In a recent PAAD “error traps in pediatric regional anesthesia”, we commented on the article’s failure to discuss the prevention and treatment of local anesthetic systemic toxicity (LAST). Indeed, we frankly were surprised by this omission because in our personal experience, LAST is THE most important error and potential for morbidity when using local anesthetics. Fortuitously, we found this recent article in Regional Anesthesia and Pain Medicine, a journal we recently added to the PAAD reading list.
Original article
Ramesh AS, Boretsky K. Local anesthetic systemic toxicity in children: a review of recent case reports and current literature. Reg Anesth Pain Med 2021;46: 909-914. doi: 10.1136/rapm-2021-102529. PMID: 34099573
Infographic
Gupta RK, Schwenk ES. Local anesthetic systemic toxicity in children: a review of recent case reports and current literature – an infographic. Reg Anesth Pain Med 2021;46: 915. doi: 10.1136/rapm-2021-102993. PMID: 34230193
Local anesthetic systemic toxicity (LAST) is a long recognized potential complication of regional anesthesia, which has long presented a conundrum to anesthesiologists regarding prevention, recognition, and treatment. Prior to the discovery of the surprising efficacy of lipid emulsion administration for the treatment of LAST, a wide range of less effective treatments were used, including benzodiazepines, epinephrine, and anticonvulsants (especially phenytoin), with a resultant high incidence of mortality, especially in the obstetric population after bolus epidural administration of 0.75% bupivacaine. In the early 2000’s the effectiveness of lipid emulsion was demonstrated in animals. The first reports of successful treatment in humans and subsequent guidelines were published in 2010. Since then, ASRA has published updated guidance based on the evolution of case reports and knowledge of the mechanism of action of lipid rescue, with the most recent 2017 review published in 2018. (1)
Cases continue to be reported both individually and as case series, often with successful rescue. Although some of these case series have included patients under 18 years of age, there had been no comprehensive analysis of pediatric cases of the occurrence and treatment of LAST. The Pediatric Regional Anesthesia Network (PRAN) noted 7 cases of LAST in more than 100,000 regional blocks in its analysis published in 2018, an incidence of 0.8 per 1000 which is lower than that reported in adults (0.27 per 1000).(1) These reports have the limitation of being a compilation of voluntarily reported cases and include only those in which the local anesthetic was administered in an anesthesia setting.
For this reason, Ramesh and Boretsky sought to review reported cases of LAST in children < 17 years of age in the 5 year period 2014-2019, comparable to the adult case review by Gitman and Barrington (2). In addition to the literature review, the authors captured pediatric cases reported to the LAST registry – lipidrescue.org. This search resulted in 31 reviewed cases.
The authors documented the patient age and weight (if documented), drug administered (type and amount), specialty of administering provider, practice setting, site of administration, level of consciousness of patient (general anesthesia, sedation or awake), timing of onset of symptoms, and technique used for nerve localization (e.g. landmark, ultrasound, or fluoroscopy).
None of the 31 children suffered permanent sequelae or death, in contrast to reported 4.3-10% mortality in adults. Of the reported cases, neonates and infants predominated (71%), which is similar to the PRAN cases in which infants <12 months comprised 22.8% of the blocks administered, but 71% of the LAST cases. The most common block sites associated with LAST were penile (37%), caudal (26%) and local infiltration (13%). Of the provider types, surgeons and others (including dentists), more often administered the recommended maximum dose while anesthesiologists more often administered less than the recommended maximum dose. The authors point out that the maximum allowable dose should be regarded as a hard stop upper limit NOT a target dose to be administered! Further, the dose administered should be the minimum effective dose (for both concentration and volume). The authors point out that the maximum allowable dose can be up to 5 times the minimum effective dose.
With regard to timing, LAST occurred within 5 min of bolus administration in 81% of cases, probably related to inadvertent intravascular injection, indicating that preventive measures should include “incremental injection, frequent aspiration, utilization of an intravascular marker with attention paid to T-wave morphology, and use of ultrasound guidance.” Only 1 of case (3%) occurred in the setting of continuous infusion – “an infant with hepatic compromise with bupivacaine infusion running at the maximum allowable dose for 3 days”. This is consistent with what is know about the risk of local anesthetic accumulation due to immature/impaired metabolic (hepatic metabolism and renal clearance) and pharmacodynamic (reduced alpha-1 acid glycoprotein levels) in young infants and patients with hepatic impairment. Indeed, this is why some advocate for the use of chloroprocaine or lidocaine instead of bupivacaine in newborn local anesthetic infusions. (Chloroprocaine is an ester and should be metabolized quickly. Lidocaine is an amide, but unlike bupivacaine, blood levels are easily obtainable in any hospital laboratory and can be used to guide dosing.)
Treatment included lipid emulsion in 42% of cases, with 1/3 of cases resolving rapidly with only supportive therapy (fluids and airway support). Sixty seven percent of the 9 children who had cardiovascular collapse received lipid emulsion within 10 min of onset of LAST, compared to delay in lipid administration until after CPR was ineffective reported by PRAN investigators in 2013 (2).
The authors provide a useful review of the risks, prevention, diagnosis and treatment of LAST, drawing our attention to the possibility of this serious event. As we noted last week, anesthesiologists should be alert to the risk of the occurrence of last, undertake measures to minimize its likelihood, and be aware of the effective treatment which should be available and employed promptly. In addition to last week’s PAAD recommendation to download the Society for Pediatric Anesthesia’s PEDI-CRISIS v 2 app, it is essential that you are aware of where the lipid emulsion is stored in your practice setting and how to access it. Another mobile resource for calculating safe local anesthetic doses (including in situations in which multiple local anesthetics are mixed) is SafeLocal from Johns Hopkins which is available in the App Store. This resource allows you to enter the local anesthetic (with or without epinephrine), the patient weight and comorbidities including age < 4 months, although it does not distinguish between routes of administration.
PS: (from Myron): It is said of (Julius) Caesar that his “drills were bloodless battles and his battles were bloody drills”. I would urge all of you when doing your next regional anesthetic, to pretend that you had evidence of an intravascular injection and open the PediCrisis app to go through the many steps in treatment. The app is a fantastic learning, teaching and memory tool and can and should be used BEFORE a crisis occurs. To underline this point, in the treatment of LAST there is, what I think, is an unusual epinephrine dose. Look it up today. I’ll reveal the dose in a forthcoming PAAD. MY
References
1. Neal JM, Barrington MJ, Fettiplace MR, Gitman M, Memstoudis SG, Morwald EE, Rubin DS, Weinberg G. The third American Society of Regional Anethesia and Pain Medicine practice advisory on local anesthetic systemic toxicity. Reg Anesth Pain Med 2018;43: 113-23.
2. Gitman M, Barrington MJ. Local anesthetic systemic toxicity: a review of recent case reports and registries. Reg Anesth Pain Med 2018;43: 124-30.
3. Taenzer AH, Walker BJ, Bosenberg AT, Martin L, Suresh S, Polaner DM, Wolf C, Krane EJ. Asleep versus awake: does it matter? Pediatric regional block complications by patient state: a report from the pediatric regional anesthesia network. Reg Anesth Pain Med 2014;39: 279-83.
Local anesthetic systemic toxicity (LAST) in children
Wonderful review! Thanks for sharing these articles. One additional thought: Should we work with 503b compounding facilities (these companies who deliver our prefilled syringes with a long shelf life) to make 20 or 30ml intralipid rescue syringes for pediatric use. That would be a potential huge time saver in a crisis….