Is there any data in term of clinical trials that show benefit of using nebulized lidocaine for treatment of refractory cough, or cough post-tracheostomy?

Comment by InpharmD Researcher

Pooled data from clinical trials provide conflicting evidence regarding the use of nebulized lidocaine for refractory or intractable cough. Overall, many studies suggest no significant advantage, though outcomes appear to vary by clinical context. For instance, literature in hospice populations reports that nebulized lidocaine can provide rapid cough suppression in a substantial proportion of patients, whereas studies in patients undergoing bronchoscopy found no difference between nebulized and non-nebulized lidocaine in physician- or patient-reported cough scores. Published evidence specific to post-tracheostomy cough management with nebulized lidocaine is sparse, although one small postoperative study reported favorable outcomes.

PubMed

Background

A 2025 review undertook a comprehensive evaluation of the efficacy and safety of nebulized lidocaine for managing intractable cough in hospice care settings. The study encompassed a systematic literature search spanning from 1973 to 2023, examining 265 studies and selecting 58 that met rigorous inclusion criteria. The principal findings indicated that nebulized lidocaine, administered in concentrations of 1–4%, provided rapid cough suppression within 15 minutes in 70% of cancer patients, with effects lasting up to four hours. Reported side effects were generally mild and transient, such as oropharyngeal numbness and a bitter taste. However, bronchoconstriction was noted in 25% of asthmatic patients, necessitating bronchodilator intervention. Notably, lidocaine was effective in reducing opioid usage and enhancing patient comfort in 80% of cases. Despite its efficacy, variability in results was observed, particularly in patients with severe chronic obstructive pulmonary disease (COPD), suggesting limited benefits in those with acute respiratory failure. The narrative synthesis revealed differential responses in disease-specific contexts. For instance, while lidocaine was beneficial in mild-to-moderate asthma cases, it posed risks in severe cases due to potential bronchoconstriction. These findings underscore the critical need for personalized treatment approaches based on individual disease severity and patient phenotype. The review also highlighted methodological challenges, such as inconsistent dosing regimens and small sample sizes, impeding robust meta-analysis. Consequently, it advocates for future research focusing on standardized dosing, long-term safety evaluations, and the inclusion of randomized controlled trials to substantiate the therapeutic utility of nebulized lidocaine in diverse hospice populations. Additionally, the authors emphasize the importance of adopting preservative-free lidocaine formulations to mitigate airway irritation risks, particularly in sensitive patients. [1]

An older comprehensive review from 2013 synthesized efficacy and safety data concerning nebulized lidocaine use in intractable cough and asthma.This review incorporated 17 studies, comprising seven investigations on intractable cough, which revealed favorable outcomes at doses ranging from 10 mg to 400 mg. In contrast, the five clinical trials addressing asthma presented inconsistent results regarding the improvement of pulmonary functions and glucocorticoid-sparing effects. Specific attention was given to initial bronchoconstriction in subjects with baseline bronchial hyperreactivity, underscoring the need for cautious interpretation. The analysis, while acknowledging the potential therapeutic role of nebulized lidocaine, highlights significant study limitations, including small sample sizes and methodological inconsistencies. Despite the varied outcomes, nebulized lidocaine may serve as an alternative for patients with intractable cough unresponsive to conventional treatments. The tolerability profile is promising, though instances of bronchoconstriction warrant careful monitoring. The findings propose that while not a first-line therapy, nebulized lidocaine emerges as a viable option under certain clinical scenarios demanding individualized approaches. [2]

