Setting and design
This retrospective study was conducted at the IRCCS Ospedale Pediatrico Bambino Gesù, a referral center for the treatment of pediatric patients in Italy, from January 2018 to January 2019. The local Ethical Committee has approved the study design (protocol number 1587_OPBG_2018), and the legal guardians of all patients signed an informed consent for the use of the patient’s data for research purposes.
In total, 106 children of any gender, aged 2–10 years who underwent plastic and reconstructive surgery (first and elective) lasting 60–90 minutes were considered. All patients had to be classified as American Society of Anesthesiologists (ASA) grade I and II; patients were not considered if they presented psychiatric disorders or mental retardation, alterations of metabolism or neurological deficit, or could not receive dexmedetomidine (e.g. due to known intolerance, history of cardiac disease, stroke, heart block, intracranial bleeding, -blocker or digital therapy).
All patients received anesthesia induction via facemask with increasing concentrations of sevoflurane (max: 8%) in 40% oxygen and 60% nitrous oxide. When bispectral index values were between 50 and 40, a venous access was acquired, through which 2 g/kg of fentanyl and 0.6 mg/kg of rocuronium were administered before intubation. Anesthesia was then maintained with 2.5% sevoflurane end tidal (40% oxygen and 60% air).
All patients received a fluid therapy with physiological saline solution 5–10 ml/kg/h and ranitidine 2 mg/kg to ensure gastric protection. At awakening, intravenous paracetamol was administered at a dose of 15 mg/kg and ketorolac 0.5 mg/kg if required by internal protocols.
Clinical monitoring throughout the course of anesthesia for all patients comprised continuous ECG, SpO2, temperature, bispectral index, mean arterial pressure every 3 minutes.
All patients were extubated and transferred to the recovery room where they were monitored for vital signs (SpO2, continuous ECG, mean arterial pressure every five minutes and temperature).
The onset of ED was evaluated during this period using the Postanesthetic Emergence Delirium Scale . Furthermore, this scale assigns scores from 0 to 20 based on the ability of the child to maintain a visual contact with those around him, if his/her movements are finalized, patient restlessness and inconsolability. Postanesthetic Emergence Delirium Scale scores >12 indicate the onset of ED [19,20].
The Aldrete scale was used to determine whether the child could be discharged , with scores >9 indicative of possible discharge.
Use of dexmedetomidine
Among the 106 evaluated patients, 50 have been premedicated with dexmedetomidine (dexmedetomidine group), at the dose of 2.5 g/kg administered intranasally 30 minutes before anesthesia induction . The decision to administer dexmedetomidine was taken by the anesthesiologist, according to the consideration of the grade of anxiousness of that patient at the moment of the preoperatory visit and according to internal protocols. A nasal mucosal atomization device was used for premedication .
Patients who did not receive dexmedetomidine premedication represented the control group (n = 56; control group).
We evaluated the incidence of ED according to the use of dexmedetomidine premedication. A subgroup analysis was also performed with respect to the use of general anesthesia or combined anesthesia (general anesthesia and locoregional block that could be brachial plexus block, tap block, sciatic and femoral nerve block or penile nerve block). Patients were also stratified within each group according to age (2–3 years, 3–6 years, 6–10 years) to investigate the potential effects of age on the onset of ED.
The length of anesthesia and duration of staying in the surgical area were also evaluated to analyze whether the premedication with dexmedetomidine could affect these parameters. Hemodynamic parameters (heart rate, mean arterial pressure) were also monitored, and safety considerations were performed by the CTCAE, version 4.0; the potential association of adverse events with dexmedetomidine was judged by the treating physicians.
Our sample size estimation was based on the incidence of ED in children who received preoperative intranasal dexmedetomidine and in children who received only saline solution.16 In total, 27 patients were required in each group to detect a 45% difference in the incidence of ED between the groups with a statistical power of 90% and a type I error α equal to 1%. Considering a dropout rate of 20%, the minimum number of patients to include was increased to 34 per group.
Data were analyzed by descriptive statistics. For the incidence of ED and the hemodynamic parameters, statistical comparisons among groups were performed by the Chi square test or Fisher’s exact test, the Student t-test or the Mann-Whitney test as appropriate.
Results were considered statistically significant for p-values <0.05. Stata software (StataCorp. 2019. Stata Statistical Software: Release 16. College Station, TX: StataCorp LLC) was used for statistical analysis.