Download - Ossipov GeneralAnesthetics
General Anesthetics
Michael H. Ossipov, Ph.D.Department of Pharmacology
Surgery Before Anesthesia
Fun and Frolics led to Early Anesthesia
History of Anesthesia(150 years old)
Joseph Priestly – discovers N2O in 1773
Crawford W. Long – 1842. Country Dr. in Georgia first used ether for neck surgery. Did not publicize, in part because of concerns about negative fallout from “frolics”. Tried to claim credit after Morton’s demonstration but…
Important lesson learned – if you don’t publish it, it didn’t happen.
Sir Humphrey Davy – experimented with N2O, reported loss of
pain, euphoria
Traveling shows with N2O (1830’s – 1840’s)
Colt (of Colt 45 fame)
Horace Wells 1844. Demonstrated N2O for tooth extraction – deemed
a failure because patient “reacted”.
History of Anesthesia
William Morton, dentist – first demonstration of successful surgical anesthesia with ether 1846
John C. Warren, surgeon at MGH says “Gentlemen, this is no humbug!” – birth of modern anesthesia
Dr. John Snow administers chloroform to Queen Victoria (1853)– popularizes anesthesia for childbirth in UKHe becomes the first anesthesia specialist.
Note that ether became anesthesia of choice in US, chloroform in UK
Anesthesia
• Allow surgical, obstetrical and diagnostic
procedures to be performed in a manner
which is painless to the patient
• Allow control of factors such as physiologic
functions and patient movement
Anesthetic techniques
• General anesthesia • Regional anesthesia • Local anesthesia • Conscious Sedation
(monitored anesthesia care)
What is “Anesthesia”
• No universally accepted definition
• Usually thought to consist of: – Oblivion – Amnesia – Analgesia – Lack of Movement – Hemodynamic Stability
What is “Anesthesia”
• Sensory
-Absence of intraoperative pain
• Cognitive:
-Absence of intraoperative awareness-Absence of recall of intraoperative events
• Motor:
-Absence of movement -
Adequate muscular relaxation
• Autonomic:
-Absence of hemodynamic response
-Absence of tearing, flushing, sweating
Goals of General Anesthesia
• Hypnosis (unconsciousness) • Amnesia • Analgesia • Immobility/decreased muscle tone
– (relaxation of skeletal muscle)
• Inhibition of nociceptive reflexes • Reduction of certain autonomic
reflexes – (gag reflex, tachycardia,
vasoconstriction)
Desired Effects Of General Anesthesia(Balanced Anesthesia)
• Rapid induction • Sleep • Analgesia • Secretion control • Muscle relaxation • Rapid reversal
PhasesStagesofOfGeneralGeneralAnesthesiaAnesthesia
• Induction- initial entry to surgical anesthesia
• Maintenance- continuous monitoring and medication – Maintain depth of anesthesia, ventilation, fluid
balance, hemodynamic control, hoemostasis
• Emergence- resumption of normal CNS function – Extubation, resumption of normal respiration
Stages Of General Anesthesia
Phases of General AnesthesiaStage I: Disorientation, altered consciousness
Stage II: Excitatory stage, delirium, uncontrolled movement, irregular
breathing. Goal is to move through this stage as rapidly as possible.
Stage III: Surgical anesthesia; return of regular respiration. Plane
1: “light” anesthesia, reflexes, swallowing reflexes.
Plane 2: Loss of blink reflex, regular respiration (diaphragmatic and chest). Surgical procedures can be performed at this stage.
Plane 3: Deep anesthesia. Shallow breathing, assisted ventilation needed. Level of anesthesia for painful surgeries (e.g.; abdominal exploratory procedures).
Plane 4: Diaphragmatic respiration only, assisted ventilation is required. Cardiovascular impairment.
Stage IV: Too deep; essentially an overdose and represents anesthetic crisis. This is the stage between respiratory arrest and death due to circulatory collapse.
