Implementation of an Intravenous Lidocaine Guideline for Children and Adolescents with Sickle Cell Vaso-Occlusive Pain
Authors: Agbakwuru Ugochukwu , AuBuchon Jacob D , Toebe Bobi , LaBarge Anne , Di Paola Jorge , Hulbert Monica L 
Published: November 2021

Abstract
Introduction
Sickle cell disease (SCD) affects approximately 100,000 Americans.[1] Vaso-occlusive episodes (VOEs) are the leading cause of hospitalization in SCD; in 2016, out of 134,000 SCD hospitalizations, 81% included VOE. [2] Opioids are the mainstay of VOE treatment, but side effects include sedation, hyperalgesia, and dependency risk. Lidocaine, which inhibits voltage-gated sodium channels in peripheral sensory nerves, is given intravenously (IV) for postoperative pain management and holds promise for VOE treatment.[3]
At St. Louis Children's Hospital (SLCH), children admitted with VOEs receive an opioid by continuous infusion plus patient-controlled analgesia (PCA) and non-opioid adjuvants. In 2019, the Sickle Cell Disease Program and Pain Management Service jointly developed a guideline for VOE management that includes:
1. Standardized dosing of IV opioids and IV or oral NSAIDs
2. Pain management service consultation for all children age ≥10 y admitted with VOE
3. Initiation of IV lidocaine infusion (1-1.5 mg/kg/h x 48 h) within 24 h of admission for severe pain
4. Addition of non opioid adjuvants, such as muscle relaxants, topical agents, and agents for neuropathic pain
5. IV lidocaine is prescribed by the Pain Management Service. Patients are monitored for lidocaine side effects including tinnitus, perioral tingling, vital sign changes, and seizures. A 24 h serum lidocaine level is drawn to ensure levels are not supra-therapeutic.
We aimed to evaluate the implementation of this care guideline, focused on IV lidocaine as a safe, tolerable and effective adjunct to opioids for VOE treatment in children.
Methods
This retrospective cohort study reviewed records of children with SCD age ≥10 years admitted for VOE at SLCH during 2018-2020. Data collected included patient demographics, impact on pain, lidocaine levels, and reported side effects. This study was approved by the institutional review board.
Results
We identified 61 patients (31 males), median age 15.7 y (range 9-21), with 174 IV lidocaine administrations during 164 hospitalizations. Hemoglobin (Hb) SS comprised 60.7% of the cohort; 32.8% had Hb SC disease, 4.9% had Hb Sβ0 thalassemia and 1.6% had Hb Sβ+ thalassemia. IV lidocaine was started within 24 h for 78.7% (129/164) of included admissions. The mean blood lidocaine level was 2.14 mcg/ml (SD 1.23). Of the 164 admissions, 9 individuals had lidocaine levels above the limit of 4.5 mcg/ml, none had symptoms of toxicity. Few side effects were noted: lip paresthesia in 1 child (lidocaine stopped, but received in future admissions); nausea in 1 child (declined lidocaine in future admissions); pain increase in 1 teen (lidocaine was stopped). One child stopped lidocaine infusions prematurely during 2 admissions due to refusal of phlebotomy for the lidocaine level. Overall, 59 children perceived benefit of IV lidocaine and chose to receive it again during later admissions. During 10 prolonged hospitalizations, a second 48-hour lidocaine infusion was given due to patient reported benefit.
We identified falsely elevated lidocaine levels when subcutaneous lidocaine was used before phlebotomy, but no patients with high lidocaine levels experienced toxicity. We altered our response to supratherapeutic levels by pausing the lidocaine infusion, redrawing lab at a peripheral site without subcutaneous lidocaine contamination, and resuming lidocaine infusion if level was normal. Every repeated lidocaine level was within normal limits.
Discussion
In our cohort, IV lidocaine was safe, tolerable, and improved pain control. The care guideline was initiated within 24 hours for 78.7% of admissions. Mild side effects occurred in only 3 patients, highlighting safety. Future considerations include a prospective study focused on length of stay, patient-reported outcomes, opioid exposure, and factors influencing the care guideline's utilization.
References:
1. American Society of Hematology. Sickle Cell Disease. www.hematology.org/Patients/Anemia/Sickle-Cell.aspx
2.Fingar K, Owens P, et al (2019). Characteristics of Inpatient Hospital Stays Involving Sickle Cell Disease, 2000-2016. Agency for Healthcare Research and Quality. https://hcup-us.ahrq.gov/reports/statbriefs/sb251-Sickle-Cell-Disease-Stays-2016.jsp
3.Dunn L, Durieux ME, (2017). Perioperative use of intravenous lidocaine. Anesthesiology, 126(4), 729-737. https://doi.org/10.1097/aln.0000000000001527

Disclosures
Di Paola: CSL Behring: Consultancy, Honoraria. Hulbert: Pfizer: Current Employment, Current holder of individual stocks in a privately-held company; bluebird bio: Consultancy; Global Blood Therapeutics: Research Funding; Forma Therapeutics: Consultancy, Research Funding.