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Selection of medications for pediatric procedural

sedation outside of the operating room
Authors: Joseph P Cravero, MD, Mark G Roback, MD
Section Editors: Anne M Stack, MD, Adrienne G Randolph, MD, MSc
Deputy Editor: James F Wiley, II, MD, MPH

All topics are updated as new evidence becomes available and our peer review process is complete.

Literature review current through: Oct 2022. | This topic last updated: May 20, 2022.

INTRODUCTION

This topic will discuss the selection of medications for pediatric procedural sedation outside of
the operating room. The properties of agents commonly used for procedural sedation in
children; the assessment, preparation, and proper performance of procedural sedation in
children outside of the operating room are discussed separately:

● (See "Pharmacologic agents for pediatric procedural sedation outside of the operating
room".)

● (See "Preparation for pediatric procedural sedation outside of the operating room".)

● (See "Procedural sedation in children outside of the operating room".)

Recommendations for procedural sedation in children undergoing gastrointestinal endoscopy,

bronchoscopy, cardiac catheterization, or interventional radiology are beyond the scope of this
topic.

NONPHARMACOLOGIC INTERVENTIONS

Nonpharmacologic interventions include behavioral and cognitive approaches, such as

desensitization, distraction, reinforcing coping skills, positive reinforcement, and relaxation.
These techniques are complementary to pharmacologic interventions and, in some children,
may prevent the need for sedation altogether. (See "Procedural sedation in children outside of
the operating room", section on 'Nonpharmacologic interventions'.)

CHOICE OF SEDATIVE AGENTS

The targeted depth of sedation and the agents used largely depend upon the anticipated
degree of pain, the allowable amount of motion during the procedure, and the following
patient factors [1,2] (see "Preparation for pediatric procedural sedation outside of the operating
room", section on 'Presedation evaluation'):

● Comorbidities (eg, asthma, upper respiratory tract infection)

● Fasting status
● Age and development level
● Ability to cooperate
● Degree of anxiety
● Any prior problems with specific medications

The dosing, administration, and properties of commonly used medications for pediatric
sedation are listed in the tables and discussed in detail separately ( table 1 and table 2).
(See "Pharmacologic agents for pediatric procedural sedation outside of the operating room".)

In some facilities, the use of specific sedatives may be restricted to use by anesthesiologists or
other specialists (eg, pediatric critical care or pediatric emergency medicine specialists). For
example, in some settings, propofol is only approved for use by anesthesiologists or others
with specialized pediatric procedural sedation training. Otherwise, bolus propofol use for
procedural sedation in children requires special privileging. The clinician should be aware of
local requirements.

Safety requirements — Safe use of sedative agents outside of the operating room requires
careful attention to the following factors:

● Selection and preparation of patients – The patient should be evaluated and prepared
for sedation in accordance with guidelines designed to maximize patient safety. This
assessment, includes an American Society of Anesthesiologists (ASA) physical status
classification ( table 3) and helps to identify patients at higher than normal risk for
sedation. (See "Preparation for pediatric procedural sedation outside of the operating
room", section on 'Presedation evaluation' and "Preparation for pediatric procedural
sedation outside of the operating room", section on 'Preparation'.)
 Those patients with ASA class IV, and V, functional needs, or airway abnormalities warrant
consultation with a pediatric anesthesiologist. These patients are at increased risk for
sedation-related adverse events and should be cared for by individuals who are specifically
trained and experienced with high-risk pediatric procedural sedation. For elective
procedures, high-risk patients should ideally receive sedation in an organized pediatric
sedation service that has ancillary personnel with sedation expertise and an ongoing
quality improvement program.

● Competency of the sedation provider – Health care providers who perform procedural
sedation in children should have strong resuscitation and advanced pediatric life support
skills, including advanced training in the assessment and management of the pediatric
airway as well as specific training in pediatric procedural sedation. (See "Procedural
sedation in children outside of the operating room", section on 'Performing procedural
sedation'.)

● Institutional oversight – Institutions should develop guidelines and requirements that

support the safe practice of pediatric sedation, including credentialing of individual
providers and measurement and assessment of the quality of sedation care. In settings
where pediatric procedural sedation is routine (eg, children's hospitals), a pediatric
sedation service can provide efficient and effective sedation and is a systematic support
for the safe performance of sedation. (See "Procedural sedation in children outside of the
operating room", section on 'Adverse outcomes'.)

SEDATION FOR IMAGING STUDIES

Imaging can often be performed without sedation in older cooperative children and young
infants (up to six months of age) who are bundled and recently fed. Furthermore, as newer
technologies decrease the image capture time for computed tomography (CT), some younger
infants and many uncooperative patients can be imaged without sedation [3].

However, a significant number of older infants, toddlers, and older children with intellectual
disability cannot cooperate even for brief imaging tests (eg, helical CT) and warrant sedation to
ensure accurate imaging without excessive radiation exposure. Thus, imaging tests that are
negatively impacted by motion (eg, noninterventional CT or magnetic resonance imaging [MRI])
constitute the most common nonpainful procedures for which children undergo sedation [4].

Ideally, the chosen agent or agents should have a quick onset of action that permits successful
and safe completion of the imaging study, maintains airway reflexes, and has limited impact on
breathing and hemodynamic stability [5]. The regimen should also permit rapid recovery with
few side effects, such as nausea or agitation. Because imaging studies are not painful,
analgesia is not necessary.

Computed tomography

Approach — Successful imaging with helical CT is less sensitive to patient movement than MRI
and, given the rapid speed of imaging, can frequently be done without sedation or requires
only brief sedation (approximately 5 to 10 minutes). As an example, in one case series of 104
patients undergoing helical CT, only 9 percent received sedation [6].

When sedation is required, the clinician has a choice of several different agents as discussed
below.

The intravenous (IV) route is preferred where maximal efficiency and throughput is desirable,
such as patients undergoing urgent imaging for diagnostic purposes, because the onset of
action is shorter and more predictable, titration is easier, and (depending upon the agent),
recovery is quicker ( table 1) [5]. (See 'Intravenous medications' below.)

Other routes of administration are feasible for children without IV access, especially in settings
where CT imaging is elective and longer sedation duration and recovery times are acceptable
( table 2). However, if inadequate sedation or serious adverse events occur, lack of IV access
may impede further management [7]. Thus, we prefer to provide IV sedation whenever
possible. (See 'No intravenous access' below.)

Intravenous medications — We recommend that healthy infants and children (American

Society of Anesthesiologists [ASA] class I or II) ( table 3) who have vascular access and are
undergoing sedation for CT receive IV propofol, dexmedetomidine, ketamine, or etomidate
rather than IV short-acting barbiturates (eg, pentobarbital or methohexital) or midazolam
( table 1).

