Society for Pediatric Pain Medicine
Better Care for Children in Pain

Correct Answer: B. Alpha-1 antiglobulin


Hypoproteinemia reduces patients’ capacity for protein-binding of local anesthetics and other medications. Local anesthetics primarily bind to albumin (high capacity for binding with low affinity) and α1-acid glycoprotein (low capacity for binding with high affinity). Various local anesthetics exhibit protein binding to different extents, which influences duration of action. For example, lidocaine is approximately 65% protein-bound, whereas ropivacaine is about 95% bound to protein in healthy patients. Since the free fraction (not protein-bound) of the drug contributes to clinical effect as well as toxicity, factors that reduce protein binding have a greater effect on highly protein-bound local anesthetics. Furthermore, metabolism of amide local anesthetics by hepatic cytochrome P450 enzymes are reduced in our youngest patients due to limited hepatic function (and therefore protein production) in the first months of life. To a lesser degree, immature renal development also contributes to poor amide metabolism. Collectively, these physiologic and pharmacologic properties make the risk of toxicity from amide local anesthetics significantly higher in the neonate and infant populations. This makes ester local anesthetic agents the preferred choice for neonates and young infants receiving local anesthetics.


References:


1. Neal JM, Barrington MJ, Fettiplace MR et al. The third american society of regional anesthesia and pain medicine practice advisory on local anesthetic systemic toxicity: Executive summary 2017. Reg Anesth Pain Med 2018;43:113-123.


2. Suresh S, Ecoffey C, Bosenberg A, Lonnqvist PA, de Oliveira GS Jr, de Leon Casasola O, de Andrés J, Ivani G. The European Society of Regional Anaesthesia and Pain Therapy/American Society of Regional Anesthesia and Pain Medicine Recommendations on Local Anesthetics and Adjuvants Dosage in Pediatric Regional Anesthesia. Reg Anesth Pain Med. 2018 Feb;43(2):211-216.


3. Veneziano G, Tobias JD. Chloroprocaine for epidural anesthesia in infants and children. Paediatr Anaesth. 2017 Jun;27(6):581-590. doi: 10.1111/pan.13134. Epub 2017 Mar 21.

The correct answer is - C : Increase FiO2 to 100% and stop volatile anesthetic


In this LAST scenario, recognition of the problem occurred quickly and PALS was initiated. The patient already has a secured airway. While many of the above answers would all be happening simultaneously, the next step should be to remove the volatile anesthetic which will contribute to the hypotension which is caused by the intravascular injection of local anesthesia. Before lipid infusion was used, there was only supportive therapy until the local anesthestic could be metabolized.


The definitive treatment of LAST is Intralipid which creates a lipid “sink” or gradient to draw bupivacaine out of the tissue into lipid micelles so that the cardiac and neurological pharmacodynamic effects are minimized. The initial treatment is 1.5 ml/kg bolus over one minute followed by the initiation of an infusion of lipid at 0.25 mL/kg/min. If after 5 min, there is no change in the patient status, then another bolus of 1.5 mL/kg may be given and the infusion should be increased to 0.5 mL/kg/min. The lipid infusion should last for 10 min after return of hemodynamic stability. PediCrisis notes that the maximum intralipid volume is 10 mL/kg over the first 30 minutes.


Epinephrine is a very important component of standard PALS protocols. However, in LAST, epinephrine decrease lipid resuscitation and should be used in small bolus doses.


References:


1. Jones Oguh, S; Kraemer, F. Pediatric Local Anesthetic Systemic Toxicity. SPPM News. Spring 2022.


2. Pedi Crisis application on iOS (Apple Inc., Cupertino, CA)


3. Weinberg, G., Rupnik, B., Aggarwal, N., Fettiplace, M., & Gitman, M. (2020, February). APSF Newsletter. Retrieved June 30, 2022, from https://www.apsf.org/article/local-anesthetic-systemic-toxicity-last-revisited-a-paradigm-in-evolution/.