Total Intravenous Anaesthesia (TIVA)
What is Total Intravenous Anaesthesia (TIVA)?
What is the definition of TIVA?
Total Intravenous Anaesthesia (TIVA) is the technique of administering general anaesthesia using only intravenous agents and avoiding all inhalation anaesthetics.
Why might TIVA be preferred over inhalation anaesthesia?
Inhalation anaesthetics are potent respiratory depressants and necessitate airway instrumentation and associated ventilation for maintenance.
IV anaesthetics directly enter the central compartment, bypassing the lungs.
Useful IV agents like ketamine and dexmedetomidine can maintain adequate spontaneous ventilation while providing surgical anaesthesia.
What are the Key Pharmacokinetic Principles for TIVA?
What happens to an IV anaesthetic drug after injection?
An intravenously injected anaesthetic drug first disperses in the plasma, which is the central compartment (V1). From there, it rapidly equilibrates to well-perfused tissues like muscles (V2) and slowly to poorly perfused tissues like fat (V3).
Elimination occurs through metabolism or excretion.
What is the 'effect site' in the context of TIVA?
The effect site for anaesthesia is the brain. It is considered a small sub-compartment of the central compartment (V1). There is a lag in equilibration (hysteresis) between plasma concentration and effect-site concentration.
What is Context-Sensitive Half-Time (CSHT) and why is it important?
Context-Sensitive Half-Time (CSHT) is the time in which the plasma concentration of a drug is reduced by 50% after discontinuing an infusion. A short CSHT is desirable for a quick recovery from anaesthesia, making an agent suitable for TIVA.
What are the Common Drugs Used in TIVA?
Propofol
Why is propofol the preferred hypnotic agent for TIVA?
Propofol is suitable for the induction and maintenance of TIVA due to its favourable pharmacodynamic and kinetic properties. These include a rapid onset, short CSHT, and no active metabolites. It also does not trigger malignant hyperthermia.
What is the mechanism of action of propofol?
The complex mechanism of propofol is not fully understood, but it acts on GABA-A receptors in the central nervous system.
What is the onset and duration of action for propofol?
The onset of action for propofol is rapid, within one arm-brain circulation time of 30 to 60 seconds. It is quickly redistributed and has a short duration of action of 5 to 10 minutes.
How is propofol eliminated from the body?
The primary elimination of propofol is hepatic. It also undergoes extra-hepatic metabolism in the lungs, kidneys, and brain.
What are the effects of propofol on the cerebral and respiratory systems?
Propofol use is associated with a fall in cerebral metabolic rate and blood flow, while cerebral autoregulation appears unaffected. Large doses of propofol can cause respiratory depression, accompanied by a decrease in protective airway reflexes and a blunting of hypoxic pulmonary vasoconstriction.
What is the manual infusion plan for propofol as described by Prys-Roberts?
The manual infusion plan involves an induction dose of 1 mg/kg, followed by an infusion of 10 mg/kg/hr for the next 10 minutes, 8 mg/kg/hr for the following 10 minutes, and 6 mg/kg/hr thereafter.
How do propofol dosing requirements differ in neonates versus infants and children?
Neonates have an increased sensitivity to IV anaesthetics, so doses must be decreased. Infants and children have a larger central compartment volume and increased metabolic clearance, leading to decreased sensitivity, so they need higher doses.
Opioids (Fentanyl and Remifentanil)
What is the role of opioids like fentanyl in TIVA?
Potent opioids like fentanyl and remifentanil have a fast onset and allow for daily emergence. They provide intense analgesia and reduce the requirement for propofol in TIVA. They act on mu, delta, and kappa opioid receptors to facilitate descending inhibition of pain at supraspinal, spinal, and peripheral levels.
Fentanyl
What are the key pharmacokinetic features of fentanyl?
Fentanyl is extremely lipid-soluble, leading to rapid uptake by the brain and a fast onset of action within 60 seconds, peaking in 2 to 5 minutes.
Its short duration of action (30-60 minutes after a single bolus) is due to redistribution to muscles and fat, and metabolic clearance by the liver into inactive metabolites.
What are the advantages and side effects of fentanyl?
Advantages include haemodynamic stability, blunting of responses to noxious stimuli, and permitting rapid recovery. Side effects can include muscle rigidity and chest wall stiffness, which can be avoided with a smaller induction dose.
What are the typical doses for fentanyl in TIVA?
For induction, the dose is 0.25 to 1 microgram/kg. For maintenance, it is 0.1 to 0.2 microgram/kg/hr.
Remifentanil
What makes remifentanil's pharmacokinetics unique and ideal for TIVA?
