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Detection and Management of Intravascular Epidural Catheters

Preetham Suresh, MD

What are the anesthetic implications of liver disease? What lab values would you check to assess the severity of
this patients liver disease?
FUNCTION DETAILS ANESTHETIC RELEVANCE
Blood 10-15% of total blood volume can be sequestered Many anesthetics suppress sympathetic tone
reservoir and quickly released after sympathetic and response.
stimulation
Blood Both pro- and anticlotting factors are synthesized Coagulopathies may lead to increased
coagulation in the liver. Vitamin K absorption depends on bile perioperative bleeding requiring aggressive
excretion. Liver-produced thrombopoietin correction and resuscitation.
modulates platelet production.
Endocrine Synthesizes and secretes: insulinlike growth Perioperative endocrine abnormalities may be
control factor-1, angiotensinogen, thrombopoietin, more common in patients with liver disease.
thyroid-binding globulin. Converts T4 to T3.
Inactivates: corticosteroids, aldosterone,
estrogen, androgens, insulin, and antidiuretic
hormone.
Bilirubin Absorbs bilirubin from the bloodstream, Hyperbilirubinemia detected by preoperative
excretion conjugates, and excretes it into the biliary system. screening tests may detect occult liver disease.
Synthesizes haptoglobin and scavenges
hemoglobin.
Carbohydrate Stores and releases glycogen. Site of Abnormal glycemic control is common in
metabolism gluconeogenesis from amino acids, lactate, and patients with liver disease and may manifest as
glycerol. perioperative hyper- or hypoglycemia.
Lipid Major site of fatty acid synthesis, and cholesterol Dysfunction leads to wide-reaching systemic
metabolism and lipoprotein metabolism. abnormalities of cellular function, involving cell
membranes, and hormones, possibly affecting
pharmacokinetics and pharmacodynamics of
anesthetic agents.
Amino acid Major site of protein and amino acid metabolism, Dysfunction leads to elevated ammonia levels
metabolism and urea production. and associated encephalopathy.
Protein Production of albumin, acute-phase proteins, Alterations of pharmacokinetics and
synthesis coagulation factors, and globulins. pharmacodynamics of many anesthetic agents.
Immunologic Largest reticuloendothelial organ. Filters out Immunocompromise associated with liver
modulation toxins, bacteria and debris from the GI tract. disease renders patients susceptible to
Hepatic macrophages, T cells, and Kupffer cells perioperative infection and sepsis.
then trigger and amplify the systemic
inflammatory response.

A broad array of biochemical tests is available to assess the multiple functions of the liver (Table above) and to
evaluate patients with suspected or established liver disease.7 Although collectively called liver function tests (LFTs),
many (e.g., aspartate aminotransferase [AST] and alanine aminotransferase [ALT]) do not assess a function of the liver
but rather are indicative of liver cell injury or dysfunction. LFTs are used to screen for the presence of liver disease,
suggest a general category of disease as the etiology, assess prognosis, and monitor the effectiveness of therapy. Many
of the routine tests are not specific for liver disease; however, when combined in a battery of tests, the sensitivity and
specificity for liver disease is high.

LFTs can be classified into several broad categories. These include tests that reflect (1) hepatocellular damage; (2)
obstructed bile flow; (3) hepatic synthetic function; (4) hepatic uptake, conjugation, and excretion; and (5) other
aspects of liver function.1
What happens to the plasma volume during pregnancy? What impact does this have on the albumin and
pseudocholinesterase concentrations in pregnancy? Are there any clinical implications of this?