A 2023 meta-analysis aimed to assess the superiority of airway nerve blocks (ANBs) versus airway anesthesia without nerve blocks for awake tracheal intubation (ATI), including local anesthesia and local anesthetic nebulization. A total of 14 randomized controlled trials (RCTs) with 658 participants (ANBs group: 328 participants; No-ANBs group: 330) were included. Topical anesthesia included 2% atomized lidocaine, 2% nebulized lidocaine, 4% lidocaine by ultrasonic nebulizer, 4% lidocaine by jet nebulization, or lidocaine spray. The meta-analysis revealed that ANBs resulted in a reduced intubation time compared to no-ANBs (standardized mean difference [SMD] -2.57, 95% confidence interval [CI] −3.59 to −1.56; p <0.00001, I2 = 96%). The pooled analysis indicated that ANBs resulted in a greater absence of reaction to the placement of flexible score and tracheal tube compared to no-ANBs (77.18% versus 6.62%, relative risk [RR] 9.87; 95% CI 4.10 to 23.75, p <0.00001, I2 = 47%). The cough or gag reflex during intubation was also significantly lowered in the ANBs group than in the no-ANBs group (25.29% versus 72%, RR 0.35; 95% CI 0.27 to 0.46; p <0.00001; I2 = 17%). The satisfaction of patients was notably higher in the ANBs group compared to the no-ANBs group (68.22% versus 36.15%, RR 1.88; 95% CI 1.05 to 3.34; p = 0.03; I2 = 78%). Additionally, the overall complications was significantly lower in the ANBs group than in the no-ANBs group (15.50% versus 53.13%, RR 0.29; 95% CI 0.19 to 0.45; p <0.00001; I2 = 9%). The findings suggest that ANBs offer improved airway anesthesia quality for ATI, characterized by a shorter intubation time, enhanced intubation conditions with higher tolerance to the placement of the flexible score and tracheal tube, reduced cough or gag reflex during intubation, higher levels of excellent patient satisfaction, and a decrease in overall complication. [3]

A 2020 meta-analysis sought to identify differences in outcomes with or without nebulized lidocaine when used in bronchoscopy. Seven RCTs (N= 1,366) were included, with doses of nebulized lidocaine ranging from 60 mg to 300 mg (mean total dose 235 mg). Nebulized lidocaine, when compared to no nebulized lidocaine, did not amount to a difference in physician-reported cough score (SMD -0.09; 95% CI -0.7 to 0.51; I^2= 95%; p= 0.76). Subgroup analyses showed that in studies that only used local anesthesia, no nebulized lidocaine showed better cough scores (SMD 0.32; 95% CI 0.12 to 0.51; I^2= 77%; p= 0.001), however this difference was not statistically significant when moderate sedation was used. Additionally, for patient-reported cough scores no difference was seen between nebulized lidocaine and no nebulized lidocaine groups (SMD -0.12; 95% CI -0.82 to 0.59; I^2= 95%; p= 0.75). No differences were seen between groups for operator’s satisfaction score, ease or procedure, patient’s discomfort, and unwillingness to repeat the procedure. The additional nebulized lidocaine groups required higher doses of lidocaine in comparison to the no nebulization group (MD 86.9; 95% CI 34.83 to 138.96; I^2= 100%; p= 0.001). In a subgroup analysis of studies which used moderate sedation, the additional nebulized lidocaine group showed a decrease in midazolam dose and duration of procedure. Of note, this analysis is limited by differing scales used among studies to measure cough and significant heterogeneity between studies. Overall, the authors concluded that the additional administration of nebulized lidocaine did not have a significant effect on cough symptoms. [4]

A 2023 randomized, double-blind, double-dummy, placebo-controlled, 3-way crossover study was conducted to evaluate the efficacy of nebulized lidocaine versus lidocaine throat spray in patients with refractory chronic cough (RCC). This investigation involved 26 participants, predominantly female, with a mean age of 53.5 years. The study's primary outcome focused on cough frequency over a 10-hour period post-treatment, while secondary outcomes included visual analog scale scores for urge-to-cough and cough severity. An exploratory component also examined hourly cough rates up to 5 hours following treatment administration. The findings revealed that lidocaine throat spray significantly reduced cough frequency compared to placebo, with a notable impact within the first hour post-administration (31.7 coughs/h vs. 74.2 coughs/h; P = 0.004). Conversely, nebulized lidocaine did not exhibit a significant difference in cough frequency over the full 10-hour observation period. Both delivery methods, however, led to significant improvements in urge-to-cough and cough severity scores when compared with placebo (P <.05). No serious adverse events were linked to lidocaine use, indicating its safety profile. The results underline the potential of voltage-gated sodium channel inhibitors, specifically lidocaine throat spray, as promising therapeutic interventions for RCC, especially given their efficacy in reducing immediate cough frequency. [5]