Routes of Induction
•Intravenous–Safe, pleasant and rapid
•Mask–Common for children under 10
–Most inhalational agents are pungent, evoke coughing and gagging
•Avoids the need to start an intravenous catheter before induction of anesthesia
–Patients may receive oral sedation for separation from parents/caregivers
•Intramuscular–Used in uncooperative patients
Anesthetic Techniques
• Inhalation anesthesia – Anesthetics in gaseous state are
taken up by inhalation
• Total intravenous anesthesia • Inhalation plus intravenous
(“Balanced Anesthesia”) – Most common
Anesthetic drugs have rapid onset and offset
• “Minute to minute” control is the “holy grail” of general anesthesia
• Allows rapid adjustment of the depth of anesthesia
• Ability to awaken the patient promptly at the end of the surgical
procedure
• Requires inhalation anesthetics and short-acting intravenous drugs
Anesthetic Depth
• During the maintenance phase, anesthetic doses are adjusted based upon signs of the depth of anesthesia
• Most important parameter for monitoring is blood pressure
• There is no proven monitor of consciousness
Selection of anesthetic technique
• Safest for the patient • Appropriate duration
– i.v. induction agents for short procedures
• Facilitates surgical procedure • Most acceptable to the patient
– General vs. regional techniques
• Associated costs
MAC – Minimal Alveolar Concentration• "The alveolar concentration of an inhaled anesthetic that prevents
movement in 50% of patients in response to a standardized stimulus (eg, surgical incision)."
• A measure of relative potency and standard for experimental studies.
• MAC values remain constant regardless of stimuli, weight, sex, and even across species
• Steep DRC: 50% respond at 1 MAC but 99% at 1.3 MAC
• MAC values for different agents are approximately additive. (0.7 MAC N2O + 0.6 MAC halothane = 1.3 MAC total)
• "MAC awake," (when 50% of patients open their eyes on request) is approximately 0.3.
• Light anesthesia is 0.8 to 1.2 MAC, often supplemented with adjuvant i.v. drugs
Factors Affecting MAC
• Circadian rhythm • Body temperature • Age • Other drugs
– Prior use – Recent use
How do Inhalational Anesthetics Work?Surprisingly, the mechanism of action is still largely unknown.
• "Anesthetics have been used for 160 years, and how they work is one of the great mysteries of neuroscience," James Sonner, M.D. (UCSF)
• Anesthesia research "has been for a long time a science of untestable hypotheses," Neil L. Harrison, M.D. (Cornell University)
How do Inhalational Anesthetics Work?Meyer-Overton observation: There is a strong linear correlation between lipid solubility and anesthetic potency (MAC)
How do Inhalational Anesthetics Work?
•Membrane Stabilization Theory:– Site of action in lipid phase of cell membranes
(membrane stabilizing effect) or – Hydrophobic regions of membrane-bound proteins
– May induce transition from gel to liquid crystalline state of phospholipids
– Supported by NMR and electron-spin resonance studies
– Anesthesia can be reduced by high pressure
How do Inhalational Anesthetics Work?
• Promiscuous Receptor Agonist Theory: Anesthetics may act at GABA receptors, NMDA receptors, other receptors
• May act directly on ion channels
• May act in hydrophobic pouches of proteins associated with receptors
• May effect allosteric interaction to alter affinity for ligands
• Immobility is due to a spinal mechanism, but site is unknown
• “Overall, the data can be explained by supposing that the primary target sites underlying general anesthesia are amphiphilic pockets of circumscribed dimensions on particularly sensitive proteins in the central nervous system.” – Franks and Lieb,Environmental Health Perspectives 87:199-205, 1990.
Receptors Possibly Mediating CNSEffects Of Inhaled Anesthetics
• Potentiation of inhibitory ‘receptors’ – GABAA – Glycine – Potassium channels
• Inhibition of excitatory ‘receptors’ – NMDA (glutamate) – AMPA (glutamate) –
Nicotinic acetylcholine
– Sodium channels
Inferred from demonstration of effect on receptor at clinically relevant concentrations and lack of effect in absence of receptor
Inhaled Anesthetics
• Gases – Nitrous oxide – Present in the gaseous state at room temperature and pressure – Supplied as compressed gas
Inhaled Anesthetics
• Volatile anesthetics – Present as liquids
at room temperature and pressure
– Vaporized into gases for administration
Inhaled Anesthetics
• Volatile anesthetics – Present as liquids at
room temperature and pressure – BUT NOT ALWAYS!
