General anesthetics(VK)


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  • An acutely disturbed state of mind that occurs in fever, intoxication, and other disorders.Wild excitement or ecstasy.  drowsiness, disorientation, and hallucination
  • Have a student read this slide out loud to the rest of the class
  • Paresis:partial paralysis! Apneic:Temporary absence or cessation of breathing. 
  • Have a student read this slide out loud to the rest of the class
  • Retching:an involuntary spasm of ineffectual vomiting
  • NOTES:
    Time from emergence to full recovery (orientation) following an induction is very rapid.
  • NOTES:
    Induction doses are associated with apnea and hypotension secondary to direct myocardial depression and a decrease in systemic vascular resistance with minimal change in heart rate. Stay on top of respiration rate and profusion!
    The drug obtunds (dulls) the hemodynamic response to laryngoscopy and intubation.
  • NOTES:
    Popofol potentates CNS and circulatory depressant effects of narcotics, sedative hypnotics, volatile anesthetics.
    Possible burning/stinging at injection site. Propofol is water insoluble and is formulated in a soybean-fat emulsion.
  • NOTES:
    Propofol reduces cerebral blood flow, intracranial pressure, and cerebral metabolic rate. The book still said precaution for ICP? WHY?
    Propofol may activate the epileptogenic foci with in the gray matter.
  • NONE
  • Onset: IV = 30 seconds to 1 minute, IM = 15 minutes, PO/Rectal = less than 10 minutes
    Question: Should we avoid giving a large bolus of Midazolam?
    Answer: Yes, midazolam is a rapid acting drug, large doses could cause respiratory depression or arrest.
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  • General anesthetics(VK)

    1. 1. General Anesthesia
    2. 2. General Anesthesia  Definition:The word anaesthesia is derived from the Greek: meaning insensible or without feeling  Is the loss of response to & perception of all external stimuli.  General anaesthetics are the drugs which causes reversible loss of all the sensations and consciousness
    3. 3. Components of General Anesthesia:  1.Unconsciousness  2. Analgesia  3. Muscle relaxation
    4. 4. ROLE OF ANAESTHESIOLOGIST So we can summarize the role of anaesthesiologist in: 1. Knowing physiology of body well. 2. Knowing the pathology of patient disease and co-existing disease 3. Study well the pharmacology of anaesthetic drugs and other drugs which may be used intra-operatively. 4. Use anaesthetics in the way and doses which is adequate to patient condition and not modified by patient pathology with no drug toxicity. 5. Lastly but most importantly administrate drug to manipulate major organ system, to maintain homeostasis and protect patient from injury by surgeon or theatre conditions.
    5. 5. APPROACH TO ANAESTHESIA The empirical approach to anaesthetic drug administration consists of selecting an initial anaesthetic dose {or drug} and then titrating subsequent dose based on the clinical responses of patients, without reaching toxic doses. The ability of anaesthesiologist to predict clinical response and hence to select optimal doses is the art of anaesthesia
    6. 6. TOOLS OF ANAESTHESIA Knowing physiology, pathology ,and pharmacology is not enough to communicate safe anesthesia But there is need for two important tools: 1. Anaesthetic machine. 2. Monitoring system.
    7. 7. ANAESTHETIC MACHINE 1. Oxygen gas supply. 2. Nitrous oxide gas supply. 3. Flow meter 4. Vaporizer specific for every agent 5. Mechanical ventilator 6. Tubes for connection.
    8. 8. MONITORING 1. Pulse, ECG 2. Blood pressure 3. Oxygen saturation. 4. End tidal CO2 5. Temperature 6. Urine output, CVP, EEG, bispectral index, muscle tone, ECHO, drug concentration.
    9. 9. Phases of Anesthesia  Induction: keeping the patient to sleep  Maintenance: keeping the patient asleep  Emergence: waking the patient up
    10. 10. STAGES OF GENERAL ANESTHESIA  STAGE 1 (Analgesia): From induction of anesthesia to loss of conciousness (loss of eyelid reflex). Pain is progressively abolished in this stage.  STAGE 2 (Delirium/Excitement): From loss of consiousness to beginning of regular respiration. Characterized by uninhibited excitation. Pupils are dilated and eyes divergent. Agitation, delirium, irregular respiration, and breatholding are commonly seen. Potentially dangerous responses can occur during this stage including vomiting, laryngospasm, HTN, tachycardia, and uncontrolled movement.
