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ISOFLURANE OUT OF STOCK: TIVA or not to TIVA?

INTRODUCTION

Intravenous anaesthesia was first observed as an incidental finding in the 17th Century when scientists were investigating the circulatory system.  Intravenous injections of opium, wine or ale were administered to dogs via sharpened quills by Sir Christopher Wren and D. J. Major. They observed that the dogs appeared “inebriated”. In 1664, Daniel Meyer, a German scientist, noticed that dogs receiving intravenous opium appeared to be less responsive to pain.  However, these observations were not explored further for another 200 years, and total intravenous anaesthesia (TIVA) only entered human medicine with the advent of rapid onset, short acting opioids and anaesthetics in the late 20th and early 21st Centuries (Henshaw, 2007).

Total intravenous anaesthesia (TIVA) is the induction and maintenance of anaesthesia via purely intravenous means.  Drugs used for TIVA should allow anaesthetic depth to be rapidly changed by altering the infusion rate and should not produce significant accumulation.  The most suitable drugs will have rapid onset of action, short duration of clinical effects, high clearance rates, rapid metabolism to inactive products, and rapid excretion (Duke-Novakovski, 2016).

DRUG SELECTION

The idea drug for TIVA should be infusible for long periods of time and should not accumulate. Infusion rates are generally adjusted based on observations of the animal, although individual responses can vary depending on species, breed, sex, individual reactions to the drugs, degree of analgesia/sedation, and surgical stimulation.

Alfaxalone and propofol are both licenced for TIVA in the UK, and the individual SPCs should be referred to for doses and duration of maintenance.  Alfaxalone and propofol produce unconsciousness and muscle relaxation but little analgesia, therefore pain relief should be provided at the time of premedication and throughout the maintenance and recovery periods (Duke-Novakovski, 2016; Alfaxan Multidose SPC, 2018).

Alfaxalone is licenced for maintenance of anaesthesia in cats and dogs for up to 1 hour with no maximum cumulative dose or minimum intervals between anaesthetic events stated on the SPC.  The data sheets for some propofol products recommend maximum total administration doses per anaesthetic, a potential for oxidative damage and Heinz body formation, and advise maintenance for greater than 30 minutes may lead to prolonged recoveries, especially in cats. The individual SPC should be referred to for further details (Alfaxan Multidose SPC, 2018; Propofol-Lipuro Vet SPC, 2013; PropoFlo Plus SPC, 2016).

Cats may experience prolonged recoveries following propofol TIVA as they are sensitive to the phenol-based propofol, and they have restricted capacity for metabolism of this drug (Duke-Novakovski, 2016).

Both alfaxalone and propofol have no significant analgesic action therefore pain relief should be provided by the administration of other products.  Fentanyl, medetomidine and dexmedetomidine can be also administered by infusion during the maintenance period, providing analgesia and a dose-sparing effect.  Fentanyl is a potent analgesic and can cause respiratory depression, particularly when administered during anaesthesia. Any apnoea should be managed by IPPV, as should respiratory depression resulting from the administration of other CNS depressants. Endotracheal intubation and provision of supplementary oxygen are recommended throughout the anaesthetic period (Psatha et al., 2011; Duke-Novakovski, 2016).

PRINCIPLES OF TIVA ADMINISTRATION

Both sedation and anaesthesia can be maintained by intermittent bolus or by constant rate infusion (CRI). 

TIVA generally involves a loading (induction) dose followed by maintenance, with the aim of sustaining a constant plasma concentration of the drug. Therefore, the rate of drug administration during maintenance should compensate for distribution, excretion & metabolism (Duke-Novakovski, 2016).

Bolus administration
Bolus administration does not require specialised equipment however, large variations in plasma concentration of the drug occur.  At the time of bolus administration plasma concentration rises steeply and may produce undue clinical effects e.g. anaesthetic depth, respiratory depression.  Just prior to the next bolus the plasma concentrations will have decreased, and inadequate clinical effects may be observed. 

