Injectable Anesthesia

1. Injectable Anesthesia S. HabibianDehkordi D.V.M, Ph.D, Postdoctral Research Assistant in Neuropharmacology, Postdoctral Research Associate in Neuroscience

2. Injectable anesthesia Adventage Disadventage

3. Pharmacokinetics of Injectable Anesthetics • Partition into the highly lipophilic tissues of the brain and spinal cord • Produce rapid anesthesia • Immediate low concentrations of anesthetic in blood stream causes the drug to leave the CNS and enter the peripheral tissues via the blood • Effect can wear off in about 10 minutes unless continuously infused

4. Injectable Anesthetics • Brabiturates • Propofol • Cyclohexamines • Etomidate • Guaifenesin • Fentanyl

5. Injectable Anesthetics • Barbiturates • Oxybarbiturates • Phenobarbital • Considered an anticonvulsant, not an anesthetic • Pentobarbital (Nembutal, Somnotol • Thiobarbiturate • Thiopental (pentothal) • Methylated oxybarbiturates • Methohexital (Brevital)

6. Injectable Anesthetics • Barbiturates • Also classified by speed of onset of action • Long acting • Phenobarbital 8-12 hours • Short acting • Pentobarbital 45 to 90 minutes • Ultra short acting • Thiopental 5-15 minutes

7. Injectable Anesthetics • Barbiturates • Can be used for sedation, anticonvulsants and anesthesia • Commonly used as an induction agent • Cause unconsciousness at adequate dosages • Depress respiration and cardiovascular system to varying extents • Give to effect • Give as a bolus

8. Injectable Anesthetics • Barbiturates • Nonreversible • Are protein binding • Plasma protein levels can alter the rate and amount of absorption of the barbiturates • The amount of free drug in the blood will increase if the patient is hypoproteinemic • More drug will be available to penetrate into the CNS and cause unconsciousness

9. Injectable Anesthetics • Barbiturates • Are lipid soluble to varying degrees • Lipid solubility increases from the long acting to the ultra short acting • The more lipid soluble the easier it is for the drug to cross the blood brain barrier • Also recover from the effects of the barbiturate quicker • Recovery depends on a combination of redistribution and hepatic metabolism

10. Injectable Anesthetics • Barbiturates • As blood levels decline because of metabolism, small quantities of the drug will re-enter the bloodstream from muscle and fat • Occurs at such a low level and rate that this pathway does not significantly alter levels of consciousness • Eliminated from the body by liver metabolism and excretion of the metabolites in the urine

11. Injectable Anesthetics • Barbiturates • Examples • Phenobabital • Used mostly as a sedative for excitable dogs or as an anticonvulsant for epileptic type seizures • Sedation can last up to 24 hours depending on the dose

12. Injectable Anesthetics • Barbiturates • Examples • Pentobarbital • Once commonly used for induction (now the ultra short is most common) • Can be used to control seizures but EEG seizure activity will still exist • Relatively non-irritating, can be given IM • IV significant effect on the animal at one minute with maximum effect at 5 minutes • Sheep recover fast and smooth. All other animals have a long rough recovery

13. Injectable Anesthetics • Barbiturates • Examples • Thiopental • Comes as a crystalline powder in multidose vials • So can be reconstituted in varied concentrations • Limited stability once reconstituted • Avoid injecting air which may cause premature precipitation

14. Injectable Anesthetics • Barbiturates • Examples • Thiopental • Has a high lipid solubility • Enters the brain rapidly • Redistributes from the brain to other tissues, quicker recovery • Redistributed to muscle and fat readily which slows metabolism by the liver • Should be avoided in sight hounds because of prolonged recovery

15. Injectable Anesthetics • Barbiturates • Examples • Thiopental • Prolonged recovery will occur if subsequent doses have been given for maintenance of anesthesia and if the muscle and fat have been saturated • Cumulative effect • Recovery slow and rough • Best to use only for induction or for a maximum maintenance effect of 30 minutes

16. Injectable Anesthetics • Barbiturates • Examples • Thiopental • Significant effect is noted 30 to 60 seconds after injection • This barbiturate has a transient arrhythmogenic potential, especially if given by rapid bolus • Transient apnea may also be noted • Perivascular administration can cause extreme irritation and sloughing of tissue, especially at concentration greater than 2.5% • Irrigate the affected tissue with saline • Poor relaxation and analgesia when used alone • Can be used in combination with propofol for induction

17. Injectable Anesthetics • Barbiturates • Examples • Methohexital • Highly lipid soluble, rapidly metabolized • Quickest onset, shortest duration and quickest recovery • Good choice in sight hounds or animals with extremely lean bodies • Extremely sensitive due to poor ability to metabolize and lack of fat storage • Liver metabolism is rapid, additional administration is not cumulative

18. Injectable Anesthetics • Barbiturates • Examples • Methohexital • Good choice for brachycephalics to obtain smooth, quick induction and intubation • Rapid recoveries without hangover effects • Induction effect is noted 15 to 60 seconds after injection • Can get some convulsive activity in some animals during recovery • Lethal dose is only 2 to 3 times the anesthetic dose • Can cause profound respiratory depression

19. Propofol • highly lipophilic • Large Vd • Triphasic distribution • Rapid redistribution – 2-3 min • Metabolism • Slow elimination from adipose tissues

20. Advanatges of Propofol • Rapid onset • Rapid offset • Optimal sedation level • Antiemetic

21. Propofol Metabolism • Eliminated as sulfate and/or glucuronide conjugates in the urine • Less than 0.3% excreted as the parent compound • Extra hepatic metabolism • Hepatic and renal dysfunction do not significantly alter the pharmacokinetics of propofol • Elderly – lower Vd and lower clearance, lower doses needed

