1. LOCAL ANESTHETICS AND REGIONAL ANESTHESIA
Dr Mahmoud Al-mustafa

2. Local Anesthetics- History
cocaine isolated from erythroxylum coca
Koller uses cocaine for topical anesthesia
Halsted performs peripheral nerve block with local
Bier first spinal anesthetic
Koller also used cocaine powder on floors to anesthetize the noses of Nazi dogs, is credited with saving many lives.
Bier also described first PDH.

3. Local Anesthetics - Definition
A substance which reversibly inhibits nerve conduction when applied directly to tissues at non-toxic concentrations
Local anesthetics block generation, propagation, and oscillations of electrical impulses in electrically excitable tissue.
Mainly by acting on Na channels.

4. PHARMACOLOGY AND PHARMACODYNAMICS
Clinically used local anesthetics consist of lipid-soluble, substituted benzene ring linked to amine group via alkyl chain containing either an amide or ester linkage.
• Type of linkage separates local anesthetics into either aminoamides (metabolized in liver) or aminoesters (metabolized in liver or by plasma cholinesterase).

5. PHARMACOKINETICS
Systemic toxicity depends on blood levels of local anesthetic.
• End organs of main concern for toxicity are CV and CNS.
• Determinants of systemic absorption
» Site of injection (intercostal > caudal > brachial plexus > sciatic/femoral)
» Dose
» Physiochemical properties (lipid solubility, protein binding)
» Addition of epinephrine

6. Local anesthetics - Mechanism
Limit influx of sodium, thereby limiting propagation of the action potential.
This slide depicts the effect of sodium influx on overall membrane potential. By limiting influx, local anesthetics inhibit the depolarization of the membrane thereby interfering with propagation of the action potential.

7. Local Anesthetics - Classes
Esters

8. Local anesthetics - Classes
Esters
Cocaine
Chloroprocaine
Procaine
Tetracaine
Amides
Bupivacaine
Lidocaine
Ropivacaine
Etidocaine
Mepivacaine

9. Bupivacaine
Amide
• Infiltration: use 0.25%, fast onset, 2- to 8-hr duration, max dose 175 mg (225 mg with epinephrine)
• Peripheral nerve block: use %, slow onset, 4- to 12-hr duration, max dose 175 mg (225 mg with epinephrine

10. Bupivacaine
Epidural anesthesia: Use %, moderate onset, 2- to 5-hr duration, max dose 175 mg (225 mg with epinephrine)
• Spinal anesthesia: Use %, fast onset, 1- to 4-hr duration, max dose 20 mg
levo (-) bupivacaine less cardiotoxic than racemic bupivacaine, same

11. Lidocaine
Amide
• Infiltration: use 0.5-1%, fast onset, 2- to 8-hr duration, max dose 300 mg (500 mg with epinephrine)
• Peripheral nerve block: use %, fast onset, 1- to 3-hr duration, max dose 300 mg (500 mg with epinephrine)

12. Lidocaine
Epidural anesthesia: use 1.5-2%, fast onset, 1- to 2-hr duration, max dose 300 mg (500 mg with epinephrine)
• Spinal anesthesia: use 1.5-2%, fast onset, 0.5- to 1-hr duration, max dose 100 mg
• Topical anesthesia: use 4%, fast onset, 0.5- to 1-hr duration, max dose 300 mg
• IV regional: Use %, fast onset, hr duration, max dose 300 mg

13. Ropivacaine
Amide
• Infiltration: use %, fast onset, 2- to 6-hr duration, max dose 200 mg
• Peripheral nerve block: use %, slow onset, 5- to 8-hr duration, max dose 250 mg
• Epidural anesthesia: Use %, moderate onset, 2- to 6-hr duration, max dose 200 mg
·       less cariac toxicity than bupivacaine

14. Local anesthetics - Formulation
Biologically active substances are frequently administered as very dilute solutions which can be expressed as parts of active drug per 100 parts of solution (grams percent)
Ex.: 2% solution =
_2 grams__ = _2000 mg_ = __20 mg__
100 cc’s cc’s cc

15. Local Anesthetics - Allergy
True allergy is very rare
Most reactions are from ester class - ester hydrolysis (normal metabolism) leads to formation of PABA - like compounds
Patient reports of “allergy” are frequently due to previous intravascular injections

