Pediatric Procedural Sedation and Analgesia in the Emergency Department

AUTHORS

Derya Caglar, MD, Associate Professor, Program Director, Pediatric Emergency Medicine Fellowship, University of Washington School of Medicine, Attending Physician, Division of Emergency Medicine, Seattle Children’s Hospital

Richard Kwun, MD, Attending Physician, Department of Emergency Medicine, Swedish Medical Center, Issaquah, WA

PEER REVIEWER

Humberto Liriano, MD, Assistant Professor of Emergency Medicine, University of South Alabama, Mobile

Executive Summary

• The ideal seda­tion minimizes the patient’s emotional and physical discomfort and maximizes amnesia to any painful elements. It allows the physician to control the patient’s behavior adequately, providing for a safe and effective procedure with minimal potential for harm. Risk reduction has been demonstrated with a careful preprocedure review of underlying conditions, adherence to a prescribed process, and minimization of the number of sedating agents.

• Any history of snoring, sleep apnea, or hypoventilation may indicate an increased risk of obstruction or air­way compromise with sedation.

• Although the Mallampati score may be useful to help predict a difficult intubation before general anesthesia, there is no specific evidence that it improves on the baseline clinical judgment of a standard airway evaluation prior to procedural sedation and analgesia (PSA).

• Patients with ASA classes I and II generally are acceptable candidates for mild, moderate, and deep sedation outside of the operating room. Patients with American Society of Anesthesiologists physical status class III and above, airway abnormalities, or any additional special needs may benefit from anesthesiology consultation to deter­mine the best and safest location for seda­tion, which may or may not be the emergency department (ED).

• Fasting times present a challenge to the care of children in the ED, since pediatric patients rarely are fasted and often require urgent or emergent procedures. Several studies have shown no difference in the incidence of adverse events between those who met fasting guidelines and those who did not.

• Child life programs in pediatric set­tings, including the ED, have become widely accepted and advocated by the American Academy of Pediatrics. With expertise in child behavior and development, child life specialists promote effective coping during stressful situations through play, distraction, psychologi­cal preparation, education, and support, potentially decreasing the need for deep sedation.

• Etomidate has been Food and Drug Administration-approved since 1983 and is an ultra-fast and ultra-short acting agent with no analgesic properties. It is a favorite of emergency physicians for sedation for minor, brief procedures. It has been used safely in chil­dren as young as 2 years old.

• Intranasal midazolam has a shorter time of onset than oral administration and has been used successfully in conjunction with local anesthesia for laceration repair in pediatric patients.

• Dexmedetomidine is a sedative-hypnotic with an increasing array of appli­cations, including PSA. It is administered intravenously and has a short half-life of six minutes. The lack of respiratory depression distinguishes this medication from opioids, benzodiaz­epines, and other sedatives.

• Intranasal fentanyl is well-tolerated and provides quick and effective pain control. It has been used successfully in the initial treatment of pediatric orthopedic injuries when deter­mining the need intravenous access and further intervention. Ketamine provides both analgesia and sedation by working at N-methyl-D-aspartate and glutamate recep­tors.

• Before discharge, the patient should no longer be at risk for airway compromise or cardio­pulmonary depression and should return to their baseline level of consciousness.

Children in the acute care setting may require nonpharmacologic and pharmacologic adjuncts for anxiety, pain, or to successfully complete diagnostic testing or therapeutic interventions. The authors review the requirements and pharmacologic agents necessary to complete a successful pediatric procedural sedation and analgesia.

— Ann M. Dietrich, MD, FAAP, FACEP, Editor

Introduction

Procedural sedation and analgesia (PSA) has been provided safely to children in the emergency department for decades. When patients are evaluated properly, and adequate equipment, personnel, and medications are used, effective and safe PSA is delivered by the emergency physician (EP), whether in a university or community setting, over a wide range of ages, and with a broad selection of medications.^1-3 This article will review goals and levels of sedation, pre- and post-procedure evaluation, necessary equipment and personnel, as well as medication choices.

