Executive Summary
- In the pediatric emergency department (ED), procedural sedation is performed for several reasons outside of pain alone. The goal of a procedural sedation is to keep both the patient and provider safe to complete a procedure that will medically benefit the patient. Prior to the sedation, providers should take time and care to minimize the child’s pain, which may help to reduce anxiety surrounding their diagnosis or procedure.
- The Pediatric Sedation State Scale (PSSS) is a tool that can be used to objectively score various sedation methods. The PSSS is a way of evaluating and documenting the goal vs. the quality of sedation that is observed. It consists of a scale with six levels of sedation and documents physiologic measures, level of patient interference, use of restraints, and overall behavior.
- Capnography or end tidal carbon dioxide monitoring can be used for detecting the absence or presence of respirations during sedation. Its use can be beneficial in scenarios where it may be difficult to see the patient, such as when the patient is in the scanner or during a lumbar puncture, where their body may be folded.
- A systematic review of 20 randomized controlled trials revealed that, in children who were monitored via capnography, there was no major adverse event that required assisted ventilation or apneic periods. In theory, the use of capnography should reduce the incidence of hypoventilation and oxygen desaturation.
- Intranasal sedatives and analgesics are a good option for anxiolysis or short procedures that only involve minor pain, such as a small laceration repair or wound irrigation.
- Distraction techniques, such as music, toys, games, and glucose for infants, can be very effective in reducing preprocedural anxiety as well as gaining the trust of a child. Child life specialists, if available, are invaluable at assisting with cognitive strategies of care.
- In general, patients must be at their mental status baseline, tolerate food or drink intake by mouth without vomiting, ambulate without difficulty (if age-appropriate), and have remained hemodynamically stable throughout the procedure and recovery phase to be suitable for discharge.
Every acute care clinician needs to know and be familiar with the process of procedural sedation, medication selections, options, and contraindication for different procedures. The authors comprehensively review procedural sedation, emphasizing evidence-based choices.
— Ann M. Dietrich, MD, FAAP, FACEP, Editor
By Courtney Botkin, DO, and Daniel Migliaccio, MD, FPD, FAAEM
Introduction
Sedation involves the use of medication to depress the central nervous system to decrease awareness of one’s surroundings. Procedural sedation is known as “a technique of administering sedatives or dissociative agents with or without analgesics to induce a state that allows the patient to tolerate unpleasant procedures while maintaining cardiorespiratory function.”1
The benefit of procedural sedation is that it allows patients to tolerate painful and anxiety-provoking procedures while maintaining their own airway reflexes and oxygenation.1 It is crucial that emergency medicine physicians are knowledgeable and prepared before performing a pediatric procedural sedation.
One must have a thorough understanding of the levels of sedation, medications, and adverse events that may occur. Pediatric patients can easily delve into a deeper level of sedation than intended, which makes knowledge of sedation and pediatric resuscitation essential to the success and safety of a procedure.2,3
Background
In the pediatric emergency department (ED), procedural sedation is performed for several reasons outside of pain alone. The goal of a procedural sedation is to keep both the patient and provider safe to complete a procedure that will medically benefit the patient. Prior to the sedation, providers should take time and care to minimize the child’s pain, which may help to reduce anxiety surrounding their diagnosis or procedure.2 When met with the decision of whether a procedural sedation is necessary, it is important that the comfort and safety of both the patient and clinician are considered.
Requiring care in an ED can be distressing for children and their caregivers, and it is important for providers to build rapport and create a safe and calm environment. As with adults, each child may differ in their level of anxiety, pain, and discomfort in this unfamiliar environment. Accordingly, the use and level of sedation should be tailored to each patient.2 Anxiety alone may lead to the patient being unable to remain immobile, yet this is necessary for most procedures in the ED. Given this, there may be times where minimal sedation for anxiolysis may be beneficial. A sampling of cases in which procedural sedation may be indicated includes lumbar punctures, catheterization, fracture reductions, or laceration repairs.3
Levels of Sedation
Procedural sedation levels are classified as minimal, moderate, deep, and general anesthesia. The first level is minimal sedation, also known as anxiolysis. In this state, the patient is still awake and responsive to questions and commands but is more relaxed. Anxiolysis for pediatric patients frequently is performed for obtaining radiologic studies in the ED, such as computed tomography (CT), magnetic resonance imaging, ultrasound, or echocardiograms. Many providers and protocols do not consider anxiolysis true sedation and, thus, may have different guidelines for administration when anxiolysis alone is used.3,4 Moderate sedation previously was called conscious sedation. However, this term has fallen out of favor because it does not accurately describe the level of patient alertness. During this state, the patient’s level of consciousness is decreased, but they can respond to verbal stimuli or touch. In a state of moderate sedation, there is no additional respiratory support required, since breathing remains intact.3,4
In a deep state of sedation, patients may be arousable after repetitive or painful stimuli. In this depth of sedation, breathing may need to be supported, since it often is impaired. General anesthesia typically is not electively performed in the ED and should be attempted only by experienced anesthesiologists. When under general anesthesia, patients are unconscious and not arousable despite repeated stimulation attempts. Patients under general anesthesia usually require clinician intervention to maintain a patent airway and are unable to maintain independent ventilation.3,4
In addition, there is a separate level of sedation known as a dissociative state that is specific to the medications used for sedation. In the dissociative state, patients do not feel pain and are unaware of what is going on. However, they maintain a state of wakefulness that is described as “trance-like” because patients still can follow commands but have no memory of what took place. Additionally, their airway reflexes are preserved. This state frequently is observed with the drug ketamine, which will be discussed later.1,3,4
Preparation
Benjamin Franklin said, “By failing to prepare, you are preparing to fail.”5 This quote is applicable to every aspect of emergency medicine and especially to procedural sedation. Emergency medicine physicians should challenge themselves to thoroughly prepare for each sedation they perform despite their level of experience and familiarity. Preparation includes a thorough history, physical exam, discussing the plan for procedural sedation with guardians, obtaining consent, and notifying supporting staff.
