Question | Answer |
Define regional anesthesia: | Insensibility of a part induced by interrupting the sensory nerve conductivity of that region of the body. |
Regional anesthesia results from... | The result of a conduction blockade of specific peripheral nerves or nerve groups. |
When was Cocaine first isolated from the coca plant? | 1855. |
1884- Carl Koller did what? | An ophthalmologist, he used topical cocaine for the first time during eye surgery. |
1884- Surgeon William Halsted (Hall) used cocaine for... | Mandibular and brachial plexus nerve blocks. |
What happened in 1885? | Corning 1st use of spinal/epidural anesthesia in a dog (cocaine) |
Who was the first to perform a lumbar puncture? | 1891- Heinrick Quinke performed a lumbar puncture for hydrocephalus. |
When did Heinrick Quinke perform the first LP? | 1891. |
1898- August Bier... | Administered spinal anesthetic using 3 ml of 0.5% cocaine intrathecally for surgical anesthesia & published his results. |
When was the first Bier block? | 1908- August Bier described intravenous regional anesthesia (Bier Block). |
When was the first synthetic LA and who synthesized it? | 1904- Alfred Einhorn, synthesized Procaine (Novacaine). |
1905- Heinrich Braun... | Used Procaine as a local anesthetic. He also was the first to add epinephrine to prolong the effect of the local. |
1901- Ferdinand Cathelin and Jean Sicard introduced... | Caudal epidural anesthesia. |
1921- Fidel Pages reported using... | Epidural anesthesia for abdominal surgery. |
What LA was introduced in 1855? | Cocaine. |
What LA was introduced in 1904? | Procaine (Novocaine). |
What LA's were introduced in the 1920's? | Dibucaine (Nupercaine) & Tetracaine (Pontocaine). |
What's the brand name of Dibucaine? | Nupercaine. |
What's the generic name of Nupercaine? | Dibucaine. |
What's the generic name of Pontocaine? | Tetracaine. |
What's the brand name of Tetracaine? | Pontocaine. |
1940’s- Lofgren and Lundquist introduced... | Lidocaine. |
When was Lidocaine discovered and who was responsible? | 1940's, Lofgren and Lundquist. |
1955 what LA was discovered? | Chloroprocaine (Nesacaine). |
When was Chloroprocaine (Nesacaine) discovered? | 1955. |
What is the brand name of Chloroprocaine? | Nesacaine. |
What is the generic name of Nesacaine? | Chloroprocaine. |
1957 what LA was discovered? | Mepivacaine (Carbocaine). |
When was Mepivacaine (Carbocaine) discovered? | 1957. |
What is the brand name of Mepivacaine? | Carbocaine. |
What is the generic name of Carbocaine? | Mepivacaine. |
1969, what LA was discovered? | Prilocaine (Citanest). |
When was Prilocaine (Citanest) discovered? | 1969. |
What is the brand name of Prilocaine? | Citanest. |
What is the generic name of Citanest? | Prilocaine. |
1963, what drug was synthesized? | Bupivacaine (Marcaine). |
When was Bupivacaine (Marcaine) synthesized? | 1963. |
What is the brand name of Bupivacaine? | Marcaine. |
What is the generic name of Marcaine? | Bupivacaine. |
1972, what LA was discovered? | Etidocaine (Duranest). |
What is the brand name of Etidocaine? | Duranest. |
What is the generic name of Duranest? | Etidocaine. |
1996, what LA was discovered? | Ropivacaine (Naropin). |
What is the brand name of Ropivacaine? | Naropin. |
What is the generic name of Naropin? | Ropivacaine. |
What are some common characteristics of LA's? | 1. Poorly H2O soluble
2. Weak base
3. Benzoic acid derivative joined by an ester linkage to a tertiary amine |
Synthetic derivatives possess same 3 essential functional units: | 1. Hydrophilic chain (tertiary amine), joined to
2. Lipophilic portion (aromatic ring) by
3. An ester or amide linkage (hydrocarbon chain) |
What are the ester LA's? | Cocaine, Procaine, Chloroprocaine, Tetracaine. |
What are the amide LA's? | Lidocaine, Bupivacaine, Ropivacaine, Mepivacaine, Prilocaine, Etidocaine. |
What are some general characteristics of LA esters? | 1. Are less stable (shorter shelf life)
2. Metabolized in the plasma by pseudocholinesterases
3. More prone to cause allergic reactions |
What are some general characteristics of LA amides? | 1. More stable
2. Metabolized by liver
3. Rare allergies |
LA's are poorly soluble in H2O. How are they prepared? | Commercially prepared as H2O soluble HCL salts. |
LA'S are commercially prepared as H2O soluble HCL salts, making them acidic with a pH range of 4-7. This acidity is important for two reasons: | 1. At this pH they are highly ionized, it is this portion that is H2O soluble.
