Stephen Wilson Sedation Lecture

Basic Considerations Of Sedating Children In The Dental Setting Stephen Wilson DMD, MA, PhD Professor & Chair Division of Dentistry Department of Pediatrics Cincinnati Children’s Hospital Medical Center


Options for Sedation

• Depth of sedation
– Minimal
– Moderate
– Deep

• Route of administration
– Enteral (oral, rectal)
– Parenteral
• Nasal
• Submucosal
• Intramuscular
• Intravenous

• You can get to any depth
using any of the routes
• The only thing that
“route” changes is how
fast you get there
– Oral – slowest
– Intravenous – fastest
• And it’s the dose that
determines the final
depth

And there is always GENERAL ANESTHESIA


Your State Practice Act
• Types of permits
– GA
– Parenteral
– Oral conscious sedation
• wouldn’t include nasal?!
•
 Minor tranquilizers (i.e. hydroxyzine or
diazepam) can only be administered
outside of facility by responsible adult

• Supervised team capable of
reasonably assisting dentist with
procedures, problems, and
emergencies incident thereto

Arguably, the route
doesn’t really make any
difference in depth of
sedation, but just how fast
blood levels are attained

No evidence to show this
practice is beneficial!!!!
So why take a chance?
This could include:
• Laryngospasm
• Bronchospasm
• Depressed
respiratory/cardio
• Anaphylactic Rx



Anti-Anxiety Agents
• Purpose: knowing you will undergo a
procedure tomorrow, obsessing on it, causing
you prolonged anxiety
– Most likely doesn’t apply to toddlers
– Might be helpful for school-aged children, but is
such a practice evidenced based?


Drugs & Their Classes with Sedative
Properties
• General anesthetics (e.g., nitrous oxide, ketamine)
• Hypnotics
• Benzodiazepines
• Opioids
• Anti-histaminics
• α2 agonists (e.g., clonidine, dexmedetomidine)


Nitrous oxide
Pharmacologic class Inhalational agent (GA adjunct)
Timing Onset: within 2-4 minutes
Working time: as long as flowing
Advantages Mild sedation when used alone
Mild analgesic
Great distracting agent – wonderful for hypnotic suggestion
Good for some gaggers
Excellent for “settling” the patient (“titrator” for orally administered “fixed” agents)
Shortcomings Weak inhalational agent
Easy for child to dislodge nasal hood
Significant reduction in concentration at lung level
Dose Normally: 20% – 50% concentration
For “settling” difficult patients: 50% – 70% concentration (if not
successful after 10 minutes – cancel sedation?) - also don’t forget to reset to 50% or less after settled
Relative Contraindications:
• Chronic rhinitis
• Mouth breathers
• Recent eye surgery
• Otitis media
• Cystic fibrosis
• URI
• Some psychiatric patients