PSA is a standard practice of EPs recognized by the American College of Emergency Physicians (ACEP) as integral to the practice of emergency medicine and as a core competency of emergency medicine training.⁴ It is defined by the use of pharmacologic agents to provide anxiolysis, analgesia, sedation, and motor control during procedures or diagnostic tests.⁵ The need for PSA outside of the operating room (OR) setting has led to its use by many non-anesthesiologist practitioners, both in the inpatient and outpatient settings. From 2007 to 2018, the Pediatric Sedation Research Consortium reported 432,842 sedation encounters in patients younger than 21 years of age.⁶ The National Anesthesia Clinical Outcomes Registry reported 349,518 cases in patients aged 19 years and younger from 2010-2013, with lower morbidity and mortality rates than OR cases.⁷

According to the Joint Commission on Accreditation of Healthcare Organizations, “the standards for sedation and analgesia care apply when patients in any setting receive, for any purpose and by any route, moderate or deep sedation.”⁸ Guidelines for the practice of PSA by non-anesthesiologists were developed by the American Society of Anesthesiologists (ASA) in 2002.⁹ Guidelines for PSA in the pediatric population followed. These were developed by the American Academy of Pediatrics (AAP) and the American Academy of Pediatric Dentistry and were updated in 2019.¹⁰

In contrast to adults, PSA in children often is administered to control behavior in addition to reducing pain to facilitate the safe completion of a procedure. Children’s abilities to control their behavior during a procedure depend both on cognitive and developmental age. Children younger than 6 years of age or with developmental delay often require deeper levels of sedation to gain control of their behavior. Children also are particularly vulnerable to medication effects on respiratory drive, airway patency, and hemodynamic stability. A thorough understanding of the unique anatomy and physiology of children is required to perform effective and safe PSA.

Goals of Procedural Sedation and Analgesia

The EP must determine the appropriate level of sedation and/or analgesia required for a particular procedure. Ideal sedation minimizes the patient’s emotional and physical discomfort and maximizes amnesia to any painful elements. (See Table 1.) It allows the physician to control the patient’s behavior adequately, providing for a safe and effective procedure with minimal potential for harm. Risk reduction has been demonstrated with a careful preprocedure review of underlying conditions, adherence to a prescribed process, and minimizing the number of sedating agents.¹¹

Upon completing an ideal sedation, patients return to their presedation baseline in a timely manner with minimal post-sedation side effects.

Levels of Sedation

Sedation can be thought of as a continuum of states ranging from minimal sedation (anxiolysis) to general anesthesia, as defined by the ASA. When considering sedation, the EP must first determine the level of sedation needed for a procedure. Analgesia is the relief of pain without intentionally producing a sedated state, but altered mental status may be a secondary effect of analgesic medications. The levels of sedation described are consistent with those defined by the ASA.⁹ (See Table 2.)

Minimal sedation, or anxiolysis, allows patients to respond normally to verbal commands. While cognitive function and coordination may be impaired, ventilatory and cardiovascular functions remain intact. Most patients generally will not require more than observation and intermittent evaluation of their level of sedation.

Moderate sedation (formerly conscious sedation) allows patients to respond purposefully to verbal commands either alone or accompanied by light touch. Older patients remain interactive while younger patients will show age-appropriate behaviors (for example, crying or pushing away from painful stimuli). Patients maintain their airway, can ventilate without intervention, and cardiovascular function is maintained.

With deep sedation, patients cannot be aroused easily but respond purposefully to noxious stimulation. These patients may require assistance to maintain their airway and adequate ventilation. Cardiovascular function usually is maintained.

Under general anesthesia, patients cannot be aroused and often require assistance to maintain their airway and positive pressure ventilation for adequate oxygenation. Cardiovascular function may be impaired.

Presedation Evaluation

A thorough presedation evaluation should be completed on all patients, with the primary goal of determining the appropriate anesthetic plan.¹² Any chronic medical conditions, particularly cardiac, respiratory, and metabolic disorders; hospitalizations; medications; and allergies that could affect the patient’s safety with sedation should be noted from the medical history. Any history of snoring, sleep apnea, or hypoventilation may indicate an increased risk of obstruction or airway compromise with sedation. Previous experience with anesthesia or sedation and associated complications should be reviewed. A family history of significant problems with anesthesia may indicate the potential for increased risk with sedation. The time and type of last oral intake also should be documented.

