Local anesthetic agents in anesthesia

1. LOCAL ANAESTHETIC AGENTS
By, DR. P. AKSHARA 1ST YR PG
MODERATOR : DR. PROF. S N KRISHNAMOORTY

2. SPECIFIC LEARNING OBJECTIVES
• Introduction & History
• Molecular structure
• Peripheral nerve –Anatomy & Conduction
• Mechanism of action
• Pharmacodynamics
• Pharmacokinetics
• Individual drugs and their metabolism
• Effects of LA drugs
• Toxicity
• Uses

3. Introduction
• Provide analgesia and anaesthesia for various surgical & non surgical
procedures.
• Used for acute and chronic pain management to reduce perioperative
stress , to improve perioperative outcomes, and to treat
dysrhythmias.
• Produce reversible conduction blockade of impulses along central and
peripheral nerve pathways.
• Applied to mixed nerves causes interruption of sensory and motor
impulses resulting in loss of autonomic control and muscular
paralysis.

4. History
• First LA discovered and isolated was COCAINE – which was extracted
as an oily substance from coca leaves of erythoxylon coca –German
chemist GADCKE 1855
• In 1880 – ALBERT NEIMAN pupil of Wohler , characterized the
substance as alkaloid and named it COACINE.
He also reported that it numbed the tongue on application
• The ability of cocaine to relive pain of pinpick was noted by Von
ANREP in 1880 after sc administration , but this was not publicized.
• A pupil of von arep, SIGMUND FREUD became interested in caocaine
as a stimulant and published a book – “ON COCA”

5. • In 1884 , CARL KOLLER, Vienese ophthalmologist, showed that
anesthesia would develop after application of cocaine to the eye of
the patient. He publicised its use in eye surgery , especially its topical
potency.
• In the following year 1885 HALSTED demonstrated in a tent near
Bellevue hospital in New York , that injection of cocaine solution
around the nerve tracts would completely wipe away the painful and
other sensations from periphery of the region.
• KNAPP , of New York, in 1884, summarized the literature on cocaine’s
use in surgery . He also reported on its use by retrobulbar injections
for eye enucleation.

6. • 1st synthetic LA was ester derivative procaine formed by combination
of PABA and diethylamine produced by ALFRED EINHORN, a chemist
in 1904 .
• Tetracaine , synthetic derivative of PABA was first prepared by EISLEB
in 1928, used clinically by KLESS in 1930 [PANTOCAINE, PONTOCAINE
OMETHOCAINE]
• DIBUCAINE was prepared by MIESCHER and introduced by MCELWAIN
in 1928 [PERCAINE NUPERCAINE]
• Lidocaine was synthesised as an amide LA by NILS LOFGREN in 1943.
Standard LA to which all other anaesthetics are compared
• Chloroprocaine synthetic compound , analogue of procaine –
introduced clinically by FOLDES IN 1952. [NESCAINE]
• Bupivacaine , synthetic drug, prepared by A.F EKENSTAM in 1957
[MARCAINE]

7. Molecular Structure
• Lipophilic portion- essential for
anaesthetic activity & therapeutically
useful LA require a delicate balance
between lipid solubility & water
solubility.
• Lengthening the connecting
hydrocarbon chain or ↑no. of carbon
atoms on tertiary amine or aromatic
ring often results in LA with different
lipid solubility , potency , rate of
metabolism and duration of action.
• Important differences between ester
and amide LA- the site of metabolism
& the potential to produce allergic
reactions.
• Poorly soluble in water and hence
marketed as water-soluble
hydrochloride salts –acidic (pH 6),
contributing to the stability of LA.

8. Classification – Nature of Linkage
ESTER AMIDES
a) Cocaine a) Lidocaine
b) Procaine b) Bupivacaine
c) Chloroprocaine c) Ropivacaine
d) Tetracaine d) Mepivacaine
e) Prilocaine

9. • Substituting a butyl group for
the amine group on the benzene
ring of procaine results in
tetracaine -↑lipid solubility ,10
times more potent, longer
duration of action → 4-5 fold
↓rate of metabolism.
• Halogenation of procaine –
chloroprocaine – 3 to 4 fold
↑hydrolysis rate of
chloroprocaine, which limits
duration of action & systemic
toxicity of this LA.