2. Epi (if added) needs an acidic pH as it is unstable in alkaline environments. |
What is the method of action of LA's? | They inhibit the transmission of nerve impulses by preventing the passage of Na ions through their channels in the nerve membranes. |
What are Na channels? | Na channels are integral membrane proteins that initiate and propogate action potentials. |
What is the specific receptor for the LA's? | The alpha subunit of the Na channel in the nerve membrane. |
What form of LA crosses the membrane? | Unionized (free base). |
What happens after the free base crosses the membrane? | Once in the axoplasm; the base and the cationic (ionized) form “re”equilibrate. |
When do LA's have the highest affinity for the Na channel? | When the Na channels are in the open and activated state (rather than in the resting state). |
What form of the LA keeps the Na channel in a closed, inactivated state? | The unionized free base. |
The ionized form sneaks in after an action potential has passed (and Na channels are open), and... | Attaches to a receptor site inside the Na channel and blocks it. |
What is CM? | Minimum concentration. The minimum amount of drug needed to produce a block. |
What factors influence minimum concentration? | 1. Potency of local anesthetic
2. Nerve diameter
3. Myelination
4. “frequency dependent blockade priniciple”
5. Position of nerve in nerve bundle |
Blocking of impulse requires a defined length of fiber to be... | "Nonexcitable." |
Myelinated fibers: conduction proceeds in jumps from one node of Ranvier to next. How many nodes need to be blocked for successful block? | To successfully block myelinated fibers; LA’s must generally inhibit 3 successive nodes of Ranvier. |
Unmyelinated fibers: | 1. Usually conduct more slowly.
2. Often relatively resistant to LA’s despite smaller size. |
Because of the “dual action” of the locals, the more action potentials that occur... | The more likely the local will encounter the Na channel in the open or inactive state. |
The more action potentials that occur the more likely the local will encounter the Na channel in the open or inactive state. What is this called? | "Frequency dependent blockade” or “use dependence.” |
What does "frequency dependent blockade" or "use dependence" explain? | This explains why some nerves that have a lot of action potentials are more sensitive to locals than others that have less action potentials. |
Position of nerve in nerve bundle indicates what? | Those closer to the “mantle” blocked before those closer to “core.” |
Fiber diameter indicates what? | 1. Smaller fibers “more sensitive”
2. Larger fibers “less sensitive”
“Locals will block smaller fibers at lower concentrations than are required by larger fibers of same type.” |
As a group unmyelinated fibers... | Are more resistant to LA’s compared with some larger myelinated fibers. |
Nerve fibers are classified as <blank> based on anatomical and functional properties. | A, B, and C. |
A-fibers = | Motor efferent conduction. |
How many A-fibers are there? | Four. Alpha, beta, gamma, and delta. |
A-alpha: | Innervate skeletal muscle motor/proprioception. |
A-beta: | Sensations of touch/pressure. |
A-gamma: | Skeletal muscles for muscle tone. |
A-delta: | Sensations of pain/temperature/touch. |
Are A-fibers myelinated? | Yes, all of them. |
T or F:
A fibers: motor afferent conduction
A-alpha: innervate skeletal muscle motor/proprioception
A-beta: sensations of touch/pressure
A-gamma: skeletal muscles for muscle tone
A-delta: sensations of pain, temp., touch
A fibers are all myelinat | False.
A fibers: motor EFFERENT conduction
A-alpha: innervate skeletal muscle motor/proprioception
A-beta: sensations of touch/pressure
A-gamma: skeletal muscles for muscle tone
A-delta: sensations of pain, temp., touch
A fibers are all myelinat |
T or F:
A fibers= motor efferent conduction
A-alpha: innervate skeletal muscle motor/proprioception
A-beta: skeletal muscles for muscle tone
A-gamma: sensations of touch/pressure
A-delta: sensations of pain, temp., touch
A fibers are all myelin | False.
