Transcript Document

Advanced Sedation
Fellows’ Conference
9-26-07
Thao M. Nguyen, MD
PEM fellow
Emory University
Children’s Healthcare of Atlanta
Objectives
 Review historical perspective of pain & sedation
 Review presedation factors
 Review common agents of procedural sedation
 Review more restricted or up-and-coming agents
 Review common complications of sedation
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Historical perspective
Pain in children are underreported, undertreated, and
misunderstood
Children do not get the same treatment as adults who have
similar painful conditions
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Misconceptions
 Children….
• cannot experience pain due to a immature CNS
• have no memory of pain
• cannot quantify or qualify their pain (thereby pain
underestimated)
 Physicians…
• are concerned about masking symptoms
• fear adverse effects
 cardio-pulmonary decompensation
 addiction
• lack sedation training
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Development Milestones
5
< 6 mo
reflect parent’s anxiety, withdraw from pain,
grimace, cry
6-18 mo
increase anxiety, fear pain, withdraw
18-24 mo
anxious, express pain – “ouch”
3 years
localize pain and identify cause visually;
environment and distraction are very important
5-7 years
understand pain, localize pain,
more able to cooperate
The old way
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The new way
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Sedation Goals
 Alleviate anxiety
 Minimize pain
 Minimize negative psychological impact
 Maximize amnesia
 Control behavior to expedite efficiency and improve
quality
 Maintain safety and minimize risks
 Ensure safe discharge
 BETTER OUTCOME
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Definitions
 Sedation occurs along a continuum…
 Analgesia
• Relief of pain
 Minimal Sedation (anxiolysis)
• Responds to verbal commands
• Cognitive function and coordination may be impaired
• Ventilatory and cardiovascular not affected
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Definitions
 Moderate
• Responds to verbal commands alone or accompanied
by touch. Airway, ventilation and cardiovascular
maintained
 Deep
• Cannot be easily aroused but responds to noxious
stimuli. May require assistance to maintain airway
and adequate ventilation, cardiovascular maintained
 General Anesthesia
• Patient cannot be aroused. Often requires assistance
to maintain airway and positive pressure ventilation.
Cardiovascular status may be impaired
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Presedation Factors
 Factors relating to procedure:
• Duration of the procedure
• Pain as a side effect of a procedure
• Position required for the procedure
• Anxiety/Stress/inability to cooperate as a side effect of the
procedure
• Availability of rescue resources
 Factors relating to patient:
• Discussed in further slides
 Factors relating to provider:
• Dedicated sedation monitor
• Skills related to depth of sedation
• Back-up systems and ability to rescue
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ASA Physical Status Classification
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Class
Physical status
I
Healthy patient
II
Mild systemic disease, no functional limitation
III
Severe systemic disease that limits activity
IV
Incapacitating systemic disease that is a constant treat to life
V
Moribund not expected to survive 24 hrs without an operation
add E to any of above for emergent procedure
ASA examples
• Class I
• Class II
Unremarkable PMHx
Mild asthma, controlled SZ,