Evidence identifying the best sedative agent for children undergoing CT is limited. Based upon
observational studies, IV propofol, dexmedetomidine or etomidate is associated with effective
sedation in over 99 percent of children undergoing CT compared with 97 to 98 percent of
children receiving short-acting barbiturates or midazolam ( table 1) [5,8-12]. Although lower
efficacy was described for IV etomidate (76 percent of 17 patients) in one small trial, more than
99 percent of 446 children receiving etomidate for imaging successfully completed the
procedure in a subsequent observational study [8,9,13]. Based upon a review of prospectively
collected registry data from over 22,000 children, IV ketamine is also frequently used for
imaging; radiologic procedures accounted for almost 25 percent of reported use in the study
[13]. Although not specifically reported for radiologic procedures, 99.8 percent of all procedures
were successfully completed which suggests that IV ketamine has similar efficacy for CT when
compared with propofol, etomidate, or dexmedetomidine. However, when used as a single
agent, ketamine may be associated with random movement in some patients.

IV ketamine, etomidate and propofol have a more rapid onset of action than dexmedetomidine
(1 to 2 minutes versus 8 to 16 minutes, respectively) and etomidate has a shorter duration of
action than dexmedetomidine (approximately 15 minutes compared with 30 minutes,
respectively) [8-12]. Duration of action with ketamine and propofol varies by dose and mode of
administration (bolus or continuous infusion) and compares favorably with etomidate.

Evidence is lacking to suggest that major adverse events (eg, laryngospasm, aspiration, apnea
requiring airway intervention, or need for resuscitation) varies by the medication used to sedate
for CT. Adverse events that are not necessarily life-threatening have been described in 2 percent
of infants and children receiving etomidate or propofol sedation for imaging and 1 percent
receiving dexmedetomidine. By contrast, approximately 5 percent of patients receiving IV short-
acting barbiturates (eg, pentobarbital or methohexital) and up to 7 percent receiving IV
midazolam experience adverse events, primarily respiratory depression with transient oxygen
desaturation [8,10,14]. Less commonly apnea has been described, especially in patients
receiving short-acting barbiturates.

Other adverse reactions that are specific to the agent are described in the table ( table 1) and
discussed separately. (See "Pharmacologic agents for pediatric procedural sedation outside of
the operating room", section on 'Sedative-hypnotic agents'.)

No intravenous access — We prefer administration of IV medications, whenever possible, for

uncooperative children undergoing CT. (See 'Intravenous medications' above.)

When an IV cannot be placed, medication options and route of administration include

( table 2):

● Oral or intranasal (IN) midazolam

● Intramuscular (IM) ketamine
● IN dexmedetomidine

Midazolam by the oral or IN route achieves successful minimal sedation in 50 to 87 percent of

patients undergoing CT, with higher efficacy when delivered IN [15-17]. Onset of sedation is
more rapid when midazolam is administered IN (generally, less than 10 minutes) [18], while oral
midazolam takes approximately 30 minutes [19]. IM ketamine may be preferred when timely
imaging is necessary. Dissociative sedation with IM ketamine is associated with more adverse
events and serious adverse events than minimal sedation with midazolam or
dexmedetomidine. Furthermore, random motion may occur during ketamine sedation which
can impair successful completion of the study. (See "Pharmacologic agents for pediatric
procedural sedation outside of the operating room", section on 'Ketamine'.)

Limited evidence from two randomized trials suggests that IN dexmedetomidine in a dose
range of 2.5 to 3 mcg/kg produces adequate sedation in 60 to 74 percent of children
undergoing CT. The onset of sedation (approximately 30 minutes) and time to discharge
(approximately 40 minutes) appears similar to oral midazolam [20,21]. Further study is needed
to determine the optimal dosing for intranasal dexmedetomidine.

Regardless of agent and route chosen, children should undergo monitoring of oxygen
saturation and heart rate according to recommendations because the risk of adverse events is
significant regardless of the route of administration. (See "Procedural sedation in children
outside of the operating room", section on 'Monitoring'.)

Despite their relatively high efficacy when compared with oral or intranasal midazolam or
intranasal dexmedetomidine, we do not endorse the use of oral or rectal short-acting
barbiturates (eg, pentobarbital or methohexital) because of their long duration of sedation
relative to the short imaging time, high rates of adverse events during sedation, and potential
for delayed adverse events, including prolonged sleepiness and ataxia [15-17,22-27].

Chloral hydrate is no longer recommended for sedation in children and is not available in many
countries, including the United States. Some countries have removed chloral hydrate from
national health formularies because of potential carcinogenicity although the risk of cancer
from a single dose is inconclusive [28,29].

Magnetic resonance imaging — MRI often necessitates sedation for up to one hour.

Furthermore, machine noise and lack of patient access pose additional challenges to achieving
safe and effective sedation. We suggest that healthy infants and children (ASA class I or II)
( table 3) undergoing MRI receive sedation using propofol, dexmedetomidine, or
dexmedetomidine bolus followed by propofol sedation ( table 1). Because it has a shorter
time to recovery and discharge [30], experienced providers often administer propofol given as a
bolus of 2 to 4 mg/kg followed by an infusion at 150 to 200 mcg/kg/minute. The use of
dexmedetomidine reduces the dose of propofol during sedation. (See "Pharmacologic agents
for pediatric procedural sedation outside of the operating room", section on 'Propofol'.)

Propofol may also be preferred in children with increases in pulmonary artery pressure,
decreases in cardiac output, children with AV node conduction delay, or those receiving digoxin,
beta blockers or other medications that slow AV node conduction.
For some providers, dexmedetomidine may be preferred to propofol for sedation of children
with sleep apnea. As an example, in an observational study of 82 children undergoing MRI sleep
studies, dexmedetomidine provided an acceptable level of anesthesia with fewer patients
requiring an artificial airway compared with propofol (13 versus 30 percent) [31].

Sedation with continuous infusion of propofol or dexmedetomidine permits successful

completion of MRI in approximately 97 to 99 percent of children when administered by
experienced practitioners [12,30,32-34]. Time to sedation is longer with dexmedetomidine than
with propofol (10 versus <1 minutes, respectively) [12,30,32,33]. Recovery is typically complete
20 to 30 minutes after stopping a propofol infusion and 25 to 40 minutes after ending a
dexmedetomidine infusion [12,30,32,33,35,36].

However, to achieve this level of success with dexmedetomidine infusion alone typically
requires dosing that exceeds current manufacturer recommendations ( table 1) [33].
Alternatively, although less commonly used and based upon limited experience, midazolam
combined with dexmedetomidine can be efficacious. As an example, the combination of
dexmedetomidine administered to 20 children according to manufacturer's suggested dosing
along with midazolam (0.1 mg/kg) permitted successful completion of MRI studies in all
patients [30]. Current evidence does not support one approach to dexmedetomidine dosing
over the other. (See "Pharmacologic agents for pediatric procedural sedation outside of the
operating room", section on 'Dexmedetomidine'.)