Change* or
Actual
Parameter Measurement
Blood volume +45%*

Plasma volume +55%*

RBC volume +30%*

Hemoglobin 11.6 g/dL

Hematocrit 35.5%

Trimester
Non-
Protein pregnant First Second Third
Total protein (g/dL) 7.8 6.9 6.9 7.0
Albumin (g/dL) 4.5 3.9 3.6 3.3
Globulin (g/dL) 3.3 3.0 3.3 3.7
Albumin/globulin ratio 1.4 1.3 1.1 0.9
Plasma cholinesterase 25% 25% 25%
Colloid osmotic pressure (mm Hg) 27 25 23 22

Tables and diagrams2

Plasma cholinesterase (aka butyrylcholinesterase, pseudocholinesterase) metabolizes succinylcholine, ester local


anesthetics and mivacurioum. The 25% reduction seen in pregnancy is typically not clinically significant until less
than 50% enzymatic activity is left.

Systemic conditions other than pregnancy that can reduce plasma cholinesterase activity are: liver disease, renal
disease, malnutrition, malignancy (esp hepatic), burns and CPB.

Medications that can inhibit plasma cholinesterase include metoclopramide (25%), acetylcholinesterase inhibitors
like neostigmine, MAO-I like phenelzine, OCPs. 3

What epidural kits do we have and what are the differences?


Braun
18 G 9cm Touhy 1.5 cm
20 G catheter
Multiported
Stiff
Slick
Arrow
17 G 9 cm Touhy

0.5 cm
19 G catheter
Wire reinforced
Less kinking
the intravascular incidence compared to Braun multiported catheter
More likely to coil than be directed
Single ported

What is the definition of a positive test dose? Is a


test dose required? Discuss the sensitivity and specificity of this test as an intravascular marker. Are there ways
to improve the accuracy of the test?

Blood vessel puncture - 9% to 20% of obstetric patients


IV epidural catheter - 7% to 8.5% of obstetric patients.

IV test dose = 15 mcg Epi.

Increase heart rate of 20 bpm within 60 seconds. To improve sensitivity, some use increase in maximum heart
rate of 10 bpm. An accompanying increase in systolic blood pressure of between 15 and 25 mm Hg is often
seen. The most effective way to use the test dose is to time its administration immediately after the HR returns to
baseline following a contraction, and use it in conjunction with the BP, and clinical symptoms, and the presence of a
sensory block.

Downsides
- Decrease in uterine blood flow comparable to what a contraction would cause.
- May lack specificity increase HR could be from painful contraction
o Always give test dose immediately after HR returns to baseline from ctx
- May lack sensitivity use change in maximal heart rates to improve sensitivity.
- Multiport catheters could be in multicompartmental so inject firmly to ensure testing of distal port.

TABLE 23-2 Epidural Test Dose Regimens*Modified from Yilmaz M, Wong CA. Technique of neuraxial anesthesia. In
Wong CA, editor. Spinal and Epidural Anesthesia. New York, McGraw-Hill, 2007:27-73.
Positive IT
Test Dose Components Positive IV Test Dose Test Dose
Combined Intrathecal and Intravenous Test Dose:
Increase in heart rate
Lidocaine 1.5% with epinephrine of 20 bpm within 1 Motor blockade
5 g/mL (1:200,000): 3 mL minute at 3-5 minutes
Bupivacaine 0.25% with
epinephrine 5 g/mL
(1:200,000): 3 mL
Intravenous Test Dose:
Lidocaine 100 mg
Tinnitus, circumoral
Bupivacaine 25 mg numbness, dizziness
2-Chloroprocaine 100 mg
Fentanyl 100 g Dizziness, drowsiness
Change in Doppler
heart sounds over
Air 1 mL right side of heart

From: Chestnut, David H. Chestnut's obstetric anesthesia principles and practice. Philadelphia: Mosby/Elsevier, 2009.
Print.
What strategies are there to reduce the chance of a subsequent catheter going intravascular?

The risk of intravascular placement of a lumbar epidural catheter in pregnancy may be reduced with the lateral
patient position, fluid predistension, a single orifice catheter, a wire-embedded polyurethane epidural catheter and
limiting the depth of catheter insertion to 6 cm or less. In general, low manuscript quality weakens the strength of
these conclusions.4

How are amide local anesthetics metabolized? How about esters?

