Identification and Treatment of Pediatric Perioperative Anxiety

Children experience heightened anxiety and fear in the hospital.1,2 Perioperatively, these feelings are amplified by a loss of control and separation from their caregivers.3 Due to the high incidence of needle-phobia in two-thirds of the pediatric population, most children undergo inhalation induction when presenting for anesthesia. However, needle avoidance only partially mitigates preoperative anxiety since introduction of the mask during inhalational induction is also associated with significant distress, often requiring physical restraint.4 Sequalae of undertreated pediatric perioperative anxiety include increased anesthetic requirements, pain perception, and emergence delirium, as well as decreased parental satisfaction.5,6 Physiologic responses to stress during anesthesia induction can trigger increased cortisol and susceptibility to postoperative infections due to immune function dysregulation.7–9 Long-term postoperative maladaptive behaviors can occur, including enuresis, sleep disturbances, post-traumatic stress, fear of hospital settings, and generalized anxiety1,10 Healthcare-induced distress predisposes children to general anxiety and major depressive disorders in adulthood.11 Effective management of pediatric perioperative anxiety substantially impacts patients and their families. Improved patient experiences reduce caregiver stress as well, which is advantageous given the reciprocating influence of caregiver anxiety on patients.12 Interventions that decrease caregiver apprehension improve patient cooperation and mood.12 Positive experiences during childhood medical care leads to improved engagement in their own adult medical care years later.13 Treatment of pediatric perioperative anxiety not only enriches the immediate surgical experience for children and their families but also compliance with routine preventive healthcare as adults. Appropriate interventions of perioperative anxiety cannot occur without consistent identification.14 Research assessment scales have driven the definition, classification, and consequences of perioperative anxiety.14 Although these research scales reliably identify distress, they are cumbersome to clinically use. Several facile anxiety assessment tools have been correlated to research scales, offering the potential for widespread, real-time clinical assessments through electronic medical records.14 However, what newer clinical scales gain in efficiency is tempered by a loss in robust cross-validation studies. With improvements in anxiety identification, the treatment of pediatric perioperative anxiety has advanced as well. While parent present induction of anesthesia and oral midazolam are the most common treatments, the use of non-pharmacologic interventions have increased.15,16 Additionally, newer pharmacologic agents, such as dexmedetomidine, offer alternatives to midazolam. Given the introduction of novel, efficient anxiety scales via standardized electronic medical records and expanding anxiolytic treatments, the purpose of this review is to detail the identification and treatment of pediatric perioperative anxiety. This review will describe research-based anxiety scales and their relationship to clinically efficient scales, followed by an evidence-based summary of traditional and non-traditional anxiolytics. Assessment of Pediatric Perioperative Anxiety Identifying and measuring pediatric perioperative anxiety is challenging.14 Due to heterogenous intrinsic personalities and variable extrinsic factors, anxiety fluctuates not just between patients of similar demographics but also within patients as their environment changes.17 Reliance on provider assessments is not consistent, necessitating age-appropriate and efficient anxiety scales, analogous to pain.18 Validated assessment scales are more sensitive than personal appraisals, providing quantification of anxiety to treatment response. Research Affect Scales Investigators use research-based affect assessment scales to identify the effectiveness of perioperative anxiolytics and consequences of untreated anxiety (table 1). Used extensively to measure pediatric anxiety, the State Trait Anxiety Inventory-Children is a self-reported questionnaire that assesses intrinsic and situational anxiety within many healthcare contexts.19 The Modified Yale Preoperative Anxiety Scale is an observational scale specifically developed to assess pediatric perioperative anxiety.20 Containing five behavioral domains during four time-points, a trained observer grades each domain to produce an aggregate score. Originally developed to measure procedural distress, the Observation Scale of Behavioral Distress is often used to measure distress during mask induction and perioperative intravenous (IV) placements.21 This observational scale consists of 11 categories that sum to a total score, divided by procedural duration and measured in 15-s intervals.Table 1.: Research and Clinical Pediatric Perioperative Affect and Cooperation Assessment ScalesCooperation is linked to anxiety and is vital to a smooth anesthetic induction.22 Although not a measure of affect, the Induction Compliance Checklist assesses cooperation during anesthesia induction.23 It is often used in conjunction with anxiety assessment scales to quantify the quality of induction. Although these scales have been essential for guiding improvements in anxiety treatment and improving cooperation, their practical application in a clinical environment poses challenges due to their