Transcript A touch of anesthesia - McMaster Faculty of Health Sciences

A touch of anesthesia
•
Local anesthetics and other things
purpose
local anesthetics- mechanisms of action,
pharmacology and toxicity
conscious sedation- definition, drugs and dilemmas
Components of anesthesia
Anesthesia
Amnesia
Areflexia
Autonomic areflexia
Anxiolysis
spectrum of sedation
minimal sedation
moderate sedation
deep sedation
general anesthesia
benefit
sedation and analgesia allows patients to tolerate
unpleasant procedures by relieving anxiety,
discomfort and pain
children and uncooperative adults sedation analgesia
may expedite procedures that may not necessarily
painful but requires that the patient does not move
minimal sedation
normal response to verbal stimulation
airway unaffected
spontaneous ventilation unaffected
cardiovascular function unaffected
cognitive and cordination may be impaired
conscious sedation
drug induced depression of consciousness in which
patients respond purposefully to verbal commands
no interventions are required to maintain the airway
spontaneous ventilation is maintained
cardiovascular function is maintained
deep sedation
drug induced depression of consciousness during
which patients can not be aroused easily but respond
purposefully when stimulated repeatedly or painfully
ability to maintain respiration may be impaired
support of the airway may be needed
spontaneous respiration may be impaired
cardiovascular function is maintained
general anesthesia
loss of consciousness patients are not rousable even
to pain
the ability to maintain ventilation is often impaired
assistance is required in maintaining an airway and
spontaneous ventilation
may be associated drug induced depression of
neurological function
cardiac function may be impaired
Induction
Maintenance
Emergence
Recovery
•But a whole lot of other stuff too
History
be familiar with the sedation oriented aspects of the
patients History
abnormalities of major organs
adverse events with sedation or ANESTHESIA
DRUG ALLERGIES AND MEDICATIONS
NPO STATUS
TABACCO, ALCOHOL AND SUBSTANCE ABUSE
PHYSICAL
AIRWAY AIRWAY AIRWAY
NPO
6 HOURS FOR light meals, FORMULA AND
MILK
4 HOURS FOR BREAST MILK
2 HOURS FOR CLEAR FLUIDS
VENTILATION
MAJOR MORBIDITY DRUG INDUCED
RESPIRATORY DYSFUNCTION AND AIRWAY
OBSTRUCTION
VENTILATION AND OXYGENATION ARE
DIFFERENT
PULSO OXYMETRY IS NOT A SUBSTITUTE FOR
VENTILATION MONITORING
MODERATE/DEEP
SEDATION
LEVEL OF CONSCIOUSNESS
OXYGENATION STATUS
HEMODYNAMICS
EMERGENCY
EQUIPMENT
PHARMACOLOGIC ANTAGONISTS
EQUIPMENT FOR ESTABLISHING AN AIRWAY
DEFIBRILLATOR
EMERGENCY DRUGS INCLUDING THOSE TO
TREAT ANAPHYLAXIS
DRUGS
SMALL INCREMENTAL DOSES
sufficient TIME ELAPSED TO ALLOW FOR THE
EFFECT OF THE DRUG
three step approach to
sedation
environment (equipment, monitors, suction,
personnel, resuscitation equipment)
procedure (diagnostic v therapeutic, duration of time,
level of discomfort, position of the patient, special
requirements)
patient (ability to tolerate sedation vs general
anesthesia, ASA Grade and morbidity, Allergies,
monitoring requirements)
benzodiazapines
anxiolytic
amnesic
hypnotic
recovery of psychomotor and amnesic function
may be significantly delayed
midazolam
water soluble
non- irritant to the vein
short elimination half time( 1-4 hrs)
clearance unaffected by H2 antagonists
inactive metabolites
resedation unlikely
diazepam
Lipid soluble
pain on injection
thrombophlebitis common
long elimination half life (>20 hrs)
Active metabolites (desmethyl-diazepam, oxazepam)
opioids
fentanyl, hydromorphone, morphine
equally effective analgesia with equal side effect
profiles
used for a balanced effect
regional or local anesthesia techniques are n effective
or inappropriate
awareness - lack amnestic properties
effect
mu1
analgesia supraspinal
affect
euphoria
pupil
miosis
respiratory
mu2
kappa
theta
spinal
spinal
spinal
hallucinatio
n
sedation
miosis
mydrasis
depression depression tachypnea
GI
nausea
GU
retention
dependanc
e
yes
nausea
yes
morphine
acts presynaptically to decrease substance P
hyper-polarizes post synaptic neurons in the dorsal
column
periaqueductal grey matter
CNS effect of morphine
