REVIEW ARTICLE

Computer simulations of propofol infusions for total intravenous anaesthesia in dogs

K E Joubert

Veterinary Anaesthesia, Analgesia & Critical Care Services, PO Box 1898, Lonehill, 2062 South Africa. E-mail: hypnyx@wbs.co.za

ABSTRACT

The volatile anaesthetic agents halothane, isoflurane and enflurane are all chlorofluoro-carbons and according to international treaties, their emission into the atmosphere will be prohibited from the year 2030. The agents desflurane and sevoflurane are fluorinated hydrocarbons and act as greenhouse gases. The future of veterinary anaesthesia could be dependent on the development of total intravenous anaesthesia. Drugs utilised in total intravenous anaesthesia (TIVA) should have a short duration of action and no tendency to accumulate in the body. Propofol has been the dominant agent used. Computer technology has enabled targeted plasma concentration controlled infusions to replace manual infusion regimens. This study simulated the pharmacokinetics of various infusion regimens similar to those used in clinical practice using previously published pharmocokinetic data. Bolus doses of 0, 4, 6 and 8 mg/kg were simulated in combination with infusion rates of 0, 0.2, 0.3 and 0.4 mg/kg/min for either 240 or 1440 min. The computer was also programmed to maintain a steady state plasma concentration based on the previous simulated data. Generated data were then compared with published data. Changes in the context-sensitive half-life for propofol were also evaluated. Results showed that the generated data were similar to published data. A decrease in plasma concentration to levels associated with a light plane of anaesthesia was evident even when the highest bolus dose and infusion rate were used. There was a slow rise in plasma concentration when only an infusion was used. A lightening of anaesthetic plane may be evident early in the course of TIVA and careful monitoring of anaesthetic depth is required. As the duration of the infusion increased, plasma concentration steadily rose but achieved 95% of the steady state by 204 min. The most dramatic changes in plasma concentration occurred in the first hour of an infusion. Similarly, the infusion rates decreased most in the first 70 min. Most changes in anaesthetic depth are likely to occur early in the course of TIVA and careful observation of anaesthetic depth is required.

Key words: computer-controlled infusions, pharmacokinetics, propofol, simulations, total intravenous anaesthesia

“Full text available only in PDF format”

REFERENCES

1. Aguiar A J A, Luna S P L, Oliva V N L S, Castro G B 2001 Continuous infusion of propofol in dogs premedicated with methotrimeprazine. Veterinary Anaesthesia and Analgesia 28: 220-22        [ Links ]

2. Beths T Glen J B, Reid J, Monteiro, A M, Nolan A M 2001 Evaluation and optimisation of a target-controlled infusion system for administering propofol to dogs as part of a total intravenous anaesthetic technique during dental surgery. Veterinary Record 148: 198-203        [ Links ]

3. Brandon R A, Baggot J D 1981 The pharmacokinetics of thiopentone. Journal of Veterinary Pharmacology and Therapeutics 4: 79-85        [ Links ]

4. Chambers J P 1989 Induction of anaesthesia in dogs with alfentanil and propofol. Journal of the Association of Veterinary Anaesthetists 16: 14-17        [ Links ]

5. Cockshott I D, Douglas E J, Plummer G F Simons P J 1992 The pharmacokinetics of propofol in laboratory animals. Xenobiotica 22: 3: 369-375        [ Links ]

6. Coetzee J F, Glen J B, Wium C A, Boshoff, L 1995 Pharmacokinetic model selection for target controlled infusions of propofol: assessment of three parameter sets. Anesthesiology 82: 6: 1328-13        [ Links ]

7. Colburn W A 1981 Simultaneous pharmaco-kinetic and pharmacodynamic modeling. Journal of Pharmacokinetics and Biopharmaceutics 9: 3: 367-38        [ Links ]

8. Flecknell P A, Kirk A J B, Fox C E, Dark J H 1990 Long-term anaesthesia with propofol and alfentanil in the dog and its partial reversal with nalbuphine. Journal of the Association of Veterinary Anaesthetists 17: 11-1        [ Links ]

9. Fonda D 1991 Continuous infusion of anaesthesia with propofol in dogs: clinically optimized dosages. Proceedings of the 4th International Congress ofVeterinary Anaesthesia: 159-161        [ Links ]

10. Glowaski M M,Wetmore L A 1999 Propofol: application in veterinary sedation and anesthesia. Clinical Techniques in Small Animal Practice 14: 1: 1-9        [ Links ]

11. Hall L W, Clarke K W, Trim C M 2002 Anaesthesia of the dog In Hall L W, Clarke K W, Trim C M (eds) Veterinary anaesthesia (10th edn). W B Saunders, London: 385-439        [ Links ]

12. Hall L W, Chambers J P 1987 A clinical trial of propofol infusion anaesthesia in dogs. Journal of Small Animal Practice 28: 623-637        [ Links ]

13. Hall L W, Lagerweij E, Nolan A M, Sear J W 1994 Effect of medetomidine on the pharmacokinetics of propofol in dogs. American Journal of Veterinary Research 55: 1: 116-120        [ Links ]

14. Hughes J M L, Nolan A M 1999 Total intravenous anaesthesia in Greyhounds: pharmacokinetics of propofol and fentanyl - a preliminary study. Veterinary Surgery 28: 513-524        [ Links ]

15. Hughes, M A Glass P S A,Jacobs J R 1992 Context-sensitive half-time in multi-compartment pharmacokinetic models for intravenous anesthetic drugs. Anesthesiology 76: 334-341        [ Links ]

