LAST (Local Anesthetic Systemic Toxicity): A practical update for clinicians

Summary

This video script delves into Local Anesthetic Systemic Toxicity (LAST), a rare but serious complication of local anesthetic use that can lead to severe injury or death. It outlines the evolving clinical presentation of LAST, emphasizing the necessity for vigilance in prevention and the importance of understanding its mechanism. The script also discusses the multimodal antidotal role of lipid emulsion, risk factors, preventive measures, and management strategies, including the crucial steps to take in the event of an LAST episode.

Takeaways

• 🚨 Local anesthetic systemic toxicity (LAST) is a potentially fatal complication of local anesthetic use, with permanent injury or death as possible outcomes.
• 🔍 LAST is an overdose situation that can occur due to accidental intravascular injection or exceeding a patient's toxic threshold.
• 📈 The incidence of LAST is estimated to be between one to two in every thousand nerve blocks, but this number may be higher due to unreported cases.
• 🌐 The presentation of LAST has evolved and can vary, with about half of cases starting with neurologic signs and symptoms, and a quarter with only cardiac signs.
• 👨‍⚕️ The risk of LAST is not limited to a specific site of injection, and vigilance is required to prevent it, especially with the rise of outpatient procedures.
• 💊 The toxic mechanism of LAST involves blockade of sodium channels and mitochondrial poisoning, affecting primarily the heart and brain.
• 🩺 An antidote for LAST is the lipid emulsion, which works by scavenging local anesthetic molecules from the heart and brain, providing an inotropic effect, and improving cardiac output.
• 👶 Certain populations are at higher risk for LAST, including the elderly, infants under six months, pregnant patients, and those with reduced ventricular function or arrhythmias.
• ⚠️ Prevention strategies include being aware of dose limits, using fractional injection techniques, aspirating before injecting, and using epinephrine as a marker for intravascular injection.
• 🔬 Ultrasound guidance is associated with a significantly reduced incidence of LAST, emphasizing its importance in procedural practices.
• 🆘 In the event of LAST, immediate steps include stopping the injection, calling for help, maintaining airway, ventilating the patient, and administering lipid emulsion as the primary treatment.

Q & A

What is Local Anesthetic Systemic Toxicity (LAST)?

LAST is a potentially fatal complication that can occur from the use of local anesthetics, either due to accidental intravascular injection or because the administered dose is too high for the patient, leading to toxic plasma levels.

How common is LAST and what are its historical presentation symptoms?

LAST is considered a rare complication, occurring in approximately one to two in every thousand nerve blocks. Historically, it presented with prodromal symptoms such as numbness around the mouth, metallic taste, and ringing in the ears, followed by agitation, twitching, and seizures as plasma concentrations increased.

How has the understanding of LAST presentation evolved?

Contemporary data shows that not all cases of LAST present with the classic order of symptoms. About half of the cases now present initially with neurologic signs and symptoms, a third with both neurologic and cardiovascular manifestations, and a quarter with only cardiac signs.

Why is it important to remain vigilant about preventing LAST?

Preventing LAST is crucial because the traditional method of catching it early through prodromal symptoms is not reliable. Being vigilant helps in early detection and intervention, which can be life-saving.

What are some changes in where LAST occurs and which professionals are involved?

While the majority of LAST cases still occur in hospitals, there has been an increase in cases in outpatient settings such as urology, cosmetic surgery, and dental offices. The proportion of LAST due to non-anesthesiologists has also increased, partly due to tumescent anesthesia for liposuction.

What is the toxic mechanism of LAST and how does it affect the body?

The toxic mechanism of LAST involves blockade of sodium channels in the heart and CNS, inhibition of other ion channels, and primarily poisoning of the mitochondrial oxidative phosphorylation pathway, leading to metabolic asphyxiation. This results in cardiac and neurotoxicity due to the heart and brain's intolerance to intracellular energy depletion.

How does the lipid emulsion work as an antidote for LAST?

Lipid emulsion works multimodally, primarily by scavenging lipid-soluble local anesthetic molecules from the heart and brain, reducing their concentration at ion channels, and providing fatty acid substrate for poisoned mitochondria. It also has a volume effect that helps generate cardiac output.

Which patient populations may be at higher risk for LAST?