16. Local Anesthetics - Toxicity
Tissue toxicity - Rare
Can occur if administered in high enough concentrations (greater than those used clinically)
Usually related to preservatives added to solution
Systemic toxicity - Rare
Related to blood level of drug secondary to absorption from site of injection.
Range from lightheadedness, tinnitus to seizures and CNS/cardiovascular collapse

17. Local anesthetics - Duration
Determined by rate of elimination of agent from site injected
Factors include lipid solubility, dose given, blood flow at site, addition of vasoconstrictors (does not reliably prolong all agents)
Some techniques allow multiple injections over time to increase duration, e.g. epidural catheter

18. Local anesthetics - vasoconstrictors
Ratios
Epinephrine is added to local anesthetics in extremely dilute concentrations, best expressed as a ratio of grams of drug:total cc’s of solution. Expressed numerically, a 1:1000 preparation of epinephrine would be
1 gram epi
1000 cc’s solution
1000 mg epi
1000cc’s solution =
1 mg epi
1 cc

19. Local anesthetics - vasoconstrictors
Therefore, a 1 : 200,000 solution of epinephrine would be
1 gram epi
200,000 cc’s solution
1000 mg epi
200,000 cc’s solution = or
5 mcg epi
1 cc solution

20. Local anesthetics - vasoconstrictors
Vasoconstrictors should not be used in the following locations
Fingers
Toes
Nose
Ear lobes
Penis

21. REGIONAL ANESTHESIA

22. Regional anesthesia - Definition
Rendering a specific area of the body, e.g. foot, arm, lower extremities, insensate to stimulus of surgery or other instrumentation

23. Regional anesthesia - Uses
Provide anesthesia for a surgical procedure
Provide analgesia post-operatively or during labor and delivery
Diagnosis or therapy for patients with chronic pain syndromes

24. Regional anesthesia - types
Topical
Local/Field
Intravenous block (“Bier” block)
Peripheral (named) nerve, e.g. radial n.
Plexus - brachial, lumbar
Central neuraxial - epidural, spinal

25. Topical Anesthesia
Application of local anesthetic to mucous membrane - cornea, nasal/oral mucosa
Uses :
awake oral, nasal intubation, superficial surgical procedure
Advantages :
technically easy
minimal equipment
Disadvantages :
potential for large doses leading to toxicity

28. Local/Field Anesthesia
Application of local subcutaneously to anesthetize distal nerve endings
Uses:
Suturing, minor superficial surgery, line placement, more extensive surgery with sedation
Advantages:
minimal equipment, technically easy, rapid onset
Disadvantages:
potential for toxicity if large field

29. IV Block - “Bier” block
Injection of local anesthetic intravenously for anesthesia of an extremity
Uses
any surgical procedure on an extremity
Advantages:
technically simple, minimal equipment, rapid onset
Disadvantages:
duration limited by tolerance of tourniquet pain, toxicity

31. Peripheral nerve block
Injecting local anesthetic near the course of a named nerve
Uses:
Surgical procedures in the distribution of the blocked nerve
Advantages:
relatively small dose of local anesthetic to cover large area; rapid onset
Disadvantages:
technical complexity, neuropathy

34. Plexus Blockade
Injection of local anesthetic adjacent to a plexus, e.g cervical, brachial or lumbar plexus
Uses :
surgical anesthesia or post-operative analgesia in the distribution of the plexus
Advantages:
large area of anesthesia with relatively large dose of agent
Disadvantages:
technically complex, potential for toxicity and neuropathy.

37. Central neuraxial blockade - “Spinal”
Injection of local anesthetic into CSF
Uses:
profound anesthesia of lower abdomen and extremities
Advantages:
technically easy (LP technique), high success rate, rapid onset
Disadvantages:
“high spinal”, hypotension due to sympathetic block, post dural puncture headache.

38. Central Neuraxial Blockade - “epidural”
Injection of local anesthetic in to the epidural space at any level of the spinal column
Uses:
Anesthesia/analgesia of the thorax, abdomen, lower extremities
Advantages:
Controlled onset of blockade, long duration when catheter is placed, post-operative analgesia.
Disadvantages:
Technically complex, toxicity, “spinal headache”

39. TOXICITY OF LOCAL ANESTHETICS
Rx of systemic toxicity is primarily supportive:
» Stop injection
» Administer oxygen
» Support ventilation
» Tracheal intubation and control ventilation if necessary
» Suppress seizure activity (thiopental, midazolam, propofol)