A fibers= motor efferent conduction
A-alpha: innervate skeletal muscle motor/proprioception
A-beta: SENSATIONS OF TOUCH/PRESSURE
A-gamma: SKELETAL MUSCLES FOR MUSCLE TONE
A-delta: sensations of pain, temp., touch
A fibers are all myeli |
B-fibers: | 1. Preganglionic autonomic nerve fibers
2. Myelinated, frequently firing |
Are B-fibers myelinated? | Yes. |
True or false: B-fibers are
1. Postganglionic autonomic nerve fibers
2. Myelinated, frequently firing | False. B-fibers are
1. PREganglionic autonomic nerve fibers
2. Myelinated, frequently firing |
True or false: B-fibers are
1. Preganglionic autonomic nerve fibers
2. Unmyelinated, frequently firing | False. B-fibers are
1. Preganglionic autonomic nerve fibers
2. MYELINATED, frequently firing |
C-fibers: | 1. Pain (slow), reflex responses
2. Postganglionic autonomic
3. Unmyelinated, small fibers |
Are C-fibers myelinated? | No. |
True or false: C-fibers
1. Pain (slow), voluntary responses
2. Postganglionic autononic
3. Unmyelinated, small fibers | False. C-fibers
1. Pain (slow), REFLEX responses
2. Postganglionic autonomic
3. Unmyelinated, small fibers |
True or false: C-fibers
1. Pain (slow), reflex responses
2. Preganglionic autonomic
3. Unmyelinated, small fibers | False. C-fibers
1. Pain (slow), reflex responses
2. POSTganglionic autonomic
3. Unmyelinated, small fibers |
Talk about blocking B-fibers. | Blocked 1st. Exception to rule d/t rapid conduction velocity. So requires a minimum concentration of LA to block. |
What fibers are these:
Pain fibers, blocked by same conc. of local. | A delta and C fibers. |
Order of nerve block recovery: | 1. A-alpha
2. A-beta
3. A-gamma
4. C and A-delta
5. Beta |
STPTPMVP: | 1. Sympathetic
2. Temperature
3. Pain
4. Touch
5. Pressure
6. Motor
7. Vibration
8. Proprioception |
Lipid solubility is related to... | Potency. |
Potency is related to... | Lipid solubility. |
Protein binding is related to... | Duration of action. |
Duration of action is related to... | Protein binding. |
PKa is related to... | Onset. |
Onset is related to... | PKa. |
All currently used locals have pKa's... | Higher than body pH. |
A lower pKa will give you a... | More unionized drug at body pH. |
The pH of the tissue becomes relevant in conditions of infection or inflammation, in which the pH may be more acidic. This acidity results in a... | Greater proportion of the ionized (charged) form of the anesthetic, thereby delaying or preventing the onset of action. |
What vasoconstrictors are used with LA's? | Epinephrine and Phenylephrine. |
What does Epinephrine do to the pH of your LA? | Makes it more acidic and increases its shelf life. |
What are the two ways Epinephrine acts in conjunction with your LA? | 1. Decreases blood flow to area thus less taken up in blood and carried away; also increasing time fibers are exposed to increased concentrations (incr. block)
2. Also thought to exert presynaptic adrenergic receptor activity that contributes to analgesi |
Talk about Sodium Bicarb and LA: | 1. Used clinically to speed onset of block
2. Increases amount of “nonionized” form available to cross membrane
3. Inconsistent
4. May see more effect with epinephrine containing locals |
When and why do we use opioids with LA? | 1. Used with central blocks
2. Improves perioperative analgesia |
Talk about alpha-2 adrenergic agonists. | 1. Used in central blockade
2. Enhances analgesia without opioid side effect profile
3. Binds to a-2 receptors on primary afferent fibers and several brainstem nuclei
4. Increases AcH and norepi in CSF and inhibits release of several neurotransmitters |
Where do alpha-2 adrenergic agonists bind? | Alpha-2 receptors on primary afferent fibers and several brainstem nuclei. |
Alpha-2 adrenergic agonists bind to alpha-2 receptors on primary afferent fibers and several brainstem nuclei. What do they do there? | Increase ACh and Norepi in CSF and inhibits release of several neurotransmitters. |
What's the most common alpha-2 adrenergic agonist? | Clonodine. |
True or false: Clonodine is an alpha-2 adrenergic antagonist that binds to alpha-2 receptors on primary afferent fibers and several brainstem nuclei. It increases ACh and Norepi in CSF and inhibits release of several neurotransmitters. | False. Clonodine is an alpha-2 adrenergic AGONIST that binds to alpha-2 receptors on primary afferent fibers and several brainstem nuclei. It increases ACh and Norepi in CSF and inhibits release of several neurotransmitters. |
