Effects of Dexmedetomidine Combined With Lidocaine Topical Administration on Cough Reflex During Extubation in Thyroidectomy Patients: A Randomized Clinical Trial
The Takeaway
topical administration of dexmedetomidine, when combined with lidocaine, significantly enhances the reduction in both the incidence and intensity of cough reflex during extubation
Study Design
- 180 patients (60 per group)
- Inclusion criteria: female patients aged 18 to 65, ASA I or II, BMI 18 to 30 kg/m², undergoing elective thyroidectomy
- Exclusion criteria: allergy to lidocaine or dexmedetomidine, significant cardiovascular, hepatic, or renal disease, difficult airways, a history of maxillofacial or neck surgery, chronic respiratory conditions such as chronic obstructive pulmonary disease or asthma, recent respiratory infections, chronic cough, or the need for reoperation
- 3 groups: Dexmedetomidine combined with Lidocaine (Dex-Lido) group, Lidocaine (Lido) group, and Normal Saline (Control) group
- Spray intervention: Dex-Lido group received 1 ml of 2% lidocaine (20 mg) combined with 2 ml of dexmedetomidine (0.5 µg/kg); the Lido group received 3 ml of 2% lidocaine (60 mg); and the Control group received 3 ml of normal saline. The sprays were evenly applied to the supraglottic, glottic, and subglottic regions.
Physiology Review
Precedex is a highly selective alpha-2 adrenergic receptor agonist that works primarily through the following mechanisms:
Primary Mechanism: Alpha-2 Adrenergic Receptor Activation
Dexmedetomidine binds with high selectivity to alpha-2 receptors (particularly the alpha-2A subtype) with an alpha-2 selectivity ratio of approximately 1600:1. This is significantly higher than clonidine, another alpha-2 agonist.
Central Nervous System Effects
- Locus Coeruleus: The primary site of action is the locus coeruleus in the brainstem, where dexmedetomidine inhibits norepinephrine release by presynaptic activation of alpha-2 receptors.
- Sedation: Unlike traditional sedatives (benzodiazepines, propofol), dexmedetomidine produces a unique "arousable sedation" resembling natural sleep. Patients can be easily awakened and remain cooperative even during sedation.
- Anxiolysis: Reduces anxiety without significant respiratory depression.
Analgesic Effects
Dexmedetomidine produces analgesia through:
- Inhibition of substance P release in the dorsal horn of the spinal cord
- Activation of alpha-2 receptors in the spinal cord
- Modulation of descending noradrenergic pathways
The analgesic effect is moderate but can significantly reduce opioid requirements.
Sympatholytic Effects
- Hemodynamic effects: Produces a biphasic cardiovascular response:
- Initial transient hypertension (due to peripheral alpha-2B receptor activation)
- Followed by hypotension and bradycardia (due to central sympatholytic effects)
- Reduces plasma catecholamine levels by up to 90%
Other Physiological Effects
- Minimal respiratory depression: Unlike opioids and other sedatives, dexmedetomidine preserves respiratory drive even at higher doses.
- Anti-shivering properties: Useful for hypothermia management and post-anesthetic shivering.
- Neuroprotective potential: May reduce ischemic injury through several mechanisms including modulation of apoptosis.
- Organ-protective effects: Some evidence suggests protective effects on heart, kidney, and brain tissue, likely through anti-inflammatory and anti-oxidant properties.
Abstract
Background: Cough reflex during extubation can lead to complications such as increased bleeding and hemodynamic instability, especially in thyroidectomy, therefore, effective suppression of cough reflex is clinically important. The aim of the study was to investigate the inhibitory effect of dexmedetomidine combined with lidocaine on the cough reflex during extubation in thyroidectomy.
Methods: A total of 180 female patients, aged 18 to 65 years, undergoing elective thyroidectomy under general anesthesia, were randomized into 3 groups: dexmedetomidine combined with lidocaine (Dex-Lido group, n = 60), lidocaine alone (Lido group, n = 60), or normal saline (Control group, n = 60). Before tracheal intubation, patients in the Dex-Lido group received dexmedetomidine combined with 2% lidocaine spray, those in the Lido group received 2% lidocaine spray, and those in the Control group received 0.9% normal saline spray, applied to the supraglottic, glottic, and subglottic areas. The primary outcome was the incidence of cough reflex at extubation. Secondary outcomes included cough severity, postoperative sore throat, hoarseness, nausea, and vomiting, as well as the need for analgesics and antiemetics, pain levels, sedation scores, and length of hospital stay.