10. • Mepivacaine ,Bupivacaine &
Ropivacaine –Pipecoloxylidides.
• Mepivacaine methyl group on the
piperidine nitrogen atom.
• Addition of butyl group to the
piperidine nitrogen atom-
Bupivacaine which is 35 times
more in lipid solubility , potency
and duration 3 to 4 times that of
mepivacaine.
• Ropivacaine structurally resembles
bupivacaine and mepivacaine, with
propyl group on the piperidine
nitrogen atom.

11. Liphophillic–Hydrophillic Balance
• Lipophillic vs hydrophilic character of LA depends on the size of the
alkyl substituents on or near the tertiary amine and on the aromatic
ring.
• Lipophillicity : tendency of a compound to associate with lipids ,
membrane lipids in particular – a property usually approximated by
equilibrium partitioning into a hydrophobic solvent such as a octonol.
• Hydrophobicity: as octonol/ buffer partitioning , describes a
physicochemical property of LA.
• Hydrophobic agents are more potent and produce long-lasting blocks
than their less hydrophobic congeners do
Lignocaine- 366
Bupivacaine 3420
Tetracaine-5822.

12. Peripheral Nerve Anatomy
• A typical peripheral nerve consists
of several axon bundles/fascicles.
• Each axon has its own connective
tissue covering-the Endoneurium.
• Each fascicle of many axons is
encased by a second connective
tissue layer- the epithelial like
Perineurium.
• The entire nerve is wrapped in a
loose outer sheath called the
Epineurium.
• To reach the nerve axon,a LA must
traverse 4-5 layers of connective
tissue / lipd membranes barriers /
both.

13. • Nonmyelinated nerves- autonomic
postganglionic efferent & nociceptive
afferent C fibres –many axons encased
in a single Schwann cell sheath.
• All motor and sensory fibres are
enclosed in many layers of myelin-
plasma membranes of specialised
schwann cells that wrap around the
axon during the axonal growth.
• Myelin markedly ↑speed of nerve
conduction by insulating the
axolemma from the surrounding
conducting salt medium & forcing
“action current” generated by an
impulse to flow through the axoplasm
→nodes of ranvier (periodic
interuptions in the myelin sheath)
where the action impulse is
regenerated.

14. • Peripheral nerves are composed of myelinated – A & B fibres ,
unmyelinated C fibres.
• A minimal length of myelinated nerve fibres must be exposed to an
adequate concentration of LA for conduction blockade of nerve
impulses to occur.
• If only one node of ranvier is blocked , nerve impulses can skip across
this node and conduction blockade can occur.
• So , for a conduction blockade to occur, preferably 2-3 nodes of
ranvier should be exposed ~1cm to adequate concentration of LA.

15. Classification of Peripheral Nerves

16. Order of sensitivity to blockade
• Vasomotor and sympathetic efferent
• Temperature –cold
• Warm
• Slow pain
• Fast pain
• Cutaneous discrimination
• Touch
• Pressure
• Motor fibres
• Muscle, tendon joint sensation
• Deep pressure

17. Mechanism of action
• LA binds to specific sites in voltage-gated Na+ channels, block Na+
ions current, prevent transmission of nerve impulses.
• Na+ channels – a specific receptor for LA
• Failure of Na+ ion channel permeability to increase- slows the rate of
depolarization- threshold potential is not reached- action potential is
not propagated.
• LA do not alter the resting membrane potential.