Either propofol or dexmedetomidine can be used safely for MRI sedation, propofol may cause
more need for airway intervention or IV fluid administration. Dexmedetomidine can be
associated with marked bradycardia. (See "Pharmacologic agents for pediatric procedural
sedation outside of the operating room", section on 'Propofol' and "Pharmacologic agents for
pediatric procedural sedation outside of the operating room", section on 'Dexmedetomidine'.)

Evidence from observational studies supports the combination of moderate-dose

dexmedetomidine 1 mcg/kg with low-dose propofol infusion for MRI sedation. The combination
appears effective and with fewer adverse effects than propofol used alone. However, a large
randomized trial is needed to confirm these findings [37,38].

Although pentobarbital by the oral or IV route was used in the past to sedate children
undergoing MRI, the potential for adverse events may be increased and recovery time tends to
be longer with a high rate of delirium during emergence when compared with propofol or
dexmedetomidine infusion ( table 1) [23,39-42].

Proper administration, dosing, adverse effects, contraindications, and precautions for propofol
and dexmedetomidine are discussed in greater detail separately. (See "Pharmacologic agents
for pediatric procedural sedation outside of the operating room", section on 'Sedative-hypnotic
agents'.)

SEDATION FOR OTHER NONPAINFUL PROCEDURES

In some children, physical examination (eg, genital examination to document sexual assault or
routine physical examination in children with intellectual disability) or other nonpainful
procedures (eg, echocardiography or electroencephalogram) can cause anxiety and lack of
cooperation with the medical provider. In many situations, nonpharmacologic interventions can
permit completion of the examination or test. (See "Procedural sedation in children outside of
the operating room", section on 'Nonpharmacologic interventions'.)

When nonpharmacologic interventions are not sufficient and mild sedation is necessary for
nonpainful procedures, we suggest that healthy children (American Society of Anesthesiologists
class I or II) ( table 3) receive sedation with oral, sublingual (SL), or intranasal (IN) midazolam
or IN dexmedetomidine rather than short-acting barbiturates ( table 2). Inhaled nitrous oxide
is also a reasonable option, although use of a nasal or face mask can be challenging in selected
patients. In addition, a combination of IN ketamine and dexmedetomidine or "ketodex" (1
mg/kg ketamine and 2 mcg/kg dexmedetomidine) shows promise for sedation, at least for
nonpainful procedures. For example, in two large, retrospective observational studies, this
combination had a success rate of 93 to 96 percent for sedation of children undergoing
nonpainful procedures [43,44]. However, further study comparing this combination with
midazolam or dexmedetomidine alone, as described above, is warranted before use is routine.

Intravenous (IV) sedation as described for CT is suggested for patients who fail midazolam or
dexmedetomidine sedation by the routes described above. (See 'Computed tomography'
above.)

Multiple trials describe acceptable efficacy for pediatric sedation with IN dexmedetomidine for
pediatric sedation that appears equivalent or superior to oral midazolam, depending upon the
procedure [45-49]. In a systematic review of 12 trials that compared IN dexmedetomidine with
other sedatives for nonpainful procedures, dexmedetomidine provided adequate sedation,
according to validated sedation instruments, for 86 percent of 1021 children compared with 77
percent of 277 children receiving other types of sedation (eg, IN or oral midazolam or oral
ketamine) and was similar to IN midazolam in two trials [49]. Adverse effects after IN
dexmedetomidine administered in doses ranging from 1 to 4 mcg/kg included bradycardia (2.2
percent), hypotension (1.2 percent), oxygen desaturation (0.5 percent), and vomiting (0.4
percent); none required advanced life support.
Midazolam has both anxiolytic and amnestic properties. After oral or SL administration, it has
an onset of action of 5 to 10 minutes with recovery occurring in approximately 60 minutes [50].
Onset of action with IN midazolam administration is typically more rapid than oral
administration but duration of sedation is shorter (20 to 30 minutes) [51]. Due to the low pH
and the benzyl alcohol preservative, IN midazolam can be irritating when administered.
Pretreatment with lidocaine spray (10 mg per puff) 1 minute prior to IN midazolam
administration decreases nasal mucosal irritation. An atomizer is preferred for the IN delivery
of midazolam because of more reliable nasal mucosa absorption, better comfort, and reduction
of sneezing and cough when compared with direct instillation [51]. Although midazolam may be
administered rectally, this route is less reliable.

Midazolam has good efficacy for nonpainful procedures that permit motion [50,51] and has a
shorter duration of action than oral or rectal pentobarbital (<1 hour versus 1 to 4 hours,
respectively). Unlike barbiturates, midazolam is not associated with prolonged symptoms of
ataxia, sleepiness, or irritability ( table 2). (See 'No intravenous access' above.)

Flumazenil is an effective reversal agent for the few patients who develop significant respiratory
depression or apnea after sedation with midazolam. Flumazenil should not be used in patients
with seizure disorders or those who receive benzodiazepines on a chronic basis because of the
risk of precipitating seizures or withdrawal symptoms, respectively. The use of flumazenil to
reverse adverse effects of benzodiazepines, including dosing and re-dosing recommendations
is discussed in detail separately. (See "Benzodiazepine poisoning and withdrawal", section on
'Role of antidote (flumazenil)'.)

SEDATION FOR PAINFUL PROCEDURES

Clinicians frequently employ procedural sedation for infants and children undergoing a variety
of painful procedures including fracture reduction, laceration repair, bone marrow aspiration,
central line placement, and lumbar puncture. For these procedures, chosen agents or
combinations of agents must safely provide sedation and analgesia.

Approach — Patient factors (eg, last oral intake, urgency of the procedure, prior sedation
experience, and comorbidities [eg, asthma, upper respiratory infection]) are key considerations
for sedation strategies in children undergoing painful procedures and are discussed in detail
separately. (See "Preparation for pediatric procedural sedation outside of the operating room",
section on 'Presedation evaluation'.)
In healthy infants and children, anticipated pain during the procedure is also an important
determinant of the depth and type of sedation:

● Minimally painful procedures (eg, peripheral intravenous [IV] cannula insertion or

laceration repair in regions of the body where occasional movement does not interfere
with the procedure) – Minimal sedation, often best achieved with midazolam or inhaled
nitrous oxide. (See 'Minimally painful procedures' below.)

● Moderate to severely painful procedures (eg, fracture reduction) or laceration repair where
movement will interfere significantly with performance of the procedure) – Deep sedation,
typically reached with ketamine alone, propofol alone (brief procedures), ketamine
combined with propofol, or propofol combined with fentanyl. The provider should be
aware that any of these regimens can produce general anesthesia depending upon the
initial dose and frequency of re-dosing. (See 'Moderately or severely painful procedures'
below.)

Effective local or regional anesthesia can often lower the amount of sedative agent needed to
provide adequate sedation and increase the safety of the procedure.

