LOCAL ANESTHETIC & TOXICITY Procaine, chloroprocaine, cocaine, tetracaine

Amino-amides
Local Anesthetic Amide linkage
Reversible inhibition of sensory nerve impulse Lidocaine, bupivacaine, ropivacaine,
conduction levobupivacaine
No loss of consciousness
Prevent transmission to CNS Mechanism of Action
+
Local anesthetic binds to receptor so Na cannot bind to Prevent generation & conduction of nerve impulses by
+
it (Voltage gated Na channel) decreasing or preventing the large transient increase in
Also blocks synaptic transmission permeability of excitable membranes to Na
Blocks calcium release Agents of low anesthetic potency & short duration of
Inhibits excitatory neurotransmitter action, that is, procaine & chloroprocaine
+
Blocks Na ion channel Agents of intermediate anesthetic potency & duration of
+ -
Enhance K & Cl ion channel action that is lidocaine, mepivacaine & prilocaine
Agents of high anesthetic potency & prolonged duration
Clinical usefulness depends on of action that is tetracaine, bupivacaine, ropivacaine &
Inherent anesthetic property etidocaine
Rate of onset In terms of onset, chloroprocaine, lidocaine,
Duration of effect (Action) mepivacaine, prilocaine & etidocaine possess a
Which in turn depends on relatively rapid onset of action. Procaine & tetracaine
Physiocochemical properties have a long latency period except when used for spinal
Inherent vasodilator activity anesthesia, & bupivacaine is intermediate in terms of
onset of anesthesia
Physiocochemical Properties
Lipid solubility Local Anesthetic Toxicity
Potency increases as a function of lipid Systemic: CNS, CVS
solubility until a partitions coefficient of about 4 Local: Neural & skeletal muscle irritation
< Lipid solubility < potency > Specific: Addiction, allergy, methemoglobinemia
concentration needed (Prilocaine)
Protein binding Depend on blood level of local anesthesia delivered to
Duration brain & heart
> Protein binding at the site of action > Appropriate dose & technique rarely cause adverse
Duration of action reaction
pKa Toxic level: Usually due to intravascular injection or
Determine onset of anesthesia excess dose in extravascular administration
Pka-ph at which ionized & non-ionized form
are present in equal amount Extravascular injection blood concentration depends in
Uncharged form of the local anesthetic is Absorption
responsible for diffusion across the nerve Tissue redistribution
sheath & the membrane thus determine onset Metabolism
of action Excretion
pH of tissue is 7.4: pKa above this, local
anesthetic in the base form, the slower the Factors that Effect Absorption
onset of action Site of injection: More blood supply, greater absorption
Choice of drugs: Characteristics of the drug may effect
Vasodilator Properties absorption
All except cocaine exhibit a biphasic effect on vascular Dosage
smooth muscle Addition of epinephrine: Depends on sensitivity of the
Extreme low concentration vasoconstriction vessels at site of injection & local anesthesia itself
Concentration for regional anesthesia vasodilators (pharmacokinetic & metabolic property)

Non Pharmacologic Factors Influencing Anesthetic Activity CNS Toxicity: Related to intrinsic anesthetic potency
Dosage Low dose
Volume & concentration of drug Excitatory
Primary qualities of regional anesthesia Mechanism: Selective blockade of inhibitory
(Onset, depth & duration) are related to mass pathway in cerebral cortex allowing facilitatory
of the drug (Volume x concentration) neurons to function unopposed
Addition of vasoconstrictor: Epinephrine Subjective CNS symptoms
Limits, prevents rapid absorption of local Light headedness
anesthetic into circulation Dizziness
Dilution: 1:200,000 Visual & auditory disturbances:
Prolongs duration of local anesthetic available difficulty in focusing & tinnitus
at the site Disorientation
Site of injection Drowsiness
The difference in onset & duration is due to Objective CNS signs
the particular anatomy of the area of injection, Shivering
variation in the rate of vascular absorption & Muscular twitching
amount of drug used Tremors: Muscles of face & distal
In spinal anesthesia, the lack of nerve sheath parts of extremities
around the spinal cord & deposition of local Convulsions: Tonic, clonic
anesthesia near spinal cord are responsible Large dose
for rapid onset CNS depression
In brachial plexus, local anesthetic has to Mechanism: Inhibition of both inhibitory &
traverse thru nerve sheaths & connective facilitatory pathway
tissue thus have a slower onset Sign: convulsion ceases, respiratory
Additives depression, arrest
CO2 Factors that effects CNS toxicity
-
NaHCO3 : Increase pH near pka: more Potency
ionized: Faster entry faster onset Rate of injection
KCI Rate a particular blood level is attained
Dextran Effect of increase PCO2 on CNS toxicity
Mixtures of local anesthetic: The basis for using mixture pCO2 level is inversely related to convulsive
of local anesthesia is to compensate for the short threshold
duration of action of certain local anesthesia & the long Enhance cerebral blood flow so more local
latency of other agents anesthesia is delivered to the brain
Decrease plasma protein binding of local
Clinically Useful Local Anesthetic anesthesia, more local anesthesia available to
Amino-esters the brain
Ester link between aromatic & amine portion of Effect of decrease arterial pH
molecule
 Arterial pH is directly related to convulsive
threshold
Decrease intracellular pH will increase
conversion of base form of IA to cationic form.