18. Action potential / Nerve impulses/ Spikes.
• Brief , localised spikes of positive charge
or depolarizations on the cell membrane
caused by rapid influx of sodium ions
down the electrochemical gradient.
• Phases :
a) Rising phase: depolarization occurs.
b) Peak phase : point where
depolarization stops (membrane
potential is max)
c) Falling phase: membrane potential
becomes negative, returning towards
resting potential.
d) Undershoot : afterhyperpolarization
where the membrane potential more
negative than resting membrane.
e) Refractory phase: subsequent action
potential is impossible to occur.

20. Sodium channel

21. • Binding affinity of LA to Na+ channel
are stereospecific and depends on the
conformational state of Na+ channel.
• Exists in Open(activated), Inactivated-
closed and rested .
• In the resting membrane , Na+
channels are distributed in
equilibrium between rested closed
and inactivated closed.
• LA selectively binds to inactivated –
closed Na+ channels& stabilizes these
channels in this configuration and
prevents their change to rested-closed
& activated-open states in response to
nerve impulse.
• Hence Na+ channels inactivated state ,
not permeable to Na+ & conduction
of nerve impulses cannot occur.

22. Frequency Dependent Blockade
• Na+ channels recover from LA induced conduction blockade between
action potentials.
• Additional conduction blockade develops each time Na+ channel open
during an action potential.
• LA molecules can gain access to receptors only when the Na+ channels are
in activated-open states.
• LA binds more strongly to inactivated- closed states.
• For this reason, selective conduction blockade of nerve fibres by LA may be
related to the nerve’s characteristic frequencies of activity (nerves that fire
frequently ) as well as to its anatomic properties- diameter.

23. Local anaesthetic agent
↓
In tissue, pH increases ,Dissociates to release free base(N)
↓
Free base is lipid soluble.
↓
Enter into the interior of the axon
↓
Re-ionisation takes place
↓
Re-ionised portion block the Na+ channel and prevent influx of sodium ions
↓
Fails to initiation and propagation of action potential
↓
Impulse cannot go to the Higher centre
↓
No pain

24. Other sites of Action Targets
• LA block voltage- dependent K+ ion channels.
• Compared with Na+ channels, LA inhibits a much lower affinity for K+
channels.
• Blockade of K+ channels - broadening of action potential in the
presence of local anaesthetics.
• Structural similarity between voltage – dependent Ca+ channels &
Na+ ion channels – calcium ion currents may also be blocked by local
anaesthetics.

25. Minimum effective Concentration-Potency
• Minimum concentration of LA necessary to produce conduction blockade of
nerve impulses – Cm- MAC(minimum alveolar concentration) for inhaled
anaesthetics
• Affected by
1)Lipid solubility
2)Fiber size,type,myelination
3)pH
4)Frequency of nerve stimulation
• Nerve fibre diameter influences Cm, with larger diameter requiring higher
concentrations of local anaesthetics for production of conduction blockade.
• An increased tissue pH or high frequency of nerve stimulation decreases Cm.

26. • Each LA has a unique Cm, reflecting differing potencies of each drug.
• Cm of motor fibres is twice that of sensory fibres – sensory
anaesthesia may not be accompanied by skeletal muscle paralysis.
• Despite an unchanged Cm, less local anaesthetics is needed for SAB
than for epidural anaesthesia, reflecting greater access of local
anaesthetics to unprotected nerves in the subarachnoid space.

27. Differential conduction blockade
• On basis of differing Cm values of LA for different nerve fibres ,
selective blockade of certain fibres and their function without
blockade of other fibres can be accomplished –DIFFERNTIAL NERVE
BLOCK.
• In peripheral nerves, the small pain fibres of the A𝛿 fibres and C fibres
are readily blocked at lower conc than the A motor , proprioceptive ,
and sensory fibres.
• In the subarachnoid space, the block of spinal nerve root study
revealed- preganglionic autonomic B fibres are blocked quickly by a
Cm similar to that of small A fibres.

28. Pregnancy
• Increased sensitivity (more rapid onset of conduction blockade ) .
• Spread of neuraxial block more rapid in a pregnant mother.
• Mechanical effect – dilated epidural veins, ↓ subarachnoid space.
• Direct effect – hormone progesterone, more susceptible to
conduction blockade.
• LA drug dose should be ↓ in all stages of labour.

