Pharmacology - TIVA Flashcards
- PR_BK_23 Context-sensitive half-time: comparison of drugs e.g. propofol, fentanyl and remifentanil. Target-controlled infusions [TCI] - PR_BK_24 TCI in practice: accuracy, applicability, cost. Variations due to patient differences: predictable and unpredictable (11 cards)
What is TIVA?
Total IntraVenous Anaesthesia - inducing and maintaining general anaesthesia with only IV agents - no vapours
Usually involves a combination of a sedative and an analgaesic - often remifentanil and propofol.
This can be delivered either manually by using formulae to calculate require infusion rates, or by using target controlled infusions
Physical & patient characteristics
Describe the ideal TIVA agent
Physical
Cheap & easy to manufacture
No reconstitution needed
Stable to store and transport
Inert in standard anaesthetic ampoules, syringes and giving sets
Compatible with other medications
Clinical
Painless on administration
Rapid & predictable onset/offset
Predictable, reproducible plasma concentrations and clinical effect using a given pharmacokinetic model
Minimal and rapid metabolism, with no active metabolites
Depression of airway reflexes
Minimal cardiovascular compromise
Break down into physical & clinical characteristics
Discuss propofol as a TIVA agent
Most commonly used hypnotic for TIVA in the UK - with a favourable pharmacokinetic & pharmacodynamic profile, and also due to our familiarity with its use.
Extremely fat soluble, prepared as an emulsion - it will rapidly redistribute & accumulate into fatty tissues, with a Vd of 4L/kg
Undergoes hepatic metabolism to inactive metabolytes
When given as a bolus, has rapid onset, often within 30s, and offset within a few minutes. Peak action at 1.5-2 mins post-injection on reaching the CNS. Offset due to redistribution from the plasma (and thus CNS), with a distribution half-life of 1-2 minutes.
Terminal elimination half-life of 5-12 hours, in the liver and at extra-hepatic sites
Discuss remifentanil as a TIVA agent
Synthetic opioid fentanyl derivative - pure μ agonist
Metabolised by plasma & tissue esterases, particularly in muscle, to essentially inactive metabolytes
Low context-sensitive half-life, remaining around 5-8 minutes even after long infusions. Due to rapid metabolism and small Vd (confined to plasma)
Drawbacks:
Negligible post-op analgaesia (due to rapid metabolism) - mitigated with regional or longer acting opioids
Hyperalgaesia - potentially due to downregulation of μ receptors - can be mitigated by loading a longer acting opioid before cessation of infusion
Chest wall rigidity & bradycardia - especially with the induction bolus dose
Target concentration at induction is often 4-8ng/ml, and 3-6ng/ml intra-op. At the end of surgery, a continued infusion with a target of 1-2ng/ml can facilitate smooth extubation
The minto model will give an initial bolus dose 3x higher to overpressurise the plasma, if the effect site target is used, compared to the plasma target.
Why are propofol and remifentanyl used together in TIVA?
IMAGE - Isobologram
They are synergistic - meaning a smaller dose of both drugs is required to achieve adequate depth of anaesthesia.
Together, they are very effective at obtunding laryngeal reflexes for intubation. Both may be started together, but if remifentanil is started first and allowed to equilibrate, much less propofol is required for induction, although there is a risk of apnoea.
Propofol lasts longer than remifentanil, so will often be the limiting factor during emergence.
The decrement time is the time estimated by the model for the blood concentration to drop to 1.2μg/ml, after the infusion is stopped
Explain the concept of TCI
IMAGE - TCI plasma vs effect
TCI refers to the use of a syringe driver with a pre-programmed microprocessor, using a three-compartment model for the specific drug bing infused.
Drug concentration and patient parameters (weight, age, height) are programmed, which uses the algorithm to determine infusion rate. As there is no measurement of plasma concentrations, the target level may need adjusting based on clinical effect.
The target is either plasma, or effect side (brain) concentration. Using effect site will overpressure the plasma compartment to establish equilibrium as quickly as possible.
Propofol models:
Marsh traditionally targets plasma, and uses a larger, weight-dependent central compartment, giving more propofol as an initial bolus.
Schneider traditionally targets effect site
Patients will usually fall asleep at effect sites of 2.5-3μg/ml on propofol alone, or 2-2.5μg/ml alongside remifentanil.
Remifentanil
Minto may be used in effect site or plasma mode
If the TCI target is changed during the infusion, the pump will either deliver a bolus, or stop the infusion temporarily, before restarting at the new rate.