nausea and vomiting
muscle rigidity
cough reflex
urinary retention
histamine release
respiratory depression
fentanyl
remifentanyl
specific groups
opioid tolerant groups
morbidly obese patients
OSA
elderly patients
ketamine
Phencyclidine derivative
dissociative sedation
Analgesic
Induction of anesthesia especially in the setting of
bronchospasm and hypotension
Antagonist at the calcium channel pore of the NMDA
receptor and inhibitor of the NMDA receptor at
phencyclidine binding site
Onset 30 seconds IV, IM 2-8 minutes
ketamine
Stimulation of respiration
Bronchodilation
Sympathetic stimulation with an increase in circulating
epinephrine and norepinehrine
Increased cerebral metabolic rate increased cerebral
blood flow and increased metabolic rate
Post-operative nausea and vomiting
Side effects of ketamine
Rashes
Pain on injection
Hallucinations
Emergence delerium and unpleasant dreams (less
likely in children and the elderly)
exerts its sympathomimetic activity by
inhibiting the re-uptake of
catacholamines
Severe heart disease
Hypertension
Porphyria
ketamine
Duration
IV 5- 10 minutes
Intramuscular 10-20
minutes
• Dose 1 - 2 mg/kg
• Intramuscular 5- 10
mg/kg
Propofol
Phenol derivative
White oil in water emulsion 0f 1% or 2% propofol in
soybean oil
Induction, maintenance, sedation, intractable nausea
vomiting, status epileticus
Potentates inhibitory neurotransmitters glycine, and
gamma aminobutyric acid
propofol
Onset 30 seconds
Duration 10 minutes for a single dose, but an infusion
context sensitive half life increases with duration
Dose 1.5- 2.5 mg
100 ug/kg minute
Propofol
Pain on injection
Anaphylaxis
Not to be used for sedation in PICU as reported
metabolic acidosis, myocardial failure and lipaemic
serum
context sensitive half life is short even after long
infusions
easy titratable drug
low incidence of nausea and vomiting
local anesthetics
the anatomy, the
chemistry and everything
else in between
April 11 2007
the anatomy
mixed nerves that contain both
afferent and efferent fibers
each axon is surrounded by
endoneurium -non neural glial cells
individual nerves are bundled into
fascicles and and surrounded by
perineurium -connective tissue
the entire peripheral nerve is
wrapped in epineurium composed
of dense connective tissue
nerve fiber
classification
size
conduction velocity
function
the more myelin and the bigger the
nerve the faster the conduction
velocity
nerve
Aalpha,
diamet
myelin
er
6-22
+
A-beta
Adelta
B
C
conductio
n
locatio
function
n
fastes
t
muscles
a/e joints,
and
muscles proprioce
ption
6x
1-4
+
slowe
r
1.5 x
<3
0.31.3
+
slowe
r
sensory
nerves
pain,
touch,
temp
sympathe
tic
auto
sympatheti
c
auto,
pain,
temper
afferent
5-10x
-
slow
er
O
intermediate
N
chain
CnHn
CnHn
Aromatic ring
lipid soluble
amide group
water soluble
proton acceptor
acidi
c
alkaline
influenced by PH of
surroundings
LA H +
Cation
water soluble,
IONIZED
LA + H+
uncharged base
lipid soluble
NON-IONIZED
pK
a
the pH at which the ratio of ionized
to non-ionized molecules is 1:1
dissociatic constant
lidocaine
pK of lidocaine is 7.7 and the acid solution has a pH
of 6 ( hydrochloride salt)
lidocaine hydrochloride solution in a syringe 99% of
the total is in the ionized form and 1% is in the nonionized form. maintains its water solubility
once injected ....
injected into the tissues, where the pH is 7.4 the
ionized portion drops to 76%
24% is now non-ionized or lipid soluble
able to diffuse passively down the concentration
gradient across the nerve cell membrane
through the cell membrane
the pH is now 7.1
shifts the equilibrium between the ionised and nonionized form
86% of the total is now back towards the ionized
ionized form now means that it can
pass into and block the sodium
channels
reduces the amount of non-ionized
form on the inside of the cell to
increase the concentration gradient
across the cell membrane
mechanisms of blockade
sodium channel blockade leads to a
reduction in the action potential
formation and propagation
animal studies suggest that there
must be a decrease in 50% of the
action potential before a loss of
function is observed
do local anesthetics block
the smallest fibers first?
