Local anesthesia works on a nerve by inhibiting the alpha-1 subunit of the sodium channel and blocking nerve signals. This prevents the entry of sodium ions into the neurons and the generation of an action potential, hence preventing pain transmission. This is similar to both types of local anesthesia drugs – classified into ester and amide. 

By Dr. Rajeev Iyer, MBBS, MD, FASA; Board Certified Anesthesiologist

Associate Professor of Anesthesiology,

The University of Pennsylvania, Perelman School of Medicine, Philadelphia, USA

What is the mechanism of action of local anesthetics?

Neurons like other living cells in the body have a resting membrane potential of -60 to -70 mV. This is maintained by sodium, chloride, and potassium ions. The transmission of pain occurs via an action potential generated by the movement of Sodium ions from outside to inside the cells.

Local anesthetics inhibit this transmission of sodium channels. The sodium channel has two subunits – alpha and beta. The local anesthesia drugs block the alpha subunit on the sodium channel and prevent the transmission of pain or block pain.

The sodium channel has a resting membrane potential of -60 to -70 mV

Here is a full guide on local anesthesia pharmacology in a video format.

How long does it take for local anesthesia to work?

The onset and duration of local anesthetics depend on the following factors:

1. pH of the solution
2. Fat Solubility
3. Protein binding
4. Underlying patient conditions

How does pH affect local anesthetics?

Local anesthetics are weak bases. Their action depends on the availability of the unionized form of the
drug. Commercially available lidocaine has a pH of 6-7. The pH is further lowered when epinephrine is added to make it stable.

Sodium bicarbonate is added to make the pH more alkaline to increase the unionized form of the drug. In clinical practice, a rule of thumb is to add 8.4% NaHCO3 in 10ml of local anesthetic.

Mannitol, as an osmotic diuretic, can also be added to increase the efficacy of local anesthesia during dental dentistry. I have not personally seen this being done, however, there is a recent meta-analysis published in the International Endodontic Journal showing differing efficacy in dental anesthesia.

How does solubility affect local anesthetics?

I will explain this by considering an example of two water tanks, as you see below the tank on the left
the side has butter in it and the one on the right side has water in it, so we will call them fat-soluble local
anesthetics and less fat soluble in brackets water local anesthetics.

Fat-soluble local anesthesia drugs are on the left side. Less fat-soluble or water-soluble drugs on the right side.

Fat-soluble anesthesia: First, I will tell you about fat-soluble local anesthetics represented on the left side of the above figure in yellow. Let’s mix fat-soluble local anesthetics in a bucket of butter. Now fat loves fat. They merge well. The ultimate site of action is the nerves. The fat-soluble local anesthesia drugs move out from the fat tank very slowly. Remember they are well dissolved. So this makes them

  • Longer Onset
  • Longer duration of action (they move out slowly, stay longer, and work longer)
  • Slow metabolism

Water-soluble anesthesia: The water-soluble local anesthetics are represented on the right side of the above figure in blue. Let’s mix water soluble local anesthetics in a bucket of water. You can imagine what happens if you mix water in water and have a hole at the bottom of the bucket. They move outside super quickly outside toward the neurons. This makes them

  • Shorter Onset
  • Shorter Duration of action (they move out quickly, and stay for a shorter duration)
  • Fast metabolism

I have summarized this in the below table:

Fat SolubleWater Soluble
Slow OnsetFast Onset
Longer Duration of ActionShorter Duration of Action
Slow MetabolizingFast Metabolizing
E.g., BupivacaineE.g., Lidocaine (lignocaine)

Why do they put adrenaline in local anesthetic?

Adding epinephrine to local anesthetics does the following:

  • Reduces the speed of uptake of local anesthesia
  • It increases the quality of the block
  • It prolongs the duration of action of the local anesthetic
  • It reduces the peak blood concentration because the absorption is slowed
  • Hence reduces the side effects.

What to do if I don’t have epinephrine with local anesthesia?

This is a common scenario. I used to freshly prepare lidocaine (lignocaine) with epinephrine (adrenaline) because this is more stable for a few years during my anesthesia experience.
Here is an example of how to do it.

I will show you how to prepare 1:200,000 epinephrine in local anesthesia.

  • 1:200,000 epinephrine is 5 mcg/mL of local anesthesia
  • Epinephrine comes as a 1 mg vial
  • Dilute 1 mg epinephrine in 10 mL – This will give you 100mcg per mL of epinephrine
  • 100 mcg of epinephrine added to 20 mL of local anesthesia gives 5 mcg/ml of local anesthesia
  • The final effective local anesthesia will be with 5 mcg/mL of epinephrine.
This figure shows how to add epinephrine to local anesthesia

If you need to prepare 1:100,000 epinephrine in local anesthesia this will be 10 mcg/mL of epinephrine. Instead of adding 100 mcg of epinephrine to 20 mL of local anesthesia, you add 200 mcg of epinephrine.