    11. 11.  STAGE 3 (Surgical Anesthesia): Regular respiration to caessation of spontaneous breathing Central gaze, constricted pupils, and regular respirations. Target depth of anesthesia is sufficient when painful stimulation does not elicit somatic reflexes or deleterious autonomic reflexes.
    12. 12. Plane 1 From the return of regular respirations to the cessation of REM. Plane 2 The Surgical Plane From the cessation of REM to the onset of paresis of the intercostal muscles. Plane 3 From the onset to the complete paralysis of the intercostal muscles. Plane 4 From the paralysis of the intercostal of this plane the patient will be apneic.
    13. 13.  STAGE 4 (Impending Death/Overdose): Onset of apnea, dilated and nonreactive pupils, and hypotension to complete circulatory failure.
    14. 14. Classic Stages of Anesthesia*  Stage 1: Analgesia – decreased awareness of pain, amnesia  Stage 2: Disinhibition – delirium & excitation, enhanced reflexes, retching, incontinence, irregular respiration  Stage 3: Surgical Anesthesia – unconscious, no pain reflexes, regular respiration, BP is maintained  Stage 4: Medullary Depression – respiratory & CV depression requiring ventilation & pharmacologic support. * Seen mainly with Ether. Not all stages are observed with modern GAs.
    15. 15. Mechanisms of Action Enhanced GABA effect on GABAA Receptors 1. – – – - Etomidate - Propofol Block nicotinic receptor subtypes (analgesia) 1. – Moderate to high conc’s of inhaled anesthetics Activate K channels (hyperpolarize ) 1. – Nitrous oxide, ketamine, xenon Inhibit NMDA (glutamate) receptors 1. – 1. Inhaled anesthetics Barbiturates Benzodiazepines Nitrous oxide, ketamine, xenon, high dose barbiturates Enhance glycine effect on glycine R’s (immobility)
    16. 16. Regional Effects  Immobilization in response to surgical incision (spinal cord)  Sedation, loss of consciousness (↓thalamic firing)  Amnesia (↓hippocampal neurotransmission)
    17. 17. CLASSIFICATION  INTRAVENOUS INDUCING AGENTS Thiopentone sodium Methohexital Propofol Etomidate SLOWER ACTING Diazepam Lorazepam Midazolam DISSOCIATIVE ANAESTHESIA Ketamine OPIOID ANALGESIA Fentanyl  INHALATIONAL GAS Nitrous oxide LIQUID Ether Halothane Enflurane Desflurane Sevoflurane
    18. 18. Parenteral Anesthetics (Intravenous)  Most commonly used drugs to induce anesthesia – – – – – Barbiturates (Thiopental* & Methohexital) Benzodiazepines (Midazolam) Opioids (Morphine & Fentanyl) Propofol* Etomidate * Most commonly used for induction
    19. 19. Barbiturates & Benzodiazepines MOA: GABA Barbiturate BZDS 1) Both bind to GABAA receptors, at different sites • Both cause increase Clinflux in presence of GABA • BNZ binding can be blocked by flumazenil. 2) Barbs at high doses - are also GABA mimetic, block Na channels NMDA/glutamate R
    20. 20. Dose Response Relationships Coma Barbiturates CNS Effects Medullary depression Benzodiazepines Anesthesia Hypnosis Sedation, disinhibition, anxiolysis Increasing dose Possible selective anticonvulsant & musclerelaxing activity
    21. 21. Barbiturates  Thiopental & methohexital are highly lipid soluble & can produce unconsciousness & surgical anesthesia in <1 min.  Rx: induction of anesthesia & short procedures  Actions are terminated by redistribution  With single bolus - emergence from GA occurs in ~ 10 mins  Hepatic metabolism is required for elimination
    22. 22. Thiopental (3-5mg/kg)  Barbs are respiratory & circulatory depressants (Contraindicated: hypovolemia, cardiomyopathy, betablockade,etc.)  Psychomotor impairment may last for days after use of a single high dose  Taste of garlic prior to anesthesia  Potentially fatal attacks of porphyria in pts with a history of acute or intermittent porphyria.  Delay giving other drugs (e.g. NMJ blockers) until barb has cleared the i.v. line to avoid precipitation.