Populations at higher risk for LAST include the extremes of age (elderly with cardiac comorbidities and infants under six months with immature hepatic pathways), pregnant patients with reduced plasma binding proteins, and patients with reduced ventricular function or pre-existing arrhythmias.

What preventive strategies can be employed to reduce the risk of LAST?

Strategies include being conscious of published dose limits, using the lowest effective dose, fractional injection with pauses, aspirating before injecting, using epinephrine as a marker for intravascular injection, and utilizing ultrasound guidance for blocks.

What are the special considerations for managing LAST in the case of a cardiac arrest?

In a cardiac arrest due to LAST, standard ACLS should be followed with modifications: avoid using high doses of epinephrine or vasopressin, and do not use lidocaine to treat arrhythmias. Chest compressions are key to improve coronary perfusion with lipid emulsion.

What steps should be taken if LAST is suspected during a procedure?

If LAST is suspected, immediately stop injecting the local anesthetic, call for help, prepare a lipid emulsion kit, maintain the airway, and if necessary, ventilate the patient. Administer benzodiazepines for seizures and start the lipid emulsion as soon as possible.

Outlines

00:00

🚨 Local Anesthetic Systemic Toxicity Overview

This paragraph introduces the concept of Local Anesthetic Systemic Toxicity (LAST), a serious complication arising from the use of local anesthetics. It explains that LAST is an overdose situation that can lead to permanent injury or death. The paragraph outlines the evolution of understanding regarding the presentation of LAST, moving from a classic symptom pattern to a more varied and unpredictable one. It also touches on the frequency of occurrence, the changing locations where LAST happens, and the shift in demographics of those affected. The toxic mechanism of LAST is described as involving sodium channel blockade and mitochondrial poisoning, leading to cardiac and neurotoxicity. The paragraph concludes with the introduction of lipid emulsion as an antidote for LAST, explaining its multimodal action in mitigating the toxic effects.

05:03

👶👵 Populations at Higher Risk for LAST

The second paragraph delves into the populations that are at a higher risk for LAST, including the elderly and infants under six months due to their physiological differences. It discusses how pregnant patients and those with reduced ventricular function or pre-existing arrhythmias are also at increased risk. The paragraph emphasizes the importance of preventive measures such as adhering to published dose limits, using the lowest effective dose, and utilizing techniques like fractional injection and aspiration before injection to minimize the risk of LAST. It also highlights the benefits of using epinephrine as a marker for intravascular injection and the advantages of ultrasound-guided blocks in reducing the incidence of LAST. Special attention is given to fascial plane blocks, catheters, and the use of intravenous lidocaine, with recommendations for cautious dosing.

10:04

🆘 Managing LAST: Immediate Actions and Treatment

The final paragraph focuses on the immediate steps to take in the event of a LAST occurrence. It provides a clear protocol for managing the crisis, starting with stopping the injection of the local anesthetic, calling for help, and preparing a lipid emulsion kit. The paragraph outlines the dosage and administration of lipid emulsion, including the bolus dose and infusion rate, and advises on adjusting these based on the patient's response. It also discusses the importance of maintaining the patient's airway and the use of benzodiazepines to control seizures. The paragraph advises against the use of certain medications during a LAST event that could exacerbate the situation and emphasizes the importance of standard ACLS procedures with modifications, such as prioritizing chest compressions for better lipid flow. It concludes with guidelines for post-stabilization monitoring and the potential need for advanced interventions like cardiopulmonary bypass or ECMO in severe cases, along with references to management flowcharts from professional organizations.

Keywords

💡Local Anesthetic Systemic Toxicity (LAST)

Local Anesthetic Systemic Toxicity, or LAST, refers to a potentially fatal condition that arises from an overdose of local anesthetic. It is the main theme of the video, emphasizing the importance of understanding its mechanism and management. The script discusses how it can occur due to accidental intravascular injection or excessive dosage relative to the patient's tolerance, highlighting the need for vigilance among clinicians using local anesthetics.

💡Plasma Levels

Plasma levels in this context refer to the concentration of local anesthetic in the blood plasma. The video explains that a toxic threshold of local anesthetic in plasma can lead to LAST, emphasizing the importance of monitoring and controlling dosage to prevent reaching such levels. The script mentions that the classic presentation of LAST is associated with rising plasma levels, starting with mild symptoms and potentially escalating to seizures and cardiac issues.