Benzodiazepines
(Midazolam is most frequently used)
• Benzodiazepine characteristics (profile varies depending on agent)
– Anxiolytic
– Sedative
– Hypnotic
– Anticonvulsant
– Muscle-relaxant
– Anterograde amnestic
– Provides no analgesia!
• Actions due to:
– Interaction with GABA receptors increasing their inhibitory actions
Benzodiazepines
(Midazolam is most frequently used)
• Midazolam (water-soluble)
– Orally & parenterally (e.g., nasally)
• Other notable effects
– Hypoventilation and associated hypoxemia.
– Interacts with other agents (e.g., erythromycin; cimetidine)
– Negligible cardiovascular effects in therapeutic doses
(otherwise cardiac depression)
– Can interact with other sedatives causing respiratory &
cardiovascular depression
Benzodiazepines
(Midazolam is most frequently used)
• “Angry child syndrome”
– Paradoxical hyperactivity occurs
– Attentional depression
– Agitated toxic psychosis
– Manic behavior
– Increased anxiety
– Hostility
– Rage
– Poor impulse control or aggressive behavior (more common in young children)
• It has become very popular today in pediatrics and pediatric dentistry.
Reference: Lexi-Comp
Midazolam (Versed)
The major risks associated with high doses are hypoventilation and associated hypoxemia. There are interactive effects when used in patients who are on other types of drugs such as erythromycin (producing unconsciousness) and thus should be used very cautiously under such circumstances.
In therapeutic doses, its effect on the cardiovascular system is negligible; however, higher doses produce decreased blood pressure and cardiac output.
Occasionally in children, the expected sedation does not occur, but rather, a paradoxical hyperactivity occurs and is called the “angry response”.
Dose – Oral route
Mechanism of Action Pharmacokinetics Stability Contraindications Warnings Adverse reactions
0.25 – 1.0mg/kg
Depresses all levels of the CNS, including the limbic and reticular formation, by binding
to the benzodiazepine site on the gammaaminobutyric acid (GABA) receptor
complex and
modulating GABA,
which is a major
inhibitory
neurotransmitter in the
brain
Onset of action:
Oral: Within 10-20
minutes
Metabolism:
cytochrome P450
CYP3A4 enzyme
Half-life,
Children: syrup: 2.2-6.8
hours
Elimination: 63% to
80% excreted in urine
Store at 15°C
to 30°C (59°F
to 86°F).
Hypersensitivity to
midazolam, any
component, or
cherries (syrup);
cross-sensitivity
with other
benzodiazepines
may occur;
narrow-angle
glaucoma
Midazolam may cause respiratory
depression/arrest; deaths and hypoxic
encephalopathy have resulted when
these were not promptly recognized
and treated appropriately; dose must
be individualized and patients must
be appropriately monitored; serious
respiratory adverse events occur
most often when midazolam is used
in combination with other CNS
depressants; severe hypotension and
seizures have been reported; risk may
be increased with concomitant
fentanyl use. Paradoxical reactions,
including hyperactive or aggressive
behavior, have been reported in both
adult and pediatric patients.
Cardiovascular: Bradycardia,
cardiac arrest, hypotension
Central nervous system: Amnesia,
ataxia, combativeness, dizziness,
drowsiness, headache,
hyperactivity, nystagmus,
paradoxical excitement, rhythmic
myoclonic jerking in preterm
infants (~8% incidence), sedation
Gastrointestinal: Nausea, vomiting
Local:
I.M., I.V.: Pain and local reactions
at injection site (severity less than
diazepam)
Nasal: Burning, discomfort,
irritation
Neuromuscular & skeletal: Muscle
tremor, tonic/clonic movements
Ocular: Blurred vision, diplopia,
lacrimation
Respiratory: Apnea,
bronchospasm, cough,
laryngospasm, oxygen
desaturation, respiratory
depression
Miscellaneous: Hiccups, physical
and psychological dependence
with prolonged use
Meperidine (Demerol)
• Synthetic analgesic, sedative, antispasmodic agent.
• Liquid
–Non-palatable (bitter)
–Administered orally or parenterally (oral route is less
efficient)
–Metabolized in the liver
• Reversible with naloxone
• Behavior effects
–Mood change (euphoric or dysphoric)
–Affects several areas of brain
Meperidine (Demerol)
• Other notable effects
– Respiratory depression (less with oral route)
– Hypotension
– Analgesic
– Nausea & emesis (chemotrigger area of medulla)
– Histamine released from mast cells (localized
erythematous wheals, urticaria, and itching – care
w/asthma)
– Lowers seizure threshold
Reference: Lexi-Comp
Meperidine (Demerol)
A major drawback to this agent is its likelihood to cause respiratory depression and hypotension. This is particularly true when administered parenterally with a
lessened risk anticipated when delivered via the oral route. Its use in combination with other sedatives should be carefully assessed because of the additive or
synergistic properties of sedative agents.
