Anesthetics

1. Anesthetics

2. Overview • General anesthesia is essential to surgical practice, because it renders patients: • analgesic • amnesic • unconscious • provides muscle relaxation and suppression of undesirable reflexes. • No single drug is capable of achieving these effects both rapidly and safely.

3. Preanesthetic medication serves to: • calm the patient • relieve pain • protect against undesirable effects of the subsequently administered anesthetic or the surgical procedure. • Skeletal muscle relaxants: • facilitate intubation • suppress muscle tone to the degree required for surgery.

4. a patient is intubated and connected to an anesthesia breathing machine

5. Potent general anesthetics are delivered via: • Inhalation • intravenous injection

7. Induction, Maintenance, and Recovery from Anesthesia • Anesthesia can be divided into three stages: • Induction • Maintenance • Recovery • Inductionis defined as the period of time from the onset of administration of the anesthetic to the development of effective surgical anesthesia in the patient. • Maintenanceprovides a sustained surgical anesthesia. • Recoveryis the time from discontinuation of administration of the anesthesia until consciousness and protective physiologic reflexes are regained.

8. A. Induction • General anesthesia is normally induced with an intravenous anesthetic like thiopental • It produces unconsciousness within 25 seconds after injection. • At that time, additional inhalation or intravenous drugs comprising the selected anesthetic combination may be given to produce the desired depth of surgical (Stage III) anesthesia. • [Note: This often includes coadministration of an intravenous skeletal muscle relaxant to facilitate intubation and relaxation.

9. Currently used muscle relaxants include pancuronium, doxacurium, rocuronium, vecuronium, cisatricurium, atracurium, mevacurium and succinylcholine. • For children, without intravenous access, nonpungent agents, such as halothane or sevoflurane, are used to induce general anesthesia. This is termed inhalation induction.

10. B. Maintenance of anesthesia • Anesthesia is usually maintained by the administration of volatile anesthetics, because these agents offer good minute-to-minute control over the depth of anesthesia. • Along with inhalation agents, opioids, such as fentanyl, are often used for pain, because inhalational agents are not good analgesics.

11. C. Recovery • Postoperatively, the anesthesiologist withdraws the anesthetic mixture and monitors the return of the patient to consciousness. • For most anesthetic agents, recovery is the reverse of induction; that is, redistribution from the site of action (rather than metabolism of the anesthetic) underlies recovery.

12. D. Depth of anesthesia • The depth of anesthesia has been divided into four sequential stages. • Each stage is characterized by increased central nervous system (CNS) depression, which is caused by accumulation of the anesthetic drug in the brain.

13. Stage I—Analgesia: • Loss of pain sensation • The patient is conscious and conversational. • Amnesia and a reduced awareness of pain occur as Stage II is approached.

14. Stage II—Excitement: • The patient experiences delirium and possibly violent, combative behavior. • There is a rise and irregularity in blood pressure. • The respiratory rate may increase. • To avoid this stage of anesthesia, a short-acting barbiturate, such as thiopental, is given intravenously before inhalation anesthesia is administered.

15. Stage III—Surgical anesthesia: • Regular respiration and relaxation of the skeletal muscles occur in this stage. • Eye reflexes decrease progressively, until the eye movements cease and the pupil is fixed. • Surgery may proceed during this stage.

16. Stage IV—Medullary paralysis: • Severe depression of the respiratory and vasomotor centers occur during this stage. • Death can rapidly ensue unless measures are taken to maintain circulation and respiration.

17. Molecular mechanism of the GA : • GABA –A : Potentiation by Halothane, Propofol, Etomidate • Ligand-gated potassium (K+) channels, increase potassium conductance to hyperpolarize and inhibit neuronal membrane activity. • NMDA receptors : inhibited by Ketamine

18. The main target of inhalation anesthetics is the brain.

19. There are two types of anesthetics : • Inhalational --- for maintenance • Intravenous --- for induction for short procedures

20. Inhalation anesthetics: • Advantage of controlling the depth of anesthesia. • Metabolism is very minimal. • Excreted by exhalation.

21. Inhalational anesthetics : • Non-halogenated gas: • Nitrous oxide • Halogenated hydrocarbons: • Halothane • Enflurane • Isoflurane • Desflurane • Sevoflurane • Methoxyflurane– nephrotoxicity.

22. The important characteristics of Inhalational anesthetics which govern the anesthesia are : • Solubility in the blood (blood : gas partition co-efficient) • Solubility in the fat (oil : gas partition co-efficient)

23. Blood : gas partition co-efficient: • the ratio of the concentrations of anesthetic gas in the blood and gas phases at equilibrium • represents the capacityof the blood or a specific tissue to absorb the anesthetic • It is a measure of solubility in the blood. • is the single most important factor in determining the speed of induction and recovery

24. Isoflurane for example has a blood/gas partition coefficient of 1.4 • This means that if the gas is in equilibrium the concentration in blood will be 1.4 times higher than the concentration in the alveoli. • A higher blood gas partition coefficient means a higher uptake of the gas into the blood and therefore a slower induction time. • It takes longer until the equilibrium with the brain partial pressure of the gas is reached

25. It determines the rate of induction and recovery of Inhalational anesthetics. • Lower the blood : gas co-efficient – faster the induction and recovery – Nitrous oxide. • Higher the blood : gas co-efficient – slower induction and recovery – Halothane.