References: [1] Pan J, Khan AA, Yu W, Rui L. "Nebulized lidocaine for intractable cough in hospice care: a comprehensive review of efficacy, safety, and future perspectives". BMC Palliat Care. 2025 Apr 30;24(1):123. doi: 10.1186/s12904-025-01752-z.
[2] Slaton RM, Thomas RH, Mbathi JW. Evidence for therapeutic uses of nebulized lidocaine in the treatment of intractable cough and asthma. Ann Pharmacother. 2013;47(4):578-585. doi:10.1345/aph.1R573
[3] Zheng J, Du L, Du B, Zhang W, Zhang L, Chen G. Airway nerve blocks for awake tracheal intubation: A meta-analysis of randomized control trials and trial sequential analysis. J Clin Anesth. 2023;88:111122. doi:10.1016/j.jclinane.2023.111122
[4] Ho ATN, Gandhiraj D, Jamkhana Z, Nayak R, Patolia S. Is Additional Nebulized Lidocaine Helpful in Flexible Bronchoscopy?: A Meta-Analysis. J Bronchology Interv Pulmonol. 2020;27(4):266-273. doi:10.1097/LBR.0000000000000656
[5] Abdulqawi R, Satia I, Kanemitsu Y, et al. A Randomized Controlled Trial to Assess the Effect of Lidocaine Administered via Throat Spray and Nebulization in Patients with Refractory Chronic Cough. J Allergy Clin Immunol Pract. 2021;9(4):1640-1647. doi:10.1016/j.jaip.2020.11.037
Literature Review

A search of the published medical literature revealed 4 studies investigating the researchable question:

Is there any data in term of clinical trials that show benefit of using nebulized lidocaine for treatment of refractory cough, or cough post-tracheostomy?

Level of evidence

C - Multiple studies with limitations or conflicting results  Read more→



Please see Tables 1-4 for your response.


A Randomized Controlled Trial to Assess the Effect of Lidocaine Administered via Throat Spray and Nebulization in Patients with Refractory Chronic Cough

Design

Randomized, double-blind, double-dummy, placebo-controlled, three-way crossover study

N= 26

Objective

To investigate the efficacy of nebulized lidocaine and lidocaine throat spray versus matched placebos in refractory chronic cough (RCC)

Study Groups

Nebulizer-spray-placebo (n= 4)

Nebulizer-placebo-spray (n= 5)

Placebo-nebulizer-spray (n= 4)

Placebo-spray-nebulizer (n= 4)

Spray-nebulizer-placebo (n= 4)

Spray-placebo-nebulizer (n= 4)

Inclusion Criteria

Adult patients with RCC, resistant to treatment of possible underlying causes

Exclusion Criteria

Upper respiratory tract infection in last 4 weeks; current or ex-smokers of < 6 months abstinence; > 20 pack year cigarette smoking history; diabetes; pregnancy; clinically significant comorbidities (i.e., ischemic heart disease, heart failure, sinoatrial disease, bradycardia, and all types of heart block); any medications likely to affect cough reflex sensitivity (i.e., ACE inhibitors, codeine, low dose morphine, gabapentin, pregabalin, baclofen)

Methods

Study treatments were administered in random order with at least 2-day minimum and 3-day maximum washout period between treatments. Study medications were dispensed as lidocaine 10% w/v and placebo (0.9% normal saline) in matching glass bottles; one was labelled for nebulization and the other for use as throat spray.