Narcotics, including Demerol, should be used with caution with local anesthetics. The threshold level for seizures apparently is lowered when both are used in
combination.
Dose – Oral route Mechanism of Action Pharmacokinetics Stability Contraindications Warnings Adverse reactions
1-2 mg/kg Binds to opiate
receptors in the CNS,
causing inhibition of
ascending pain
pathways, altering
the perception of and
response to pain;
produces generalized
CNS depression
Onset of action:
Oral, Within 10-15
minutes
Duration:
 2-4 hours
Metabolism: In the
liver
Half-life,
3 hours
Elimination:
in urine
Incompatible
with
aminophylline,
heparin,
phenobarbital,
phenytoin, and
sodium
bicarbonate
Hypersensitivity to
meperidine or any
component; use of
MAO inhibitors
within 14 days
(potentially fatal
reactions may
occur)
CNS and respiratory depression
may occur. Use with great caution
(and only if essential) in patients
with head injury, increased ICP, or
other intercranial lesions (potential
to depress respiration and increase
ICP may be greatly exaggerated in
these patients). Use with extreme
caution in patients with COPD, cor
pulmonale, acute asthmatic
attacks, hypoxia, hypercapnia, preexisting
respiratory depression,
significantly decreased respiratory
reserve. Severe hypotension may
occur; use with caution in
postoperative patients, in patients
with hypovolemia, or in those
receiving drugs which may
exaggerate hypotensive effects
(including phenothiazines or
general anesthetics). Meperidine
may be given I.V., but should be
administered very slowly and as a
diluted solution; rapid I.V.
administration may result in
increased adverse effects including
severe respiratory depression,
apnea, hypotension, peripheral
circulatory collapse, or cardiac
arrest; do not administer I.V. unless
a narcotic antagonist and
respiratory support are
immediately available.
Cardiovascular: Palpitations,
hypotension, bradycardia, peripheral
vasodilation, tachycardia, syncope,
orthostatic hypotension
Central nervous system: CNS
depression, dizziness, drowsiness,
lightheadedness, sedation, intracranial
pressure elevated, headache, euphoria,
dysphoria, agitation, transient
hallucinations, disorientation; active
metabolite (normeperidine) may
precipitate twitches, tremors, or
seizures
Dermatologic: Pruritus, rash, urticaria
Endocrine & metabolic: Antidiuretic
hormone release
Gastrointestinal: Nausea, vomiting,
constipation, biliary tract spasm,
xerostomia
Genitourinary: Urinary tract spasm,
urinary retention
Local: Pain at injection site; phlebitis,
wheal, and flare over the vein (with I.V.
use); induration, irritation (repeated
SubQ use)
Neuromuscular and skeletal: Tremor,
weakness, uncoordinated muscle
movements
Ocular: Miosis, visual disturbances
Respiratory: Respiratory depression,
respiratory arrest
Miscellaneous: Physical and
psychological dependence, histamine
release, anaphylaxis, hypersensitivity
reactions, diaphoresis
Chloral hydrate (CH)
• Sedative/hypnotic
– Long history & relatively safe
– Margin of safety – dose dependent
• Liquid
– Non-palatable
– Administered orally or rectally
– Mucosal irritant (can induce larngospasms)
– Usual concentration - 100 mg/ml.
• Absorbed via GI tract
– Converted in liver to trichlorethanol (“alcohol” breath)
– Excreted by kidney
Chloral Hydrate - continued
• No reversal agent available
• Behavioral effects relatively consistent (cerebral cortex)
– Initial phase of hyperactivity/giddiness/irascibility
– Secondary phase of less activity & sleepiness
– Can induce sleep (higher doses, patient characteristics & state)
– Respiratory depression & coma
• Other notable effects:
– Cardiac arrhythmias (halothane like)
– Non-analgesic, possibly hyperalgesic
– Hypotonicity of tongue muscles (airway blockage)
– Gastric irritation, nausea, emesis
– Interactive drug effects (increase’s liver’s microsomial enzymes –
coumarin)
Reference: Lexi-Comp
Chloral Hydrate
Usually one’s sedation goals are the first 2 depths of sedation of the American Academy of Pediatric Dentistry guidelines (i.e., minimal and moderate sedation).
However, in small uncooperative children the optimal level of sedation is that of very light sleep from which one can be easily aroused with minimal verbal or
tactile stimulation. The therapeutic dose range that usually produces this type of effect, when used alone, in the majority of children is 30 to 50 mg/kg of body
weight. This dose also can cause hypotonicity of the muscles of the tongue causing it to fall backward against the posterior oro-pharyngeal structures. Appropriate
patient monitoring (pulse oximetry and capnography) is necessary because of the possibility that airway compromise due to hypotonicity of glossal muscles; deep
sleepand/ or some respiratory depression may occur.
