This prospective, randomized and controlled trial was carried out from June, 2020 to March, 2021 after approved by the Institutional Review Board of Shanghai Children's Medical Centre, Shanghai, China on 30 April 2020 (no: SCMCIRB-K2020036-1). This study was registered in the Chinese Clinical Trial Registry (ChiCTR2000033583) on 6 June 2020. Written informed consent was obtained from a parent or legal guardian for each subject. The trial carried out in accordance with the declaration of Helsinki and good clinical practical guidelins, and the authors guaranteed the accuracy and completeness of the data and analysis of this paper.
Children, aged 3 to 6 years, ASA physical status Ⅰ-Ⅱ, and underwent elective minor surgery under general anesthesia (herniorrhaphy, tonsillectomies etc.) were recruited. The exclusion criteria included parental refusal, significant hearing or visual impairments, developmental delay or neurological diseases, and having any previous surgeries.
Randomization and blinding
Based on a computer-generated randomization list, participants were assigned either to picture book group or control group in a 1:1 ratio. The group assignment slips were concealed in an envelope, which was opened only by a designated nurse who was not involved other parts of study.
The children and their family were not blinded to the grouping process. The research date collector, anesthesiologists, surgeons and nurses in the operating room were blinded to the group assignment.
The general information about fasting, surgical procedure, risks of anaesthesia, and pain management were given to both groups during their first visit at anaesthesia outpatient clinic within two weeks prior to surgery. In addition, an animated picture book with the illustrated story of perioperative events was mailed to the patient’s home in picture-book group one week before surgery for them to read with their parents.
The picture book
The animated picture book titled “Tom is in Hospital “was written by Christophe Le Masne, illustrated by Marie-Aline Bawin and translated by Li Mei. With the help of colorful illustrations and a few of simple and easily understanding words, this book vividly told the perioperative story of a bunny rabbit (named Tom) who had went through. Tom was worried and scared at the beginning for something going to happen to his body, which he never heard of. With his parents’ encouragement and instructive explanation, he took sessions of preoperative psychological preparation and education, started understanding the surgical process step by step, and gradually overcame his fears. With full curiosity and eager to participate, he bravely followed the doctors and walked into the operating room and laid himself on the surgical bed with smile, etc. At last, surgery and anesthesia went through successfully and safely. This book briefly described the events and scenes about surgery and anesthesia in a light and humorous way through a lovely animated character, and gave children the basic information what they expect from the surgery(Figure 1).
All participants were assessed for eligibility after the surgery had been confirmed by surgeons in the outpatient clinic. After recruitment, baseline characteristics were collected for both children and parents, such as, birth order, temperament of children (emotionality, activity, sociability, and impulsivity, EASI) , and educational level of parents, etc. In addition, general information about anesthesia and surgery was given. Parents in picture book group were also given verbal instruction at outpatient clinic about the book reading protocol.
One week before patients’ hospitalization, the picture books and the detailed reading tips were mailed to study participants’ home. Parents were instructed not to hide the information about the surgery from their children, instead to help kids to get the most basic surgical and anesthetic knowledge through the picture book. Guided by parents, children would go over the series of pictures first to get familiar with the character (Tom) and surgical environment, and so that the children can form a preliminary impression of the operation. Then the child and adult look through those pictures and read the context together at least three times. During this process, parents would ask the child’s thought about this story and provoke the kids for questions, specifically who, what, when, where, why and how, to get the child become more involved in the shared reading session.
The subjects were admitted to the surgical ward in our hospital early on the day of surgery, and were evaluated during a pre-anesthesia visit by an anesthesiologist from the research team. This allowed delivering more details to parents and children about surgery and anesthesia and addressing concerns and answering questions. To make sure the child have basic impression or knowledge about this book, at least three simple questions were asked for kid to answer, such as, “Do you know the name of this lovely ‘rabbit’ (point to the picture)?” “Why did ‘Tom’ come to hospital with his parents?” and “Did ‘Tom’ made more friends in play room with other kids?” “Did you see ‘Tom’ waking-up smiling and happy after surgery” If parents did not follow the reading instruction, or if the child could not answer any one of those questions, the child was seen as not receiving interventions.
Anesthesia induction and the patients’ compliance
As required, all subjects arrived at the preoperative holding area about 30 mins before the anesthesia start time, and no premedication was given. One of parents, in our hospital, was allowed to accompany in the holding area, and parent was separated from his or her child just before OR time started. All patients were induced by intravenous anesthesia. Child’s compliance during the induction of anesthesia was evaluated with the Induction Compliance Checklist (ICC), which was previously developed by Kain and his colleagues and it contains 11 items .
Preoperative anxiety measurements
The modified Yale Preoperative Anxiety Scale Short Form (mYPAS-SF)  was used to assess children’s anxiety. The mYPAS-SF is a simplified version of mYPAS, originally developed by Kain et al, and it is more convenient to apply to clinical research settings . This scale contains 18 items in 4 dimensions (activity, emotional expressivity, state of arousal, and vocalization). For each dimension, a blinded investigator recorded the highest scoring behavior witnessed during the observation period .
Children’s anxiety was assessed at the six time points as following: in the anesthesia outpatient clinic (baseline, T0), during a pre-anesthesia visit by anesthesiologist shortly after admitted to surgical ward (T1), in the preoperative holding area (T2), at the time of separation from parent to OR (T3), on entrance to OR (T4), and at the time of ready for intravenous cannulation (T5) (Figure 2).
Parental anxiety was measured from T0 to T3 using a visual analogue scale (VAS) (ranging from 1 to 10, “no anxiety” to “extreme anxiety”) .
The primary outcome was children’s anxiety measured in the OR just before intravenous cannulation. The secondary outcomes included children’s compliance during the induction of anesthesia, children’s anxiety during the pre-anesthetic visit and at separation to OR, and parental anxiety.
Sample size calculation
Our pilot study reported a mean anxiety score of 63.9 ± 21.9 just before the intravenous anesthesia induction in control group. We expected mYPAS-SF scores in the picture book group to decrease by ≥15 points. A sample size calculation of a value of 0.05 and a test power of 90% was performed using the PASS software (Power Analysis and Sample Size software, vision 11.0.7). The minimum of 45 patients in each group was required. To allow for potential post-recruitment drop-out, we initially aimed to recruit 112 participants.
Outcome data were analyzed in the intention to treat (ITT) population. The Shapiro-Wilk test was run to assess the normality. Normally distributed data were reported as mean (standard deviation) and compared with the student’s t - test. Non-normally distributed data or ordinal data were presented as median (interquartile range) and compared with Mann-Whitney U - test. Categorical data were presented as number (percentage) and compared with the c2 test or Fisher’s exact test. Changes in anxiety over time were analyzed using generalized estimated equation, with Bonferroni adjustment for multiple tests.
All statistical analyses were performed using SPSS 25.0 (SPSS Inc., Chicago, IL). A P-value < 0.05 was considered to be statistically significant.