TOTAL INTRAVENOUS

ANESTHESIA (TIVA)

CHAIRPERSON: DR. VENKATESHWARLU (PROF & HOD)

CO CHAIRPERSON: DR. SRINIVAS NAIK (ASSOC PROF)
MODERATOR: DR. MADHAVI (ASST PROF)
SPEAKER: DR. SAMARASIMHA REDDY (POSTGRADUATE)
 From where did the concept comes
from????

The concept of total intravenous anesthesia has evolved from

primarily intravenous induction of anesthesia to induction
as well as maintenance of anesthesia with intravenously
administered drugs
DEFINITION

Total intravenous anesthesia (TIVA) can be defined as a

technique of general anesthesia using a combination of
agents given solely by the intravenous route and in the
absence of all inhalational agents including nitrous oxide
BALANCED ANESTHESIA

 Coined by LUNDY.
 Balance of agents &
technique(premedication,regional
anesthesia,general anesthesia with one or
more agents) used to produce different
components of anesthesia i.e, Analgesia,
Amnesia,Muscle relaxation,loss of
consciousness,abolition of Autonomic
reflexes.
 Why TIVA?
Search for suitable drugs and techniques to meet changing demands of

 Advanced diagnostic and therapeutic treatment modalities

requiring alleviation of patient discomfort

 Need to provide safe anesthesia with rapid patient turnover

as in ambulatory care setting, to facilitate maximum no of
patients

 Anesthesia in non operative locations where inhalational

anesthetics are logistically difficult
 Contd…
Availability of

 Rapid short acting, easily titratable intravenous hypnotic,

analgesic and muscle relaxant drugs

 Pharmacokinetic and dynamic based IV delivery systems

which are portable

 Monitors to measure the depth of the hypnotic component

of the anaesthetic state
 Advantages of TIVA
 Induction is very rapid in onset

 Rapid onset of action independent from alveolar ventilation

 Improved quality of emergence from anesthesia

 Very smooth and peaceful recovery

 No risk of environmental pollution

 Advantages of TIVA

 Reduction in the incidence of postoperative nausea and vomiting

 Method of choice in patients at risk of malignant hyperthermia

 In patients undergoing airway procedures

 Increased patient comfort

 Disadvantages of TIVA
 Pain during injection

 Needs sophisticated infusion pumps

 Difficult to monitor continuous administration of i.v. agents into the patient

 Greater pharmacokinetic and pharmacodynamic interindividual variability

 Depth of anesthesia monitoring has interindividual variability

 No reliable technique for monitoring plasma concentration of drugs

 Disadvantages of TIVA

 Nosingle intravenous anaesthetic agent provides all

components of anaesthesia in its therapeutic dose like
• Amnesia
• Hypnosis
• Analgesia
• +/- muscle relaxation
 Basically most of the analgesic and muscle relaxant components of TIVA are the
same as those which supplement inhalational anaesthetics in current use

 The difference is mainly in the choice of drugs for the hypnotic component
 An ideal intravenous anesthetic agent should be

 Water soluble
 Stable in solution and also on exposure to light
 Non-irritant to blood vessels or tissues
 Painless on injection
 Be rapidly metabolised with no accumulation
 Not increase muscle tone
 Possess minimum cardiovascular effects
 Have no effect on respiration
 Have no interaction with other drugs
 Have no allergic reactions
 Not induce nausea or vomiting
What is important to know before
giving TIVA?
 Patient evaluation
As for any anesthetic
 Procedure specifications

 Basic pharmacological actions and interaction of the drugs

used

 Effective concentration range of the drugs used or

therapeutic window
Pharmacokinetics

 Three compartment model: Drug first goes to first/central

compartment, the drug then distributes to
• second compartment/ highly perfused tissues by
repid distribution phase.
• third compartment/ less perfused tissues by slow
distribution phase.
Context Sensitive Half Time (CSHT)

 Time for plasma concentrations take to reduce by 50% after

discontinuing an infusion

 This has approximation to awakening time. Is independent

of elimination half time

 TIVA requires drugs with short CSHT

 But CSHT is a poor predictor of recovery

 Effect Site Equilibration
 There is a time lag between achieving plasma concentration and observing a
particular clinical response

 It indicate the time to reach the peak effect after bolus dose
 It depends on :
1, physical properties of the drug.
2, Receptor binding properties.
 Can be used to predict recovery.
 Drugs in TIVA

Individually or in combination, depending upon the Patient

and Procedure:
 Hypnotics

Propofol, Ketamine, Benzodiazepines, Etomidate,

Barbiturates
 Analgesics

Fentanyl, Remifentanil, Sufentanil, Alfentanil,

Methadone, Morphine
 Muscle relaxants
Atracurium, Vecuronium
OPIOIDS
 Short acting opioids used for TIVA are Remifentanil, Alfentanil, Sufentanil and
Fentanyl
 Remifentanil
 Loading dose- 0.5-1 μg/kg/min
 Maintanence dose- 0.25 μg/kg/min
 Sufentanil
 Loading dose 1-5 μg/kg
 Maintanence dose 0.01-0.05 μg/kg/min.
 Fentanyl
 Loading dose 1-10 μg/kg
 Maintanence dose 0.1-0.2 μg/kg/min
Mech of Action:

