TOTAL INTRAVENOUS ANESTHESIA

Dr Brijesh Savidhan,Department of Anaesthesiology,Travancore Medical College.

INTRODUCTION Total intravenous anesthesia

Technique of GA

Anesthesia via intravenous agents (propofol, narcotics, muscle relaxants)

In boluses/drips

No volatile agents

DEFINITION Method of inducing and maintaining GA exclusively by IV admd

drugs , without simultaneous admn of any inhalnl agents.

Search for suitable drugs and techniques to meet changing demands of advanced diagnostic and therapeutic modalities requiring alleviation of patient discomfort

Safe anaesthesia with rapid pt turnover as in ambulatory care setting, to maximise no of patients

WHY TIVA?

Anaesthesia in non operative locations where inhalational anaesthetics are difficult

Availability of rapid, short acting, easily titratable analgesic and relaxant drugs

Pharmaco-kinetic and -dynamic based IV delivery systems which are portable Eg.TCI

o Monitors to measure the depth of the hypnotic component of the anaesthetic state Eg.entropy

TIVA EQUIPMENTS

ADVANTAGES

Easy titratability of drugs

Superior recovery profile and early discharge

Portable delivery system

Less operating room pollution

No risk of MH

Less PONV

Preserves HPV

Avoid distention air filled spaces in the patient’s body- so better operating conditions for surgeons

Better hemodynamic control

Improved V/Q matching

Better preservation of cerebral autoregulation

Reduced stress response

SPECIFIC INDICATIONS

Airway procedures

Remote locations

MH susceptible

Neurosurgery

Neuro monitoring

PONV risk

Short procedures-CT,MRI

PHARMACOKINETICS AND TIVA

There are different types of pharmacokinetic models -

1. Compartmental models.

2. Physiological models.

3. Hybrid models.

THREE COMPARTMENT MODEL

do not represent any real anatomical entities.

quantify drug movement mathematically

drug is distributed to different tissues within the body at different rates -declining exponential processes- by drug elimination , drug distribution.

Rate constants - describe the rate of these separate exponential processes

The rate constants describe the rate of movement by the drug between the central compartment and each of the other compartments and also the rate of elimination, usually from the central compartment.

LIMITATIONS inter individual pharmacokinetic variability.

They assume immediate mixing of drug in the compartments and therefore cannot be used to describe lung uptake

In practice, a dose of drug given IV does not equilibrate instantaneously

‘static’ model

does not incorporate -altered protein binding, blood loss, haemodilution, which are aspects of the dynamic state

Physiological models

describes drug uptake in the different tissues and the influence of circulation and recirculation on drug distribution.

adjusts the model to the pathological state of the patient.

require a large set of mostly unknown parameters not expected much use outside the research envt.

Hybrid models compartmental models adjusted to physiological parameters

such as cardiac output

Using pharmacokinetic compartmental modeling , computer programs can simulate profiles of drug distribution and elimination.

different pharmacokinetic profiles can grossly affect drug suitability for use by TIVA.

CONTEXT SENSITIVE HALF TIME The time in which the plasma concentration of the drug reduces by

50% after discontinuing an infusion ; ie in the ‘context’ of a specified duration of infusion.

short CSHT desirable if a drug is to be used for TIVA, as it would infer a quick recovery following anesthesia

The time a pt takes to recover from a drug does not necessarily correlate with a in plasma conc. of 50%- practically CSHT -poor predictor of recovery

The plasma concentration at this point may not be one where recovery expected.

EFFECT SITE EQUILIBRIUM lag time between achieving a specific plasma conc. and

observing a particular clinical response.

mathematical or temporal relationship between the conc. in the plasma and the clinical response observed- time taken to equilibrate described by a rate constant (Keo).

time to equilibrate with the effect site -different for different drugs

physical properties of the drug , receptor binding properties influence the delay between achieving plasma concentrations and observing a response .

effect site decrement time, the time taken for the effect site concentration to decrease by a specified percentage- used to predict recovery.

CLINICAL APPLICATION OF TIVATo achieve and maintain a constant plasma conc. over a period

of time

A bolus dose (B) calculated to fill the central compartment to the required concentration.

A constant-rate infusion to replace drug lost by elimination (E) and

An exponentially decreasing infusion that will replace drug lost from the plasma by transfer or distribution (T) to peripheral tissues.

MANUALLY CONTROLLED INFUSION

Bristol infusion regimen for propofol (‘10-8-6’) based on LBW plasma conc of 3.5 µg/ml- adeq. for body surface surgery

premed -3 µg/kg fentanyl – indn with1.0 mg/kg bolus of propofol infusion of 10 mg/kg/h - 10 minutes , 8 mg/kg/h -10 minutes 6 mg/kg/h.