Patient Assessment
When determining whether a patient is a candidate for procedural sedation, it is important to comprehensively evaluate the patient and determine their associated risk for undergoing procedural sedation. While there are no absolute contraindications to performing pediatric procedural sedation outside of the operating room (OR), past medical history, physical exam, and procedural urgency should be considered.6,7 It also is important to consider comorbidities, medication allergies, and prior surgeries or sedations. While children generally have fewer comorbidities than adults, they remain crucial to review to determine whether the patient is an appropriate candidate for procedural sedation. The clinician should consider American Society of Anesthesiologists (ASA) classification, a history of obstructive sleep apnea, obesity, and high blood pressure — all of which are factors that may increase the risk of sedation.8,9 (See Table 1.)
Table 1. High-Risk Qualities for Pediatric Procedural Sedation |
American Society of Anesthesiologists class III or higher |
History of obstructive sleep apnea or snoring |
Obesity |
Hypertension |
History of recurrent upper respiratory tract infections |
In a study including 8,000 children, it was determined that obesity, sleep apnea, or a history of snoring in children, history of recurrent upper respiratory tract infections, and classification as ASA III or higher were risk factors for hypoxic or apneic events during sedation.9 Additionally, there are data revealing that pediatric patients with developmental delays for any reason are at a three times higher risk of desaturation during procedural sedation.2
ASA Classification
When reviewing a patient to determine whether they are a candidate for procedural sedation, the ASA airway assessment classification should be used in conjunction with history, physical exam, hemodynamic stability, and urgency of the procedure to determine whether sedation is necessary and can be safely performed. ASA classification ranges from I-VI, with the healthiest candidate being a class I. Class I is described as a healthy patient who has no known comorbidities and a normal body mass index for their age. Class II is a patient with mild systemic disease who does not have an ongoing acute exacerbation of the disease process. An example of ASA class II is a patient with asthma who currently is not having an exacerbation at the time they are being evaluated. ASA class III is a patient with severe systemic disease who is without immediate risk of death, such as morbid obesity, poorly controlled epilepsy, or metabolic disease. Classes IV-VI are patients with more severe disease processes that represent an active threat to their lives.3,10
Multidisciplinary resources for pediatric procedural sedation recommend limiting procedural sedation outside of the OR to ASA I and II for emergent scenarios only. This recommendation exists, but responsibility ultimately falls on the provider to identify whether a procedural sedation in the pediatric ED may be unsafe despite ASA classification and advocate for their patient to be taken to the OR if needed.2,3,6
Physical Exam
The physical exam is a tool that should be factored in when determining the safety of a sedation. A thorough physical exam should be performed, including neurologic status and baseline cardiac and lung auscultation, abdominal exam, skin exam, examination of injury requiring procedure, and circulation. Knowing a patient’s baseline cardiovascular and neurologic status can help determine the safety of performing procedural sedation in the ED. It also is important to ensure children return to their neurologic baseline after procedural sedation is performed and prior to discharge. A thorough airway assessment also should be performed if a clinician is considering procedural sedation. It is important to acknowledge key anatomical differences between pediatric and adult airways and airway management, since advanced airway maneuvers may become inadvertently required during procedural sedation.
Pediatric Airway Assessment
To begin, children tend to have a larger head, occiput, and tongue proportional to their body in comparison with adults. They tend to have smaller mandibles and floppy epiglottises, which can obstruct the airway. In addition to a floppy epiglottis, large adenoids and tonsils in children often can occlude the upper airway. In pediatric patients, especially infants, the larynx generally is more cephalad and anterior, which can make the view of the vocal cords more difficult. This can be overcome by rolling a towel and placing it under patients’ shoulders to increase cervical extension like a “sniffing” position that is taught during pediatric advanced lifesaving courses. While clinicians should be prepared to move to intubation if necessary, positive pressure ventilation with a bag valve mask (BVM) and a tidal volume of 8 mL/kg often is adequate when expeditious recovery is expected because of a deeper level of sedation than intended. While it can be difficult to assess tidal volume being delivered via BVM, this recommended tidal volume reduces the risk of gastric insufflation and barotrauma.2,3
Part of the airway assessment involves determining a patient’s Mallampati score. A Mallampati assessment can be performed by having the child open their mouth while sticking their tongue out. The examiner should look at the posterior oropharynx to evaluate visualization of the hard palate and uvula. This is a tool that can be useful in estimating the difficulty of intubation, should that become necessary. The score ranges from I-IV, with higher classes being associated with decreased visualization of the hard palate, which is associated with a more difficult intubation.11,12 (See Figure 1.)
Figure 1. Mallampati Scores |
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Source: Relias |
A study evaluated whether higher Mallampati scores in pediatric patients undergoing procedural sedation correlated with a higher level of adverse events. This study revealed that, although patients with Mallampati III or IV required more frequent repositioning during the sedation, they did not have higher rates of adverse events compared to patients that were Mallampati classes I-II. Although there was no direct correlation with increased adverse events, physicians should assess Mallampati scores before sedation and continuously monitor for airway changes that may require intervention.11
Clinicians should be proficient in advanced airway techniques and have adjuncts readily available during procedural sedations. Supraglottic airway devices may be used, but, ultimately, clinicians should be aware of surgical cricothyrotomy and contraindications. Surgical cricothyrotomy is contraindicated in patients younger than 10 years of age because of how small the cricothyroid membrane is. A needle cricothyrotomy may be used if the patient is both younger than 10 years of age and a more advanced airway is necessary.3
Fasting Status
Although the ED often is dynamic, it is important that procedural sedations are set up in a well-controlled and prepared environment. A key element that should be elicited in the history is determining a patient’s last oral intake and what was ingested at that time. While general fasting guidelines will be covered here, it is recommended that clinicians investigate their hospital-specific protocols prior to performing procedural sedation.