The physical examination should focus on areas for potential decompensation under anesthesia. Vital signs, including baseline heart rate, respiratory rate, pulse oximetry, and blood pressure should be documented. Any oral or airway abnormalities (for example, facial dysmorphism, micrognathia, macroglossia, dental anomalies or hardware, or tracheal deviation) that could interfere with resuscitation and intubation should be noted. Wheezing or crackles may indicate decreased pulmonary reserve that sedation could aggravate. An accurate weight should be documented for appropriate medication dosing. Although the Mallampati score may be useful to help predict a difficult intubation before general anesthesia, there is no specific evidence that it improves on the baseline clinical judgment of a standard airway evaluation prior to PSA.¹³ Laboratory studies should be ordered only when indicated by the patient’s medical status, drug therapy, or the nature of the proposed procedure. Routine studies are not needed in otherwise healthy patients.

Every patient should be assigned an ASA physical status classification. (See Table 3.) Patients with ASA classes I and II generally are acceptable candidates for mild, moderate, and deep sedation outside of the operating room. Patients with ASA class III and above, airway abnormalities, or any additional special needs may benefit from anesthesiology consultation to determine the best and safest location for sedation, which may or may not be the ED.

Fasting times present a challenge to the care of children in the ED, since pediatric patients rarely are fasted and often require urgent or emergent procedures. Several studies have shown no difference in the incidence of adverse events between those who met fasting guidelines and those who did not.^14-16 Outdated fasting guidelines were based on OR patients and, more typically, deep sedation and general anesthesia. Aspiration is associated with deeper levels of sedation, as well as ASA class III or IV. Fasting, as currently practiced, often substantially exceeds recommended time thresholds and has known adverse consequences, including irritability, dehydration, and hypoglycemia. Concerns for aspiration are out of proportion to actual risk, and the frequency of aspiration is lower than during general anesthesia.¹⁴ In urgent and emergent situations in which complete gastric emptying is not possible, moderate PSA should not be delayed based on fasting time alone.¹⁷ Ultimately, the risks, benefits, and urgency of the procedure must be balanced with the anticipated depth of sedation and available fasting time.

Equipment and Monitoring

Age-appropriate equipment for airway management and resuscitation should be immediately available at the location of sedation. (See Table 4.) This includes oxygen, suction, a bag-valve mask device with age and size appropriate masks, and intubation equipment. AAP guidelines use the acronym SOAP-ME in the planning and preparation of a procedure. (See Table 5.) Patients requiring deep sedation should have intravenous (IV) access for administration of multiple doses of sedatives and resuscitation medications, as needed. If access is not obtained initially, trained personnel and equipment should be immediately available to establish vascular access. With lighter sedation given orally, nasally, rectally, or intramuscularly, vascular access is not required, but it should be available for adverse reactions.

Designated personnel trained to manage potential complications of sedation, including hemodynamic instability, respiratory depression, apnea, and airway compromise, should closely monitor and continuously visualize the patient. Both AAP and ACEP guidelines call for practitioners to have “the skills to rescue the patient from a deeper level than intended” with any sedation.^8,10 Medical providers must be able to rescue patients and provide cardiopulmonary support if needed. At least two trained providers should be present for each sedation, with one person dedicated to the continuous monitoring of the patient while the other performs the procedure. The provider ultimately responsible for airway management must be able to recognize early signs of respiratory depression, apnea, obstruction, or bronchospasm and act appropriately to address and reverse problems.

Continuous pulse oximetry and cardiac monitors should have audible and visual signals. Vital signs should be recorded at specific intervals, including at the start of the procedure, after administration of any medications, when the procedure is completed, during the recovery period, and when recovery is completed. If deep sedation is used or patients have significant underlying illness, measure vital signs at least every three to five minutes.

