Giving yourself the best chance of a smooth recovery

Propofol

• PD effects of propofol usually ensure a smooth, clear-headed awakening
• PK characteristics and TCI infusion models allow reasonable recovery times from anaesthesia
• Emergence agitation and delirium is less compared with inhalational agents particularly in children
  • Sevoflurane produces higher glucose and lactate levels in the human brain compared to propofol
  • These levels are associated with increased neuronal activity
    • Enhanced glutamate-neurotransmitter cycling
    • Increased glycolysis and lactate shuttling from astrocytes to neurons
    • Mitochondrial dysfunction
• PONV decreased
  • Propofol has anti-emetic properties

Opioids

• Remifentanil is our intraoperative opioid of choice
  • Recovery is much faster than when another opioid of equipotent concentration are used
• When a combination of remifentanil and propofol recovery times can be hastened when compared to propofol alone
• PD effects of remifentanil are short-lived and planning is required to provide adequate postoperative analgesia
• PK characteristics of remifentanil result context insensitive half-life after infusion therefore effect will dissipate rapidly after discontinuation

Synergy

• Remifentanil and other opioids decrease propofol requirement
• We recommend titrating propofol to loss of consciousness and then using an opioid to suppress noxious stimuli
• Higher doses of remifentanil can be maintained towards the end of surgery while propofol is titrated down to cover noxious stimulus
• Remifentanil’s dissipation is more rapid and predictable compared to propofol
• Suggested optimal dosing of propofol TCI effect site of 2.5-2.8 μg.ml−1 in combination with a remifentanil concentration at 4.7 to 8.3 ng.ml−1
• Wake up time for these combinations
  • 5.1 minutes for a 15-minute infusion
  • 11.3 minutes for a 10-hour infusion
• Observing decrement concentrations of both agents at any time will indicate the projected time course of current concentrations if the infusions are stopped
• This information allows us to understand which drug is most likely to have the biggest impact on the rate of recovery
• Delay in waking for longer infusion correlates to the increase in the context-sensitive half-life of propofol
• If remifentanil is not available optimal recovery times are achieved by combining higher doses of propofol with lower doses of other opioids that have longer pharmacokinetic recovery profiles
• Analgesic effect of remifentanil will dissipate within 10-15 minutes from discontinuation of the infusion
• Alternative analgesia for the postoperative will be requried

Multi-modal analgesia regime

• If morphine is required it should be administered at least 40 minutes before the end of surgery
• Our practice usually involves giving morphine early in the intra-operative course
  • Additive effect with other opioids such as remifentanil
  • Reduce tolerance to remifentanil
  • Higher doses are associated with a greater risk of
    • Respiratory depression
    • Delayed awakening
    • Sedation
    • PONV

Sedative

• Dexmedetomidine
  • Short-acting sedative agent of choice.
  • Decrease propofol requirements and improve the haemodynamic profile
  • Discontinue infusion one hour before the end of surgery to avoid delays in return of consciousness
• Benzodiazepine may reduce the speed and quality of recovery of normal mental functions.
  • Increase postoperative neurobehavioural disorders (PND)
  • Postoperative cognitive dysfunction
  • Postoperative delerium
  • Emergence delirium

Ketamine

• Analgesic, amnesic and dissociative anaesthetic agent
• Low dose provides analgesia, propofol sparing whilst minimising adverse effects
• Induction: single dose (0.1–0.5 mg.kg−1)
• Maintenance: consider for procedures lasting more than two hours infusion (0.25–0.5 mg.kg−1.h−1).
• Discontinue: at least 30 minutes before the end of surgery in our practice we usually recommend 1 hour to avoid adverse psychiatric effects and delays in recovery

Strategy when using different drug combinations

• Titrate down the drug with the slowest kinetics first
  • Sequence will depend on your local drug availability and personal preference
  • Propofol is slower than Remifentanil
  • Fentanyl is slower than Propofol
• If other adjuncts are used such as dexmedetomidine and ketamine we recommended discontinuing before the end of the procedure
• At the end of the surgery, we suggest setting the target site to zero instead of powering off the TCI pump
  • This allows us to see the calculated effect site, decrement time and helps us judge when the patient will regain consciousness
• Wakening can be abrupt with a combination of propofol/remifentanil TIVA
  • Be prepared to extubate
• Consciousness may return before the respiratory drive

Caveat: the speed and quality of recovery is multifactorial and will also depend on the types and doses of other drugs administered, the experience of the anaestheist with TIVA and the nature of the surgery