Amide-type local anesthetic agents undergo hepatic biotransformation. In patients with cirrhosis, the half-life of
lidocaine increases almost threefold (from 108 to 296 minutes), and the volume of distribution increases from 1.3 to
2.3 L/kg.118 An expanded volume of distribution offers some protection against toxicity despite impaired clearance.
2-Chloroprocaine undergoes hydrolysis with pseudocholinesterase. Although hepatic pseudocholinesterase
production may be decreased in patients with liver disease, the effect (if any) on the overall clearance of 2-
chloroprocaine is unclear.

In patients with end-stage liver dysfunction being evaluated for liver transplantation, the clearance of ropivacaine was
found to be approximately 60% lower than in healthy volunteers, although plasma concentrations were similar.119
Thus, when repeated doses or continuous infusions of local anesthetic are administered, the accumulation of
bupivacaine and ropivacaine (and their metabolites) should be considered, and doses should be reduced accordingly.
Even in patients with end-stage liver dysfunction, alpha-1-acid glycoprotein is synthesized, providing some protection
against local anesthetic toxicity. Because of the high volume of local anesthetic agent required, some anesthesiologists
have discouraged the administration of epidural anesthesia in patients with liver disease, although no studies of drug
disposition after such administration have been published.113 Ascites and portal hypertension lead to engorged
epidural veins; the use of a test dose to exclude intravascular injection is essential. Heriot et al.120 reported the
successful administration of epidural anesthesia to a parturient with portal hypertension and esophageal varices.
Although one might infer that spinal anesthesia is safer than epidural anesthesia because it requires administration of
a smaller dose of local anesthetic, spinal anesthesia also leads to the rapid onset of sympathetic blockade. 2

What are the symptoms of LAST and how do they correlate with plasma concentrations?

Older studies suggest a biphasic sequence of symptoms for both CNS and CVS
toxicity. Typically, there is CNS stimulation followed by depression and CVS
stimulation followed by collapse. This comes from data in volunteers who were
given infusions of local anesthetics and monitored for symptoms 5,6. 5 volunteers got
infusions of IV bupivacaine at 10mg/min until 125 mg given or symptoms were
severe enough to stop infusion. One week later got lidocaine at 20mg/min until
250mg given. This was compared to symptoms using etidocaine. The first finding is
the local effect on the tongue and mouth from the LA leaving the vascular space and
anesthetizing the nerve endings causing tongue or perioral numbness. Following
this, neuroexcitatory symptoms were seen due to blocking inhibitory pathways
followed by neurodepression due to blockage of inhibitory and facilitatory pathway.
CVS effects have a similar excitatory effect with hypertension and tachycardia,
followed by myocardial depression and decreased CO. Below is list of symptoms
from a recent case scenario in Anesthesiology. 7
In situations where large doses of local or rapid IV injections are given, seeing this gradual progression of symptoms is
unlikely as evidenced by more recent data describing the presenting symptoms in known LAST cases 8.

In the presence of CNS symptoms with lidocaine, what is the likelihood of impending cardiac instability?

This depends on the local anesthetic used. With lidocaine, the dose at which CVS symptoms are seen is ~4x as the
dose required to generate CNS symptoms. Whereas for the more potent lipophilic local anesthetics like bupivacaine,
the dose to generate CVS toxicity is much closer to the one required for CNS toxicity.9

If there is CV instability with lidocaine, what is the likelihood of a successful resuscitation?

Success of resuscitation of dogs after cardiovascular collapse from intravenous infusions of lidocaine, bupivacaine,
levo-bupivacaine (L-bupiv), and ropivacaine was evaluated10,11. Success rates were greater for lidocaine (100%), than
ropivacaine (90%), than levobupivacaine (70%), and than bupivacaine (50%). Required doses to induce
cardiovascular collapse were greater for lidocaine (127 mg/kg), than ropivacaine (42 mg/kg), than levobupivacaine
(27 mg/kg), and than bupivacaine (22 mg/kg).