29. PHARMACOKINETICS

30. Hydrogen ion concentration
• LA in solutions exists in a rapid equilibrium between the base,
uncharged form (B) and the charged cationic form (BH+).
• At certain H+ concentration , specific for each LA drug ,conc of base=
conc of charged cation.
• The logarithm of this H+ concentration – pKa.
• The retionship between the fraction of charged drug and the pH is
defined by,

31. Dissociation constant (pka) of LA
• It is the pH at which drug is present in 50% undissociated (unionized)
& 50%in dissociated (ionized ) form.
• pKa of commonly used LA is between 7.6-8.9
• Lignocaine -7.8
bupivacaine, levobupivacaine & ropivacaine-8.1
• Unionized (active/base) form facilitates diffusion across the nerve
membrane . Hence no. of molecules of unionized form determines
the speed of onset.
• Low pka – increased unionized form.
• High pka –uptake is slow & onset delayed.

32. Fraction nonionized (%) Fraction nonionized(%)
@ pH 7.4 @pH 7.6
Lignocaine (7.9) 25 33
Bupivacaine(8.1) 17 24
Levobupivacaine (8.1) 17 24
Ropivacaine (8.1) 17
• LA are weak bases that have pka values somewhat above
physiological pH - <50% of LA exists in lipid soluble unionized form @
pH.
• This is consistent with poor quality of of LA when injected into an
acidic infected area
• pka nearby pH – most rapid onset of action reflecting optimal ratio of
ionized to nonionized drug fraction.

34. Absorption and distribution • Rate of systemic absorption : injected
LA depends on
1) Site of injection: Intercostal (peak
level 8-9mins) > paracervical
(10mins) >IM (12mins) Caudal >
epidural(15mins) >axillary(20mins)>
Brachial plexus(25mins)> SAB(20-
30mins)> sciatic-
femoral(30mins)>Subcutaneous
sites
2) Vasoconstrictors :↓ the systemic
absorption.
3) LA agent : more lipid soluble , highly
bound to tissues , more slowly
absorbed.

35. • Lung extraction : after rapid entry of LA into venous circulation –
pulmonary extraction – limits the drug reaches the systemic
circulation.
• Placental transfer : plasma protein binding
• Renal elimination : poor water solubility of LA usually limits the
excretion of unchanged drug to less than 5%.

36. Local anesthetics process sequale
Onset & establishment of anesthetic block
1)Diffusion : movement of molecules of LA agent to vascular and nerve
cell compartments . Depends on water solubilty and dissociation to
free undissociated base
2)Penetration: entrance through cell membrane . Depends on non
ionized base form.
3) Distribution : movement into nerve bundle mantle and core.
Depends on the concentration gradient & aqueous solubility.
4) Fixation : to the nerve cell components. depends on the affinity of
the cationic form to the channel receptors.

37. Reversal and recovery
5) Absorption : initially excess of anaesthetic in extra cellular space
enters capillaries. This extracellular anesthetic enters vascular
compartment. Depends on conc gradient between extracellular space
and vascular compartment.
6)Reversal / release process : nerve fibres releases the drug as the
gradient of conc reverses with time.
7)Redistribution : drug in the plasma is distributed to regions(organs&
tissues) beyond the site of injection
8)Destruction & elimination : hydrolysis in plasma –esters &
conjugation in liver –amides. Elimination of free & conjugate products
in kidneys.

38. Metabolism of AMIDE LA
• Liver: metabolised by microsomal P-450 enzymes.
• Initial step is conversion of amide base into
a) amino carboxylic acid (N- alkylation)
b) cyclic aniline derivative(hydroxylation)
• ↓ n hepatic function – ↑conc. in blood- systemic toxicity
• Unmetabolised LA excreted by kidneys
• order from most rapidly degraded LA to those more slowly
degraded
Prilocaine>etidocaine> lidocaine > mepivacaine > bupivacaine.