Fasting guidelines for unplanned procedures remain a controversial topic and often revolve around clinical judgement rather than absolutes. Most of the data investigate side effects, such as aspiration risk in patients who are undergoing elective procedures in an OR, which can make extrapolation of these data challenging.
In the ED, the urgency of the procedural sedation will dictate how strictly these recommendations are adhered to. Guidelines that have been created by anesthesiologists have established “safe” fasting periods for a variety of food and drink options. For example, the risk of pulmonary aspiration was found to be lessened if the minimum fasting period is two hours for clear liquids; four hours for breast milk; six hours for infant formula, nonhuman milk, or a light meal; and eight hours or more for fried or fatty foods, including meat. Specifically, the study referenced defined clear liquids as water, black coffee, juices without pulp, and carbonated beverages.3,6,9,10,13,14 It is important to ascertain these details, since nonhuman milk is more like solid food in its gastric emptying time than other liquids. A light meal in the study is defined as toast and clear liquids.14 Another study investigating preprocedural fasting and incidence of adverse reactions in healthy children ASA I or II revealed no cases of pulmonary aspiration despite nearly half of the study’s participants not meeting the guidelines for eight or more hours for solid food fasting. This Canadian study evaluated 6,180 children and determined there was no association between fasting duration and any adverse event investigated, such as pulmonary aspiration, vomiting, or apnea.10
While adhering to recent guidelines regarding preprocedural fasting maximizes safety, the urgency and safety of the procedure should determine whether moving forward outweighs delaying the procedure while in the ED. If a procedure is deemed urgent despite recent oral intake, providers should consider ketamine use because of its propensity to protect airway reflexes, although clinicians should consider premedication with ondansetron, given ketamine’s tendency to cause emesis. It is crucial to consider the urgency of the procedure, last intake, ASA classification, and overall health of a patient when debating a pediatric procedural sedation.2,8
Preparation
Physicians should discuss their plan for sedation with support staff and ensure that team members are available for the procedural sedation. It is recommended to check local protocols, since hospitals may have varying requirements regarding who is required to be in the room for procedural sedation. In general, it is recommended that, for moderate or deeper sedation, there should be a clinician performing the procedure, a physician in charge of the sedation, a nurse, and a respiratory therapist.
The American Academy of Pediatrics states that all staff taking part in the procedural sedation should be Pediatric Advanced Life Support (PALS) certified. In the American College of Emergency Physicians protocol, it is acceptable for a nurse trained in procedural sedation to be watching the monitors and evaluating the patient along with the respiratory therapist while the physician performs the procedure. While there are data showing the rate of adverse events is similar whether one or two physicians are present, it is recommended that two physicians be present if available.3,15
Preparation includes obtaining written consent after thoroughly explaining to the patient and guardian what to expect from the sedation, including the procedure itself, the risks of, benefits of, and alternatives to sedation. The patient’s legal guardian(s) should understand the procedure and sedation. They should be able to recite the task at hand, risks, benefits, and alternatives. Additionally, physicians should offer alternatives, such as local, regional, and general anesthesia, if appropriate.2,9
The sedation and procedure itself should be explained as two separate events. It is important that risks and alternatives for both sedation and the procedure are discussed prior to signing a consent form. If a consultant, such as an orthopedic colleague, is performing the procedure, it is important they discuss their role and obtain consent for the procedure that they will complete in addition to the ED physician obtaining consent for the sedation. While it may not be necessary, it is recommended that two separate consent forms be completed to reiterate that there are risks of sedation as well as of the procedure that will be performed simultaneously.9
There should be proper documentation surrounding the details of a procedural sedation. This includes consent forms, medications to be used, vitals, and recovery. The staff member documenting the sedation generally is a registered nurse. Prior to the sedation and procedure being performed, there should be a timeout to verify patient identification, details of the procedure and sedation, medications to be used, allergies, and staff roles. The nurse will obtain and document a full set of vitals before, during, and after a sedation is performed, which includes heart rate, respiratory rate, blood pressure, oxygen saturation, and, in some protocols, expired carbon dioxide. Before administering medications to be used for the sedation, the nurse should confirm and document the medication to be used as well as the dose, route, site, and rate it is to be given.16
A key element in preparing for a procedural sedation is having the equipment needed and ensuring monitoring devices are working. It is crucial for clinicians to be prepared for the worst-case scenario before every sedation and have equipment readily available to address these concerns. This includes a crash cart and defibrillator that is easily accessible as well as reversal agents for the medications that will be administered. Given the potential for airway compromise, providers should be competent in pediatric airway management.9
To prevent delays in care during critical times of need, providers should ensure they have airway equipment that is appropriately sized for their patient at the bedside. For some clinicians, this may mean video-assisted intubation, a direct laryngoscope, bougie, or supraglottic devices. Clinicians should formulate a stepwise approach to the airway adjuncts they will use to prevent delays if necessary. In addition to airway equipment, clinicians should ensure monitoring devices that will be used during the sedation are connected and functioning properly prior to the start of the procedure.3,9
The Pediatric Sedation State Scale (PSSS) is a tool that can be used to objectively score various sedation methods. The PSSS is a way of evaluating and documenting the goal vs. the quality of sedation that is observed. It consists of a scale with six levels of sedation and documents physiologic measures, level of patient interference, use of restraints, and overall behavior. (See Table 2.) This tool provides a more thorough review of events during sedation as compared to simply tracking the depth of sedation achieved. A benefit of using the PSSS is that it can be used to compare nonpharmacologic as well as pharmacologic methods. Therefore, this tool can be used as an objective measure for evaluating the effectiveness of behavioral and cognitive strategies that can be used with analgesia instead of sedation.6
Table 2. Pediatric Sedation State Scale6 | |
State | Behavior |
0 |
|
1 |
|
2 |
|
3 |
|
4 |
|
5 |
|
Sedation Monitoring