Results: The incidence of cough reflex during extubation was significantly lower in both the Dex-Lido and Lido groups compared to the Control group (23% vs 70%; odds ratio [OR], 0.13; 95% confidence interval [CI], 0.06-0.29; P < .001 for Dex-Lido; 47% vs 70%; OR, 0.38; 95% CI, 0.18-0.79]; P = .010 for Lido), with a statistically significant difference between the Dex-Lido and Lido groups (23% vs 47%; OR, 0.35; 95% CI, 0.16-0.76; P = .007). Additionally, the severity of the cough reflex was markedly lower in the Dex-Lido group compared to the Control group (8/60 vs 26/60; OR, 0.20; 95% CI, 0.08-0.50; P < .001).
Conclusions: The combination of dexmedetomidine and lidocaine laryngopharynx spray effectively suppresses the cough reflex during extubation, reduces postoperative sore throat, and stabilizes hemodynamics in female patients undergoing thyroid surgery.
Excerpts
The cough reflex during extubation after general anesthesia is a common occurrence, affecting 40% to 76% of intubated patients
Although intravenous dexmedetomidine is US Food and Drug Administration (FDA)-approved for clinical use, it may cause side effects such as bradycardia and hypotension. To mitigate these concerns, local administration of dexmedetomidine via nasal, respiratory, or buccal mucosa has emerged as a promising alternative
The incidence of the cough reflex during extubation was 23% (14/60; 95% confidence interval [CI], 0.23 [0.13–0.36]) in the Dex-Lido group, 47% (28/60; 95% CI, 0.47 [0.34–0.60]) in the Lido group, and 70% (42/60; 95% CI, 0.7 [0.57–0.81]) in the Control group. The differences among the 3 groups were statistically significant (P < .001).
Postoperative sore throat (POST) incidence was lower in the Dex-Lido and Lido groups compared to the Control group at 1, 6, and 24 hours after surgery (P < .0167). The 48-hour POST incidence was also lower in the Dex-Lido group than in the Control group (8/60 vs 24/60; OR, 0.23; 95% CI, 0.09–0.57; P = .001)
The average awakening times in the Dex-Lido, Lido, and Control groups were 16 (±8.26) minutes, 12 (±6.69) minutes, and 12 (±5.93) minutes, respectively
The combination of dexmedetomidine and lidocaine laryngopharynx spray, applied to the supraglottic, glottic, and subglottic regions before intubation, effectively reduces the cough reflex and hemodynamic fluctuations during extubation in female patients undergoing thyroid surgery, without increasing the risk of adverse reactions such as hypotension or bradycardia. Additionally, this treatment may reduce the incidence and severity of postthyroidectomy sore throat, as well as agitation in the PACU.
The effect of dexmedetomidine combined with lidocaine laryngopharynx spray on the cough reflex during extubation may involve several mechanisms. First, it optimizes the route and method of administration. By administering dexmedetomidine locally via the respiratory mucosa, first-pass metabolism is avoided, reducing the risk of adverse reactions caused by peak plasma drug concentrations. Furthermore, spray delivery under direct vision allows for greater precision, producing smaller aerosol particles that enhance drug diffusion, absorption, absolute bioavailability, and prolong the elimination half-life
Minogue et al. found that in nonsmoking patients undergoing general anesthesia, lidocaine sprayed on the trachea reduced the incidence of the cough reflex after intubation in patients with anesthesia durations of less than 2 hours compared to placebo. In our trial, the median anesthesia times for the Dex-Lido, Lido, and Control groups were 96, 99, and 98 minutes, respectively, aligning with Minogue et al.‘s findings.
In our study, the incidence of POST at 1, 6, and 24 hours after thyroid surgery in the Control group was 61.2%, 78.3%, and 83.3%, respectively, which aligns with previous research findings of 68.9% (1h postoperative) and 84% (6h postoperative). The mechanistic basis for POST likely involves pressure from the endotracheal tube on the tracheal wall, resulting in airway inflammation, tracheal mucosal injury, vocal cord hematoma, mucosal dehydration, or laryngeal edema...When combined with the anti-inflammatory and analgesic properties of dexmedetomidine, as well as its enhancement of lidocaine’s local anesthetic action, the combination of dexmedetomidine and lidocaine (Dex-Lido group) effectively reduced the incidence of POST and improved POST scores.
Citation
Wang K, Wei B, Wang X, Gao Y, Cao Y, Zhang L, Ning M, Chen L. Effects of Dexmedetomidine Combined With Lidocaine Topical Administration on Cough Reflex During Extubation in Thyroidectomy Patients: A Randomized Clinical Trial. Anesth Analg. 2025 May 8. doi: 10.1213/ANE.0000000000007560. Epub ahead of print. PMID: 40338875.
