Local Anesthetic Systemic Toxicity and Lipid Emulsion Therapy

Local Anesthetic Systemic Toxicity and Lipid Emulsion TherapyManaging injuries is all too common when caring for children. Whether it is a Fish Hook where it shouldn’t be or a Tongue Laceration or whether it is Mandibular Fracture or a Facial Laceration, anticipating and managing the child’s pain is critical! We have previously discussed using Intranasal Analgesics and Nitrous Oxide to provide relief of pain, but most often good ol’ fashioned lidocaine is all that is needed. Certainly topical preparations work amazingly well, even for our tiniest of patients (Neonatal Analgesia), but sometimes we need to use it locally or for regional blocks. That is when we need to remember LAST (Local Anesthetic Systemic Toxicity). Let us take a minute to review LAST and its therapy, Lipid Emulsion:

 

Local /Regional Anesthetic: Basics

  • Regional anesthesia has become more commonly used in children. [Walker, 2018]
    • From the ED to the OR.
    • In the ED, they can be used for laceration repairs as well as pain management of extremity injuries… and they let us use our cool Ultrasounds for another procedure (what fun!).
  • Overall, regional anesthesia is safe when performed correctly!
    • Risk of nerve injury is very low. [Walker, 2018]
    • Risk of severe Local Anesthetic Systemic Toxicity (LAST) is also low – 0.76:10,000 in one study. [Walker, 2018]
  • Anesthetic Basic Science:
    • Local anesthetics inhibit sodium channels in neurons
    • They also effect GABA pathways leading to unopposed excitatory activity. [Nelsen, 2009]
    • Classified as Esters or Amides
      • Esters = Benzocaine, Cocaine, Procaine, Tetracaine, Chloroprocaine
      • Amides = Lidocaine, Mepivacaine, Ropivacaine, Bupivacaine
    • Can be classified as either Short-Acting or Long-Acting local anesthetics.
      • Long-Acting, like Bupivacaine, have greater potency and duration. [Lonnqvist, 2012]
      • Toxicity duration and severity is also greater with Long-Acting.

 

Local Anesthetic Systemic Toxicity

  • Local Anesthetic Systemic Toxicity (LAST) is a severe and life-threatening adverse reaction due to local anesthetic reaching significant systemic levels.
    • Can be do to inadvertent injection into the vascular system.
    • Can be do to excessive absorption from highly vascularized area.
    • Can be do to accidental overdose.
      • ex, use of anesthetic at dose greater than recommended
      • ex, consumption of over the counter product by toddler [Nelsen, 2009]
  • Symptoms:
    • Early signs of toxicity can be subtle (especially if patient is sedated):
      • Muscle fasciculations / tremors
      • Paresthesias
      • Perioral and tongue numbness
      • Metallic taste in mouth, tinnitus
      • Hypertension
      • Drowisness, lightheadedness
      • Agitation, confusion
      • Headache
    • Severe clinical toxicity is characterized by a dose-related CNS and Cardiovascular toxicity.
      • CNS Toxicity
        • Seizures
        • Coma
      • Cardiovascular
        • Bradycardia
        • Progressive Hypotension
        • Myocardial depression
        • Wide QRS complexes, Ventricular dysrhythmias
        • Torsades de Pointes, Ventricular Fibrillation
        • Cardiac arrest
  • Children are at greater risk for systemic toxicity of local anesthetics.
    • Plasma protein binding of the local anesthetic is reduced in neonates and infants. [Lonnqvist, 2012]
    • Amides are metabolized by the Liver (although, metabolism of esters also involves liver products) – so patients with liver disease, or reduced liver function, LIKE CHILDREN, may have potentiated effects.
    • Region of administration is a smaller target in young children… so may be missed, or inadvertently affecting adjacent structures in close proximity.

 

LAST Management

  • It is best to avoid LAST from occurring!
    • Double check your dosing of the specific anesthetic.
    • Always aspirate as you advance the needle looking to avoid injecting into blood vessels.
  • Pay attention to the subtle signs of toxicity!
    • Stop any infusion of local anesthetic at the first sign of symptoms.
    • Establish IV and place on monitors, if not already.
    • Consider LAST in any patient with altered mental status, new neurologic symptoms, or signs of cardiovascular instability that develop after use of local anesthetic. [ASRA.com]
  • Order Lipid Emulsion 20%
    • Exact mechanism is not understood:
      • “Lipid Sink” metaphor – the lipid emulsion acts as another compartment for the lipophilic drugs to reach equilibrium with, thus reducing the available free drug. [Presley, 2013; Lonnqvist, 2012]
      • Augments cardiac energy source delivery, which the local anesthetics interrupted. [Presley, 2013]
      • Restores calcium transport, which was interrupted by anesthetics. [Presley, 2013]
    • Lipid Emulsion therapy has been used and is well tolerated in children. [Presley, 2013]
      • Acute use has few side effects.
      • Can see hypertriglyceridemia and pancreatitis develop several days after emulsion therapy.
      • Emulsion therapy also interferes with many clinical labs (Glucose, Magnesium, Creatinine, Phosphate, ALT, Bilirubin). [Presley, 2013]
    • The timing of administration is debated: [Lonnqvist, 2012]
      • Some recommend use after traditional therapies have failed.
      • Some recommend early use when LAST is suspected. (I’d favor this) [Presley, 2013; Lonnqvist, 2012]
      • So, order it right when you suspect it… as it’ll likely take some time to arrive from pharmacy (unless you have it in the ED).
    • Dosing is debated and whether a continuous infusion is required afterwards. [Presley, 2013]
      • The American Society of Regional Anesthesia and Pain Management recommends:
        • Lipid Emulsion 20%, 1.5 mL/kg (100 mL if > 70 kg) BOLUS over 2-3 minutes
        • Then infusion of ~0.25 mL/kg/min
        • If patient remains unstable, reBolus once or twice more (after ~ 5minutes) and double infusion rate
        • Max total dose limit = 12 mL/kg.
  • Basics Resuscitation with Adjustments
    • Fluid boluses may still be of benefit.
    • Calcium boluses also may be advantageous.
    • Sodium Bicarbonate (1-2 mEq/kg) can provide sodium load to counteract the blocked channels. [Nelsen, 2009]
    • Standard dose epinephrine may impair resuscitation success in patients with LAST; consider smaller doses. [ASRA.com]
    • Avoid Propofol as it may potentiate cardiovascular decompensation.
    • But, standard ACLS may not be enough, and that is why the Lipid Emulsion therapy is necessary to get started early!