Prior to procedural sedation, a provider should evaluate the patient’s baseline mental status, vitals, level of pain, and overall stability for the procedure and sedation. Monitoring blood pressure, capnography, oxygenation, and heart rate is recommended. In addition to monitoring vital signs, providers continuously should be observing the patient’s face, mouth, and chest wall during the procedure.3,9
There is some variance among protocols about how often vitals should be recorded throughout sedation and during the recovery period, but most resources recommend every five to 10 minutes. Despite recording vitals every five to 10 minutes, clinicians constantly should monitor patients and evaluate their hemodynamic stability and respiratory status.2
Capnography or end tidal carbon dioxide (CO2) monitoring can be used for detecting the absence or presence of respirations during sedation. Its use can be beneficial in scenarios where it may be difficult to see the patient, such as when the patient is in the scanner or during a lumbar puncture, where their body may be folded. During sedation, children often may have a nasal cannula with supplemental oxygen, which can prolong the amount of time until desaturation is evident on the monitor, given the increased oxygen reserve. In these situations, capnography can be monitored as a measure of ventilation.2,17
Some studies have revealed that clinicians can detect changes in respiratory status more readily by evaluating for a change in CO2 levels before the child becomes hypoxemic or hypoventilates.17 A systematic review of 20 randomized controlled trials revealed that, in children who were monitored via capnography, there was no major adverse event that required assisted ventilation or apneic periods.6 In theory, the use of capnography should reduce the incidence of hypoventilation and oxygen desaturation. A study performed in a pediatric ED found the incidence of desaturation or hypoventilation dropped from 7% to 1% if capnography was used.2,17 This was accredited to the timelier interventions by providers using capnography.17 Capnography can be used as a tool that adds to a patient’s overall clinical picture, but it should not replace a thorough exam or continuous assessment by the clinician throughout the sedation.
During the Sedation
It is important for physicians to remain vigilant throughout the entirety of a sedation, since studies have shown that adverse effects are concentrated around five to 10 minutes after the last dose of medication and after painful stimuli are withdrawn. However, the medication used, route of administration, and amount given may alter this timeframe.7,18 A study evaluated more than 1,300 pediatric procedural sedations and determined that 92% of adverse events occurred during the procedure. Serious adverse events, such as hypoxia, apnea, or hypotension, were reported with a median of two minutes after the last medication was administered. Patients who experienced serious adverse events more than 25 minutes after the last dose were those who experienced similar responses during the peak drug effect, suggesting that those who do not experience adverse effects during the sedation may be safe for discharge 30 minutes following the last dose, if they meet discharge criteria.18
Another study performed on 1,367 patients revealed that those who did not experience adverse effects during sedation were able to be discharged 30 minutes after the last dose of medication was given. These data support the general idea that, if children remain stable during a procedural sedation and during the recovery phase without side effects, they can be discharged 30 minutes post-sedation. However, clinician discretion is recommended.7
Potential Adverse Reactions During Sedation
As with the administration of any medication or intervention, complications during sedation may arise. When a procedural sedation is underway, the remainder of the staff in the department should be aware in case additional support is required. If the patient inadvertently obtains a deeper level of sedation, providers should evaluate the patient’s airway to determine if intervention is required.3 Emergency physicians should follow standard practice when a patient’s airway becomes tenuous by applying oxygen if not already in place, jaw thrusting, bag-valve masking, and even intubation if necessary. Airway management is crucial in pediatric patients because most pediatric cardiac arrests are caused by hypoxia and respiratory compromise.2,3 In addition to airway management, providers should be familiar with items in the code cart and other supplies they may need for resuscitation. Rarely, patients may require fluids or pressors for support during a procedural sedation. Other items that may be used are general resuscitation medications such as epinephrine or lidocaine.3 While cardiac arrest is rare in children during pediatric procedural sedation, providers should be prepared and follow typical PALS protocols.3
Medications
It is important that providers intending to use sedative medications understand and can determine the level of sedation, drug mechanism of action, associated risks, side effects, proper dosing, and medication length of duration prior to performing procedural sedation. There are numerous routes through which sedatives can be given such as intranasal, intramuscular, and intravenous. The first step when choosing a medication is to determine the goal of sedation. Along with determining the goal of the procedure, it is important to consider pain levels, length of sedation, and the route of medications. For instance, if a child already has an intravenous (IV) line placed, then the IV route may be preferred. In other situations, obtaining IV access for a short or mildly painful procedure may worsen the child’s anxiety and fear surrounding the actual procedure. These questions and considerations can act as a framework to determine the best medication options for pediatric procedural sedation.2,6,19
In addition, providers should have a thorough understanding of the medications they are using, including dosing, time to peak effect, titratability, and safety with additional doses. Performing a sedation with the fewest number of medications generally is the safest method because side effects may be additive when using multiple agents. Providers should understand when to expect peak effectiveness for the agent selected, which ultimately will determine when it is appropriate and necessary to give additional doses. Additionally, clinicians should be versed on expected recovery time and side effects that may arise post-sedation.2,16
Intranasal Medications: Properties and Side Effects
Intranasal (IN) sedatives and analgesics are a good option for anxiolysis or short procedures that only involve minor pain, such as a small laceration repair or wound irrigation.3 IN medications use the extensive blood supply of the nose, which increases surface area for absorption of medications.19 IN administration is not recommended if the patient has congested nares, since this decreases the absorption of the medication administered.9,19 First-pass metabolism by the liver also is avoided, given the venous drainage of the nose ends in the superior vena cava. Intranasal medications often require higher doses than other routes of administration and because of such frequently are underdosed.19 Most IN medications take roughly three to five minutes to become therapeutic and 10-15 minutes before reaching peak effectiveness. Because of this delay in effectiveness, IN medications will rarely reach levels high enough to cause respiratory depression if appropriate doses are given.9