On study days, the nebulized treatment was administered first followed by the throat spray (10 actuations); patients were randomly assigned to receive the following interventions: nebulized lidocaine 600 mg followed by placebo throat spray; nebulized placebo followed by placebo throat spray; or nebulized placebo followed by lidocaine throat spray 100 mg. Study treatments were delivered by continuous nebulization by a Porta-neb VentStream®; the nebulized lidocaine dose of 600mg was anticipated to deliver approximately 100 mg in the throat; as such the lidocaine throat spray was dosed to match this. A 24-hour ambulatory cough recording device was provided to the patient and initiated recording immediately prior to the study drug administration. Patients reported urge-to-cough (UtC) intensity and severity of cough on 100 mm visual analogue scales (VAS) prior to treatment, every 15 minutes for 2 hours, then hourly for 8 hours at home. Patients were nil by mouth after drug administration, with clear liquids allowed 2 hours after and food 4 hours after; patients were observed in the research ward for 4 hours after treatment then discharged with cough monitor and diary for 24 hours after treatment. 

Duration

February 2011 to May 2011

24 hours after study treatment 

Outcome Measures

Primary: cough frequency over 10 hours following treatment

Secondary: change in VAS score for UtC and cough severity; adverse events 

Baseline Characteristics

 

Total cohort (N= 26)

Age, years

53.5 ± 12.1 

Female

85% 

Never-smokers

69% 

Cough duration, years

10 (7-16) 

FEV1% predicted, L

FVC% predicted, L

105.2 ± 16.8

112.4 ± 18

FEV1: forced expiratory volume in 1 second; FVC: forced vital capacity; IQR: interquartile range

Results

Endpoint

Total cohort (N= 26)

p-Value

Cough frequency over 10 hours, mean, cough/hour (95% CI)

Placebo spray

Lidocaine throat spray

Nebulized lidocaine spray

n= 25

27.6 (18.6-41.3)

22.2 (14.5-33.8)

26.9 (18.5-39.2)

0.04*

Cough severity VAS score, mean difference compared to placebo, mm

Lidocaine throat spray

Nebulized lidocaine

 

-6.2

-7

 

0.029

0.022

Urge to cough, VAS score, mean difference compared to placebo, mm

Lidocaine throat spray

Nebulized lidocaine

 

-6.1

-8.62

 

0.014

0.005

CI: confidence interval

*Lidocaine throat spray compared to placebo

Reduction in cough frequency compared to placebo: lidocaine spray (20%; 95% CI -52% to 22%; p= 0.017); nebulized lidocaine (p= 0.84)

Exploratory analysis of treatment effect by hour suggested a significant effect of intervention on hourly cough frequency in 5 hours after treatment administration (p= 0.004); lidocaine spray resulted in greatest effect (compared to placebo) in first hour with little difference by hours 4 and 5. 

Coughs during nebulization: placebo: 2 (0-19); lidocaine throat spray: 1 (0-15.5); nebulized lidocaine: 14 (0-35); p= 0.018

Adverse Events

Common Adverse Events: swallowing difficulty (nebulized lidocaine, n= 1); sore throat (nebulized lidocaine, n=1; placebo, n= 2); heartburn (nebulized lidocaine, n= 1); breathlessness (nebulized lidocaine, n= 1); headache (nebulized lidocaine, n= 1; lidocaine throat spray, n= 1; placebo, n= 1); panic attack (lidocaine throat spray, n= 1); itching (lidocaine throat spray, n=1; placebo, n= 1); palpitation (lidocaine throat spray, n= 1); skin bruise (lidocaine throat spray, n= 1); painful hand (lidocaine throat spray, n= 1)

Study Author Conclusions

Lidocaine throat spray was effective in reducing cough frequency in RCC patients. Voltage gated sodium channel inhibitors applied to pharynx have potential as therapies in RCC. 

