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Republished: Infant with status epilepticus secondary to systemic lidocaine toxicity from topical application
  1. Erica Walters1,
  2. Victoria Wurster Ovalle2,
  3. Shan Yin34,
  4. Timothy Dribin24
  1. 1 Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA
  2. 2 Emergency Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA
  3. 3 Drug and Poison Information Center, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA
  4. 4 Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
  1. Correspondence to Dr Timothy Dribin; timothy.dribin{at}cchmc.org

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In conjunction with BMJ Case Reports, DTB will feature occasional drug-related cases that are likely to be of interest to readers. These will include cases that involve recently marketed drugs for which there is limited knowledge of adverse effects and cases that highlight unusual reactions to drugs that have been marketed for several years.

Summary

A previously healthy 11-month-old infant presented to the emergency department in status epilepticus. There was no clear trigger of her seizure activity which resolved with benzodiazepines and fosphenytoin. On further review, her parents disclosed that she had been prescribed topical 4% lidocaine cream for a groin rash and was ultimately diagnosed with lidocaine toxicity in the emergency department. She was monitored in the intensive care unit without cardiovascular abnormalities or recurrence of seizure activity. Emergency medicine providers must maintain a broader differential of status epileptics and be able to recognise and manage potential complications from systemic lidocaine toxicity.

Background

Status epilepticus is a common presentation to paediatric emergency departments with the potential for significant morbidity and mortality, including the need for intubation, intensive care unit (ICU) admission, persistent neurological deficits and mortality in 3%–5% of children.1 Emergency department providers are responsible for maintaining a broad differential of undifferentiated status epilepticus (eg, infections, trauma, electrolyte derangements, epilepsy, inborn errors of metabolism, toxins/ingestions) as well as evaluating and treating reversible causes.2 Although systemic lidocaine toxicity is a known complication of local or parental administration, it is less commonly associated with topical application, especially among infants.3–6 We present a case of an infant who developed status epilepticus secondary to systemic lidocaine toxicity from local application to treat a diaper rash.

Case presentation

A previously healthy 11-month-old infant presented to the emergency department for first time seizures in status epilepticus. Prior to presentation, she had been well other than a diaper rash for which the family sought treatment from her primary care physician as well as multiple local emergency departments. The rash did not improve despite over-the-counter diaper creams, topical nystatin and oral fluconazole. On the night of presentation, she developed generalised tonic-clonic seizures prompting presentation to our emergency department.

On arrival to the resuscitation room, the family denied history of fever, trauma, medication or other oral ingestions, recent illness, prior seizure activity or a family history of epilepsy. Her vitals were as follows: weight, 8.5 kg; temperature, 37.5°C; pulse, 141; respiratory rate, 33; blood pressure, 117/83; and oxygen saturation, 97% on room air. On initial physical examination, she was unresponsive with generalised tonic-clonic seizure activity without focal features. The remainder of her physical examination was normal except for an erythematous and macerated diaper rash.

Investigations

Initial laboratory studies demonstrated normal venous blood gas, lactate and electrolytes. Complete blood cell count was significant for an elevated white cell count of 19.6×109/L.

Differential diagnosis

Given the duration and unclear aetiology of her seizure activity, a non-contrast CT scan of the head was obtained (to rule out trauma, mass lesions and other aetiologies of new onset seizure activity) which was normal. Although the patient had no fever, blood cultures were obtained with plan to perform lumbar puncture to exclude infectious aetiologies. Given the potential for toxin exposure or medication overdose as a cause of the seizure activity, the family was again questioned about medications exposures. This prompted the family to disclose that on the day of presentation she was prescribed topical 4% lidocaine cream which they applied copiously to the diaper rash multiple times during the day.

Treatment

Clinical seizure activity resolved after treatment with two doses of lorazepam and a loading dose of fosphenytoin; total seizure duration was approximately 30 min during which she maintained spontaneous ventilation and normal haemodynamics.

Outcome and follow-up

Owing to the risk of systemic lidocaine toxicity as the aetiology of her seizure activity and to evaluate for other complications associated with lidocaine toxicity, we obtained a serum lidocaine level, venous co-oximetry to evaluate for methaemoglobinaemia and an ECG to assess for cardiac toxicity (eg, arrhythmias). The initial lidocaine level was 9.3 μg/mL (upper limit of normal therapeutic range is 5.0 μg/mL); she had normal carboxyhaemoglobin and methaemoglobin levels and an ECG was sinus rhythm with normal intervals. We avoided performing a lumbar puncture given lidocaine toxicity was the presumed aetiology of her seizures. There is some evidence that performing emergent electroencephalogram (EEG) may provide meaningful clinical information that may influence patient care, particularly in patients with ongoing seizures or status epilepticus.7 However, an EEG was not performed on our patient because this was her first provoked seizure, her seizures resolved while in the emergency department, and it would not alter her care or disposition.