The need for supplementary analgesia varies by the agents used for sedation:

● Ketamine has both sedative and analgesic properties and can thus be used alone to
provide sedation for moderate to severely painful procedures. However, for wound repair,
local anesthetic (eg, topical lidocaine-epinephrine-tetracaine [LET] gel or infiltration of a
local anesthetic) or a regional nerve block is also typically used, especially if the repair is
estimated to take longer than 10 to 15 minutes. (See 'Moderately or severely painful
procedures' below.)

● Dexmedetomidine and nitrous oxide have limited analgesic properties that may be
inadequate and warrant additional analgesic medications for moderately or severely
painful procedures.

● Propofol, midazolam, and etomidate do not have analgesic properties and should be
combined with other analgesic agents. Although propofol is used alone for brief, painful
procedures by some practitioners, the doses necessary to achieve adequate analgesia and
control unwanted motion during the procedure may approach those used for general
anesthesia. Propofol alone may be appropriate when local or regional anesthesia provides
complete pain control. (See 'Moderately or severely painful procedures' below.)

Although options vary, typical approaches to analgesia by type of procedure include:

● Wound repair

• Topical anesthetic (eg, lidocaine-epinephrine-tetracaine) (see "Clinical use of topical

anesthetics in children")

• Local infiltration of anesthetic (see "Subcutaneous infiltration of local anesthetics" and

"Subcutaneous infiltration of local anesthetics", section on 'Procedure')

• Regional anesthesia (eg, lacerations of the face, fingertip, distal toe, plantar foot, or
penis) as described separately:

- Facial lacerations (see "Assessment and management of facial lacerations", section

on 'Facial nerve blocks')
- Fingertip and distal toe (see "Digital nerve block", section on 'Digital block
procedures')
- Plantar foot (see "Lower extremity nerve blocks: Techniques", section on 'Ankle
block')
- Penis (see "Management of zipper entrapment injuries", section on 'Dorsal penile
block')

● Closed reduction of fractures

• Opioid analgesia (eg, fentanyl or morphine; IV opioids have been associated with an
increased risk of oxygen desaturation, vomiting, or need for positive-pressure
ventilation, especially when administered less than 30 minutes prior to sedation) (see
'Moderately or severely painful procedures' below)

• Hematoma block (distal radial fractures) (see "Distal radius fractures in adults", section
on 'Hematoma block')

• Bier block (fractures of the hand or forearm) (see "Overview of anesthesia", section on
'Intravenous regional anesthesia')

• Regional anesthesia (eg, pain control for femoral fractures) (see "Lower extremity nerve
blocks: Techniques")

● Lumbar puncture or bone marrow aspiration – Topical anesthetic followed by local

infiltration of anesthetic (see "Clinical use of topical anesthetics in children" and
"Subcutaneous infiltration of local anesthetics")
 Minimally painful procedures — In many children undergoing IV cannula insertion or
laceration repair, local anesthetics can be delivered topically or by direct infiltration to diminish
or abolish the pain without the need for sedation, especially when age-appropriate
nonpharmacologic interventions are used. (See 'Nonpharmacologic interventions' above and
"Clinical use of topical anesthetics in children", section on 'Lidocaine-prilocaine' and
"Subcutaneous infiltration of local anesthetics".)

When nonpharmacologic interventions and local anesthetics are not sufficient and minimal
sedation is necessary for minimally painful procedures (eg, peripheral IV line placement,
urethral catheterization, small laceration repair, or nasogastric tube placement), we suggest
that healthy children (American Society of Anesthesiologists [ASA] class I or II) ( table 3)
receive sedation with inhaled nitrous oxide (N2O); oral, sublingual, or intranasal (IN) midazolam;
or IN dexmedetomidine rather than short-acting barbiturates ( table 2). When N2O is
available and tolerated by the patient, it is preferred to midazolam as summarized below. IN
dexmedetomidine has been used for minimal sedation but requires more study before best
practice guidelines for administration are determined.

When compared with N2O, IN midazolam, or IN dexmedetomidine, oral or rectal barbiturates

are associated with higher rates of adverse effects, especially respiratory depression,
(thiopental or methohexital) or prolonged duration of sedation (pentobarbital) ( table 2).

● Nitrous oxide – Because it has a shorter recovery time and fewer overall adverse effects,
nitrous oxide (N2O) may be preferred to midazolam in cooperative children for the
following reasons [52-55]:

• The onset of action is short (<1 minute).

• Recovery is typically faster (<20 minutes versus 30 to 60 minutes, respectively).

• For selected procedures, N2O may also have greater efficacy. For example, in a trial, of
over 250 children undergoing facial laceration repair, N2O or N2O combined with
midazolam decreased distress to a greater extent than midazolam alone or lidocaine
with comforting [52]. In another trial of 90 children in whom IV access was expected to
be difficult, use of N2O was associated with a significantly increased success rate for IV
placement when compared with oral midazolam [53]. Procedure time was also
significantly shorter for patients who received 50 percent N2O when compared with
oral midazolam.

• Adverse events following N2O use are typically self-limited with vomiting being most
common (approximately 6 to 7 percent of patients, primarily those with longer
 duration of inhalation or who also received opioids) [52,54-56]. Serious adverse effects
(eg, postprocedure desaturation, apnea, stridor, aspiration, laryngospasm, or airway
obstruction) are rare (eg, 0.2 percent in two observational studies and one case report
of aspiration and laryngospasm) [55-57]). Thus, N2O use requires the same level of
preparation and vigilance as other sedative agents. (See "Preparation for pediatric
procedural sedation outside of the operating room" and "Procedural sedation in
children outside of the operating room", section on 'Performing procedural sedation'.)

The method for administering N2O for procedural sedation and additional precautions are
discussed in greater detail separately. (See "Pharmacologic agents for pediatric procedural
sedation outside of the operating room", section on 'Nitrous oxide'.)

● Midazolam – Based upon one large observational study, up to one-third of patients,

especially children younger than 4 years of age, may not tolerate N2O delivery [58]. Such
patients are good candidates for oral or IN midazolam [54]. Midazolam is also a
reasonable alternative when N2O is not available. If the IN route of administration is
chosen, pretreatment with lidocaine spray (10 mg per puff) 1 minute prior to
administration and use of an atomizer is suggested [51].

● Dexmedetomidine – Preliminary evidence suggests that IN dexmedetomidine may be

equivalent to midazolam for minimally painful procedures. As an example, in a trial of 40
young children (mean age three years) undergoing laceration repair, intranasal (IN)
dexmedetomidine (2 mcg/kg) was similar to IN midazolam (0.4 mg/kg) for anxiolysis
during repair but was associated with less anxiety during positioning with significantly
more children showing no anxiety at this time point (70 versus 11 percent) [48]. Although
evidence for safety and efficacy for this specific use of IN dexmedetomidine in children is
limited, results from small trials where IN dexmedetomidine was used for other purposes
(eg, nonpainful procedures, dental procedures, or preoperative sedation) support safety
and efficacy that is potentially equivalent to midazolam [49,59-64]. Larger studies are
needed to determine optimal dosing and to identify more infrequent side effects.