16. Keegan R D, Greene S A 1993 Cardiovascular effects of a continuous two-hour propofol infusion in dogs: comparison with iso- flurane anesthesia. Veterinary Surgery 22: 6: 537-543        [ Links ]

17. Kenny G N C, Mantzaridis H 1999 Closed-loop control of propofol anaesthesia. British Journal of Anaesthesia 83: 2: 223-228        [ Links ]

18. Kenny G N C, White M 1990 A portable computerised infusion system for propofol. Anaesthesia 45: 8: 692-693        [ Links ]

19. Kusters A H A, Vijn P C M, van den Brom W E, Haberham Z L, Venker-van Haagen A J, Hellebrekers L J 1998 E E G-burst-suppression-controlled propofol anesthesia in the dog. Veterinary Quarterly 20: Suppl 1: S105-S106        [ Links ]

20. Mandsager R E, Clarke C R, Shawley R V, Hague C M 1995 Effects of chloramphenicol on infusion pharmacokinetics of propofol in Greyhounds. American Journal of Veterinary Research 56: 1: 95-99        [ Links ]

21. Marx T, Schmidt M, Schirmer U, Reinelt, H 2001 Pollution of the environment and workplace with anesthetic gases. International Anaesthesiology Clinics 39: 15-27        [ Links ]

22. Mertens M J, EngbersFHM,BurmAGL, Vuyk J 2003 Predictive performance of com-puter-controlled infusion of remifentanil during propofol/remifentanil anaesthesia. British Journal of Anaesthesia 90: 2: 132-141        [ Links ]

23. Milne S E, Toy A, Irwin M G, Kenny G N C 2003 Relationship between bispectral index, auditory evoked potential index and effect-site EC50 for propofol at two clinical end-points. British Journal of Anaesthesia 90: 2: 127-131        [ Links ]

24. Morgan D W T, Legge K 1989 Clinical evaluation of propofol as an intravenous anaesthetic agent in cats and dogs. Veterinary Record 124: 31-33        [ Links ]

25. Nolan A, Reid J 1993 Pharmacokinetics of propofol administration by infusion in dogs undergoing surgery. British Journal of Anaesthesia 70: 546-551        [ Links ]

26. Nolan A M, Reid J, Grant S 1993 The effects of halothane and nitrous oxide on the pharmacokinetics of propofol in dogs. Journal of Veterinary Pharmacology and Therapeutics 16: 335-342        [ Links ]

27. Raiha M P Raiha J, Short C E 1989 A comparison of xylazine, acepromazine, meperidine and medetomidine as preanesthetics to halothane anesthesia in dogs. Acta Veterinaria Scandanavia 85: 97-102        [ Links ]

28. Reid J, Nolan A M 1993 Pharmacokinetics of propofol in dogs premedicated with acepromazine and maintained with halo-thane and nitrous oxide. Journal of Veterinary Pharmacology and Therapeutics 16: 501-505        [ Links ]

29. Robertson S A, Johnston S, Beemsterboer J 1992 Cardiopulmonary, anesthetic, and postanesthetic effects of intravenous infusions of propofol in Greyhounds and non-Greyhounds. American Journal of Veterinary Research 53: 6: 1027-1032        [ Links ]

30. Schüttler J, Schwilden H, Stoekel H 1983 Pharmacokinetics as applied to total intravenous anaesthesia. Anaesthesia 38: Suppl: 53-56        [ Links ]

31. Shafer S L, Varvel J R 1991 Pharmaco-kinetics, pharmacodynamics and rational opioid selection. Anesthesiology 74: 53-63        [ Links ]

32. Thurmon J C, Ko J C H,Benson G J, Tranquilli W J, Olson W A 1994 Hemodynamic and analgesic effects of propofol infusion in medetomidine premedicated dogs. American Journal of Veterinary Research 55: 3: 363-367        [ Links ]

33. Vainio O 1991 Propofol infusion anaesthesia in dogs pre-medicated with medetomidine. Journal of Veterinary Anaesthesiology 18: 35-37        [ Links ]

34. Vickery R G, Maze M 1989 Actions of the stereoisomers of medetomidine, in halothane-anesthetized dogs. Acta Veterinaria Scandanavia 85: 71-76        [ Links ]

35. Watkins S B, Hall L W, Clarke K W 1987 Propofol as an intravenous anaesthetic agent in dogs. Veterinary Record 120: 326-329        [ Links ]

36. Watney G C G, Pablo L S 1992 Median effective dosage of propofol for induction of anesthesia in dogs. American Journal of Veterinary Research 53: 12: 2320-2322        [ Links ]

37. White M, Schenkels M J, Engbers F H M, Vletter A, Burm A G L, Bovill J G, Kenny G N C 1999 Effect-site modelling of propofol usingauditory evoked potentials. British Journal of Anaesthesia 82: 3: 333-339        [ Links ]

38. Young L E, Brearley J C, RichardsD L S, Bartram D H, Jones R S 1990 Medetomidine as a premedicant in dogs and its reversal by atipamezole. Journal of Small Animal Practice 31: 554-559        [ Links ]

39. Zoran D L, Riedesel D H, Dyer D C 1993 Pharmacokinetics of propofol in mixed-breed dogs and Greyhounds. American Journal ofVeterinary Research 54: 5: 755-760        [ Links ]

Received: August 2008
Accepted January: 2009