Due to the risk of developing life-threatening arrhythmias from systemic lidocaine toxicity, she was admitted to the ICU on telemetry. The toxicologist advised trending lidocaine levels which returned to reference range after approximately 10 hours (6.4 and 2.5 μg/mL by 3.5 and 10 hours, respectively). She had an uneventful ICU course without arrhythmias or seizure activity and returned to her baseline neurological status. At the time of hospital discharge, the family was instructed to discontinue the lidocaine cream.

Discussion

Lidocaine is a local anaesthetic commonly used as an infiltrative or topical analgesic for paediatric procedures such as lumbar punctures and laceration repairs. It is important for clinicians to be knowledgeable of lidocaine dosing and adverse reactions associated with systemic toxicity. While other cases of systemic anaesthetic toxicity from topical exposure have been reported, our case is unique because our patient was an infant who developed systemic toxicity from topical application for treatment of a common paediatric condition.3–6

In children, topical 4% lidocaine cream without epinephrine should be applied as a thin film to the affected area no more than two to three times daily as needed; the maximum dose is 4.5 mg/kg (0.0045 g/kg) not to exceed 300 mg per dose. These dosing instructions, specifically what constitutes a thin film, highlight the small volume of 4% lidocaine cream required to achieve the maximal dose and the low margin for error when applying topical lidocaine especially when the involved area is large.8 Compared with intact skin, mucous membranes provide minimal barrier penetration, thereby lowering the drug concentration required to achieve effective analgesia.9 Thus, particular attention must be made when applying local anaesthetics to mucous membranes. Lidocaine toxicity occurs when plasma concentrations exceed 5 μg/mL, with more serious symptoms at higher concentrations.10 In general, central nervous system effects are seen first; cardiovascular involvement may occur simultaneously or be delayed.11 At plasma concentrations of 5 μg/mL, symptoms may be subtle especially in preverbal children. Early symptoms include perioral numbness, metallic taste, tinnitus and mild drowsiness or agitation. At higher concentrations, symptoms include visual changes, muscle twitching followed by convulsions, coma and respiratory depression.11–14

Cardiovascular effects of lidocaine toxicity include hypertension, tachycardia, arrhythmias, heart failure and cardiac arrest.9 11–14 Thus, patients with suspected or confirmed lidocaine toxicity warrant close haemodynamic monitoring and an ECG.14 Although methaemoglobinaemia is more commonly associated with application of prilocaine and benzocaine, it also occurs with lidocaine toxicity.15 16 Symptoms may be vague and range from mild to severe including unexplained cyanosis, anxiety, fatigue, tachycardia, arrhythmias, seizures and coma.17

Management of local anaesthetic systemic toxicity is primarily supportive and includes avoiding additional anaesthetic exposure, cardiopulmonary resuscitation and treating seizures with benzodiazepines. Among patients with systemic lidocaine toxicity, care should be made to reduce dosing of vasoactive medications (eg, epinephrine), medications that impair cardiac contractility (eg, beta blockers, calcium channel blockers) and Class I antiarrhythmics, which may potentiate cardiovascular toxicity.14 18 The American Society of Regional Anesthesia and Pain Medicine and the American College of Medical Toxicology recommend considering intravenous lipid emulsion (ILE) therapy for patients with life-threatening overdoses and cardiovascular collapse.14 19 Although the precise mechanism of action is unclear, ILE may accelerate drug elimination, interfere with drug binding to sodium channels and improve cardiac contractility.20–22 While ILE may help reverse cardiovascular and neurological features in some cases of local anaesthetic toxicity, there is currently no convincing evidence supporting its use in haemodynamically stable patients, and thus was not indicated in our patient.23

Treatment of methaemoglobinaemia includes supportive care and administration of methylene blue, and in severe or refractory cases, packed red blood cell or exchange transfusions. Ideally, patients should be evaluated for glucose-6-phosphate dehydrogenase deficiency before receiving methylene blue as administration may precipitate haemolysis in these patients.16

Patient’s perspective

Patient’s parents: the entire experience was incredibly stressful for our entire family. We were not aware that a topical medication could lead to potentially life threatening complications. We are extremely grateful for the care we received during this terrifying experience and are happy to report that our daughter is doing very well.

Learning points

  • Status epilepticus is a common presentation to paediatric emergency departments; clinicians should maintain a broad differential and a take a thorough medication history as medication overdoses are an often unrecognised aetiology of seizure activity.

  • Our case reinforces the importance of correctly dosing topical anaesthetics, especially among young children, and how to recognise and treat complications from systemic toxicity.

  • Although management of lidocaine toxicity is primarily supportive, patients should be observed in settings equipped to recognise and treat neurological and cardiovascular complications.

References

Footnotes

  • Contributors EW, VWO and TD contributed to conception and design of manuscript. EW wrote the manuscript with critical feedback from TD, VWO and SY. All authors gave final approval and agree to be accountable for all aspects of work ensuring integrity and accuracy.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Patient consent for publication Parental/guardian consent obtained.

  • Provenance and peer review Not commissioned; externally peer reviewed.