When ordering IN medications, it is important to use the highest potency formulation available that is appropriate for the patient’s weight to maximize the dose while minimizing the volume that must be given. For instance, IN midazolam often comes in 1 mg/mL or 5 mg/mL formulations. For a 10-kg patient receiving IN midazolam at 0.3 mg/kg to 0.5, the IN midazolam 5 mg/mL formulation should be used, which would only require 1 mL administered initially vs. the 1 mg/mL formulation, which would require 5 mL.16,20
In general, no more than 0.2 mL to 0.3 mL should be administered into each nostril to avoid runoff and drug loss. If it is still greater than 0.3 mL when using the maximum potency, it is best to use both nares to maximize surface area for greater absorption. A benefit of IN medications in the pediatric population is that IV placement often can be avoided, which can be an additional painful and anxiety-provoking procedure.16
IN Midazolam
The most extensively studied IN sedative options are midazolam and dexmedetomidine. IN midazolam can burn with administration and is sometimes given with IN lidocaine for this reason. IN midazolam can be given at 0.3-0.5 mg/kg. IN midazolam itself does not cause deep sedation and, if administered alone, is considered to cause anxiolysis.16,20 IN midazolam is a great option in pediatrics for non-painful procedures, such as anxiety in the CT scanner or a small laceration repair where local anesthetic will be used.3
IN Dexmedetomidine
IN dexmedetomidine provides deeper sedation that lasts longer than midazolam. Dexmedetomidine dosing is 0.05 mcg/kg to 3 mcg/kg. An advantage of dexmedetomidine is that it does not cause hemodynamic instability. A disadvantage of this medication when given intranasally is that it must be administered 25 minutes before it takes effect.16,20
IN Fentanyl
IN fentanyl is an option for pain management that works well for moderate to severe pain. However, fentanyl should be used only for short procedures, given that the duration of action is short. Fentanyl is acts rapidly and can be administered intranasally at 1 mcg/kg to 2 mcg/kg with a maximum dose of 100 mcg.9,16 Thirteen studies have shown that IN fentanyl is comparable to IV morphine in terms of analgesia. This is a good option for pain control if an IV is not needed.9,16,20
IN Ketamine
IN ketamine can be used for pain control at subdissociative doses. IN ketamine for subdissociative analgesia is dosed at 0.5-1 mg/kg. It can be advantageous in situations when IV access is not necessary and a longer period of analgesia is needed compared to IN fentanyl. IN ketamine at subdissociative doses provides analgesia for roughly 60 minutes vs. 30 minutes for IN fentanyl.16,20
Table 3 summarizes IN medications used for pediatric procedural sedation.
Table 3. Intranasal Medications Used for Pediatric Procedural Sedation | |||
Medication | Dose | Uses | Disadvantages/Side Effects |
Midazolam | 0.3 mg/kg to 0.5 mg/kg | Anxiolysis | Can burn and sometimes is given with intranasal lidocaine to decrease pain |
Dexmedetomidine | 0.05 mcg/kg to 3 mcg/kg | Hypnotic/sedative | Takes 25 minutes before taking effect |
Fentanyl | 1 mcg/kg to 2 mcg/kg, 100 mcg max | Analgesia | Short duration of action |
Ketamine | 0.5 mg/kg to 1.0 mg/kg | Subdissociative analgesia | Emergence agitation |
Intravenous Medications
There are numerous IV options for procedural sedation, including ketamine, propofol, a combination of ketamine and propofol, etomidate, benzodiazepines, and pure analgesics, such as fentanyl. Although there are not overwhelming data to support sedation medication being safer when administered intravenously vs. other routes, the principle of slowly titrating medication and having established access for use if side effects occur or if reversal or resuscitation medications are needed can be desirable.7 Emergency medicine physicians should know the properties of each medication and ensure that sedation and analgesia are being maintained when appropriate. For instance, propofol, etomidate, and benzodiazepines are not analgesic, and other medications would need to be co-administered with these if analgesia is a goal of the sedation.21
The trend of preferred sedation drugs has shifted over the years. Benzodiazepines and analgesia used to be a mainstay for sedation medications, but this has waned in popularity because of their increased risk of side effects. Studies have shown that, compared to the preferred agents used today, such as ketamine, propofol, and analgesics, the combination of benzodiazepines and analgesics confers an increased risk of cardiorespiratory depression.19
In a study analyzing adverse events from all procedural sedation medications used in a large urban pediatric ED, there was no one specific medication that was associated with increased adverse events. In addition, no statistically significant difference was found when comparing the mean dose of medications in children who experienced adverse events vs. those who did not. This study’s adverse event rate for pediatric emergency providers administering procedural sedation was 2.3%. Among those who experienced adverse events in this study, no children required reversal agents, intubation, or hospital admission.21
Opioids: Properties and Side Effects
Opioids, such as fentanyl, often are used as analgesia during or prior to a procedural sedation. Fentanyl is the most frequently used IV opioid in the pediatric ED for procedural sedation at this time. The initial dose for IV fentanyl is 0.5 mcg/kg to 1.0 mcg/kg.9,16 A feared complication of fentanyl is that rapid pushes or high doses of the medication in infants may cause chest wall rigidity and lead to respiratory depression. While this is a rare complication, it is important to recognize, since it could lead to rapid respiratory collapse. If the provider is concerned that such complications are occurring, naloxone should be administered.16 Naloxone works by outcompeting and displacing opioids from receptors. It has a short duration of action and, thus, additional doses may be needed. It can be administered at 0.1 mg/kg/dose every two to three minutes as needed and may be repeated at that dose every two to three minutes. If a child is opioid-dependent, reversal of this may cause the child to experience withdrawal symptoms, such as diarrhea, sweating, or irritability.22
Benzodiazepines: Properties and Side Effects
Benzodiazepines given intravenously are no longer preferred for pediatric sedation, since they need to be administered with analgesia, which can cause cardiorespiratory depression. Additionally, these medications can cause a paradoxical reaction involving the patient becoming excited and agitated instead of sedated. Benzodiazepines also have potential drug interactions, since they inhibit the cytochrome P450. This can lead to prolonged sedation if the patient has received other cytochrome P450-inhibiting medications.2 In the event of its use, IV midazolam for sedation is dosed at 0.05 mg/kg to 0.2 mg/kg, and IV lorazepam is dosed at 0.05 mg/kg to 0.1 mg/kg.16
Given that benzodiazepines can cause respiratory depression, it is important to be familiar with its reversal agent flumazenil. Flumazenil works to counteract the effects of benzodiazepines by binding to the gamma-aminobutyric acid (GABA) receptors without activating them. Flumazenil may need to be redosed, given its short effect duration. It can be given at 0.01 mg/kg IV and can be redosed at 0.005 mg/kg to 0.01 mg/kg IV in 45 seconds to one minute if the patient has not reached the desired level of sedation.22 Flumazenil should not be provided to patients on chronic benzodiazepines because it can precipitate seizures.