Dose – Oral route Mechanism of Action Pharmacokinetic
s
Stability Contraindications Warnings Adverse reactions
10-50 mg/kg when
used alone
10-25 mg/kg if used
with other agents such
as meperidine and
hydroxyzine
Central nervous
system depressant
effects are primarily
due to its active
metabolite
trichloroethanol,
mechanism unknown
Onset of action:
10-20 minutes
Maximum
effect: Within
30-60 minutes
Duration:
4-8 hours
Mean half-life:
10 hours
Elimination:
Metabolites
excreted in
urine; small
amounts
excreted in feces
via bile
Sensitive to light;
exposure to air
causes volatilization;
store in lightresistant,
airtight
container at room
temperature; do not
refrigerate
Hypersensitivity to
chloral hydrate or any
component; hepatic
or renal impairment;
severe cardiac
disease.
Oral forms are also
contraindicated in
patients with gastritis,
esophagitis, or gastric
or duodenal ulcers.
Deaths and permanent neurologic
injury from respiratory
compromise have been reported
in children sedated with chloral
hydrate; respiratory obstruction
may occur in children with
tonsillar and adenoidal
hypertrophy, obstructive sleep
apnea, and Leigh's
encephalopathy, and in ASA
class III children; depressed
levels of consciousness may
occur;
chloral hydrate should not be
administered for sedation by
nonmedical personnel or in a
non-supervised medical
environment; sedation with
chloral hydrate requires careful
patient monitoring (Cote, 2000);
animal studies suggest that
chloral hydrate may depress the
genioglossus muscle and other
airway-maintaining muscles in
patients who are already at risk
for life-threatening airway
obstruction (eg, obstructive sleep
apnea)
Central nervous system:
Disorientation, sedation,
excitement
(paradoxical), dizziness,
fever, headache, ataxia
Dermatologic: Rash,
urticaria
Gastrointestinal: Gastric
irritation, nausea,
vomiting, diarrhea,
flatulence
Hematologic:
Leukopenia,
eosinophilia
Respiratory: Respiratory
depression when
combined with other
sedatives or narcotics
Chloral Hydrate & Eyes!
Be Careful
Adjunctive Agents
• Hydroxyzine (Atarax or Vistaril)
– Minor psychotherapeutic agent
– antispasmodic, antihistaminic, and sedative properties
– Relatively pleasant tasting agent (vanilla – Atarax; lemon – Vistaril)
– Popular in combination with CH and/or meperidine
– Slight depressant effects on the cardiovascular and respiratory systems
– Anti-arrhythmic properties and may cause bronchodilation
– Slight analgesic effects.
• Promethazine (Phenergan)
– Same as above
– May lower the seizure threshold and cause extrapyramidal responses
(i.e., limb movements/jerking.)
Major Pediatric Sedation Drugs
Drug Dose Characteristics Warnings Sedation considerations
(timing)
Reversibility
Chloral hydrate 20-50 mg/kg
Max:
1 Gram
Oily
Not-palatable
Irritability
Sleep/drowsiness
Airway blockage
Mucosal irritant;
Laryngospasms
Respiratory
depressant
Cardiac
arrhythmias
Onset: 30-45 min
Separation time: 45 min
Work: 1-1.5 hrs
No
Meperidine 1-2 mg/kg
Max:
50 mgs
Clear
Non-palatable
Analgesia
Euphoria
Dysphoria
Respiratory
depression
Hypotension
Onset: 30 min
Separation time: 30 min
Work: 1 hr
Yes
(Narcan)
Midazolam 0.3-1.0 mg/kg
Max: 15 mgs
(young child)
20 mgs
(older child)
Clear
Non-palatable
Relaxation
Anterograde
amnesia
Angry child
syndrome
(AC/Sxd)
Respiratory
depression
Loss of head
righting reflex
Onset: 10 min
Separation time: 10 min
Work: 20 min
Yes
(Flumazenil)
Other Pediatric Sedation Drugs
Drug Dose Characteristics Warnings Sedation considerations
(timing)
Reversibility
Hydroxyzine 1-2 mg/kg
Max:
50 mg/day
Palatable
Sleep/drowsiness
Anti-histamine
Bronchodilator
Anti-emetic
Dry mouth
Pregnancy
Hypotension
Potentiates other
CNS depressants
Onset: 30 min
Separation time: 30 min
Work: 30-45 min ???
No
Promethazine 0.5 - 1 mg/kg
Max:
50 mgs
Palatable
Sleep/drowsiness
Anti-histamine
Anti-emetic
Dry mouth
Not recommended
in children less
than 2 years of
age
Lowers seizure
threshold
Hypotension
Onset: 20-30 min
Separation time: 30 min
Work: 30-45 min ???
No
Diazepam 1 mg peryear of
age; 0.25 mg/kg
Max: 10 mg
(Varies with
age)
Non-palatable
Relaxation
Anterograde
amnesia
Sedation
Respiratory
depression
Possible
hypotension
Avoid grapefruit
juice
Onset: 1 hour
Separation time: 1 hour
Work: 1 hour ???
Yes
(Flumazenil)
Reasons
• To use single agents
– Minimize likelihood of adverse events
– Minimize response options in managing adverse events
– Less likelihood of drug dosing error
• To combine drugs
– Potentiate or summate drug effects
– Complement or expand drug classes or effects (e.g., analgesic
with sedative)
– Increase working time
Popular Combinations of Sedatives
Drug Dose – oral
(mg/kg)
Characteristics Warnings Sedation considerations
(timing)
Reversibility
Choral Hydrate
+ hydroxyzine
+ meperidine
(Demerol) &
hydroxyzine
CH (20-50)
Vis (1-2)
CH (15-25)