Cationic form will not diffuse out well, so will
have increase local anesthesia
Decrease plasma protein binding of local
anesthesia: More free local anesthesia
available
Increase cationic form of local anesthesia:
Decrease diffusion into cell
CVS Toxicity: Cardiac, Vascular
Cardiac Effect
Dose dependent negative inotropic action:
Depends on potency of local anesthesia
+
Inhibit Na conductance in fast channels
High concentration of lidocaine, procaine &
tetracaine can block slow calcium channel
Increase LV EDP, direct pulmonary
vasoconstrictive effect
Lidocaine
Decrease maximum rate of
depolarization without altering
resting membrane potential
Action potential duration & effective
refractory period decrease
Ratio of effective refractory period to
action potential is increased in
Purkinje Fibers & ventricular
muscles
Decreased firing of muscles:
Treatment of premature ventricular
contractions
Increase dose
Prolongation of
conduction time, increase
PR interval & QRS
duration
Decrease pacemaker
activity in SA node: Sinus
bradycardia & sinus arrest
Decrease AV node:
Increase PR interval,
partial, complete AV
dissociation
Overdose: Blocks firing of SA node
even leading into arrest
Indirect effects of Lidocaine on CVS
Blocks sympathetic
innervation
CNS-mediated
mechanisms
Direct effects
+
Blocks Na channels,
conduction delay & QRS
prolongation
+ ++
Blocks K & Ca
channels
Metabolites related to PABA
(allergenic) are produced
Bupivacaine
Cause ventricular arrhythymia
Mechanism
Depresses the rapid
phase of depolarization (V
max)
Slow rate of recovery
resulting incomplete
restoration of V max
between action potentials
when heart rate
exceeds100/min
Unidirectional block & re-
entry type of arrhythmia
Used in regional anesthesia
Good motor & sensory block
Less associated with tachyphylaxis:
metabolism does not produce
metabolites like PABA (Allergenic)
Potential for CNS & CVS toxicity
Difference of Bupivacine to lidocaine toxicity
Ratio of dosage required for
irreversible cardiovascular collapse
& the dosage that will produce CNS
toxicity (convulsion) lower for
bupivacaine
Ventricular arrhythmia & fatal
ventricular fibrillation with
bupivacaine, not with lidocaine:
Depress rapid phase of
depolarization
Pregnant patient more sensitive to
cardiotoxic effect of bupivacaine that
non-pregnant
Resuscitation more difficult with
bupivacaine
Acidosis & hypoxia potentiate
cardiotoxicity of bupivacaine
Peripheral vascular effect Biphasic
Low dose: Stimulates myogenic contraction &
augments basal tone leading to
vasoconstriction
High dose: Inhibits myogenic activity leading
to vasodilation, except cocaine
Coccaine: Initial effect is vasodilation followed
by vasoconstriction at low & high dose
Mechanism: Inhibitis the uptake of NE by
tissue binding site, therefore no re-uptake
leading to increase free NE
Relationship of Local Anesthesia Toxicity to Lidocaine Plasma
Concentration
CVS depression: High concentration
Respiratory depression: Higher concentration
Coma
Convulsion
Unconsciousness
Muscular twitching
Visual & auditory disturbances
Lightheadedness
Numbness of tongue: Low concentration
CNS is more susceptible to the effect of local anesthetic,
hence CNS signs & symptoms preceed CV signs &
symptoms of depression
Molecular pKa Protein Maximum dose (mg)
Weight binding
Lidocaine 234 7.9 65% 300 mg for IV
500 mg with epinephrine
2-4 mg/kg
7mg/kg w/ epinephrine
L- 324.9 8.09 >97% 150-375 mg
Bupivacaine 2-3 mg/kg
**Epinephrine with L-bupivacaine has no greater effect, since L-
bupivacaine has greater affinity to lipids of tissue making it not
readily available (Longer duration)
Local Toxicity
The more potent longer acting local anesthesia, e.g.