Critique

The small sample size is a limitation of the study, as well as the fact that most patients were able to correctly identify study treatments they received at each visit, limiting the effect of the planned blinding of interventions. As this study only evaluated a single, dose the effects of multiple doses is unknown and possible may have been more effective. Additionally, it is unclear whether the order of received nebulization or throat spray had an effect on the outcomes as this aspect was not randomized. 
References:
[1] Abdulqawi R, Satia I, Kanemitsu Y, et al. A Randomized Controlled Trial to Assess the Effect of Lidocaine Administered via Throat Spray and Nebulization in Patients with Refractory Chronic Cough. J Allergy Clin Immunol Pract. 2021;9(4):1640-1647. doi:10.1016/j.jaip.2020.11.037

Effect of Lidocaine Nebuliser Compared with NSS Nebuliser in Reducing Cough Symptom and Pain in Early Tracheostomy Care

Design

Prospective, randomized, single-blind, cross over study

N= 32

Objective

To compare the effectiveness of pain and cough reduction in the early postoperative period following tracheostomy between a lidocaine-normal saline solution (NSS) and a NSS nebulizer

Study Groups

AB, lidocaine-NSS nebulizer then NSS nebulizer (n= 16)

BA, NSS nebulizer then lidocaine-NSS nebulizer (n= 16)

Inclusion Criteria

Age ≥ 18 years with tracheostomy

Exclusion Criteria

Pregnancy; chronic lung disease; lung infection; skin infection at the neck; lidocaine or amide allergy; cancer with metastasis to the neck skin; had to receive another operation other than tracheostomy; use of ventilator after operation; chronic liver or kidney disease

Methods

Patients were randomized to two groups: the AB group received lidocaine-NSS nebulizer at 10 AM and 8 hours later received NSS nebulizer at 6 PM; the BA group received NSS nebulizer at 10 AM, then the lidocaine-NSS nebulizer 8 hours later at 6 PM. Treatment was administered on postoperative day 2 after deflation of tracheostomy cuff and after adequate time for the intraoperative analgesic drug which was administered to wear off. Pain and cough were scored by patients using a visual analog scale (VAS; 0= no symptom, 10= severe symptom) before and 60-90 minutes after each nebulization. Those with severe pain were capable of requesting an analgesic (i.e., acetaminophen, tramadol, or morphine) for pain relief; those who requested painkillers between 6 AM and 6 PM were excluded in the pain score analysis.

Duration

June 2016 to June 2017

Outcome Measures

Cough, pain

Baseline Characteristics

 

All patients (N= 32)

Age, years

61.34 ± 10.19 

Female

12.5%  

Anesthesia

General

Local

 

56.3%

43.8%

Indication

Bilateral vocal cord paralysis

CA larynx

CA esophagus

CA oropharynx

CA hypopharynx

CA oral cavity

 

9.4%

43.8%

3.1%

25%

6.3%

21.9%  

Painkiller requested

31.3%

CA: cancer

Results

Endpoint

AB (n= 16)

BA (n= 16)

Delta (95% CI); p-value

Cough

Lidocaine-NSS

Pre-treatment

Post-treatment

Delta

NSS

Pre-treatment

Post-treatment

Delta

 

 

6.06 ± 1.81

3.63 ± 2.73

2.44 ± 2.48

 

4.44 ± 2.31

3.75 ± 2.79

0.69 ± 2.21

 

 

5.44 ± 1.79

3.69 ± 2.24

1.75 ± 1.77

 

5.13 ± 2.03

4.06 ± 2.54

1.06 ± 1.73

 

 

0.63 (-0.67 to 1.92); 0.333

-0.06 (-1.87 to 1.74); 0.944

0.69 (-0.87 to 2.24); 0.373

 

-0.69 (-2.26 to 0.88); 0.378

-0.31 (-2.24 to 1.62); 0.743

-0.38 (-1.81 to 1.06); 0.597

Pain

Lidocaine-NSS

Pre-treatment

Post-treatment

Delta

NSS

Pre-treatment

Post-treatment

Delta

 

 

3.88 ± 2.39

2.69 ± 2.63

1.19 ± 1.17

 

3.31 ± 3.16

2.81 ± 2.64

0.5 ± 1.55

 

 

3.88 ± 2.16

2.56 ± 1.59

1.31 ± 1.74

 

4.06 ± 2.29

3 ± 2.45

1.06 ± 1.73

 

 