End-tidal capnography is a noninvasive way to monitor a patient’s ventilatory status. Respiratory gases are sampled either from a chamber attached in-line to an endotracheal tube or at the nares via nasal cannula. Output is analyzed and given a numeric value and waveform. Increases in end-tidal carbon dioxide (ETCO₂) with respiratory depression are detected before hypoxemia is, particularly in those who are receiving supplemental oxygen. Respiratory depression caused by over-sedation will manifest as an abnormally high or low (when respirations are not reliably detected) ETCO₂ level well before pulse oximetry detects a declining oxyhemoglobin saturation, especially in patients receiving supplemental oxygen.¹⁸ However, several review articles and meta-analyses demonstrated a lack of convincing evidence that capnography in ED PSA reduced the rate of adverse events, although one analysis showed less mild and severe oxygen desaturation, which may have avoided needing assisted ventilation.^18-20

Bispectral (BIS) index monitoring is another noninvasive method of evaluating a patient’s level of sedation. The BIS monitor uses highly processed electroencephalogram (EEG) signals that are obtained from a probe placed on the patient’s forehead. EEG waveforms change with a patient’s level of alertness. These EEG waveforms are high frequency and low amplitude when a patient is awake and low frequency and high amplitude when a patient is deeply sedated. Based on a study of healthy adult volunteers, a numeric scoring system was developed, known as the BIS index, that ranges from 0 to 100.²¹ A BIS index of 0 denotes coma, 0 to 40 denotes a deep hypnotic state, 40 to 60 is general anesthesia, 60 to 70 is deep sedation, 70 to 90 is light to moderate sedation, and 100 is awake.²² The ASA critically reviewed BIS data and found that “a specific numerical value may not correlate with a specific depth of anesthesia.”²³ Several studies have found inconsistent BIS scores and levels of sedation in pediatric patients.^24,25 BIS monitoring may prove to be a useful adjunct in evaluating the status of the sedated patient, but, at present, data do not support its regular use in PSA.

Child Life Programs

Child life programs in pediatric settings, including the ED, have become widely accepted and advocated by the AAP. With expertise in child behavior and development, child life specialists promote effective coping during stressful situations through play, distraction, psychological preparation, education, and support, potentially decreasing the need for deep sedation.^26-28 This, in turn, has been shown to increase patient satisfaction and lower associated hospital costs.²⁹ Preparation is patient-focused and includes sensory aspects of the procedure (what the child will see, feel, hear, smell, and touch) and what the child can do during the procedure (count, read, watch television, etc.). Frequently, teaching dolls are used to help children understand where on the body a procedure will be performed. These techniques are known to decrease fear, anxiety, and discomfort during painful procedures. Child life specialists also provide support to parents and help families support their children through anxiety-inducing and/or painful procedures.

Pharmacologic Agents

There are five general categories of agents used in PSA: sedative-hypnotic, analgesic, dissociative, inhalational, and antagonistic. (See Table 6.) Sedative-hypnotics are the most widely used and include benzodiazepines, barbiturates, and unique agents, such as propofol, etomidate, and chloral hydrate. When used in combination, lower dosages of these agents can achieve similar results. For example, when opioids and benzodiazepines are used together, they exhibit synergy not only in the desired effects, but also in side effects, such as respiratory depression.

Sedative-Hypnotics

Chloral hydrate use has decreased significantly, both because the only commercially available product in the United States was discontinued in 2012 and because of the increased availability of alternatives. However, some hospitals continue to compound an available oral suspension for pediatric sedation. Chloral hydrate is a nonreversible agent that does not provide analgesia. It has decreased efficacy in children older than 48 months.³⁰ It may cause paradoxical excitement and may predispose patients to airway obstruction.³¹ Because of its depressive effects on myocardial contractility, chloral hydrate is contraindicated in patients with severe cardiac dysfunction and those on vasopressor support. Rectal use has been described, but absorption is erratic.³²

Etomidate has been Food and Drug Administration (FDA)-approved since 1983 and is an ultra-fast and ultra-short acting agent with no analgesic properties. It functions at the gamma-aminobutyric acid receptor and offers relative cardiovascular stability compared to many other agents in this group. It is a particular favorite of EPs for rapid sequence intubations as well as sedation for minor, brief procedures. It has been used safely in children as young as 2 years old. It may cause adrenal suppression four to 24 hours after administration and should be avoided when adrenal insufficiency is a concern, as in sepsis. Side effects include myoclonus, nausea, and vomiting.³³

Benzodiazepines provide sedation without analgesia, and paradoxical excitement has been described. Midazolam acts as a sedative, anxiolytic, hypnotic, muscle relaxant, antegrade amnestic, and anticonvulsant. Intranasal midazolam has a shorter time of onset than oral administration and has been used successfully in conjunction with local anesthesia for laceration repair in pediatric patients.^34,35 Benzodiazepines can cause respiratory depression as well as hypotension, so close monitoring should continue until the patient has returned to baseline. Paradoxical excitement also has been described, with patients becoming more agitated after administration, particularly in preschool-age patients. As an adjunct to ketamine, midazolam decreases the incidence of emesis, but not of emergence reactions, and is not recommended for routine prophylaxis.

