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.
Patients
We enrolled 40 children (age 6 to 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.
In preparation, all patients fasted from solids for 6 h, breast milk for 4 h, and clear fluids for 2 h before intervention. They were premedicated with atropine at 10 ug·kg−1 i.v. 30 min before the induction of anesthesia. The patients were randomly assigned to one of two groups (Dexmedetomidine (DEX) group and control group) using a simple computerized concealed-envelope method. At 25 min before anesthesia induction, the patients were administered either intranasal dexmedetomidine (20171202; Nhwa Pharmaceutical Co., Ltd., Jiangsu, China) 1 ug·kg−1 (100 µg in 1 ml) or intranasal normal saline 0.01 ml·kg−1 (Figure 1). The intranasal drugs were prepared by a dispensing nurse of our department, then administered by a doctor who was unware
Fiberoptic bronchoscopy
Anesthesia was induced via mask using 5%-8% sevoflurane in 100% oxygen at 6 L·min−1 until the BIS decreased to 40 or 4mins after , at which point the LMA (Henan Tuoren Medical Equipment CO., Ltd.; common LMA-classic) was inserted. Anesthesia was maintained using 3%-6% sevoflurane in fresh gas at 4 L·min−1 with the BIS at 40-60. The external diameters of the two widely used flexible bronchoscopes for FBs removal were 2.8mm and 4.0mm, respectively. At the beginning of the procedure, lidocaine 2mg·Kg-1 was sprayed on the epiglottis and larynx. FBs were removed in an FB basket (Boston Scientific Corporation; Zero TipTM Airway Retrieval Basket; OD 1.0mm) through the bronchoscope’s suction channel, the sizes of the channels were 1.2mm and 2.0mm for 2.8mm and 4.0mm bronchoscopies (Figure 2). At the end of the procedure, before withdrawing the fiberoptic bronchoscope from the trachea, acetylcysteine was sprayed into the trachea via the bronchoscope. Sevoflurane was discontinued after completion of the procedure, and the patient was allowed to spontaneously breathe 100% oxygen at 6 L·min−1. The LMA was removed when the patient moved spontaneously or exhibited a jaw thrust. After removing the LMA, the child was transferred to the postoperative care unit (PACU) for recovery, where he or she was given oxygen at 4-6 L·min−1 via mask, and underwent heart rat (HR) and oxygen saturation (SpO2) monitoring. The patient was discharged from the PACU when the SpO2 had stabilized at >92% for 10 min on room air.
Monitoring
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).
Outcome measurements
The primary outcome measurements were the incidence of adverse events including: oxygen desaturation, CO2 retention, coughing, body movements, bronchospasm, laryngospasm, breath-holding during the procedure, and coughing in the PACU. Oxygen desaturation was defined as SpO2 <90% for 10s. CO2 retention was defined as EtCO2 ≥45 mmHg at the end of the procedure. Emergency treatment measures are shown in Table 1.
The secondary outcome measurements were (1) the separation score at the time of separating the patient from their parents and entrance into the operation room, tolerance of the anesthetic mask during anesthesia induction, the agitation score of each patient in the PACU (Table 2) [19]; (2) consumptions of sevoflurane and other extra medications; (3) anesthesia induction time, Extubation time, and recovery time. Anesthesia induction time was defined as the time from beginning induction to LMA insertion. Extubation time was defined as the time from discontinuing the sevoflurane to LMA removal. Recovery time was defined as the time from discontinuing of sevoflurane to opening of the eyes either spontaneously or by vocal command. All outcome parameters were recorded by another doctor who was unaware of patient randomization.
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.
Statistical analysis
A t-test and Wilcoxon’s rank-sum test were used to access continuous variables, and the 𝜒2 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.