Your colleague suggests giving lipid emulsion. How does Lipid emulsion work?

There are two major theories on how lipid emulsion reverses LAST.12
1) Lipid sink introduces an expanded lipid compartment to sequester lipid soluble drugs.
a) lipid emulsion counters both the CNS and CVS toxicity effects
b) myocardium relies primarily on fatty acid metabolism for ATP whereas the brain requires glucose. Reversal
of toxicity for both organ systems argues against a metabolic hypothesis
c) lipid emulsion can serve as an antidote for drugs with various mechanisms of action which suggests there
isnt a specific effect of the local anesthetic that is being countered by the lipid
2) Metabolic hypothesis local anesthetics inhibit carnitine-acylcarnitine translocase (CAT). This is the intracellular
enzyme responsible for the transfer of long chain fatty acids into mitochondria for ATP production. The theory is
that the enzymatic inhibition by local anesthetics is overwhelmed by the massive amounts of fatty acids allowing
ATP production to resume.
a) A patient with carnitine deficiency was particularly sensitive to developing arrhythmias with low dose
bupivicaine.
b) Lipid emulsion improves contractility in a rat model of LAST and a canine model of myocardial stunning.
c) CVS toxicity is proportional to a local anesthetics ability to inhibit carnitine dependent fatty acid transport.
If lipid emulsion is serving as a sink for the local anesthetic, what
physiochemical property of the local anesthetic will predict the utility
of lipid emulsion in LAST.

Lipid solubility is the primary determinant of a local anesthetic getting


absorbed by an infusion of lipid emulsion. Lipid solubility is secondary to
the carbon groups on the benzene ring. The more lipid soluble a local
anesthetic is, the more easily it can cross through a neural membrane
allowing it to be more potent. This is reflected by more lipid soluble local
anesthetics being used at lower concentrations than the less potent ones.
See table below for relative lipid solubilities measured in octanol:water
binding coefficients.

pKa % union- Onset Typical Lipid Protein


ized @ pH (Fast or Conc solubility binding
7.4 Slow)
Mepivicaine 7.7 33 Fast 1.5% 130 77%

Lidocaine 7.8 28 Fast 1% 366 64%

Ropivicaine 8.1 17 Slow 0.5% 775 94%

Bupivicaine 8.1 17 Slow 0.25% 3420 95%

Tetracaine 8.4 9 Slow 0.2% 5822 93%

What is the likelihood that lipid emulsion will work on less lipid soluble local anesthetics?

In vitro studies have revealed that local anesthetics will inhibit the flow of a current across a membrane by inhibiting
a voltage gated proton pumps. When exposed to lipid emulsion this effect is blocked for bupivacaine but not
significantly for lidocaine13. Similarly, when rat hearts were pretreated with lipid emulsion (0.25 ml/kg/min x 10
min) prior to the administration of bupivacaine, the onset of asystole was delayed. No such beneficial effects were
seen in preventing mepivacaine-induced cardiotoxicity and the recovery period was prolonged in the rats that got
lipid emulsion.14 This would suggest that lipid emulsion was actually detrimental to the resuscitative efforts from
mepivacaine.

Furthermore an earlier study from the same group showed that lipid emulsion hastens the electrical and
hemodynamic recovery of isolated rat hearts from bupivacaine but not for ropivacaine or mepivacaine.15 Despite the
lack of experimental evidence supporting the use of lipid emulsion for the resuscitation from less lipophilic local
anesthetics and animal data to suggest potential for harm, there are several case reports and anecdotes on the
lipidrescue.org supporting its success and encouraging its use.

Despite the lack of evidence supporting lipid emulsion therapy in the context of lidocaine toxicity, are there any
risks of giving lipid emulsion to the mother?

