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
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
Induction: keeping the patient to sleep
Maintenance: keeping the patient
asleep
Emergence: waking the patient up
13. 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.
14. 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. STAGE 4 (Impending Death/Overdose):
Onset of apnea, dilated and nonreactive pupils, and
hypotension to complete circulatory failure.
17. 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.
18. 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)
19. Regional Effects
Immobilization in response to surgical incision
(spinal cord)
Sedation, loss of consciousness (↓thalamic firing)
Amnesia (↓hippocampal neurotransmission)
21. 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
22. 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
24. 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
25.
26. 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.
27. 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
28. 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
30. 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
31. 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
32. 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
33. 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.)
34. 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.
35. INDICATIONS Midazolam
pre-op sedative
induction of anesthesia
Conscious sedation
commonly used for short diagnostic or
endoscopic procedures
36. 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
37. • 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
38. 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).
39. Ketamine
Nonbarbiturate, rapid acting general
anesthetic
Dissociated from the environment,
immobile, and unresponsive to pain
Profound analgesic
40. Ketamine
Selectively blocks the associative pathways
producing sensory blockade
Preserved pharyngeal-laryngeal reflexes
Normal or slightly enhanced skeletal
muscle tone
Cardiovascular and respiratory stimulation
41. 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
42. 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.
43. 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
45. 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
48. 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)
49. 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).
50. 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.
51. 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
52. 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
53. 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
54. 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
55. 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).
57. 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.
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
•
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 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.
60. 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.
61. 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
62. 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
Notes de l'éditeur
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.