.

)~

>

In a failing heart venous pressure is increased because if the heart action fails there is
backing up of blood on the venous side of circulation.
An increase in CVP with a normal cardiac function suggests:
1. Hypervolemia
2. Vasoconstriction
3. Increase in intrathoracic pressure
An i ncrease in CVP in the presence of arterial hvpotension suggests cardiac dysfunction .
.

CVP

-- ----

Blood Pressure

Diagnosis

Fluids

Drugs

1. low

Low or normal

Hypovolemi<1

Increase

Jilh:IF@~i~

2. High

Normal

Hypervolemia

Stop or decrease

Diuretics

3. High

Low

Cardiac failure

Restrict

Diuretics and Digitalis

Indications for CVP monitoring:

1. In elderly patients undergoing extensive surgical operation.

2. Patients in whom a large blood or fluid exchange is expected to prevent overhydration or
overtransfusion.

.
'
3. In patients known to have cardiac disease.
4. Major traumatic surgery.
5. Anticipation of major blood loss during surgery.
6. In patients with uncertain preoperative volume status.
7. Facilitation of postoperative care In critically ill patients;
8. Craniotomy or Cervical laminectomy when either is done in the upright position to treat
potentia~ air embolism.
9. Multiple transfusion.
10. Open heart surgery:
11. During and following removal of pheochromocytoma.
ECHOCARDlOGRAPHY
Transesophageal echocardiography (TEE) is expensive but can be useful continuous
perioperative monitor for heart anatomy and function.

>

TEE useful in differentiat ing hypovolemia from poor myoca rdia l contractility as a cause for
depressed cardiac output syndrome.
- in addition to the assessment of myocardial function and ischemia anatomic and
functional disorders of heart valves are frequently best assessed with the use of TEE.

INHILATlfJNAL ANESTHETICS
GENERAL ANESTHESIA- an altered physiologic: state characterized by reversible loss of
consciousness, analgesia of the entire body, amnesia and some degree
of muscle relaxation.
Jw
> Anesthetic drugs have been shown to thE). press excitatory transmission in the spinal
cord particularly at the level of the dorsaf'horn interneurons that are involved in pain
transm ission.
Unconsciousness and amnesia probably mediated by cortical anesthetic action.
> Suppression of purposeful withdrawal from pain is related to subcortical structures such
as thE! spinal cord or brain stem .

Inhaled anesthetics are sufficient alone to provide complete anesthesia.

PROPERTIES OF AN IDEAL INHALATIONAL ANESTHETIC:

1. Predictable in onset and emergence.
2. Pro1 1ide muscle relaxation.
3. Cardio stability and bronchodilatation.
4. ShJuld not trigger malignant hyperthermia and other significant side effects like nausea

5.

Inflammable

6. Undergo no bio transformation within the body.

7. Allow easy estimation of concentration atthe sight of action.
I. OLDER INHALATIONAL ANESTHETIC AGENTS:
,,......_____~
1. Ether - flammability
2. Cyclopropane - flammability
3. Fluoroxene - flammability, hepatoxicity
4. Methoxyflurane - nephrotoxicity

5. Chloroform - hepatoxicity
6. Trichloroethylene - re acted with soda lime to form toxic gas known as phosgene
7. Nitrous oxide - lack potency

The above inhafationaf anesthetic have unfortunate properties and side effects.

II. NEWER !NHALTIONAL ANESTHETIC AGENTS :

1. Halothane - substituted halogenated alkane
2. f1flurane

3.

lsoflurane }

4. Sevoflurane
5. Desflurane

substituted hak>genated ether

Despite the effectiveness of the inhaled anesthetics, they are the most difficult
drug to use for the follow ing reasons :
1. Narrow margin of safety
2. Variation among patients
So that constant attention of the dose and continuous physiologic monitoring
of
.
the patient are required.
Concentration effective f1:>r producing surgical anesthesia frequently cause
significant effect on the central nervous system, respiratory, circulatory and
neuromuscular function.
Thus this requires continuous life support.
~