complexity and time to complete. Clinical Affect Scales Since research scales are difficult to clinically implement, investigators have developed several efficient scales for routine use (table 1). Derived from the Induction Compliance Checklist scale, the Childhood Behavioral Induction Assessment tool consists of three categories, each with multiple anchors of observed behaviors, affect, and cooperation.24,25 Although the Childhood Behavioral Induction Assessment scale has been successfully integrated into electronic medical records, a disadvantage is its reliance on the Induction Compliance Checklist for concurrent validity, which itself has not been tested. Additionally, the Childhood Behavioral Induction Assessment tool has not been correlated to robust affect scales, such as the Modified Yale Preoperative Anxiety Scale and State Trait Anxiety Inventory-Children scale. The Pediatric Anesthesia Behavior scale rates affect during induction as happy, sad, or mad.26 Strong correlations were observed with the Modified Yale Preoperative Anxiety Scale, however, the scale lacks a measure of cooperation.26 In addition, its generalizability to mask inductions is limited as the majority of the study patients were IV inductions undergoing dental procedures.26 The Verbal-Numeric-Anxiety-Fear-Rating-Scale is a numeric scale, from 0 to 10, with numbers and word anchors displayed on a 10-cm-long line.27 Word anchors consist of various levels of affect with descriptions ranging from “no anxiety or fear at all” to “the worst possible anxiety or fear.”27 The scale demonstrated excellent inter-rater reliability with moderate correlation to the Modified Yale Preoperative Anxiety Scale.27 However, similar to the Pediatric Anesthesia Behavior scale, no measurement of cooperation is included. The Happy, Relaxed, Anxious, Distressed with a yes or no answer to Cooperation scale is another observational scale used during anesthesia induction.28 Based off a national survey of pediatric anesthesiologists, four affect domains were chosen from the Positive Affect Negative Affect Schedule-Children.29 Unlike the Childhood Behavioral Induction Assessment tool, the Happy, Relaxed, Anxious, Distressed with a yes or no answer to Cooperation scale does not include anchor descriptors given the etiology of the domains from the Positive Affect Negative Affect Schedule-Children survey which are intuitively and commonly understood words. The scale was tested with physician and non-physician providers with strong correlations to the Modified Yale Preoperative Anxiety, Observation Scale of Behavioral Distress and Induction Compliance Checklist scales.28,30 However, similar to other clinical tools, the Happy, Relaxed, Anxious, Distressed with a yes or no answer to Cooperation scale lacks multi-site validation. Practical clinical scales have emerged recently, in tandem with wide-scale electronic medical record adoption. Given the relative ease of standardizing electronic charting, electronic medical records provide the ideal conduit for clinical scale integration. While current clinical scales may lack multi-site validation studies, the improvements in patient care may outweigh the risk of not routinely assessing perioperative anxiety.18 In addition, comprehensive electronic induction tools have been developed, such as the Standardized Anesthesia Induction Tool, to document anxiety and negative behaviors during induction.31 Although the Standardized Anesthesia Induction Tool incorporates scales that would benefit from robust validation studies, it addresses the need for a standardized induction tool to inform future anesthetics as well as quality improvement measures targeted at preoperative anxiolysis treatments.18 Treatment of Pediatric Perioperative Anxiety Appropriate identification precedes anxiety treatment. Sequalae from unrecognized pediatric perioperative anxiety can be profound to both patient and family, however effective treatments can ameliorate the short- and long-term consequences.32 Even though midazolam and parent present induction of anesthesia account for the majority of perioperative anxiety treatment, anxiolytics have expanded recently in both the pharmacologic and non-pharmacologic domains.33–36 Pharmacologic Anxiolytics Pharmacologic therapies are the most common approach to treating pediatric anxiety in the United States (Table 2).33,36 Due to needle-phobia and an emphasis on patient-centered care, the majority of pediatric anesthesia inductions are inhalational, requiring non-IV preoperative sedatives.37,38 Although per os (PO) is the most common non-IV route, intranasal, intramuscular, per rectum, and nebulized routes are also considerations.Table 2.: Pharmaceutical Options for Anxiolysis in Pediatric AnesthesiologyBenzodiazepines Within the class of benzodiazepines, midazolam is the most commonly administered premedication due to its relatively short onset and consistent anxiolysis.23,33,39 Disadvantages include its bitter taste, paradoxical reactions in 5-10% of children, respiratory depression when used with other sedatives, and nasal irritation with intranasal administration.40,41 Also, the risk of perioperative respiratory adverse events increases with concomitant administration of midazolam in patients with upper respiratory infections or sleep disordered breathing.42,43 Although there may be an association of emergence delirium with midazolam, the use of midazolam with other anesthetic adjuncts such as dexmedetomidine may have a synergistic effect against emergence delirium.44 While