TIVA, Dr Brijesh Savidhan, Travancore Medical College

1. TOTAL
INTRAVENOUS
ANESTHESIA
Dr Brijesh Savidhan,
Department of Anaesthesiology,
Travancore Medical College.

2. INTRODUCTION
 Total intravenous anesthesia
 Technique of GA
 Anesthesia via intravenous agents (propofol,
narcotics, muscle relaxants)
 In boluses/drips
 No volatile agents

3. 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?

4.  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

5. TIVA EQUIPMENTS

6. 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

7.  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

8. SPECIFIC INDICATIONS
 Airway procedures
 Remote locations
 MH susceptible
 Neurosurgery
 Neuro monitoring
 PONV risk
 Short procedures-CT,MRI

9. PHARMACOKINETICS AND TIVA
There are different types of pharmacokinetic
models -
1. Compartmental models.
2. Physiological models.
3. Hybrid models.

10. THREE COMPARTMENT MODEL

11.  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

12.  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.

13. 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

14. 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.

15. 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.

16. 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.

17. 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

18.  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.

19. CLINICAL APPLICATION OF TIVA
To 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.

20. 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

21. MANUAL INFUSION SCHEMES
Anesthesia Sedation or Analgesia
Drug
Loading 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

22. 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.

23.  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

24.  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.

25. 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

26. 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

27. 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

28.  Rapid onset of action
 rapid and predictable recovery
 Devoid of adverse side effects
 Potent and lipid-soluble
 Relatively cheap
 Chemically compatible with other drugs.

29. 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

30. 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.

31.  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

32. 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

33.  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.

34. DISADVANTAGES
 It suppresses the production of cortisol.
 High concentration of propylene glycol in etomidate
preparation causes hemolysis resulting in
hemoglobinuria
 Expensive

35.  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

36.  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

37. 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

38.  Highly lipid soluble
 Highly protein bound
 Minimal pharmacological activity of fentanyl
metabolites
 Short CHST
 Stable hemodynamics

39. 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%.

40.  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.

41.  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

42. 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

43. 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

44. 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%)

45.  less respiratory depression
 Avoid latency in reaching effect site
 Discharge times faster with infusions-30%
 Faster PACU requirements -30 minutes

46. USES OF TIVA
 General anaesthetic-neurosurgery, day
care surgery
 Supplement to regional, local anaesthetic
 Sedation analgesia for diagnostic/therapeutic
procedures

47. 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

48. 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

49. 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.

50.  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

51. THANK YOU