0 (-1.64 to 1.64); 1.0

0.13 (-1.44 to 1.69); 0.872

-0.13 (-1.19 to 0.94); 0.813

 

-0.75 (-2.74 to 1.24); 0.448

-0.19 (-2.03 to 1.65); 0.836

-0.56 (-1.75 to 0.62); 0.34

CI: confidence interval 

Pre-treatment and post-treatment analysis:

Cough

-lidocaine-NSS: delta 2.09; 95% CI 1.32 to 2.87; p< 0.001

-NSS: dellta 0.88; 95% CI 0.17 to 1.58; p= 0.017

Pain

-lidocaine-NSS: delta 1.25; 95% CI 0.72 to 1.78; p< 0.001

-NSS: delta 0.78; 95% CI 0.19 to 1.37; p= 0.011

Adverse Events

None observed 

Study Author Conclusions

A 1% lidocaine mixed 4:1 (v/v) with NSS and administered via a nebulizer caused a significant reduction in cough and pain symptoms in early postoperative tracheostomy patients, particularly for the cough symptom compared with using only a NSS nebulizer. 

Critique

The study is limited by its small sample size and short duration of the intervention and follow-up period. Additionally, outcomes were assessed in a subjective manner which may lead to interpatient variability. 

References:
[1] Panprapakorn K, Tangjaturonrasme N, Rawangban W. Effect of lidocaine nebuliser compared with NSS nebuliser in reducing cough symptom and pain in early tracheostomy care. Clin Otolaryngol. 2020;45(3):424-428. doi:10.1111/coa.13521

Comparison of lidocaine and bronchodilator inhalation treatments for cough suppression in patients with chronic obstructive pulmonary disease

Design

Single-center, randomized, controlled trial

N= 127 

Objective

To examine and compare short term effectiveness of lidocaine and bronchodilator inhalation treatments for cough suppression in patients with chronic obstructive pulmonary disease (COPD) during their visits to the emergency department (ED)

Study Groups

Nebulized lidocaine (n= 62)

Nebulized terbutaline (n= 65)

Inclusion Criteria

Adult patients who presented to ED with the subjective complaint of an intractable cough, clear and alert mental state, documented past medical history of COPD, and verbal consent for cough suppression via inhalation treatment

Exclusion Criteria

Patients with unstable initial vital signs (systolic blood pressure < 90 mm Hg, pulse rate < 50 or > 120 per minute, respiratory rate < 10 or > 30 breaths per minute), respiratory distress (labored breathing), hypoxemia (oxygen saturation < 90%) documented on pulse oximetry, or evidence of pneumonia or neoplasm on chest x-ray

Methods

Patients were randomized 1:1 to either nebulized lidocaine or terbutaline inhalation administered over 15-25 min. In lidocaine patients, solution was prepared by diluting 1 mg/kg cardiac lidocaine with saline for a total volume of 4 mL. Alternatively, 2 mL terbutaline was mixed with 2 mL saline solution to result in 4 mL total volume. No other antitussives were administered in ED prior to completion of questionnaire, and patients were asked not to eat or drink for one hour after inhalation. A questionnaire was completed to measure cough severity, assessed on a 10-point scale (1 point = no cough, 10 points = most severe cough). Patients were monitored for at least 2 hours after administration of treatment.

Duration

Enrollment occurred over a 6-month period in 2003

Treatment was administered over 15-25 minutes

Outcome Measures

Cough severity scores after treatment, safety

Baseline Characteristics

 

Nebulized lidocaine (n= 62)

Nebulized terbutaline (n= 65)

 

Age, years

68.5 ± 12.4

69.9 ± 11.9

 

Female

22 (35.5%)

20 (30.8%)

 

Prior over the counter antitussives

53 (85.5%)

58 (89.2%)

 

Wheeze on auscultation

58 (93.6%) 55 (83.6%)  

Experience of nebulized bronchodilator use

52 (83.9%)

56 (86.2%)

 

Vital signs

Systolic blood pressure, mm Hg

Pulse rate, min

Respiratory rate, breaths/min

Body temperature, °C

 