– Vaporized into gases for administration
Concentration of Inhaled AnestheticsDetermines Dose
• Partial pressure (mmHg) – Applies to gas phase or to dissolved gases
• Volumes % – Percentage of total gas volume
contributed by anesthetic – Percentage of total gas molecules
contributed by anesthetic – Partial pressure/atmospheric pressure
Solubility of Inhaled AnestheticsDetermines Dose and Time-course
• Ratio of concentration in one phase to that in a second phase at equilibrium
• Important solubility coefficients for inhaled anesthetics
– Lower blood-gas partition coefficient leads to faster induction and emergence
– Higher oil-gas partition coefficient leads to increased potency
Chemistry
(CF3)2CH-O-CH3
10%, excellent anesthesia
CF3CHFCF2-O-CH3
5%, light anesthesia, tremors
CF3CH2-O-CF2CH2F
3%, convulsions
CF3CH2-O-CH2CF3 (Indoklon)
0.25%, marked convulsions
CF3CF2-O-CF2CF3 Inert
From: F.G. Rudo and J.C. Krantz, Br. J. Anaesth. (1974), 46, 181
Inhaled Anesthetics
Inhaled Anesthetics - Historical•Ether – Slow onset, recovery, explosive
•Chloroform – Slow onset, very toxic
•Cyclopropane – Fast onset, but very explosive
•Halothane (Fluothane) – first halogenated ether (non-flammable)
• 50% metabolism by P450, induction of hepatic
microsomal enzymes; TFA, chloride, bromide released
• Myocardial depressant (SA node), sensitization
of myocardium to catecholamines
• Hepatotoxic
•Methoxyflurane (Penthrane) - 50 to 70% metabolized
• Diffuses into fatty tissue
• Releases fluoride, oxalic acid
• Renotoxic
Inhaled Anesthetics – Currently•Enflurane (Ethrane) Rapid, smooth induction and maintenance
• 2-10% metabolized in liver
• Introduced as replacement for halothane, “canabilized” to
make way for isoflurane
•Isoflurane (Forane) smooth and rapid induction and emergence
• Very little metabolism (0.2%)
• Control of Cerebral blood flow and Intracranial pressure
• Potentiates muscle relaxants, Uterine relaxation
• CO maintained, arrhythmias uncommon, epinephrine can be
used with isoflurane; Preferential vasodilation of small
coronary vessels can lead to “coronary steal”
• No reports of hepatotoxicity or renotoxicity
• Most widely employed
Inhaled Anesthetics – New Kids on the Block
•Desflurane (Suprane) – Very fast onset and offset (minute-to
minute control) because of its low solubility in blood
• Differs from isoflurane by replacing one Cl with F
• Minimal metabolism
• Very pungent - breath holding, coughing, and laryngeal
spasm; not used for induction
• No change in cardiac output; tachycardia with rapid increase in
concentration, No coronary steal
• Degrades to form CO in dessicated soda-lime (Ba2OH
/NaOH/ KOH; not Ca2OH)
• Fast recovery – responsive within 5-10 minutes
Inhaled Anesthetics – New Kids on the Block
•Sevoflurane (Ultane) – Low solubility and low pungency =
excellent induction agent
•Significant metabolism (5%; 10x > isoflurane); forms inorganic
fluoride and hexafluoroisopropranolol
•No tachycardia, Prolong Q-T interval, reduce CO, little tachycardia
•Soda-lime (not Ca2OH) degrades sevoflurane into “Compound A”
•Nephrotoxic in rats
•Occurs with dessicated CO2 absorbant
•Increased at higher temp, high conc, time
•No evidence of clinical toxicity
•Metallic/environmental impurities can form HF
Inhaled Anesthetics – Currently•Nitrous Oxide is still widely used
•Potent analgesic (NMDA antagonist)
•MAC ~ 120%
•Used ad adjunct to supplement other inhalationals
•Xenon
•Also a potent analgesia (NMDA antagonist)
•MAC is around 80%
•Just an atom – what about mechanism of action?
Malignant Hyperthermia
Malignant hyperthermia (MH) is a pharmacogenetic hypermetabolic state of
skeletal muscle induced in susceptible individuals by inhalational
anesthetics and/or succinylcholine (and maybe by stress or exercise).