POTENCIES OF ANESTHETIC GASES COMPARED

Using minimal alveolar concentration (MAC}

MAC - concentration of l atmosphere that abolishes motor response in 50016 of patients in response
noxious stimuli (surgical incision)
Measurement of MAC assumes that alveolar concentration directly
reflects partial pressure of the anesthetic at its sight of action.
FACTORS THAT INFLUENCES MAC
1. Age
> The highest MAC are found in infants at 6-12 months of age
> MAC decreases with increasing age as well as in prematurity
2. Temperature
Hypothermia decreases MAC ( for every Celsius degree drop in temperature
MAC decreases approximately 2-5%
Hyperthermia increa~es MAC
3. Electrolytes
Hypernatremia decreases MAC
4. Drugs
> Opioids , barbiturates, alpha 2 blockers , calcium channel blockers decreases
MAC

>

~-

Alcohol !ntoAlcath;m

Acute alcohol intoxication decreases MAC

. Chronic alcoholism increases MAC

FACTORS THAT DO NOT AFFECT MAC:

1. Hypocarbia I hypercarbia
2. Gender
3. Thyroid function
4. Hyperkalemia
BLOOD GAS PARTITION COEFFICIENT (SOLUBILllY OF INHALED ANESTHETICS IN THE BLOOD)

>
~
~

Describes the distribution of anesthetic between blood and gas at the same partial

pressure.
A higher blood gas partition coeffident correlates with a greater concentration of
anesthetic in the blood ~higher solubility
A greater amount of anesthetic is taken by the blood which acts as a reservoir thus
reducing the alveolar concentration and thus slowing the rate of induction.

Alveolar concentration - the principal factor in determining the onset of action.

Enflurane
lsoflurane
Desflurane
Halothane
Nitrous Oxide
Sevoflurane
~

MA:
1.6B
1.1!)

Blood-Gas Partition Coefficient

6.C

0.42

1.8
1.4

o.n

2.3

104

0.47
0.65

1.7

The higher the blood gas partition coefficient the greater the anesthetic solubility and
the greater its uptake by the pulmonary circulation, as a consequence of this high
solubility alveolar partial pressure riSE!S more slowly and thus induction is prolong.
The second factor that affects uptake is alveolar blood flow which is essentially equal to
cardiac output In the absence of pulmonary shunting.
If the cardiac output drops to zero, so will anesthetic uptake.
As cardiac output increases, anesthetic uptake increases. The rise in
alveolar partial press1Jre slows and thus induction is delayed.
The final factor affecting uptake is the partial pressure difference between alveolar gas
and venous blood.
The greater the uptake of the anesthetic agent, the greater the
difference between inspired and alveolar concentration, the slower the
rate of induction.
Low output states predisposes patient to overdosage with soluble agents since the rate
of rise in alveolar concentration will be markedly increased.

- The most important route for inhalational anesthetic is the alveolus.

Factors that would influence speed of induction (that which increases alveolar anesthetic
concentration - speed onset):
1. Increasing the delivered concentration of anesthetic.
2. High flow within the breathing circuit.
3. Increasing minute ventilation.

1.
2.

:>.
4.

That which decrease alveolar c.:mcenfration slow onset of volatile induction:

An increase ip cardiac output.
Decreased minute ventilation.
Uia~ llpit! aM t!thotk 1:l'!!uhi!itv.
Low flow within the breathing circuit.
Many factors that speed induction also speed recovery.

NITROUS OXlDE

The only i~organicanestheticgas io.diriical use.~.~

);.- Non-flammable but like oxygen jt supports.;,oeo11doeti:on,
Its circulatory effects are explained by its tendency to stimulate the sympathetic
nervous system ..
Unlike other inhalationai agents, it does not provide significantmuscle relaxatron
It may increase the incidence of postoperative nausea and vomiting;

>

=CAN EXPAND CLOSED AiRSPACES.