True or false: Clonodine is an alpha-2 adrenergic agonist that binds to alpha-2 receptors on primary efferent fibers and several brainstem nuclei. It increases ACh and Norepi in CSF and inhibits release of several neurotransmitters. | False. Clonodine is an alpha-2 adrenergic agonist that binds to alpha-2 receptors on primary AFFERENT fibers and several brainstem nuclei. It increases ACh and Norepi in CSF and inhibits release of several neurotransmitters. |
True or false: Clonodine is an alpha-2 adrenergic agonist that binds to alpha-2 receptors on primary afferent fibers and several brainstem nuclei. It increases ACh and Norepi in CSF and inhibits release of several neurotransmitters. | True. |
Tissue blood flow from most to least absorption of LA: | 1. IV
2. Intercostal
3. Tracheal
4. Caudal/paracervical
5. Epidural
6. Brachial plexus
7. Spinal
8. SubQ |
What four factors influence absorption of locals? | 1. Tissue blood flow
2. Protein binding
3. Lipid solubility
4. Metabolism |
Talk about metabolism of locals. | Very small amounts excreted unchanged in urine
Amides: primarily metabolized by the liver
Esters: hydrolysis by plasmacholinesterases |
What is the active metabolite of Lidocaine? | Mono ethyl glycine xylidide. |
What is a precaution of using Lidocaine in a patient with liver problems? | More chance of toxicity. |
What is the metabolite of Prilocaine? | Ortho Toluidine. |
What does Ortho Toludine do? | Converts hemoglobin to methemoglobin. |
What is the treatment for Methemoblobinemia? | Methyline Blue. |
Do locals easily cross the BBB? | Yes. |
What are the two ways we can get CNS toxicity from locals? | Direct IV infusion or systemic absorption. |
List the s/s of LA CNS toxicity from earliest and least dangerous to latest and most dangerous. | 1. Vertigo/Lightheadedness
2. “Tinnitius” Visual/auditory disturbances
3. Circumoral numbness
4. Ominous feelings
5. Muscle twitching
6. Convulsions
7. unconsciousness
8. Coma
9. Resp collapse
10. CV collapse |
How can we prevent LA CNS toxicity? | 1. Choice of appropriate drug/dose
2. Frequent aspiration from catheter (epid)
3. Small “test doses”
4. Checking for systemic effects
5. Monitors
6. Slow injection |
Treatment of LA CNS toxicity is dependent on severity. Know s/s and stop injection. How do you treat? | 1. Maintain patent airway
2. O2/barbs/benzo’s
3. Tx CV s/s
Initially excitation
Tachy, hypertension
Followed by depression
4. Decr CO, hypotension
Phenylephrine, ephedrine, norepi
Amniodarone, bretylium, vasopressin
5. Increased resuscitation tim |
What is lipid resuscitation (20% intralipid)? | 1. Administer 1.5 mL/kg as an initial bolus; the bolus can be repeated 1- 2 times for persistent asystole.
2. Start an infusion at 0.25 mL/kg/min for 30-60 minutes; increase infusion rate up to 0.50 mL/kg/min for refractory hypotension. |
What's the bolus dose for lipid resuscitation (20% intralipid)? | Administer 1.5 mL/kg as an initial bolus; the bolus can be repeated 1- 2 times for persistent asystole. |
What's the infusion dose (after the bolus dose) for lipid resuscitation (20% intralipid)? | Start an infusion at 0.25 mL/kg/min for 30-60 minutes; increase infusion rate up to 0.50 mL/kg/min for refractory hypotension. |
Where is Pseudocholinesterase produced, and where does it go? | Pseudocholinesterase is an enzyme produced by the liver and circulates in the plasma. |
Ester LA's are derivatives of... | Benzoic acid. |
What is a metabolic end product of ester LA? | Para-aminobenzoic acid (PABA). |
Dibucaine (Nupercaine) Very potent, <blank> times as toxic as procaine. (Not used in clinical practice) | 15. |
Dibucaine depresses the activity of... | Pseudocholinesterase. |
Dibucaine number:
If the individual is Heterozygote (one norm and one abnorm gene) how much depression? | 40%. |
Dibucaine number:
If the patient is Homozygote (2 abnormal genes) how much depression? | 20%. |
If you have atypical plasma cholinesterase you are incapable of... | Metabolizing ester locals. |
Talk about Dibucaine numbers and times. | Dibucaine number 80 = normal
Dibucaine number 40 = 20-30 minute block
Dibucaine number 20 = Very long wait, pt goes intubated to RR. Can last up to 8 hours. |
What is a Dibucaine number? | Percentage of inhibition of Pseudocholinesterase. |
Can Prilocaine induce methemoglobinemia? | Yes. |
Normal Hb has iron in what state? | Ferrous (Fe++). |
Met-Hb has iron in what state? | Ferric (Fe+++). O2 carrying capacity is poor. |
What is the dose of Methylene Blue for methemoglobinemia? | Methylene blue 1-2mg/kg over 5 minutes. |
Talk about Parabens. | 1. Paraben derivatives (have microbial actions) can cause allergic rxns.