 Propofol & Etomidate: acts on GABA A receptors,decreases

the rate of dissociation of GABA from its receptors,thereby
increasing the duration of opening of cl channel.
 Ketamine: acts on NMDA receptors, it decreases
presynaptic release of Glutamate & inhibits the action of
NMDA receptors thus potentiating the effects of GABA.
 Opioids: Presynaptic inhibition of substance p release.
 Dexmedetomidine: Centrally acting alpha 2 agonist.
Advantages of individual drugs:
Propofol:
 Advantages: antipruriritic effect/ antiemetic effect/ anticonvulsant
 Disadvantages: pain on intravenous injection/ hypotension/ bradycardia/ transient
apnoea
Ketamine:
 Advantages: dissociative anaesthesia / preserves airway reflexes
 Disadvantages: emergence delirium
Etomidate:
 Advantages: highly cardiostable/ minimum respiratory depression’
 Disadvantages: causes adrenocortical suppression
Dexmedetomidine:
 Advantages: conscious sedation/ anxiolysis/ analgesia
 Disadvantages: decreases heart rate and blood pressure
Metabolism

 Propofol : mainly by liver glucuronidation, sulfation. Extra

hepatic by lungs (30%), kidneys.
 Ketamine: liver by cytochrome P450 to form nor ketamine
& eliminated in urine.
 Etomidate: by liver.
 Opioids: by liver.
Drug interactions & TIVA

 Alfentanyl increases the duration of propofol by 20%,due to

its effects on clearance & redistribution.
 Alfentanyl concentration is increased by propofol due to
inhibition of oxidative phosphorylation of alfentanyl via cyt
P450.
 Propofol with midazolam &propofol with opioids have
synergistic effects.
Propofol infusion syndrome

 Rare syndrome seen with prolonged infusions of high doses

of propofol( >4mg/kg/hr for more than 48 hrs)
 Clinical features are acute refractory bradycardia leading to
asystole in the presence of
1. Metabolic acidosis(base deficit <10mmol/lit)
2. Rhabdomyolysis
3. Hyperlipidemia
4. Enlarged / fatty liver
 Other features include cardiomyopathy with acute cardiac
failure,skeletal myopathy, hyperkalemia,hepatomegaly and
lipemia.
 Theories: Mitochondrial toxicity,Mitochondrial defects,
impaired tissue oxygenation,carbohydrate deficiency.
 Risk factors: poor oxygen delivery, sepsis,serious cerebral
injury, high propofol dosage.
 An increasing lipemia may be the first indication of
impending propofol infusion syndrome onset.
 Treatment: supportive. Early recognition of syndrome and
discontinuation of propofol reduces morbidity & mortality.
 Best cocktail!!!!
Propofol : Remifentanil solution
Induction bolus:
 Propofol (10 mg/ml) at 150 μg/kg/min
 Remifentanil (20 mcg/ml) at 0.25 μg/kg/min
Maintenance Infusions
 1st propofol 150 mcg/kg/min for 15 minutes
 2nd propofol 125 mcg/kg/min for 15 minutes
 3rd propofol 100 mcg/kg/min thereafter
 Remifentanil Infusion- 0.25 to 1 μg/kg/min
How is TIVA delivered?
 Manually controlled infusion

 Target controlled infusion

 Target controlled infusion
 Computer driven infusion device with specific
pharmacokinetic parameters to achieve a preset target
plasma concentration.

 Prototype TCI model – 1988 at university of Glasgow

 Calculate their infusion rates according to patient factors

like age and weight

 Pumps the measured plasma concentration of the drug

 TCI system can rapidly achieve and maintain a desired concentration at the effect
site making it as convenient as the use of a vaporizer
 It use a bolus elimination transfer technique to administer drugs
Bolus, Elimination, Transfer (BET) regimen

 In1968, Kruger-Theimer illustrated how pharmacokinetic

models can be used to design efficient dose regimens

 This regimen consists of:

• a bolus dose calculated to fill the central (blood)
compartment,
• a constant-rate infusion equal to the elimination rate,
• an infusion that compensates for transfer to the
peripheral tissues: [exponentially decreasing rate]
Advantages of continuous variable rate infusion

 Greater hemodynamic stability

 More stable depth of anesthesia

 More predictable and rapid recovery

 Potential lower total dose of drug used

 OPEN LOOP SYSTEM
 Anesthesiologist chooses “target” blood or brain (effective site) drug concentration
on the basis of clinical response

 Microprocessor of the pump infuses the drug at the rate needed to rapidly achieve
and maintain the desired concentration

 No feedback signal of output

 CLOSED LOOP SYSTEM
IT IS THE FUTURE

 Feedback signal of effect site concentration built into the delivery system

 Programmed to alter the infusion rate on the feedback signal till the desired target is
achieved
 CONCLUSION

 The availability of
 short acting, potent hypnotic and analgesic drugs and modern TCI systems make
TIVA a straight forward alternative to inhalational anesthesia

THANK YOU