N2 0 is .301< is more soluble than nitrogen; N20 will diffuse into an air filled space
much more rapidiy than N2 that diffuse out~ so that as a result N 20 oxide can incre ase
the volume in a dosed body cavity with distensible walls such as an obstructed bc 1wel
cavity, pneumothorax, pneumopericardium or air emboli.
= SECOND GAS EFFECT
Nitrous oxide has the highest MAC (104) - it is not potent enough to be
used alone and. must be used ih combination wjth other anesthetic.
High concentration of nitrous oxide will augment not only its owr,
uptake but that of aconcurrentty administer-ed anesthetic. Nitro Ls
oxide is insoluble in bl.oot:Lso that its rapid.absorption in the ahmdi
results in an abrupt rise in alveolar concentration ofthe accompanying

volatile anesthetic.
The concentration effect of one gas upon another results in secor1d gas
effect. This phenomenon should speed the onset of anesthetic
induction.
=DIFFUSION HYPOXIA
~

When nitrous oxide ls abruptly discontinued, its rapid diffusion from the
blood to the alveolus decreases the oxygen concenj:ration (tensio1) in
the.lung leading to a brief period of decreased oxygen concentr~tion.
Administer 100% oxygen at the end ofthe case can eliminate the

above problem.
=BONE MARROW TOXICITY

>

Prnlonged exposuie to anesthetic concentration of nitrous oxide results

in bone marrow depression ieading to megaloblastic anemia.

VENTILATORY EFFECTS OF VOLATILE ANESTHET1CS

Dose dependent depression of ventilation mediated directly throl1gh

medullary centers and indirectly through effects on int1;;>rcostal muscle

function.

>
~

Volatile anesthetics !ead to a decrease in tidal volume and an incr ~ase

in respiratory rate ~ rapid shallow breathing pattern.
The ventilatoiyresponse to hyper carbia is also attenuated by incrE,asing
the delivered concentration of anesthetic.

AIRWAY IRRITATION:
)- Lack of airway irritation for sevoflurane and nitrous oxide so that 1hese
two agents could be used along w ith o>e-ygen for a pleasant mask
induction in children.

fso.f !urane and

de~f! ur2 ne h~ve

a pung@nt cd_c r dr~ qui~t

~ rr~td ting

and mnv c~us@ couuhina ~nd gvP-n l:;1ryngQ:f ~p;]t:m_

Desf!urane is us~d oniv for rnJir.t'1n:mrn nf :modhad::;.
AIRWAY RESISTANCE:
~ VolatHe anesthetics appear to decrease air-Nay resistance by a dire,ct

relaxing effect on bronchial smooth muscles and by decreasing th~

broncho constricting effect of hypocapnia.

. ';>

Oesflurane has no effect on airway resistance/. non- smokel'S but

pr.oduce broncho constriction. in.smokers.
Nitrous.oxide. has no effect on airway resistance .
The brocncho constricting effect of histamine release also appear to be
decreased when an inhalational anesthetic is administered.

MUCOCILIARY CLEARANCE:
> Appear to be diminished by volatile anesthetics. principatly throuE:h
interference with c:iliary beatfrequeni:y.
~ The effects of.dry inhaled gases, positive pressure ventilation and high
inspired oxygen content also contribute to ciliary impairment
The physiologic response to hypoxia and hypercarbia is blunt1~d by
volatile anesthetic in a dose dependent fashion.
11

These effects maybe summarized .a ccording to "3Rs

- rapid respiration
- reduced tidal volume
- regular duration with loss of the awake respiratory variability

CARDIOVASCULAR EFFECTS OF VOLATILE ANESTHETICS

I.
Maintenance of mean arterial pressure:
.~ All of the volatile inhaled anesthetics reduce arterial pressure in a dose dependent
fashion.
>- N20 is the only inhaled anesthetic that does not d rop the blood pressure'
Suppression of sympathetic nervous system activity:
IL
:;... Three inhaled anesthetics -N 2 0,/tq}flurane and D esflurane actually increase
sympathetic activity usually in a dose dependent fashion.
Ill.
Maintenance of heart rate:
J;;o. All of the inhaled anesthetics tend to increase the heart rate at least at the same
concentration.
- These effects may represent sympathetic stimulation, a reflex tachycardia from
the reduction in arterial pressure or actions .on the baroreceptors.
Ha!othane
~ Shown to increase the sensiiivity of the myocardium to the action of
catecholamines resulting. 1n prematu.re ventricularcontraction and
tachydysrrhythmi.:is.
Compared with adults, ch ildren undergoing halothai'le anesthesia appear t o be
relatively resistant to this sensitizing effect although halothane had been ~hown
to have a cholinergic vagaliy induced bradycardic effect in children.