other benzodiazepines, such as lorazepam and diazepam, also decrease anxiety in the pediatric population, their use is limited by longer onset times and duration of action. Lorazepam has been helpful as a home premedication for those patients requiring sedation before arrival to the hospital. Recently, remimazolam, an ester-based benzodiazepine rapidly hydrolyzed by tissue esterases, has been introduced within pediatric anesthesiology. Remimazolam facilitates IV induction and maintenance of anesthesia and when given at the end of a sevoflurane anesthetic, can reduce the incidence of emergence delirium.45 Additionally, intranasal remimazolam demonstrated decreases in preoperative anxiety in children with minimal side effects.46 Despite its promising potential, further research is required to examine its efficacy and safety within pediatrics before widespread adoption. Alpha-2-agonists Dexmedetomidine, a potent, selective alpha two receptor agonist, is a popular benzodiazepine alternative due to its mild analgesic, anti-emetic properties, maintenance of respiratory drive, and decreased risk of perioperative respiratory adverse events in patients with URIs.47–49 Disadvantages include a long onset time, inconsistent sedation, and poor oral bioavailability, necessitating intranasal or nebulized administration.48,50 Hemodynamic perturbations at higher doses include bradycardia and hypotension, coupled to inconsistent yet profound hypertension if the bradycardia is treated with anticholinergics.51,52 Despite these drawbacks, when compared to midazolam in several meta-analyses, dexmedetomidine produces satisfactory sedation at parental separation with fewer postoperative rescue analgesics.48,53–56 However, there were no differences in mask acceptance, emergence delirium, and discharge times from the recovery room between midazolam and dexmedetomidine.48,53–55 Clonidine is a central alpha two receptor agonist used for pediatric anxiolysis, prevention of emergence delirium, and sedation.57 It has analgesic properties and a higher oral bioavailability than dexmedetomidine however, its longer onset time and prolongation of postoperative emergence can be difficult to utilize in a fast-paced perioperative setting.57 Clonidine is also associated with occasional hypotension and bradycardia, although it typically does not require intervention in healthy patients.58,59 Miscellaneous In the uncooperative child or patient with developmental delay, where PO administration may be difficult, intramuscular ketamine, a N-methyl-D-aspartate receptor antagonist, facilitates separation from caregivers and improves compliance with inhalational inductions.36 Advantages include its preservation of respiratory drive, dissociative sedation, and potent analgesia.60 Although its oral bioavailability is 17 to 24%, it can be used in combination with midazolam PO, increasing its versatility.61 Disadvantages to ketamine intramuscular include dysphoria, hallucinations, nystagmus, imbalance, excessive secretions and postoperative nausea and vomiting at higher doses.60 Also, its slow metabolism after high dose intramuscular ketamine injections in combination with other sedatives can prolong emergence and recovery room discharge.62 Given the pain of intramuscular injections, children may be uncooperative, require physical restraint, and incur emotional distress during intramuscular administration, limiting its routine use. In addition to potential needle stick injuries among providers and caregivers, physically restraining an unwilling child is increasingly subject to ethical scrutiny, placing additional emotional burdens on healthcare providers.63,64 Although melatonin, an indoleamine, has historically treated sleep disorders, anesthesiologists less commonly use it as an anxiolytic given its hypnotic properties.65 Advantages include its marketability as a naturally occurring compound, favorable safety profile, and mild analgesic properties.65,66 Disadvantages include disruptions to natural circadian rhythms and unreliable effectiveness due to intrinsic patient factors and time of day.66 Compared to commonly used anxiolytics, melatonin does not consistently improve parent separation and mask induction.65 Melatonin may better be suited as a home premedication to facilitate transport to the hospital. If given at home on the day of surgery, liquid melatonin is recommended in lieu of the gummy formulations to reduce aspiration risk. Diphenhydramine is a histamine receptor antagonist with anticholinergic properties used to treat allergies, motion sickness, Parkinson’s disease, and insomnia due to its efficacy as a sedative-hypnotic.67 While diphenhydramine is typically not used as a perioperative anxiolytic due to its anticholinergic effects, higher rates of paradoxical reactions and variability in duration of action, its accessibility allows home administration for those patients experiencing high anxiety before hospital arrival. Despite the multitude of premedication options with varying advantages, there is no ideal pharmaceutical agent due to each one’s limitations. Comparisons between these sedatives all offer varying degrees of anxiolysis, although melatonin distinguishes itself as the least reliable.68 In practice, clinicians should select an appropriate premedication by balancing its properties, considering each patient’s medical history and unique circumstances. Non-pharmacologic Anxiolytics Undesirable side effects and a recent Federal Drug Administration Drug Safety Communication on the use of sedatives in