💡Prodromal Symptoms

Prodromal symptoms are the initial signs that indicate the onset of a disease or condition. In the video, these symptoms are associated with the early stages of LAST and include numbness around the mouth and tongue, ringing in the ears, and a metallic taste. The script notes that the understanding of how LAST presents has evolved, and these symptoms are not always the first to appear, making prevention and early detection more complex.

💡Neurologic Signs and Symptoms

Neurologic signs and symptoms relate to the nervous system's responses to stimuli or injury. The video script indicates that nearly half of all LAST cases present initially with such signs and symptoms, which can include agitation, restlessness, twitching, and seizures. This highlights the importance of recognizing these signs in the context of local anesthetic use.

💡Cardiovascular Manifestations

Cardiovascular manifestations refer to the effects of a condition on the heart and blood vessels. The script explains that a third of LAST cases present with both neurologic and cardiovascular signs, such as arrhythmias and cardiac pump failure, underscoring the systemic impact of LAST on the body.

💡Mitochondrial Poisoning

Mitochondrial poisoning is a key toxic mechanism discussed in the video, where local anesthetics interfere with the mitochondria's ability to generate ATP, leading to cellular energy depletion. This concept is central to understanding the severe cardiac and neurotoxic effects of LAST, as it explains why organs like the heart and brain are particularly affected.

💡Lipid Emulsion

Lipid emulsion is presented as an antidote for LAST in the video. It works by scavenging local anesthetic molecules from sensitive tissues like the heart and brain, reducing their concentration at ion channels and allowing tissue function to recover. The script details its multimodal mechanism of action and emphasizes its effectiveness and safety in treating LAST.

💡Risk Factors

Risk factors in the context of the video are conditions or characteristics that increase the likelihood of LAST occurring. The script mentions age extremes (elderly and infants), pregnancy, and certain patient conditions like reduced ventricular function or coronary disease as factors that may predispose individuals to LAST, guiding clinicians to adjust dosages and practice caution.

💡Ultrasound Guidance

Ultrasound guidance is a technique used to administer local anesthetics more safely and effectively. The video script notes that the use of ultrasound has been associated with a significantly reduced incidence of LAST, making it a best practice for clinicians to adopt.

💡Fractional Injection

Fractional injection is a safe practice mentioned in the script where the local anesthetic is injected in small aliquots, with pauses in between to allow plasma concentrations to decrease. This approach is recommended to minimize the risk of LAST, especially in patients with multiple risk factors.

💡Epinephrine

Epinephrine is used in local anesthetic solutions as a marker for inadvertent intravascular injection and to help reduce the peak plasma level of local anesthetics. The script discusses its role in preventing LAST by providing early warning signs of potential complications.

Highlights

Local anesthetic systemic toxicity (LAST) is a potentially fatal complication of local anesthetic use.

LAST can result in permanent injury or death, emphasizing the importance of understanding its mechanisms.

LAST occurs due to accidental intravascular injection or an excessive dose for the patient's tolerance.

The incidence of LAST is estimated to be 1-2 in every thousand nerve blocks, but likely underreported.

Classic presentation of LAST includes numbness, metallic taste, and neurologic symptoms, followed by agitation and seizures.

Contemporary data shows varied presentations of LAST, not always following the classic order.

Prevention of LAST is crucial due to the unreliability of prodromal symptoms for early detection.

LAST can occur in various settings, including outpatient clinics and dental offices, not just in hospitals.

The toxic mechanism of LAST involves sodium channel blockade and mitochondrial poisoning, affecting the heart and brain.

Lipid emulsion is an effective antidote for LAST, working through multiple mechanisms including scavenging local anesthetics.

High-risk populations for LAST include the elderly, infants, and pregnant patients, requiring dose adjustments.

Patients with cardiac issues are more susceptible to LAST-induced myocardial depression.

Preventive strategies include adhering to dose limits, fractional injection, and aspirating before each dose.

Epinephrine is used in local anesthetics to detect intravascular injection and reduce peak plasma levels.

