2. General Anesthesia
ï Definition:The word
anaesthesia is derived from
the Greek: meaning insensible
or without feeling
ï Is the loss of response to &
perception of all external
stimuli.
ï General anaesthetics are the
drugs which causes reversible
loss of all the sensations and
consciousness
7. 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.
8. 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
9. 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.
10. 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.
11. 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.
12. Phases of Anesthesia
ï Induction: keeping the patient to sleep
ï Maintenance: keeping the patient
asleep
ï Emergence: waking the patient up
13. STAGES OF GENERAL
ANESTHESIA
ï STAGE 1 (Analgesia):
From induction of anesthesia to loss of conciousness (loss of
eyelid reflex). Pain is progressively abolished in this stage.
ï 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.
14. ï 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.
15. 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.
16. ï STAGE 4 (Impending Death/Overdose):
Onset of apnea, dilated and nonreactive pupils, and
hypotension to complete circulatory failure.
17. Classic Stages of Anesthesia*
ï Stage 1: Analgesia
â decreased awareness of pain, amnesia
ï Stage 2: Disinhibition
â delirium & excitation, enhanced reflexes, retching,
incontinence, irregular respiration
ï Stage 3: Surgical Anesthesia
â unconscious, no pain reflexes, regular respiration, BP is
maintained
ï Stage 4: Medullary Depression
â respiratory & CV depression requiring ventilation &
pharmacologic support.
* Seen mainly with Ether. Not all stages are observed with modern GAs.
18. Mechanisms of Action
Enhanced GABA effect on GABAA Receptors
1.
â
â
â
- Etomidate
- Propofol
Block nicotinic receptor subtypes (analgesia)
1.
â
Moderate to high concâs of inhaled anesthetics
Activate K channels (hyperpolarize )
1.
â
Nitrous oxide, ketamine, xenon
Inhibit NMDA (glutamate) receptors
1.
â
1.
Inhaled anesthetics
Barbiturates
Benzodiazepines
Nitrous oxide, ketamine, xenon, high dose barbiturates
Enhance glycine effect on glycine Râs (immobility)
19. Regional Effects
ï Immobilization in response to surgical incision
(spinal cord)
ï Sedation, loss of consciousness (âthalamic firing)
ï Amnesia (âhippocampal neurotransmission)
21. Parenteral Anesthetics
(Intravenous)
ï Most commonly used drugs to induce
anesthesia
â
â
â
â
â
Barbiturates (Thiopental* & Methohexital)
Benzodiazepines (Midazolam)
Opioids (Morphine & Fentanyl)
Propofol*
Etomidate
* Most commonly used for induction
22. Barbiturates & Benzodiazepines MOA:
GABA
Barbiturate
BZDS
1) Both bind to GABAA
receptors, at different sites
âą Both cause increase Clinflux in presence of GABA
âą BNZ binding can be
blocked by flumazenil.
2) Barbs at high doses - are
also GABA mimetic, block
Na channels
NMDA/glutamate R
24. Barbiturates
ï Thiopental & methohexital are highly lipid soluble & can produce
unconsciousness & surgical anesthesia in <1 min.
ï Rx: induction of anesthesia & short procedures
ï Actions are terminated by redistribution
ï With single bolus - emergence from GA occurs in ~ 10 mins
ï Hepatic metabolism is required for elimination
25.
26. Thiopental (3-5mg/kg)
ï Barbs are respiratory & circulatory depressants
(Contraindicated: hypovolemia, cardiomyopathy, betablockade,etc.)
ï Psychomotor impairment may last for days after use of a
single high dose
ï Taste of garlic prior to anesthesia
ï Potentially fatal attacks of porphyria in pts with a history of
acute or intermittent porphyria.
ï Delay giving other drugs (e.g. NMJ blockers) until barb has
cleared the i.v. line to avoid precipitation.
27. Propofol
ï Propofol is a diisopropylphenol intravenous
hypnotic agent that produces rapid
induction of anesthesia with minimal
excitatory activity
ï It undergoes extensive distribution and
rapid elimination by the liver
28. Propofol
ï Produces anesthesia as rapidly as i.v. barbâs & but
recovery is more rapid than barbâs.
ï Recovery is not delayed after prolonged infusion (due
to more rapid clearance).**
ï Patients are able to ambulate sooner & patients âfeel
betterâ in the post-op period compared to other i.v.
anesthetics.
ï Antiemetic effects (pts w/ ârisk of nausea), marked
hypotension (>barbs)
ï Commonly used as component of âbalanced
anesthesiaâ for maintenance of anesthesia following
induction of anesthesia.