Vis (1-2)
Dem (1-2)
Hyperexcitable
Drowsiness
Sleep
Euphoria,
dysphoria, hyper,
mellow
Loss of
consciousness
AIRWAY!!!!!
Same as above,
Respiratory
depression
Onset: 20 min
Separation time: 45 min
Work: 1-1.5 hours
Same as above
No
Only Demerol
(Narcan)
Demerol
+ hydroxyzine
+ midazolam
Dem (1-2)
Vis (1-2)
Mid (0.3-0.5)
Dem (1)
Same as above
Same as above;
initial relaxation
AC Sxd/fussy
Respiratory
depression
Respiratory
depression; loss of
head right reflex
Onset: 20-30 min
Separation time: 30 min
Work: 1 Hour ???
Same as above
Only Demerol
Both are
(Narcan &
Flumazenil)
Midazolam
+ hydroxyzine Mid (0.3-0.7)
Vis (1-2)
initial relaxation
AC Sxd/fussy
difficult
Respiratory
depression; loss of
head right reflex
Onset: 10 minutes
Separation time: 20 min
Work: 30-45 min ???
Yes
(Flumazenil)
General Outcomes
• Sedated, safe & comfortable – the good
– Usually easy going child, light - moderate sedation (deep sedation is not “comfortable”)
– No need for papoose board; quality of work is good
– Chatting with child
• Sedated, disruptive & challenging – the bad
– Usually paradoxical emotional reactions, little likelihood of responding appropriately to your
suggestions
– Papoose board – “hold and go”; poor quality of work
– Frustrating
• Sedated, out of control – the ugly
– No likelihood of responding to your suggestions
– Papoose board used, but useless; “crap” dentistry
– Stated mildly: Exasperating!!!!
• Sedated & dangerous
– No response & can’t arouse
– Great likelihood of aspiration and laryngospasm!!!!
– Much better to simply use an anesthesiologist
Route Advantage Disadvantage Comments
ENTERAL
Oral Convenience
Economy
Toxicity decreased
Inexpensive
Variability of effect (no
titration)
Onset time (slow)
Can be spit out
Most commonly used in pedo;
parents like it
PARENTERAL
Intranasal Requires little cooperation
Eliminates spitting
Relatively inexpensive
Injury to nose
Eyes vulnerable
Atomizer is recommended
Helps w/ obstreperous child
Intramuscular Relatively fast absorption
Technically easy to do
Relatively inexpensive
Onset may be delayed
No titration
Trauma to injection site
Higher potential for side
effects/toxicity
Liability costs & licensure
Relatively fast
Potentially scary
2 Pokes!!! Fear of needles
Dentists are not use to this route
Submucosal Easy to administer for dentists
Relatively fast
Tissue sloughing & trauma
Potentially rapid onset
Liability costs & licensure
Dentists very familiar with route
2 Pokes!!! Fear of needles
Intravenous Ideal drug route
Most rapid onset of effects
Titration (also test dose)
IV already established for
emergency management
Gaining access
Increased likelihood for
anaphylaxis
Requires highest level of
monitoring
Liability costs & licensure
Pediatric dentists are not trained well
and consistently in this technique
Works well for those who are
properly trained
Route Advantage Disadvantage Comments
Oral Convenience
Economy
Toxicity decreased
Inexpensive
Variability of effect (no
titration)
Onset time (slow)
Can be spit out
Most commonly used in
pedo; parents like it
Route Advantage Disadvantage Comments
Intranasal Requires little
cooperation
Eliminates spitting
Relatively inexpensive
Injury to nose
Eyes vulnerable
Atomizer is
recommended
Helps w/ obstreperous
child
Intramuscular Relatively fast absorption
Technically easy to do
Relatively inexpensive
Onset may be delayed
No titration
Trauma to injection site
Higher potential for side
effects/toxicity
Liability costs & licensure
Relatively fast
Potentially scary
2 Pokes!!! Fear of
needles
Dentists are not use to
this route
Submucosal Easy to administer for
dentists
Relatively fast
Tissue sloughing & trauma
Potentially rapid onset
Liability costs & licensure
Dentists very familiar
with route
2 Pokes!!! Fear of
needles
Intravenous Ideal drug route
Most rapid onset of
effects
Titration (also test dose)
IV already established for
emergency management
Gaining access
Increased likelihood for
anaphylaxis
Requires highest level of
monitoring
Liability costs & licensure
Pediatric dentists are
not trained well and
consistently in this
technique
Works well for those
who are properly
trained
Shortcomings of Agents
• Really no shortcomings of current agents
• Issue is the route of administration (oral)
– no possibility of titration (except with nitrous oxide)
• IV titration is really a 2-step process
– A given bolus is added to blood stream causing the effect
– Drug metabolizes, blood levels declines, patient becomes
light, another bolus is added
• IM, intranasal, and submucosal have same issues as
oral route
Drugs of the Future
• Probably not much different than today
• State regulations
– Ketamine – oral (but lots of emesis!!)
• May rely on narcotics and other agents given
via intranasal route
– Fentanyl
– Remifentanyl
– Clonidine
Thank You!!!