Ketamine: Properties and Side Effects
Ketamine frequently is used in procedural sedation in children and adults because of its amnestic, analgesic, and dissociative sedating effects. Given these properties, ketamine is a great option for painful procedures, such as abscess drainage or fracture reduction. Ketamine is an attractive sedation medication, given that it does not impair airway reflexes, cardiovascular hemodynamics, or respiratory drive. Ketamine is an N-methyl-D-aspartate and GABA antagonist that works by decreasing pain activation via central desensitization, thus providing analgesic as well as amnestic effects. It has a rapid onset, and a single dose generally is adequate for procedures 20-30 minutes long.16,23 Ketamine can be used for patients of almost any age, which is an attractive feature of the medication. Two absolute contraindications of ketamine are children younger than 3 months of age and patients with known schizophrenia, given the risk of inducing active psychosis.6,9,16
Ketamine can be given intravenously at a subdissociative dose at 0.3 mg/kg. When given at this dose, it still is analgesic and amnestic without the dissociative effect. This dose is sometimes referred to as pain-dose ketamine, given its analgesic properties even at lower doses. Studies have shown that subdissociative levels of ketamine are equivalent to IN fentanyl or IV morphine for fracture pain. Subdissociative doses also are associated with increased emergence agitation.16,23
Anesthetic dosing of ketamine starts at 1.0 mg/kg to 1.5 mg/kg IV and often is used for painful procedures. Sedation when this dose of ketamine is given intravenously lasts five to 10 minutes, but the anesthetic effect is one to two hours.23 An advantage of ketamine is that additional doses at the anesthetic dosing level typically do not affect hemodynamic stability or deepen sedation. This means that additional doses of ketamine work only to lengthen sedation time without increased adverse events.3,16,23 Ketamine also can be given intramuscularly if needed, but that is not recommended because of the increased association of side effects, such as emesis, and longer recovery time. It also is more difficult to titrate intramuscular ketamine compared to the slow IV push.9 Ketamine is associated with an increased risk of emesis, and studies support premedication with ondansetron in certain age groups. However, studies have yet to demonstrate that premedication prior to ketamine use in children younger than 5 years of age is beneficial.6,8,9,19
Laryngospasm is another adverse event that can occur in children after ketamine administration. The glottis closes when the superior laryngeal nerve causes the vocal cord muscles to uniformly close. This blocks the airway when swallowing to prevent aspiration. Laryngospasm is thought to be caused by a hyperactivation of this normal physiologic response. Laryngospasm with ketamine is thought to be caused by hypersalivation, causing airway obstruction. A high-pitched inspiratory stridor may be heard when a patient is experiencing laryngospasm. Although there may be auditory cues, it is important to stay vigilant when monitoring patients during sedation because there could be silence if there is complete airway obstruction. Clinicians may notice increased work of breathing, oxygen desaturation, decreased chest wall movement, or loss of end tidal capnography in complete airway obstruction.2,9,24
While this adverse event can lead to rapid respiratory compromise, the risk of this occurring in children after ketamine administration is only 0.3%.16 However, the incidence is three times higher for children 3-6 months of age. Some clinicians attribute this to smaller airways, medication sensitivity, and increased parasympathetic tone.16,24 For these reasons (and the lack of data showing successful trials in children younger than this age), ketamine is contraindicated in children younger than 3 months of age.16
When a clinician has identified that a child is having a laryngospasm, they should perform a jaw thrust maneuver and begin positive pressure ventilation. A jaw thrust may help to lift the tongue away from the posterior pharyngeal wall, which ultimately may lift supraglottic tissue. Positive pressure acts to improve the obstruction in the glottic space. If this is unsuccessful, deeper sedation may be required. In this case, regardless of what the inducting agent was, ketamine should be avoided for further sedation. The general recommendation in this situation is that propofol can be used for deeper sedation and airway protection.2 The use of propofol alone has been shown to reverse laryngospasm in 75% of cases. If laryngospasm continues despite these interventions, anesthesia should be called to the bedside and paralysis with succinylcholine should be used.2,25
Succinylcholine can be given at 0.1 mg/kg to 0.2 mg/kg IV to combat laryngospasm. Succinylcholine also can be given intramuscularly at 4 mg/kg if there is not established IV access. Succinylcholine works to break laryngospasm via the quick relaxation of laryngeal muscles even before skeletal muscle relaxation. Because of this, succinylcholine often can break laryngospasm within one minute of IV administration. During this time, patients should be continued on 100% oxygen. Atropine also can be given with succinylcholine because it has anti-sialagogue effects, which often are thought to be a trigger for laryngospasm. If the paralytic fails to break the laryngospasm, clinicians should move toward intubation.2,25
Upon waking from ketamine, an emergence reaction sometimes is observed. Emergence agitation after ketamine use is described as restlessness, irritability, or crying. This exists on a continuum with emergence delirium, which is described as extreme agitation and combativeness.26 While there is some evidence supporting reduced emergence reaction with midazolam administration five minutes before giving ketamine, numerous studies in children have reported that there is no difference in occurrence of emergence reactions despite premedication with benzodiazepines.7
Although their use is not supported for premedication, benzodiazepines can be used to treat agitation and restlessness associated with emergence reactions in children.16 Overall, it seems that negative emergence reactions after ketamine use are not very common in children and may occur in roughly 2% of pediatric patients. Therefore, they should not discourage the use of ketamine in the pediatric population.15
Propofol: Properties and Side Effects
Propofol is an extremely fast-acting sedation medication. Along with a quick onset, the recovery time after propofol administration is only eight to 10 minutes. Propofol does not have analgesic properties, meaning it must be administered with another agent for painful procedures. On the contrary, it has antiemetic properties and does not need to be administered with ondansetron like ketamine does.16,19 Propofol for sedation is dosed at 1.0 mg/kg to 2.0 mg/kg IV. Propofol is a great option for procedures that are not extremely painful, such as a lumbar puncture or a CT scan.
