PEM Board Review Chapter 23: Procedural Sedation Different types

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PEM Board Review
Chapter 23: Procedural Sedation
Different types of agents are used for procedural sedation and analgesia for pediatric
patients in the emergency department. These include the dissociative agent ketamine,
opioids, benzodiazepines, and two newer agents, propofol and etomidate.
Ketamine, a phencyclidine derivative that produces dissociative anesthesia and amnesia,
has been well researched in the pediatric setting. It can induce a trancelike state in which
the child may appear to be awake and may retain some purposeful movement. Ketamine
has intrinsic analgesic and amnestic properties, making it an ideal choice for procedural
sedation and analgesia. In addition, it has bronchodilator properties that make it a
potential agent for rapid sequence induction (RSI) in patients who have asthma
exacerbations.
Ketamine is associated with increased airway reflexes, including hypersalivation and
laryngospasm. Fortunately, laryngospasm and subsequent obstructive apnea are relatively
rare events. Some factors that seem to increase the risk of laryngospasm are manipulation
of the pharynx, laryngeal stimulation, and upper respiratory infections. In a pediatric
study, laryngospasm occurred in 9% of children undergoing upper gastrointestinal
endoscopy compared with none of those undergoing lower gastrointestinal endoscopy. In
most cases, laryngospasm associated with ketamine use can be treated effectively with
airway repositioning and gentle bag-valve-mask ventilation. Occasionally, administration
of a neuromuscular blocking agent and subsequent endotracheal intubation are required.
Opioids commonly used in procedural sedation and analgesia include morphine and
fentanyl. As with other opioids, common adverse effects include respiratory depression,
hypotension, nausea, and vomiting, but laryngospasm is not seen. Fentanyl has the
advantage of being relatively short-acting. However, it is associated with apnea,
bradycardia, and chest wall rigidity and laryngospasm, which occurs primarily with rapid
infusion and high doses (>5 mcg/kg). Morphine has a slower onset and longer duration of
action.
Benzodiazepines such as midazolam function as sedatives, anxiolytics, and amnestics by
potentiating the inhibitory effects of gamma-aminobutyric acid (GABA). They also are
used to relieve musculoskeletal spasticity and short-term insomnia. It is important to
remember that benzodiazepines have no analgesic properties and generally are used in
concert with another agent for painful procedures. Common adverse effects include
respiratory depression and hypotension but not laryngospasm.
Etomidate is a nonbarbiturate sedative hypnotic agent that is being used with increasing
frequency in children. The advantages of etomidate include rapid onset and short duration
of action as well as minimal hemodynamic effects. Adverse effects include myoclonus
and adrenal suppression (with prolonged use). Laryngospasm is not an associated adverse
effect. Some common indications for etomidate use include relatively short procedures,
such as reduction of shoulder/hip dislocation and RSI. Doses range 0.1 to 0.3 mg/kg.
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Propofol is a general anesthetic agent that causes dose-dependent sedation. The usual
bolus dose is 1 mg/kg over 2 minutes, followed by an infusion at 50 to 100 mcg/kg per
minute. This medication has a very fast onset of action (0.5 to 1 minutes), a short
duration of action (5 to 10 minutes), and minimal residual sedation. Long-term
administration rarely is associated with refractory metabolic acidosis. Compared with
ketamine, propofol is associated with increased incidences of apnea. Compared with
etomidate, propofol more frequently causes hypotension. However, propofol use is not
associated with laryngospasm. Common indications for propofol use include sedation for
cross-sectional imaging. Administration of an analgesic agent is required for painful
procedures because propofol has no analgesic properties.
Maximum local dose of Lido without Epi per procedure= 5mg/kg
Maximum local dose of Lido with Epi per procedure=7mg/kg
Calculating appropriate Lido dose:
1% Lido=1g/100cc, therefore, 1000mg/100cc, therefore 10mg/cc; if the child weighs
10kg and the max dose is 5mg/kg, the max dose for that child would be 50mg, which
would be 5cc.
Signs of Lido toxicity: develops in an orderly progression from CNS effects to CV
involvement. Early signs are numbness of tongue and mouth, metallic taste, lightheadedness, tinnitus, visual disturbance, nystagmus, and slurring of speech. This may
progress to muscle twitching, confusion, unconsciousness, and seizures. Cardiac effects
include ectopy, AV conduction disturbances, hypotension, dysrhythmias, and cardiac
arrest. If a patient doesn’t inform the physician of the early symptoms—especially can
be the case in the pediatric patient—the first sign of toxicity may be a seizure. Give IV
Lorazepam. Bupivacaine-induced cardiac toxicity carries a high mortality—benzo’s may
prolong the half-life and even preferentially raise cardiac levels!! Therefore, use
Phenytoin for treatment of bupivacaine-induced seizures or cardiac dysrhythmias.
