Study design, setting, participants
The medical records of patients aged <18 years who visited the pediatric emergency room of Seoul Asan Medical Center between January and December 2019, and were sedated for diagnostic testing, were reviewed. Patients who required advanced airway interventions, such as tracheostomy or endotracheal intubation, before the test were excluded. This study was approved by the institutional review board of the Asan Medical Center, Seoul, Korea (IRB number: 2020–1635). All methods were performed in accordance with the relevant guidelines and regulations by including a statement in the Methods section.
Baseline demographic and clinical characteristics were recorded, including patient age and gender; results of presedative assessment; sedative regimens, including types and dosages of sedative agents and intervals between doses; and vital signs, level of consciousness, and AEs during sedation. The type of tests conducted during sedation and patient diagnosis determined by the examination were investigated.
All patients and/or their parents provided written informed consent after the purpose and method of sedation, and its possible AEs, were explained to them. Prior to sedation, patients’ vital signs, oxygen saturation, weight, age, predicted diagnosis, test modality, dental condition, signs of upper airway obstruction, modified Mallampati score , and American Society of Anesthesiologists (ASA) physical status  were determined. Patients with sedation-associated risk factors for AEs or their parents were required to sign an augmented informed consent form and were carefully monitored during sedation. A percutaneous oxygen saturation monitor was attached to each patient, and a portable oxygen tank, oxygen supply tools, and airway devices were prepared.
A standardized sedation protocol was formulated by physicians in the anesthesiology and pediatrics departments, and was based on the pharmacokinetics and pharmacodynamics of chloral hydrate, midazolam, and ketamine (Fig. 1). The dosage and usage of all sedatives were checked twice with the nurse or doctor in the ED. Per oral (PO) chloral hydrate 50 mg/kg was administered, and the patient was monitored for 30 min. If PO administration was not possible, intravenous (IV) drugs were administered initially. If the depth of sedation was suboptimal, 25 mg/kg PO chloral hydrate, IV midazolam 0.1 mg/kg (maximum 3 mg), and IV midazolam 0.1 mg/kg (maximum 2 mg) were administered sequentially, with observation periods of 20, 10, and 10 min, respectively. If the required depth of sedation was not attained, IV ketamine doses of 1 and 0.5–1 mg/kg were administered sequentially at 10 min intervals. If the depth of sedation remained suboptimal, the test was postponed, or an anesthesiologist was consulted.
This study utilized standardized definitions from the Quebec Guidelines, a consensus-based document developed by North American experts in pediatric procedural sedation, as well as general medical terms . Head concussion was defined as a traumatic head injury that temporarily affected brain function, including loss of consciousness, vomiting, and lethargy. Dental abnormalities were defined as abnormalities of the teeth, jaw, or oropharynx that could prevent mouth opening or obstruct the airways. Upper airway obstructions were defined as those with a potential for airway complications, including tracheomalacia, laryngomalacia, congenital anomalies of the airways and neck, sleep apnea, and severe snoring. The duration of sedation was defined as the time from the administration of the first sedative to physiologic recovery. ED recovery was defined as the time from the end of sedation to physiologic recovery state allowing safe discharge from the ED.
Hypopnea was defined as oxygen desaturation requiring airway repositioning, oxygen administration, or increased oxygen, without the need for vigorous tactile stimulation or positive pressure ventilation. Apnea was defined as oxygen desaturation requiring administration of reversal agents, vigorous tactile stimulation, or positive pressure ventilation. Vomiting was defined as the expulsion of gastric contents through the mouth or nose during the induction or maintenance of sedation or during recovery in the ED. Hypotension was defined as systolic blood pressure (BP) <90 mm Hg, mean arterial pressure <70 mm Hg, <5th percentile for age, or systolic BP <2 standard deviations (SDs) below normal for age. Pre-hypotension was defined as BP lower than initially observed but not corresponding to the definition of hypotension. A paradoxical response was defined as unanticipated restlessness or agitation in response to the administration of sedative drugs during sedation. Myoclonus was defined as involuntary, brief contractions of some muscle fibers, of an entire muscle, or of several muscles in one group, leading to movements of the corresponding body parts, but usually lasting <100 milliseconds . Serious AEs included apnea, laryngospasm, hypotension, bradycardia, complete airway obstruction, clinically apparent pulmonary aspiration, permanent neurologic injury, or death, requiring significant interventions. Failure to test was defined as the suspension of a test due to serious AE, or postponement of a test due to a suboptimal depth of sedation despite administration of maximum doses of sedative agents according to protocol.
Patients were categorized into groups with and without AEs. Continuous variables were compared using Mann–Whitney U-tests, and categorical variables were compared using χ-square tests. Associations of clinical characteristics with AEs were analyzed by grouping patients by regimen and sedative dosages. The total dosage was calculated by adding the following doses as a single dose: chloral hydrate, 50 mg/kg; midazolam, 0.1 mg/kg; and ketamine, 1 mg/kg. All statistical analyses were performed using PASW Statistics Version 18.