• Genetic susceptibility-Ca+ channel defect (CACNA1S) or RYR1 (ryanodine receptor)
• Excess calcium ion leads to excessive ATP breakdown/depletion, lactate production, increased CO2 production, increased VO2, and, eventually, to myonecrosis and rhabdomyolysis, arrhythmias, renal failure
• May be fatal if not treated with dantrolene – increases reuptake of Ca++ in Sarcoplasmic Reticulum
• Signs: tachycardia + tachypnea + ETCO2 increasing + metabolic acidosis; also hyperthermia, muscle rigidity, sweating, arrhythmia
• Detection: – Caffeine-halothane contracture testing (CHCT) of biopsied muscle;
– Genetic testing for 19 known mutations associated with MH
Intravenous Anesthetics
•Most exert their actions by potentiating GABAA receptor
•GABAergic actions may be similar to those of volatile anesthetics, but act at different sites on receptor
•High-efficacy opiods (fentanyl series) also employed
•Malignant hyperthermia is NOT a factor with these
Intravenous Anesthetics
Organ Effects
• Most decrease cerebral metabolism and intracranial pressure. Often used in the treatment of patients at risk for cerebral ischemia or intracranial hypertension.
• Most cause respiratory depression • May cause apnea after
induction of anesthesia
Cardiovascular Effects
• Barbiturates, benzodiazepines and propofol cause cardiovascular depression.
• Those drugs which do not typically depress the cardiovascular system can do so in a patient who is compromised but compensating using increased sympathetic nervous system activity.
Intravenous Anesthetics - BarbituratesIdeal: Rapid Onset, short-acting
Thiopental (pentathol)- previously almost universally usedFor over 60 years was the standard against which other injectable induction agents/anesthetics were compared
Others: Suritol (thiamylal); Brevital (methohexital)
Act at GABA receptors (inhibitory), potentiate endogenous GABA activity at the receptor, direct effect on Cl channel at higher concentrations.
Effect terminated not by metabolism but by redistributionrepeated administration or prolonged infusion approached equlibrium at redistribution sites. Redistribution not effective in terminating action, led to many deaths.
Build-up in adipose tissue = very long emergence from
anesthesia (e.g.; one case took 4 days to emerge)
Propofol (Diprivan)
• Originally formulated in egg lecithin emulsion • anaphylactoid reactions • Current formulation: 1% propofol in 10% soybean oil,
2.25% glycerol, 1.2% egg phosphatide • Pain on injection
• Onset within 1 minute of injection • Not analgesic • Enhances activity of GABA receptors (probably) • Vasodilation, respiratory depression, apnea (25% to 40%) • Induction and maintenance of anesthesia or sedation • Rapid emergence from anesthesia • Antiemetic effect • Feeling of well-being • Widely used for ambulatory surgery
Etomidate (Amidate)• Insoluble in water, formulated in 35% propylene glycol (pain
on injection)
• Little respiratory depression
• Minimal cardiovascular effects
• Rapid induction (arm-to-brain time), duration 5 to 15 minutes
• Most commonly used for induction of anesthesia in patients with cardiovascular compromise; or where cardiovascular stability is most important
• Metabolized to carboxylic acid, 85% excreted in urine, 15% in bile
• Rapid emergence from anesthesia
• Adverse effects: Pain, emesis, involuntary myoclonic
movements, inhibition of adrenal steroid synthesis
Ketamine• Chemically and pharmacologically related to PCP
• Inhibits NMDA receptors
• Analgesic, dissociative anesthesia
• Cataleptic appearance, eyes open, reflexes intact, purposeless but coordinated movements
• Stimulates sympathetic nervous system
• Indirectly stimulates cardiovascular system, Direct myocardial depressant
• Increases cerebral metabolism and intracranial pressure
• Lowers seizure threshold
• Psychomimetic – “emergence reactions”
• vivid dreaming extracorporeal (floating "out-of-body") experience misperceptions, misinterpretations, illusions
• may be associated with euphoria, excitement, confusion, fear
Benzodiazepines
•Diazepam (Valium, requires non-aqueous vehicle, pain on injection); Replaced by Midazolam (Versed) which is water-soluble.•Rapidly redistributed, but slowly metabolized
•Useful for sedation, amnesia
-Not analgesic, can be sole anesthetic for non-painful procedures (endoscopies, cardiac catheterization)-Does not produce surgical anesthesia alone
•Commonly used for preoperative sedation and anxiolysis•Can be used for induction of anesthesia
•Safe – minimal respiratory and cardiovascular depression when used alone, but they can potentiate effects of other anesthetics (e.g.; opioids)•Rapid administration can cause transient apnea
Opioids•i.v. fentanyl, sufentanil, alfentanil, remifentanyl or morphine
•Usually in combination with inhalant or benzodiazepine
•Respiratory depression, delayed recovery, nausea and vomiting post-op•Little cardiovascular depression; Provide more stable hemodynamics•Smooth emergence (except for N & V)
•Excellent Analgesic: intra-operative analgesia and decrease early postoperative pain
–Remifentanil: has ester linkage, metabolized rapidly by nonspecific esterases (t1/2 = 4 minutes; fentanyl t1/2 = 3.5 hours)
–Rapid onset and recovery
–Recovery is independent of dose and duration – offers the high degree “minute to minute” control
Conscious sedation• A term used to describe
sedation for diagnostic and therapeutic procedures throughout the hospital.
