This randomized, double-blind study enrolled 108 children who were classified as American Society of Anesthesiologists physical status I or II (i.e. normal/healthy or with mild systemic disease; http://www.asahq.org), aged 3–9 years, who were scheduled to undergo strabismus surgery or epiblepharon repair surgery under general anesthesia at the Department of Ophthalmology, Hallym University Sacred Heart Hospital, College of Medicine, Hallym University, Anyang, Republic of Korea.
Patients were excluded for any of the following reasons: developmental delay, neurological or psychological disease, history of sleep apnea, or history of general anesthesia.
This study was approved by the Institutional Review Board of Hallym University Sacred Heart Hospital (reference numbers: IORG0004993, IRB00005964). Written informed consent was obtained from the parents or legal guardians.
No premedication was administered. While in the operating room, all patients were monitored by standard limb lead electrocardiography, pulse oximetry, non-invasive blood pressure measurements, end-tidal anaesthetic gas concentration, and capnography(CARESCAPE Monitor B650; GE Healthcare, Helsinki, Finland). Anesthesia was induced with 5 mg/kg of thiopental sodium intravenous (i.v.). After loss of consciousness, children were ventilated with 3–3.5 vol. % of sevoflurane in oxygen via a face mask and fully relaxed with 0.6 mg/kg of rocuronium bromide i.v.. They were intubated with an endotracheal tube of appropriate size for age. A half dose of thiopental sodium was administered before transferring children to the operating room in cases of children with a separation score of 3 or 4 (Parental Separation Anxiety Scale (PSAS);1 = excellent; separation easily, 2 = good; not clinging, whimpers, calms with reassurance, 3 = fair; not clinging, will not calm or quiet, 4 = poor; crying, clinging to parent) . Anesthesia was maintained with 1.5–3 % sevoflurane and air in oxygen (FIO2 0.5). Mean arterial pressure (MAP), heart rate (HR), and end-tidal sevoflurane concentration (Et-sevo) were recorded at baseline and 15, 30, and 45 min after induction of anesthesia.
Study drugs were prepared by an anesthesiologist, who did not participate in data collection, in 3-ml and 20-ml syringes: normal saline with or without alfentanil in a total volume of 2 mlin a 3-ml syringe and normal saline 20 ml with or without 50 μg/ml of remifentanil in a 20-ml syringe. Patients were randomly allocated into one of three groups (S, R, RA) by a sealed-envelope method. Patients in group S received continuous infusion of normal saline from a 20-ml syringe (infusion rate comparable to remifentanil0.1 μg/kg/min)from induction of anesthesia to the end of surgery and 2 ml of normal saline10 min before the end of surgery. Patients in group R received continuous infusion of remifentanil(0.1 μg/kg/min) from induction to the end of surgery and 2 ml of normal saline 10 min before the end of surgery. Patients in group RA received continuous infusion of remifentanil(0.1 μg/kg/min) and 5 μg/kg of alfentanil 10 min before the end of surgery.
The concentration of sevoflurane was adjusted to maintain blood pressure and heart rate within a 20 % deviation from baseline values. Mechanical ventilation was adjusted to maintain a partial pressure of end-tidal carbon dioxide of 35–40 mmHg throughout the procedure. At the end of surgery, sevoflurane and the study drug prepared in 20-ml synringe (with or without remifentanil) were discontinued. All children received eye ointment in both eyes without eye patches. Antagonism of muscle relaxation was achieved with i.v.administration of 0.05 mg/kg neostigmine and 0.008 mg/kg glycopyrrolate. The endotracheal tube was removed when the patient displayed adequate spontaneous ventilation, motor activity, and facial grimacing. The time to extubation(ET) was defined as the time from the end of sevoflurane administration to removal of the endotracheal tube. On arrival to the post-anesthetic care unit (PACU), one of the patient’s parents stayed with their child until discharge. Patients were discharged from the PACU when the postanesthetic Aldrete recovery score was ≥ 9, and the duration of PACU stay was recorded.
Demographic data andthe duration of anesthesia were recorded for each patient. MAP, HR, and end-tidal sevoflurane concentration were recorded before induction of anesthesia and at 15, 30, and 45 min after induction of anesthesia.
The primary outcome of this study was the incidence of EA. The degree of agitation was graded on the four-point scale ofWatcha et al.  (1 = calm, 2 = crying, but can be consoled, 3 = crying, cannot be consoled, and 4 = agitated and thrashing around) from immediately after extubation and the highest score during emergence was used for the evaluation. For statistical purposes, grades 3 or 4 were considered EA. Alfentanil(5 μg/kg) was given for severe agitation (grade 4) lasting longer than 5 min. Secondary outcomes were the time to extubation and duration of PACU stay. All data were recordedby another anesthesiologist who did not know which syringe contained remifentaniland which containedalfentanil.
In a preliminary study conducted in 15 patients who received sevoflurane alone, 11 patients who underwent pediatric ophthalmic surgery showedEA. A sample-size calculation was made using a power analysis (α = 0.05, β = 0.8) to detect a 50 % reduction of the incidenceinEA (from 73 to 37 %) and was found to require 32 patients per group. Assuming a potential dropout rate of 10 %, the final sample size was set at 36 patients per group. The data are expressed as mean ± standard deviation or as numbers of patients. All statistical analyses were performed using the SPSS for Windows software package(SPSS Inc, IL, USA). A one-way analysis of variance (ANOVA) was employed in the intergroup comparisons of age, height, weight, duration of anesthesia, extubation time, and PACU time. Sex, numbers of patients with separation score (≥3), incidence of EA, and use of rescue drug were compared using a chi-square test. MAP, HR, and End-tidal Sevoflurane concentration were analyzed by repeated measured ANOVA and intergroup differences at the same time points were compared using one-way ANOVA. And all significant results were further analyzed with the scheff’s post hoc test. A p-value < 0.05 was considered to indicate statistical significance.