The eleveld model is becoming increasingly popular, especially for propofol, although there is also a remifentanil eleveld model, having been experimentally validated in a far wider range of ages and weights than any other model, and can be used in effect site, or plasma target modes.
Compared with Marsh, it gives a larger initial bolus, before pausing and backing off, while the overpressured plasma redistributes. In contrast, for the Marsh model to give an acceptable induction bolus, a higher TCI target is often used temporarily.
It has a better adjustment for context-sensitive half-life, leading to a more predictable wake up
How can TIVA be manually administered?
The Bristol model is most commonly used - aiming to achieve a target plasma propofol concentration of 3μg/ml within 2 minutes, assuming premedication with temazepam, followed by induction with 3μg/kg fentanyl
1mg/kg bolus of propofol at the start
10mg/kg/hr infusion for 10 minutes
8mg/kg/hr infusion for 10 minutes
6mg/kg/hr infusion therafter
Generally results in more propofol being administered than a TCI model, with more resultant haemodynamic instability, and slower wake up
What are the risks, and which safety features are used during TIVA?
Most risks relate to accidental awareness, given difficulty measuing depth of anaesthesia, especially if a non-visible cannula falls out or tissues.
Pump safety features
Pump calculates TCI targets using two separate circuits - only administers the drug if equal.
Should be plugged into the mains, and serviced in last 12 months.
If the pump turns off, it cannot just be turned back on, as it will forget where it was in the algorithm, so options include switching to volatiles, manual TIVA using the most recent administration rate or the Bristol model. Restarting the TCI model risks significant over-administration
Equipment considerations
Anti-siphon valves, high and low-pressure alarms, keeping cannulas visible, with fluids running to demonstrate patency.
Depth of anaeshesia monitoring, such as BIS is essential if NMBDs are being used, and desirable even if they are not.
Drug factors
Co-administration of a benzodiazepine can reduce risk of awareness, and use of nitrous can provide added analgaesia (although not TIVA by definition)
Single-syringe TIVA is increasingly uncommon, and carries a risk of drug settling during a long infusion.
Human factors
Avoid drug errors - remifentanil should only be labelled once the drug is confirmed to be drawn up into the syringe.
Clear communication about the use of 1% or 2% propofol - AAGBI guidance is that only one strength is stocked/used
By noting the plasma concentration at which the patient goes to sleep, the anaesthetist can calibrate the target concentration to the individual patient. Other options include the loss of response to voice and to jaw thrust - the NMBD should not be given until loss of repsosne to jaw thrust.
What are the indications & benefits of TIVA?
Indications
Hx of PONV
Risk of MH
Tubeless surgery where volatiles are impractical
Anticipated difficult intubation or need for smooth extubation
Neurosurgery
Surgery requiring neuromuscular monitoring
Neuromuscular disease where paralysis is contraindicated
Long QT syndrome
Benefits
Reduced PONV
Smoother wake up, reduced laryngospasm
Intra-operative wake up with maintenance of analgaesia (such as awake craniotomy)
Avoids complications of nitrous
Avoids volatiles (reduced fluoride ion production, reduces risk of cancer recurrence - particularly breast cancer with sevoflurane, and MH)
Logistically easier in some cases (Bronchoscopy & tracheostomy)
Can TIVA be used in morbidly obese patients?
Yes - traditional TCI models aren’t validated, but can be used
Servin’s formula (used to adjust calculations for lipophilic drugs in obesity) can be used for the input body weight.
Marsh will only program up to 150kg.
Schneider and Minto models calculate lean body mass using the James equation, which underestimates above a BMI of 40.
This results in schneider overdosing, and minto underdosing.
Elevend is shown to perform better at extremes of age and BMI, but results in a faster wake-up time than Marsh, which can alarm anaesthetists when they first use it.
What is Propofol-related Infusion Syndrome?
PIS is associated with prolonged, high-dose propofol infusions, and most commonly seen in PICU settings.
Thought to be caused by metabolic dysfunction & mitochondrial uncoupling as a result of abnormally high plasma lipid levels.
Characterised by metabolic acidois & cardiovascular dysfunction, plus at least one of:
Rhabdomyolysis
Hypertriglyceridaemia
Renal failure
May be mitigated through the use of 2% propofol, and keeping longer infusions under 4mg/kg/hr, to a maximum of 400mg/hr