N20 not potent enough to be used alone and must be used in combination with other
anesthetics.
CLINCAL PEARL.
ISOFLURANE
Dilates coronary arteries particularly If its concentration is abruptly increased tho1Jgh
not as a potent dilator as nitroglycerin.
Dilation of normal coronary arteries could theoretically divert blood away from the
stenotic le5'ons (CORONARY STEEL SYNDROME) causing myocardial ischemia duri1lg
episodes of tachycardia or drop in perfusion pressure thus. avoided in patients with
coronary artery disease.
DESFLURANE
Its low solubility in blood and body tissues cause a very rapid wash'.'.in and wash-oJt of
the anesthetic (fastest induction and emergence).
SEVOFLURANE

An excellent choice for smooth and rapid inhalational induction in pediatrics and adult
patients due to its non- pungency and rapid increases in alveolar anesthetic
concentration.
_Metabolized to fluoride ion, strong bases that accumulate Iii the carbon dioxide
absorbent at low gas flows can degrade sevoflurane to a nephrotoxic bi product.
Produces compound A which is potentially nephrotoxic metabolite.

ENFLURANE
Can produce fast frequency and high voltage activiti/ on the EEG that often progresses
to spike-wave activity which is in distinguishable from changes that accompany a
seizure.
This likelihood of enflurane evokes seizure activity Is increased when the concentration
of enflurane exceeds 2MAC or when hyperventilation of the lungs lowers the PAC02
below 30 mmHg.
Like most general classes of anesthetics, inhalation anesthetics vary in their properties. Some are
desirable, some are not. Thus, their use is tailored to a specific patient or a_ specific situation.

LOCAL ANESTHETICS

> drugs that block the generation and propagation of impulses in excitable tissues most
notably the spinal cord, spinal nerve roots, and peripheral nerves but also skeletar
muscles, cardiac muscle and brain.
WHAT ROLE DO LOCAL ANESTHETICS PLAY IN THE PRACTICE OF ANESTHESIOLOGY:

>
>
>

use to provide regional anesthesia for surgery.

To provide .post operative analgesia for painful surgical procedures.
Attenuate the pressor response to tracheal Intubation, decrease coughing during
intubation and extubatlon

:>

For anti arrhythmic effect.

Local anesthetic molecule consists of three building blocks
ESTER OR AMIDE LINKAGE

<

CH

CH

AROMATIC RING
. (Lipophilic)

QUARTERNARY AMINE
(Hydrophilic)

- the intermediate chain connecting the 1ip0philic head and the hydrophilic tail contains an amide Jr an
ester llnkagf'; thus subdividing the clinically useful local anesthetic info:
I. AMINO C:JTCJ'l;:i

1.) Cocaine
2.) Chloror1rocaine
3.) procaine
4.) tetracaine

\\, AMINO AMIOll

1.) Lldocalne
2.) Bupivacaine
3.) Mepivacalne
4.) Prilocalne
S.) Oebucalne
6.) Ropivacaine
METABOLISM OF LOCAL ANESTHETICS:
ESTERS - undergo hydrolysis by pseudocholinesterases found principally in plasma.
AMIDES- undergo enzymatic biotransformatlon primarily in deliver.

\.

ELECTROPHYSILOGIC EFFECTS OF LOCAL ANESTHETICS :

The accepted mechanism of action for clinically utilized local anesthetics is direct inhibition of
the voltage gated sodium channels
)- Initiated by binding of the local anesthetic molecule with receptors located in the channel this
receptor local anesthetic interaction prevents the sodium flux needed for initiation and
propagation of the action potential.
ALLERGIC POTENTIAL
);;> Esters produces metabolites related to PABA (responsible for the allergic reaction) so that they
are more likely to produce allerglc reaction thari the amides.
Allergic reaction following the use of focal anesthetics may also be due to methylparaben or
other preservatives in commercial preparation of local anesthetics
)- There is no cross sensitivity between classes of local anesthetics
)- Patients may experience palpitations induced by epinephrine containing local anesthetics.
WHAT DETERMINES LOCAL ANESTHJETIC POTENCY
)- The higher lipid solubility the greater the potency.
)- Lipid solubility correlates potency

