydrate) Drs. Waters & Lundy 1934 (Thiopentane) Dr. Stoelting 1957 (Methiohexital)

HISTORY:

Ketamine 1959 Propanidid, Althesin, Etomidate, Diazepam (In 1960-80) Propofol & Newer Opioids 1980s

INTRODUCTION: Volatile Inhalational Agents & N2O avoided

PROBLEMS: IN THE PAST

- Unavailability of satisfactory drugs

- Inadequate methods of administration

Nowadays these problems have been solved.

BENEFITS OF TIVA:

1. Rapid & Smooth Induction2. Better Control of Depth3. Decreased Awareness4. Fast Recovery5. Reduced Nausea Vomiting6. Reduced Stress Response7. No Organ Toxicity

8. N2O Side Effects Avoided

BENEFITS (contd.):

9. Better for Neurosurgery

10.Higher conc. of O2 possible11. Better for Airway Endoscopies12.For Transits of Remote Locations Better13.During CPB (Cardiac Surgery)14.No atmospheric pollution, No

environmental damage15.For prevention of MH in susceptible cases

DISADVANTAGES OF TIVA

1. Once IV drug given, can’t be retrieved

2. Phlebitis, Venous Irritation

3. High Cost

4. Infection in Propofol

5. Special Equipment is required

Can Be Administered By:

1. Intermittent Boluses

2. Continuous Infusion

Advantages of Infusion

1. Oscillations in Drug conc. Avoided

2. Overdosing & Underdosing Avoided

3. Provides stable depth of anaesthesia

4. Side Effects reduced

5. Recovery time reduced

6. Total Drug requirements decreased

(by 25-30%)

Disadvantages:

1. More Expensive & Complicated Equipment

2. Difficult to Use

RECENT ADVANCES:

TCIS (Target Controlled Infusion Systems)

- DiprifusorTIVA with Closed Loop Control of

Anaesthesia with

- AEPI

- BISCLAN (Closed Loop Anaesthesia)

INDUCTION OF TIVA:

Factors Influencing the Dose:KeO--Rate constant, is proportional to onset

of actionConcentration Gradient between the blood &

the effect site, is inversely proportional to onset of action

CLINICAL SIGNIFICANCE

Propofol & Thiopentone because of their large KeO are better for induction

Induction doses vary depending upon pharmacokinetic & pharmacodynamic factors

Addition of 2 inhalational agents is simply additive but of IV agents is synergistic

Synergism helps it providing adequate depth for stronger stimuli

CLINICAL SIGNIFICANCE (contd.)

Decreased dose requirement provides more haemodynamic stability

However synergism for side-effects (respiratory depression) should be kept in mind

INDUCTION WITH INDIVIDUAL/COMBINATION OF DRUGS

1. Propofol: Induction dose is 1-2.5 mg/kg.Blood conc. reqd. is 2.5-5.5 μg/mlOnset of action is <60 sec.Time to peak effect is 90 sec.Duration of hypnosis is 5-10 min.Premedication with Opioids reduces the Induction Dose

2. Propofol with Opioids:

Effect is Synergistic

Reduced dosage required

3. Ketamine:

As a supplement to Propofol– Effect is additive

Ketamine+Benzodiazepines+Opioids have also been used

MAINTENANCE WITH TIVA

Factors controlling the dosage:Intensity of Surgical stimulationClinical signs of depth of anaesthesia

CLINICAL SIGNIFICANCE

Adjust the dose depending upon the response to Surgical stimulus

Higher dose required during Laryngoscopy & Intubation

Lower dose requirement during scrubbing, prep & draping

Requirement of max. conc.(2xCP50) at the time of skin incision

CLINICAL SIGNIFICANCE (contd.)Patients movement, haemodynamics &/or

autonomic responses indicate inadequate anaesthesia

Other indicators like BIS, AEPI, Train of 4 have been tried with variable success

If no response for 10-15 min., decrease infusion rate by 20%

Once patient starts responding, administer a bolus & set the new infusion rate midway between previous & present new rate

CLINICAL SIGNIFICANCE (contd.)