• Ambiguous because no one really knows how to measure consciousness in the setting of a patient receiving sedation.
Depth of sedation
Conscious sedation
•Each health care facility should have policies and procedures defining conscious sedation and specifying the procedures and training required for its use.•Before sedating patients one should review and follow these policies and procedures.•One should also understand sedative medications and have the knowledge and skills required for the treatment of possible complications (e.g. apnea).
Conscious sedation•The most common mistake is to over-sedate the patient. If the patient is comfortable, there is no need for more medication.
•The safest method of sedation is to carefully titrate sedative medications in divided doses.
•Allow enough time between doses to assess the effects of the previous dose.
•Administer medications until the desired level of sedation is reached, but not past the point where the patient is capable of responding verbally.
•Midazolam and fentanyl are among the easiest drugs to use. Midazolam provides sedation and anxiolysis and fentanyl provides analgesia.
What is Balanced Anesthesia?
• Use specific drugs for each component • Sensory
• N20, opioids, ketamine for analgesia
• Cognitive: • Produce amnesia, and preferably unconsciousness,
with N2O, . 25-.5 MAC of an inhaled agent, or an IV hypnotic (propofol, midazolam, diazepam, thiopental)
• Motor: • Muscle relaxants as needed
• Autonomic:
• If sensory and cognitive components are adequate, usually no additional medication will be needed for autonomic stability. If some is needed, often a beta blocker +/- vasodilator is used.
What is Balanced Anesthesia?
• Garbage Anesthesia (everything but the kitchen sink)
• LOT2 (Little Of This, Little of That) • Mixed Technique • The Usual
MAC Reduction
Isof
lura
ne C
once
ntra
tion
(%
) 2.00
1.50
1.00
0.50
0.00 0 10 20 30 40 50 60
Target
Remifentanil Concentratio
n (ng/ml)S=success (no response to skin incision) F=failure (response to skin incision)
Lang et al, Anesthesiology 85, 721-728, 1996
Bolus Dose Equivalents
• Fentanyl 100 g (1.5 g/kg) • Remifentanil 35 g (0.5
g/kg)
• Alfentanil 500 g (7 g/kg) • Sufentanil 12 g (0.2 g/kg)
What is the role of N2O?• Excellent analgesic in sub-MAC doses • MAC is around 110%.
• MACasleep tends to be about 60% of MAC. • MACasleep for N2O is 68-73%
• Well tolerated by most patients but bad news if you are subject to migraine.
• At N2O concentrations of 70%, there may be no need for additional drugs to ensure lack of awareness.
• Has the fastest elimination of any hypnotic agent used in anesthesia.
• If you want your patients to wake up quickly, keep them within N2O of being awake!