39. Metabolism
1)LIDOCAINE
↓(principal metabolic pathway)oxidative dealkylation
monoethylglycinexylidide(80% protective against cardiacarrythmias)
↓hydrolysis
xylidide
2)PRILOCAINE – orthotoluidine (oxidizing compound capable of converting
Hb to methemoglobin)-Methemoglobinemia.
3) MEPIVACAINE- similar to lidocaine
4) BUPIVACAINE-(binds to AAG protein site )
a)aromatic hydroxylation
b)N-dealkylation
c)amide hydrolysis
d)conjugation
5) ROPIVACAINE: metabolized to 2,6 –pipecoloxylidide and 3-hydroxyropivacaine

40. Metabolism of ESTER LA
• Undergo hydrolysis by plasma cholinesterases
• PABA (metabolite)-allergic reactions.
• Only exception cocaine-hepatic carboxyesterase
• CSF has little or no enzyme – drug persists until has been absorbed
into systemic circulation.

41. Alkalinization of LA drugs
• Addition of sodium bicarbonate→
a) accelerate onset , decreases Cm
b)enhances the depth of sensory & motor blockade
• Addition of sodium bicarbonate-↑pH-↑amount of drug in the
uncharged base(lipid soluble form) →rate of diffusion across the
nerve sheath →rapid onset of anaesthesia.

42. Addition of Vasoconstrictor
• Vasoconstrictors, usually EPINEPHRINE (5𝜇g/ml or1:200000) are
frequently used.
• Limits vascular absorption by vasoconstriction , maintains the drug
conc in the vicinity of nerves to be anaesthetized→ improve the
depth and duration of anaesthesia
• Epinephrine may also enhance conduction blockade by increasing the
neuronal uptake of the LA.
• Marker for inadvertent intravascular injection.
• LA containing epinephrine used with inhaled anesthetics – possibility
of enhanced cardiac irritation.

43. Procaine
• Procaine is p-amino benzoyl diethyl amino ethanol hydrochloride .
• Synthesised by Einhorn in 1905.
• Duration of action is 20-30 mins & 30-45 mins when epinephrine is
added.
• Major anesthetic use : topical -200mg/ml , infiltration(1-2%) : 10-20mg/ml
solutions & spinal : 100mg/ml solutions
• Available preparations : 0.5 % , 1%, 2% & 10% without epinephrine.
1 &2 % with epinephrine 1:100000 or 1:50000 respectively.
• 0.5% & 1% - infiltration ; 1% & 2% solutions –nerve blocks . Ampoules from
50mg to 500mg crystals of hydrocholoride salts are available for spinal
anesthesia.

44. Chloroprocaine
• Analogue of procaine clinically introduced by Foldes in 1952.
• Addition of chlorine atom to benzene ring of procaine.
• 2-4 times more potent than procaine and used for nerve block
anesthesia.
• Rapid onset adequate duration with low potency for toxicity.
• Rapidly hydrolysed by plasma cholinesterase into inactive metabolites
2-chloro aminobenzoic acid and 2- diethylaminoethanol.
• Most acidic of all LA (pH 3.3 )
• Lack of systemic toxicity.

45. Dibucaine
• 1st amide LA
• Quinoline derivative with an amide bond in the connecting
hydrocarbon chain
• Known for its ability to inhinit plasma cholinesterase .
• Atypical plasma cholinesterase –prolonged effects and toxicity of
succinylcholine and chloroprocaine that are metabolised by this
enzyme.
• Measurement of degree of enzyme suppression by dibucaine-
dibucaine number (lab evaluation of pts with atypical
pseudocholinesterase )
• Mainly used as surface anesthetics on less delicate mucous
membrane.