Ketamine provides analgesia as well as sedation and can be used as a single agent.
Benzos, chloral hydrate, pentobarbital, and propofol are all sedatives but provide no
analgesia and should be combined with an analgesic (such as fentanyl) to achieve
appropriate PS&A.
Minimal sedation: responds normally to verbal commands, not asleep
Moderate sedation: should not require repeated painful stimulation to be aroused and
should not require intervention to maintain a patent airway.
Deep sedation: patient cannot be easily aroused but responds purposefully after repeated
verbal or painful stimulation. The ability to independently maintain ventilatory function
may be impaired.
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Dissociative Sedation: a trancelike cataleptic state induced by the dissociative agent
ketamine, characterized by profound analgesia and amnesia, with retention of protective
airway reflexes, spontaneous respirations, and cardiopulmonary stability.
Anesthesia: patient not arousable, even by painful stimulation.
Flumazenil reverses the CNS and respiratory depression associated with Benzo’s.
Dose=0.01-0.02 mg/kg/dose IV/IM (maximum initial dose of 0.2mg) Dose may be
repeated every minute to a maximum cumulative dose of 1 mg. Because of the risk of
seizures, it should not be used in patients receiving long-term benzos, cyclosporine, INH,
Lithium, propoxyphene, theophylline, or TCA’s. The onset of action is 1 minute and the
duration between 30-60 minutes.
Pentobarbital is a barbiturate, and there are no approved reversal agents for barbiturates.
Ketamine possesses catecholamine-like properties, thus inducing bronchodilatiion and
hypertension. Its side effects include laryngospasm, apnea, respiratory depression,
increased ICP, increased IOP, emergence reactions, and hypersalivation; because it
increases ICP and IOP, it should not be used in patients with head injury, increased ICP,
glaucoma, or acute globe injury.
The initial step in the patient who has apnea during procedural sedation is to stimulate the
patient with a sternal rub. Then try repositioning the airway, then O2, then consider
reversal agents.
Patients are at highest risk for respiratory depression during 2 separate periods:
1) during the first 5-10 min after IV administration of meds, and
2) during the immediate post-procedure period, when painful procedural stimuli
have ceased.
Chest wall rigidity, known as “wooden chest syndrome” is a side effect best known to be
associated with the use of fentanyl. It is most often associated with doses greater than
15mcg/kg but may also be seen with rapid infusions of smaller doses. It has not been
reported in the low bolus doses of 1-2mcg/kg recommended for procedural sedation. If
chest wall rigidity occurs, it is not usually reversible with naloxone. Neuromuscular
paralysis and intubation may be required to achieve adequate ventilation.
The usual duration of action from intermittent IV dosing of Etomidate is 4-10 minutes.
Onset of action is less than 1 minute. It is critical to provide additional sedatives if the
noxious stimuli is anticipated to last longer than 4-10 minutes.
Propofol possesses inherent antiemetic and euphoric properties. The most serious
adverse effect of it is potent respiratory depression and apnea, which can occur suddenly
and without warning. It can also produce hypotension by direct negative inotropy as well
as arterial and venodilation.
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ETCO2 detection via side-stream capnography is the most reliable method of monitoring
adequate ventilation during sedation in non-intubated patients. Absent ET CO2
waveforms and levels indicate apnea, laryngospasm, or complete airway obstruction.
Rising levels of ETCO2 and change in shape of the CO2 waveform indicate
hypoventilation. With an obstructed airway, chest excursions may occur without air
movement.
Chloral hydrate is metabolized in the liver to the active metabolite 2,2,2-trichlorethanol.
This active metabolite has a long half-life in neonates (24 hrs) and children (12 hours). It
is a pure sedative-hypnotic agent without analgesic properties. When given orally, the
average time to peak sedation is 30 minutes, with an additional recovery time of 2 hours.
Despite a wide margin of safety, chloral hydrate can cause airway obstruction and
respiratory depression, especially at high doses (75-100mg/kg).
Benzos lack analgesic properties.
Pentobarbital can lead to respiratory depression and hypotension as it is a negative
inotrope.
The usual duration of dissociation provided by typical IV doses of ketamine (1-2mg/kg
IV) is 10-15 minutes. Using IM Ketamine at 4mg/kg can increase the duration to 30-60
minutes.
The most common side effect of fentanyl is facial pruitis and nasal itching. It may also
induce hypotension in high doses (uncommon).