Simple Combinations
• Morphine • 10 mg iv 3-5 minutes prior to induction • Additional 5 mg 45 minutes before the end
of the procedure, if it lasts longer than 2 hours
• Propofol • 2-3 mg/kg on induction
• N2O • 70%
• Sevoflurane
• 0.3-0.6%
• Relaxant of choice
Simple Combinations• Fentanyl
• 75-150 on induction • 25-50 g now and then during the
case
• Propofol • 2-3 mg/kg on induction
• N2O • 70%
• Sevoflurane • 0.3-0.6%
• Relaxant of choice
Local/Regional Anesthetics
Michael H. Ossipov, Ph.D.Department of Pharmacology
General concepts
•Cocaine isolated from Erythroxylon coca plant in Andes
•Von Anrep (1880) discovers local anesthetic property, suggests clinical use
•Koller introduces cocaine in opthalmology
•Freud uses cocaine to wean Karl Koller off morphine
•Halstead demonstrates infiltration anesthesia with
cocaine •Rapidly accepted in dentistry
General concepts
• Halstead (1885) shows cocaine blocks nerve conduction in nerve trunks
• Corning (1885) demonstrates spinal block in
dogs • 1905:
Procaine (NOVOCAINE) synthesized – analog of
cocaine but without euphoric effects, retains vasoconstrictor effect
– Slow onset, fast offset, ester-type (allergic reactions)
General concepts
• First “modern” LA (1940s): lidocaine (lignocaine in UK; XYLOCAINE) – Amide type
(hypoallergenic) – Quick onset, fairly long duration (hrs) – Most widely used
local anesthetic in US today, along with bupivacaine and tetracaine
General concepts
• Cause transient and reversible loss of sensation in a circumscribed area of the body – Very safe, almost no reports of
permanent nerve damage from local anesthetics
• Interfere with nerve conduction • Block all types of fibers (axons) in a
nerve (sensory, motor, autonomic)
Local anesthetics: Uses
• Topical anesthesia (cream, ointments, EMLA)
• Peripheral nerve blockade • Intravenous regional anesthesia • Spinal and epidural anesthesia • Systemic uses (antiarrhythmics,
treatment of pain syndromes)
Structure
•All local anesthetics are weak bases. They all contain:
•An aromatic group (confers lipophilicity)
-diffusion across membranes, duration, toxicity increases with lipophilicity
•An intermediate chain, either an ester or an amide; and
•An amine group (confers
hydrophilic properties)
– charged form is the major active form
Structure
•Formulated as HCl salt (acidic)
for solubility, stability
•But, uncharged (unprotonated N)
form required to traverse tissue to
site of action
•pH of formulation is irrelevant since
drug ends up in interstitial fluid
•Quaternary analogs, low pH
bathing medium suggests major
form active at site is cationic,
but both charged and
uncharged species are active
PKa
Mepivicaine 7.6
Etidocaine 7.7
Articaine 7.8
Lidocaine 7.9
Prilocaine 7.9
Bupivicaine 8.1
Procaine 9.1
% RN at PH Onset in7.4 minutes
40 2 to4
33 2 to4
29 2 to4
25 2 to4
25 2 to4
18 5 to8
2 14 to 18
O C2H
5 ⊕ O C 2
H 5
H 2 N COCH 2CH 2 H 2 N COCH 2CH 2 N +N H + H
C 2 H
5 C 2 H 5Cationic acid
Log Base
Acid = pH – p
Ka
(Henderson-Hasselbalch equation)
For procaine (p Ka =
8.9) at tissue pH
(7.4)
BaseAcid = 0.03
Nonionized base
Lipoid barriers
(nerve sheath)
ExtracellularBase
fluid
Nerve membrane * [3.1]
Axoplasm Base Acid [2.5]
Structure
Structure
Mode of action• Block sodium channels • Bind to specific sites on channel protein • Prevent formation of open channel • Inhibit influx of sodium ions into the neuron • Reduce depolarization of membrane in response to action
potential
• Prevent propagation of action potential
Mode of action
Mode of action
Mode of action
Sensitivity of fiber types• Unmyelinated are more sensitive than
myelinated nerve fibers • Smaller fibers are generally more
sensitive than large-diameter peripheral nerve trunks
• Smaller fibers have smaller “critical lengths” than larger fibers (mm range)
• Accounts for faster onset, slower offset of local anesthesia
• Overlap between block of C-fibers and Aδ-fibers.