bupivacaine & etidocaine cause > degree of localized
skeletal muscle damage than less potent shorter acting
agents like lidocaine & prilocaine
Reversible
No clinical signs of local irritation
Specific
Methhemoglobinemia: Prilocaine
Mechanism: Degraded in the liver to otoluidine
which cause oxidation of hemoglobin
Requires 600 mg of prilocaine to produce
clinical level of methhemoglobinemia
Reversed with methylene blue
Allergy
Amino esters: Derivatives of para-amino-
benzoic acid (Allergenic)
SPINAL ANESTHESIA, EPIDURAL ANESTHESIA, CAUDAL
ANESTHESIA
Spinal Anesthesia
Spinal Anesthesia (subarachnoid nerve block, intrathecal
nerve block -- Results from the deposition of a local
anesthetic drug within the subarachnoid space. Causes
reversible nerve block of the anterior & posterior roots, &
posterior root ganglion leading to loss autonomic,
sensory & motor functions
Not on the substance of the spinal cord
Redistributed via vascular absorption
Indications
a. Surgery - operations in the lower half of the
body:
Lower extremities
Perineum
Lower abdomen
Upper abdomen
b. Obstetrics Gynecology
Vaginal delivery
Caesarian section
Gynecology procedures
 c. Painful diagnostic & therapeutic procedures
below the diaphragm
Contraindications
d. Absolute
Bleeding disorders (may bleed
into subarachnoid space clot
formation spinal cord
compression)
Septicemia: Bring organism into
the spine
Increased intracranial pressure
Patient refuses consent
Chronic dermatitis or skin
infection near puncture site
Systemic diseases with
neurologic sequelae
Pre-existing spinal cord injury
Hypotension
Relative
e. Hemorrhage
f. Back problems due to muscle strain, arthritis,
etc.
g. Respiratory diseases
h. Extremely tense or psychotic patients
i. Children: Uncooperative, give sedation first
Anatomy
j. General considerations
The vertebral column consists
of 33 vertebrae: 7 cervical, 12
thoracic, 5 lumbar, 5 sacral and
4 coccygeal
Vertebral column is bounded
together by several ligaments:
supraspinous, interspinous,
ligamentum flavum &
longitudinal ligaments
nd
Spinal cord ends at the 2
lumbar (L2) vertebra
Puncture sites:
Can be made safely at the interspaces
between L2 & L3, L3 & L4, or L4 & L5
The line joining the highest points of the iliac
th
crests crosses either the body of the 4
th
lumbar vertebrae or the interspace between 4
th
& 5 lumbar vertebra: Tuffiers Line
k. Structures traversed by the spinal needle
during lumbar puncture:
Skin
Subcutaneous tissue
Supraspinous ligament
Interspinous ligament
Ligamentum flavum
Dura
Technique
l. Position
Lateral decubitus: knees flexed
to the chest, chin placed down
on the chest & head supported
by a pillow.
Sitting position: less frequently
used, when the lateral
approach cannot be attained as
in obese patients
m. Asepsis, antisepsis & drape. Choose
interspace & raise a skin wheal of local
anesthetic. Spinal needle is introduced
through the ligaments until the dura is pierced
(identified by a feeling of a sudden click or
give). Successful puncture is followed by a
free flow of CSF after removal of the needle
stylet. Local anesthetic is injected.
n. Approach:
Median: more common
approach
Paramedian: used only when
difficulty is encountered in the
median approach as in arthritic
vertebra.
