Efficacy of premedication with intranasal dexmedetomidine for removal of inhaled foreign bodies in children by flexible fiberoptic bronchoscopy: a randomized, double-blind, placebo-controlled clinical trial
Tracheobronchial foreign body aspiration in children is a life-threatening, emergent situation. Currently, the use of fiberoptic bronchoscopy for removing foreign bodies is attracting increasing attention. Oxygen desaturation, body movement, laryngospasm, bronchospasm, and breath-holding are common adverse events during foreign body removal. Dexmedetomidine, as a highly selective α2-adrenergic agonist, produces sedative and analgesic effects, and does not induce respiratory depression. We hypothesized that intranasal dexmedetomidine at 1 μg kg − 1 administered 25 min before anesthesia induction can reduce the incidence of adverse events during fiberoptic bronchoscopy under inhalation general anesthesia with sevoflurane.
In all, 40 preschool-aged children (6–48 months) with an American Society of Anesthesiologists physical status of I or II were randomly allocated to receive either intranasal dexmedetomidine at 1 μg·kg − 1 or normal saline at 0.01 ml kg− 1 25 min before anesthesia induction. The primary outcome was the incidence of perioperative adverse events. Heart rate, respiratory rate, parent-child separation score, tolerance of the anesthetic mask, agitation score, consumption of sevoflurane, and recovery time were also recorded.
Following pre-anesthesia treatment with either intranasal dexmedetomidine or saline, the incidences of laryngospasm (15% vs. 50%), breath-holding (10% vs. 40%), and coughing (5% vs. 30%) were significantly lower in patients given dexmedetomidine than those given saline. Patients who received intranasal dexmedetomidine had a lower parent–child separation score (P = 0.017), more satisfactory tolerance of the anesthetic mask (P = 0.027), and less consumption of sevoflurane (38.18 ± 14.95 vs. 48.03 ± 14.45 ml, P = 0.041). The frequency of postoperative agitation was significantly lower in patients given intranasal dexmedetomidine (P = 0.004), and the recovery time was similar in the two groups.
Intranasal dexmedetomidine 1 μg·kg− 1, with its sedative and analgesic effects, reduced the incidences of laryngospasm, breath-holding, and coughing during fiberoptic bronchoscopy for FB removal. Moreover, it reduced postoperative agitation without a prolonged recovery time.
The study was registered with the Chinese Clinical Trial Registry (registration number: ChiCTR1800017273) on July 20, 2018.
KeywordsForeign body Fiberoptic bronchoscopy Dexmedetomidine
both right and left bronchus
- DEX group
end-tidal carbon dioxide
laryngeal mask airway
post-anesthesia care unit
Tracheobronchial foreign body (FB) aspiration in children may be a life-threatening, emergent situation . Undiagnosed or delayed treatment of a tracheobronchial FB may result in pneumonia, atelectasis, a lung abscess, or fatal airway obstruction [2, 3, 4]. Prompt, successful removal of an FB is associated with fewer complications and deaths [5, 6]. Rigid bronchoscopy is the main diagnostic and therapeutic procedure for patients suspected to have aspirated a foreign body. It allows an excellent control of the airway, provides a large working channel and permits the removal of foreign bodies and thick mucus plug. The use of fiberoptic bronchoscopy to remove tracheobronchial FBs is currently attracting increased attention [7, 8]. The flexible bronchoscopy compared with the rigid bronchoscope is relatively atraumatic, allows the visualization of the upper lobes as well as the natural dynamics of the palate and larynx. The procedure is performed via a laryngeal mask airway (LMA) under general anesthesia. Oxygen desaturation, body movements, laryngospasm, bronchospasm, and breath-holding are common adverse events during FB removal [2, 9].