controlled diabetes, anemia
• Class III Moderate to severe asthma, pneumonia,
moderate obesity, uncontrolled SZ or DM
• Class IV Severe BPD, advanced degrees of
pulmonary, cardiac, hepatic, renal, or
endocrine insufficiency
• Class V Septic shock, severe trauma
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ASA I and II are usually appropriate candidates
ASA III cases should be individually considered
ASA IV and V, consult anesthesia or ICU
Presedation evaluation
 History
 Allergies
 Meds
 Past History – prior sedation/anesthesia
 Last meal
 Events
 Exam
 Airway--Mallampati
 Heart
 Lungs
 Other
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Mallampati
Class I: soft palate, OP, uvula, pillars
Class II: soft palate, OP, portion of uvula
Class III: soft palate, base of uvula
Class IV: hard palate only
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Fasting
 ASA Guidelines
• 2 hours clears
• 4 hours breast milk
• 6 hours light meal
• 8 full stomach
 ACEP
• “recent food intake is not a contraindication for
administering procedural sedation and analgesia, but
should be considered in choosing the timing and target
level of sedation”
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Informed Consent
 Make sure you have discussed it with the parents, signed
and in the chart
 We have a CHOA sedation video in English and Spanish
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Preparations
 Expect and be prepared for the worse
 You should have the skills to rescue from one level higher than
anticipate
SOAPS
Suction
Oxygen
Airway equipment
BVM, blades, ETT
Pharmacy
Appropriate meds,
reversal agents,
emergency drugs
Special monitors
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MSMAID
Monitor
CR monitor (EKG, HR, RR),
BP, continuous pulse ox,
capnography
Suction
Medicine / Machine
Airway equipment
IV access
Drugs for rescue (includes O2)
Be familiar…
 Route
 Mechanism of action
 How metabolized
 Adverse reactions
 Time to onset/offset
• Avoid dose stacking
• Avoid multiple drugs
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Common Agents
 Chloral Hydrate
 Benzodiazepines
• Midazolam
• Diazepam
 Barbiturates
• Pentobarbital
• Thiopental
• Methohexital
 Opiates
• Morphine
• Fentanyl
 Ketamine
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chloral hydrate
 Unknown mechanism of
action
 Contraindicated in hepatic
or renal disease
 May have paradoxical
excitement
 Side Effects:
• Hypotension
• Cardiopulmonary
depression
• GI upset
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 Dose: 25-100 mg/kg PO/PR
• Max 1 gram in infants
2 grams in children
 Onset: 30-60min
 Duration 4-9 hours
30 hrs in neonate
midazolam (Versed®)
 Shortest acting benzodiazepine
 PO
 The most commonly used sedation
• Dose: 0.5-1 mg/kg, max 20mg
agent in children and adults
• Onset: 15 min
 Provides potent sedation,
• Duration: 30-90 min
anxiolysis, and amnesia
 Intranasal or Sublingual
 No analgesia
• Dose: 0.2-0.5 mg/kg, max 10 mg
 May be given IV, PO, IN, IM, PR
• Onset: 10-15 minutes
 Bitter aftertaste so mix in Syrpalta
• Duration: 60 minutes
 Burns in nose
 IV
 Contraindicated with narrow angle
• Dose: 0.05-0.1mg/kg, max
glaucoma and shock
0.6mg/kg or 10mg
• Onset: 2-3 min
• Duration: 60-90 min
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pentobarbital
 barbiturates
 drug of choice for head trauma, status
epilepticus
 Side effects:

• Hypotension
• Myocardial depression
• Respiratory depression
• Bronchospasm- stimulate

histamine release

 Contraindications:
• liver failure
• CHF
• hypotension
 NO analgesia!