Potent Opioid should be given for adequate analgesia

Continuous titration of hypnotic must be done & concept of CSHT kept in mind

Net requirement of dose depends not only upon pharmacokinetics but also on pharmacodynamic variables

MAINTENANCE WITH INDIVIDUAL/COMBINATION OF DRUGS1. Propofol:

Should be used along with an analgesicA manual infusion scheme is

Loading dose 1-2mg/kg, followed by 10 mg/kg-hr for 10 min., followed by8 mg/kg-hr for next 10 min. &6 mg/kg-hr thereafter

This provides a blood Propofol conc. of 3.7 μg/ml within 2 min.

Propofol

Induction of GA: 1-1.2 mg/kg IV, dose decreased in patients >50yrsMaintenance of GA: 80-150 Μg/kg-min. IV with Opioids, dose decreased in patients >50 yrsSedation: 10-50 μg/kg-min. IV infusion

Other agents used are Opioids, Benzodiazepines & KetamineOnly Ketamine can be used as a sole agentIts disadvantages being long recovery time & emergence phenomena

Recommended Ketamine infusion regimen is:

0.5-1 mg/kg IV, as required, with 50% N2O in O2

10-15 μg/kg-min., with 50% N2O in O2

30-90 Μg/kg-min., without N2O

Recommended Opioid infusion regimen for maintenance of anaesthesia along with a hypnotic are

Drug Target plasma Conc. (ng/ml)

Bolus μg/kg

Infusion rate

μg/kg/minFentanylAlfentanilSufentanilRemifentanil

1400.53

3200.51

0.0200.2

0.010.1

RECOVERY FROM TIVA

Recovery is due to redistribution & not due to elimination

Decline in plasma conc. is due to distribution from central to peripheral comp. & elimination

Distribution & elimination depends upon eqbm. between central & peripheral comp.

CONTEXT SENSITIVE HALF TIME (CSHT)

It is the time taken for plasma conc. to decline by 50% after infusion of different duration designed to maintain a constant plasma conc.

This concept takes into consideration

- Elimination &

- Distribution

CSHT increases with the increase in duration of infusion

CLINICAL SIGNIFICANCEDrugs that are metabolised & eliminated rapidly

have short CSHT which is not affected by longer periods of infusion

Recovery time for a drug varies depending upon its duration of infusion & desired %age decline required for recovery

Time to recovery depends upon the difference between the maintenance conc. & threshold conc. (%age decline) required for recovery. This %age decline may vary from 20%(with Opioid+Hypnotic) to 80%(when only hypnotic is used

RECOVERY CHARACTERISTICS OF INDIVIDUAL AGENTS

1. Propofol:- Avg. Propofol blood conc. for:

awakening is 1.6 μg/mlorientation is 1.2 μg/ml

- CHST for Propofolafter 3 hrs is 25 min.after 8 hrs is 40 min.

The required %age decrease in Propofol conc. for awakening is <50% so recovery will remain rapid even after prolonged infusions. When combined with Opioids recovery time is even shorter(9-12 min. with Fentanyl)

2. Opioids:

CSHT for Fentanyl, Sufentanil & Alfentanil are:

after 1 hr infusion-20% ↓ in 15-20 min.

after 4 hr infusion-20% ↓ for Sufent & Alfent takes half as long as for

Fentanyl

after 10 hrs infusion-20% ↓ for Fentanyl is 45 min & for Sufent & Alfent is ¼ of that

With Remifentanil as it has shortest CSHT, most patients recover within 3-

5 min. after stopping its infusion

SUMMARY

TIVA in 21st Century has come a long wayPropofol (1986) First syringe driver by OhmedaDiprifusor chip softwareTCI & CLAN