Prepare and monitor anaesthesia in animals

1. Prepare and monitor anaesthesia in animals INJECTABLE (PARENTERAL) ANAESTHETICS

2. Common parenteral anaesthetics

3. Uses if injectable anaesthetics • Induction of anaesthesia • All • Maintenance of anaesthesia • Propofol

4. The Ideal Anaesthetic Agent • Produces a state of unconsciousness, analgesia and amnesia • Is reversible • Is able to be administered by a wide range of routes without irritation • Produces smooth & reliable induction & recovery • Is able to be topped up without delayed recovery • Has minimal effects on the cardiovascular and respiratory systems • Produces good muscle relaxation • Is easily metabolized and excreted without damage to organs

5. Question • What are 2 problems with perivascular injection of Thiopentone?

6. Answer • Very alkaline (high pH) • Perivascular irritation • Pain • Skin slough days later (less likely if <2.5%) • Unsure of dose given • Slow recovery

7. Question • What should be done if peri-vascular injection of 5% thiopentone is known to have occurred?

8. Answer • Inject site with isotonic saline with at least 4 X the estimated volume of perivascular thiopentone • Some people also use local anaesthetic (acidic) to counteract alkaline effects • Some rub DMSO on the affected area

9. Questions • What is meant by the term induction? • Name two induction agents • What is meant by the term maintenance? • Name two maintenance agents

10. Question • What are four aims of general anaesthetics?

11. Answer • Unconsciousness & Amnesia • Muscle relaxation • Decreased reflex activity • Analgesia or a least loss of pain perception

12. Other Uses of Anaesthetics • Anti-convulsants • Euthanasia agents

13. Parenteral anaesthetics • Thiopentone, Pentobarbitone • Barbiturate • Propofol • Phenol • Alfaxalone • Steroidal • Ketamine, Tiletamine • NMDA (N-methyl-D-aspartate)

14. Barbiturates • Depress the CNS from sedation to hypnosis to basal narcosis to general anaesthesia to death • Depress the respiratory and CVS • Probably no analgesic action (maybe even hyperalgesic) • Muscle and fat act as reservoirs for barbiturates • Recovery time is extended in sight hounds • Contraindicated in animals with liver or kidney disease • Cross the placenta and depress the foetus

15. Barbiturates • Classified according to duration of action: • Long acting: phenobarbitone • Short acting: pentobarbitone • Ultra-short acting: thiopentone

16. Barbiturates • Thiopentone • Short acting • General anaesthetic inductions • Pentobarbitone • Long acting • Convulsant poisonings • Euthanasia • Methohexitone • Phenobarbitone • Epilepsy treatment

17. Thiopentone • Presented in powder form that needs to be reconstituted • If make up standard bottle = 5% • Ideally use a sterile transfer device to add water • Safer to dilute 50:50 in water to make 2.5% before injection • Once made up lasts for 3 days at room temperature or seven days in a refrigerator • “Truth Serum” - once used at light doses to make people speak the truth!

18. Sterile Transfer Device Insert into water bottle first

19. Administration of thiopentone • Initial ‘quick’ bolus • In healthy animals • Half (1/2) of the calculated dose • Prevents recovery before induction • Rapid transition through excitement phase • In sick animals • Quarter (1/4) of the calculated dose • Remainder given ‘to effect’ ½ bolus ¼ bolus

20. Thiopentone • Short acting barbiturate • rapid onset, • decreases intracranial pressure • good if history seizures • Initial recovery due to tissue (muscle & fat) redistribution • Slow recovery in lean dogs & sight hounds • Advised to give 50% of recommended dose then to effect

21. Tissue distribution of thiopentone after single injection

22. Thiopentone • Disadvantages- • Dose-dependent respiratory & cardiovascular depression • Extra-vascular irritant (skin slough) • Possible initial apnoea & transient arrhythmias • Splenic engorgement • No analgesia • May cause laryngospasm • Not good for sight hounds/lean dogs • Unless small doses with potent premeds • Advise not to top up as it greatlyprolongs recovery time • Not advised in patients with liverproblems as metabolised mainly in liver

23. Skin slough Necrosed Sloughed To prevent: Infiltrate area with enough saline to dilute leaked thiopentone to 1% - so for 1 mL 5% thiopentone use 4 mL saline (4x) Scarred

24. Pentobarbitone • Longer acting barbiturate • Slow recovery and excitable if not given a premedicant • More commonly used for euthanasia and to control convulsions

25. Propofol Milky white Clear

26. Propofol formulations • Diprivan® – milky white fluid • Has to be used up straight away once vial opened as oil and egg good microbial culture medium • Or can keep in fridge for 24 hours in syringe with all air expelled • Aquafol® – water soluble, clear fluid • Multi dose vial can be used for 28 days after opening • Reports of ‘allergic’ reactions?