Barbiturates, such as methohexital, pentobarbital, and thiopental, can cause hypotension and respiratory depression. Methohexital, whether administered intravenously, intramuscularly, or rectally, and pentobarbital can provide effective and safe sedation for painless procedures, such as imaging studies.³⁶ However, keep in mind that paradoxical excitation can occur in pediatric patients. Barbiturates are contraindicated in patients with porphyria, which they can exacerbate. Of note, this class of drugs is not reversible.

Propofol is the most commonly used anesthetic agent for pediatric procedures. Despite its popular use in the pediatric ED, it was only approved by the FDA for use in children younger than 3 years of age in 2017. Propofol has minimal to no analgesic properties and should be used in combination with short-acting opioids or ketamine for brief, painful procedures. Its site of action is believed to be at the gamma-aminobutyric acid receptor. Propofol is known to depress mitochondrial function by uncoupling oxidative phosphorylation and should be used with caution in children with mitochondrial defects. It has side effects of hypotension and pain at the site of infusion.

To prevent infusion pain, EPs may consider premedicating patients with IV lidocaine 0.5 mg/kg, 30 to 120 seconds before propofol infusion with a rubber tourniquet applied. This prevents pain in 60% of patients treated.³⁷ Propofol use in the ED has been well-documented and proven to be effective and safe.³⁸ Recent studies suggest that the risk of adverse reactions to propofol in children with egg and soy allergies may be minimal.^39,40 Fospropofol is a newer prodrug that is metabolized to propofol with less pain on initial injection, fewer allergic reactions, and less hyperlipidemia. The onset of action is slightly delayed, and the duration of action is longer than for propofol, with a peak effect in eight minutes and a clinical effect lasting four to 13 minutes. Sedation-related hypoxemia and hypotension occur in a dose-dependent fashion, but they are less frequent and less intense than with propofol.⁴¹

Dexmedetomidine is a sedative-hypnotic with an increasing array of applications, including PSA. It is administered intravenously and has a short half-life of six minutes. Other routes of administration described include intramuscular, oral, buccal, subcutaneous, and intranasal. The lack of respiratory depression distinguishes this medication from opioids, benzodiazepines, and other sedatives. Respiratory rate, carbon dioxide levels, and oxygen saturation generally are maintained during dexmedetomidine sedation in children. Side effects include hypotension and bradycardia.^42,43 There may be a neuroprotective effect.

Analgesics

At higher doses, opioids, such as fentanyl and morphine, can cause sedation in addition to analgesia. Intranasal fentanyl is well-tolerated and provides quick and effective pain control.⁴⁴ It has been used successfully in the initial treatment of pediatric orthopedic injuries when determining the need for an IV and further intervention. Side effects include respiratory depression, hypotension, nausea, and pruritus. When opioids are combined with propofol, effective and safe PSA can be provided.³⁰ Traditionally, remifentanil has been used in combination with other agents, such as propofol, and in an elective setting. Currently, there is a lack of high-quality data on the use of remifentanil in the ED, particularly in children.⁴⁵

Dissociative

Ketamine provides both analgesia and sedation by working at N-methyl-D-aspartate (NMDA) and glutamate receptors. Seizure disorder is not a contraindication, and ketamine has even demonstrated anticonvulsant properties.⁴⁶ Involuntary movements may occur, and ketamine should be avoided for imaging studies, such as computerized tomography and magnetic resonance imaging. An emergence reaction occurs in a significant minority of patients, and other side effects include hypersalivation, bronchorrhea, laryngospasm, and nausea. Anticholinergic agents, such as glycopyrrolate and atropine, traditionally have been administered as adjuncts to limit excessive mucosal secretions, but they have not been found to be effective in the ED setting.^46-48 For laceration repairs, IV ketamine in combination with midazolam, as well as intramuscular ketamine used alone, were superior to intranasal midazolam in terms of sedation onset and efficacy.³⁶

Inhalational

Nitrous oxide is combined with 30% to 70% oxygen and inhaled by a demand-valve mask, requiring a cooperative patient to generate sufficient negative inspiratory pressure.⁵ Used by pediatric dentists for many years, nitrous oxide has been increasing in use across pediatric EDs. Systemic opiates or regional or local anesthesia usually also are provided, since there is only mild analgesia if nitrous oxide is used alone.