Drugs Used in Spinal Anesthesia
o. Tetracaine:
Administered as a 1.5%
solution mixed with 10%
Dextrose Water (Crystalline
form dissolved in dextrose
Onset of action 5-10 minutes &
duration of action 1 - 2 hours.
p. Lidocaine
Supplied as 5% solution mixed
with 7.5% Dextrose Water
Onset of action is rapid, 2 mins
& duration of action is 1 - 2
hours.
q. Bupivacaine
relatively new long acting local
anesthetic that is currently used
as 0.5%-0.75%.
Duration of action 3-4 hours.
Factors in determining levels of anesthesia
r. Volume of solution: High volume may go high
s. Concentration of solution
t. Barbotage (Inject, withdraw, inject, withdraw,
creating turbulence)
u. Speed of injection
v. Position of the patient
w. Specific gravity of solution
x. Site of injection
y. Height of patient
z. Increased intra abdominal pressure
Levels of Spinal Anesthesia and the Dermatomes
Involved
aa. Saddle Block: Sensory loss involves lower
lumbar & sacral segments. Ex. Hemorrhoids &
episiotomy, areas that sits on the saddle
bb. Low spinal anesthesia: sensory block is at the
level of the umbilicus (T10) & the lower
thoracic, lumbar & sacral segments.
cc. Midspinal anesthesia: sensory loss at costal
margin (T6), lower thoracic, lumbar & sacral
segments.
dd. High spinal anesthesia: sensory block at the
level of the nipple line (T4), thoracic segments
T4-T12, lumbar and sacral segments.
Immediate complications of spinal anesthesia
(physiologic effects)
ee. Circulatory: Cardiovascular changes are due
to partial or total sympathetic blockade
Decrease total peripheral
resistance (Vasodilation),
Management: increase flow of
IV fluids
Hypotension: Management:
Fluid infusions, vasoconstrictors
Bradycardia: Management:
Vagal blockers (Atropine SO4)
ff. Respiratory
Difficulty of breathing
Apnea (at high levels)
Causes:
Lack of propioception (sensation of
dyspnea)
Hypotension (cerebral
hypoperfusion)
Motor block to C3-C5 & phrenic
paralysis
gg. Nausea & vomiting: occurs in 25% of patients
Causes:
Hypotension
Hypoxia from respiratory inadequacy
Parasympathetic hyperactivity
Delayed complications
hh. Spinal Headache: CSF leakage Decreased
intracranial pressure Retract meninges (Big
needle)
ii. Backache
jj. Urinary retention: Urogenic bladder
kk. Hemiplegia/ Hematoma: Coagulopathy
ll. Chronic Adhesive arachnoiditis
Epidural Anesthesia
Epidural anesthesia is accomplished by injecting the
local anesthetic solution into the epidural space of the
vertebral canal. Spinal nerve roots are blocked as they
traverse the epidural space & also sympathetic fibers
traveling with the anterior roots.
Different types according to level of puncture
mm. Thoracic epidural thoracic spine
nn. Lumbar epidural lumbar spine (spinal
epidural block)
oo. Caudal epidural solution deposited into
caudal canal through sacral hiatus
pp. Cervical epidural cervical spine for neck
surgeries
Factors influencing the spread of solution in the epidural
space
qq. Height of the patient
rr. Drugs use
ss. Volume
tt. Concentration
uu. Level of insertion of the catheter
 Anatomy gggg. Metabolic disturbances
vv. Epidural space extends from base of the skull hhhh. When general anesthesia is
(foramen magnum) to the coccyx contraindicated
(sacrococcygeal membrane) iiii. When spinal anesthesia is contraindicated
ww. O the average, the distance between skin & jjjj. For various painful conditions including post
the epidural space is 4-5 cm. operative patients
xx. The epidural space contains loose areolar Contraindications of Epidural anesthesia (Similar to
connective tissue, fat, arterial & venous spinal)
networks, lymphatics & the spinal nerve roots. kkkk. Severe hemorrhage
Technique llll. Uncooperative or apprehensive patients
yy. Methods of doing epidural block mmmm. Previous laminectomy
Single dose injection of local nnnn. Coagulation defects
anesthetic oooo. Local inflammation on site of
Fractional technique insertion
(continuous epidural pppp. Refusal of the patient
anesthesia): repeated injections
of local anesthetic agent Caudal Anesthesia
through a catheter inserted into Accomplished by introducing local anesthetic solution
the epidural space. through the sacral hiatus into the epidural space of the
zz. Patient is placed in the lateral decubitus sacral canal. The nerves involved are part of the lumbo-
position with full flexion of the spine. For sacral plexus (T12, L1-L5, S1-S3), the coccygeal plexus
lumbar epidural, insertion of needle is at L4-L5 (S4-S5) and the coccygeal nerve.