26. BLOOD GAS PARTITION CO-EFFICIENT Lower anesthetic solubility  in blood results in the "blood" compartment becoming saturated with the drug following fewer gas molecules transferred from the lungs into the blood

27. Oil: gas partition co-efficient: It is a measure of lipid solubility. Lipid solubility - correlates strongly with the potency of the anesthetic. Higher the lipid solubility – potent anesthetic. e.g., halothane

28. Anesthesiology

29. MAC value: • It is defined as the minimum alveolar anesthetic concentration ( % of the inspired air) at which 50% of patients do not respond to a surgical stimulus. • is a measure of inhalational anesthetic potency. • MAC values are additive

30. OIL GAS PARTITION CO-EFFICIENT The higher the Oil: Gas Partition Co-efficient lower the MAC . E.g., Halothane 0.8 1.4 220

32. Inhalational anesthetics • Nitrous oxide: • Safest inhalational anesthetic. • Weak anesthetic but a good analgesic. • No toxic effect on the heart, liver and kidney. • Caution about • diffusional hypoxia:a transient hypoxic episode after the cessation of nitrous oxide anesthesia if air is inhaled instead of pure oxygen; caused by the rapid diffusion of nitrous oxide out into the alveoli diluting the oxygen that is there. • megaloblastic anemia:

33. Halothane: It is a potent anesthetic. Induction is pleasant. It sensitizes the heart to catecholamines. It dilates bronchus – preferred in asthmatics. It inhibits uterine contractions. Halothane hepatitis and Malignant hyperthermia can occur.

34. Malignant hyperthermia • is a rare life-threatening condition seen in genetically susceptible individuals. • triggered by exposure to halogenated anesthetics, and the neuromuscular blocking agent succinylcholine. • Syndrome: characterized by • muscle rigidity • Hypermetabolic activity in skeletal muscles • Sudden increase in body temperature • if not treated quickly can lead to circulatory collapse and death. • Due to genetically defective Ca ++ release channel of skeletal muscle sarcoplasmic reticulum • Dantroline is a clinical antidote (blocks Ca++ from SR)

37. Enflurane: Sweet and ethereal odor. Generally does not sensitize the heart to catecholamines. Seizures occurs at deeper levels –contraindicated in epileptics. Caution in renal failure due to fluoride.

38. Isoflurane: It is commonly used with oxygen or nitrous oxide. It does not sensitize the heart to catecholamines. Its pungency can irritate the respiratory system.

39. Desflurane: It is delivered through special vaporizer. It is a popular anesthetic for day care surgery. Induction and recovery is fast, cognitive and motor impairment are short lived It irritates the air passages producing cough and laryngospasm. Malignant hyperthermia may occur with desflurane.

40. Sevoflurane: Induction and recovery is fast. It is pleasant and acceptable due to lack of pungency. It do not cause air way irritancy. Concerns about nephrotoxicity.

42. Parenteral anesthetics (IV): • These are used for induction of anesthesia. • Rapid onset of action. • Recovery is mainly by redistribution. • Also reduce the amount of inhalation anesthetic for maintenance. • E.g., includes thiopental, midazolam, propofol, etomidate, ketamine.

43. Thiopental (Pentothal): • It is an ultra short acting barbiturates. • It produces unconsciousness ~ 20 seconds. • Consciousness regained within 10-20 mins by redistribution to skeletal muscle. • It does not increase Intracranial Temperature. • It is eliminated slowly from the body by metabolism and produce hang over. • It can be used for rapid control of seizures.

44. Propofol(Diprivan): • Most commonly used IV anesthetic. • Unconsciousness in ~ 45 seconds and lasts ~15 minutes. • Anti-emetic in action. • Suited for day care surgery - residual impairment is less marked. • It is used for sedation in intensive care units.

45. Etomidate: • It is a short acting anesthetic (5-10 min) • It suppress the production of steroids from the adrenal gland and no repeated injections. • It is a pro-convulsant and emetic. • CVS stability is the main advantage over anesthetics. • used for: • the induction of general anesthesia • sedation for short procedures such as reduction of dislocated joints and cardioversion

46. Ketamine : Dissociative anesthesia • Produce - profound analgesia, cataleptic state, immobility, amnesia with light sleep. • Acts by blocking NMDA receptors • Heart rate and BP are elevated due to sympathetic stimulation. • Respiration is not depressed and reflexes are not abolished.

47. Ketamine: • Emergence delirium: hallucinations and involuntary movements occurs in 50% cases during recovery. • It is useful for burn dressing and trauma surgery. • Dangerous for hypertensive and ischemic heart disease .

48. Innovar analgesic (Fentanyl )+ a neuroleptic (Droperidol) = Neuroleptanalgesia : • It is characterized by general quiescence, psychic indifference and intense analgesia without total loss of consciousness. • Produced by a combination of an opioid analgesic (Fentanyl )and a neuroleptic (Droperidol) as Innovar

49. Neuroleptanalgesia : • It is associated with decreased motor functions, suppressed autonomic reflexes, cardiovascular stability with mild amnesia. • It causes drowsiness but respond to commands. • Used for endoscopies, angiography and minor operations.