Sedation Article

A retrospective study of chloral hydrate, meperidine, hydroxyzine, and midazolam regimens used to sedate children for dental care.

Stephen Wilson, DMD, MA, PhD Jillian Easton Kirsty Lamb Robin Orchardson, BSc, BDS, PhD Paul Casamassimo, DDS, MS Dr. Wilson is a professor and director of the Postgraduate Pediatric Dentistry Program, The Ohio State University & Columbus Children’s Hospital,Columbus, Ohio; Jillian Easton is a dental student at Glasgow Dental Hospital and School, University of Glasgow, Glasgow, Scotland UK; Kirsty Lamb is a dental student at Glasgow Dental Hospital and School, University of Glasgow, Glasgow, Scotland UK; Dr. Orchardson is a professor at the Institute of Biomedical & Life Sciences, Laboratory of Human Anatomy, University of Glasgow, Scotland UK; and Dr. Casamassimo is a professor and chair, Section of Pediatric Dentistry, The Ohio State University & Columbus Children’s Hospital, Columbus, Ohio. Correspond with Dr. Wilson at wilson.42@osu.edu Abstract Purpose: The purpose of this retrospective study was twofold: a) to examine the behavior and physiology of pre-school children each sedated with 1 of 3 drug regimens based on patient age, dental needs, and pre-operative clinical impression; and b) to determine the association between pre-operative behaviors to the behavior and physiology of the sedated children. Method: Records of more than 600 patients sedated at Columbus Children’s Hospital dental clinic over a two-year period were culled for patients who ranged in age from 2 to 5 years of age and had received one of three different drug regimens: a) chloral hydrate and hydroxyzine (CH-H), b) chloral hydrate, meperidine, and hydroxyzine (CH-D-H), or c) midazolam (M). A minimum of 300 patients (100/drug regimen) were randomly selected. The standard sedation sheet used in all sedations at the clinic included, among other factors, pre-operative assessments of patient behavior, interaction, and cooperation. Physiological and behavioral variables during the intraoperative sedation periods were also available. These periods included initial baseline vitals, vitals following drug administration, topical and local drug administration, rubber dam placement, and a minimum of the first 15 minutes of restorative procedures. The three drug regimens were compared for these variables. Data were entered into SPSS for data analysis using one-way ANOVA, Chi-square, regression analysis, and descriptive statistics. Results: The results indicated significant mean differences in patient age, weight, and duration by drug regimen (F=20.3, P<0 .001="" 0.001="" 0.32="" 0.4="" 1.="" 10.="" 100="" 108="" 109="" 10:94-101="" 10="" 11.="" 110="" 111="" 112="" 11="" 12.="" 12:222-27="" 12:288-91="" 12:33-37="" 12:364-67="" 13.7="" 13.="" 13:9-="" 14.="" 14:171-77="" 15.3="" 15.8="" 15.="" 15:186-90="" 15:237-41="" 15:348-52="" 15:422-="" 15="" 16.2="" 16.6="" 16.="" 16:121-27="" 16="" 17.="" 17:406-12="" 17:413-18="" 17:424-31="" 17="" 18.="" 18:287-93="" 18:35-41="" 19.="" 1986.="" 1987.="" 1988.="" 1988="" 1989.="" 1990.="" 1991.="" 1992.="" 1993.="" 1994.="" 1995.="" 1996.="" 1998.="" 1999-2000.="" 1999.="" 1999="" 19="" 1:570-76="" 1="" 2.="" 20.3="" 20.="" 2000="" 20:253-58="" 21.="" 21:12-="" 21:235-41="" 21:68-73="" 22.="" 22:107-112="" 22:2="" 23.1="" 23.="" 231-45="" 24.="" 24="" 25.="" 26.="" 26="" 27.="" 27="" 28.="" 28="" 29.="" 2="" 3.8="" 3.="" 30.="" 300="" 31.="" 33="" 35.9="" 36="" 382="" 38:1309-24="" 39:789-816="" 3="" 4.="" 40.7="" 40="" 41="" 42.4="" 42.5="" 43.1="" 43:231-45="" 43="" 45="" 48.5="" 48.7="" 4="" 5.="" 50:225-29="" 50="" 53:425-29="" 54:437-44="" 56:302-309="" 5="" 6.="" 600="" 63:421-25="" 67="" 6="" 7.="" 71="" 76="" 7="" 8.="" 84="" 8="" 9.="" 9="" a="" aapd="" ab:="" abilities="" able="" above="" academy="" acceptance="" accepted="" accomplished="" according="" accounted="" acquisition="" acs="" action.="" action="" activities="" activity="" addition="" additionally="" adjacent="" administered.="" administered="" administration="" adverse="" adversely="" affect="" after="" again="" age-specific="" age.="" age="" agents="" al="" albeit="" all="" almost="" alone="" also="" although="" always="" am:="" am="" america="" american="" among="" amp="" an="" analgesia="" analgesic="" analysis.="" analysis="" analyzed="" analyzing="" and="" anderson="" anesthesia.2-9="" anesthesia.="" anesthesia="" anesthetic.="" anesthetic="" angry.23="" angry="" anova="" anxious="" any="" ap:="" ap="" appear="" appears="" application="" applications.="" appointment.="" approachable="" appropriate="" approximately="" arbitrarily="" are="" arm="" around="" arousable="" arterial="" as="" asdc="" asked="" aspect="" aspects="" assessed="" assessment.="" assessment="" assessments="" assist="" associated="" at="" attached="" attempt="" auscultation="" automatic="" available="" average="" awake="" b:="" b="" bad="" badalaty="" barnhart="" based="" baseline="" basis="" be="" became="" because="" been="" begin="" beginning="" behavior="" behavioral="" behaviors.="" behaviors="" being="" better="" between="" beyond="" big="" bl:="" blinded="" blood="" board.="" board="" both="" botzer="" buccal="" burke="" but="" by="" c="" ca="" calibrated="" campbell="" can="" candidates="" capnograph="" capnography.