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Dose:
• 2-6 mg/kg/dose PO/PR/IM
• 1-3 mg/kg/dose IV
• Max dose is 150mg
Onset: 15-60 min
Duration: 1-4 hours
morphine
 Opioid
 Slower onset, longer duration
 Better for procedures that have a
longer duration ( ≥ 30 minutes)
 Histamine release can cause
flushing and itching
 Side effects
 Respiratory Depression
 Hypotension
 Bradycardia
 Nausea
 Urticaria
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 Dose: 0.1-0.2 mg/kg IV/IM/SQ,
max 10-15 mg bolus, no ceiling
 Onset: 5-10 minutes
 Peak effect: 15-30 minutes IV
30-60 minutes IM
 ½ life = 2-9 hours (neonates)
 Duration: 2-4 hours
fentanyl
 Synthetic opioid
 Excellent choice for pain
management & sedation with short
duration
 75-200 times more potent with
much shorter half-life than MSO4
 Rapid onset, elimination, and lack
of histamine release; metabolize in
liver
 chest wall rigidity syndrome
associated with doses > 15 mcg/kg
and rapid infusion; reverse with
naloxone and/or paralytics
 Respiratory depression may last
longer than the period of analgesia
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 Dose is 1-2 mcg/kg over 3-5
minutes
 Titrate to effect every 3-5 minutes
 Onset: 1-2 minutes
 Peak effect: 10 minutes
 Duration: 30-60 minutes
Reversal Agents
 Naloxone
• Competitive opiate antagonist
• 0.1 mg/kg IV/IM/SC/ET (min 0.1 mg & max 2 mg) Q2-3 minutes
until response; may repeat Q2-3 min
• ½ life = 1-2 hr
• 30 minute duration; monitor for re-sedation
• Reverses resp depression, sedation, and analgesia
• Rebound sedation and apnea may occur
 Flumazenil
• 0.01mg/kg IV (max 0.2 mg) then 0.005-0.01 mg/kg Q1 min to total
max dose 1 mg. May repeat doses in 20 min, max 3 mg in 1hr
• Do not use in kids on chronic benzo due to seizure risk
 If a reversal agent is required the patient must be observed for an
additional 2 hours from the time the reversal agent is given
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ketamine
 Provides both analgesia and
sedation
 Releases endogenous
catecholamines
• Preserves respiratory drive
and airway protective
reflexes
• Bronchodilator effect (good
for asthmatics)
• Maintains hemodynamic
stability
 Rapid infusion causes
respiratory depression and
apnea
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 Dose: 1-3 mg/kg IV
3-5mg/kg IM
 Onset: 1 minute IV
5 minute IM
 Duration:
• 60 min for sedation
• 40 to 45 min for analgesia
ketamine
 COMPLICATIONS
• Laryngospasm (1%)
• Hypersalivation
• Apnea
• Vomiting
• Agitation/Hallucinations/Emergence Reactions
 Older aged population
• Hypertension
• Increased Intracranial and Intraocular Pressure
• Myoclonus
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Less common agents
 Propofol
 Ketofol
 Brevital
 Etomidate
 Dexmedetomidine
 Nitrous oxide
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propofol (Diprivan®)
 Diprivan
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propofol
 Ultra short acting sedative
 No analgesic
 Dose dependent level of sedation
with rapid recovery time (high
lipid solubility)
 Common adverse effects:
cardiopulmonary depression,
upper airway obstruction,
hypoventilation and apnea leading
to hypoxemia
 Attending needs to be present
during the entire infusion!
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 Dose:
• 1-3 mg/kg IV
• Repeat 0.5mg/kg Q2-3 min
 Onset: 40 secs
 Duration: 1-3 mins
 Contraindicated in patients
with egg or soybean allergy.
 IV site pain: 1% lidocaine
propofol
 Lidocaine 1% 1 cc in PIV (use with tourniquet) 1 minute prior to
propofol
 INDUCTION
• Draw up 3-5 mg/kg
• Give 1-1.5 mg/kg initially over 30-60 secs, then increments of
0.5 mg/kg
• Babies < 6mos or pts with CNS pathology usually require higher
dose (at least 5 mg/kg)
• Bigger kids start @ 1 mg/kg then 0.5 mg/kg
 INFUSION
• Infusion 5 mg/kg/hr, titrate by 1-2 mg/kg/hr increments, max 18
 Concurrent opioid therapy can be associated with an increased risk
of respiratory depression and hypotension
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Why is propofol so restricted in the pediatric population,
especially in the PICU settings?
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propofol infusion syndrome
 1992, report of 5 children with croup or bronchiolitis in
an ICU, sedated with propofol and subsequently died of
metabolic acidosis and myocardial failure
- Bray -
 1998, 18 critically ill pediatric pts experienced
bradycardia, asystole, severe metabolic acidosis, lipemia,
hepatomegaly and rhabdomyolysis
- CMAJ 2001
 2001 FDA noted of higher death rates in PICU pts given
propofol for sedation in a randomized controlled trial.