** More rapid discharge from the recovery room
30. DOSE AND ROUTES
ï Conscious sedation
25 - 50 mg IV, Titrate slowly to desired effect
(on set of slurred speech)
ï Induction
2 - 2.5 mg/kg IV, given slowly over 30
seconds in 2 - 3 divided doses
ï Maintenance
25 - 50 mg IV bolus
Infusion 100 - 200 mcg/kg/min
ï Antiemetic
10mg IV
31. ADVERSE REACTIONS,
PRECAUTIONS, AND
INTERACTIONS
ï Reduce doses in elderly, hypovolemic, high
risk surgical patients and with use of
narcotics and sedative hypnotics
ï Minimize pain by injecting into a large vein
and/or mixing IV lidocaine (0.1 mg/kg)
with the induction dose of Propofol
32. ADVERSE REACTIONS,
PRECAUTIONS, AND
INTERACTIONS
ï Not recommended for patient with
increased intracranial pressure
ï Should be administered with caution to
patients with a history of epilepsy or
seizures disorder
33. Etomidate
ï Rapid induction (~1 min), Short duration of action (3-5
mins)
ï Used as a supplement with nitrous oxide for short surgical
procedures
ï Hypnotic, but not analgesic
ï Little effect on CV & Respiration
ï Can cause post-op nausea & decrease cortisol production w/
long term infusion*.
ï Primarily used in pts w/ limited cardiac or respiratory
reserve (safer than barbs or propofol in pts w/ coronary
artery dx., cardiomyopathy, etc.)
34. Benzodiazepines
ï Midazolam (> Diazepam & Lorazepam)
â Used to produce anxiolysis, amnesia & sedation
prior to induction of GA w/ another agent.
â Sedative doses achieved w/in 2 min, w/ 30 min
duration of action (short duration).
â Effects are reversed with flumazenil.
35. INDICATIONS Midazolam
ï pre-op sedative
ï induction of anesthesia
ï Conscious sedation
ï commonly used for short diagnostic or
endoscopic procedures
36. DOSE AND ROUTES
Midazolam
ï may be given IM, PO, or IV
ï Pre-op sedation: 0.07-0.08 mg/kg IM 1 hr
prior
ï Induction of anesthesia: 0.050 - 0.350
mg/kg IV
ï Basal sedation: 0.035 mg/kg initially, then
titrated slowly to a total dose of 0.1 mg/kg
37. âą Recovery half times from anesthesia can be
Recovery Half Time (mins)
âContext Sensitiveâ
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
38. Opioids (Fentanyl & Remifentanil*)
ï GAs do not produce effective analgesia (except for ketamine).
ï Given before surgery to minimize hemodynamic changes
produced by painful stimuli. This reduces GA requirements.
ï High doses can cause chest wall rigidity & post-op respiratory
depression
ï Therapeutic doses will inhibit respiration (âCO2)
ï Used for post-op analgesia, supplement anesthetic in balanced
anesthesia.
ï Remifentanil is an ester opioid metabolized by plasma
esterases. It is very potent but w/ a short t (3-10 mins).
39. Ketamine
ï Nonbarbiturate, rapid acting general
anesthetic
ï Dissociated from the environment,
immobile, and unresponsive to pain
ï Profound analgesic
40. Ketamine
ï Selectively blocks the associative pathways
producing sensory blockade
ï Preserved pharyngeal-laryngeal reflexes
ï Normal or slightly enhanced skeletal
muscle tone
ï Cardiovascular and respiratory stimulation
41. INDICATIONS Ketamine
ï Sole agent for procedures that do not
require skeletal muscle relaxation
ï Induction of anesthesia prior to the
administration of other anesthetic agents
ï Supplementation of low potency agents
42. DOSE AND ROUTES
Ketamine
ï may be injected IM or IV
ï Induction: 1-2 mg/kg Slow IV
ï Maintenance: 30-90 mcg/kg/min IV drip
ï Intramuscular: 6.5-13 mg/kg IM
ï 10 mg/kg IM will produce approximately
12-25 min of surgical plane.
43. ADVERSE REACTIONS,
PRECAUTIONS, AND
INTERACTIONS Ketamine
ï contraindicated in pts. with known
hypersensitivity or can't tolerate a
significant increase in blood pressure
ï IV dose should be administered over 60
seconds. Rapid administration may cause
respiratory depression or apnea
45. Ketamine (1.5mg/kg)
ï A âdissociative anestheticâ that produces a cataleptic state
that includes intense analgesia, amnesia, eyes open,
involuntary limb movement, unresponsive to commands or
pain.
ï Increases heart rate & blood pressure (opposite of other
GAs)
ï Can be used in shock states (hypotensive) or patients at
risk for bronchospasm.