interspace. Indications (Lower abdomen & perineum)
aaa. Cervical: Sitting C7, Thoracic T7 qqqq. Pediatric patients undergoing lower
bbb. Beyond ligamentum flavum abdominal & lower extremity surgeries, for
ccc. Methods of identifying the epidural space post-op analgesia (ex: Correction of
(Principle: Negative pressure in the space) hypospadias or inguinal hernia repair)
Loss of resistance method: rrrr. Obstetric patients undergoing vaginal
when the point of a needle to a deliveries
syringe with air enters the ssss. Operations of the perineum (ex.
space, resistance disappears Hemmorhoidectomy, fistulectomy)
and air in the syringe is sucked Technique
in. tttt. Patient is in prone position or lateral
Hanging drop method: a drop of uuuu. Needle is inserted into the sacral
saline placed into the hub of the hiatus between the sacral cornua, about 4 cm,
needle is sucked in once the above the tip of the coccyx. Sacral hiatus
needle enters the space. located by a distinct V depression. Inject 15-20
Drugs used: mL. of 2% Lidocaine after a test dose of 3-5
ddd. Lidocaine: 15-30 mL. of 1-2% solution with or mL.
without epinephrine. Onset is 10-20 minutes Complications
& duration of analgesia is 1 hours. vvvv. Accidental puncture of the dura
eee. Bupivacaine: 15-30 mL. of 0.25-0.75% wwww. General systemic reactions to local
solution. Onset is 10-20 minutes & duration is anesthetics & epinephrine
3 - 5 hours. xxxx. Rarely, infection develops at the site
fff. Ropivacaine 0.29%, 0.75%, 10% low pain of puncture
relief post operative labor analgesic. Disadvantages
ggg. Opoids, opiates, low dose local anesthesia yyyy. It is difficult to obtain high levels of
Complications of Epidural Anesthesia anesthesia (Needs big amount)
hhh. Total subarachnoid block: due to zzzz. Systemic reactions are
unrecognized dural puncture possible
iii. Hypotension: due to sympathetic blockade aaaaa. Infections are possible
jjj. Hypertension (especially with bbbbb. Due to anatomic abnormalities or
vasoconstrictors) incorrect methods, there is 5-15% chance of
kkk. Convulsions failure
lll. Neurologic: persistent paresthesia, prolonged
headache. POSTOPERATIVE CARE
mmm. Damage due to catheter in the
epidural space Post anesthesia care
nnn. Physiologic decrease of intensity of sensory or Post operative pain
motor block (Similar to those observed in
spinal anesthesia) Recovery room
Advantage of Epidural Blockade Postoperative recovery starts in the post anesthesia care
ooo. Well defined area of anesthesia unit (PACU) where patients are closely monitored. This
ppp. Longer duration compared to spinal block; unit is dedicated to meet the patients needs thereby
good for long surgeries minimizing post-operative complications. Life threatening
qqq. More severe disturbances of spinal anesthesia complications occur mandating that patients be
are minimized (headache, meningitis, etc.) monitored one-to-one basis
rrr. GI complaints are minimized (nausea,
vomiting) PACU
sss. Catheterization incidence minimum Pain
ttt. Less respiratory defects
Nausea & vomiting: Maybe because of pre anesthetic
uuu. Intraoperative or Postoperative analgesia is
medications, must identify cause then treat
achieved
Respiratory depression
Disadvantages of Epidural Blockade
Cardiovascular system
vvv. Technically more difficult to administer due to
Hypertension/ hypotension
need of accurate needle placement
Arrhythmias
www. Muscle relaxation not complete
Hypothermia
xxx. Large volume of solution necessary
Fluid, electrolyte, acid base balance
yyy. Danger of dural puncture
zzz. Bleeding in epidural space
Anesthesia & Waking Up
aaaa. Incomplete or patchy block
Recovery from anesthesia takes time. During
bbbb. Slower onset
maintenance anesthesia throughout surgery, muscles &
cccc. Less intensity of motor & sensory
fats absorbs some of the anesthetic agents. It takes time
blocks
for its elimination from the bodys tissues
Indications of epidural anesthesia: all operations below
the diaphragm, may also be used in the following
Factors that Affect the Amount of Time a Patient may Spend in
circumstances
PACU
dddd. Poor risk patients
Pre-operative medication
eeee. Cardiac diseases
Type of anesthetic used
ffff. Pulmonary diseases
 Length of time an anesthetic was administered during by Aldrete & Kroulik (1970), assigns a score to provide
surgery objective information on the physical condition of
patients arriving in the recovery room after anesthesia.