Recovery after procedures lasting up to 90 minutes -5-10 mins

MANUAL INFUSION SCHEMES

Anesthesia Sedation or Analgesia

DrugLoading Dose (µg/kg)

Maintenance Infusion (µg/kg/min)

Loading Dose (µg/kg)

Maintenance Infusion (µg/kg/min)

Alfentanil 50–150 0.5–3 10–25 0.25–1

Fentanyl 5–15 0.03–0.1 1–3 0.01–0.03

Sufentanil 1–5 0.01–0.05 0.1–0.5 0.005–0.01

Remifentanil 0.5–1.0 0.1–0.4 † 0.025–0.1

Ketamine 1500–2500 25–75 500–1000 10–20

Propofol 1000–2000 50–150 250–1000 10–50

Midazolam 50–150 0.25–1.5 25–100 0.25–1

Methohexital 1500–2500 50–150 250–1000 10–50

TARGET CONTROLLED INFUSION

Computer driven infusion device used to achieve a pre-set target plasma concentration of drug

For predictability of drug effect, a specific PK model and control algorithm devpd eg: Diprifusor.

Has dual microprocessor component incorporated into an infusion pump enables to deliver propofol in TCI mode.

Pt body wt, target conc. entered. Visual display- calculated conc. for plasma and

effect compartment, and actual infusion rate.

Total dose infused recorded

Target level selected for induction - adjusted in response to clinical signs -maintain adeq. anesthetic depth.

no need for a bolus induction -initial plasma conc. set

Depth of anesthesia - changed rapidly selecting a new target blood concentration, similar to adjusting a vapouriser during volatile anesthesia.

microprocessor makes relvnt calculns of bolus increment or alterns in the infusion rate to achieve, maintain and alter the blood concentration to any target level.

PUMPS Safe and continuous admn of IV anesthetics - reliable

delivery system, vigilant anesthetist

A simple gravity intravenous infusion can be “piggy-backed” to a carrier line

Pump offers the adv. of more precise dose selection, lower risk of overdose, minimal flow variation from changes in venous pressure or bag height

TYPE OF PUMPS Syringe Pumps:

Use a driver that pushes fluid out of a syringe by advancing its plunger while the barrel is kept stationary.

Small units, light weight, cordless, accurate at very low flow rates. May have program library

Volumetric Pumps:

Use a disposable cassette within IV system that controls rate by a variety of methods

Larger size, added cost of cassette tubing, more susceptible to air bubbles

IDEAL PROPERTIES OF DRUGS USED IN TIVA

Water-soluble to minimize toxicity associated with the solvent

Stable in solution

No perivascular sloughing if extravasated

Given in conc. soln to avoid fluid overloading

Not absorbed by plastics

Does not promote bacterial growth

Rapid onset of action

rapid and predictable recovery

Devoid of adverse side effects

Potent and lipid-soluble

Relatively cheap

Chemically compatible with other drugs.

DRUGS USED IN TIVA Individually or in combination, depending upon the Patient and

Procedure:

Hypnotics Propofol, Ketamine, Benzodiazepines, Etomidate, Barbiturates

Analgesics fentanyl, Remifentanyl, sufentanil, alfentanil,

Muscle relaxants Atracurium, Vecuronium

HYPNOTICS Propofol- most commonly used hypnotic for TIVA No active metabolites

Short CSHT(8 minutes)

Rapid onset

Antiemetic

Not an MH trigger

CBF: Autoregulation and CO2 responsiveness not affected.

Proportional Reduction in CMRO2 and CBF, decrease in ICP

Free radical scavenging-prevention of free radical induced lipid peroxidation

Membrane stabilisation

Anticonvulsant

Induction dose is 0.5 to 1.5mg/kg for loss of consciousness with a maintenance infusion of 80 to 120 µg/kg/min

DISADVANTAGES Propofol related infusion syndrome -Metabolic acidosis, cardiac dysfunction, rhabdomyolysis,

hypertriglyceridemia

Myoclonic phenomenon-imbalance between excitatory and inhibitory phenomena

Pain on injection

Allergic reactions

Bacterial growth

Etomidate – maintains a good cardiopulmonary function and has been used in tiva.

Initial i.v dose 1-2 mg/kg Maintainence 0.02-0.3 mg/kg/min

infusion may be terminated 10 to 15 minutes before the anticipated end of the surgical procedure.

DISADVANTAGES It suppresses the production of cortisol.