Remifentanil has a methyl ester side chain that is hydrolysed by non-specific blood and tissue esterases into inactive metabolites. This leads to very low tissue storage and no accumulation. Its CSHT remains flat at around 8 minutes regardless of infusion duration, making it an ideal agent for co-administration with propofol in TIVA.
How does the CSHT of remifentanil compare to that of fentanyl?
The CSHT of remifentanil remains flat at around 8 minutes whatever the duration of infusion. In contrast, the CSHT of fentanyl rises steeply after 60 minutes due to increased tissue sequestration.
Ketamine
What is ketamine and what type of anaesthesia does it produce?
Ketamine is a phencyclidine derivative that produces a painless and amnesic cataleptic state, described as dissociative anaesthesia.
What is the mechanism of action of ketamine?
Its main mode of action is NMDA receptor antagonism, but it also interacts with opioid, muscarinic, and monoaminergic receptors. It inhibits voltage-gated sodium and potassium channels and the reuptake of serotonin and dopamine.
What are the key pharmacokinetic features of ketamine?
Ketamine is highly lipid-soluble and rapidly distributes to the brain, ensuring a rapid onset of analgesic effect. It undergoes rapid metabolism and redistribution to peripheral tissues. Its main metabolite, norketamine, is 20-30% as potent as the parent compound.
What are the effects of ketamine on the cardiovascular and respiratory systems?
Ketamine has a direct negative inotropic effect on the heart, but this is counteracted by an indirect stimulatory effect secondary to sympathetic nervous system activation. It produces airway relaxation and has minimal effects on the central respiratory drive.
What is the main side effect of ketamine and how can it be managed?
The predominant and distressing side effect of ketamine is psychoactive effects (emergence phenomenon). The introduction of midazolam in 1989 was a game-changer, as it can effectively counter most of the psychoactive, sympathetic, and cholinergic side effects. Propofol is also very useful for this purpose.
In what advantageous settings is ketamine used for anaesthesia?
Ketamine is advantageous for patients with haemodynamic instability, paediatric patients, uncooperative patients, traumatic brain injury, bronchospasm, and outside operating room anaesthesia.
Dexmedetomidine
What is dexmedetomidine and what are its main effects?
Dexmedetomidine is a new-generation, highly selective alpha-2 adrenoceptor agonist with sedative and analgesic effects. Its hallmarks are maintenance of muscle tone, lack of respiratory depression, and analgesia, which helps maintain spontaneous breathing under TIVA.
What are the key pharmacokinetic features of dexmedetomidine?
The onset of action is slower (5-10 minutes), with a peak effect at 15-30 minutes. Duration of action is less than an hour due to fast redistribution. It can accumulate, with CSHT rising to 250 minutes after an 8-hour infusion.
What are the typical doses and adverse effects of dexmedetomidine?
The dose is 1 microgram/kg for induction followed by 0.2-0.7 microgram/kg/hr for maintenance. Frequent adverse effects include hypotension and bradycardia caused by rapid bolus administration.
How are Drugs Combined in TIVA?
Why are combinations of agents used in TIVA?
Various combinations are used to add favourable anaesthetic properties and control untoward effects. Due to synergy, lower doses of individual drugs are needed.
What is a 'ketofol' combination and what are its benefits?
Ketofol is a mix of ketamine and propofol in the same syringe. Ketamine's psychoactive effects and tendency to accumulate are countered by propofol. The dose of propofol is low and does not produce respiratory depression or airway collapse.
What is a 'ketodex' combination and why are ketamine and dexmedetomidine complementary?
Ketodex is a combination of ketamine and dexmedetomidine. Both are good analgesics, and their effects are additive. Dexmedetomidine produces sedation similar to natural sleep and antagonises ketamine's hallucinations. Ketamine increases secretions while dexmedetomidine is a drying agent. Ketamine increases heart rate and blood pressure while dexmedetomidine does the opposite.
What is the 'KPD mix' or 'ketodexofol'?
Adding propofol to ketodex (ketamine and dexmedetomidine) helps to reduce the requirements of both ketamine and dexmedetomidine and promotes faster onset and smoother emergence.
What are the advantages and disadvantages of using fixed-dose premixes versus separate syringes?
Premixed combinations are useful only for short procedures, as long-acting drugs tend to accumulate over time. Using separate syringes allows more versatility, adjusting doses according to the patient's physical status and the surgical scenario.
What are the Overall Advantages of TIVA?
What are the key advantages of using TIVA?
TIVA allows the preservation of spontaneous breathing and can avoid airway instrumentation and assisted ventilation for short procedures. It is also a feasible and preferred option for prolonged anaesthesia with muscle relaxation and IPPV.