There have been no reported adverse affects on giving lipid emulsion for treatment of LAST. Most risks associated
with lipid emulsion are from long-term use except anaphylaxis, which can occur acutely. 16,17 In rats, the LD50 for lipid
emulsion was 68 ml/kg which was approximately 3x the therapeutic dose 18. The triglycerides were noted to be
elevated for less than 48hrs and there was a subsequent increase in Phos, amylase, AST, and BUN.

phosphorus, 5.3-7.2 mEq/dL (2.5-4.5 mEq/dL)


amylase 1816-2804 U/L (40-140 U/L)
AST 45-284 U/L (8-35 U/L),
BUN 21.6-30.6 mg/dL (4-20 mg/dL)

The histiologic appearance of the brain, heart, pancreas and kidneys were all normal. The lung had thickening of the
alveolar septae and a few intra alveolar foamy hisitiocytes at 60ml/kg and hemorrhagic vascular congestion at 80
ml/kg. There was also a dose related finding of hepatic microvascular steatosis with extensive necrosis at the highest
dose.

It has been suggested that other possible consequences of high dose lipid emulsion may be extrapolated from findings
associated with the use of lipid infusion for nutrition16. Of note typical duration of exposure is much longer when
used for nutritional purposes but the peak dosing is less. For example the dosing for infants who had histopathologic
evidence of pulmonary fat embolism is shown below19:

Case 1 Case 2 Case 3 Case 4


Body Weight (kg) 1.65 1.48 2.76 3.13
Mean rate (mL/kg/hr) 0.7 0.75 0.4 0.6
Max rate (mL/kg/hr) 0.9 1.05 2.55 3.5
Total duration (days) 11 14 12 18

Another consideration when giving a large dose of lipid emulsion is allergic reaction. Lipid emulsion contains soybean
oil 20% = 200 mg/mL (long chain triglycerides) and egg yolk derived phosphatides 12 mg/mL and glycerin 22
mg/mL. Phosphatides serve the purpose of emulsification or mixing of two immiscible materials. The phosphatide in
lipid emulsion comes from egg lecithin. Typically, allergic individuals are sensitive to the glycoproteins in soy or egg
white albumin and not to the lecithin. Regardless, there is a theoretical risk of protein contamination in the lipid and
subsequent allergic reaction in a sensitive individual.

What factors affect if local anesthetics will cross the placenta?

Local anesthetics cross the placenta by simple diffusion, not active transport or pinocytosis. The factors that affect
how much crosses are protein binding, lipid solubility, maternal plasma concentration, maternal pH and fetal pH.20 At
equilibrium the fetal:maternal ratio is ~0.3 for bupivacaine and ~0.6 for lidocaine. However, the lower fetal
concentrations of plasma proteins like 1 acid glycoprotein cause a higher fetal free fraction of drug and a similar
concentration of drug capable of causing toxicity.21 In the context of fetal acidosis, ion trapping can take place through
protonation of the local anesthetic making it unable to diffuse back to the maternal circulation and eventual
accumulation on the fetal side.22

Are there any risks to the fetus in utero by giving the mother lipid emulsion?

Triglycerides are too large to cross the placenta and are broken down by the placenta into fatty acids, which do cross.

There is currently only one report in the literature of giving lipid emulsion in pregnancy and it worked effectively
without any known negative effects.23 That case was an 18yo G1P0, 86kg @38wks for induction if labor. The patients
BP was 160/81 and she had mild proteinuria with occasional FHR decelerations. CLE placed and negative test dose 4
cc 2% lidocaine. 6 cc 0.25% bupivacaine given w good pain relief. Over the next 15 min, BP increased to 172/114 and
HR 86 with pronounced FHR decelerations. After negative aspiration, 100 mcg fentanyl + 10cc 0.5% bupivacaine
given via epidural in preparation for CS. Following injection patient become restless, agitated and then began
twitching and became unresponsive. Aspiration of catheter at that time, was clearly positive for blood. At that time 2
50cc boluses of 20% lipid emulsion were given and the patient regained full consciousness but there was ongoing
fetal bradycardia. Emergency CS performed under GA. 6 lb infant with APGAR 0 1, 75, and 1010 after intubation and
suctioning. Both mother and baby were discharged home on POD#4 without complication.