What is Local Anesthesia Made of?

All local anesthetics have a common structure. They have a lipophilic benzine ring, a hydrophilic sidearm, and an intermediate chain that connect them. The intermediate change determines whether the
local anesthetic is an Ester or an Amide. The structure is based on how the following elements are arranged:

  • Carbon
  • Hydrogen
  • Nitrogen
  • Oxygen

Here is the structure that I have modified and adapted from this excellent article.

Local anesthesia consists of an aromatic ring, side chain, and intermediate arm that classifies into either ester or amide local anesthetics. 

Here are the examples of Ester and Amide local anesthetics:

Ester Local AnesthesiaAmide Local Anesthesia
CocaineLidocaine (Lignocaine)
ProcaineMepivacaine
BeznocainePrilocaine
TetracaineBupivacaine
Ropivacaine

Here is a simple way to remember the names (thankfully!)

Esters have one “i” in their names

Amides have two “i” in their names

How long does local anesthesia stay in your system?

Local anesthesia is classified into short-acting, intermediate-acting, and long-acting. The Esters are intermediate-acting as they are rapidly metabolized by an enzyme in the plasma – pseudocholinesterase.

The amide local anesthetics are intermediate or long-acting. They are metabolized in the liver by the Cytochrome P450 system and then excreted by the kidneys.

Here are examples of these medications

Short Acting (Esters)Intermediate Acting (Amides)Long Acting (Amides)
CocaineLidocaineBupivacaine
ProcainePrilocaineRopivacaine
ChlorprocaineMepivacaine
Benzocaine
Tetracaine

How long does local anesthesia last?

The action of local anesthesia lasts for minutes to hours depending on which local anesthetic is used. This ranges from less than one hour with chloroprocaine to up to 10 hours for bupivacaine.

Local AnestheticDuration
Chloroprocaine30-60 minutes
Lidocaine100-200 minutes
Mepivacaine120-240 minutes
Ropivacaine200-500 minutes
Bupivcaine200-600 minutes

 

What is the maximum dose of local anesthesia?

The maximum dose depends on whether epinephrine is used or not. I will provide this information in the table below.

Local AnesthestheticWithout EpinephrineWith Epinephrine
Lidocaine5 mg/kg7 mg/kg
Bupivacaine3 mg/kg3 mg/kg
Ropivacine3 mg/kgEpinephrine is not added to Ropivacaine
Lidocaine in Liposuction/tumescent anesthesia (Special situation)Not used without epinephrineUp to 55 mg/kg

Should I always use the maximum dose?

The dose of local anesthesia should be enough to provide pain relief with consideration of the safety profile of that particular patient.

The maximum dosage is of course maximum. This should be thought of as an up to X mL dose than using the whole dose. For example, if a person is 50 kg and is getting lidocaine with epinephrine 1% they can get a maximum of 7 mg/kg. This is 350 mg or 35 mL of lidocaine. If the surgery is laparoscopy, they may need only a few mL of lidocaine.

The dose of lidocaine should be reduced in the following situations

  • Infants – a rule of thumb is to reduce the dose by 30% in infants less than 6 months old
  • Hepatic disease – significant for amide local anesthetics since they are metabolized in the liver
  • Cardiac disease – Depends on where the block is placed
  • Respiratory disease – Depends on where the block is placed
  • Reduction in hepatic blood flow

Can local anesthesia spread into the whole body?

The local anesthetics are absorbed into the blood from the site of injection. The esters get metabolized in the blood while amides are metabolized in the liver. This process happens gradually over a period of minutes to hours. However, if there is inadvertent local anesthesia injection into the veins or artery, this can precipitate local anesthesia toxicity.

The absorption depends on the site of injection based on the vascularity of the area. The sequence is important for exams and during clinical practice. I am going to give you this conceptual model which will make it easy for you to remember.

Imagine a human body and draw an “S” across the body. See the below figure. Start the “S” from the trachea, then move to the side towards the perineum, come back up in the midline, touch the shoulders, and then down to the legs. Based on this the site of absorption from highest to least is Intravenous (obviously) to subcutaneous.

This is a conceptual model showing the least to most absorption of local anesthetics. Most absorption occurs via the intravenous route and the least via subcutaneous. 

How does local anesthesia systemic toxicity occur?

As local anesthesia is administered, the toxicity can occur primarily due to two reasons

  • Inadvertent vascular administration (even with recommended doses)
  • Use of doses above the maximum recommended dose

The use of ultrasound where feasible is used to reduce the risk of inadvertent vascular administration. The New York School of Regional Anesthesia is a good resource to know about the performance of nerve blocks.

What is the most toxic local anesthetic?

Local anesthetics are safe but any local anesthetic can be toxic. If I have to pick the most toxic one, bupivacaine would probably be my choice. This is because of the sodium channel block with bupivacaine is described as “slow in – slow out”. This means the cardiac arrest with bupivacaine can be prolonged and severe compared to other local anesthetics.