2. Parabens are cytotoxic – do not use for spinal , epidural or intravenous regional anesthesia.
3. Needs to say Methylparaben Free or MPF |
Novocaine/Procaine: max dose, duration, duration with epi: | Max dose: 12mg/kg
Duration: 30-60 minutes
Duration with epi: 30-90 minutes |
Nesacaine/Chloroprocaine: max dose, duration, max dose with epi, duration with epi: | Max dose: 12 mg/kg
Duration: 30-60 minutes
Max dose with epi: 14 mg/kg
Duration with epi: 30-90 minutes |
Pontocaine/Tetracaine: max dose, duration, duration with epi: | Max dose: 3 mg/kg
Duration: 1.5-2.5 hours
Duration with epi: 4-6 hours |
Cocaine: max dose, duration: | Max dose: 3 mg/kg
Duration: 30-60 minutes |
Lidocaine/Xylocaine: max dose, duration, max dose with epi, duration with epi: | Max dose: 4 mg/kg
Duration: 30-120 minutes
Max dose with epi: 7 mg/kg
Duration with epi: 120-360 minutes |
Mepivacaine/Carbocaine: max dose, duration, max dose with epi, duration with epi: | Max dose: 4 mg/kg
Duration: 45-90 minutes
Max dose with epi: 7 mg/kg
Duration with epi: 120-360 minutes |
Ropivacaine: max dose, duration: | Max dose: 3 mg/kg
Duration: 90-240 minutes |
Bupivacaine/Marcaine: max dose, duration, max dose with epi, duration with epi: | Max dose: 2.5 mg/kg
Duration: 120-240 minutes
Max dose with epi: 3.2 mg/kg
Duration with epi: 180-420 minutes |
Etidocaine/Duranest 1%: max dose, duration, max dose with epi, duration with epi: | Max dose: 6 mg/kg
Duration: 120-180
Max dose with epi: 8 mg/kg
Duration with epi: 180-420 minutes |
How do LA affect CV system? | 1. Generally depressant (exception cocaine)
2. Cardiac Na channel blockade
3. Inhibition of ANS |
How do LA affect Resp system? | 1. Lidocaine depresses hypoxic drive
2. Relax bronchial smooth muscle (IV)
3. Apnea from phrenic nerve paralysis (C-4) |
What can IV Lidocaine do to CNS? | 1. Lidocaine (IV) decreases cerebral blood flow
2. Attenuates the rise in ICP from laryngoscopy
3. IV can reduce MAC up to 40% |
What does Cocaine do to the CNS? | Stimulates it. |
What LA's are the biggest culprits for CNS toxicity? | Chloroprocaine
Lidocaine 5%
Continuous subarachnoid, lithotomy, ischemia |
What risk factors are associated with TNS (transient neurologic symptoms)? | Lido, litho, obesity, parasthesia. |
How do LA's affect the immunologic system? | 1. Rare allergic rx
2. Uncommon to local
3. Usually preservative or rx to epi |
MS and LA? | Myonecrosis with direct injection. |
How do LA's affect the hematologic system? | 1. Decrease coagulation
2. Enhance fibrinolysis |
How does the use of epi affect toxicity? | Use of epi reduces risk of toxicity (due to reducing blood flow). |
Is Cauda Equina syndrome transient? | No. It is permanent. |
What are some factors implicated in Cauda Equina syndrome? | Several things: usually 5% Lidocaine, Lithotomy position, ischemia to the nerve by hypothermia and hypotension and the use of continuous subarachnoid catheters (not common). |