    23. 23. Propofol  Propofol is a diisopropylphenol intravenous hypnotic agent that produces rapid induction of anesthesia with minimal excitatory activity  It undergoes extensive distribution and rapid elimination by the liver
    24. 24. Propofol  Produces anesthesia as rapidly as i.v. barb’s & but recovery is more rapid than barb’s.  Recovery is not delayed after prolonged infusion (due to more rapid clearance).**  Patients are able to ambulate sooner & patients “feel better” in the post-op period compared to other i.v. anesthetics.  Antiemetic effects (pts w/ ↑risk of nausea), marked hypotension (>barbs)  Commonly used as component of “balanced anesthesia” for maintenance of anesthesia following induction of anesthesia. ** More rapid discharge from the recovery room
    25. 25. INDICATIONS  Conscious sedation  Induction agent of anesthesia  Maintenance of anesthesia  Antiemetic
    26. 26. DOSE AND ROUTES  Conscious sedation 25 - 50 mg IV, Titrate slowly to desired effect (on set of slurred speech)  Induction 2 - 2.5 mg/kg IV, given slowly over 30 seconds in 2 - 3 divided doses  Maintenance 25 - 50 mg IV bolus Infusion 100 - 200 mcg/kg/min  Antiemetic 10mg IV
    27. 27. ADVERSE REACTIONS, PRECAUTIONS, AND INTERACTIONS  Reduce doses in elderly, hypovolemic, high risk surgical patients and with use of narcotics and sedative hypnotics  Minimize pain by injecting into a large vein and/or mixing IV lidocaine (0.1 mg/kg) with the induction dose of Propofol
    28. 28. ADVERSE REACTIONS, PRECAUTIONS, AND INTERACTIONS  Not recommended for patient with increased intracranial pressure  Should be administered with caution to patients with a history of epilepsy or seizures disorder
    29. 29. Etomidate  Rapid induction (~1 min), Short duration of action (3-5 mins)  Used as a supplement with nitrous oxide for short surgical procedures  Hypnotic, but not analgesic  Little effect on CV & Respiration  Can cause post-op nausea & decrease cortisol production w/ long term infusion*.  Primarily used in pts w/ limited cardiac or respiratory reserve (safer than barbs or propofol in pts w/ coronary artery dx., cardiomyopathy, etc.)
    30. 30. Benzodiazepines  Midazolam (> Diazepam & Lorazepam) – Used to produce anxiolysis, amnesia & sedation prior to induction of GA w/ another agent. – Sedative doses achieved w/in 2 min, w/ 30 min duration of action (short duration). – Effects are reversed with flumazenil.
    31. 31. INDICATIONS Midazolam  pre-op sedative  induction of anesthesia  Conscious sedation  commonly used for short diagnostic or endoscopic procedures
    32. 32. DOSE AND ROUTES Midazolam  may be given IM, PO, or IV  Pre-op sedation: 0.07-0.08 mg/kg IM 1 hr prior  Induction of anesthesia: 0.050 - 0.350 mg/kg IV  Basal sedation: 0.035 mg/kg initially, then titrated slowly to a total dose of 0.1 mg/kg
    33. 33. • Recovery half times from anesthesia can be Recovery Half Time (mins) “Context Sensitive” 150 Diazepam 100 Midazolam 50 0 Thiopental* Propofol Etomidate 0 2 4 6 8 Infusion Duration (hours) *Unconsciousness can last for days after prolonged administration 10
    34. 34. Opioids (Fentanyl & Remifentanil*)  GAs do not produce effective analgesia (except for ketamine).  Given before surgery to minimize hemodynamic changes produced by painful stimuli. This reduces GA requirements.  High doses can cause chest wall rigidity & post-op respiratory depression  Therapeutic doses will inhibit respiration (↑CO2)  Used for post-op analgesia, supplement anesthetic in balanced anesthesia.  Remifentanil is an ester opioid metabolized by plasma esterases. It is very potent but w/ a short t (3-10 mins).
