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
2
Historical perspective
Pain in children are underreported, undertreated, and
misunderstood
Children do not get the same treatment as adults who have
similar painful conditions
3
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
4
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
6
The new way
7
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
8
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
9
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
10
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
11
ASA Physical Status Classification
12
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
13
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
14
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
15
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”
16
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
17
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
18
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
19
Common Agents
 Chloral Hydrate
 Benzodiazepines
• Midazolam
• Diazepam
 Barbiturates
• Pentobarbital
• Thiopental
• Methohexital
 Opiates
• Morphine
• Fentanyl
 Ketamine
20
chloral hydrate
 Unknown mechanism of
action
 Contraindicated in hepatic
or renal disease
 May have paradoxical
excitement
 Side Effects:
• Hypotension
• Cardiopulmonary
depression
• GI upset
21
 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
22
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!
23
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
24
 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
25
 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
26
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
27
 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
28
Less common agents
 Propofol
 Ketofol
 Brevital
 Etomidate
 Dexmedetomidine
 Nitrous oxide
29
propofol (Diprivan®)
 Diprivan
30
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!
31
 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
32
Why is propofol so restricted in the pediatric population,
especially in the PICU settings?
33
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
34
propofol infusion syndrome
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
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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
35
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
36
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
37
+++
---
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
38
 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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39
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





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
40
 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
41
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
42
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
43
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
44
 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
45
 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
46
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)
48
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…
49
Sniffing position
50
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
51
BVM
52
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
53
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)
54
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…
55
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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