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"Nebulized lidocaine for intractable cough in hospice care: a comprehensive review of efficacy, safety, and future perspectives"

BMC Palliative Care volume 24, Article number: 123 (2025) Cite this article

Abstract

Background and Objective

Intractable cough, affecting 10–50% of terminally ill patients, significantly impairs quality of life. Conventional therapies often fail due to dose-limiting side effects or inadequate efficacy, necessitating alternative treatments. This review evaluates the efficacy, safety, and clinical applicability of nebulized lidocaine for managing intractable cough in hospice care.

Methods

A systematic literature search (1973–2023) across PubMed, MEDLINE, Embase, and Cochrane Library identified studies on nebulized lidocaine in hospice or palliative populations. Inclusion criteria the Cochrane Risk of Bias Tool and Newcastle–Ottawa Scale. Data on cough reduction, side effects, and dosing were synthesized thematically.

Results

Among 265 screened studies, 58 met inclusion criteria. Nebulized lidocaine (1–4%) demonstrated rapid cough suppression (within 15 min) in 70% of cancer patients, with effects lasting 2–4 h. Mild side effects, including oropharyngeal numbness (15%) and bitter taste (10%), were transient. However, 25% of asthmatic patients experienced bronchoconstriction (forced expiratory volume in 1 s FEV1FEV1 decline ≥ 15%), resolving with bronchodilators. Lidocaine reduced opioid reliance and improved comfort in 80% of cases. Variability in efficacy was noted, with limited benefits in severe chronic obstructive pulmonary disease (COPD) with acute respiratory failure.

Conclusion

Nebulized lidocaine offers a safe, non-invasive option for intractable cough in hospice care, minimizing systemic side effects. Its rapid action and compatibility with opioid-sparing regimens enhance palliative outcomes. However, cautious use is warranted in asthma and (COPD) due to bronchoconstriction risks. Future research should prioritize standardized dosing, long-term safety, and Randomized controlled trials(RCTs in diverse hospice populations.

Peer Review reports

Introduction

Intractable cough, defined as a persistent and refractory cough unresponsive to conventional therapies, is a debilitating symptom affecting 10–50% of terminally ill patients, particularly those with advanced cancer or chronic respiratory diseases [1, 2]. In hospice populations, as many as 60% of lung cancer patients experience severe cough, often due to tumor invasion, airway compression, or pleural effusions [3, 4]. Similarly, patients with interstitial lung diseases (ILDs), including idiopathic pulmonary fibrosis (IPF), report cough as a dominant symptom, with prevalence rates ranging from 59 to 100% [5, 6]. Chronic cough is also prevalent in non-cancer conditions, such as connective tissue disease-related ILD and post-COVID- 19 interstitial lung disease, where mechanical distortion of airways and neuropathic pathways contribute to the persistence of symptoms [7, 8].

The impact of intractable cough on quality of life is profound, exacerbating physical and psychological distress, leading to fatigue, insomnia, and social isolation [9, 10]. In cancer patients, cough is frequently accompanied by dyspnea, pain, and vomiting, which collectively reduce the ability to engage in meaningful end-of-life interactions [2]. The psychological burden is significant, as anxiety and depression often accompany uncontrolled symptoms [11, 12]. For instance, 40% of people living with advanced lung disease and chronic cough report feeling'trapped'by their symptoms, resulting in withdrawal from family activities [13, 14]. In ILD patients, cough severity has been shown to correlate with lower health-related quality of life scores, highlighting the need for more effective, targeted interventions [8].

The management of intractable cough in people approaching the end of life presents substantial challenges. Standard therapies, including opioids, corticosteroids, and benzonatate, often fail due to dose-limiting side effects such as sedation and constipation, or inadequate efficacy [15, 16]. Opioids may reduce cough frequency by only 30–50% in cancer patients, but their use is often limited by significant side effects such as constipation, sedation, opioid toxicity, and opioid-induced hyperalgesia [17, 18]. Anticholinergics, conversely, may exacerbate dry mouth [19]. Non-pharmacological interventions, such as bronchoscopic stenting or radiation, are invasive or impractical in hospice settings [20]. Though compounded medications may occasionally be effective, they lack standardized formulations [21]. Emerging therapies, such as P2X3 inhibitors, have shown promise but remain investigational, leaving a significant gap in available accessible, non-invasive options [8, 22].