Constant Rate Infusion
CRI produces a smaller variation in plasma concentration, and fewer oscillations of the haemodynamic, respiratory and central effects, than bolus administration. Duke-Novakovski (2016) considers CRI to be safer than bolus administration. In addition to the reduced anaesthetic “swings” when compared to bolus administration, CRI can be adjusted easily in response to observations of clinical parameters in a manner similar to the adjustments made to volatile settings during inhalation anaesthesia (variable rate infusion).  CRI is also more economical than bolus techniques (Duke-Novakovski, 2016).

RECOVERY

Recovery following TIVA depends on the half-life of the product(s), the rate of equilibrium between plasma and brain, and the duration of the infusion.  

CONSTANT RATE INFUSION DEVICES

Syringe drivers
Syringe drivers use a motor & screw mechanism to manage the accurate delivery of drugs. They are suitable for the administration of most anaesthetics and CNS depressants, and some designs are capable of delivering volumes down to 0.01ml/hour, although the apparatus should be selected carefully if such volumes are to be used, and regularly calibrated.  Many have inbuilt calculators allowing drug concentration, animal bodyweight, infusion rate (dose/weight/time) to be entered and the device then automatically calculates the infusion volume/time. Some equipment will also automatically recognise syringe size. Delivery rates of drugs, in response to changes in the physiological parameters of the patient, can be easily adjusted during infusions (Duke-Novakovski, 2016).

Fluid pumps
Active fluid delivery pumps are more accurate than simple drips but are not ideal for the precise delivery of anaesthetic agents. Careful calculations are necessary, as drugs generally have to be diluted (not always possible), and there is a tendency for the equipment to administer mini-boluses. Specialised infusion tubing is also required. 

Drips (gravity controlled). 
Drips, either basic or rate controlled, deliver drugs with even less accuracy than fluid pump, and are not generally recommended for TIVA.

CONCLUSION

TIVA is becoming increasingly used in both human and veterinary practice.  With the correct protocols and equipment anaesthetic depth can be maintained very accurately, even in very small patients. Henshaw (2007) goes as far as to suggest that in human patients, where multiple drugs, including opioids and anaesthetic agents are administered by CRI, the quality and speed of recovery are greater that with inhalation agents.


The Jurox User Guide to Achieving the Best Outcome When Using Alfaxan® for the Induction and Maintenance of Anaesthesia is available here

Alfaxan for Maintenance of Anaesthesia: Frequently Asked Questions is available here.

A downloadable Dose Chart for Alfaxan® TIVA by CRI and Intermittent Bolus Administration is available here

Article by
Jurox UK Veterinary Technical Team

Originally published: Thursday, 13th December 2018

References

Alfaxan Multidose SPC. (2018). Jurox UK Ltd

Duke-Novakovski, T., ed. (2016). BSAVA Manual of Canine and Feline Anaesthesia and Analgesia. 3rd ed. British Small Animal Veterinary Association.

Henshaw, K. (2007). Total Intravenous Anaesthesia. In: Smith, B., Rawling, P., Wicker, P., Jones, C., eds. Core Topics in Operating Department Practice: Anaesthesia and Critical Care. 2nd ed. Cambridge University Press.

Maddison, J., ed. (2008). Small Animal Clinical Pharmacology. 2nd ed. Saunders Elsevier.

Propofol-Lipuro Vet SPC. (2013). Virbac Ltd.

PropoFlo Plus SPC. (2016). Zoetis UK Ltd

Psatha, E., Alibhai, H.I.K., Jiminez-Lozano, A., Armitage-Chan, E., Broadbelt, D. (2011). Linical efficacy and cardiorespiratory effects of alfaxalone, or diazepam/fentanyl for induction of anaesthesia in dogs that are a poor anaesthetic risk. Vet Anaesth Analg. 38, 24-36

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