46. Lignocaine
• An amide formed from reaction of diethyl amino acetic acid and
xylene.
• Freely soluble in water.
• Causes maximal vasodilatation so rapid systemic absorption without
vasoconstrictor.
• Class 1B antiarrythmic agent→ventricular tachycardia and digitalis
toxicity.
• When systemically administered 1.5mg/kg-↓cerebral blood flow and
attenuate the rise of ICP, attenuates haemodynamic response of
largyngoscopy during intubation.
• Therapeutic plasma concentration 2-3 mcg/ml safe dose -5mg/kg
• ↓hepatic metabolism of lidocaine when pts are anaesthesised with
volatile anesthetics.

47. Bupivacaine
• Aminoamide LA
• Not used for I.V anesthesia- cardiotoxicity.
• Severe ventricular suppression and myocardial suppression
• Lignocaine & bupivacaine both block cardiac Na+ channel.
• Cardiac toxicity is difficult to treat and is enhanced by hypercarbia,
hypoxemia, acidosis.
• Most important plasma protein binding site –alpha1 acid
glycoprotein.
• Urinary excretion->40% dose (dealkylation , aromatic hydroxylation,
amide hydrolysis and conjugation)

48. Ropivacaine
• Recently developed LA
• A pipecolic acid derivative of xylide with propyl group on piperidine
nitrogen atom of molecule.
• Long acting but less cardiotoxic (pure S enantiomer) ,also binds to
AAG site.
• Lipid solubility intermediate between lidocaine and bupivacaine
• Metabolised to 2,6-pipecoloxylidide and 3-hydroxyropivacaine by
hepatic cytochrome P450 enzyme.
• Both metabolities -↓ potency than ropivacaine.
• Strength -0.25 – 1%
• Very popular in epidural, PNB (less motor block)

49. Toxicity
• Principal side effects of LA :
a) allergic reactions
b)systemic toxicity (excessive tissue & plasma conc.)
ALLERGIC REACTIONS:
• Esters are metabolised to PABA – related to allergic reactions
• Allergic reaction may also be due to methylparaben – preservatives
used in preparation of amide and esters.
• These preservatives are structurally similar to PABA .

50. • rash, urticarial, laryngeal edema with/out hypotension &
bronchospasm
-LA induced allergic reaction
• Hypotension with syncope/ tachycardia – accidental intravascular
administration of epinephrine containing LA
CROSS SENSITIVITY:
• Cross sensitivity between LA reflects common metabolite PABA.
• A similar cross – sensitivity does not exists between classes of LA.
• Eg : pt with known allergy to an ester LA can receive an amide LA
without any risk of allergic reactions & vice versa.
• It is important that the “safe” LA be preservative – free

51. Local Anaesthetic Systemic Toxicity - LAST
• ↑plasma conc of LA.
• Plasma conc determined by rate of entrance into systemic circulation
relative to their redistribution to inactive tissues and clearance by
metabolism.
• Magnitude of systemic absorption depends on
a) Dose administered
b) Vascularity of injection site
c) Presence of epinephrine in the solution.
d) Physiochemical properties of the drug.
• CV/CNS ratio – describes the dose required to produce arrhythmias vs
dose required to produce seizures.

53. CNS toxicity
↓plasma conc of LA – numbness of tongue and circumoral tissues,
reflecting the delivery of the drug to high vascular tissues.
↓
As plasma conc ↑, LA crosses blood barrier –restlessness, vertigo,
tinnitus, difficulty in focussing.
↓
Further ↑in CNS conc. – slurred speech , skeletal muscle twitching(first in
face later in extremities)
↓
drowsiness followed by seizures(selective depression of inhibitory cortical
neurons by LA , leaving excitatory pathways uninhibited.)
↓
CNS depression , systemic Hypotension (↓CO, ↓SVR) & apnea.

