Nebulized Medications in the Emergency Department: A Narrative Review of Nontraditional Agents

Authors: Kyle A. Weant, PharmD; Regan A. Baum, PharmD; Garrett B. Hile, PharmD; Roger L. Humphries, MD; Elise L. Metts, PharmD

Journal Name, Year, Volume, Issue: American Journal of Health-System Pharmacy, 2024;81(4)

Type of Study: Narrative Review

DOI: https://doi.org/10.1093/ajhp/zxad273

Quick Reference Summary

Aerosolized drug delivery in the emergency department (ED) offers a rapid and less invasive alternative to traditional administration routes, potentially enhancing therapeutic responses while minimizing systemic adverse effects. Pharmacists play a crucial role in optimizing medication preparation and administration to ensure efficacy and safety of nebulized nontraditional therapies.

Core Clinical Question

In emergency department patients where traditional medication administration routes are less appropriate, does the use of nebulized nontraditional therapies provide effective and safe alternatives in terms of therapeutic outcomes and adverse effects?

Background

Disease or Condition Overview:

In the ED setting, patients present with a variety of conditions requiring prompt and effective medication administration. Traditional routes like intravenous (IV) and oral delivery may not be suitable for all patients due to factors such as consciousness level, intolerance, or trauma.

Prior Data on the Topic:

• Intramuscular (IM) and intranasal (IN) routes have been shown to reduce needle-stick injuries, decrease administration time, and eliminate the need for IV access in certain scenarios.
• Aerosolized drug delivery (nebulization) has been increasingly explored for both respiratory and systemic conditions, offering direct delivery to the site of action.

Current Standard of Care:

IV, oral, IM, and IN routes remain the mainstays for medication administration in the ED.

Knowledge Gaps Addressed by Study:

Limited comprehensive analysis of the efficacy, safety, and practical implementation of nebulized nontraditional medications in the ED.

Study Rationale:

To evaluate existing literature on nebulization as a route of administration, examine factors influencing drug efficacy, and assess the viability of novel, noncommercial nebulized therapies in the ED.

Methods Summary

Study Design: Narrative Review

Setting and Time Period: Not explicitly specified

Population Characteristics: Emergency department patients requiring medication administration where traditional routes are less appropriate

Inclusion/Exclusion Criteria: Included primary literature, review articles, and double-blind clinical trials on nebulized nontraditional medications; included open-label studies if double-blind studies were unavailable

Intervention Details: Administration of nontraditional medications via nebulization

Control/Comparison Group Details: Traditional routes of administration (e.g., IV, IM)

Primary and Secondary Outcomes: Efficacy and safety of nebulized medications, practical considerations for administration

Statistical Analysis Approach: Not applicable due to the narrative nature of the review

Sample Size Calculations: Not applicable

Ethics and Funding Information: No conflicts of interest declared

Detailed Results

Participant Flow and Demographics

Not applicable as the study is a narrative review.

Primary Outcome Results

• Calcium Gluconate: Effective as an antidote for inhalational hydrofluoric acid exposure with no reported adverse effects in observational studies.
• Furosemide: Comparable efficacy to IV administration in treating pulmonary edema; mixed results in COPD and asthma exacerbations.
• Ketamine: Effective for acute pain management with minimal adverse effects; insufficient data for routine use in asthma or procedural sedation.
• Magnesium: Modest benefits in adult asthma exacerbations; limited efficacy in pediatric populations.
• Naloxone: Effective in reversing opioid overdose in patients with intact respiratory drive; allows self-titration, minimizing withdrawal symptoms.
• Nitroglycerin (NTG): Effective pulmonary vasodilator with selective action; limited evidence for routine ED use.
• Opioids (Fentanyl, Hydromorphone): Comparable analgesic efficacy to IV administration for acute pain; higher doses may be required.
• Sodium Bicarbonate: Effective in managing chlorine and chloramine gas exposures with significant improvements in FEV₁ and quality-of-life scores.
• Tranexamic Acid (TXA): Effective in controlling post-tonsillectomy hemorrhage and hemoptysis with minimal adverse effects.

