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INTRODUCTION
Pediatric sedation plays a crucial role in enabling accurate diagnosis and appropriate treatment for pediatric patients. It alleviates pain and anxiety associated with painful or unpleasant procedures. However, administering sedatives during the process can potentially compromise respiratory or cardiac function, leading to significant complications.
Minimizing adverse reactions and achieving an optimal depth of sedation are paramount considerations [1]. Pediatric patients are more susceptible to respiratory complications due to anatomical and physiological factors, increasing the risk of hypoxemia. Therefore, safe sedation practices are essential to prevent complications and ensure effective execution, ultimately achieving the intended diagnostic or therapeutic goals.
Previous guidelines have laid a strong foundation for safe and effective sedation [2-4]. However, methods and policies for sedation may evolve with advancements in medicine, techniques, and societal changes [5]. Consequently, continuous knowledge and skill updates are crucial. This review addresses both the fundamentals and recent developments in pediatric sedation.
DEPTH OF SEDATION AND EVALUATION
Sedation levels can range from minimal to moderate, deep, and general anesthesia. These levels are not distinctly separated. Thus, it is crucial to recognize that the intended sedation level may unintentionally progress to a deeper state. Practitioners must be prepared to manage patients who reach a deeper level of sedation than initially planned.
Several methods exist to assess sedation levels. The Michigan Sedation Scale is a simple, reliable tool that allows for quick and frequent assessment and documentation of sedation depth in children [6]. The Ramsay scale is another valid and reliable option for monitoring invasive procedures in deeply sedated pediatric patients [7]. However, for optimal evaluation in pediatric sedation, a method specifically designed for this age group is recommended. The 6-point Pediatric Sedation State Scale is a simple and user-friendly tool that facilitates documentation, and provides a standardized measure of pediatric procedural sedation effectiveness (Table 1) [8].
PRE-SEDATION EVALUATION AND FASTING
The pre-sedation evaluation involves initial risk stratification based on patient characteristics, existing medical conditions, the type of procedure, and the planned sedation technique. This helps identify risk factors for adverse events before administering specific sedatives.
For example, a study on pediatric procedural sedation for esophagogastroduodenoscopy and colonoscopy identified several independent predictors of increased adverse events: being ≤ 5 years old, having a higher American Society of Anesthesiologists physical status score (≥ 2), undergoing esophagogastroduodenoscopy ± colonoscopy, and having coexisting medical conditions such as obesity or lower airway disease [9].
Therefore, a thorough airway assessment is crucial before initiating sedation. If there is a risk of upper airway obstruction after receiving a sedative, a cautious approach is necessary. Assessing respiratory patterns during sleep at home can also be helpful. Attention should be given when pronounced sleep apnea or snoring is observed. Information about comfortable sleeping position is also crucial.
The airway assessment should also identify risk factors for difficult intubation, such as micrognathia, short neck, limited head and neck movement, small mouth, short thyromental distance, large tongue, and narrow submandibular space. A history of oromaxillofacial or otolaryngological surgery, or tracheostomy should also be considered. Conditions like microtia (abnormal outer ear development), micrognathia, and certain congenital syndromes like Pierre Robin sequence, Treacher-Collins syndrome, and Goldenhar syndrome are associated with a higher incidence of difficult airway [10]. In emergencies, tracheal intubation may be necessary. Patients younger < 1 year, underweight patients, and those with an American Society of Anesthesiologists physical status of 3 or 4 have a slightly higher risk of difficult laryngoscopy compared to their counterparts [11].
Pre-sedative fasting requirements depend on the risk level. For elective procedures, graded fasting recommendations for liquids and solids are based on an assessment of negligible, mild, or moderate aspiration risk [12]. Standard fasting guidelines can be applied to patients with risk factors or undergoing moderate-to-deep sedation: clear liquid for 2 h, breast milk for 4 h, and food, formula, and nonhuman milk for 6 h [13,14]. However, for patients with no risk factors or undergoing minimal sedation, more relaxed fasting criteria can be used (Table 2).
Utilizing a procedural sedation checklist can significantly improve patient safety. The checklist should include risk factors, airway assessment findings, fasting status, sedation plan, and basic preparations (Fig. 1).
MEDICAL PERSONNEL
Personnel responsible for pediatric sedation must possess a comprehensive understanding of both the child’s overall health and the specifics of the planned examination or procedure. This knowledge is crucial for determining the appropriate medication and dosage.