    35. 35. Ketamine  Nonbarbiturate, rapid acting general anesthetic  Dissociated from the environment, immobile, and unresponsive to pain  Profound analgesic
    36. 36. Ketamine  Selectively blocks the associative pathways producing sensory blockade  Preserved pharyngeal-laryngeal reflexes  Normal or slightly enhanced skeletal muscle tone  Cardiovascular and respiratory stimulation
    37. 37. INDICATIONS Ketamine  Sole agent for procedures that do not require skeletal muscle relaxation  Induction of anesthesia prior to the administration of other anesthetic agents  Supplementation of low potency agents
    38. 38. DOSE AND ROUTES Ketamine  may be injected IM or IV  Induction: 1-2 mg/kg Slow IV  Maintenance: 30-90 mcg/kg/min IV drip  Intramuscular: 6.5-13 mg/kg IM  10 mg/kg IM will produce approximately 12-25 min of surgical plane.
    39. 39. ADVERSE REACTIONS, PRECAUTIONS, AND INTERACTIONS Ketamine  contraindicated in pts. with known hypersensitivity or can't tolerate a significant increase in blood pressure  IV dose should be administered over 60 seconds. Rapid administration may cause respiratory depression or apnea
    40. 40. ADVERSE REACTIONS, PRECAUTIONS, AND INTERACTIONS Ketamine  BP, pulse rate, and respiratory rate are often stimulated  Concomitant use of barbiturates or narcotics prolong recovery time
    41. 41. Ketamine (1.5mg/kg)  A “dissociative anesthetic” that produces a cataleptic state that includes intense analgesia, amnesia, eyes open, involuntary limb movement, unresponsive to commands or pain.  Increases heart rate & blood pressure (opposite of other GAs)  Can be used in shock states (hypotensive) or patients at risk for bronchospasm.  Used in children & young adults for short procedures  Side Effects: nystagmus, pupillary dilation, salivation, hallucinations & vivid dreams
    42. 42. Inhaled Anesthetics
    43. 43. Inhaled Anesthetics  Easily vaporized liquid halogenated hydrocarbons  Administered as gases (gas)
    44. 44. Inhaled Anesthetics  Partial pressure or “tension” in inspired air is a measure of their concentration  The speed of induction of anesthesia depends on: – Inspired gas partial pressure (GA concentration) – Ventilation rate – GA solubility (less soluble GAs equilibrate more quickly with blood & into tissues such as the brain)
    45. 45. Minimum Alveolar Concentration  The minimum alveolar anesthetic concentration required to eliminate the response to a painful stimulus in 50% of patients  A measure of GA potency.  It’s “a population average”.  1.3 MAC - 100% will not respond to stimuli.  When several GAs are mixed, their MAC values are additive (e.g. nitrous oxide is commonly mixed w/ other anesthetics).
    46. 46. Elimination  Anesthesia is most commonly terminated by redistribution of drug from brain to the blood & out through the lungs.  The rate of recovery from anesthesia for GAs with low blood: gas PCs is faster than for highly soluble Gas.  Time is $$ in the O.R. & recovery room Blood: Gas P. Coeff – Haltothane – Desflurane – Sevoflurane 2.30 0.42 0.69  Halothane & methoxyflurane undergo hepatic metabolism & can cause liver toxicity.
    47. 47. Properties of Inhaled anesthetics Nitrous Oxide – MAC > 100% : Incomplete anesthetic – Good analgesia – No metabolism – Rapid onset & recovery – Used along w/ other anesthetic; fast induction & recovery * fewer side effects also seen in children
    48. 48. Halothane •The first halogenated inhalational anesthetic •Not pungent (use for induction w/ children)* •Medium rate of onset & recovery •Although inexpensive, its use has declined •Sensitizes the heart to epi-induced arrhythmias •Rare halothane induced hepatitis
    49. 49. Desflurane – Most rapid onset of action & recovery of the halogenated GAs – Widely used for outpatient surgery – Irritating to the airway in awake patients & causes coughing, salivation & bronchospasm (poor induction agent) – Used for maintenance of anesthesia Sevoflurane – Very low blood:gas partition coefficient w/ relatively rapid onset of action & recovery * – Widely used for outpatient surgery* – Not irritating to the airway – Useful induction agent, particularly in children * Similar to Desflurane
    50. 50. Isoflurane – Medium rate of onset & recovery – Used for induction & maintenance of anesthesia – Isoflurane “was” the most commonly used inhalational GA in the US. Has been largely replaced by Desflurane Methoxyflurane – Now widely considered obsolete – Slow onset & recovery – Extensive hepatic/renal metabolism, w/ release of F- ion causing renal dysfunction
    51. 51. Toxicity  Malignant Hyperthermia – Esp. when halogenated GA used with succinylcholine – Rx: dantrolene (immediately)  Halothane: – Halothane undergoes >40% hepatic metabolism – Rare cases of postoperative hepatitis occur – Halothane can sensitize the heart to Epi (arrhythmias)  Methoxyflurane – F release during metabolism (>70%) may cause renal insufficiency after prolonged exposure.  Nitrous oxide – Megaloblastic anemia may occur after prolonged exposure due to decreases in methionine synthase activity(Vit B12 deficiency).