Hospice care aims to maximize comfort and dignity through a holistic, multidisciplinary approach to symptom management, which includes addressing intractable cough using multimodal strategies. These may integrate pharmacological agents, psychosocial support, and patient education [23]. For example, 75% of palliative care teams use individualized plans designed to balance efficacy with minimal invasiveness [15, 24, 25]. Speech pathology interventions, such as cough suppression techniques, are increasingly recognized for their role in reducing laryngeal hypersensitivity. However, their application in terminally ill patients requires further study [26, 27].

Effective suppression of cough is critical in hospice care, as uncontrolled symptoms can hasten terminal decline [28,29,30,31]. Palliative care guidelines emphasize early intervention for symptoms like dyspnea and cough, recognizing their role in accelerating functional deterioration [32]. In advanced ILD patients, 80% require tailored regimens to address concurrent dyspnea and cough [5]. Neuromodulators, such as gabapentin, have shown partial efficacy, though their systemic side effects limit their use in frail populations [33, 34]. Lidocaine, a sodium channel blocker, inhibits neuronal excitability in sensory nerves, including airway C-fibers and rapidly adapting receptors (RARs), thus offering a potential mechanism for cough suppression [9, 35]. Its anti-inflammatory properties help reduce airway hyperresponsiveness by suppressing cytokine release and neurogenic inflammation, positioning it as a promising candidate for managing intractable cough [34, 36]. Nebulized formulations of lidocaine deliver localized anesthesia to the tracheobronchial tree, minimizing systemic absorption and toxicity [9]. Preclinical studies indicate that silencing nociceptor neurons with lidocaine analogs reduces allergic airway inflammation, which highlights its dual role in modulating both immune and neural pathways [37, 38].

Nebulized lidocaine has demonstrated efficacy in reducing cough intensity in both chronic refractory and cancer-related coughs. For instance, a pilot study reported that 70% of cancer patients achieved significant symptom relief with nebulized lidocaine administered twice daily [9, 37, 39, 40]. Additionally, topical pharyngeal lidocaine has been shown to reduce respiratory adverse events during procedures, further suggesting its broader applicability in palliative care settings [41,42,43].

Lidocaine’s versatility extends beyond cough management. It is used in the management of neuropathic pain and airway hypersensitivity. For instance, intravenous lidocaine has been shown to reduce postherpetic neuralgia pain by 60% in patients with advanced cancer receiving palliative care [35, 44]. Its anti-inflammatory effects have also been explored in the context of COVID- 19-related hyperinflammation, though clinical evidence in this area remains preliminary [45]. These properties underscore lidocaine's potential for multimodal symptom control in hospice care [16, 46]. In hospice care, nebulized lidocaine is ideal due to its rapid onset, minimal side effects, and compatibility with opioid-sparing regimens [9, 28]. For bedbound patients, its non-invasive administration avoids the risks of sedation or aspiration associated with systemic therapies [10, 29]. A retrospective analysis of 34 cancer patients found that 71% experienced significant cough reduction with lidocaine, although larger trials are needed to confirm these findings [10, 47]. Moreover, lidocaine’s safety profile in pediatric populations, demonstrated through its use in laparoscopic procedures, supports its adaptability across various age groups [48, 49].While the existing literature remains limited, there is promising evidence regarding the use of lidocaine. A randomized trial of TRPV4 inhibitors highlighted the challenges of cough-specific therapies and the need for targeted treatments like lidocaine [50]. In contrast, studies on gabapentin and paroxetine demonstrate partial efficacy, but their systemic side effects limit their utility in frailer populations [34, 51, 52]. Emerging research on P2X3 inhibitors and speech therapy combinations offers promising new directions, yet lidocaine’s immediacy and accessibility make it a pragmatic choice in hospice settings [29, 33].

This review evaluates the safety, efficacy, and practicality of nebulized lidocaine for managing intractable cough in hospice patients, synthesizing evidence from palliative, respiratory, and pharmacological studies. By addressing gaps in current research—such as optimal dosing, long-term tolerability, and patient selection—the review aims to inform clinical practice and advocate for standardized protocols in end-of-life cough management. Ultimately, improving cough control aligns with the ethical principles of autonomy and beneficence, ensuring that patients experience dignity in their final days [53].