="" care.1-10="" care.="" care="" casamassimo="" cases="" categories="" categorize="" category.="" category="" causes="" cc="" certain="" ch-d-h.="" ch-d-h="" ch-dh="" ch-h-d="" ch-h-m="" ch-h="" change="" characteristics.="" characteristics="" characterized="" chd-h="" chest="" chi-square="" child.="" child="" children.="" children:="" children="" chloral="" classified="" clear="" clin="" clinging="" clinic="" clinical="" clinician="" clinics="" close="" closed="" clothed="" clue="" clues="" cm:="" cognitive="" collected="" collection.="" columbus="" combative="" combination="" combinations="" combined="" common="" compared="" comparison="" compatible="" completed="" comply="" component="" comprehending="" compromised="" computed="" computer="" concept.="" concept="" conclusion:="" conclusions="" condition="" conditions="" confirm="" congruent="" conscious="" consent="" consequently="" considerations="" consistency="" consistent="" consistently="" contained="" continue="" continued="" contraindicated="" contrary="" contrast="" contributing="" cook="" cooperation.="" cooperation="" cooperative="" cope="" coping="" corresponded="" could="" coury="" cried="" cry="" crying="" cuff.="" cuff="" culled="" cup="" curr="" current="" dam="" data="" dc="" december="" decreased="" deep="" deeply="" degree="" delivered="" delivery="" demands="" demonstrated="" demonstrating="" dent="" dental="" dentist.="" dentist="" dentistry.="" dentistry:="" dentistry="" dentists="" depending="" depressive="" derived="" descriptors="" desjardins="" detailed="" determination="" determine="" determined="" development="" dg:="" diazepam="" difference="" differences="" different.="" different="" difficult="" difficulty="" dilley="" dinamap="" directed="" directives="" directors.="" discussion="" display="" displayed="" disruptive="" distribution="" distributions.="" dl:="" dl="" do="" done="" dosages="" dose-response="" dose-responsive="" dose="" dr="" dramatic="" drawn="" drug="" drugs.="" drugs="" due="" duration="" during="" e.g.="" e="" each="" ease="" easily="" ediatr="" educ="" effect="" effectiveness="" effects="" eh="" either="" elective="" electronic="" elements="" elevated="" emphasis="" empirically="" enough="" entered="" environment.29="" escape="" estimated="" evaluated="" evaluations="" event="" every="" evidence="" ew="" examination="" examinations="" exception="" excluded="" exhibit="" exhibited="" expectations="" expected="" experience.12-15="" experience.="" experience="" expressing="" extensive="" extent="" extraction="" eyes="" f="" fact="" factor="" factors:="" factors="" failed="" fairly="" fairness="" farrington="" fear="" fearful="" febiger="" fg="" fh="" fig="" final="" finding="" findings.="" findings="" first="" five="" flu="" follow="" following="" follows:="" for="" foreign="" format="" found="" four="" fraone="" freely="" frequency="" frequent="" frequently="" from="" front="" fuks="" fully="" function="" further="" furthermore="" g="" gave="" general="" generally="" global="" goals="" good="" griffen="" griffith="" group.="" group="" groups="" guardian="" guidelines.29="" guidelines="" gws="" h="" had="" hands="" has="" hasty="" have="" having="" head="" healthy="" heart="" helping="" hence="" high="" higher="" highest="" history="" hl="" holan="" hood="" hospital.17="" hospital.="" hospital="" houpt="" however="" hydrate-hydroxyzine="" hydrate="" hydroxyzine.="" hydroxyzine="" hypothesis.="" hypothesis="" hypothesize="" i="" ideally="" identify="" if="" ig="" igs="" ii="" iii="" immature="" immediately="" immobilized="" important="" in="" inability="" incisors="" included:="" included="" including:="" including="" increase="" increased="" increasing="" indicated="" individual="" inducing="" informed="" initial="" initially.="" initiated="" injection.="" injection="" instance="" instructions="" interaction.="" interaction="" interactions="" interactive.="" interactive="" interested="" interesting="" interpretation="" into="" intra-="" intra-operative="" intraoperative="" intraoperatively.="" intraoperatively="" investigation="" involved="" is="" it="" its="" j:="" j="" ja:="" ja="" jackson="" je:="" je="" jg="" joshi="" jr.="" jr:="" kc="" keeping="" kg="" kgs.="" knowledge="" koenigsberg="" kupietzky="" kupieztky="" labeled="" language="" larsen="" lasted="" lasting="" lasts="" latter="" lea="" least="" less="" level="" levels="" life.="" likelihood="" likely="" likewise="" limitations="" limited="" limits="" line="" liters="" little="" local="" lochary="" longer="" longest="" lower="" m.="" m:="" m="" ma="" made="" mainly="" maintaining="" major="" manage="" management="" managing="" many="" map="" match="" materials="" mature="" matusak="" maxillary="" maximize="" maxwell="" may="" mccann="" mckee="" me="" mean="" measured="" measurements="" medical="" mellow-like="" membership:="" mentioned="" meperidine.="" meperidine="" met="" methodology.="" methodology="" methods="" mf="" mi:="" mi="" midazolam:="" midazolam="" mild="" minimal="" minimally="" minimum="" minute="" minutes.