 

Moral of the Morsel

  • First Do No Harm! Consider your medication (short vs long acting) and calculate the dose correctly.
  • Be vigilant for the subtle signs! Children are at greater risk for LAST developing so do not overlook some lip tingling or funny taste in mouth.
  • Order the Lipids early! If you believe the symptoms are due to anesthetic toxicity (whether from your actions or even from an at home exposure), start your ACLS, but get the Lipids as soon as possible (unfortunately, you can’t just squeeze the leftover donuts that are in your ED into the kid’s mouth).

 

References

Walker BJ1, Long JB, Sathyamoorthy M, Birstler J, Wolf C, Bosenberg AT, Flack SH, Krane EJ, Sethna NF, Suresh S, Taenzer AH, Polaner DM, Martin L, Anderson C, Sunder R, Adams T, Martin L, Pankovich M, Sawardekar A, Birmingham P, Marcelino R, Ramarmurthi RJ, Szmuk P, Ungar GK, Lozano S, Boretsky K, Jain R, Matuszczak M, Petersen TR, Dillow J, Power R, Nguyen K, Lee BH, Chan L, Pineda J, Hutchins J, Mendoza K, Spisak K, Shah A, DelPizzo K, Dong N, Yalamanchili V, Venable C, Williams CA, Chaudahari R, Ohkawa S, Usljebrka H, Bhalla T, Vanzillotta PP, Apiliogullari S, Franklin AD, Ando A, Pestieau SR, Wright C, Rosenbloom J, Anderson T; Pediatric Regional Anesthesia Network Investigators. Complications in Pediatric Regional Anesthesia: An Analysis of More than 100,000 Blocks from the Pediatric Regional Anesthesia Network. Anesthesiology. 2018 Jul 30. PMID: 30074928. [PubMed] [Read by QxMD]

Najafi N1, Veyckemans F, Du Maine C, van de Velde A, de Backer A, Vanderlinden K, Poelaert J. Systemic Toxicity Following the Use of 1% Ropivacaine for Pediatric Penile Nerve Block. Reg Anesth Pain Med. 2016 Jul-Aug;41(4):549-50. PMID: 27315186. [PubMed] [Read by QxMD]
Presley JD1, Chyka PA. Intravenous lipid emulsion to reverse acute drug toxicity in pediatric patients. Ann Pharmacother. 2013 May;47(5):735-43. PMID: 23613099. [PubMed] [Read by QxMD]

Lönnqvist PA1. Toxicity of local anesthetic drugs: a pediatric perspective. Paediatr Anaesth. 2012 Jan;22(1):39-43. PMID: 21672079. [PubMed] [Read by QxMD]

Nelsen J1, Holland M, Dougherty M, Bernad J, Stork C, Marraffa J. Severe central nervous system and cardiovascular toxicity in a pediatric patient after ingestion of an over-the-counter local anesthetic. Pediatr Emerg Care. 2009 Oct;25(10):670-3. PMID: 19834416. [PubMed] [Read by QxMD]

Sean M. Fox

I enjoy taking care of patients and I finding it endlessly rewarding to help train others to do the same. I trained at the Combined Emergency Medicine and Pediatrics residency program at University of Maryland, where I had the tremendous fortune of learning from world renown educators and clinicians. Now I have the unbelievable honor of working with an unbelievably gifted group of practitioners at Carolinas Medical Center. I strive every day to inspire my residents as much as they inspire me.

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2 Responses

  1. October 1, 2018

    […] EM Morsels recently reviewed Local Anesthetic Systemic Toxicity (LAST) and lipid rescue therapy in children. Considerations for selecting long vs. short-acting local anesthetics and the value of calculating […]

  2. October 1, 2018

    […] EM Morsels recently reviewed Local Anesthetic Systemic Toxicity (LAST) and lipid rescue therapy in children. Considerations for selecting long vs. short-acting local anesthetics and the value of calculating […]

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