Agent
Lipid solubility
Procaine
<1
2 Chloroprocaine
>1
Mepivacaine
1
Lidocaine .
3
Bupivacaine
28
Tetracaine
80
Etidocaine
140
Ropivacaine
14

Relative potency
1

3
1.5
2

8
8
8
8

Protein Binding

5
75

65
95
85
95

94

Duration
short
short
medium
medium
long
long
long
long

There are multiple measurements of local anesthetic potency that are analogous to the MAC of
inhalational anesthetics.
Cm - minimum concentration of local anesthetics that will block nerve impulse conduction.
This measure of relative potency is affected by several factors :
1. Nerve fiber size , type and myelination

2. pH (acidic antagonize block)

3. frequency of nerve stimulation (access oflocal anesthetic to the sodium receptor is enhanced
by repeatedly opening the sodium channel )
4. electrolyte concentration ( hypokalemia and hypercalcemia antagonize blockade
WHAT FACTORS INFLUENCE THE DURATION OF ACTION OF LOCAL ANESTHETICS
the greater the protein binding , the longer the duration of action
> the duration of action is also influenced by peripheral vascular effects ofthe local anesthetics.
> Lidocalne, prilocaine and mepivacaine provide anesthesia of similar duration.
Udocalne is a more potent vasodilator, increasing absorption and metabolism of the drug thus
hai: thg thortor cll nicI blockade than that produced by prilocaine or mepivacaine.
)-

>

WWAT OCTCnUllJCC LOCAL lll ~HMHI C ONSH TIME

The clegree of ionization; the closer the pKa of the local anesthetic to tissue pH the more rapid
the c nset time.
.
pKa defined as the pH at which the ionized and unionized form exist in equal concentration .
0

The latency of 1 local anesthetic can also be shortened by uslns a hiaher concentration and by
using carbonated local anesthetic solution to adjust the local pH

Agent
Procaine
2 Chloroprocalne
Mepivacaine
Lidocaine
Bupivacalne
Tetratcaine
Etldocaine
Ropivaca ine

Onset Time
Slow
Very quick
Quick
Quick
Moderate
Slow
Quick
Moderate

pKa

8.9
9.1
7.7
7.8
8.1
8.4
7.9
8.1

How does the onset of anesthesia proceed in a peripheral nerve block?

Conduction blockade proceeds from the outermost (mantle) to the innermost (core) nerve
bundles.
1
Mantle fibers inervate proximal sturctures and core fibers inervate distal structures
DIFFERENTIAL BLOCKADE
Describes blockade of the components of a peripheral nerve that proceet;ls at different rates:
a) Loss of sympathetic functions
b) Loss of pinprick sensation
c} Touch and temperature descrimlnation
d} Loss of motor functions
MAXIMUM SAFE DOSES OF LOCAL ANESTHETICS
DRUG
MAXIMUM DOSE (mg/kg}
Procaine
7
Cloroprocaine
8-9
Tetracalne
1.5
5 or 7 (w/ epinephrine)
Lidocaine
Meplvacalne
s
Bupivacaine
2.5
Etidocaine

WHY ARE -EPINEPHRINE AND PHENYLEPHRINE OFTEN ADDED TO LOCAL ANESTHETICS?

These drugs cause local tissue vasoconstriction thus limiting the uptake of the local anesthetic
into the vasculature therefore prolonging its effect and reducing its toxic potential.
CONTRAINDICATIONS TO LOCAL ANESTHETIC WITH EPINEPHRINE
1. Unstable angina pectorls
2. Cardiac dysrrhythmlas
3. Hypertension
4. Peripheral nerve blocks to fingers

lipid solubility of the local anesthetic determines potency.

pKa of the local anesthetic determines onset.
Protein binding of the local anesthetic determines duration of action.
TOXICITY OF LOCAL ANESTHETICS
Systemic toxicity is due to :
1. Elevated plasma local anesthetic level
a. Inadvertent lntravascular injection
b. Less frequently as a result of systemic absorption of local anesthetic .from the injection

site

SYSTEMIC VASCUlAR ABSORPTION OF LOCAL AN~~TMCTtc vAi\1C AT 01~~1:'.0t:MT ~IT~

lntercostal nerve block > caudal > eoidural > brachia! olexus > sciatic > subcutaneous