Monitoring personnel also require proper education and training. Vital signs can deteriorate rapidly during pediatric sedation, necessitating the ability to perform appropriate emergency interventions, including advanced airway management and cardiopulmonary resuscitation.
To enhance patient safety, a separate healthcare professional dedicated solely to sedation monitoring is mandatory for pediatric patients. This individual operates independently of the team performing the procedure, ensuring focused patient monitoring throughout the process.
MONITORING AND PREPARATION
Comprehensive documentation is crucial for patient safety. It should include patient assessment, informed consent, detailed sedation records (medication route, dose, and time), vital sign monitoring (every 5 min during sedation and every 15 min during recovery), sedation depth, side effects, any interventions required, and recovery and discharge instructions [2].
An emergency cart stocked with various airway management devices and medications is essential for preparedness. Monitoring equipment, including pulse oximetry, electrocardiography (ECG), heart rate monitors, blood pressure cuffs, and tools for respiration monitoring, all contribute to patient safety during sedation. The American Academy of Pediatrics and the American Academy of Pediatric Dentistry published guideline for pediatric procedural sedation in 2019 and recommend specific equipment based on the sedation depth [2]. Moderate sedation requires pulse oximetry, heart rate, blood pressure, and respiration monitoring, while ECG and capnography are recommended additions. For deep sedation, pulse oximetry, heart rate, blood pressure, and respiration monitoring are mandatory, along with ECG and capnography.
Magnetic resonance imaging (MRI) usually requires sedation, but the strong magnetic field presents limitations. Monitoring equipment must be MRI-compatible and positioned at a safe distance [15]. Although MRI-incompatible infusion/syringe pumps must be positioned outside the MRI suit, the infusion lines should be connected close to the patient for rapid adjustments. Since most equipment for emergent airway management and cardiopulmonary resuscitation (e.g., laryngoscope, and defibrillator) are MRI-incompatible, healthcare providers involved in MRI sedation must be trained to efficiently transfer patients outside the suite in emergencies.
Intravenous (IV) access is typically used for moderate to deep sedation. Early detection of respiratory depression and cardiovascular collapse is critical to prevent adverse events. A meta-analysis suggests that capnographic monitoring reduces the risk of respiratory compromise (from respiratory insufficiency to failure) during sedation [16]. For moderate sedation, continuous monitoring of ventilation using capnography is recommended unless impractical due to the patient, procedure, or equipment [17]. In uncooperative patients, capnography can be performed after sedation is achieved. Since oxygen can mask apnea by maintaining oxygen saturation, capnography can be particularly helpful in these cases. Emerging technologies for breath sound-based respiratory monitoring also hold promise.
EEG-based monitoring can be a valuable tool for physicians competent in airway and hemodynamic management to guide propofol titration and achieve deep sedation in children undergoing painful procedures [18].
SELECTION OF SEDATIVES (Table 3)
Chloral hydrate
For over a century, chloral hydrate was a mainstay in pediatric sedation due to its effectiveness, affordability, and familiarity among healthcare professionals [19,20]. However, its use has declined significantly. While chloral hydrate is no longer recommended and has not been manufactured in the United States since 2012, it remains a common choice for pediatric sedation in South Korea [5,21].
Administered orally at doses ranging from 25–100 mg/kg, chloral hydrate has a broad onset (15–45 min) and duration (20–280 min) [22]. Patients are typically observed for 30–40 min to assess sedation depth. Common side effects include nausea and vomiting (28–37%), motor imbalance (31–66%), restlessness (14–29%), agitation (0.5–29%), prolonged sedation (0.18-30%), and drowsiness the following day (27–35%). Caution is essential when administering repeated doses of chloral hydrate or combining it with other sedatives, as this can increase the risk of serious complications like respiratory depression (0.2–3.6%) [21], respiratory arrest (0.06%), and cardiac arrest (0.3%) [23].
Midazolam
Midazolam, a water-soluble, short-acting benzodiazepine, offers both anxiolytic and amnestic effects [24]. It can be administered through various routes, including IV, intramuscularly (IM), intranasally (IN), rectally, and orally [25].