- Medwatch 2001
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propofol infusion syndrome
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Cornfield & Tegtmeyer
“Continuous Propofol Infusion in 142 Critically Ill Children”
Retrospective review of a case series
18 mo period; PICU & BMT; age 2 mo – 18 yo
Propofol infusion < 50 mcg/kg/min = 3 mg/kg/h
• Additional bolus of 1 mg/kg Q1h
 RESULTS
• Median infusion 16.5 hrs; longest < 20 hrs
• Adequate sedation (no extubation or CVL dislodgement)
• Not assoc with metabolic acidosis or hemodynamic compromise
• Conclusion: continuous infusion of propofol for extended periods
of time should not exceed 67 mcg/kg/min = 4 mg/kg/h
Pediatrics 2002;110(6):1177-1181
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propofol infusion syndrome
 Described in critically ill children given long term
propofol infusion
 Severe metabolic acidosis and rhabdomyolysis
associated with hepatomegaly, lipemia, myocardial
failure and hyperkalemia
 Relative absence in adults
 Not associated with brief procedural sedation
 Limited use to the physicians on the sedation team
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ketofol
 1:1 mixture of ketamine
10 mg/ml and propofol
10 mg/ml
 In theory, the opposing
hemodynamic &
respiratory effects of each
drug might be
complementary and
minimize overall adverse
effects
 Prospective study of 114
procedural sedation and
analgesia events for
orthopedic procedures;
effective & safe; fast
recoveries (median 15
minutes)
- Willman 2007
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+++
---
Ketamine
Analgesia
Amnesia
Little respiratory/
CV depression
Vomiting
Laryngospasm
Propofol
Reliable sedation
Amnestic
Anti-emetic
Respiratory &
CV depression
Bradycardia
No analgesia
Dose: 1-3 mg/kg IV slow
push, usually 1-1.5 mg/kg
Onset: < 1 min
Duration: 15-20 min
methohexital (Brevital®)
 Rapid, ultra short-acting
barbiturate anesthetic
 Indication similar to propofol
and with egg or soy allergies;
$$$
 Contraindicated in porphyria,
temporal seizures
 Rapid infusion can lead to
transient hypotension &
tachycardia; respiratory
depression/apnea
 Associated with hiccups,
coughing, muscle twitching &
rigidity, salivation, emergence
delirium
 Metabolism in the liver
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 Dose:
• IV 1-2 mg/kg induction of 1%;
3 mg/kg/hr infusion, titrate by 1.5
• IM 6.6-10 mg/kg of 5% sol’n
• PR 25 mg/kg, 10%, max 500 mg
 Contraindicated in pts < 1 mo
 Onset: 30 secs IV
2-10 mins IM
5-15 mins PR
 Duration: 5-10 mins IV
etomidate
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Ultra short acting sedative-hypnotic
Unknown mechanism of action
Rapid IV induction
Minimal respiratory depression or
hemodynamic instability
No histamine release
Myocardial & cerebral protection
No analgesia
Adverse Reactions
• Nausea and vomiting – 5%
• Local burning infusion pain
• Myoclonic movements
• Inhibits steroid synthesis
Contraindications:
• Seizure disorder
• Children < 2 y/o
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Dose: 0.2-0.5 mg/kg IV
Induction 0.3 mg/kg IV over 30-60 sec
Duration: 5-10 min
Full recovery in 30 min
Re-dose with 0.1mg/kg every 5-10
minutes as needed
 Lidocaine 1% for iv site pain
etomidate
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 Synthesized in 1964
 1972 clinical practice in Europe
 1983 approved for use in the US; promoted as a safe agent for
continuous sedation in mechanically ventilated pts.