Because the intercostals nerve is surrounded by a rich vascular supply local anesthetic
increasing the likelihood
injected to this area will be more rapidly absorbed
of achieving toxic levels.
Toxicity from local anesthetics involves the cardiovascular system and the central nervous system.
The central nervous system is more sensitive to the toxic effects of the local anesthetics and is the one
that is affected first.
CENTRAL NERVOUS SYSTEM TOXICITY IS MANIFESTED BY THE FOLLOWING:
1. Light headedness, tinnitus, peri-oral numbness, confusion
2. Muscle twitching, auditory and visual hallucination
3. Tonic - clonic seizures, unconsciousness, respiratory arrest
CARDIO TOXICITY IS MANIFESTED BY THE FOLLOWING :
1. Hypertension, Tachycardia
2. Decreased contractility and cardiac output, hypotension
3. Sinus bradycardia, ventricular dysrrythmias, circulatory arrest
LOCAL ANESTHETIC INDUCED CNS TOXICITY MANIFEST WITH EXCITATION - - - SEIZURE
LOSS OF CONSCIOUSNESS
LOCAL ANSETHETIC INDUCED CVS TOXICITY MANIFEST AS HYPOTENSION - - .... CONDUCTION
BLOCKADE ----.CARDIAC ARREST
CARDIOTOXICITY WITH VARIOUS LOCAL ANESTHETICS
~ The ratio of the dosage requi;ed for irreversible cardiovascular collapse and the dosage that
produces CNS toxicity is much lower for bupivacaine and etidocaine than for lidocaine.
~ Pregnancy, acidosis, and hypoxia increases the risk of cardio toxicity with bupivacaine.
~ Cardiac resuscitation is more difficult following bupivacaine induced cardiovascular collapse.
This may be related to the lipid solubility of bupivacaine which results in a slow dissociation of
the drug from cardiac - Na channel (fast in - slow out)
~ By contrast recovery from less lipid soluble lidocaine is rapid (fast in -fast out)
~ In an effort to minimize the risk of cardiac toxicity in the event of an accidental intravenous
injection avoid the use of bupivacaine concentration greater than .5 percent especially in
obstetric epidural anesthesia.
NEUROTOXIC!TY FROM LOCAL ANESTHETICS
2 complications have been described after spinal and epidural anesthesia :
1. Transient neurologic symptom - manifest in the form of moderate to severe pain in the lower
back, buttocks and posterior thigh.
.

The symptoms appear within 24 hours of spinal and epidural anesthesia and generally
resolve within seven days.
2. Cauda equina syndrome - diffuse injury to the lumbo- sacral plexus
The mechanism of neural injury is thought to be that non- homogeneous distribution of
spinally injected local anesthetic may expose sacral n_erve roots to a high concentration
of local anesthetic with consequent toxicity
Avoid injecting large amounts of local anesthetic in the sub- arachnoid space, specially if
less than an anticipated response is obtained with the initial dose.

Important adverse effects of local anesthetics although rare may occur from:
I.
Systemic '1bsorption
II.
Local tissue toxicity
Ill.
Allergic reactions
IV.
Drug specific effects

I. Systemic Toxicity
The magnitude of local anesthetic systemic absorption depends on :
1. The dose injected
2. The specific site of injection
3. The inclusion of a vasoconstrictor in the local anesthetic solution.

SiglJS a~mptoms of CNS toxicity:

~'f.gtit"'fieadedness, tinnitus, perioral numbness, and confusion.

.; .

2. Muscle twitching, auditory and visual hallucinations.

3. Tonic-clonic seizures, unconsciousness, respiratory arrest.
Signs and symptoms of CVS toxicity:
1. Hypertension, tachycardia
2. Decreased contractility and cardiac output, hypotension
3. Sinus bradycardia, ventricular dysrrhythmias, circulatory arrest

Establishment of maximal acceptable local anesthetic doses for performance of regional

anesthesia is an attempt to limit plasma concentration that can result from systemic
absorption of these drugs.
Local anesthetic induced CNS toxicity manifest with excitation 7 seizures 7 loss of
consciousness.
Local anesthetic induced CVS toxicity manifest with hypotension 7 condu.c tion blockade
7cardiac arrest.
Local anesthetics are neuronal depressants and the onset of seizures is thought to
reflect selective depression of cortical inhibitory neurons leaving excitatory pathways
unopposed.
Higher doses may affect inhibitory and excitatory pathways resulting in CNS
depression and even coma (these effects parallel anesthetic potency).
High plasma concentration of local anesthetics can produce profound
hypotension due to relaxation of arteriolar vascular smooth muscle and direct
myocardial depression.