What are the signs of local anesthetic toxicity?

During the use of local anesthetics clinically there can be an unintentional intravenous injection and this can lead to disastrous consequences. An awake patient who is not under general anesthesia or sedation can actually have neurologic symptoms

  • The most commonly/first thing is tongue numbness. This actually should trigger your thinking about the possibility of local anesthetic toxicity.
  • Lightheadedness
  • Hallucination is mostly visual or auditory
  • Twitching
  • Finally if untreated and if the toxicity is quite severe it can lead to seizures or even coma.

If the local anesthesia toxicity is very severe and it happens in a patient who is under general anesthesia they can have significant cardiovascular toxicity. Essentially there can be reduced

  • Sino atrial node-firing
  • Increased peripheral vascular resistance
  • Negative inotropy
  • Reduced myocardial contractility
  • Essentially all types of heart function is affected which can eventually lead to
  • Ventricular tachycardia
  • Ventricular fibrillation
  • Asystole or heartbeat stops

This is a serious condition that has to be immediately paid attention to. It is important to consider the concentration, the dose, and the route of medication. Practice double checking/2-person verification of medicines should be practiced and consider the patient’s underlying factors so all this can determine a safe outcome when using local anesthesia.

What is the treatment for local anesthetic toxicity?

Local anesthesia toxicity can happen a lot more common than you think it does happen. The treatment of local anesthesia toxicity should be immediate, definitive, and post-resuscitation care.

Immediate

  • Immediate recognition of local anesthesia toxicity
  • Stop injecting any more local anesthesia
  • Immediately call for help
  • Start CPR if required
  • Use AED if you have access to it (many places globally does not have easy access to AED)

Definitive

  • Start CPR or continue (if already started). I have left a video below on how to do CPR in common conditions. 
  • Get a Defibrillator, attach the pads and check if you have a shockable rhythm.
  • Place an IV if not already done. Local anesthesia ideally has to be done after an IV injection but sometimes it’s done in office settings where IV is not always placed so placing an IV is very critical in order to give medications to treat local anesthesia toxicity.
  • Now intubate if you have the resources and skill to do so if not oxygenation and ventilation using a face mask or a laryngeal mask airway is very important to maintain the patient safe
  • Once you have a full-blown Cardiac Arrest these things might be done simultaneously. Y
  • Have inotropes to maintain blood pressure

LIPID EMULSION 20%

Post resucitation care

  • Follow the cardiac arrest guidelines
  • Typically managed in the intensive care unit.

Does local anesthesia make you tired?

Local anesthesia causes a feeling of heaviness or numbness to the part where it is injected or administered. When used for a surgery or a medical procedure it may be combined with sedation or general anesthesia. When either of these is used, there is a possibility of tiredness or grogginess. Outside of this, local anesthesia per se should not cause tiredness. However, the procedure for which the local anesthesia is used or the additional medications or both may cause tiredness.

What is the strongest local anesthetic?

Local anesthetics come in various concentrations. Higher the concentration, the stronger or denser the block. The local anesthetics can range from 5% (e.g. lidocaine) used for topical analgesia to 0.0625% (e.g. diluted bupivacaine) used for continuous infusion.

Here is an easy way to remember how much local anesthesia drug exists in each concentration of the local anesthesia vial. Move the decimal point and this will give you the answer. E.g. 0.5% bupivacaine will have 5 mg/mL and 0.25% will have 2.5 mg/ml.

This table demonstrates the concentration and the conversion to mg/mL. This will visually help you remember this important concept. This knowledge is crucial when using local anesthetics in clinical practice.

ConcentrationVolume in mg/ml
0.0625%0.625 mg/mL
0.125%1.25 mg/mL
0.25%2.5 mg/nL
0.5%5 mg/mL
1%10 mg/mL
1.5%15 mg/mL
2%20 mg/mL
4%40 mg/mL
5%50 mg/mL

What types of local anesthesia exist?

Local anesthesia can be administered in the following routes: Infiltration, peripheral nerve block, topical, spinal anesthesia, or epidural anesthesia.

Local Anesthesia DrugUse
CocaineNasal Analgesia - Topical
ChloroprocaineSpinal
Epidural
Infiltration
Peripheral Nerve Block
LidocaineSpinal
Epidural
Infiltration
Peripheral Nerve Block
Intravenous regional
Topical
RopivacaineSpinal
Epidural
Infiltration
Peripheral Nerve Block
BupivacaineSpinal
Epidural
Infiltration
Peripheral Nerve Block
Lidocaine + PrilocaineEutectic topical mixture

Can I drive home after local anesthesia?

Local anesthesia can be administered alone for dental and other superficial procedures. It may also be given in combination with sedation or general anesthesia. If local anesthesia alone is used for a minor superficial procedure, it is fine to drive back home assuming the local anesthesia is not used on the eyes (blurring of vision), hand, legs, or any situation that precludes safe driving.

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