Important Data to be Noted, Observed & Monitored This test assigns a score of 0, 1 or 2 to activity,
Diagnosis & operation respiration, circulation, consciousness & skin color, with
Patients must be kept under clinical observation at all a score of 10 indicating the best possible condition for
times discharge from the PACU. A score of 8 to 10 indicates
Level of consciousness adequacy of early recovery
Oxygen saturation
Vital signs Discharge Criteria from the PACU
Blood pressure The patient is fully conscious, able to maintain clear
Respiratory frequency & pattern airway & exhibit adequate airway reflexes
Heart rate & rhythm Respiration & oxygenation are satisfactory
Temperature: Prevention of The cardiovascular system is stable. The specific values
hypothermia of the pulse & blood pressure should approximate to
Urine output normal preoperative values or be at an acceptable level.
Assessment of patient needs Peripheral perfusion should be adequate
Activity Pain & emesis should be controlled & suitable antiemetic
Diet & analgesic prescribed
Proper breathing: Deep breathing increases Temperature should be within acceptable
circulation & promotes elimination of
anesthesia
Pain management
Intake & output
Medications
Pain medications
Anti emetics: Determine the cause
Pre anesthetic
medications
Gastric distention 5HT3
release Into the
circulation Activates
chemoreceptor trigger
zone in the medulla
Vomiting
Gastric suctioning
Anesthetic technique
Anesthetic agent
Type of operation
Antibiotics
Routine medications that need to be
renewed
PRN medications such as laxatives,
sleeping medications & antacids
Special Tests: such as follow up chest x-rays
or serial ECGs. ECG should be performed on
postoperative day 1 for high risk patients
Laboratory: Follow up CBC for possibility of
hemorrhage or large amount of blood loss. If
patient continues on IV fluid, check daily
electrolytes

Stages of Recovery
Recovery from outpatient anesthesia includes
Dissipation of anesthetic agents
Normalization of physiological functioning
Observation for medical or surgical complications
Treatment of immediate side effects of anesthesia &
surgery
Discharge & return at home

Recovery from Anesthesia maybe divided into 3 Main stages

Early Recovery (Phase I): Time from the end of
anesthesia until the patient wakes up. During that time,
protective reflexes recover, vital signs stabilize & the
patient becomes able to obey commands. Assessment
of early recovery usually involved recording of the time
when certain events occur (e.g. eye opening) or the
measurement of physiological parameters, such as
blood pressure & respiratory rate & crude measurement
of alertness
Intermediate Recovery (Phase II): Time from discharge
from the recovery room or the post anesthesia care unit
until the patient has recovered sufficiently to be safely
discharged from the hospital. During that time,
psychomotor functions recover. Full return to the
preoperative levels is not essential, & the patient maybe
escorted home by a competent adult who remains with
the patient until the stage of late recovery is achieved
Late Recovery: During this time, which takes some
hours or days after the cessation of anesthesia, the
patient returns to the preoperative fitness level. This
means complete & physiological recovery, such as going
to work & driving

Recovery Tests
Scoring systems developed to guide the transfer from
the hospital recovery room to the ward maybe used to
assess the early recovery of ambulatory surgical
patients. The most commonly used method, described