54. • Lidocaine , mepivacaine & prilocaine demonstrate effects on CNS at
plasma conc. 5-10mcg/ml.
• Plasma conc. of Bupivacaine associated with seizures is 4.5 to 5.5
mcg/ml.
• The threshold plasma conc at which CNS toxicity occurs maybe
related more to the rate of increase of the serum conc than to the
total amount of drug injected.
• ↑ sr K+ conc. facilitate depolarization - markedly↑ toxicity

55. CVS toxicity
• CVS is more resistant to the toxic effects of high plasma conc of local
anaesthetics than CNS.
• Cardiac toxicity occurs because LA blocks cardiac sodium channels.
• At ↓conc of LA , this effect on Na+ channels contributes to cardiac
antidysrhythmic property.
• When plasma conc ↑, sufficient cardiac sodium channels become
blocked so that conduction and automaticity become adversely
depressed.
• Effects of LA on calcium & potassium ion channels and LA induced-
inhibition of cAMP production may also contribute to cardiac toxicity.

56. Selective Cardiac Toxicity of Bupivacaine
• Cardiotoxic plasma conc. Of bupivacaine 8-10mcg/ml.
• After accidental IV injection of bupivacaine , the protein-binding sites
(alpha 1 acid glycoprotein and albumin ) for bupivacaine are
quickly saturated , leaving a significant mass of unbound drug
available for diffusion into the conducting system of the heart .
• Premature ventricular contractions , widening of QRS complex
& ventricular tachycardia .

57. • Both bupivacaine and lidocaine block cardiac sodium ion channels
during systole , whereas during diastole highly lipid soluble
bupivacaine dissociates these channels at a slower rate- cardiac
toxicity.
• R enantiomer of bupivacaine is more toxic than the S enantiomer.
• Ropivacaine is a pure S enantiomer –less lipid soluble , less
cardiotoxic .

58. American Society of Regional Anesthesia and Pain Medicine
recommendations for managing LAST.
A) Signs & symptoms of LAST – prompt and effective airway management to
prevent hypoxia and acidosis which are known to potentiate LAST
B) If seizures occur they should be rapidly halted with benzodiazepines(if
not available small doses of propofol / thiopental are acceptable
C) Although propofol can stop seizures, it should be avoided when there
are signs of CV compromise( large dose can further depress cardiac function)
- If seizures persist despite benzodiazepines , small doses of
succinylcholine /similar neuromuscular blocker should be given to minimize
acidosis and hypoxemia.

59. D)If cardiac arrest occurs –recommend ACLS with
-epinephrine (small initial doses 10-100mcg boluses)
-vasopressin not recommended
-avoid calcium channel blockers and beta adrenergic blockers
-if ventricular arrhythmias develop – amiodarone is preferred.
E)Lipid emulsion therapy- consider administering at the first signs of LAST,
after airway management
- Dosing : 1.5ml/kg 20% lipid bolus
0.25ml/kg/min of infusion, continued for atleast 10mins after
circulatory stability is attained.
if circulatory stability not attained, consider rebolus and ↑ infusion
to 0.5ml/kg/min.
~10ml/kg lipid emulsion for 30mins is recommended as the
upper limit for initial dosing.

60. F) Propofol is not a substitute for lipid emulsion
G)Failure to respond to lipid emulsion and vasopressor therapy
should prompt institution of cardiopulmonary bypass.

61. • NEUROTOXICITY : LA into SAB/epidural . Spectrum range from patchy groin
numbness and persistent myotomal weakness to cauda equine syndrome.
Lignocaine- induced increases in intracellular calcium ion conc-mechanism .
• TRANSIENT NEUROLOGIC SYMPTOMS : moderate to severe pain in the
lower back ,buttocks and posterior thighs that appear within 36 hrs after
complete revovery from uneventful single-shot spinal anaesthesia. Tx –
NSAIDS. Full recovery within 1 to 7 days.
• CAUDA EQUINA SYNDROME: diffuse injury across the lumbosacral plexus
producing various degrees of sensory anaesthesia , bowel an bladder
sphincter dysfuction and paraplegia.