22. Adverse Effects of Propofol • IV injection site pain • Hypotension especially in hypovolemia • Hypoxia • Microbial contamination • lipidemia > 3 days of infusion • Green discoloration of the urine

23. Injectable Anesthetics • Propofol • Used for sedation, induction, and/or anesthetic maintenance by repeated bolus injections or continuous infusion • Rapid acting with smooth, excitement free induction • Rapid smooth recovery because of redistribution to vessel rich areas such as the brain rather than to muscle and fat • More easily and rapidly biotransformed by the liver in comparison to barbiturates • Much less or no hangover effect • First choice for sight hounds or others of similar body types…..if unavailable then methohexital • Ideal for injectable maintenance of anesthesia because there is no accumulation

24. Injectable Anesthetics • Propofol • Minimal cardiovascular effects, but may cause • Tachycardia • Bradycardia • Transient arterial and venous dilation • Depressed cardiac contractility • Despite these possibilities it is still considered safe in cardiac patients

25. Injectable Anesthetics • Propofol • Contraindications and cautions • Transient apnea has been noted after rapid IV bolus injection • Very dependent on how quickly the drug is given • Has caused respiratory arrest in some cases • Avoid in animals that are hypotensive • Blood loss • Dehydration • Severe illness • Recent trauma • May see transient excitement and muscle tremors

26. Injectable Anesthetics • Propofol • Good anticonvulsant • Non-irritating with incidental perivascular injection • Some muscle relaxation occurs but analgesia is poor • Will support bacterial growth because of soy content • Opened vials should be discarded within 6 hours to avoid contamination

27. Injectable Anesthetics • Cyclohexamines • Classified as a dissociative anesthetic • Examples include ketamine and tiletamine • Produces catalepsy, amnesia and analgesia • Inhibits N-methyl-D-aspartate (NMDA) • Results in selective superficial analgesia • Visceral pain is not abolished

28. Injectable Anesthetics • Cyclohexamines • Pharyngolaryngeal reflexes are partially intact • Excessive skeletal muscle tone • Can be minimized by prior administration of tranquilizers, sedatives or benzodiazepine • Mild cardiac stimulation • Increased blood pressure • Decreased cardiac contractility • Increased heart rate • May induce pulmonary edema or acute heart failure in animals with pre-existing heart conditions

29. Injectable Anesthetics • Cyclohexamines • Apneustic breathing • Rate may increase • Arterial pCO2 may be decreased • Especially seen after IV administration • Hyperresponsive and ataxic during recovery • Small percentage of cats will show convulsive activity • Minimally sensitizes the heart to catecholamine induced arrhythmias

30. Injectable Anesthetics • Cyclohexamines • Other side effects • Tissue irritation • Increased salivation and lacrimation • Increase in CSF pressure • Open eyes with central dilated pupil • Nystagmus • Increased intraocular pressure • Temporary personality changes • Excitement on recovery

31. Injectable Anesthetics • Cyclohexamines • Effects partially reversed with adrenergic and cholinergic blockade • Dogs more likely to seizure • Combine with a tranquilizer (acepromazine or diazepam) • Metabolized by the liver and excreted somewhat in an unchanged form through kidneys in dog • Excreted primarily by kidneys in cat • Use with caution in animals with renal or hepatic disease • Can be used in cats with urethral obstruction provided no disease is present and obstruction is removed • Use with caution in seizure disorders or those undergoing neurological system procedures

32. Injectable Anesthetics • Cyclohexamines • Ketamine • Commonly combined with diazepam or other benzodiazepines as an induction agent • Provides muscle relaxation and smoother recoveries than with ketamine alone • In species where IV administration is not possible or easily accessible, ketamine can be combined with midazolam and given IM

33. Injectable Anesthetics • Cyclohexamines • Tiletamine • Combined in commercial form with zolazepam (benzodiazepine) in product called Telazol • Can be used in all animal species • Same action as ketamine/diazepam but can be given IM or subQ • Good for exotics and aggressive animals

34. Injectable Anesthetics • Etomidate • Very safe • Rapid and ultrashort acting • Rapidly distributing • Noncumulative

35. Injectable Anesthetics • Etomidate • Interacts with GABA receptors • Has little or no effect on cardiac output, respiratory rate or blood pressure • Very popular for animals with cardiac disease • Can be given as repeated bolus or continuous infusion • Occasionally may cause vomiting, diarrhea, excitement and apnea on induction and recovery • Is a mild respiratory depressant

36. Injectable Anesthetics • Etomidate • Does not produce a histamine release • Produces excessive muscular rigidity and seizures in horses and cattle • Rapidly metabolized in the liver • Does cross placental barrier but effects on the fetus are minimal as it is rapidly cleared • IV injection may be painful and may cause phlebitis especially in the smaller veins

37. Injectable Anesthetics • Guaifenesin • Glycerol guiacolate • Available in white powder; resuspended with sterile water or dextrose • Common decongestant and antitussive • Used for it’s effect as a central muscle relaxant, mostly in large animals • Minimal effects on the diaphragm at relaxant doses • Induction and recovery are excitement free • Minimal respiratory and cardiac effect • Does cross placental barrier but effects on fetus are minimal

38. Injectable Anesthetics • Fentanyl • Considered primarily an analgesic • Can produce unconsciousness • Used as an injectable induction agent often in combination with a tranquilizer, sedative or benzodiazepine • Referred to as a neuroleptanalgesic • Very safe for high risk patients because it does not cause apnea and does not affect cardiac output or contractility

39. Thanks for your attentions