Dexmedetomidine, a highly selective α2-adrenergic agonist, provides sedation without respiratory depression. Used as a preoperative medication, it reduces preoperative anxiety [10, 11], lowers the anesthetic requirement, and deepens the level of anesthesia [12, 13]. Several studies have evaluated the sedative effect of intravenous infusion of dexmedetomidine during fiberoptic bronchoscopy and confirmed that this agent is useful for reducing intratracheal stimuli (by decreasing the incidence of coughing, breath-holding, and laryngospasm) and enhancing patients’ degree of comfort without the risk of respiratory depression [14, 15, 16]. Nevertheless, the patient’s recovery time is significantly prolonged by intravenous infusion of dexmedetomidine . It has been reported that the plasma concentrations of dexmedetomidine approaches 100 pg·ml− 1 (the low end reported for sedative efficacy) within 20 min of intranasal administration of atomized dexmedetomidine 1 μg·kg− 1 in children , thereby producing satisfactory sedation before anesthesia induction . The effect of premedication with intranasal dexmedetomidine on reducing the incidence of adverse events during flexible bronchoscopy in children, however, remains undetermined.
This prospective, randomized, double-blind, placebo-controlled study was performed to evaluate whether intranasal dexmedetomidine at a dose of 1 μg·kg− 1 administered 25 min before anesthesia induction can reduce the incidence of adverse events during fiberoptic bronchoscopy under sevoflurane inhalation general anesthesia.
This study adheres the applicable CONSORT guidelines. This prospective, randomized, double-blind, placebo-controlled, single-center clinical trial was conducted at the West China Second University Hospital (Sichuan University, Chengdu, Sichuan Province, China). The study was registered with the Chinese Clinical Trial Registry (#ChiCTR1800017273). The China Ethics Committee of Registering Clinical Trials approved the study protocol (#ChiECRCT-20180113). The parents or legal guardians of each patient were supplied with comprehensive information by one of the investigators, regarding the study’s risk, objectives, and procedures. The parents/legal guardians signed informed consent before the patient’s inclusion in the study.
We enrolled 40 children (age 6–48 months) whose American Society of Anesthesiologists physical status was I or II and who were undergoing FB removal via fiberoptic bronchoscopy during the period from August 10 to December 25, 2018. Patients with congenital disease, a family history of malignant hyperthermia, coagulation disorders, asthma, severe preoperative respiratory impairment (i.e., single-lung emphysema or other type of severe atelectasis), and/or allergy to anesthetics were excluded from the study.
Routine patient monitoring included various measurements, including SpO2, respiratory rate (RR), HR, end-tidal carbon dioxide (EtCO2), and end-tidal sevoflurane (EtSevo). Additionally, each patient was monitored for his/her BIS (A-2000; Aspect Medical Systems, Norwood, MA, USA). The EtCO2 was measured by a capnography sensor placed between the L-piece and Bain circuit. The Etsevo was measured by side-stream sensor placed at the breathing circuit filter. The Gas Man anesthesia simulator (Med Man Simulations, Boston, MA, USA) was used to calculate the sevoflurane consumption.
Before induction, the HR, RR, and SpO2 were recorded at baseline (time 0, or T0). The HR, RR, SpO2, and BIS were then recorded at the following time points: LMA insertion (TLMAi), fiberoptic bronchoscope insertion (Tbron), 5 min after beginning the procedure (T5min), the end of the procedure (Tend), at LMA removal (TLMAR), 5 min after LMA removal (TLMAR5), and at discharge from the PACU (Tdis).
Emergency treatment for adverse events
Immediately remove the fiberoptic bronchoscope
Continuous positive airway pressure at 10cmH2O
2 mg·kg− 1 Propofol iv.
1 mg·kg− 1 Suxamethonium iv.
10μg Adrenaline iv.
2 mg·kg−1 Propofol and 1 μg·kg− 1 remifentanil iv.
2 mg·kg− 1 Propofol and 1 μg·kg− 1 remifentanil iv.