27. Administration of propofol • Small doses to effect • Less excitement phase problems (cf thio) • No top up problems (cf thio) increments

28. Propofol • Advantages • Rapid induction & recovery • Good for sight hounds • Can top up (even by drip) • Some use in caesarians? • Some analgesic properties? • Unlikely to cause ventricular arrhythmias • No problems if accidentally given perivascular

29. Propofol • Disadvantages – • Dose-dependent respiratory & cardiovascular depression • apnoea more severe than thiopentone and hypotension therefore use with caution in hypovolaemic, septic or cardiac patients • Septicemia following use documented (care with sterility of multi-dose bottle) • Sneezing, vomiting & paw & face licking has been observed during recovery

30. Dissociative anaesthesia • Dissociation from the surrounding • superficial sleep mediated by interruption of neuronal transmission from unconscious to conscious parts of the brain • May be dreaming/hallucinating but not perceiving physical stimuli • Animal maintains its pharyngeal, laryngeal, corneal, palpebral, and swallowing reflexes. • Eyes remain open • Increase muscle tone, spontaneous involuntary muscle movement (occasionally seizures are seen in some species) • Salivation, lacrimation increased • Somatic analgesia is good

31. Dissociative Anaesthetics • Examples • Ketamine • Tiletamine (part of Zoletil® mixture) • Also known as NMDA receptor antagonists • Phencyclidine derivative (~ ‘angel dust’) • n-methyl-d- aspartate (NMDA) receptors are part of the brain's neuro-excitatory pathway • When activated, these receptors allow calcium and sodium ions to pass freely into the nerve cells.

32. Ketamine • ‘Dissociative’ anaesthetic but also used as a sedative at smaller doses • IV – smooth/rapid induction but can be rough recoveries • Can be given IM & SC but painful • usually given with a sedative such as diazepam or midazolam to decrease muscle rigidity and seizure like activity, • Profound analgesia but only a superficial sleep • Produces an increase HR and BP • Useful for aggressive cats and dogs

33. Ketamine • Disadvantages • Pain IM or S/C as is acidic • Odd behaviour on recovery reported- vocalization, delirious • Increases salivation (best given with atropine) • Excreted mainly through kidneys therefore do not use if renal problems or dehydration • Also some hepatic metabolism (hence not used in liver failure) • Can cause seizures in dogs usually on recovery if not given with a sedative/muscle relaxant like diazepam/zolazepam • Increases blood pressure – may stress heart • Increases intracranial pressure so do not use if severe eye disease or head trauma • Eyes remain open and unblinking & cornea may become dry • Needs to be used in combination with other drugs – diazepam or midazolam

34. Tiletamine+Zolazepam (Zoletil®) • More potent than ketamine and premixed with a muscle relaxant • Can be used in dogs and cats • Can be used in sight hounds • Useful drug for sedation of aggressive dogs

35. Tiletamine+Zolazepam (Zoletil®) • Once reconstituted lasts 8 days when in refrigerator • Good muscle relaxation • Analgesic • Light to full surgical anaesthetic • Duration up to 1 hr • Prolonged & relaxed recovery but predisposes to hypothermia and hypoglycaemia • A rise in BP • Some respiratory depression • Laryngeal and pharyngeal reflexes are usually retained • Do not use with ACP • Do use with atropine

36. Alfaxalone • E.g. Alfaxan-CD 10mg/ml • Very safe now– • No allergic substances • High safety margin (eg 5x overdose is ok) • No irritation if perivascular injection • Used in cats and dogs • Rapid recovery • Keep open vials in fridge • Disadvantages • May have a period of apnoea following induction • Sometimes rough recovery

