Clinical Pearl 79: Nebulized Lidocaine

By: Katherine Tokarczyk, MD

      Michael Carr, M.D.

Lidocaine is well known to the medical community as a first line local anesthetic and cardiac antiarrhythmic agent. It acts by blocking voltage gated sodium channels in neurons (pain receptors) and in cardiac cells. In recent years its other implications have emerged into common practice for various clinicians. It has been used in the past for bronchoscopy to suppress coughing in the peri-procedural period. Perhaps more relevant to the acute care clinician, nebulized lidocaine can also be used to suppress retractable cough in patients with reactive airway disease such as asthma or COPD. Can this be used in every day practice for patients with asthma and intractable cough?

Lidocaine has recently been shown to be beneficial in asthma therapy. It can prevent eosinophilic inflammation, over production of mucus, and peri-bronchial fibrosis. Studies have recognized lidocaine as a steroid-sparing agent it has been shown to decreased airway hyperactivity.

Lidocaine inhibits conduction of nerve impulses by decreasing membrane permeability to sodium resulting increased the threshold for excitation and diminishing progression of membrane depolarization. As a cough suppressant, it thought to inhibit conduction of afferent nerve impulses and will therefore suppress the cough reflex induced by mechanical and chemical stimuli. It also prevents eosinophil activation by cytokines and thus damage to epithelial and smooth muscle cells.

What about Lidocaine toxicity? This is a concern when serum levels of lidocaine are over 5mcg/L.  Symptoms include lighthheadness, tremors, hallucinations, seizures, arrhythmias, paresthesia, and respiratory arrest.  One should use caution when giving this medication to patients with hepatic disease due to decreased rates of drug metabolism and elimination rates.  A safe range of nebulized lidocaine is100-200mg per dose. Doses as high as, 600mg have been used in young healthy patients, however.  Serum levels of greater than 1 mcg/mL are not reached until 300 to 400 mg is administered to the airway, either by means of direct instillation (i.e. down an ET tube) or by nebulization.

Dosing:

Adults: Dose up to 3mg/kg/dose (for 70kg adult, 3mg/kg is 210 mg)

If using 2% (20mg/mL) Lidocaine, 10 mL is equal to 200 mg. Dilute in 5mL normal saline Prior to nebulization.

If using 4% (40mg/mL) Lidocaine, 5mL is equal to 200mg. Dilute in 10 mL normal saline prior to nebulization.

Adults can receive 4% Lidocaine 3ml in normal saline 3-4x/day

Children: Dose up to 2.4 mg/kg/dose. Only Lidocaine 2% (20 mg/mL) should be used in children.

Children can receive 0.8mg/kg/dose to 2.5 mg/kg/dose in NS 3-4 x/day

The Evidence

Hunt et al, in a randomized, placed-controlled study in patients with mild to moderate asthma (50 people), 25 received lidocaine and 25, placebo. Inclusion criteria for the study required each subject to have prebronchodilator FEV1 64%-125%, and treatment with daily-inhaled glucocorticoids and bronchodilator for at least two months. Each subject used peak flow values and took their medication for two weeks. Everyone inhaled either nebulized saline or lidocaine 4% 100mg, four times per day. They reduced their inhaled glucocorticoids dosage by half each week for three weeks and stopped by week four. They continued nebulized treatment for total eight weeks with their bronchodilators. They recorded peak flow in the morning and at bedtime, using a scoring sheet to report their symptoms. Ultimately, those treated with 2.5 mL of 4% Lidocaine (100mg) 4 times daily decreased their inhaled glucocorticoid dosage by half each week. Also when placebo was compared to lidocaine for eight weeks, asthma severity decreased in the lidocaine group as measured by FEV1, night-time awakening, overall symptoms, bronchodilator use and blood eosinophil blood concentration (all P values  <0.05).

A literature search using PubMed, international pharmaceutical abstracts and Cochrane Library evaluating the use of nebulized lidocaine in intractable cough and asthma yielded seven studies evaluating nebulized lidocaine for intractable cough. Efficacy was reported with doses 10-400 mg. One case series of nebulized lidocaine 1 to 4% every 4-6 hours with albuterol produced relief of cough in 21 patients with obstructive, restrictive or infective airway disease. In a single blinded clinical trial, 127 patients with cough secondary to COPD compared nebulized lidocaine 1mg/kg and terbutaline 5mg for cough suppression.  Data was compiled by filling out a questionnaire. The results showed improvements in cough severity compared to baseline assessments, but they were not significant (P=0.4).

A review of five different clinical trials showed varying results of improvement in PTFs and steroid-sparing effects. One study (N= 99) nebulized lidocaine 40 mg twice daily with steroid-naïve patients with mild-moderate asthma.  They measured the change from baseline FEV1 after 12 weeks of treatment. The results overall didn’t show improvement in PFTs in FEV1%.  The other four studies, however, showed significant improvement in baseline PFTs. The studies included in this review had limitations, however, such as small sample size, design flaws, and inconsistencies in adjunctive therapies.

Although nebulized lidocaine is not first-line therapy for in intractable cough and asthma, it does provide an alternative treatment option in patients who cannot tolerate or are unresponsive to other treatments.  Keep in mind, however that appropriate monitoring precautions should be used to ensure patient safety.

References:

1) Hunt LW, Frigas E, Butterfield JH, et al. J Treatment of asthma with nebulized lidocaine: a randomized, placebo-controlled study. Allergy Clin Immunol. 2004;113:853-859.

2) Decco ML¹, Neeno TA, Hunt LW, et al, Nebulized lidocaine in the treatment of severe asthma in children: a pilot study. Annals of Alleregy, Asthma Immunology 82; 1999.

3) Magda F. Serra, Ph.D., Edna A. et al. Nebulized Lidocaine prevents Airway inflammation, peribronchial fibrosis and mucus production in a Murine model of asthma. Anesthesiology 2012; 117: 580-591.

4) Rachel M Slaton, Rachel H Thomas, Joseph Wallace Mbathi  Evidence for Therapeutic Uses of Nebulized Lidocaine in the Treatment of Intractable Cough and Asthma. The Annals of Pharmacotherapy 2013;47

5) Hunt LW, Swedlund HA, Gleich GJ. Effect of nebulized lidocaine on severe glucocorticoid-dependent asthma., Mayo Clin Proc 1996;71: 361-368.