Ultrasound guidance is associated with a reduced incidence of LAST compared to non-ultrasound techniques.

Special considerations are needed for fascial plane blocks and catheters due to higher LAST risks.

In the event of LAST, immediate steps include stopping injection, calling for help, and preparing lipid emulsion.

Management of LAST includes maintaining airway, ventilating the patient, and using benzodiazepines for seizures.

Lipid emulsion dosage and administration guidelines are crucial during LAST management.

In cardiac arrest due to LAST, standard ACLS protocols should be adapted to avoid exacerbating the situation.

Post-incident monitoring is necessary to ensure the heart and brain are no longer at risk from LAST.

LAST management guidelines from professional organizations emphasize the importance of preparedness and vigilance.

Transcripts

[Music]

local anesthetic systemic toxicity or

last is a potentially fatal complication

of local anesthetic use the presentation

can be variable but a substantial number

of these cases result in permanent

injury or death and understanding the

ins and outs of this complication is a

must for any clinician using local

anesthetics in this video we'll review

the mechanism the clinical presentation

as well as strategies for prevention and

management last is an overdose of local

anesthetic and happens either because

we've accidentally put a big dose of

local in a vessel or for whatever reason

the local we've administered into the

correct body compartment is just too

much for that particular patient and the

plasma levels hit a toxic threshold is

this a rare complication

maybe our best numbers suggest that it

happens in one to two in every thousand

nerve blocks however those are just the

ones we know about from perspective

registries or databases there are no

doubt several fold more cases that go

unreported especially if the outcome is

favorable

our understanding of how last presents

has evolved over the last several

decades and especially in the era of

ultrasound and fascial plane blocks the

classic presentation was based on rising

levels of plasma local anesthetic and

started with the prodromal symptoms

numbness around the mouth and tongue

ringing in the ears a metallic taste and

some other non-specific neurologic items

then as plasma concentration increased

the patient would become agitated

restless and start to twitch and

eventually seize

only the cases with the highest plasma

levels would develop arrhythmias and

cardiac pump failure it's important to

understand that while the syndrome can

present in that specific order it

certainly doesn't have to more

contemporary data show that just under

half of all cases present initially with

neurologic signs and symptoms makes

sense a third percent with both

neurologic and cardiovascular

manifestations at the same time so that

means that about a quarter percent with

only cardiac signs that's not good

in the old days we kind of relied on the

paradigm of hopefully i'll catch the

last early because i'll watch for the

prodrome we know that's just not

reliable anymore and this speaks to the

need to remain uber vigilant about

preventing last another thing that's

changed is where it happens while the

majority still occur in hospital about

40 happen in ascs outpatient urology

clinics cosmetic surgery clinics dental

offices and so on as anesthesiologists

we used to own this complication because

we were the ones using large volumes of

local anesthetic and running into

trouble in the last 10 years we've seen

an uptick in the proportion of last due

to surgeons and other proceduralists at

least part of that trend relates to

tumescent anesthesia for liposuction the

site of injection seems to matter too

although that picture has changed

slightly as well a commonly taught list

of injection sites ranked in order of

potential for systemic absorption

started with intercostal and epidural

and ended with subcutaneous and it made

sense that these might represent a

graded risk for last more recent case

reports suggest that procedures such as

penile blocks in children and local

infiltration analgesia for joint

replacement are bigger culprits this

probably represents inattention to

dosing limits relative to patient's size

neraxial is still up there as are upper

extremity blocks and pair vertebral

blocks but keep in mind that there is no

site that is truly safe from last the

toxic mechanism is complicated and not

fully understood we do know that part of

it relates to blockade of sodium

channels in the heart and central

nervous system but there's also

inhibition of other membrane ion

channels including potassium calcium and

others however the primary toxic

mechanism probably relates to poisoning

of the mitochondrial oxidative

phosphorylation pathway to put it more

simply the cells just can't generate atp

for energy they're metabolically

asphyxiated as you might expect the

organs that are most intolerant of

intracellular energy depletion are the

heart and brain which is why the

clinical syndrome manifests as cardiac

and neurotoxicity this mitochondrial

poisoning theory may also explain why