With only one case report of its use in pregnancy, the potential fetal risks could be extrapolated from data on the use
of TPN in pregnancy. 24 TPN also contains 10-20% lipid solutions and has been evaluated in malnourished pregnant
women who required TPN for a range of 14-220 days. In the study group of 26 woman all with conditions significant
enough to require TPN, 7 were delivered preterm without congenital malformations, and one psychiatric patient with
DM who developed a hyperglycemic coma resulted in an IUFD. In all patients there was ultrasound evidence of
improved fetal growth after starting TPN.25
In another study looking at the effect of TPN on the placenta in 20 women, all but one had a normal placenta. That
patient received TPN for 8 weeks and had placental fat deposits noted prior to a 22 wk IUFD. 26

There is data from the pediatric literature that administration of lipid emulsion to a newborn can result in pulmonary
lipid emboli27 and potentially an increase in pulmonary vascular resistance. 28

To prevent the progression of the CNS symptoms to a seizure, what are the options for treatment?

Midazolam or propofol (caution if hemodynamically unstable). Please note, propofol cannot


be used in place of a lipid emulsion. It contains 10% lipid so to give the equivalent amount of
lipid as is recommended for the initial bolus to treat LAST (1.5 mL/kg of 20% lipid
emulsion), youd be giving ~200 mL of propofol at once (Ten 20 mL syringes!).

Why is prevention of a seizure important?

There can be rapid development of hypoxia, respiratory and metabolic acidosis during and immediately after a
seizure. A clinical report of two cases of seizures from LAST where rapid blood gas values were obtained was
published by Moore et al29. In the first patient, three minutes after the first seizure, the blood gas was 7.09/59/33/17
(pH/pCO2/PO2/HCO3). In the other patient, one minute after the onset of the seizure, the blood gas was
6.99/76/87/17. Between convulsions, attempts at ventilating both patients with 100% O2 were being made.

These rapid rises in CO2 are significantly faster than what had been reported in apneic awake or anesthetized patients
where the expected rate of rise in the CO2 is 13mmHg in the first min and 6 mmHg/min after that30.

What effect does acidosis have on local anesthetics?

Local anesthetics are weak bases and cross the lipid bilayer in the uncharged form. Once intracellular they can
become protonated depending on their pKa relative to the surrounding pH. Once protonated, they bind the
intracellular portion of the Na channel to prevent depolarization and signal conduction along the nerve.

In the context of acidosis, the local anesthetics may be less likely to cross the membrane but the ones that have, will
stay protonated and bound to the sodium channel.

Resuscitation guidelines for LAST emphasize the primacy of oxygenation and ventilation. Is there evidence to
support that hypoxia and acidosis is especially harmful in the recovery from LAST.

A study that sheds light on this took ewes and invasively monitored them with31:
- femoral arterial line
- carotid artery sampling line
- pacing swan to monitor intracardiac ECG
- tracheostomy
- screws in cranium to monitor EEG
They then received either:
- Lido low (5.7mg/kg ) or high dose (11.4 mg/kg)
- Bupiv low (2.1 mg/kg) or high dose (4.2 mg/kg)

Their findings showed that the ewes spontaneously hyperventilated during the seizure and maintained pH >7.35. All
ewes survived the LAST.
In a subsequent study, they induced a respiratory acidosis (7.15/50/85) by ventilating with CO2 and then
administered the same four LA regimens 32:
They found that all of the acidotic/hypoxic sheep in high dose bupivacaine group died, whereas when the sheep
spontaneously hyperventilated the majority survived.
% that died

100

0 2 Hypoxia/Acidosis
Low dose 1 Hyperventilated
High dose
Lido Low dose
Lido High dose
Bupi
Bupi

For this patient, who got lidocaine alone and early signs of CNS toxicity, would you give any medications to treat
her?