Moderately or severely painful procedures — For healthy infants and children (ASA class I or
II) ( table 3) who are undergoing moderately or severely painful procedures of short duration
(eg, fracture reduction, bone marrow aspiration), we suggest procedural sedation with IV
ketamine, ketamine combined with propofol, or fentanyl combined with propofol rather than
opioids combined with benzodiazepines (eg, midazolam) or etomidate. When ketamine is used,
a prophylactic dose of ondansetron may reduce postprocedure vomiting. For selected
procedures, effective regional anesthesia can reduce the required medication dose or eliminate
the need for moderate or deep sedation altogether. (See "Pharmacologic agents for pediatric
procedural sedation outside of the operating room", section on 'Ketamine'.)

Dosing and administration of specific IV sedation drugs used for moderate, dissociative, or
deep sedation are provided in the table ( table 1) and discussed separately. (See
"Pharmacologic agents for pediatric procedural sedation outside of the operating room".)

Based upon observational studies and randomized trials, similar sedation efficacy for moderate
to severely painful procedures, such as fracture reduction or bone marrow aspiration, is
achieved with ketamine alone, ketamine combined with propofol, or fentanyl combined with
propofol [65] compared with regimens that combine opioids (typically fentanyl) with midazolam
[66-68] or etomidate [69,70]. All of the above IV regimens have a rapid onset of effect ranging
from 30 seconds for etomidate and propofol to 1 to 2 minutes for ketamine alone or midazolam
with fentanyl ( table 1). Recovery from sedation using ketamine alone or ketamine with
propofol ranges from 15 to 30 minutes which is longer than for etomidate or propofol (5 to 15
minutes) but shorter than for midazolam with fentanyl (15 to 60 minutes). Providers using
propofol should have specific training in the use of propofol and the provision of deep sedation
or anesthesia [71].

The IV regimens vary in terms of the frequency of important adverse events (see
"Pharmacologic agents for pediatric procedural sedation outside of the operating room"):

● With recommended dosing, ketamine sedation tends to preserve airway reflexes and is
associated with fewer airway or respiratory adverse events that require intervention than
fentanyl combined with propofol, midazolam, or etomidate. On the other hand, vomiting
and agitation during emergence are more frequent following ketamine sedation than with
the other regimens although avoidance of high dosing (≥2.5 mg/kg initial dose or total
dose ≥5 mg/kg) may reduce the frequency of these adverse events [72] and prophylactic
ondansetron significantly reduces vomiting [73]. Hypotension, which occurs frequently
during sedation with propofol, is not described following ketamine sedation. (See
"Pharmacologic agents for pediatric procedural sedation outside of the operating room",
section on 'Ketamine'.)

● The combination of propofol and ketamine for procedural sedation appears to provide
effective sedation and less vomiting than reported for ketamine alone and less
hypotension than described with propofol alone. However, adverse respiratory events
including laryngospasm can still occur [74]. Suggested dosing for this regimen is provided
separately. (See "Pharmacologic agents for pediatric procedural sedation outside of the
operating room", section on 'Ketamine'.)
 ● Propofol combined with fentanyl is preferred by some sedation practitioners because it is
equally efficacious to ketamine or ketamine combined with propofol and may produce a
shorter and smoother recovery [75]. (See "Pharmacologic agents for pediatric procedural
sedation outside of the operating room", section on 'Propofol'.)

● Nitrous oxide alone for these procedures is associated with high levels of responsiveness
to pain (up to 40 percent of patients) and need for restraint (up to one-third of patients)
and is not recommended [58].

Appropriate analgesia is an important adjunct to sedation that is frequently necessary for

children undergoing moderate to severely painful procedures. However, administration of IV
opioids prior to sedation is associated with increased frequency of oxygen desaturation,
vomiting, and need for positive-pressure ventilation during sedation although the absolute
effect on vomiting or the need for positive-pressure ventilation is small. The provider should
anticipate and be prepared to manage these adverse events and, when possible, administer
alternative, nonopioid analgesics, especially within 30 minutes prior to sedation. For example,
in a prospective, multicenter, observational study of almost 6300 children undergoing sedation
for painful procedures in the emergency department, opioid administration prior to the
procedure versus no opioid analgesia was associated with an increased risk of oxygen
desaturation (9 versus 4 percent), vomiting (7 versus 5 percent), and need for positive-pressure
ventilation (1.5 versus 0.9 percent) [76]. These risks were greatest when opioid analgesia was
administered closer to the time of sedation (eg, less than 30 minutes). Compared with
morphine, fentanyl was associated with decreased odds of oxygen desaturation (OR 0.5, 95% CI
0.3-0.8) and vomiting (OR 0.5, 95% CI 0.34-0.95), but this finding requires confirmation in
randomized trials.

SOCIETY GUIDELINE LINKS

Links to society and government-sponsored guidelines from selected countries and regions
around the world are provided separately. (See "Society guideline links: Procedural sedation in
children".)

SUMMARY AND RECOMMENDATIONS

● Nonpharmacologic interventions include behavioral and cognitive approaches such as

desensitization, distraction, reinforcing coping skills, positive reinforcement, and
relaxation. These techniques, which should be employed for all children receiving
 procedures, are complementary to pharmacologic interventions and, in some children,
may decrease the amount of sedation required or prevent the need for sedation
altogether. (See "Procedural sedation in children outside of the operating room", section
on 'Nonpharmacologic interventions'.)

● The necessary preparation, indications, contraindications, monitoring, and steps for safely
performing procedural sedation in children are discussed separately. Patient factors (eg,
last oral intake, urgency of the procedure, prior sedation experience, and comorbidities
[eg, asthma, upper respiratory infection]) are key considerations for sedation strategies in
children. (See "Preparation for pediatric procedural sedation outside of the operating
room" and "Procedural sedation in children outside of the operating room".)

● The properties of the specific agents and dosing for pediatric sedation are listed in the
tables ( table 1 and table 2) and provided separately. (See "Pharmacologic agents for
pediatric procedural sedation outside of the operating room".)

● In some facilities, the use of propofol, ketamine, dexmedetomidine, or etomidate may be

restricted to use by anesthesiologists or other specialists (eg, pediatric critical care,
hospitalists, or pediatric emergency medicine specialists). (See 'Choice of sedative agents'
above.)

● The targeted depth of sedation and the agents used largely depend upon the procedure
performed, the anticipated degree of pain, allowable patient movement, and other patient
factors. The safe performance of pediatric sedation requires proper selection and
evaluation of patients, appropriate preparation, and the performance of sedation by
providers with appropriate training and institutional support in accordance with
guidelines designed to maximize patient safety. (See "Preparation for pediatric procedural
sedation outside of the operating room" and "Procedural sedation in children outside of
the operating room", section on 'Performing procedural sedation'.)