Methods and data extraction

This review aimed to systematically explore the scientific literature on using nebulized lidocaine to manage intractable cough in terminally ill patients receiving hospice care. The methodology was designed to comprehensively and objectively synthesize the available evidence while maintaining scientific rigor. A systematic search was carried out across multiple electronic databases, including PubMed, MEDLINE, Embase, and the Cochrane Library, covering studies published from 1973 to 2023. The search terms combined keywords like"nebulized lidocaine","intractable cough","terminal illness","hospice care","palliative care","chronic cough", and"lidocaine efficacy". Boolean operators (AND, OR) were used to refine the search results. Manual searches of reference lists from relevant articles and reviews were also conducted to ensure no relevant studies were missed. Studies were included if they met specific criteria. The population was restricted to terminally ill patients or those with advanced—stage diseases (e.g., COPD, pulmonary fibrosis, cancer) experiencing intractable cough. The intervention had to involve nebulized lidocaine, either as a primary or secondary treatment for cough management. Studies also needed to report on the efficacy, safety, or side effects of nebulized lidocaine in reducing cough severity or frequency. Study designs included RCTs, observational studies, case reports, and case series. Studies focusing on non—nebulized forms of lidocaine (e.g., intravenous, epidural) or those not related to cough management in terminally ill or hospice care populations were excluded.

Data from eligible studies were extracted using a standardized template. This template included details such as study author(s), publication year, study design, duration, number of participants, demographic characteristics, disease/condition and its stage, lidocaine dosage, administration method, frequency, key findings on cough suppression, patient comfort, quality of life, reported outcomes (efficacy, adverse effects, patient tolerance), and side effects. The extracted data were then synthesized thematically, concentrating on the efficacy of nebulized lidocaine in reducing cough severity, its impact on patient comfort, and any reported side effects or limitations. Studies were grouped by disease condition to identify patterns and differences in outcomes among different patient populations.

The methodological quality of included studies was evaluated using appropriate tools for each study design. RCTs were assessed with the Cochrane Risk of Bias Tool, observational studies with the Newcastle—Ottawa Scale, and case reports with the CARE guidelines. This quality assessment enabled the findings to be interpreted in the context of each study's strengths and weaknesses. Due to the heterogeneity of study designs and patient populations, a meta—analysis was not possible. Instead, a narrative synthesis approach was used to summarize the findings. The results were organized into thematic categories, including evidence for the role of nebulized lidocaine in cough suppression and symptom relief. Reported side effects, such as oropharyngeal numbness, bitter taste, or bronchoconstriction, and their implications for use in hospice care were also considered. Finally, practical aspects of using nebulized lidocaine in terminally ill patients, such as dosing, frequency, and patient selection, were addressed. This review adhered to ethical guidelines for systematic reviews, ensuring transparency, reproducibility, and no data manipulation. Table 1. Figures 1. and 2.

Table 1 Summary of Studies on Lidocaine usage for Cough in respiratory patients
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Fig. 1
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Study flow chart

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Fig. 2
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Frequency of diseases group types reviewed in Table 1

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Statistical analysis in the study of nebulized lidocaine for intractable cough in hospice care

Data heterogeneity and the rationale for narrative synthesis

The studies included in this review presented a wide range of designs, such as randomized controlled trials (RCTs), observational studies, case reports, and case series. RCTs, known for their high—quality evidence, differed in patient groups, intervention details, and outcome measures. For example, one RCT might focus on a specific cancer patient subgroup, while another could target patients with a different stage of a respiratory disease. Observational studies provided real—world data but were prone to confounding factors. Case reports and case series, although valuable for unique cases, lacked the statistical power of larger studies. The outcome measures across these studies were equally diverse. Some studies used cough severity scores, others relied on pulmonary function tests like FEV1, and some focused-on patient—centered outcomes such as comfort and quality of life. Additionally, the dosing and administration of lidocaine varied greatly, with concentrations ranging from 1 to 4% and different frequencies of nebulization. This diversity made it difficult to conduct a traditional meta—analysis.

Data extraction

To handle the diverse data, a standardized data extraction template was developed. This template covered various aspects of each study, including the author(s), publication year, study design, duration, number of participants, demographic details, disease condition and its stage, lidocaine dosage, administration method, and frequency. It also included key findings related to cough suppression, patient comfort, quality of life, reported outcomes (e.g., efficacy, adverse effects, patient tolerance), and side effects. For instance, data from Hunt et al.'s [55] study on the impact of nebulized lidocaine on oral glucocorticoid use were extracted following this template.