children have led to increasing parent hesitation toward pharmacologic interventions.69 The most common non-pharmacologic anxiolytic alternative is parent present inductions of anesthesia however, preoperative preparation programs, separate induction rooms, low sensory environments and technology utilization are increasing in popularity.35,70 Also, anesthesiologists trained in behavior modifications use distraction, non-procedure-related conversation, medical reinterpretation, and humor to improve patient comfort.71 Other less commonly used interventions include perioperative clowning, acupuncture, hypnotherapy, and music therapy.35 Parent present inductions of anesthesia are commonly used to mitigate the additive effect of separation anxiety and situational anxiety for children.72,73 However, its effectiveness is variable.35,74 For many patients, their anxiety is reflexively amplified due to high parental anxiety, leading to distressing mask inductions despite smooth transitions into the operating room (OR).7,75 Additionally, parent present inductions of anesthesia alone result in higher anxiety levels when compared to midazolam.23,39 Coupled with OR sterility concerns and reduced OR efficiency, the use of parents have become less popular.76–78 Recently, new programs led by certified child life specialists and anesthesiologists target caregiver and patient behavior modification, teaching role-play, coping and distraction skills.79–81 With this guidance, parents can be more effective at reducing anxiety. When comparing parents plus coaching and behavior training to midazolam, this enhanced parent present induction of anesthesia protocol was not only as effective as midazolam but also had faster discharge times, less postoperative fentanyl use, and decreased severity of emergence delirium.6,82 Limitations to approaches that are contingent on preemptive caregiver and patient training include cost, personnel, and availability. However, web-based programs that incorporate similar coaching and behavior training mitigate the disadvantages of in-person preoperative preparation programs and offer greater accessibility to families.83–86 Acute distraction facilitated by technology is also an effective induction anxiolytic. Screen-based distraction using smartphones and tablets reduce preoperative anxiety and improve mask acceptance.87,88 Additionally, video gaming not only increases engagement with the care team, but also facilitates smooth inductions.89,90 While the novelty of smartphones and tablets may have waned, newer technologies remain effective, characterized by their levels of immersion.15 The Bedside Entertainment Relaxation Theater consists of a battery-powered projector clamped to the head of the gurney with a large white corrugated plastic screen mounted to the end of the gurney (fig. 1).91,92 The screen is large enough to fill most of the child’s field of vision, providing a near-immersive experience, while still allowing patient interaction between caregivers and staff. Popular movies from various streaming platforms and custom applications are projected onto the screen while the patient is transported to the procedure area.92 The projector can be angled to the ceiling, allowing the child to continue watching during induction.91 Advantages include its affordability, quick set-up, and high novelty. Disadvantages include the maintenance of the projectors and personnel needed to clean and return the Bedside Entertainment Relaxation Theater from the OR to the preoperative area.Fig. 1.: Bedside Entertainment and Relaxation Theatre (BERT) setup in the preoperative area.Augmented reality provides a partially immersive experience using superimposed projected onto the consists of and with reality (fig. reality has been used to facilitate inhalational with patients decreased anxiety and improved mask Advantages include maintenance of between the patient and their to assess the patient’s during mask and room for a anesthesia mask the and Disadvantages include cost, limited reality need for provider and of the 2.: of reality during mask induction of reality provides a immersive experience for the patient by an to a a combination of and custom is for pediatric Due to and increasing reality has expanded within healthcare specifically in the and care a of the perioperative decrease pediatric preoperative anxiety, reduce anxiety while placing and improve cooperation during mask induction (fig. pediatric reality pain and anxiety compared to of pediatric requiring general anesthetics have been to reality reality is also a for postoperative and in pediatric patients, those with pain However, disadvantages to reality in the perioperative include a with an anesthesia mask the to the patient’s during and due to its children increased anxiety from a loss of with their Additionally, and nausea occur in a of patients, commonly associated with with of motion to reality use include history of motion sickness, and Also, patients less than years are not ideal due to of the and ethical of a reality during difficult intravenous Pediatric perioperative anxiety is associated with adverse clinical identification and treatment reduce distress, postoperative maladaptive behaviors, and healthcare efficient scales in combination with widespread electronic medical record utilization can identification of perioperative anxiety large pharmacologic and non-pharmacologic provide the to facilitate patient-centered treatment research should study care with that consistent anxiety measurement with recommended The no