● Imaging tests that are negatively impacted by motion (eg, noninterventional computed
tomography [CT] or magnetic resonance imaging [MRI]) constitute the most common
nonpainful procedures for which children undergo sedation. Successful imaging with
helical CT is less sensitive to patient movement than MRI and, given the rapid speed of
imaging, can frequently be done without sedation.

The selection of medications for these procedures are determined by the duration of the
test and whether vascular access is present (see 'Sedation for imaging studies' above):
 • For providers that are trained in the use of potent short-acting sedatives and work in
well-supported sedation systems, we recommend that healthy infants and children
(American Society of Anesthesiologists [ASA] class I or II) ( table 3) who have vascular
access and are undergoing sedation for CT receive intravenous (IV) bolus doses of
propofol, dexmedetomidine, ketamine, or etomidate rather than IV short-acting
barbiturates (eg, pentobarbital or methohexital) or midazolam ( table 1) (Grade 1B).
When used as a single agent, ketamine may be associated with random movement in
some patients. (See 'Intravenous medications' above.)

• We prefer administration of IV medications, whenever possible, for uncooperative

children undergoing CT. When an IV cannot be placed, medication options and route of
administration include intramuscular (IM) ketamine, oral or intranasal (IN) midazolam,
and IN dexmedetomidine ( table 2). However, successful completion of the
procedure is lower than for IV agents. (See 'No intravenous access' above.)

• For providers that are trained in the use of potent short-acting sedatives and work in
well-supported sedation systems, we suggest that healthy infants and children (ASA
class I or II) undergoing MRI receive sedation using continuous IV infusion of propofol
or dexmedetomidine ( table 1) (Grade 2C). (See 'Magnetic resonance imaging'
above.)

● When nonpharmacologic interventions are not sufficient and minimal sedation is

necessary for nonpainful procedures, we suggest that healthy children (ASA class I or II)
( table 3) receive sedation with IN midazolam or IN dexmedetomidine rather than short-
acting barbiturates ( table 2) (Grade 2C). While oral or sublingual midazolam may also
be efficacious, longer onset of action and prolonged duration of action will limit its use in
many settings. Nitrous oxide (N2O) is also a reasonable option, but the use of a mask for
delivery can be challenging in these patients. (See 'Sedation for other nonpainful
procedures' above.)

● When nonpharmacologic interventions and topical anesthetics are not sufficient and mild
sedation is necessary for minimally painful procedures (eg, IV cannula placement), we
suggest that healthy children (ASA class I or II) ( table 3) receive sedation with inhaled
nitrous oxide (N2O); oral, sublingual, or IN midazolam; or IN dexmedetomidine (Grade 2C).
IV sedation as described for CT is suggested for patients who fail sedation with these
agents. (See 'Minimally painful procedures' above and "Pharmacologic agents for pediatric
procedural sedation outside of the operating room", section on 'Nitrous oxide'.)
 ● Moderate to severely painful procedures, including fracture reduction, laceration repair,
bone marrow aspiration, abscess incision and drainage, central line placement,
arthrocentesis, and lumbar puncture frequently require procedural sedation that
effectively combines sedation and analgesia. The type of supplementary analgesia varies
by the sedative agents used. Typical approaches to analgesia by type of procedure are
provided above. (See 'Approach' above.)

● Opioid analgesia is an important adjunct to sedation for children with moderate to

severely painful procedures that is frequently necessary. However, IV administration of
opioids prior to sedation is associated with increased frequency of oxygen desaturation,
vomiting, and need for positive-pressure ventilation during sedation although the
absolute increase for vomiting and need for positive-pressure ventilation is small. The
provider should anticipate and be prepared to manage these adverse events. (See
'Moderately or severely painful procedures' above.)

● For healthy infants and children (ASA class I or II) who are undergoing moderately or
severely painful procedures of short duration (eg, fracture reduction or bone marrow
aspiration) by providers that are trained in the use of potent short-acting sedatives and
work in well-supported sedation systems, we suggest procedural sedation with IV
ketamine, ketamine in combination with propofol, or propofol combined with fentanyl
rather than opioids combined with benzodiazepines (eg, midazolam) or etomidate
( table 1) (Grade 2C). When ketamine is used, a prophylactic dose of ondansetron may
reduce postprocedure vomiting.

● The provider should be aware that all drug combinations used to provide targeted deep
sedation for painful procedures also may result in general anesthesia depending upon the
initial dose(s) and frequency of redosing. Providers must always be prepared to provide
rescue for patients receiving procedural sedation. (See 'Moderately or severely painful
procedures' above and "Pharmacologic agents for pediatric procedural sedation outside of
the operating room", section on 'Ketamine'.)

ACKNOWLEDGMENT

The UpToDate editorial staff acknowledges Deborah C Hsu, MD, MEd, who contributed to an
earlier version of this topic review.

Use of UpToDate is subject to the Terms of Use.

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Topic 85542 Version 32.0
GRAPHICS

Commonly used intravenous agents for pediatric procedural sedation

outside of the operating room

These agents should ONLY be administered by clinicians trained and experienced in pediatric
procedural sedation using continuous noninvasive electronic monitoring of oxygenation, heart rate
blood pressure, and, whenever possible, end-tidal carbon dioxide monitoring. Resuscitation
equipment, medications, and personnel skilled in advanced pediatric life support and knowledgeab
of sedatives and reversal agents must be present. Unstable patients, patients with airway anomalie
and those with life-threatening, severe systemic disease warrant consultation with an
anesthesiologist, pediatric critical care specialist, or emergency physician prior to procedural
sedation. Please refer to UpToDate topics on procedural sedation in children for more details.

Repeat IV
dose (as
needed to
Initial IV Onset
Duration

Agent achieve Additional notes

dose* (minutes) (minutes)
desired
level of
sedation)

Ketamine 1 to 2 mg/kg; 0.5 to 1 1 to 2 15 to 30 Properties –

some experts mg/kg; Provides sedatio
do not exceed repeat every and analgesia fo
1.5 mg/kg per 5 to 10 moderately to
dose minutes, severely painful
titrating to procedures. Less
For healthy
desired level respiratory
patients
of sedation depression and
without QT
prolongation complications th
or receiving propofol alone o
medications combinations of
that prolong opioids with
the QT midazolam or wi
interval, propofol.
premedication Adverse effects
with Vomiting and
ondansetron emergence
0.15 mg/kg IV reaction are
(maximum common;
dose 4 mg) is frequency of
recommended vomiting is
reduced by
premedication
with ondansetro
(0.15 mg/kg,
typical dose 4 mg
or by co-
administration o
propofol.