37. Questions • Suggest a sedation/induction technique for a nasty cat to be radiographed • Suggest a sedation/induction technique for an aggressive dog to get groomed • Suggest an induction agent for a Greyhound

38. Dose calculations • Induction dose of Propofol (10mg/mL) for a 25 kg dog at a dose rate of 4mg/kg • Thiopentone (50mg/mL=5%) for a 17 kg dog at a dose rate of 10mg/kg • Thiopentone (25mg/mL=2.5%) for a 5kg dog at a dose rate of 10mg/kg • Alfaxalone (10mg/mL) for a 6kg cat at a dose rate of 2.5mg/kg

39. Answer 1 • 25kg dog • Dose rate 4mg/kg • Drug=10mg/ml = 1mg/0.1ml • 100mg /0.1ml x100 = 100mg/10mls • Dose rate for 25 kg = 100mg/25kg • 100 x0.1mls/25 kg = 10mls/25kg dog

40. Answer 2 • 17kg dog • Drug–50mg/ml=1mg/1/50mls =1mg/.02mls • 10mg/kg • 10x17mg/17kg = 170mg/17kg • 170x0.02mls/17kg = 170x1/50mls/17kg = 3.4mls/17kg

41. Answer 3 • Dose rate = 10mg/kg • Animal = 5kg • Drug dose 25 mg/ml = 1mg/1/25mls • Need 50mg/5kg • 50x1/25mls/5kg = 2mls/5kg animal

42. Answer 4 • Drug 10mg/ml = 1mg/1/10mls • Animal 6kg • Dose rate 2.5mg/kg • 2.5 x 6 mg/6kg = 15mg/6kg • 15x1/10mls/6kg = 1.5mls/6kg

43. Syringe Labelling • Label filled syringes, somehow, if they are not to be used immediately • Special labelling tape available or improvise

44. What would be the ideal protocol? • Old sick dog - exploratory laparotomy • Premed? • Induction? • Maintenance?

45. Appendices • Dose rates • Detailed notes • Thiopentone • Propofol • Alfaxalone

46. Dose rates (dogs/cats)

47. Thiopentone • Derivative of barbituric acid • Unstable in aqueous solution and when exposed to air • Preparation • Sterile yellow powder + sterile water / saline  2.5% / 5% / 10% solution • 2.5 % solution = 2.5 g / 100 mL • Most suitable concentration for small animals • Remains stable for only 2 weeks • Perivascular injection • Very irritant because aqueous solution is strongly alkaline (pH ~10.5) • Infiltrate the area with 3-4 times volume of saline to dilute the drug and massage thoroughly • Highly lipid soluble, one arm to brain time = 10 – 20 sec • Metabolism • Liver

48. Thiopentone • Recovery • Initial recovery = redistribution of drug • Prolonged in: • Severe hepatic dysfunction • Sight hounds • Additional doses (top-ups) to maintain anaesthesia • Effects • Cortical depression and rapid loss of consciousness after IV administration • Anticonvulsant • Reduces cerebral blood flow and cerebral metabolic rate • Poor analgesia and poor muscle relaxant • Peripheral vasodilation (often associated with hypotension) • Myocardial depression and reduced stroke volume • Increases heart rate • Induces premature ventricular contractions and bigeminy • Potent respiratory depressant • If administered too slowly, marked stage 2 excitement in unpremedicated animals

49. Thiopentone • Contraindications • Porphyria • Severe cardiac decompensation • Peripheral circulatory failure • Colour • Yellow • Dose rate • 10 mg/kg • Route of administration • IV • Concentration • 25 mg/ml (2.5% solution) • 50 mg/ml (5% solution)

50. Propofol • Alkayl phenol • Perivascular injection • Not irritant, but can be painful on IV injection (less painful if the preparation is cold) • Preparation • 20 ml glass vials and multi-use bottles • No preservative • Should be drawn up into a syringe and stored in the fridge • Should be discarded within 24 hrs of opening • Rapid onset of action, similar to thiopentone • Effects • Less excitement seen in unpremedicated animals except in young puppies • Reduces cerebral blood flow and cerebral metabolic rate • Marked systemic hypotension not associated with tachycardia  significant decreased in cardiac output • Decreases risk of catecholamine induced arrhythmia • More pronounced apnoea on induction • Dose dependent respiratory depression • May have muscle twitching that is not always responsive to muscle relaxants