Quality assessment different assessment tools were used based on the study design

RCTs: The Cochrane Risk of Bias Tool was utilized to evaluate RCTs. This tool assesses elements like randomization, which is crucial for ensuring comparable groups at the start of a trial and minimizing selection bias. Blinding, whether single—blind (where participants are unaware of treatment allocation) or double—blind (where both participants and researchers are unaware), helps reduce bias in outcomes. Reporting biases, which can occur when results are selectively reported, are also identified using this tool.

Observational Studies: The Newcastle—Ottawa Scale was employed to assess observational studies. It evaluates factors such as the selection of study participants, the comparability of groups, and the determination of outcomes. For example, it checks how well the study controls for confounding variables.

Case Reports: Case reports were evaluated according to the CARE (Case Report) guidelines. These guidelines ensure that case reports are well—structured, contain all relevant patient information, and clearly describe the intervention and its outcomes.

Narrative synthesis

Synthesis of nebulized lidocaine research

Thematic analysis of extracted data identified two primary themes: efficacy in reducing cough severity and safety profiles across patient populations. Nebulized lidocaine demonstrated rapid cough alleviation (2–4 h) in cancer patients, while safety data highlighted common side effects like oropharyngeal numbness, bitter taste, and bronchoconstriction. Disease-specific outcomes revealed differential responses: in asthma patients classified by GINA criteria, lidocaine improved symptoms in mild-to-moderate persistent asthma (GINA Steps 2–3) but triggered bronchoconstriction in severe cases (Steps 4–5 [102, 103]). Mixed results emerged for COPD and pulmonary fibrosis, with some studies reporting symptom improvement and others no significant benefit or bronchoconstriction. These findings underscore the need for tailored lidocaine use based on disease severity and patient phenotype, particularly cautioning against its use in severe asthma due to broncho- constrictive risks.

Statistical findings and their interpretation

Efficacy Variability: The narrative synthesis revealed inconsistent results regarding the efficacy of nebulized lidocaine. In some studies, it effectively reduced cough frequency and severity, improved pulmonary function, and decreased glucocorticoid use. However, in other studies, especially those with different patient populations or dosing regimens, the results were less positive. For example, Abuan et al.'s 2010 study found that inhaled lidocaine did not improve pulmonary function or reduce corticosteroid use in asthma patients.

Safety Profile: Most studies reported a generally favorable safety profile for nebulized lidocaine, with many reporting no significant adverse effects. When side effects did occur, they were often mild and short—lived, such as oropharyngeal numbness and bitter taste. However, in certain patient groups like asthmatics, there was an increased risk of bronchoconstriction. McAlpine et al.'s 1989 study showed that 25% of asthmatic patients experienced a significant decline in FEV1 after lidocaine administration. In summary, the statistical analysis in this study was adapted to the complex and diverse nature of the available evidence. While the narrative synthesis provided useful insights, future research with more consistent study designs and larger sample sizes is needed to draw more conclusive results about the efficacy and safety of nebulized lidocaine in hospice care.

