Presentations

Abstract

Introduction:

Lidocaine is a lipid soluble local anesthetic that blocks voltage-gated sodium channels. It prevents subsequent channel activation and interferes with membrane depolarization. Intravenous administration is generally well tolerated but excessive doses can lead to systemic toxicity. Mild lidocaine toxicity is known to cause symptoms such as numbness, tinnitus and blurred vision, and restlessness. Severe toxicity includes but is not limited to muscle twitches, seizures, CNS depression, unconsciousness, coma, hypotension, and bradycardia. While there is no proven treatment of lidocaine toxicity, intravenous lipid emulsion (ILE) is generally recommended for cases of severe toxicity.

Case Information:

81-year-old functionally independent female with past medical history significant for hypertension and frequent UTIs, weighing 65 kg, presented to an outside primary care office for dysuria and pyuria. The office administered Ceftriaxone 1 gram IV for presumed UTI. During preparation of the medication, powdered Ceftriaxone was inadvertently dissolved with 50 mL of lidocaine 1% instead of normal saline, yielding ~7.7 mg/kg, above the toxic dose of 4.5 mg/kg. After initiation of Ceftriaxone, the patient experienced witnessed tonic- clonic seizures, was apneic, and was briefly pulseless. CPR was performed with return of spontaneous circulation. Upon arrival paramedics administered benzodiazepines and Rocuronium, and intubated the patient.

In the ED, the patient was hypertensive with BP 211/103. She was started on propofol and midazolam for sedation and seizure abortion. ABG was significant for pH 7.046 and PaCO2 of 76.1. CT chest showed multifocal patchy groundglass opacities concerning for edema or multifocal infiltrates. EKG on admission notable for new pre-atrial complexes and delayed R-wave transition. CBC notable for WBC 15.4, Hgb 11.2, 81% Neutrophils. CMP was notable for Potassium of 3.4, bicarbonate of 18, anion gap of 21, and lactic acid was 4.0.

Upon admission to the ICU, patient was given loading dose Keppra, midazolam was continued, propofol was stopped, and Ceribell EEG was performed. EEG showed encephalopathic but no epileptiform changes. TSH was 2.39. Urinalysis was notable for positive leukocyte esterase, nitrites, urine bacteria, and WBC 51-100. Soon after arrival, patient developed shock with BP of 76/48. Decision was made to initiate LIE. An initial dose of 1.5ml/kg was given over 3 minutes, followed by a 0.25ml/kg/min dose give for 30 minutes. Thirty to sixty minutes after completion of the doses, patient had profound neurological improvement. Treatment was complicated by lipase elevation to 2088 (U/L), triglyceride elevation 1525 mg/mL, and blood draw difficulties due to increased blood viscosity. Blood draw difficulties and hypertriglyceridemia resolved with 24 hours. Lipase elevation returned to normal after 48 hours. Serum lidocaine level was 1.0 mg/dL and < 1.0 mg/dL approximately 9 hours and 23 hours after infusion, respectively. Patient was extubated after 24 hours with full neurological recovery.

Discussion:

Local anesthetic toxicity, including lidocaine, can present a clinician with complex decision making. While all have a hydrophilic group, the presence of either an ester or amide link on the intermediary chain dictates its metabolism either via plasma cholinesterases or hepatic oxidation, which could lead to worsening toxicity in patients with cirrhosis. While there is no proven antidote to lidocaine toxicity, there are ample human case reports showing the beneficial effects of ILE treatment in lidocaine induced cardiac arrest. The exact mechanism of action is still unknown. Rat and human models have shown ILE creates a "lipid sink" phenomenon, which decreased serum concentrations of lidocaine but rarely showed a benefit in primary symptom outcomes. Rat models have also shown ILE has direct end organ benefit by actively removing the toxin from the organ tissue and improve post-ischemic cardiac reperfusion via its effects on glycogen synthase kinase 3β and mitochondrial permeability.

While ILE may be an effective therapy for lidocaine toxicity, there can be significant side effects, including pancreatitis, hyperviscosity, and hypertriglyceridemia. The combination of major side effects and proven therapeutic benefit from trials, the use of ILE should be reserved for patients with significant neurological findings or cardiovascular collapse in patients with lidocaine toxicity.

Conclusion:

ILE for severe lidocaine toxicity can be an effective tool. While the exact mechanism is unknown, studies suggest it may have a multi- modal effect. The use of ILE should be reserved for severe cases as the side effects in themselves can lead to significant secondary complications.