Manual positive-pressure ventilation
Increase inhaled oxygen concentration
Manual positive-pressure ventilation
Carbon dioxide retention
Clinical scales used for the study
Separation score 
1. Excellent; separate easily
2. Good; not clinging, whimpers, easy to calm
3. Fair; not clinging, cries, not calm with reassurance
4. Poor; crying, clinging to their parent
Tolerance of the anesthetic mask during anesthesia induction 
1. Excellent; unafraid, cooperative, easy acceptance of mask
2. Good; slight fear of mask, easy to quite
3. Fair; moderate fear, not quite with reassurance
4. Poor; terrified, crying, agitated
Agitation score 
2. Awake, calm, and cooperative
3. Crying, need consolation
4. Restless, screaming inconsolable
5. Combative, disoriented, trashing
Sample size calculation
The sample size was calculated based on the ability to detect a 44.4% reduction in the incidence of laryngospasm with dexmedetomidine premedication (55.6% vs 11.1%, according to our preliminary study) with 80% power. The level of significance was set at two-sided α = 0.05. It was then concluded that the sample size required to achieve a statistically significance was 20 samples for each group.
A t-test and Wilcoxon’s rank-sum test were used to access continuous variables, and the 휒2 test to assess categorical variables. The statistical analysis was performed with SPSS software, version 20.0 (IBM Corp., Armonk, NY, USA), P < 0.05 was considered to indicate statistical significance.
17.2 ± 6.3
18.0 ± 6.6
10.9 ± 2.2
10.8 ± 1.2
Site of foreign body (T/RB/LB/BB)
Duration of foreign body aspiration (days)
Time-lag between diagnosis and retrieval of foreign body (days)
Heart rate (beats per minute)
136 ± 21
151 ± 14
Respiratory rate (beats per minute)
37 ± 9
37 ± 5
Oxygen saturation (%)
Tolerance of anesthetic mask 2/3/4
Agitation score 2/3/4/5
The characteristics and outcome of the fiberoptic bronchoscopies
Size of LMA
Size of fiberoptic scope (mm)
Duration of anesthesia induction (min)
Duration of procedure (min)
Extubation time (min)
Recovery time (min)
The extubation time and recovery time were similar in the two groups (P = 0.758 and P = 0.445, respectively). Agitation during recovery occurred in 25% (n = 5) of patients in the DEX group and 70% (n = 14) in the control group (P = 0.004). The agitation scores were significantly lower in patients premediated with dexmedetomidine (P = 0.017).
Our principal finding was that intranasal dexmedetomidine at a dose of 1 μg·kg− 1 given 25 min before anesthesia induction could reduce the incidence of laryngospasm, breath-holding, and coughing during fiberoptic bronchoscopy for FB removal in children. Furthermore, intranasal dexmedetomidine was associated with lower parent–child separation scores, frequency of agitation, and agitation scores. Moreover, it did not prolong the recovery time.
Dexmedetomidine uniquely provides sedative and analgesic effects without respiratory depression [14, 20, 21], even when administered at doses higher than recommended for sedation . These properties render dexmedetomidine a potentially useful drug during airway surgery. Dexmedetomidine infusion given to remove an airway FB removal attenuates the airway response to fiberoptic bronchoscopy similar to remifentanil . Dexmedetomidine also attenuates the airway response to endotracheal extubation [23, 24].
We also observed a lower incidence of laryngospasm, breath-holding, and coughing during fiberoptic bronchoscopy in patients given dexmedetomidine, suggesting that intranasal dexmedetomidine relieves intratracheal and laryngeal stimuli during this procedure. This effect is possibly mediated via its sedative and analgesic properties. Dexmedetomidine provides analgesia via receptors in the spinal cord, and attenuation of the stress response . As shown in previous studies [10, 11], we also found that premedication with intranasal dexmedetomidine reduced the patients’ separation anxiety and resulted in more satisfactory tolerance of the facial mask during anesthesia induction. Reduction in the secretions as a result of less crying during patient separation from the parents and also during induction of anesthesia can reduce the incidence of laryngospasm and coughing.
In contrast to previous reports [23, 24, 26], we observed a similar incidence of oxygen desaturation and coughing in the PACU in our two study groups. The time from FB aspiration to its removal was similar in the two groups. This similar time lag might cause a similar incidence of pre-procedure pneumonia. Preoperative pneumonia increases respiratory tract secretions, which causes intraoperative hypoxemia, and an increased incidence of coughing in the PACU. The similar incidences in postoperative coughing may have been associated with the intra-tracheal use of acetylcysteine during the procedure.