Laryngospasm
and apnea occur
rarely, but bag-
mask ventilation
may be necessar
in about 1% of
sedations.

Co-administratio
of anticholinergic
propofol, or
barbiturates
increases risk of
serious adverse
events.

Relative
contraindication
and precautions
Age younger tha
12 months, activ
pulmonary
infections
(including URI),
known or
suspected cardia
disease, suspecte
increased
intracranial
pressure (eg,
intracranial mass
or obstructive
hydrocephalus),
glaucoma or acu
eye injury (open
globe), porphyria
thyroid disease, o
seizures.
Absolute
contraindication
– Age younger
 than 3 months o
patients with
known or
suspected
psychosis.

Ketamine and Ketamine 0.5 Propofol 0.5 <1 15 to 30 Properties – May

propofol mg/kg bolus mg/kg every be administered
followed by 2 minutes, as simultaneously in
propofol 0.5 needed the same syringe
mg/kg
OR Optimal dosing
Propofol may has not been
Ketamine 0.5
reduce the established. Rang
to 1 mg/kg
risk of of reported dosin
every 10
vomiting is ketamine 0.2 to
minutes, as
caused by 1 mg/kg IV with
needed
ketamine; propofol 0.5 to 2
thus mg/kg IV. The
premedication higher range of
with these doses may
ondansetron be indicated in
may not be patients with mo
required painful
procedures.

Adverse effects
and
contraindication
– As above for
ketamine and
below for
propofol; in
addition,
combining the tw
drugs changes th
frequency of som
adverse effects:
Risk of apnea
laryngospasm
hypotension,
and
bradycardia
may be highe
than for
patients
receiving
 ketamine
alone
Risk of
vomiting may
be lower than
for patients
receiving
ketamine
alone
Risk of
bradycardia
and
hypotension
may be lower
than for
patients
receiving
propofol alon

Propofol¶ Initiate Not ≤0.5 5 to 15 after Properties –

infusion at applicable for single bolus Provides deep
150 mcg/kg continuous IV dose, longer sedation but can
per minute infusion; after produce general
and titrate titrate prolonged anesthesia,
gradually to infusion rate infusion or especially with
response (up as needed when multiple bolus
to 250 mcg/kg repeated doses or high
OR
per minute)Δ bolus doses continuous
Additional IV are given
OR infusion rate.
bolus dose
6 months to 2 0.5 mg/kg Provides sedatio
years of age: 2 every 3 to 5 but no analgesia
mg/kg IV minutes, For painful
bolus dose titrating as procedures, an
needed up to analgesic agent
2 years of age
3 mg/kg. Wait (eg, ketamine,
and older: 1 to
at least 3 to 5 fentanyl), region
1.5 mg/kg IV
minutes anesthetic, or loc
bolus dose
between anesthetic should
doses to be co-
assess effect. administered.
Commonly used
for diagnostic
imaging (CT, MRI

Causes periphera
injection-site pai
 Rapid onset of
sedation with
good neurologic
recovery. Reduce
intracranial
pressure.

Adverse effects
Respiratory
depression,
oxygen
desaturation,
apnea,
hypotension,
and/or rapid
transition to
deeper levels of
sedation,
especially with
overly rapid
administration o
bolus injection.
Absolute
contraindication
– Porphyria;
propofol should
avoided in patien
with cardiac
compromise.

Dexmedetomidine 1 to 3 mcg/kg Not 5 to 10 30 to 70 Properties –

loading dose applicable for Sedation and
(over 10 continuous modest analgesi
minutes), infusion; with minimal
followed by titrate respiratory
0.5 to 1 infusion rate depression.
mcg/kg per as needed Commonly used
hour for diagnostic
continuous imaging (CT, MRI
infusion Adverse effects
Children Bradycardia,
younger than hypertension, or,
5 years of age especially with
may require loading dose,
maintenance hypotension.
infusion rates Rarely, upper
at the higher airway
 end of the obstruction,
range shown including
laryngospasm.
Relative
contraindication
– Children who a
inadequately
hydrated or have
reduced cardiac
output.
Absolute
contraindication
–
Dexmedetomidin
should be avoide
in patients
receiving digoxin
or other
medications actin
on the
atrioventricular
node or with
cardiac conductio
abnormalities (eg
sinus node
dysfunction)
unless provided
physicians with
training and
expertise in
pediatric cardiac
anesthesiology.

Fentanyl 1 to 2 mcg/kg Repeat 0.5 to <3 to 5 30 to 60 Properties –

1 mcg/kg after a single Opioid analgesia
Some experts
every 3 to 5 dose
prefer to not When combined
minutes
exceed 50 with propofol, m
mcg per dose Some experts produce a state o
prefer to not general
exceed 25 anesthesia.
mcg per dose
When combined
with midazolam,
can produce
moderate or dee
sedation, but les
 effective and mo
adverse
respiratory event
reported when
compared to
sedation with
ketamine alone.

Effects can be
reversed by opio
antagonists (eg,
naloxone).

Adverse effects
Respiratory
depression, apne
bradycardia, and
hypotension.

Chest wall rigidit

especially with
rapid IV infusion

Contraindicatio
– Hypersensitivity
to fentanyl or an
of its component

Midazolam 6 months to 5 After initial IV 1 to 3 15 to 60, Properties –

years of age: dose, repeat depending Provides sedatio
0.05 to 0.1 after 2 to 5 upon total but no analgesia
mg/kg IV, minutes, dose For painful
maximum titrating to administered procedures, an
single dose 2 desired level analgesic agent
mg of sedation as (eg, ketamine,
follows: fentanyl) should
6 to 12 years
of age: 0.025 6 months be co-
to 0.05 mg/kg to 5 years administered.
IV, maximum of age: 0.2
Provides amnesia
single dose 2 mg/kg per
mild anxiolysis,
mg dose
and mild sedatio
(maximum
Over 12 years for procedures
total dose
of age: 1 to 2 that do not requi
6 mg)
mg IV full immobility (e
6 to 12 laceration repair
years of with local topical
age: 0.1 anesthesia).
mg/kg
(maximum
 total dose When combined
6 mg) with fentanyl, ca
Over 12 produce modera
years of or deep sedation
age: 1 to 2 but less effective
mg and more advers
(maximum respiratory event
total dose reported when
10 mg) compared to
sedation with
ketamine alone o
combined with
propofol.

Flumazenil can
reverse effects b
should be avoide
in patients with
seizure disorder
who are
chronically
maintained on
benzodiazepines

Adverse effects
Respiratory
depression and
apnea, especially
when combined
with opioid
medications (eg,
fentanyl);
paradoxical
reactions includi
hyperactivity,
aggressive
behavior, and
inconsolable
crying.
Contraindicatio
– Hypersensitivity
to midazolam or
any of its
components.