CARDIOTOXICITY WITH VARIOUS LOCAL ANESTHETICS

Part of the cardiac toxicity reflects the ability of local anesthetic to block cardiac sodium
iron channels ~ cardiac automaticity and conduction of cardiac impulses are impaired.
The ratio of the dosage required for irreversible cardiovascular collapse are the dosage
that produce CNS toxicity is much lower for bupivacaine and etidocaine than for
lidocaine.
- Such findings support the concept that bupivacaine has greater cardiac toxicity
which have been the driving force for the development of ropivacaine and
levobupivacaine.

- Bupivacaine has the highest risk_Qf producing severe cardiac dysrrhythmias and
irreversible cardiovascular collapse, so that use of more than 0.5 %
concentration should be avoided especially in obstetric analgesia.

- Pregnancy, acidosis and hypoxia Jncreases the risk of cardiotoxicity with

bupivacaine.
- Cardiac resuscitation is more difficult following bupivacqine induced
cardiovascular collapse. This is related to lipid solubility of bupivacaine which
result in slow dissociation of the drug from cardiac sodium channels (fast in slow out)
- By contrast recovery from less lipid soluble lidocaine is rapid (fast in - fast out)

PRILOCAINE
Local anesthetic associated with the risk of Methemoglobinemia.
Metabolized in the liver to 0-toluidine which is capable of oxidizing hemoglobin to
Methemoglobin.
In a dose greater than 600 mg can produce clinical methemoglo~inemia making the
patient appear cyanotic.
~ The above condition is spontaneously reversible or maybe treated by IV methylene blue
(1-2 mg/kg)

ROPIVACAINE
A new amide local anesthetic that is structurally and behaviorally similar to bupivacaine.
~ Like bupivacaine it is highly protein bound and has lengthy duration of action, however
it is less cardio toxic.
Capable of providing differential blockade (it is capable of separating sensory and motor
blockade)
this characteristic may make ropivacalne an ideal anesthetic for use
in obstetric procedure.

" EMLA" cream (eutectic mixture of local anesth.etic)

~ Consists of a 1:1 mixture of 5% lidocaine and 5% prilocaine
Dermal analgesia this requires a contact time of ~t least 1 hour under an occlusive
dressing.
This should not be used on :
1. Mucous membrane
2. Broken skin
3. lnJants less than 1 month old
4. Patients with predisposition to methemoglobinemia.
The rate of systemic absorption is proportionate to the vascularity of the site of injection.
The presence of vasoconstrictor causes vasoconstriction at the site of drug
administration leading to decrease in drug absorption.
Decrease absorption of local anesthetic through t he use vasoconstrictors will result in:
1. Increases neuronal uptake
2. Enhances the quality of the block
3. Prolongs the duration of action
4. limit toxic side effect
Muscle twitching heralds the onset of tonic-cloni.c seiiures--.. respiratory arrest often
follows.
Benzodiazepines and hyperventilation decreases cerebral blood flow and drug exposure (raises
the threshold of local anesthetic induced seizures)

Management of local anesthetic

toxicity :
,!
.
'

~
~

Adequate ventilation an oxygenation should be maintained

Thiopental (1-2 mg/kg) given quickly and reliably terminates seizures
Intravenous lidocaine ( 1.5 mg/kg) decreases cerebral blood flow and attenuates the rise
of in intracranial pressure that accompanies intubation in-patients with decrease
intracranial compliance.

CLINICAL PEARL
Local anesthetics will not occur in acidotic tissues
)'> Factors determining the onset duration and potential complications of a regional block
with local anesthetics include:
1. Site of injection
2. The dose of the local anesthetic
3. Physiochemical properties
~ The addition of epinephrine to local anesthetic is useful to :
1. Detect intravascular injection
2. To increase duration of the blockade
3. To prevent systemic absorption and toxicity
);>