In addition, propofol can be used with a local anesthetic or given with IV analgesia, such as fentanyl, for more painful procedures. Similarly to ketamine, sedation with propofol can be achieved with a single loading dose. Some data suggest pain at the injection site when administering propofol, but this can be reduced by using larger-bore IVs or by premedicating patients with small doses of lidocaine at the injection site.16
Adverse events associated with propofol are less frequent than those from other sedation medications, but they are important to be familiar with and be prepared to manage. Propofol can cause hypotension, apnea, bradycardia, and/or laryngospasm like ketamine. The major difference in these adverse effects when compared to ketamine is that propofol can affect hemodynamic stability, unlike ketamine.16 Using propofol in hypovolemic patients should be cautioned against, given its ability to cause vasodilation and decrease cardiac output. Additionally, it is widely debated whether propofol may decrease heart rate.27 Contraindications to the use of propofol include patients who have allergies to soy, eggs, or prior allergic reactions to propofol.28
It also is recommended that propofol administration be avoided in individuals with known mitochondrial diseases. This is because of evidence showing that patients with mitochondrial diseases who are exposed to propofol infusions long-term are at an increased risk for developing propofol infusion syndrome. The thought is that propofol administration further disrupts the mitochondrial membrane pore, thereby decreasing the membrane potential.29 Propofol-related infusion syndrome (PRIS) is characterized by bradycardia, asystole along with metabolic acidosis, rhabdomyolysis, acute renal failure, and often death. PRIS is described in the literature thus far as being associated with continuous infusion. Most of these cases are associated with use longer than 48 hours or in high doses, such as > 5 mg/kg IV.30
Given the rarity and the unlikelihood that a patient in the ED will be receiving continuous propofol for more than 48 hours or at high doses, it is unlikely that emergency medicine physicians will encounter PRIS, but it is important to be cognizant of the complications that can be caused by interventions initiated in the ED.
Ketofol: Properties and Side Effects
Gaining in popularity over the years for pediatric procedural sedation are different ratios of ketamine and propofol — called “ketofol.” In general, sedation medications are safer when administered as a single agent, although there are some combinations that appear to be advantageous in terms of decreased side effect profiles, such as ketofol. This combination is thought to confer decreased respiratory depression and hemodynamic instability while providing adequate and long-lasting analgesia.16,23
Ketamine provides analgesic effects and decreases the risk of respiratory depression and hemodynamic instability that propofol confers. Propofol is beneficial to the pair because it is ultra-short acting and antiemetic. Overall, the combination allows for reduced serum levels of each drug, ultimately minimizing side effects from each. Ketofol dosing is most often used and studied as a 1:1 ratio. In children, this means 0.5 mg/kg ketamine and 0.5 mg/kg propofol are combined and generally need to be re-dosed every two to five minutes. Several studies have investigated different ratios of ketofol from 1:1 to 1:10, but most studies have concluded that ratios from 1:1 to 1:3, with the larger proportions being propofol, are the most effective. Given that propofol and ketamine are compatible with each other, these medications can even be mixed in the same syringe for easier administration.16,23
Although studies have determined that ketofol is superior in achieving and sustaining sedation as compared to either agent alone, studies are inconclusive about whether side effects are truly reduced and whether it is statistically significant.23 Many experts have yet to back the use of ketofol in pediatrics because of the lack of objective data to support its use. A multicenter study in Canada incorporating more than 6,000 children showed significantly reduced adverse events with ketamine alone as compared to ketofol.16 However, studies have revealed that patient and provider satisfaction with ketofol is increased as compared to either agent alone.31
Etomidate: Properties and Side Effects
Etomidate is not used in procedural sedation as routinely as ketamine or propofol, but there are some advantages and certain situations that make it a preferred option. Etomidate can be dosed at 0.2 mg/kg to 0.3 mg/kg IV and has a rapid onset and short duration.9,16 A benefit of etomidate is that it confers hemodynamic stability.9 Etomidate should be considered when there is concern for increased intracranial pressure because of its ability to reduce cerebral oxygen consumption. A disadvantage of etomidate is that its use can result in myoclonus.16
Nitrous Oxide: Properties and Side Effects
Nitrous oxide (NO) is another method of sedation in the pediatric ED. NO provides weak dissociative anesthesia while also providing amnestic and anxiolytic effects, seemingly making it a great alternative medication to some of the more commonly used IV medications (ketamine, propofol, etc.). An advantage of NO is how quickly patients can recover from its use. It takes around three to five minutes for onset and recovery after use.3,9,16 While NO use can be beneficial in situations that may not otherwise require IV access, the ED must have the capability to deliver NO and oxygen in the correct ratios to be used.