small myelinated axons - gamma and delta are most
sensitive
large myelinated - alpha and beta
least suseptable the snall non-myelinated C fibers
local anesthetic block of
nerve fibers
depend on size and type of fiber
frequency of membrane
stimulation
choice of local anesthetic
O
C O
R
N
R
ester
s
commonly used esters
procaine
chloroprocaine
cocaine
tetracaine
O
R
N
amides
C
N
R
commonly used amides
lidocaine
bupivacaine
mepivacaine
ropivacaine
influential factors
temperature
ionic strength
the medium surrounding the drug which
influences the drug activity by shifting the
balance between the the relative
concentration of basic or protonated forms.
onset of action
site and type of nerve
proximity of the injection
pKa of local anesthetic agents
acidity of surroundings
systemic absorption
decreased systemic absorption will have a greater
margin of safety
most important the site of injection
the dose
the physicochemical of the local anesthetic
greater the vascularity the faster the absorption the
amount of fat in the surrounding areas
potency
the higher the lipid solubility,
the greater the potency
duration of action
dose
local blood flow
intrinsic vasoactivity
vasoactive additives
protein binding
local drug metabolism
I Can Eat Big Bowls of
Spaghetti
intercostal nerve block
caudal
epidural
brachial plexus
sciatic/femoral
subcutaneous
dr. Mark Banks,
2003
protein binding
amide anesthetics are primarily protein bound
bupivicaine, levobupivicaine and ropivicaine are
more than 90% bound to alpha acid glycoproteins (
high affinity)
and
albumin
(
high
volume
and
low
1
affinity)
free or unbound fraction of the local anesthetic is
active
distribution
organ blood flow
partition coefficients of local anesthesia between
compartments
plasma protein binding
organ regional pharmacokinetics
duration of action
dose
local blood flow
intrinsic vasoactivity
vasoactive additives
protein binding
local drug metabolism
epinephrine
prolongation of local block
increased intensity if the block
decreased systemic absorption of local anesthetic
antagonizing inherent vasodilation of local anesthetics
lipid
relative
potency
protein
binding
duration
Pka
onset
procaine
low
0.5
6
short
8.9
slow
bupivicaine
high
4
96
long
8.1
slow
7.7
rapid
8.1
med
lidocaine
med
1
64
mediu
m
ropivacaine
med
3
95
long
tachyphylaxis
repeated injections of the same dose of local
anesthetics leads to a decreasing effacy
dependance on the dosing interval, if the dosing
interval is short enough that pain does not develop
neither does the tachyphalxis. the opposite is also
true
allergies
true allergic reactions to local anesthetics are rare and
usually involve type 1 or Type IV reactions
anaphylaxis to amides is rare
increased allergic reactions to esters most likely the result of
the metabolism to PABA
may also be the result of additives methylparaben and
metabisulfite
QuickTime™ and a
GIF decompressor
are needed to see this picture.
CNS
CVS
tingling around the mouth
tinnitus, visual disturbance
light headedness
tremor, agitation
slurred speech
muscle twitching
myocardial depression
resistant cardiac
arrhythmias
coma
ventricular
respiratory arrest
arrest
readily cross the blood brain barrier
CNSanesthetic
TOXICITY
potency for generalized
CNS toxicity approximately parallels
the action potential blocking
potential
acidosis and increased PO2 may
worsen increase the risk of toxicity
(decrease the plasma protein
binding)
seizures produce hypoventilation
and a metabolic acidosis which may
worsen the CNS toxicity
cardiovascular toxicity
decrease in the rate of depolarization in the fast
conduction tissues f the purkinjie fibers and
ventricular muscle
decreased availability of fast sodium channels in
cardiac membranes
high concentration of dose dependent negative
inotropic action on cardiac muscle
cardiovascular toxicity
decrease in the rate of depolarization in the fast
conduction tissues f the purkinjie fibers and
ventricular muscle
decreased availability of fast sodium channels in
cardiac membranes
high concentration of dose dependent negative
inotropic action on cardiac muscle
comparative cardiovascular
toxicity
ratio of the dosage of bupivicaine to lidocaine
fatal ventricular arrythmias may occur more often with
bupivicaine than with lidocaine
pregnant patients may be more sensitive to
cardiotoxic effects of bupivicaine
acidosis and hypoxia enhance the cardiotoxic effects
lipid rescue
mechanism by which it works is still uncertain
carnatine deficiency
bupivicaine interfers with carnatine dependent
mitochondrial lipid transport
anesthesiology V 105 No 1, July 2006
so remember
the three Ps of sedation: place, procedure and patient
be prepared for the emergencies
smaller doses of drugs wait for their effect
monitoring, monitoring, monitoring
recovery is as important there as it is in the operating
room