Thiopental has a side effect of inducing bronchospasm so would be contraindicated in
intubating an asthmatic.
Paradoxical excitation and agitation following administration of midazolam is a common
side effect. This usually resolves without specific therapy within 20 minutes. There is no
need to administer additional sedatives or reversal agents.
Moderate sedation (formerly “conscious sedation”) is defined as a drug-induced
depression of consciousness during which patients respond purposefully to verbal
commands either alone or accompanied by light tactile stimulation. With moderate
sedation, no intervention is required to maintain a patent airway and cardiovascular
function is usually maintained.
A child who is minimally sedated would respond normally to verbal commands and
would not be asleep.
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Laryngospasm following use of ketamine is <1% of ketamine sedations in the ED; it is
classically described as stridulous (stridorous) and high-pitched. Stertorous (sonorous)
respirations are more typically lower pitched and help identify the site of the airway
obstruction as the oro or naso-pharynx. The first step here would be airway
repositioning. If the patient truly had laryngospasm then the first step would be PPV with
bag-valve-mask in an attempt to overcome the laryngospasm. If this fails, then
neuromuscular paralysis and emergency ET intubation should be performed.
Propofol is a pure sedative-hypnotic. It provides no analgesia and should be combined
with an agent with analgesic properties such as ketamine (aka “ketofol”) when used with
painful procedures. Propofol has been touted as an ideal drug for ED based procedural
sedation because of its reliability, rapid onset, short duration, easy titratability, and
intrinsic antiemetic properties. However, its use has been limited due to concerns for
respiratory and cardiovascular depression.
Etomidate’s adverse effects include respiratory depression, myoclonus, nausea, and
vomiting as well as transient adrenal suppression.
Barbiturates (thiopental and methohexital) frequently can cause hypotension at typical IV
doses so their use should be avoided in patients with volume depletion or cardiovascular
compromise.
Inhaled Nitrous oxide (40%) provides anxiolysis and only mild analgesia so for
procedures would need to be combined with an IV opioid or local analgesia; safest route
of administration is via a self-administered demand-valve mask; should be avoided in
patients with potential closed-space diseases such as bowel obstruction, middle ear
disease, pneumothorax, or pneumocephaly; it is also a known teratogen and mutagen.
LET is the only agent designed for use on non-intact skin (lacs). Ethyl chloride and
fluoromethane are topical sprays that are used to anesthetize intact skin by rapid
evaporative cooling. EMLA is a topical cream that is only approved for use on intact
skin; LET is contraindicated in areas of end arterial supply (penis, digits, pinna, tip of
nose) because it contains Epi.
ASA Physical Status Classes:
Class I: normal healthy patient
Class II: patient with mild systemic illness without functional limitation (a child with
history of well controlled asthma with no active wheezing)
Class III: patient with severe systemic disease with definite functional limitation
Class IV: patient with severe systemic disease that is a constant threat to life.
Class V: moribund patient not expected to survive without the procedure
Initial doses of fentanyl used IV for procedural sedation is 1-2mcg/kg. Subsequent doses
of 0.5-1mcg/kg are used to titrate to effect.
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Nitrous oxide can provide both sedation and analgesia. However, since the analgesic
qualities are weak in the concentrations administered in the ED setting, compared to the
OR, its use has been largely limited to procedures that: 1) require minimal sedation; 2)
are of very short duration; or 3) combine the use of regional or local anesthetics, such as
lidocaine in hematoma blocks.
Because flumazenil and naloxone may have a shorter duration of action than the
medications they are reversing, patients must be carefully monitored for the possibility of
resedation.
Reported side-effects of naloxone include hypertension, ventricular tachyarrhythmias,
cardiac arrest, and vomiting.
There are no approved reversal agents for barbiturates.
The decision to perform procedural sedation and analgesia (PSA) to
facilitate fracture manipulation must be balanced against the risks of
sedation in each patient. Careful presedation assessment begins with a
focused history and physical examination. Most organizations follow
the classification published by the ASA (Table 1). The MP classification
system can be used to identify patients at risk for having difficult
airways (Fig. 2). The adequacy of seeing the posterior oropharynx has
been shown to correlate with glottic exposure during direct
laryngoscopy. The patient described in the vignette, who has poorly
controlled asthma, obesity, and OSAS, should be classified as ASA
level 3 (ie, having moderate systemic disease that may limit his
activity but is not incapacitating). His oropharyngeal examination
findings suggest an MP class 2 airway.