A disadvantage of NO is that it does not provide much analgesic effect and is better suited for less painful procedures or to be used in conjunction with local and regional analgesics.9 Although NO has reported weak analgesic properties, a small prospective study revealed that self-administered NO 50% to oxygen 50% for fracture reduction in the pediatric ED was associated with reduced levels of patient-reported pain. In this study, 60% of children reported no pain during the procedure and only 5% of children in the study reported they experienced moderate pain during the fracture reduction.32 Other studies report the use of NO with hematoma blocks for forearm reductions in the pediatric ED as being as effective as IV ketamine or midazolam — with the bonus of quicker recovery time as compared to those alternative options.9
There have been numerous studies investigating the best ratio of NO to oxygen that should be administered. For NO to be used for sedation, it must be possible to be delivered at 100%, and oxygen should not be delivered at less than 25%. The exact concentration and ratio of NO to oxygen can vary. Data suggest that, for minor procedures and lower levels of intended sedation, NO can be used at 50% or less and be balanced with oxygen delivery. Going higher than 50% NO increases the chance of going into deeper sedation.16,33 In a prospective randomized controlled trial, measured anxiety and pain in children receiving laceration repairs were recorded. Test groups were given an inhaled 50% NO and 50% oxygen mixture vs. 100% oxygen in the control group. The modified Children’s Hospital of Eastern Ontario Pain Scale was used to score pain prior to and after the procedure.33 In addition, there was a secondary outcome measured that evaluated anxiety on a four-point scale. Although this study did not find a significant difference in anxiety or pain prior to the procedure when comparing the two treatment groups, it did reveal a statistically significant difference in anxiety during and after the repair when using NO and oxygen mixture vs. oxygen alone.33 Table 4 summarizes various IV medications used for pediatric procedural sedation.
Table 4. Intravenous Medications Used for Pediatric Procedural Sedation | |||
Medication | Initial Dose | Uses | Disadvantages/Side Effects |
Fentanyl | 0.5 mcg/kg/dose to 1.0 mcg/kg/dose | Analgesic | Can cause chest wall rigidity in infants; respiratory depression |
Midazolam | 0.05 mg/kg to 0.2 mg/kg | Anxiolysis | Respiratory depression, cytochrome P450 inhibitor |
Ketamine: subdissociative | 0.3 mg/kg | Analgesic and mild sedative | Emergence agitation |
Ketamine | 1.0 mg/kg to 1.5 mg/kg | Dissociative | Emetogenic; laryngospasm; emergence agitation |
Propofol | 1.0 mg/kg to 2.0 mg/kg | Hypnotic/sedative | Not analgesic; hypotension; bradycardia; apnea |
Ketofol 1:1 ratio | 0.5 mg/kg ketamine and 0.5 mg/kg propofol | Hypnotic/sedative/dissociative | Inconclusive data to suggest occurrence of side effects thus far |
Etomidate | 0.2 mg/kg to 0.3 mg/kg | Hypnotic/sedative | No analgesia; myoclonus |
Nitric oxide | Titrate to effect | Dissociative | Not readily available, little analgesic effect |
Cognitive Strategies
In addition to medication, behavioral and cognitive approaches can be useful in gaining trust and cooperation during procedural sedation. These approaches can lessen preprocedural anxiety. Decreased anxiety may lead to reduced amounts of medication needed, which ultimately would be associated with decreased adverse events. There are numerous behavioral strategies that can be implemented when interacting with children, such as reinforcing coping skills, positive reinforcement, desensitization, distraction, and relaxation. Distraction techniques, such as music, toys, games, and glucose for infants, can be very effective in reducing preprocedural anxiety as well as gaining the trust of a child. Child life specialists, if available, are invaluable at assisting with cognitive strategies of care.6
Discharge Criteria
In addition, the patient’s level of consciousness and mental status should be monitored and recorded during the recovery phase as well as at the time of discharge.2 In general, patients must be at their mental status baseline, tolerate food or drink intake by mouth without vomiting, ambulate without difficulty (if age-appropriate), and have remained hemodynamically stable throughout the procedure and recovery phase to be suitable for discharge.2,6,7,16,18 If a patient has an adverse event or requires medication reversal with flumazenil or naloxone, they typically require a longer period of monitoring.2 Providers should reconsider pathologies and patient stability if a child has been hypotensive or hypoxic prior to or following a sedation.7 Children should be released to reliable caregivers and, like adults, should not drive (if able) immediately after a sedation.9 Emergency medicine physicians should check their hospital protocol for specific details regarding discharge criteria following a pediatric procedural sedation.
Conclusion
Procedural sedation frequently is performed in the care of children in the ED. Preparation includes performing a detailed history and physical exam, recruitment of staff, and supplies for reversal or resuscitation at the bedside. Medication selection should be based on the clinical scenario and the child’s level of anxiety and pain. The emergency provider should have a thorough understanding of the nuances of pediatric procedural sedation.
Courtney Botkin, DO, is Resident Physician, Department of Emergency Medicine, University of North Carolina, Chapel Hill
Daniel Migliaccio, MD, FPD, FAAEM, is Clinical Associate Professor, Director of Emergency Ultrasound, Ultrasound Fellowship Director, Department of Emergency Medicine, University of North Carolina, Chapel Hill
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Every acute care clinician needs to know and be familiar with the process of procedural sedation, medication selections, options, and contraindication for different procedures. The authors comprehensively review procedural sedation, emphasizing evidence-based choices.
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