    52. 52. PREANAESTHETIC MEDICATION  Opioids: Morphine-10 mg Pethidine 50-100mg i.m.  Sedatve antianxiety : Diazepam 5-10mg orally Lorazepam 2mg i.m.  Anticholinergics : Atropine 0.6mg i.m./ i.v Glycopyrolate 0.1-0.3mg i.m  Neuroleptics: Chlorpramazine 25mg  H2 blockers : Ranitidine 150mg Famotidine 40mg  Antiemetics : Metoclopramide 10-20mg i.m
    53. 53. Airway Alveoli Blood Blood:Gas PC Brain Nitrous Oxide Airway Alveoli Blood 0.47 Brain Halothane 2.30 • Why induction of anesthesia is slower with more soluble anesthetic gases. In this schematic diagram, solubility in blood is represented by the relative size of the blood compartment (the more soluble, the larger the compartment). Relative partial pressures of the agents in the compartments are indicated by the degree of filling of each compartment. For a given concentration or partial pressure of the two anesthetic gases in the inspired air, it will take much longer for the blood partial pressure of the more soluble gas (halothane) to rise to the same partial pressure as in the alveoli. Since the concentration of the anesthetic agent in the brain can rise no faster than the concentration in the blood, the onset of anesthesia will be slower with halothane than with nitrous oxide.
    54. 54. Solubility Effects Arterial Anesthetic Levels Arterial anesthetic tension (% of inspired tension) Blood:Gas PC Nitrous Oxide 0.47 Halothane 2.30 Equilibration with a soluble GA may take hours to achieve. Time is $$ in the O.R. Methoxyflurane • Time (min) 12 Tensions of three anesthetic gases in arterial blood as a function of time after beginning inhalation. Nitrous oxide is relatively insoluble (blood:gas partition coefficient = 0.47); methoxyflurane is much more soluble (coefficient = 12); and halothane is intermediate (2.3).
    55. 55. Ventilation Rate’s Effect on Arterial Anesthetic Tension Arterial anesthetic tension (% of inspired tension) Ventilation (L/min) Nitrous Oxide Halothane Hyperventilation increases the speed of induction for Gas with normally slow onset Time (min) • Ventilation rate and arterial anesthetic tensions. Increased ventilation (8 versus 2 L/min) has a much greater effect on equilibration of halothane than nitrous oxide.
    56. 56. NMJ Blockers  Succinylcholine, Pancuronium  Used to: – relax skeletal muscle – facilitate intubation** – insure immobility  Reversed by neostigmine* & glycopyrrolate* during post-op period * quaternary drugs; * intubation is usually needed for airway maintenance & to prevent aspiration.
    57. 57. Dantrolene  Interfers with the release of calcium from the sarcoplasmic reticulum through the SR calcium channel complex.  Used to prevent or reverse malignant hyperthermia (which is otherwise fatal in ~50% of cases w/o dantrolene).  Given by i.v. push at the onset of symptoms (e.g. an unexpected rise in CO2 levels)  Supportive measures & 100% O2 are also used to treat malignant hyperthermia
    58. 58. Nausea & Vomiting  General anesthetics effect the chemoreceptor trigger zone & brainstem vomiting center (cause nausea & vomiting)  Rx: - Ondansetron (5-HT3 antagonist) to prevent - Avoidance of N2O - Propofol for induction - Keterolac vs. opioid for analgesia - Droperidol, metaclopromide & dexamethasone