129.1 ± 21.4

96.0 ± 15.8

19.4 ± 3.9

36.8 ± 1.0

 

128.8 ± 24.3

92.3 ± 14.3

19.9 ± 3.8

36.7 ± 1.0

 

Results

 

Nebulized lidocaine (n= 62)

Nebulized terbutaline (n= 65)

p-value

Cough severity score

Before treatment

After treatment 

p-value before vs. after treatment

 

8 (7-9)

3 (2-3)

< 0.01

 

8 (7-8)

3 (2-5)

< 0.01

 

0.21

0.44

-

Adverse events

Tremor

Palpitation

Oropharyngeal numbness

Bitter taste

Dyspnea

Nausea/vomiting

Dizziness

 

3 (4.8%)

5 (8.1%)

38 (61.3%)

34 (54.8%)

5 (8.1%)

4 (6.5%)

2 (3.2%)

 

60 (92.3%)

59 (90.8%)

3 (4.6%)

4 (6.2%)

4 (6.2%)

3 (4.6%)

4 (6.2%)

 

< 0.01

< 0.01

< 0.01

< 0.01

0.67

0.65

0.44

IQR, interquartile range

Adverse Events

See above. No patients discontinued due to adverse events. No allergic reactions were reported. 

Study Author Conclusions

Both lidocaine and bronchodilator inhalation treatments are equally effective for short term cough suppression in patients with COPD.

Critique

The severity of cough is subjective so ratings between patients may be inconsistent. This study also only looked at short term outcomes in this study and did not evaluate lidocaine levels for toxicity. All included patients had a documented history of COPD. 

References:
[1] Chong CF, Chen CC, Ma HP, Wu YC, Chen YC, Wang TL. Comparison of lidocaine and bronchodilator inhalation treatments for cough suppression in patients with chronic obstructive pulmonary disease. Emerg Med J 2005;22:429-32. doi: 10.1136/emj.2004.015719

Nebulization versus standard application for topical anaesthesia during flexible bronchoscopy under moderate sedation - a randomized controlled trial

Design

Randomized, controlled, parallel study

N= 60

Objective

To compare the tolerability and safety of nebulized lidocaine with conventional lidocaine administration via syringe in patients undergoing bronchoscopy with moderate sedation

Study Groups

Lidocaine syringe (n= 30)

Lidocaine nebulizer (n= 30)

Inclusion Criteria

Patients aged ≥ 18 years requiring diagnostic bronchoscopy

Exclusion Criteria

Patients requiring cryobiopsy, endobronchial ultrasound, epilepsy, severe neurological or psychiatric disorder, hemodynamic instability requiring catecholamine treatment, decompensated heart failure, severe respiratory failure (pH < 7.35, arterial oxygen pressure [PaO2] < 55 mmHg despite supplemental oxygen), history of upper airway surgery or radiation, allergy to lidocaine, propofol or midazolam, or any bleeding disorder.

Methods

Patients received midazolam IV bolus before start of bronchoscopy, with no additional doses given during procedure. Propofol boluses were administered at investigator's discretion until sufficient tolerance for procedure achieved. Fentanyl bolus doses also permitted. Lidocaine (20 mg/mL) 20 mg to 40 mg was administered during bronchoscopy by nebulizer or syringe; target zones in both groups were vocal cords, trachea, main carina, and main bronchi. Approximately 10 sec waiting period was allotted between lidocaine administration at different sites. Additional injections were administered at the discretion of bronchoscopist, e.g. for excessive cough.

Patient tolerance was assessed using Global Tolerance Score, based on visual analogue scale (VAS; 0 [non-existent] to 100 [unbearable]) to rate nausea, asphyxia, cough, and pain. ALDRETE (global assessment of post-aesthetic condition) score was used to assess recovery after bronchoscopy procedure. 