the usual hemodynamic therapies like

vasopressors and anatropic drugs are

frustratingly ineffective in severe last

in the brain high local anesthetic

levels first provoke blockade of

inhibitory neurons in the cortex which

leaves the excitatory pathways

unrestrained this explains the twitching

hallucinations and seizures that

characterize neurotoxicity at a higher

threshold plasma level the excitatory

neurons get blocked too resulting in cns

depression and coma in the heart we see

sodium channel blockade of conducting

fibers which provokes either bradycardia

or reentrant tachyarrhythmias there's

also a direct myocardial depressant

effect from calcium channel blockade and

interference with the myocardial sodium

calcium channel pump add on to that the

mitochondrial poisoning and you can see

how the heart muscle begins to fail fast

now we have an antidote for this

poisoning fat specifically a 20 emulsion

of triglycerides and phospholipids it's

amazing for its sheer effectiveness at

reversing the toxic changes after local

anesthetic poisoning and the fact that

it's cheap and plentiful makes it all

the more attractive so how does lipid

emulsion work it's actually multimodal

but the first and principle way it works

is by scavenging lipid soluble local

anesthetic molecules from the heart and

brain tissue and shuttling them to other

tissue depots notably the high mass high

flow skeletal muscle and liver this

lowers the concentration of local

anesthetic at the ion channels in the

heart and brain and when that

concentration drops sufficiently the

tissues can begin to function again

the triglycerides also provide fatty

acid substrate for the poisoned

mitochondria to use providing a little

inotropic kick there's also a volume

effect from the colloidal lipid emulsion

that helps generate cardiac output so it

really does work in a couple different

ways when we think about populations

that may be at higher risk for last the

extremes of age seem to be in that

category elderly people have cardiac

comorbidities that result in a lower

threshold for rhythm disturbances or

pump failure they also have decreased

muscle mass which means they're unable

to use that as a neutral reservoir for

local anesthetics babies under six

months of age have decreased muscle mass

too as well as immature hepatic bowel

transformation pathways so plasma levels

of local anesthetic may be elevated

particularly since they also have

reduced concentrations of alpha one acid

glycoprotein a protein that binds local

anesthetics into plasma for both the

frail elderly and children less than six

months of age a dose reduction of local

anesthetic of 10 to 20 percent seems

reasonable

pregnant patients have a reduced

concentration of plasma binding proteins

and increased cardiac output which

translates to a more rapid rise to peak

plasma levels add to that the epidural

venous engorgement from the mass effect

of the uterus and it seems reasonable to

reduce the epidural dose by 10 to 20

percent starting in the first trimester

patients with reduced ventricular

function will be more susceptible to

local anesthetic induced myocardial

depression and they won't clear local as

fast those that already have arrhythmias

are at slightly higher risk for

developing a serious arrhythmia with

last two

coronary disease doesn't seem to be a

risk in and of itself but remember you

need to feed fat to the heart in a

cardiac arrest situation and if that

muscle is poorly perfused because of

sclerotic blockages it will prolong the

resuscitation

we don't want to have to manage last so

it pays to prevent it first off be

conscious of published dose limits there

are obviously downsides to a set of

limits that don't take into account the

site of injection or other patient

factors however they're a good framework

to work from it's scary to see that

there are plenty reports of last with

sub-maximal doses a good rule is to use

the lowest dose possible that gets the

analgesia you need fractional injection

means pausing between each four to five

ml aliquot for 20-30 seconds to allow

the plasma concentration to begin to

fall this is a good safe practice it can

be somewhat impractical with small

volume blocks and will typically do this

for the elderly patient with multiple

risk factors or high volume blocks

always aspirate before injecting each

dose it's not perfect there are some

false negatives but they're rare

epinephrine is used as a marker for

inadvertent intravascular injection we

put it in virtually every local

anesthetic syringe and have had some

good saves where we were obviously

mistaken as to the needle tip position

epinephrine also truncates the peak

plasma level of local anesthetics

and finally use ultrasound we now have

evidence that ultrasound guided blocks

are associated with a significantly

reduced incidence of last over a

non-ultrasound technique so use it

three special situations deserve a brief

mention

fascial plane blocks carry a somewhat

higher risk for last for two reasons one

the target inter-muscular fascial plane

is sandwiched between two reasonably

vascular muscle bellies and so uptake is