Similar to a previous study , the RR was more stable in patients given dexmedetomidine. In addition, the lower incidence of CO2 retention indicated that dexmedetomidine did not impair the respiratory drive. We observed a lower RR in the control group during the procedure, which must have been associated with inhalation of a higher concentration of sevoflurane and/or greater consumption of propofol and remifentanil. The Et-Sevo was significantly higher in the control group during the procedure, RR decreased as the concentration of sevoflurane increased . Propofol inhibits respiration by acting on GABA receptors [28, 29], whereas remifentanil produces analgesia and respiratory depression by acting on μ receptors. Moreover, the respiratory rate, CO2 retention, and oxygen saturation are generally maintained during dexmedetomidine sedation in children [30, 31, 32].
Compare with the control group, the lower HR during the study period in the DEX group might be explained by the decreased sympathetic outflow and circulating levels of catecholamines caused by dexmedetomidine .
In the present study, intranasal dexmedetomidine did not significantly prolong the patients’ recovery time, but it did significantly reduce the incidence of postoperative agitation. Emergence agitation occurs frequently in children during recovery from sevoflurane anesthesia. Postoperative restlessness is associated with a risk of self-injury and is a source of stress for both caregivers and family members. Dexmedetomidine has been used in the management of postoperative agitation because of its sedative and analgesic effects .
This new anesthetic agent, dexmedetomidine used alone at clinical doses, has not induced neurotoxicity in juvenile animal models [35, 36]. It exhibits neuroprotective effects in vitro and attenuates neuro-apoptosis caused by other anesthetic agents, [37, 38]. It is thus considered one of the rare “neuro-safe” anesthetic agents  used in infants.
There were few limitations in our study. Firstly, we used only a single dose of dexmedetomidine and thus did not compare the effects of different doses. Yuen et al., however, in a study of patients < 4 years of age, showed that intranasal dexmedetomidine 1 μg·kg− 1 had sedative effects similar to 2 μg·kg− 1 . Indeed, our preliminary results showed that dexmedetomidine 1 μg·kg− 1 produces a satisfactory sedative effects without prolonged recovery time, whereas a 2 μg·kg− 1 or higher dose of dexmedetomidine significantly prolong the recovery time. Secondly, the sample size of this study is small. We only considered the reduction in laryngospasm (as complication) when calculating the sample size, which may not be adequately powered for other complications. Future studies should consider other complications as well such as coughing, body movements, bronchospasm etc. while calculating the sample size.
Intranasal dexmedetomidine at 1 μg·kg− 1, with its sedative and analgesic effects, reduced the incidences of laryngospasm, breath-holding, and coughing during fiberoptic bronchoscopy for FB removal. Moreover, it reduced postoperative agitation without a prolonged recovery time.
We would like to thank Liping Song, Chunlan Zheng, for helping us prepare the drugs.
Consent to publish
YMB: contributed to performing all statistical analyses, drafting the manuscript. YSM: performed all statistical analyses, recruited study participants. JN: performed data acquisition. LW: contributed to the design of the work, and writing the manuscript. All authors have read and approved the manuscript.
This study was financially supported by Science and Technology Department of Sichuan Province, China (No. 2018sz0236). The funding agents play no role in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript.
Ethics approval and consent to participate
The protocol was approved by approval by the China Ethics Committee of Registering Clinical Trials (ChiECRCT-20180113). Address: West China Hospital, Sichuan University, NO. 37, Guo Xue Xiang, Chengdu, Sichuan, China. The study was registered with the Chinese Clinical Trial Registry (registration number: ChiCTR1800017273) on July 20, 2018. Website: http://www.chictr.org.cn/edit.aspx?pid=28583&htm=4. Written informed consent was obtained from the parents or legal guardians of all participants in the trial.
The authors have no conflicts of interest.
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