Lidocaine has been widely studied, with most research indicating a favorable safety profile. Numerous studies (e.g., [11, 55, 58, 59, 61, 63, 65, 67, 101]) reported no significant adverse effects, suggesting overall good tolerability. When side effects did occur, they were generally mild, including oropharyngeal numbness and a bitter taste [11]. Some cases of bronchoconstriction were noted, particularly in asthmatic patients [83], with 25% of subjects experiencing a fall in FEV1 exceeding 15%, reaching a maximum of 42.1%. A transient bronchospasm was also observed in a pediatric patient, resolving spontaneously within five minutes [96]. Although lidocaine is well-tolerated in most cases, certain populations exhibit an increased risk of adverse events. In asthmatic patients, several studies indicate that lidocaine can induce bronchoconstriction. For example, McAlpine et al. [83] reported significant airway constriction in 25% of patients following lidocaine administration. Similarly, Chang et al. [94] observed a 7% decrease in FEV1 and a 3% narrowing of airway diameter in asthmatic subjects. However, not all findings were negative. Nebulized lidocaine has demonstrated benefits in mild-to-moderate asthma cases, improving symptoms and reducing glucocorticoid use [93]. The impact of lidocaine on patients with COPD has also been evaluated. While it has been found to be generally safe for cough suppression [11] and procedural pain management [63, 64], concerns arise in cases of acute respiratory failure. In this population, lidocaine has been linked to worsened arterial blood gases (Murciano et al., 1982). Additionally, its use in intubated patients with COPD or sepsis has been associated with post-intubation hypotension. However, this effect was likely influenced by multiple factors, including pre-existing low blood pressure and body weight [97]. Beyond adult populations, lidocaine's safety in pediatric and pregnant patients has also been examined. It has been deemed safe in children with severe asthma [58], though a single case of transient bronchospasm was reported [96]. In pregnant patients, inhaled lidocaine was found to be effective for asthma management without adverse effects [62]. A closer look at statistical findings on safety and efficacy further supports these observations. In asthma patients, McAlpine et al. [83] reported that 25% (5 out of 20) experienced a > 15% fall in FEV1, with a maximum decline of 42.1%. Similarly, Chang et al. [94] found that IV lidocaine resulted in a 7% decrease in FEV1 (P = 0.006) and a 3% reduction in airway diameter (P < 0.001). On the other hand, Hunt et al. [93] demonstrated that nebulized lidocaine significantly improved FEV1 (P ≤ 0.001) and reduced nighttime awakenings (P ≤ 0.02), with no reported side effects. However, Abuan et al. [98] found that inhaled lidocaine was well tolerated but did not improve pulmonary function or corticosteroid use. In COPD and sepsis patients, Lin et al. [97] reported that among 149 patients, 28 (18.8%) experienced post-intubation hypotension, though lidocaine was not the sole contributing factor. These findings highlight the need for a nuanced approach to lidocaine administration. In asthma patients, its use should be approached with caution due to the risk of bronchoconstriction, although pretreatment with bronchodilators (e.g., salbutamol) may help mitigate this risk [89]. For COPD patients, lidocaine is safe for cough suppression and procedural analgesia but should be avoided in acute respiratory failure due to its impact on blood gases. In pediatric and pregnant patients, it appears to be generally well-tolerated, though close monitoring is recommended given the limited data available. Regardless of the patient population, monitoring for bronchoconstriction, hypotension, and airway narrowing is crucial, particularly in individuals with preexisting respiratory conditions. Furthermore, adherence to recommended dosages minimizes the risk of systemic toxicity, such as oropharyngeal numbness and altered taste perception (Refer to Table 1).

In summary, lidocaine remains a valuable and effective medication, but its safety profile depends on the patient population and administration route. Careful patient selection, individualized treatment plans, and ongoing monitoring are essential to maximizing its benefits while minimizing potential risks. Figures 3, 4, and 5. A critical consideration not addressed in the reviewed studies is the potential role of preservatives in lidocaine solutions. Preservatives such as benzalkonium chloride, commonly found in multi-dose vials, are known to induce bronchoconstriction in sensitive populations, particularly asthmatics. This may confound the reported safety profile of nebulized lidocaine, as adverse events like bronchospasm (observed in 25% of asthmatic patients in McAlpine et al., 1989) could stem from preservative exposure rather than lidocaine itself. Notably, preservative-free lidocaine formulations are available and recommended for inhalational use to minimize airway irritation. However, none of the included studies explicitly detailed whether preservative-free solutions were utilized, limiting the ability to isolate lidocaine’s true safety profile. Clinicians should prioritize preservative-free formulations, especially in patients with airway hypersensitivity, to mitigate this risk.

Fig. 3
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Frequency of study category reviewed in Table 1

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Frequency of number of Studies in each decade on Lidocaine usage for Cough in respiratory patients reviewed in Table 1

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Frequency of study types in each decade on Lidocaine usage for Cough in respiratory patients reviewed in Table 1

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Practical considerations for nebulized lidocaine administration

Effective delivery of nebulized lidocaine requires attention to technique and patient education to optimize tolerability and adherence.

Administration technique

Mouthpiece vs. mask for reduced oropharyngeal deposition

Using a mouthpiece positioned posteriorly in the throat minimizes contact with the tongue and oral mucosa, reducing the bitter taste and oropharyngeal numbness commonly reported with standard masks. This approach may enhance patient compliance, particularly in individuals sensitive to local anesthetic effects [104].