Secondary Outcome Results

• Combination Therapies: Nebulized furosemide combined with β-agonists showed enhanced spirometric improvements in asthma and COPD patients.
• Adverse Events/Safety Data: Generally minimal adverse effects across nebulized therapies, with specific concerns such as agitation with naloxone and sedation with ketamine.

Subgroup Analyses

• Patient Populations: Efficacy varies between adults and pediatric patients, particularly noted in magnesium administration for asthma.
• Practice Settings: Applicability across different ED settings (community, rural) depends on access to appropriate nebulization equipment and trained pharmacists.

Adverse Events/Safety Data

• Calcium Gluconate: No adverse effects reported in large observational cohorts.
• Furosemide: Conflicting reports; generally low incidence of adverse effects.
• Ketamine: Dizziness, fatigue, mood changes; rarely severe.
• Magnesium: Dry mouth, bitter taste; no serious adverse events.
• Naloxone: Agitation, diaphoresis, nausea/vomiting; no cases required escalation in respiratory support.
• Nitroglycerin: Minimal to no systemic adverse effects.
• Opioids: Bitter or metallic taste, bronchospasm; lower incidence of hypotension compared to IV administration.
• Sodium Bicarbonate: No adverse effects noted in chlorine exposure cases.
• TXA: Minimal adverse effects; most reliable in hemorrhage control.

Results Tables

Note: This table summarizes selected findings from the review. For comprehensive results, refer to the full article.

Authors' Conclusions

The authors conclude that while traditional routes of medication administration have a stronger evidentiary foundation, the use of nebulized nontraditional therapies in the ED is expanding. Nebulization offers a rapid and less invasive alternative that can be advantageous in the ED setting. Pharmacists are essential in ensuring the optimal preparation and administration of these therapies to maximize efficacy and minimize adverse effects.

Critical Analysis

A. Strengths:

• Comprehensive Scope: The review covers a wide range of nebulized medications, providing a broad overview of their applications in the ED.
• Practical Focus: Emphasis on practical considerations ensures the findings are directly applicable to clinical practice.
• Pharmacist Role Highlighted: Recognizing the critical role of pharmacists aids in interdisciplinary collaboration and optimal patient care.

B. Limitations:

• Narrative Design: The lack of a systematic approach may introduce selection bias in the literature reviewed.
• Variability in Studies: Heterogeneity in study designs, dosages, and patient populations limits the ability to generalize findings.
• Limited High-Quality Evidence: Many conclusions are based on observational studies or small trials, reducing the strength of evidence.

C. Literature Context:

• Previous Studies and Meta-Analyses:
  • Earlier research has demonstrated the potential benefits of nebulized therapies in specific scenarios, such as calcium gluconate for hydrofluoric acid exposure.
  • Meta-analyses on nebulized magnesium show modest benefits in adult asthma exacerbations but limited efficacy in pediatric cases (Bhaysouri et al., 2020; Shan et al., 2013).
• Contrasting Methodological Quality:
  • Studies vary in methodological rigor, with some lacking control groups or being open-label, impacting the reliability of outcomes.
• Comparisons with Guidelines:
  • Current ED guidelines primarily endorse traditional administration routes, with nebulized therapies considered adjunctive or alternative based on specific patient needs.
• This Trial's Contribution:
  • The review consolidates emerging evidence on nebulized nontraditional agents, highlighting their potential roles and practical implementation strategies in the ED, thereby informing future guideline developments.

Clinical Application

The integration of nebulized nontraditional medications provides ED clinicians with additional therapeutic options, particularly in situations where traditional routes are impractical. These findings support the tailored use of nebulization based on patient-specific factors and clinical scenarios, enhancing overall patient care and outcomes.

How To Use This Info In Practice:

Emergency department practitioners can consider nebulized nontraditional therapies as viable alternatives to traditional administration routes, leveraging pharmacist expertise to optimize preparation and administration for effective patient outcomes.

Notes for Clarity

• Statistical Significance: Bolded within tables where applicable.
• Confidence Intervals: Included in tables where available.
• Conflicts of Interest: Authors declared no potential conflicts.
• Areas of Uncertainty: Highlighted in limitations, particularly regarding the variability and quality of existing studies.
• Number Needed to Treat/Harm: Not specifically reported in the review.
• Funding Sources: Not explicitly mentioned beyond conflict of interest disclosures.