62. • ANTERIOR SPINAL ARTERY SYNDROME: lower extremity parathesis
with a variable sensory deficit.
• VENTILATORY RESPONSE TO HYPOXIA : lignocaine at clinical plasma
conc. Depresses ventilator response to arterial hypoxemia . Patients
with CO2 retention whose resting ventilation depends on hypoxic
drive maybe at risk of ventilator failure.
• METHEMOGLOBINEMIA : decreased oxygen carrying capacity .
Follows administration of LA –oxidation of Hb to methemoglobin.
Methylene blue : 1-2 mg/kg. (total dose 7-8 mg/kg)

63. Uses
1) Topical / surface anesthesia
2) Local infiltration
3) Peripheral nerve block
4) IV regional anesthesia
5) Epidural anesthesia
6) Spinal / subarachnoid anesthesia

64. Topical anaesthesia
• Produce topical anaesthesia by placement on mucous membranes,
nose , esophagus, tracheobronchial tree and genitourinary tract.
• Cocaine : 4% , lidocaine: 2-4% and tetracaine : 1-2%
• Nebulised lidocaine(vasoconstriction) – surface anaesthesia of upper
& lower respiratory tract before FOB/FOL.
• EMLA – 5% (2.5% prilocaine &2.5 % lidocaine)
1-2 g of EMLA cream applied per 10 cm2 area of skin and covered with
occulusive dressing.
Effective in relieving pain of venepuncture, arterial cannulation, lumbar
puncture .

65. • Skin blood flow , epidermal and dermal thickness , duration of
application , skin pathology presence- factors affecting onset, efficacy,
duration of EMLA analgesia.
• Blanching of skin after 30-60 mins – vasoconstriction.
• Local skin reactions – pallor, erythema, alterations in temperature
sensation , pruritis and rash common after EMLA.
• Not recommended use on mucous membranes,skin wounds, patients
with congenital methemoglobinemia and on antidysrhythmic drugs(
mexiletine) , known history of allergy to amide LA.

66. • Physical methods to accelerate LA transit through skin- iontophoresis,
local heating, electroporation needless puncture (SYNERA-
LIDOCAINE+ TETRACAINE with heating element)
• TAC
• LET

68. Spinal anesthesia
• Lidocaine 0.5% (neurotoxicity)
• Bupivacaine widely used –
• a)hyperbaric bupivacaine- bupivacaine 0.75% + dextrose 8.25%
• b)isobaric 0.5%
• Epinephrine 0.2-0.3 mg used with LA- 50% increase in duration
• Addition of epinephrine to bupivacaine/ lidocaine may be more
effective in prolonging duration of action in lumbosacral than in
thoracic segments

70. Central neuraxial block -epidural
• Any LA can be used except tetracaine and procaine (longer onset of times)
• Drugs of intermediate potency produce 1-2 hrs of surgical anesthesia .long
acting drugs produce 3-4 hours
• Epinephrine does not affect long acting LA
• Bupivacaine commonly used.
• 0.0625-0.1%- labor anesthesia
• 0.125%- adequate analgesia with little motor deficit
• 0.25%- moderate analgesia with moderate motor deficit(epidural light GA)
• 0.75%-more intense motor block(surgical anaesthesia) not suitable for
infusions
• Etidocaine – restricted to surgeries where profound muscle relaxant is
required.

72. Intravenous regional anesthesia
• Bier block – I.V administration of LA into a tourniquet occluded limb –
LA diffuses from the peripheral vascular bed to nonvascular tissue eg :
axon, nerve ending
• Safety and efficacy depends on interruption of blood flow to the
involved limb
• Indication – upper limb surgeries and short procedures of foot
• Choice of drug - lidocaine ( 3mg/kg preservative without
epinephrine) 40 ml of 0.5% solution.
• Ropivacaine 1.2 & 1.8 mg/kg (residual analgesia)
• Mepivacaine 5mg/kg & prilocaine also used.
• thrombophlebitis with chloroprocaine : cardiotoxicity with
bupivacaine

73. Reference
• Miller’s Anesthesia -8th edition
• Stoelting’s Pharmacology & Physiology in Anesthetic Practice – 5th
edition

74. THANK YOU