Continuous flow delivery has been described, but it requires two physicians — one to deliver the agent and one to perform the procedure — which may be impractical in many ED settings.⁴⁹ There is an association with spontaneous abortions in medical providers who administer nitrous oxide for more than three hours per week in the absence of scavenging equipment.⁵⁰ Other rare contraindications include the use of bleomycin and a history of 5,10-methylenetetrahydrofolate reductase deficiency.^51,52 Nausea and vomiting occur in 0.5% of patients, and more often with longer administrations, increased nitrous oxide concentrations, and fluctuations in nitrous oxide levels.¹⁰ Higher nitrous oxide concentrations, from 50% to 70%, appear to be safe and effective in children as young as 1 year old.⁵³

Antagonistic

Naloxone is a short-acting opioid antagonist and can be administered intravenously, intranasally, and intramuscularly. It has a long safety record of use in children. Higher doses should be used when treating respiratory depression and not central nervous system depression alone.⁵⁴

Flumazenil is the only benzodiazepine antagonist available and is short-acting. It should not be used in patients with a history of long-term benzodiazepine use, since it may precipitate withdrawal symptoms and seizures. It should also be avoided when drugs that lower the seizure threshold have been ingested, such as cyclosporine, isoniazid, lithium, propoxyphene, theophylline, and tricyclic antidepressants.

Other

Ketofol is a preformed mixture combining equal parts ketamine at 10 mg/mL and propofol at 10 mg/mL. The combined agent is administered in 1-mL to 3-mL doses, with the median dose being 0.75 mg/kg. It has shown promise in PSA, since subdissociative amounts of ketamine and less-than-typical amounts of propofol are used with success, although further research is needed.⁵⁵

Post-Procedure Assessment and Discharge

Children receiving any form of sedation should be observed in an appropriately staffed and equipped recovery area after the conclusion of the procedure. One database study showed that the highest risk of serious adverse events occurred within 25 minutes of receiving the last dose of intravenous medication.⁵⁶ Before discharge, the patient should no longer be at risk for airway compromise or cardiopulmonary depression and should return to their baseline level of consciousness. Cardiac monitors and pulse oximetry should continue to monitor the patient during observation. Recommended discharge criteria are provided by the AAP (see Table 7); based on these, it should be noted that a return to pre-sedation ambulatory status is not required.¹⁰

The patient should be discharged to a responsible adult who will accompany the child and be able to monitor and react to any post-procedural complications. Discharge instructions should be reviewed prior to discharge with an emphasis on the signs of respiratory distress.

Special Considerations

The EP must remain vigilant and recognize adverse outcomes in PSA, which appear to occur more often in nonhospital-based, non-emergency department settings. This may be a reflection of the specialty and experience of the practitioner and/or the ability to recognize and treat adverse events, such as desaturation, apnea, and laryngospasm.⁵⁷ The ASA only differentiates between anesthesiologists and non-anesthesiologists, despite the considerable variability of training and experience among non-anesthesiologists to rescue patients from unintended levels of sedation as well as to perform cardiopulmonary resuscitation when needed.⁵⁸

Agitation may occur with PSA, even when standard regimens and doses are used. Although rare, intraprocedural agitation appears to be associated with an increased risk of adverse outcomes, such as cardiovascular compromise, allergic reaction, use of reversal agents, and need for resuscitation.^58,59

The EP also should consider other methods of analgesia that may not affect a patient’s level of sedation, such as topical anesthetics, local anesthetic injection, regional anesthesia, and oral sucrose for neonates. These may be used alone or in conjunction with anesthetic agents. Nonpharmacologic interventions are listed in Table 8.^60-63

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