Post-nebulization oral rinsing ("Swish and Spit")

American Association for Respiratory Care (AARC) guidelines recommend rinsing the mouth after inhaled therapies to reduce residual drug exposure and local adverse effects. While focused on corticosteroids, this principle applies to lidocaine. Instructing patients to rinse their mouth with water immediately after nebulization ("swish and spit") reduces residual lidocaine in the oral cavity, mitigating dysgeusia (altered taste) and numbness [105].

Taste mitigation with mints/candy

Sucking on a sugar-free mint or candy post-administration can alleviate the unpleasant taste, improving patient experience. demonstrated that taste-masking strategies (e.g., mints, flavoring) improve adherence to inhaled therapies by reducing dysgeusia [106].

Transient initial cough exacerbation

Patients may experience a transient increase in cough during the first 1–2 min of nebulization due to airway irritation. Clinicians should forewarn patients about this phase, emphasizing the need to persist through it to achieve subsequent therapeutic benefit. Repeated dosing at regular intervals (e.g., every 2–4 h, aligned with lidocaine’s duration of action) avoids recurrent irritation, as residual anesthetic effects diminish gradually [9].

Dosing schedule

Regular administration before the prior dose fully wears off (e.g., within 2–4 h, depending on concentration) maintains therapeutic levels and minimizes the need to endure repeated initial cough exacerbations [107].

Interpretation and clinical implications

Nebulized lidocaine has emerged as a promising therapeutic option for managing intractable cough in terminally ill patients receiving hospice care. Its localized action on the airway mucosa provides symptomatic relief without the systemic side effects commonly associated with opioids, such as sedation, constipation, and respiratory depression [29, 108]. This is particularly advantageous for frail patients who may already be experiencing polypharmacy or opioid-related complications. Unlike corticosteroids, which are often used for their anti-inflammatory properties, nebulized lidocaine does not carry the risk of immunosuppression, making it a safer alternative for patients with compromised immune systems [109, 110]. The efficacy of nebulized lidocaine in reducing cough frequency and severity has been demonstrated in various clinical settings, including asthma, chronic obstructive pulmonary disease (COPD), and post-operative cough suppression [111,112,113]. In hospice care, where the primary goal is to improve quality of life, the ability of nebulized lidocaine to provide rapid and effective relief from distressing cough symptoms is particularly valuable. Studies have shown that nebulized lidocaine can significantly reduce cough severity scores and improve patient comfort, often within minutes of administration [114, 115]. This rapid onset of action is crucial for terminally ill patients who may experience sudden and severe coughing episodes.

Moreover, nebulized lidocaine has been shown to be well-tolerated, with minimal side effects such as mild oropharyngeal numbness or a bitter taste, which are generally transient and do not require discontinuation of treatment [47, 116]. This favorable safety profile makes it a viable option for patients who may not tolerate other cough suppressants, such as opioids or antihistamines, due to their systemic effects. Figure 6, Table 2.

Table 2 Frequency of reported side effects category of lidocaine usage for Cough in respiratory patients and their examples reviewed in table
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Fig. 6
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Frequency of reported side effects category of lidocaine usage for Cough in respiratory patients reviewed in Table 1

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Limitations of current evidence

Despite the promising findings, the current evidence supporting the use of nebulized lidocaine for intractable cough in hospice care is limited by several factors. First, the heterogeneity of study methodologies, including variations in dosing regimens, administration techniques, and outcome measures, makes it difficult to draw definitive conclusions about its efficacy [117, 118]. For example, some studies have used lidocaine concentrations ranging from 1 to 4%, with doses varying from 10 to 400 mg, leading to inconsistent results regarding optimal dosing [119, 120].