• Trend toward increased mortality reported in critically ill, multitrauma pts receiving continuous infusion etomidate in the ICU;
25% vs 44%
- Ledingham and Watt
• Retrospective review of 428 multi-trauma pts from 1969-1982
 increased mortality 28% vs 47%; p< 0.05
 More pronounced with ↑ MV duration and means of sedation
(benzos 28% vs 77% etomidate; p< 0.0005)
 All showed at least one subnormal level of serum cortisol
 Long-term use of etomidate fell into disfavor
 Package insert for etomidate: “this formulation is not intended for
administration by prolonged infusion.”
etomidate
 Adrenal suppression
 Single induction dose
• ↓ cortisol &
aldosterone levels
(30 mins)
• transient < 24 hrs
 Inhibits conversion of
cholesterol to cortisol
by a reversible &
concentrationdependent blockade
of 11ß-hydroxylase
>> 17α-hydroxylase
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etomidate controversy
 Ideal first-line induction agent for select ED pts requiring
RSI intubation; stability and predictability
 Etomidate single use in septic shock
• Adrenal insufficiency is transient and clinically not
relevant VS
• Etomidate should be abandoned altogether in the ICU
 increased the risk of adrenal insufficiency by 12X;
 transient effect prolonged in critically ill pts;
 poor prognosis associated with adrenal
insufficiency in critical illness
- Annane 2005
 Meta-analyses support the use of low-dose steroid
replacement among pressor dependent septic shock pts
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etomidate controversy
 3 approaches to the use of etomidate in septic shock pts:
• eliminate etomidate use altogether in this subgroup
 Ketamine?
• use a lower dose of etomidate in conjunction with
lower doses of other induction agents
• routinely administer concomitant corticosteroids with
etomidate
 Annane study showed 94% (68/72) were
nonresponders to high-dose cosyntropin
stimulation test
 Mortality cost of adrenal suppression by etomidate
offset by corticosteroid administration
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dexmedetomidine (Precedex®)
 Relatively selective α2adrenoceptor agonist with
sedative properties
 preserves cardiorespiratory
function
 maintained RR & oxygenation
 less concurrent opiate use
 not approved in children
 adverse effects
• hypotension
• bradycardia
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 Dose:
infusion 1 mcg/kg over 10 min
infusion 0.4 mcg/kg/h (0.2-0.7)
 Onset: 6 mins
 t½ : 2 hrs
nitrous oxide
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 sweet smelling inorganic gas by Priestly in 1772
 late 1800s dental procedures
 analgesic & sedative properties
• 20% N2O = morphine
 rapid onset and recovery
• 30-80% N2O  LOC
 suitable for use when short acting analgesia/sedation required for brief
procedures
 adverse reactions:
• CNS depression
• Cardiorespiratory depression
• Exacerbate existing airway obstruction
• Worsened existing pneumothorax
• Megaloblastic anemia  affects vitamin B12 metabolism
nitrous oxide
 2 large prospective studies
• 0.35% (27 of 7679 children) major adverse events
 O2 desats, airway obstruction, apnea, bradycardia,
oversedation
• All resolved within minutes of discontinuation
• Higher adverse event in pts < 1 yo (2.3%) and
received additional psychotropic drugs
• 5% minor adverse events: euphoria, nausea, vomiting,
dizziness, parasthesia
- Pena 1999
- Gall 2001
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nitrous oxide
 Entonox
• fixed concentration of 50% N2O / 50% O2
• self-administered via a demand valve system with a
weighted mask
• oversedation less likely; young children cannot use
 The Matrix Quantiflex nitrous oxide delivery system
• Variable delivery of N2O (0-70%) with oxygen
administered via a constant gas flow system that does
not require patient effort to trigger
• oversedation & respiratory depression more likely
• Need constant monitor
47
Common Problems
 Inadequate sedation
• Assessment/reassessment
• Evaluation of efficacy and duration
• Timely intervention
 Excessive sedation/narcosis
• Special circumstances (shock, airway, CNS and concurrent
medications)
 Most common causes of death
• Hypoxemia
• Airway obstruction
• Cardiovascular collapse (myocardial depression, vasodilation,
bradycardia, hypotension, arrhythmias)
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Hypoxemia
 Is the airway patent?