I would try to prevent the seizure with midazolam.

Ensure oxygenation and ventilation.

What is the evidence that lipid emulsion works?

The initial report by Dr. Guy Weinberg in 1998 described an incidental discovery that a lipid infusion significantly
increased the LD50 of bupivacaine in rats33. Subsequently, the findings have been confirmed in other animal models
and supported by multiple clinical reports of its use during resuscitation from LAST and other lipid soluble drug
overdoses. As a result, it has been adopted into the resuscitation guidelines from multiple professional societies
including the American Society for Regional Anesthesia guidelines published in 2010 with a revision in 2012. This
widespread acceptance has preceded full understanding of the mechanism of action(s) or its specific indications. The
rapid expansion of its use has been hastened from additional research from Dr. Weinbergs group and others
cautioning against the use of what would otherwise be the drugs of choice during resuscitation like epinephrine and
vasopressin.

What is the dose of lipid emulsion?

1.5 ml/kg in 1-2min. Repeat after 5 min.


15 ml/kg/hr infusion
Stop >10 min after CV stability
Keep dose < 10 mL/kg in 1st 30 min

Heres what the dosing would look like for a 100 kg patient.

Minutes 0 5 10 15 20
Bolus 15 15
1.5 ml/kg 0 0
Infusion 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25
0.25
ml/kg/mi
n
15
ml/kg/hr
Total 25 50 60 70 80
dose (ml) 0 0 0 0 0

Minutes 20 25 30 35 40
Bolus
1.5 ml/kg
Infusion 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25
0.25
ml/kg/mi
n
15
ml/kg/hr
Total 80 90 10
dose 0 0 00

This patient was supposed to go home after their procedure, would you still send them home? Would you still do
the procedure?

Recommendation is to monitor for >12 hrs after an episode of LAST

Is using a checklist effective?

Trainees who used the ASRA checklist for management of LAST were twice as likely to complete medical management
steps correctly.34 Of note, of the trainees using the checklist, 40% only partially used it. It is recommended to have a
copy of a LAST treatment along with Lipid emulsion immediately available in any area local anesthetics are given in
significant doses.

Can we follow standard ACLS protocols? What aspects are the same/different?

As with ACLS it starts with airway management to avoid hypoxia and acidosis.

The Pharmacologic Treatment of Local Anesthetic Systemic Toxicity (LAST)


is Different from Other Cardiac Arrest Scenarios 35 - 2012 Revision to address the visual prominence issues
discovered during its use in simulation scenarios.

Get Help
Initial Focus
Airway management: ventilate with 100% oxygen
Seizure suppression: benzodiazepines are preferred; AVOID Propofol in patients having signs of cardiovascular
instability
Alert the nearest facility having cardiopulmonary bypass capability
Management of Cardiac Arrhythmias
Basic and Advanced Cardiac Life Support (ACLS) will require adjustment of medications and perhaps
prolonged effort
AVOID vasopressin, calcium channel blockers, beta blockers, or local anesthetic
REDUCE individual epinephrine doses to <1 mcg/kg
Lipid Emulsion (20%) Therapy (values in parenthesis are for 70kg patient)
Bolus 1.5 mL/kg (lean body mass) intravenously over 1 minute (-lOOmL)
Continuous infusion 0.25 mL/kg/min (~18 mL/min; adjust by roller clamp) This is equal to 15 ml/kg/hr which
is 10x the bolus dose and you may find easier to remember
Repeat bolus once or twice for persistent cardiovascular collapse
Double the infusion rate to 0.5 mL/kg/ min if blood pressure remains low
Continue infusion for at least 10 minutes after attaining circulatory stability
Recommended upper limit: Approximately 10 mL/kg lipid emulsion over the first 30 minutes
Why is the dose of epinephrine reduced?