High concentration of propylene glycol in etomidate preparation causes hemolysis resulting in hemoglobinuria

Expensive

Ketamine - Ketamine has been successfully used with propofol for TIVA technique.

Loading dose 1 to 3 mg/kg Infusion dose 5 to 20 µg/kg/min

Disadvantage: seizure activity and hypertonus during recovery may occur

Midazolam - Midazolam-opioid combinations can also provide complete anesthesia

Initial i.v bolus 0.2 mg/kg IV Maintainence 8.0 g/kg/min

TIVA for major (cardiac) and/or long operations may be effectively achieved with the combination of midazolam and sufentanil

ANALGESICS

Most commonly used are fentanyl, alfentanil with propofol

Fentanyl Phenylpiperidine derivative synthetic opioid agonist

Analgesia-75-125 times more potent than morphine

Rapid onset

Short duration of action

Highly lipid soluble

Highly protein bound

Minimal pharmacological activity of fentanyl metabolites

Short CHST

Stable hemodynamics

PROPOFOL AND REMIFENTANIL Ideal combination for TIVA. Remifentanil is a very short acting opioid with a

CSHT that varies very little regardless of infusion duration.

undergoes rapid ester hydrolysis with a clearance in excess of 3L/min.

reduced plasma concentration of propofol required for adequate anaesthesia by 50%.

Typical manually controlled remifentanil infusion rate are:

1-2 µg/kg/min for induction

0.1-1.0 µg/kg/min for maintenance, adjusted according to surgical stimulation.

TCI remifentanil target levels are 4-10 ng/L depending on the nature of surgery.

Offset of action is rapid and constant - constant and short CSHT of 3.5 minutes.

remifentanil can be continued till the end of surgery, after propofol has been discontd.

Provision of post operative analgesia essential because the analgesic effects of remifentanil disappears soon after discontinuing the infusion

PROPOFOL AND FENTANYL Most commonly used

When given as an IV bolus injection, effective in 4-7 minutes

Short CSHT of fentanyl makes it possible to continue the opioid infusion even after propofol infusion has been stopped (5-10 minutes before surgery ends

Ensure adequate anesthesia and rapid awakening

Fentanyl Loading dose : 4 - 20 ug/kg , Maintenance dose: 2 - 10 ug/kg/hr Propofol Loading dose: 0.5 – 1.5 mg/kg Maintenance dose: 80- 120 ug/kg/min

DOSES OF OPIOIDS FOR TIVA

Loading Dose (µg/kg)

Maintenance Infusion Rate

Additional Boluses

Alfentanil 25–100 0.5–2 µg/kg/min 5–10 µg/kg

Sufentanil 0.25–2 0.5–1.5 µg/kg/hr 2.5–10 µg

Fentanyl 4–20 2–10 µg/kg/hr 25–100 µg

Remifentanil 1–2 0.1–1.0 µg/kg/min 0.1–1.0 µg/kg

PHARMACOKINETICS AND DRUG SELECTION Anesthesia can be maintained either with intravenous infusions

of drug or with intermittent boluses.

Infusions are preferred because- Greater hemodynamic stability

More stable depth of anaesthesia

More predictable and rapid recovery

Potential lower total dose of drug used (25%-30%)

less respiratory depression

Avoid latency in reaching effect site

Discharge times faster with infusions-30%

Faster PACU requirements -30 minutes

USES OF TIVA

General anaesthetic-neurosurgery, day care surgery

Supplement to regional, local anaesthetic

Sedation analgesia for diagnostic/therapeutic procedures

CONSTRAINTS Cost

Availability of the most suitable drugs and delivery systems

No reliable technique for monitoring plasma concentration of drugs equivalent to End Tidal inhalational agent

monitoring

Increased risk of awareness specially with concurrent use of muscle relaxants

DISADVANTAGES Acquisition costs

Set-up and use greater workload than vaporizers

Early or late respiratory depression

Opioid side-effects- biliary, muscle rigidity, GI motility, pruritus

Adverse events if IV line disrupted

SUMMARY TIVA techniques can provide numerous advantages over volatile

anesthetics.

equipment set-up and cost is greater than using existing vaporizers, appreciable long-term savings.

Improved understanding of drug kinetics, dynamics and interactions has facilitated optimal drug selection and method of administration

Modern infusion technology and TCI lends control to IV techniques to rival vaporizer use.

TIVA is ideal for Day care surgery with large patient turnover

The increasing popularity of TIVA is testament to its ease of use and perceived benefits

TIVA represents a new technique of the speciality with major advantages

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