• Upper airway obstruction common, especially in
patients predisposed to obstructive sleep apnea (preexisting obstruction, macroglossia, micrognathia, etc)
• Don’t merely give additional oxygen, but evaluate for
obstruction, and intervene as needed…
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Sniffing position
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Hypoxemia (cont’d)
 If airway is clear, is patient breathing?
• Yes, but shallow/infrequent
 Stimulate to breathe
 Support with BVM, intubate if prolonged support
needed (or unstable airway)
 Consider reversal agent (if available for choice of
sedative)
• No
 As above, but don’t waste time attempting
stimulation or reversal – provide PPV
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BVM
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Hypotension
 Treatment based on tachy/bradycardia, perfusion, sedative
 Usually due to excessive sedation with myocardial insufficiency
(esp. with opiates) and/or vasodilation (esp. barbiturates, opiates,
benzos)
• Verify/obtain patent airway, assist ventilation, intubate if needed,
give 100% O2
• Fluid bolus 10-20 cc/kg rapidly
• Chest compressions if bradycardia or PEA
• Discontinue sedation (esp. if using continuous infusion)
• Consider reversal agent, atropine, epinephrine
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Post-sedation
 If reversal agent administered, patient must be observed
for at least 2 hours after last reversal dose
 Discharge criteria
• Airway patent and stable vital signs
• Easy arousability
• Ability to talk
• Ability to sit up unaided
• Well hydrated
• Taking po
• Patient/home care provider able to understand written
instructions
• Patient has safe transportation home (patient may
NOT drive self home)
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Conclusions
 Sedation occurs along a continuum
 Most serious adverse effects can be avoided by
appropriate patient and drug selection and assessment
• When in doubt, obtain anesthesiology consult
 Anticipate potential problems, and be prepared to
intervene
 PPV by BVM more important than sedation reversal
 Titrate, titrate, titrate…
 Evaluate, evaluate, evaluate…
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Citations
 Annane D. ICU physicians should abandon the use of etomidate! Intensive Care Med
2005;31:325-6
 Bray RJ. Propofol infusion syndrome in children. Paediatr Anaesth. 1998;8:491-9
 Chang P, Warren D et al. Use of propofol sedation in the pediatric emergency department.
Paediatrics & Child Health. 2003;8
 FDA issues warning on propofol. CMAJ 2001;164(11):1608
 Gall O. Adverse events of premixed nitrous oxide & oxygen for procedural sedation in children.
Lancet. 2001;358:1-2
 Hom J. Pediatics, Sedation. emedicine.com. Last updated January 29, 2007 Kraus & Green.
Sedation and analgesia for procedures in children. NEJM. 2000.342:939
 Jackson WL. Should we use etomidate as an induction agent for endotracheal intubation in
patients with septic shock? A critical appraisal. Chest. 2005;127:1031-8
 Morris C. Etomidate for emergency anaesthesia mad, bad and dangerous to know? [editorial].
Anaesthesia. 2005;60:737-40
 Murray H. Etomidate for endotracheal intubation in sepsis. Acknowledging the good while
accepting the bad. Chest. 2005;127:1031-8
 Pena BM. Adverse events of procedural sedation & analgesia in a PED. Ann Emerg Med.
1999;34:483-91
 Willman EV. A Prospective Evaluation of “Ketofol” (Ketamine/Propofol combination) for
Procedural Sedation and Analgesia in the Emergency Department. Annals EM. 2007; 49(1):23-30.
 Wooltorton E. Propofol: contraindicated for sedation of pediatric intensive care patients. CMAJ.
2002;167(5)
 Zed PJ. Etomidate for rapid sequence intubation in the emergency department: is adrenal
suppression a concern? CJEM. 2006;8(5):347-50
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