Choice of local anesthetics
• Onset • Duration • Regional anesthetic technique • Sensory vs. motor block • Potential for toxicity
Clinical useOnset Duration
EstersProcaine Slow ShortChloroprocaine Fast ShortTetracaine Slow LongAmidesLidocaine Fast ModerateMepivacaine Fast ModerateBupivacaine Moderate LongRopivacaine Moderate LongEtidocaine Fast Long
Choice of local anesthetics
Technique Appropriate drugsTopical Cocaine, tetracaine, lidocaineInfiltration Procaine, lidocaine, mepivacaine,
bupivacaine, ropivacaine,
Peripheral nerve blocketidocaineChloroprocaine, lidocaine,mepivacaine, bupivacaine,
Spinalropivacaine, etidocaineProcaine, tetracaine, lidocaine,
EpiduralbupivacaineChloroprocaine, lidocaine,bupivacaine, ropivacaine,
I.V. regional anesthesiaetidocaineLidocaine
Factors influencing anesthetic activity
• Needle in appropriate location (most important)
• Dose of local anesthetic • Time since injection • Use of vasoconstrictors • pH adjustment • Nerve block enhanced in
pregnancy
Redistribution and metabolism
• Rapidly redistributed • More slowly metabolized
and eliminated • Esters hydrolyzed by
plasma cholinesterase • Amides primarily metabolized in
the liver
Local anesthetic toxicity
• Allergy• CNS toxicity• Cardiovascular toxicity
Allergy
• Ester local anesthetics may produce true allergic reactions – Typically manifested as skin
rashes or bronchospasm. May be as severe as anaphylaxis
– Due to metabolism to ρ-aminobenzoic acid
• True allergic reactions to amides are extremely rare.
Systemic toxicity
• Results from high systemic levels • First symptoms are generally
CNS disturbances (restlessness, tremor, convulsions) - treat with benzodiazepines
• Cardiovascular toxicity generally
later
CNS symptoms
• Tinnitus • Lightheadedness, Dizziness • Numbness of the mouth and tongue,
metal taste in the mouth • Muscle twitching • Irrational behavior and speech • Generalized seizures
• Coma
Cardiovascular toxicity
• Depressed myocardial contractility
• Systemic vasodilation • Hypotension • Arrhythmias, including
ventricular fibrillation (bupivicaine)
Avoiding systemic toxicity
• Use acceptable total dose • Avoid intravascular
administration (aspirate before injecting)
• Administer drug in divided doses
Maximum safe doses of local anesthetics in adults
Anesthetic Dose (mg)
Procaine 500
Chloroprocaine 600
Tetracaine 100 (topical)
Lidocaine 300
Mepivicaine 300
Bupivacaine 175
Uses of Local Anesthetics
•Topical anesthesia- Anesthesia of mucous membranes (ears,
nose, mouth, genitourinary, bronchotrachial)- Lidocaine, tetracaine, cocaine (ENT
only) •EMLA (eutectic mixture of local anesthetics)cream formed from lidocaine (2.5%) & prilocaine
(2.5%) penetrates skin to 5mm within 1 hr, permits superficial procedures, skin graft harvesting
•Infiltration Anesthesia- lidocaine, procaine, bupivacaine (with
or w/o epinephrine)- block nerve at relatively small area - anesthesia without immobilization or
disruption of bodily functions- use of epinephrine at end arteries (i.e.;
fingers, toes) can cause severe vasoconstriction leading to gangrene
Uses of Local Anesthetics
•Nerve block anesthesia- Inject anesthetic around plexus (e.g.; brachial
plexus for shoulder and upper arm) to anesthetize a larger area- Lidocaine, mepivacaine for blocks of 2 to 4
hrs, bupivacaine for longer•Bier Block (intravenous)
- useful for arms, possible in legs - Lidocaine is drug of choice, prilocaine can be
used- limb is exsanguinated with elastic bandage,
infiltrated with anesthetic- tourniquet restricts circulation - done for less than 2 hrs due to ischemia, pain
from touniquet
Uses of Local Anesthetics
•Spinal anesthesia- Inject anesthetic into lower CSF (below L2) - used mainly for lower abdomen, legs, “saddle
block”- Lidocaine (short procedures), bupivacaine
(intermediate to long), tetracaine (long procedures)- Rostral spread causes sympathetic
block, desirable for bowel surgery- risk of respiratory depression, postural headache
Uses of Local Anesthetics
•Epidural anesthesia- Inject anesthetic into epidural space - Bupivacaine, lidocaine, etidocaine,
chloroprocaine- selective action of spinal nerve roots in area of
injection- selectively anesthetize sacral, lumbar, thoracic or
cervical regions- nerve affected can be determined by
concentration- High conc: sympathetic, somatic sensory,
somatic motor- Intermediate: somatic sensory, no motor block - low conc: preganglionic sympathetic fibers - used mainly for lower abdomen, legs, “saddle
block”- Lidocaine (short procedures), bupivacaine
(intermediate to long), tetracaine (long procedures)