For IV administration, midazolam is typically given at a dose of 0.025–0.1 mg/kg (maximum 2 mg), with the option of repeating half that dose after 2–5 min if needed. This route offers a rapid onset within 1–3 min and a duration of 15–60 min. Compared to rectal or oral administration, IN midazolam (0.2–0.4 mg/kg; maximum, 10 mg) boasts a faster onset (10–15 min) and recovery time (30–60 min) [22]. However, IN administration can cause a burning sensation due to mucosal irritation. To mitigate this, premedication with lidocaine spray or nasal atomizers is recommended [26].
While midazolam carries a risk of respiratory depression, particularly when combined with opioids or other sedatives, it is uncommon when used alone at appropriate doses. In case of paradoxical reactions (increased agitation), respiratory depression, or apnea, flumazenil (0.01 mg/kg; up to four repeated doses; maximum 1 mg or 0.05 mg/kg) can be used as an effective reversal agent for benzodiazepines. For patients receiving flumazenil, positive-pressure bag-mask ventilation should be employed if inadequate ventilation occurs. Additionally, close monitoring is recommended for 1–2 h post-administration. If the patient is taking benzodiazepine for seizure disorders, flumazenil should not be used to avoid benzodiazepine withdrawal.
Ketamine
Ketamine, a medication with dissociative anesthetic properties, also offers a moderate analgesic effect. It works by binding to N-methyl-D-aspartate receptors in the brain, producing sedation, analgesia, and a state of medical amnesia. Unlike some other sedatives, ketamine helps maintain muscle tone in the upper airway and sympathetic nervous system function [27]. This makes it a valuable option for short, painful procedures like laceration repair or fracture reduction.
IV ketamine is typically administered at a dose of 1–2 mg/kg, with the option of repeating half the dose after 10 min if needed. This route offers a rapid onset within 1 min and a short duration of 5–10 min [5,28]. IM ketamine, given at a dose of 4–5 mg/kg (with potential repeat dosing of 2–4 mg/kg after 10 min), has a slower onset (3–4 min) and a longer duration of 12–25 min. Common side effects include vomiting (more frequent with IM administration), hypersalivation, and potentially unpleasant recovery experiences [27]. To minimize vomiting, ketamine is often administered IV and combined with serotonin receptors antagonists, such as ondansetron [27]. It is important to note that anticholinergic medications can increase the risk of adverse events during ketamine sedation. Caution is advised when using ketamine in pediatric patients with difficult airways, hypertension, or elevated intracranial or intraocular pressure.
Propofol
Propofol is a potent sedative known for its rapid onset, short context-sensitive half-life, and antiemetic effect. However, due to the risk of deeper sedation leading to airway obstruction, respiratory depression, and hemodynamic compromise only pediatric anesthesiologists or sedation specialists with expertise in pediatric airway management and cardiopulmonary resuscitation should administer propofol.
Propofol can be administered IV in two ways: as bolus injection (0.5–2 mg/kg; maximum, 3 mg/kg) for brief sedation or as a continuous infusion (50–150 mcg/kg/min; maximum, 250 mcg/kg/min) for longer procedures like MRI [24]. A previous study found a significantly higher incidence of cardiorespiratory complications in patients who received only propofol during pediatric gastrointestinal (GI) endoscopy compared to those receiving other medications [29]. Combining propofol with dexmedetomidine (a loading dose of 0.5–2 mcg/kg over 10 min, with or without continuous infusion) can decrease the amount of propofol needed and reduce propofol-related complications like respiratory depression or hypotension [30,31]. Propofol should be used cautiously in patients with hypovolemic status or reduced cardiac output. To minimize injection pain associated with propofol, pretreatment with IV lidocaine (0.5 mg/kg) and using a large vein for injection are recommended.
Dexmedetomidine
Dexmedetomidine, a highly selective alpha-2 adrenergic receptor agonist, offers potent sedation and analgesia in children without inducing airway obstruction, respiratory depression, or neurotoxicity. This makes it a valuable option for procedures like diagnostic imaging, echocardiography, electroencephalography, and hearing tests.
Dexmedetomidine is typically administered IV. It starts with a loading dose of 1–2 mcg/kg (maximum total of 3 mcg/kg) given over 10 min, followed by a continuous infusion (1–2 mcg/kg/h) to maintain sedation. The IV route has an onset time of 5–10 min and effects last for 30–70 min. Due to its high absorption rate, dexmedetomidine is increasingly used for non-IV sedation in children [21,22,32-37]. IN dexmedetomidine, administered at doses of 2.5–4 mcg/kg (maximum 200 mcg), is safe and effective for various procedures, either as the primary sedative or combined with other medications. IN administration has a slower onset (20–30 min), sedation lasts longer (90–120 min) [38]. A study demonstrated the successful use of IN dexmedetomidine (1 or 2 mcg/kg) as rescue sedation in infants aged 1–6 months undergoing MRI scans [39]. This approach replaced additional chloral hydrate doses when the initial dose failed to achieve adequate sedation.