Duration

October 2014 - November 2017

Outcome Measures

Primary outcome: Dosages of administered propofol and lidocaine

Secondary outcome: Dosages of midazolam and fentanyl, post procedural blood gas values, duration of the bronchoscopy, occurrence of complications, time span until an ALDRETE score of at least 9 was recorded after the procedure

Baseline Characteristics

 

Lidocaine syringe (n= 30)

Lidocaine nebulizer (n= 30)

 

Age, years

64.47 ± 11.56 67.9 ± 9.08  

Male

18 (60%) 21 (70%)  

Weight, kg

79.33 ± 16.5 86.64 ± 15.81  

FEV1, % predicted

77.5 ± 21.1 74.18 ± 21.24  

PaO2, mmHg

69.29 ± 18.6 66.56 ± 12.99  

PaCO2, mmHg

38.1 ± 8.84 36.36 ± 3.64  

Indications for bronchoscopy

Lung cancer

Interstitial lung disease

Unexplained pulmonary opacities

Hemoptysis

Other

 

23.3%

40%

20%

6.7%

10%

 

40%

16.6%

13.3%

10%

20%

 

FEV1, forced expiratory volume in 1 s; PaCO2, arterial partial pressure of carbon dioxide; PaO2, arterial partial pressure of oxygen

Results

Endpoint

Lidocaine syringe (n= 30) Lidocaine nebulizer (n= 30) p-value

Endobronchial lidocaine, mg

250.4 ± 42.38 164.7 ± 20.8 < 0.0001

Medication dosage administered, mg

Propofol bolus

Intrabronchial lidocaine

Midazolam bolus

Fentanyl bolus

 

63 ± 40.36

250.4 ± 42.38

1.7 ± 0.25

0.0283 ± 0.0429

 

62.33 ± 33.6

164.7 ± 20.8

1.78 ± 0.36

0.0217 ± 0.0387

 

0.5806

< 0.0001

0.5356

0.6127

Duration of bronchoscopy, min

14.67 ± 5.44

12.17 ± 4.6

0.0594

Arterial blood gas post-procedure, mmHg

PaCO2*

PaO2**

 

42.75 ± 8.18

70.4 ± 17.5

 

41.67 ± 4.57

74.2 ± 11.2

 

0.5291

0.3271

Complications

≥ 1 reported

Rate per procedure

Episodes of SpO2 < 90%

 

14 (46.67%)

1.17 ± 1.62

1.03 ± 1.33

 

6 (20%)

0.3 ± 0.79

0.27 ± 0.78

 

0.0539

0.0121

0.0070

Time to reach ALDRETE score ≥ 9, min

4 ± 3.6

4.7 ± 4.1

0.5068

No differences in the dosage of sedative drugs were observed between the two groups (all p> 0.05). No significant differences in VAS scores for global tolerance, nausea, asphyxia, cough, and pain were reported between groups. 

*Compared with pre-procedural values, post-procedural PaCO2 was significantly higher in both groups (both p< 0.0001).

**A significant increase between pre- and post-interventional PaO2 was seen in the nebulizer group (difference 7.6 ± 12.1 mmHg; 95% CI 3.1 to 12.1; p= 0.0018) but not in the syringe group (difference 1.1 ± 16.8 mmHg; 95% CI -5.2 to 7.4; p= 0.7188)

Adverse Events

See 'complications' in Results section above. 

Study Author Conclusions

In summary, administration of topical lidocaine via nebulizer during flexible bronchoscopy under moderate sedation is associated with reduced consumption of lidocaine compared with standard administration via syringe. Furthermore, nebulizing lidocaine during bronchoscopy was associated with improved oxygenation during the procedure and fewer peri-interventional complications. Therefore, nebulizers can be recommended for usage during diagnostic bronchoscopy, especially for patients suffering from respiratory failure.

Critique

There was a slight imbalance in groups as diagnostic bronchoscopies without sampling were more common in nebulizer group, however not statistically significant.

References:
[1] Müller T, Cornelissen C, Dreher M. Nebulization versus standard application for topical anaesthesia during flexible bronchoscopy under moderate sedation - a randomized controlled trial. Respir Res. 2018;19(1):227. Published 2018 Nov 21. doi:10.1186/s12931-018-0926-5