This based primarily on animal studies that revealed that lower doses of epinephrine (1-2mcg/kg) were associated
with better metabolic and hemodynamic profiles after resuscitation from LAST than higher doses (10-25mcg/kg)36.

Lower doses of epinephrine resulted in a return of spontaneous circulation (ROSC) faster than with saline, and
allowed for maintenance of hemodynamics stability without the decompensation that was seen with higher doses of
epinephrine.

It should be noted the studies that showed higher doses of epinephrine to be detrimental, gave a single high dose and
did not give subsequent vasopressors to support the hemodynamics. Also of noted, there is animal data to show that
in the context of hypoxia or compromised coronary perfusion and LAST, epinephrine is superior to lipid for
resuscitation.37 ,38

Why is vasopressin discouraged in context of LAST?

In animal studies evaluating the use of vasopressors in resuscitation from LAST (20 mg/kg of bupivacaine), rats that
got vasopressin (0.4 U/kg) or vasopressin + epinephrine (30 mcg/kg) developed red tinged pulmonary edema and
had a measurable increase in their wet:dry lung weight ratios. Also of note, the resuscitations were less successful
from a metabolic and hemodynamic perspective when compared to Lipid emulsion alone. As a result, in the
resuscitation guidelines caution against its use because of these worse outcomes and the association with pulmonary
hemorrhage. In the paper that is referenced, however, the diagnosis of pulmonary hemorrhage is never used but
rather, the mice that received vasopressin were noted to have red tinged pulmonary edema fluid in the expiratory
limb of the breathing circuit.

Regardless, the worse outcomes with vasopressin are in direct contrast to a study done in pigs where resuscitation
from LAST was more successful with vasopressin and epinephrine compared to lipid emulsion. These conflicting
findings may be related to differences in experimental protocols. In the experiments with rats by Di Gregario and
Weinberg et al39, asystole occurred immediately with injection 20 mg/kg of bupivacaine and CPR initiated without
delay. In the study by Mayr et al 40, a lower dose of 5 mg/kg was used and CPR was not initiated until approximately 3
minutes later during which time the pigs were apneic for all of that time and pulseless for 1 minute.
41

The accompanying hypoxia and acidosis that may have been present prior to the start of CPR that wasnt present in
the rat study. This may have required the use of vasopressors to generate adequate coronary perfusion pressors,
which are required to allow for a successful resuscitation.

REFERENCES

1 Barash, Paul G. Clinical anesthesia. Philadelphia, PA: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2013. Print.

2 Chestnut, David H. Chestnut's obstetric anesthesia principles and practice. Philadelphia: Mosby/Elsevier, 2009. Print.

3Soliday, Flanna K., Yvette P. Conley, and Richard Henker. "Pseudocholinesterase deficiency: a comprehensive review of genetic,
acquired, and drug influences." AANA journal 78.4 (2010).

4
Mhyre, JM et al. A systematic review of randomized controlled trials that evaluate strategies to avoid epidural vein cannulation
during obstetric epidural catheter placement. Anesthesia & Analgesia 2009

5 Scott, D. B. "Evaluation of the toxicity of local anaesthetic agents in man." British journal of anaesthesia 47.1 (1975): 56-61.

6Cousins, Michael J., and Phillip O. Bridenbaugh. Cousins and Bridenbaugh's neural blockade in clinical anesthesia and pain
medicine. Philadelphia: Lippincott Williams & Wilkins, 2009. Print.

7Vadi, Marissa G., Neesa Patel, and Marjorie Podraza Stiegler. "Local Anesthetic Systemic Toxicity after Combined Psoas
CompartmentSciatic Nerve Block: Analysis of Decision Factors and Diagnostic Delay."Anesthesiology 120.4 (2014): 987-996.

8Di Gregorio, Guido, et al. "Clinical presentation of local anesthetic systemic toxicity: a review of published cases, 1979 to 2009."
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