Dexmedetomidine commonly causes a decrease in heart rate (20–30%), but clinically significant hypotension is uncommon. Therefore, it is generally safe even for children with complex congenital heart disease [18]. However, caution is advised in patients with heart block (atrioventricular node or conduction pathway pathology) or decompensated heart rate-dependent cardiac output status (heart failure, septic shock). It is important to note that using anticholinergic medications (e.g., atropine or glycopyrrolate) to treat dexmedetomidine-induced bradycardia can cause severe hypertension.
Thiopental sodium
Thiopental sodium, a short-acting barbiturate, is a gamma-aminobutyric acid agonists. While once common in pediatric sedation, it has been largely replaced by newer medications with fewer side effects [40]. Administered IV at a dose of 2–3 mg/kg over 1 min (with a possible repeat dose of 1 mg/kg after 2 min), thiopental sodium offers a rapid onset within 30–60 s and has a short duration of action, lasting 5–15 min [41,42]. A significant drawback of thiopental sodium is the risk of respiratory depression or apnea, which can occur in 2–11% of cases and increases when combined with other sedatives or opioids. It should also be used with caution in patients with heart failure due to the potential for myocardial depression.
Remimazolam
Remimazolam, a recently approved (2020) ultra-short-acting benzodiazepine, is currently only for adult use in general anesthesia and sedation settings. Compared to midazolam, it boasts a faster onset and recovery time, and can be reversed with flumazenil if needed. While clinical trials (NCT04720963, NCT04851717, NCT04601350, and NCT05975255) are underway to explore its use in children, remimazolam is currently considered “off-label” for pediatric sedation. Some studies and case reports suggest its potential use in pediatric general anesthesia or sedation, either alone or combined with other drugs.
Mixed drug
Ketamine and propofol, often combined as “ketofol,” are frequently used together for procedural sedation and analgesia, particularly in procedures like GI endoscopy [43]. Ketamine contributes to hemodynamic stability and analgesia, whereas propofol provides stable sedation and antiemetic effects. These drugs can be administered either independently or simultaneously. When administered independently, initial doses consist of a ketamine bolus (0.2–1.0 mg/kg) and a propofol bolus (0.5–1.0 mg/kg). Further dosing can be adjusted through infusions or repeated boluses as necessary [44]. When mixed, the ratio of ketamine to propofol typically ranges from 1:3 to 1:4. Although the combination is expected to offer a balance of effects, the risk of respiratory depression, apnea, laryngospasm, and hypotension persist. Therefore, careful adjustments to the dosage are crucial based on the stimulation by the procedure and the patient’s response to sedative.
Local anesthesia
Local analgesia using topical agents, such as subcutaneous lidocaine or eutectic mixture of local anesthetics cream combined with local anesthetics offers effective analgesia and reduces the need for systemic sedative and analgesic requirements. While medications like ketamine, dexmedetomidine, and opioids can manage pain during pediatric procedures, they can also intensify the effects of sedatives, potentially leading to complications like airway obstruction, respiratory depression, and cardiovascular instability. Therefore, local analgesia plays a critical role in ensuring safe and successful pediatric procedural sedation [45].
Nonpharmacological approach
Non-pharmacological interventions can help reduce anxiety in children, leading to less sedative requirements and potentially fewer complications [46-48]. Distraction techniques redirect a child’s attention to something engaging, such as listening to a book, counting numbers, playing with toys, using headphones with music or videos, or even video games and virtual reality [49-53]. Creating a child-friendly environment with appropriate toys, colorful walls, interesting ceiling decorations, and displays showing cartoons can provide more comfort for both the patient and caregivers.
For other children who are more cooperative, desensitization or the “tell-show-do” technique can be used. Desensitization gradually exposes the child to the environment (such as a model computed tomography scan room or medical toys) over time in a non-threatening way. The “tell-show-do” technique involves verbally explaining the procedures (tell), then demonstrating it visually, with sounds or touch, in a playful setting in a non-threatening setting (show/play), and finally completing the procedure as explained and practiced (do) [54]. Parental education and involvement are crucial because anxiety can be shared between children and parents, and their emotions can influence each other [55].