relatively quick depending on the

individual block we also use large

volumes such as 80 mils total for a

bilateral set of blocks in these cases

it's wise to dilute the local anesthetic

down to stay well within dosing

guidelines the nerves in these blocks

are generally quite small and easily

blocked with dilute local anesthetic

catheters are wonderful but be aware

that most of the data we have to date

shows that the total plasma levels of

repivocane do continue to rise for the

duration of the catheter and so care

should be taken when planning the

infusion regimen again the least amount

of local possible to get the job done is

the right dose fortunately the alpha-1

acid glycoprotein also rises following

surgery so while the total plasma level

may be high the actual free fraction is

not as high as you might think

special care should be taken with

multiple catheters intravenous laticane

has been the culprit in a number of

serious last cases even in normal doses

over 10 percent of patients report mild

cns or cardiovascular disturbances a

recent international consensus statement

has recommended that infusion rates go

no higher than 1.5 milligrams per

kilogram per hour and only infused for

24 hours a block should not be performed

within 4 hours of starting or finishing

the infusion the worst happened and

you've got a case of last what are your

first steps

first stop injecting the offending

poison call for help and if you have a

lipid emulsion kit prepared call for

that specifically maintain the airway

and if necessary ventilate the patient

the seizure produces a profound

hypercarbic state which vasodilates the

cerebral arteries promoting the delivery

of the very agent we want to avoid to

the brain you want to aim for eucapnia

or slight hypocapnia stopping the

seizure is important and benzodiazepines

are the first line two milligrams of

midazolam is usually sufficient purple

fall should be used sparingly as it will

have a negative effect on blood pressure

and cardiac output at this point you're

going to want to give the lipid i

recommend delegating one individual to

manage the lipid portion of the recess

direct him or her to withdraw 1.5 mils

per kilo using some big syringes this is

your bolus dose and you want to get it

in quick once the bolus is finished

direct him or her to start the infusion

at 0.25 mils per kilo per minute up to

two more boluses of the same dose can be

given if needed and the infusion rate

doubled if there's refractory

hypotension but the maximum dose is 12

mils per kilo

now doing math in the middle of a crisis

is no fun so here's an easy math free

version that will approximate your bolus

and infusion assuming an ideal body

weight of 70 kilos 100 ml bolus and a

thousand mils per hour on the pump in

the heat of the recess just get things

going with those two settings and then

once the dust has settled you can fine

tune your infusion if needed lipid

emulsion is very well tolerated and

there are sufficiently few side effects

that most experts recommend giving it at

the first hint of last you may over

treat some patients who are false

positives but given that last can

progress quickly you really don't want

to take that chance if you have the

clinical suspicion give the lipid it's

nice to have your lipid and the

instructions in one place here's an

example from lipidrescue.org where the

lipid is in a sealed box with

instructions pasted to the top

in a cardiac arrest setting everything

else is the same but you'll want to

carry on with standard acls standard

except for the following don't use a

milligram of epinephrine all it does is

provoke arrhythmias wildly increased

cardiac work impairs gas exchange and

provokes a rise in lactate the goal here

is to get flow of lipid through the

coronaries so chest compressions are key

don't use a vasopressin as it has been

shown to worsen outcomes and obviously

you wouldn't use lidocaine to treat

arrhythmias in the setting of last and

similarly don't use meds that reduce the

ionotropy or av conduction

once you've had the patient back and

stable for 10 minutes you can stop the

lipid infusion if the patient has

experienced cardiovascular compromise he

or she should be monitored for at least

six hours to ensure the heart and brain

are no longer at risk from

redistribution if there were only

neurologic manifestations two hours is

enough if the episode was brief and not

severe it may be best to proceed with

surgery especially if the patient has

already been blocked and the block is

sound on the other hand in cases where

the patient is not responding to these

measures consider calling in the cavalry

and getting cardiopulmonary bypass or

ecmo deployed here's a flowchart for

last management from the american

society of regional anesthesia and pain

medicine and this is a similar guideline

from the association of anesthetists of

great britain and ireland both are very

similar last is a terrible complication

of local anesthetic use that with the

right preventive strategies and

vigilance can be avoided make sure

you're prepared in any setting you use

local anesthetics

you