An ASA level 3 or greater and MP class 3 or greater have been shown
to correlate with an increased risk of sedation-related adverse events
and unexpected difficult airway, respectively. Although these data
have been extrapolated from the adult anesthesiology literature, the
American Academy of Pediatrics encourages practitioners to consult
with appropriate subspecialists or anesthesiology about patients
deemed to be at high risk for procedural sedation (Table 2). In such
cases, the practitioner may defer PSA in the emergency setting and
opt for complete control of the airway with general anesthesia outside
the emergency department or use alternative techniques such as local
or regional block anesthesia with minimal sedation.
The key steps prior to performing PSA in the emergency department
are:
1.
Risk stratification based on the ASA physical status classification.
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2.
A focused presedation history and physical examination (Table
3).
3.
Documentation of the time of last oral intake.
4.
Preparation and set up; the acronym SOAPME may be used to
review the preparatory steps (Table 4).
5.
Selection of the appropriate agents based on desired depth of
sedation to best facilitate the procedure.
Preoperative and elective procedure NPO guidelines have limited
applicability in the emergency setting. Adverse events are more
related to depth of sedation, type of procedure, and age of patients
than to NPO status. Therefore, the emergency physician should weigh
the risks and benefits of the procedure and sedation for each patient in
deciding duration of preprocedural fasting.
The indications for PSA include any procedure that is likely to invoke
significant pain or distress or one that requires a relatively motionless
state, such as advanced imaging studies or complex laceration repair
(Table 5).
The choice of agent usually involves a combination of a sedativehypnotic (or dissociative) agent and narcotic analgesic for painful
procedures. Other factors that may determine the type of medication
include familiarity with a particular class of agent, institutional
preference, or clinician credentialing for sedation in the emergency
department. Table 6 lists the properties of the various pharmacologic
agents and their major adverse effects.
Airway complications are the most common adverse events during
PSA. They include hypoventilation, apnea, airway obstruction,
aspiration, bronchospasm, and rarely laryngospasm. Respiratory
depression can be a consequence of a deeper level of sedation than
anticipated or an adverse effect of the sedative-hypnotic agent used. It
may be enhanced by concomitant use of narcotic analgesia. The
clinician administering sedation must be proficient in early recognition
of airway obstruction or hypoventilation and be prepared to intervene
to secure an adequate airway. Interventions might include airway
realignment, bag-mask ventilation, and intubation, if necessary.
Severe laryngospasm requiring neuromuscular blockade and intubation
is an infrequent complication in procedural sedation cases in the
pediatric emergency department. It is precipitated by incomplete or
complete closure of the true vocal cords. It is defined as absence of air
exchange in the presence of chest wall movement with or without
stridor, not responsive to airway repositioning and routine bag-valvemask ventilation. Occluding the pop-off valve to generate higher
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pressures with bag-mask ventilation and attempting the
“laryngospasm maneuver” may be temporizing measures before
administering a neuromuscular blocking agent and endotracheally
intubating the patient. The laryngospasm maneuver is performed by
applying firm pressure in the notch located between the angle of the
mandible anteriorly, the mastoid posteriorly, and the base of the skull
superiorly. The purported mechanism is pressure in the notch
surpassing the patient’s pain threshold that causes the vocal cords to
relax. It is similar to the jaw thrust maneuver, but the pressure is
directed toward the mandibular condyles rather than to the angles of
the mandible.