="" minutes="" mj:="" ml="" mm="" mode="" moderate="" monitoring="" monitors="" months="" moody="" moore="" more="" most="" mourino="" mouth="" movement="" ms:="" multiple="" musselman="" musson="" mutual="" n2="" nasal="" nathan="" nazif="" need="" needed="" needleless="" needleman="" needs="" neither="" nellcor="" next="" nitrous="" no="" non-interactive="" none="" nonetheless="" noninteractive="" nor="" normal="" north="" nose="" nostril="" not="" notable.="" notably="" noted="" nothing="" number="" o="" obfuscate="" observations="" observed="" obtained="" obviously="" occasionally="" occur="" occurrence="" occurring="" of:="" of="" offer="" offered.="" often="" older="" on="" one-way="" one="" only="" onset="" open="" operating="" operative="" operatory.22="" opin="" opposed="" or="" oral="" orally="" oropharyngeal="" other="" others.31="" others="" otherwise="" our="" outcome.="" outcome="" outside="" over="" overcome="" overtly="" own="" oxide="" oximeter.="" oximetry="" oxisensor="" oxygen="" p:="" p="" pa:="" page="" pamoate.="" pamoate="" papoose="" parameters.="" parameters="" paravecchio="" parent="" parents.="" participation="" patient.="" patient="" patients.="" patients:="" patients="" pattern="" pcs.="" pediatr="" pediatric="" per="" perceived="" percent="" percentage="" percents="" performing="" period.="" period="" personality="" personnel.="" personnel="" pharmacological="" phase.="" phase="" phases.="" phases="" philadelphia="" physical="" physiologic="" physiological="" pj:="" placed.="" placed="" point.="" point="" pool="" poor="" poorer="" poorman="" portion="" portions="" possible.="" possible="" post-hoc="" post-operative="" potential="" potentially="" practitioner="" practitioners.11="" pre-="" pre-operative="" precooperative="" predict="" predictable="" predicting="" predictive="" predictor="" predictors="" predoctoral="" preisch="" preliminary="" preoperative="" preoperatively="" preparation="" preschool="" preschoolers="" pressure.="" pressure="" prevented="" previously.="" primarily="" primary="" prior="" probe="" procedural="" procedure="" procedures.="" procedures="" produced="" producing="" proffered="" program="" programs.="" project="" promethazine="" promising="" promote="" prompted="" prompting:="" prompting="" properties.8="" proposed="" prospective="" provide="" provided="" provider="" providers="" ps="" pulido="" pulse="" purpose="" purposes="" q="" quadrant="" quadrants="" quiet="" r.="" radis="" randomly="" ranges="" rapid="" rate.="" rate="" rated="" rates="" ratings="" reactions="" reasonable="" received="" receiving="" recorded="" recording="" rectally="" references="" refined="" reflecting="" refuse="" refused="" refuses="" regimen.="" regimen="" regimens.="" regimens="" regression="" related="" relationship="" relatively="" remains="" rendering="" report="" reported="" requests="" required="" requirements="" requires="" requiring="" research="" respectively.="" respectively="" respiratory="" responded="" response="" responses="" responsive="" resting="" restorative="" restraint="" resulted="" resulting="" results="" retrospective="" review="" reviewed="" revision="" right="" rj:="" rl:="" roebuck="" route="" routine="" rubber="" russell="" s:="" s="" sample="" sams="" saturation.="" saturation="" saxen="" scale="" scales="" scheme="" sedate="" sedated.="" sedated="" sedating="" sedation-related="" sedation.="" sedation:="" sedation="" sedations.="" sedative="" see="" seem="" seemed="" seems="" select="" selected="" selection="" separated="" separating="" september="" setting="" settling="" several="" shapira="" shared="" sheet.="" sheet="" sheets="" shift="" short="" shown="" shy="" significant.="" significant="" significantly="" signs="" simultaneously="" single="" size.="" size="" sized="" skills.="" skills="" sl="" sleep-like="" sleep="" sleeping="" smiling.="" smiling="" smooth="" social="" some="" sometimes="" somewhat="" somewhere="" specifically="" spss="" sr="" st="" standard="" standardization="" standardized="" start="" states="" statistical="" stehle="" stepwise="" still="" stomach="" strongly="" struggle="" struggled="" struggling.="" struggling="" studied="" studies.21="" studies.="" studies="" study.="" study="" such="" suggested="" suited.="" summated="" summed="" support="" survey="" syndrome.27="" syringe="" systematic="" table="" takes="" tal="" talk="" talks="" teaching="" temperament.="" temperament="" tend="" tended="" test="" testing="" than="" that="" the="" their="" themselves="" then="" theoretically="" therapeutic="" there="" these="" they="" third="" this="" those="" three="" through="" throughout="" thus="" time="" times="" tl="" to="" toe.="" toe="" tonsil="" tooth="" topical="" total="" trained="" training="" treatment.="" treatment="" triple="" true="" two-thirds="" two="" twoyear="" unable="" uncooperative="" understood="" unless="" unpublished="" until="" unwilling="" usap:="" use="" used="" using="" usually="" values="" vann="" variable="" variables="" variance="" varied="" various="" vary="" varying="" very="" vestibule.="" via="" visit.="" visit="" visits="" vital="" vitals.="" vitals="" vs.="" w:="" w="" waggoner="" was="" weaver="" weigh="" weighed="" weight="" well-known="" were="" west="" wf:="" wf="" what="" when="" where="" whether="" which="" while="" who="" wilson:="" wilson="" with="" within="" without="" work-up="" working="" would="" year="" yearly.="" yet="" young="" younger="">