Second, many of the studies conducted to date have involved small sample sizes, which limits the generalizability of the findings. For instance, a study by Lim et al. [21] involving 99 patients reported significant improvements in cough severity, but the small cohort size raises questions about the reproducibility of these results in larger, more diverse populations. Additionally, the lack of large-scale randomized controlled trials (RCTs) specifically focused on hospice care settings further restricts the ability to establish robust evidence-based guidelines [2].Third, inconsistencies in reported efficacy have been observed, with some studies showing only partial relief of cough symptoms [121, 122]. This variability may be attributed to differences in patient populations, underlying etiologies of cough, and the presence of comorbid conditions. For example, patients with advanced lung cancer or COPD may respond differently to nebulized lidocaine compared to those with non-malignant causes of cough [123, 124].These discrepancies highlight the need for more standardized assessment tools and outcome measures to better evaluate the effectiveness of nebulized lidocaine. A significant constraint in this review is the inconsistent reporting of preservative content in lidocaine formulations across studies, which complicates the interpretation of safety outcomes such as bronchoconstriction. Without explicit details on preservative type and concentration, differentiating between lidocaine-related adverse effects and those caused by formulation additives remains challenging, potentially skewing risk assessments. Additionally, variability in administration techniques (e.g., mouthpiece vs. mask use, post-nebulization care protocols) among studies introduces ambiguity in comparing efficacy and tolerability. These methodological inconsistencies highlight the need for standardized reporting of formulation details and aerosol delivery practices in future research to enhance transparency and reproducibility. Such improvements would enable more precise evaluation of lidocaine’s therapeutic potential and safety profiles across diverse patient populations.

Future research directions

To address these limitations, future research should focus on several key areas. First, there is a need for well-designed, large-scale RCTs to evaluate the efficacy and safety of nebulized lidocaine in hospice care settings. These trials should aim to establish standardized dosing regimens and administration protocols, as well as identify patient subgroups that are most likely to benefit from this treatment [11, 125].

Second, long-term safety profiles of nebulized lidocaine need to be established, particularly in patients with advanced illness who may require prolonged use. While short-term studies have shown that nebulized lidocaine is generally well-tolerated, the potential for cumulative side effects, such as systemic absorption leading to lidocaine toxicity, warrants further investigation [9, 126].

Third, future studies should incorporate patient-reported outcomes, such as quality of life measures, to better understand the impact of nebulized lidocaine on overall symptom burden and patient satisfaction. This is particularly important in hospice care, where the primary goal is to improve comfort and quality of life rather than to cure disease [127, 128]. Finally, research should explore the potential synergistic effects of combining nebulized lidocaine with other palliative therapies, such as opioids or corticosteroids, to enhance symptom control while minimizing side effects. For example, a study by Subedi et al. [33] demonstrated that the combination of lidocaine and dexamethasone was effective in reducing postoperative sore throat and cough, suggesting that similar combinations could be explored in hospice settings.

Conclusion

Nebulized lidocaine offers a promising approach for managing intractable cough in hospice care, leveraging localized action and rapid symptom relief with minimal systemic impact, particularly beneficial for patient’s intolerant to opioids. However, evidence is constrained by methodological inconsistencies, small sample sizes, and limited randomized controlled trials. Future research should prioritize defining optimal dosages, evaluating long-term safety, and measuring patient-reported outcomes to establish clinical guidelines. Current practice requires tailored administration, considering patient tolerance, response, and symptom burden. Use of preservative-free formulations is critical to minimize broncho-constrictive risks, especially in asthma or COPD populations. Standardized reporting of lidocaine preparation details (e.g., preservative presence) in trials is essential to clarify safety profiles. To enhance utility, protocols should integrate patient-centered techniques such as mouthpiece delivery, post-treatment oral rinsing, and taste-masking strategies. Educating patients on transient cough exacerbation and structured dosing schedules may improve adherence. Prospective studies should systematically evaluate these practices to refine administration guidelines, ensuring safe and effective use of nebulized lidocaine in palliative care.

Data availability

No datasets were generated or analysed during the current study.

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  1. Jumei Pan and Akhtar Ali Khan contributed equally to this work.

Authors and Affiliations

  1. Department of Hospice Care of Linfen Road Community Health Care Center, Jing An District, Shanghai, 200435, China

    Jumei Pan, Wenkai Yu & Lei Rui

  2. Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China

    Akhtar Ali Khan

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Contributions

J.P. oversaw the study design, executed data collection and analysis, and provided overall supervision as corresponding author. K.A.A. authored the introduction and discussion sections, contributing an equal and critical insights to the manuscript. W.K.Y and R.L conducted a comprehensive review of the study methodology and findings, ensuring scientific rigor and adherence to publication standards.

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Pan, J., Khan, A.A., Yu, W. et al. "Nebulized lidocaine for intractable cough in hospice care: a comprehensive review of efficacy, safety, and future perspectives". BMC Palliat Care 24, 123 (2025). https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s12904-025-01752-z

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Keywords

BMC Palliative Care

ISSN: 1472-684X

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