Table 6: Overview of Medications
Agent
Pediatric Dosing
Onset
(min)
Duration
(min)
Comments
Choral
hydrate
PO: 25 to 100 mg/kg,
after 30 min can
repeat 25 to 50
mg/kg. Maximum total
dose: 2 g or 100
mg/kg (whichever is
less). Single use only
in neonates
15 to 30
60 to 120
Effects unreliable if age <3
years
Diazepam
IV: initial 0.05 to 0.1
mg/kg, then titrate
slowly to maximum
0.25 mg/kg
4 to 5
60 to 120
Reduce dose when used in
combination with opioids
Sedativehypnotics
8
Etomidate
IV: 0.1 mg/kg; repeat
if inadequate response
<1
5 to 15
Adverse effects include
respiratory depression,
myoclonus, nausea, emesis
Midazolam
IV (0.5 to 5 years):
initial 0.05 to 0.1
mg/kg, then titrated
to maximum 0.6
mg/kg
IV (6 to 12
years): initial 0.025 to
0.05 mg/kg, then
titrated to maximum
0.4 mg/kg
2 to 3
45 to 60
Reduce dose when used in
combination with opioids;
may produce paradoxic
excitement
IM: 0.1 to 0.15 mg/kg
10 to 20
60 to 120
PO: 0.5 to 0.75 mg/kg
15 to 30
60 to 90
IN: 0.2 to 0.5 mg/kg
10 to 15
60
PR: 0.25 to 0.5 mg/kg
10 to 30
60 to 90
PR: 25 mg/kg
10 to 15
60
Avoid if temporal lobe
epilepsy or porphyria
IV: 1 to 6 mg/kg,
titrated in 1- to 2mg/kg increments
every 3 to 5 min to
desired effect
3 to 5
15 to 45
May produce paradoxic
excitement; avoid in
patients who have
porphyria
IM: 2 to 6 mg/kg,
maximum 100 mg
10 to 15
60 to 120
PO/PR (<4 yrs): 3 to 6 15 to 60
mg/kg, maximum 100
mg PO/PR (>4 yrs):
1.5 to 3 mg/kg,
60 to 240
Methohexital
IV: 0.5 to 1.0 mg/kg
Pentobarbital
9
maximum 100 mg
Propofol
IV: 1.0 mg/kg,
followed by 0.5 mg/kg
repeat doses as
needed
<1
5 to 15
Frequent hypotension and
respiratory depression;
avoid with egg or soy
allergies
Thiopental
PR: 25 mg/kg
10 to 15
60 to 120
Avoid in patients with
porphyria
Fentanyl
IV: initial 1.0 mcg/kg
up to 50 mcg/dose,
may repeat every 3
min, titrate to effect
3 to 5
30 to 60
Reduce dosing when
combined with
benzodiazepines
Morphine
IV: initial 0.05 to 0.15
mg/kg up to 3
mg/dose, may repeat
every 5 min, titrate to
effect
5 to 10
120 to 180
Reduce dosing when
combined with
benzodiazepines
IV: 1 to 1.5 mg/kg
slowly over 1 min,
may repeat every 10
min as needed
1
Dissociation:
15
Recover
y: 60
Multiple contraindications.
Unpleasant dreams or
hallucinations rare in
kids.
Dissociation:
15 to 30
Often given with
concurrently atropine or
glycopyrrolate to counter
hypersalivation
Analgesics
Dissociative
Drug
Ketamine
IM: 4 to 5 mg/kg, may 3 to 5
repeat (2 to 4 mg/kg)
after 10 min
Recovery:
90 to 150
Inhalational
Drug
10
Nitrous oxide
Preset mixture with
minimum 30% oxygen
self-administered by
demand valve mask
(requires cooperative
child); continuous flow
nasal mask in
uncooperative child
with close monitoring
<5
<5 following
discontinuati
on
Requires specialized
apparatus and gas
scavenger capability;
several contraindications
Reversal
Drugs
Naloxone
IV/IM: 0.1
IV: 2
mg/kg/dose up to
maximum of 2
mg/dose, may repeat
every 2 min as needed
IV: 20 to
40
IM: 60
to 90
If shorter acting than the
reversed drug, serial doses
may be required
Flumazenil
IV: 0.02 mg/kg/dose,
may repeat every 1
min up to 1 mg
30 to 60
If shorter acting than the
reversed drug, serial doses
may be required
1–2
Alterations in dosing may be indicated depending on the clinical situation and the
practitioner’s experience with the drugs. Individual doses may vary when used in combination
with other drugs, especially when benzodiazepines are combined with opiates.
Ketamine is absolutely contraindicated in patients <3 months (airway risk) or when known
psychosis (may exacerbate). Relative contraindications include age <12 months, procedures
involving stimulation of posterior pharynx, history of tracheal surgery or stenosis, active
pulmonary infection or disease (including upper respiratory tract infection), known or
suspected cardiovascular disease, suspected raised intracranial or intraocular pressure, globe
injury, porphyria or thyroid dysfunction.
IM=intramuscular, IN=intranasal, IV=intravenous, PO=oral, PR=rectal
Reprinted from Pershad J, Kost S. Emergency department based
sedation services. Clin Pediatr Emerg Med. 2007;8:253-261. Copyright
© 2007, Elsevier
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Table 1: American Society of Anesthesiologists (ASA) Risk
Classification
Class
I
A normal, healthy patient.
Class
II
A patient who has mild systemic disease (no functional limitation).
Class
III
A patient who has moderate or severe systemic disease that limits activity but is
not incapacitating.
Class
IV
A patient who has an incapacitating systemic disease that is a constant threat to
life.
Class
V
A moribund patient who is not expected to survive 24 hours with or without the
procedure.
Reprinted from Pershad J, Kost S. Emergency department based
sedation services. Clin Pediatr Emerg Med. 2007;8:253-261. Copyright
© 2007, Elsevier
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