Etomidate 0.1 to 0.3 0.05 mg/kg ≤0.5 5 to 15 Properties – Rap

mg/kg IV every 3 to 5 onset and
minutes; recovery.
Lower dose in titrate up to Commonly used
children with 0.6 mg/kg for brief diagnos
renal or total dose to imaging (eg, hea
hepatic desired CT).
insufficiency sedation
Reduces
intracranial
pressure.
Hemodynamic an
respiratory
stability
maintained in
most patients,
making it a good
choice if
cardiovascular
status is unknow
or compromised
(eg, trauma
patient).

Adverse effects
Pain at the
injection site,
transient
nonepileptiform
myoclonus,
vomiting.
Myoclonus and
vomiting reduced
by premedication
with midazolam.
Relative
contraindication
– Children with
severe illness,
such as suspecte
sepsis due to
adrenal
suppression.
Absolute
contraindication
– Children with
congenital or
acquired adrena
insufficiency.
IV: intravenous; URI: upper respiratory tract infection; CT: computed tomography; MRI: magnetic
resonance imaging.

* Doses are given as a suggested range for the initial dose. Children may differ markedly with
respect to efficacy of any single dose, and careful titration to effect by using repetitive dosing to
achieve the desired depth and duration of sedation is necessary for any individual patient.

¶ In some institutions, propofol is ONLY approved for use by anesthesiologists or others with
specialized pediatric procedural sedation training. Check local recommendations.

Δ Administering dexmedetomidine 0.5 to 1 mg/kg IV bolus prior to propofol infusion may reduce the
total amount of propofol needed for sedation and has been associated with fewer adverse effects.

Graphic 83512 Version 15.0

Commonly used agents for pediatric procedural sedation in children
without IV access

Sedation with these agents can result in significant respiratory depression and other adverse
effects. Children should receive appropriate monitoring by personnel skilled in pediatric
resuscitation until full recovery has occurred. Please refer to UpToDate topics on procedural
sedation in children for more details.

Onset Duration
Agent Dose Comments
(minutes) (minutes)

Nitrous oxide 50 to 70 <0.5 Recovery Primarily used in children

(N2O) percent N2O typically older than 4 years of age.
administered within 3 to 5 Provides amnesia, mild to
with oxygen minutes of moderate anxiolysis, mild to
typically cessation of moderate sedation, and mild
delivered N2O analgesia.
through a delivery Common adverse effects:
demand Vomiting and dysphoria.
valve system
Clinicians must know how to
with
test and use the equipment in
scavenging
use in their facility. In
capability
addition, equipment must be
carefully maintained and
periodically tested to ensure
adequate safety.
Relatively contraindications
and precautions: Nausea and
vomiting.
Absolute contraindications:
Pregnancy and conditions
with trapped gas within body
cavities (eg, bowel
obstruction, pneumothorax,
middle ear infection).

Midazolam 0.25 to 0.5 20 to 30 30 to 60 Midazolam has poor oral

mg/kg PO or bioavailability (15 to 35
SL, percent). IN, SL, and buccal
maximum 20 has bioavailability
mg approaching 70 to 80 percent
0.2 to 0.3 during gradual
mg/kg IN, administration.
maximum 10 Provides amnesia, mild
mg* anxiolysis, and mild sedation
 Buccal for procedures that do not
dosing is as require full immobility (eg,
for IN laceration repair with local
topical anesthesia).
Flumazenil can reverse effects
but should be avoided in
patients with seizure disorder
or who are chronically
maintained on
benzodiazepines.
Common adverse effects:
Respiratory depression and
apnea, especially if combined
with opioids or other
sedatives; paradoxical
reactions including
hyperactivity, aggressive
behavior, and inconsolable
crying.

Dexmedetomidine 2.5 to 3 20 to 30 30 to 45 Provides amnesia, mild

mcg/kg IN anxiolysis, and mild sedation.
Common adverse events:
Bradycardia or hypertension
with IV administration, not
described with IN use.
Relative contraindications and
precautions: Children with
dehydration or reduced
cardiac output.
Absolute contraindications:
Patients receiving digoxin or
other medications acting on
sinus node or with sinus node
dysfunction.

Ketamine 4 to 5 mg/kg 5 to 10 30 to 60 Provides sedation AND

IM analgesia for moderately to
severely painful procedures.
Common adverse events:
Vomiting, emergence
reaction; frequency of
vomiting is reduced by
premedication with
ondansetron (0.15 mg/kg,
 typical dose 4 mg) or by co-
administration of propofol.
Compared with IV
administration, IM ketamine
increases the risk of vomiting
and the duration of sedation
and recovery.
Laryngospasm and apnea
occur rarely, but bag-mask
ventilation may be needed in
about 1 percent of sedated
patients.
Relative contraindications and
precautions: Age younger
than 12 months, active
pulmonary infections
(including URI), known or
suspected cardiac disease,
suspected increased
intracranial pressure (eg,
head trauma with signs or
symptoms, intracranial mass,
or hydrocephalus), glaucoma
or acute eye injury (open
globe), porphyria, thyroid
disease, or seizures.
Absolute contraindications:
Age younger than 3 months
or patients with known or
suspected psychosis.

PO: oral; SL: sublingual; IN: intranasal; IM: intramuscular; URI: upper respiratory infection.

* Pretreatment with lidocaine spray (10 mg/puff) one minute prior to intranasal midazolam
decreases nasal mucosal irritation. Intranasal preparation is not commercially available in the United
States; 5 mg/mL injectable solution may be given IN.

Graphic 83889 Version 7.0

American Society of Anesthesiologists (ASA) Physical Status Classification
System

Classification Description

ASA 1 A normal healthy patient.

ASA 2 A patient with mild systemic disease.

ASA 3 A patient with severe systemic disease.

ASA 4 A patient with severe systemic disease that is a constant threat to life.

ASA 5 A moribund patient who is not expected to survive without the operation.

ASA 6 A declared brain-dead patient whose organs are being removed for donor
purposes.

ASA Physical Status Classification System is reprinted with permission of the American Society of Anesthesiologists, 520 N.
Northwest Highway, Park Ridge, Illinois 60068-2573.

Graphic 113973 Version 1.0

Contributor Disclosures
Joseph P Cravero, MD No relevant financial relationship(s) with ineligible companies to disclose. Mark G
Roback, MD No relevant financial relationship(s) with ineligible companies to disclose. Anne M Stack,
MD No relevant financial relationship(s) with ineligible companies to disclose. Adrienne G Randolph, MD,
MSc Other Financial Interest: International Sepsis Forum [Council Member].
All of the relevant financial
relationships listed have been mitigated. James F Wiley, II, MD, MPH No relevant financial relationship(s)
with ineligible companies to disclose.

Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are
addressed by vetting through a multi-level review process, and through requirements for references to be
provided to support the content. Appropriately referenced content is required of all authors and must
conform to UpToDate standards of evidence.

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