PREVENTING SEDATION-RELATED COMPLICATIONS
Procedural sedation is a dynamic process. Both the stimuli from the procedure itself and the patient’s response to sedatives can change rapidly. This necessitates close monitoring by appropriately trained independent medical personnel who are readily available to address any complications arising from sedation. It is important to note that sedation/anesthesia administered outside an operating room carries a 2–4 times higher risk of adverse events compared to procedures within an operating room [56], although serious complications leading to death are uncommon [57].
The spectrum of complications following pediatric sedation can vary depending on the child’s health condition and the specific sedatives administered. Common adverse effects include nausea, vomiting, agitation, and inadequate sedation [58]. The most serious complications often involve the respiratory system (2–5%), and can manifest as airway obstruction, hypoventilation, laryngospasm, hypoxemia, or apnea [2,56,57]. Cardiovascular complications typically arise as a consequence of respiratory issues. Sedation providers must be prepared and equipped to effectively manage these various side effects.
Studies have shown the safety and efficacy of well-organized pediatric sedation teams specifically dedicated to managing a high volume of patients [59-61]. A recent meta-analysis focused on non-IV sedation for MRI scans highlighted the critical importance of well-organized teams, even suggesting this factor may be more crucial than the specific sedation medication or regimen chosen [22].
A thorough understanding of procedure-related pain and anxiety, along with the patient’s characteristics, is essential. The planned depth of sedation should be determined collaboratively by all involved team members, including parents. To prevent over-sedation, it is important to observe the patient’s response to sedatives and analgesics at appropriate intervals. When two or more medications are used, it should be considered as moderate-to-deep sedation [55].
Topical local anesthetics, oral glucose, or formula (for neonates) can be helpful strategies. Additionally, allowing for slight movements while immobilizing the patient through comfortable positioning by parents or other personnel can be useful.
Regular data collection and analysis through sedation record statistics and team meetings/audits are crucial for improving the quality of sedation services. One example of such an initiative is the ongoing online registry site in Korea (http://www.pedisedation.com/), which collects data on pediatric procedural sedation and related complications.
RECOVERY FROM SEDATION
The most serious complications typically occur within 25 min of the last medication dose. Following procedural sedation, patients should be observed for at least 30 min after the final medication is administered or until the procedure is complete for safety reasons, It is important to note that reversal agents (e.g., flumazenil and naloxone) have shorter half-lives compared to the sedatives they reverse. Therefore, monitoring should continue for 1–2 h after administering reversal medications. The goal of post-sedation monitoring is to ensure the patient achieves the following: (1) maintain a patent airway without respiratory depression, (2) return to their baseline vital signs, (3) regain their baseline motor function, (4) return to their baseline level of consciousness, (5) achieve adequate hydration without nausea and vomiting, and (6) have adequate pain control. Before discharge, a Modified Aldrete Score (Table 4) [62] should be assessed. Ideally, the score should be ≥ 9, or return to the patient’s pre-sedation level [63,64].
It has not been conclusively investigated whether the risk of apnea after neonatal sedation is as high as that observed with general anesthesia [65,66]. However, due to immature hepatic and renal function in neonates and infants, which can affect how they metabolize and eliminate sedatives, longer monitoring is recommended for safety, as the effects of medications may last longer [2]. For example, chloral hydrate, can be detected for several hours after oral administration in neonates and infants. Furthermore, the active metabolite of chloral hydrate, trichloroethanol, is responsible for the prolonged sedation effect, and its half-life can be as high as 39.8 h in very preterm infants (born between 31–37 weeks post-conceptional age) [67]. Therefore, it is recommended to monitor neonates and preterm infants < 50 weeks post-conceptual age for a longer duration than other pediatric populations.
An additional study suggests that preterm and formerly preterm children may be nearly twice as likely to experience complications following anesthesia or sedation up to 23 years of age [68]. This highlights the importance of careful planning and monitoring during sedation for patients born premature.
CONCLUSION
Procedural sedation plays a vital role in facilitating pediatric clinical care. Given their expertise in patient evaluation, monitoring, airway management, sedative medications, and resuscitation, anesthesiologists are central figures in this field. To ensure safe and effective pediatric sedation, a well-functioning pediatric sedation team is essential. This team should be proficient and experienced in managing the diverse range of pediatric conditions, procedures, and sedation techniques encountered.
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