ï Used in children & young adults for short procedures
ï Side Effects: nystagmus, pupillary dilation, salivation,
hallucinations & vivid dreams
48. Inhaled Anesthetics
ï Partial pressure or âtensionâ in inspired air is a measure
of their concentration
ï The speed of induction of anesthesia depends on:
â Inspired gas partial pressure (GA concentration)
â Ventilation rate
â GA solubility (less soluble GAs equilibrate more
quickly with blood & into tissues such as the brain)
49. Minimum Alveolar
Concentration
ï The minimum alveolar anesthetic concentration
required to eliminate the response to a painful stimulus
in 50% of patients
ï A measure of GA potency.
ï Itâs âa population averageâ.
ï 1.3 MAC - 100% will not respond to stimuli.
ï When several GAs are mixed, their MAC values are
additive (e.g. nitrous oxide is commonly mixed w/
other anesthetics).
50. Elimination
ï Anesthesia is most commonly terminated by redistribution
of drug from brain to the blood & out through the lungs.
ï The rate of recovery from anesthesia for GAs with low
blood: gas PCs is faster than for highly soluble Gas.
ï Time is $$ in the O.R. & recovery room
Blood: Gas P. Coeff
â Haltothane
â Desflurane
â Sevoflurane
2.30
0.42
0.69
ï Halothane & methoxyflurane undergo hepatic metabolism
& can cause liver toxicity.
51. Properties of Inhaled anesthetics
Nitrous Oxide
â MAC > 100% : Incomplete anesthetic
â Good analgesia
â No metabolism
â Rapid onset & recovery
â Used along w/ other anesthetic; fast induction &
recovery
* fewer side effects also seen in children
52. Halothane
âąThe first halogenated inhalational anesthetic
âąNot pungent (use for induction w/ children)*
âąMedium rate of onset & recovery
âąAlthough inexpensive, its use has declined
âąSensitizes the heart to epi-induced arrhythmias
âąRare halothane induced hepatitis
53. Desflurane
â Most rapid onset of action & recovery of
the halogenated GAs
â Widely used for outpatient surgery
â Irritating to the airway in awake patients & causes
coughing, salivation & bronchospasm (poor induction
agent)
â Used for maintenance of anesthesia
Sevoflurane
â Very low blood:gas partition coefficient w/ relatively
rapid onset of action & recovery *
â Widely used for outpatient surgery*
â Not irritating to the airway
â Useful induction agent, particularly in children
* Similar to Desflurane
54. Isoflurane
â Medium rate of onset & recovery
â Used for induction & maintenance of anesthesia
â Isoflurane âwasâ the most commonly used inhalational GA in
the US. Has been largely replaced by Desflurane
Methoxyflurane
â Now widely considered obsolete
â Slow onset & recovery
â Extensive hepatic/renal metabolism, w/ release of F- ion
causing renal dysfunction
55. Toxicity
ï Malignant Hyperthermia
â Esp. when halogenated GA used with succinylcholine
â Rx: dantrolene (immediately)
ï Halothane:
â Halothane undergoes >40% hepatic metabolism
â Rare cases of postoperative hepatitis occur
â Halothane can sensitize the heart to Epi (arrhythmias)
ï Methoxyflurane
â F release during metabolism (>70%) may cause renal insufficiency
after prolonged exposure.
ï Nitrous oxide
â Megaloblastic anemia may occur after prolonged exposure due to
decreases in methionine synthase activity(Vit B12 deficiency).
57. Airway
Alveoli
Blood
Blood:Gas PC
Brain
Nitrous
Oxide
Airway
Alveoli
Blood
0.47
Brain
Halothane
2.30
âą
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.
58. 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
âą
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).
59. Ventilation Rateâs 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)
âą
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.
60. NMJ Blockers
ï Succinylcholine, Pancuronium
ï Used to:
â relax skeletal muscle
â facilitate intubation**
â insure immobility
ï Reversed by neostigmine* &
glycopyrrolate* during post-op period
* quaternary drugs; * intubation is usually needed for
airway maintenance & to prevent aspiration.
61. Dantrolene
ï Interfers with the release of calcium from the
sarcoplasmic reticulum through the SR calcium
channel complex.
ï Used to prevent or reverse malignant hyperthermia
(which is otherwise fatal in ~50% of cases w/o
dantrolene).
ï Given by i.v. push at the onset of symptoms (e.g. an
unexpected rise in CO2 levels)
ï Supportive measures & 100% O2 are also used to treat
malignant hyperthermia
62. Nausea & Vomiting
ï General anesthetics effect the chemoreceptor
trigger zone & brainstem vomiting center
(cause nausea & vomiting)
ï Rx:
- Ondansetron (5-HT3 antagonist) to prevent
- Avoidance of N2O
- Propofol for induction
- Keterolac vs. opioid for analgesia
- Droperidol, metaclopromide & dexamethasone
Hinweis der Redaktion
An acutely disturbed state of mind that occurs in fever, intoxication, and other disorders.Wild excitement or ecstasy. Â 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.Â
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.