This observational study was approved by Muğla Sıtkı Koçman University Clinical Research Ethic Committee (approval number: XII, 26.04.2018) and registered at anzctr.org.au (Trial ID: ACTRN12618000551291) and conducted in accordance with the current Declaration of Helsinki. Signed informed consents were obtained both from parents of all children and children themselves who were over 6 years of age. Patients between 3-18 years old with American Society of Anesthesiologists (ASA) physical status I-II and scheduled for a T or AT surgery were prospectively included in the study. The exclusion criteria were patients with known acute or chronic ophthalmic diseases, history of previous ophthalmic surgery, increased ICP, receiving ß blocker, calcium canal blocker, statin or nitrate treatment, more than one attempt for endotracheal intubation and duration of mouth gag application < 20 minutes.
All children received preoperative medication with midazolam 0.5 mg kg-1 orally (maximum dose of 15 mg) approximately 15-20 minutes prior to the induction of anaesthesia. A standard monitoring was employed to all children with electrocardiography, non-invasive arterial blood pressure, pulse oximetry, bi-spectral index (BIS) (Datex-Ohmeda S/5 monitor M-BIS module, Helsinki, Finland), nasopharyngeal temperature, end-tidal CO2 (EtCO2) measurement and gas analysis. Anaesthesia was induced with intravenous propofol 1-2 mg/kg, fentanyl 1 mcg/kg and rocuronium bromide 0.6 mg/kg. When BIS score decreased under 60, the patients were intubated by an experienced anaesthesiologist at the first attempt. Anaesthesia was maintained with sevoflurane in 40% O2 and 60% air mixture, and the inspired concentration of sevoflurane was targeted to maintain a BIS score between 40-60. Peak inspiratory pressure was strictly maintained between 11 and 13 cmH2O not to effect ICP. Following endotracheal intubation, the ear-nose-throat (ENT) specialist placed the Boyle-Davis mouth gag. The extension of mouth opening and head position of patients were adjusted by the same ENT specialist to enhance the exposure of adenoid and tonsillar tissue. When the placement of the mouth gag was completed, operating room (OR) anaesthesiologists took a photograph of the neck extension in the lateral view. The degree of neck extension was assessed by the angle between the Frankfort plane and horizontal plane of the operation table in natural position (Frankfort plane angle). The angle was calculated by using an application (Angles in Photos, 2015 kublaidos) (Fig. 1). The anesthesiologist recorded the average of 2 Frankfort plane angle measurements. A Frankfort plane was officially described in the anthropologic conference in Frankfort in 1884. It is an imaginary line passing from left orbitale to left porion point and it has been used as a reference plane for cephalometric studies. Recently, Frankfort plane angle was used for the assessment of neck flexion-extension in the study of Kobayashi et al (12). The horizontal plane was created by drawing an imaginary line touching the porion and passing parallel to the operation table while the table was in neutral position. A very recent study used a similar method to calculate the degree next extension to evaluate its effect on ONSD of children undergoing palatoplasty surgery (13).
ONSD was measured by two investigators who had experience in over 50 cases. A linear 6-13 Hz probe (Fujifilm Sonosite, Bothwell, USA) was used for the sonographic measurements at four different time-points. A thick layer of water-soluble ultrasound-transmission jelly was applied over the left upper eyelid of each patient. Then the probe was gently placed over the eyelid without exerting excessive pressure. The probe was moved with careful attention to find the best image of optic nerve entering into the globe. The ONSD was measured 3 mm posterior to the globe (Fig. 2). The investigators measured ONSD 3 times from the same eye and recorded the average of these measurements at four different time-points: (T0) after induction of anaesthesia, (T1) after endotracheal intubation, (T2) after the placement of the mouth gag and (T3) 20 minutes after the placement of the mouth gag. At each time-point, heart rate (HR), mean arterial pressure (MAP), EtCO2 and nasopharyngeal temperature (temp) were also recorded. The haemodynamic parameters, temp and EtCO2 which are known to be associated with intracranial pressure (14), were maintained in normal ranges in order to minimize their effects on ONSD.
The primary out-come of the study was the change in ONSD measurements between T3 and T4 and the secondary out-come was the effect of degree of next extension on mean ONSD changes between T2 and T3 time-points.
Sample size
Power estimation analysis conducted a priori concluded a sample size of 30 with 80% power with alpha error of 0.05, then we decided to include 35 patients with assuming possible drop-outs. The mean ONSD measurement in healthy pediatric population is 3.08±0.36 mm. An increase ³ 0.3 mm in mean ONSD measurement (10% of mean ONSD value in healthy pediatric population) was considered clinically significant (15). Considering a 0.05 significance level for type 1 error and 0.20 significance level for type two error, the collected data was sufficient for the power of statistical tests that were used.
Statistical Analysis
Statistical analyses were conducted using SPSS version 25 (made by SPSS Incorporated, located in Chicago, Illinois, USA). All continuous variables including age, weight, globe size, ONSD, EtCO2, Temp, HR, MAP are presented as mean and standard deviation (±SD), and the categorical variables, gender and surgical type, are presented as both numbers and percentile (%). The relationship between Frankfort plane angle and ONSD changes analyzed by regression model. Linear mixed model was used to observe the variation of repeated ONSD measurements and the other parameters (EtCO2, Temp, HR, MAP) over time. Post hoc analyses were performed using Bonferroni correction for multiple comparisons, for time-level as pairwise comparisons, since the time wise differences were statistically significant in all parameters observed. Additionally, figure for parameters changed by time is plotted, and presented. A p value of < 0.05 was considered significant for the analyses conducted.