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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 - PowerPoint PPT Presentation
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Advanced SedationFellows’ Conference
9-26-07
Thao M. Nguyen, MDPEM fellow
Emory UniversityChildren’s Healthcare of Atlanta
2
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
3
Historical perspective
Pain in children are underreported, undertreated, and misunderstood
Children do not get the same treatment as adults who have similar painful conditions
4
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
5
Development Milestones
< 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
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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
9
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
11
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
12
ASA Physical Status Classification
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
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ASA examples
• Class I Unremarkable PMHx• Class II 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
ASA I and II are usually appropriate candidatesASA III cases should be individually consideredASA IV and V, consult anesthesia or ICU
14
Presedation evaluation
History Allergies Meds Past History – prior sedation/anesthesia Last meal Events
Exam Airway--Mallampati Heart Lungs Other
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MallampatiMallampati
Class I: soft palate, OP, uvula, pillarsClass II: soft palate, OP, portion of uvulaClass III: soft palate, base of uvulaClass 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
SOAPSSOAPSSSuctionuctionOOxygenxygenAAirway equipmentirway equipment BVM, blades, ETTBVM, blades, ETTPPharmacyharmacy
Appropriate meds, Appropriate meds, reversal agents, reversal agents, emergency drugsemergency drugs
SSpecial monitorspecial monitors
MSMAIDMMonitoronitor
CR monitor (EKG, HR, RR), CR monitor (EKG, HR, RR), BP, continuous pulse ox, BP, continuous pulse ox, capnographycapnography
SSuctionuctionMMedicine / Machineedicine / MachineAAirway equipmentirway equipmentIIV accessV accessDDrugs for rescue (includes O2)rugs for rescue (includes O2)
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Be familiar…
Route Mechanism of action How metabolized Adverse reactions Time to onset/offset
• Avoid dose stacking• Avoid multiple drugs
20
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
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
22
midazolam (Versed®)
Shortest acting benzodiazepine The most commonly used sedation
agent in children and adults Provides potent sedation,
anxiolysis, and amnesia No analgesia May be given IV, PO, IN, IM, PR Bitter aftertaste so mix in Syrpalta Burns in nose Contraindicated with narrow angle
glaucoma and shock
PO• Dose: 0.5-1 mg/kg, max 20mg• Onset: 15 min• Duration: 30-90 min
Intranasal or Sublingual • Dose: 0.2-0.5 mg/kg, max 10 mg• Onset: 10-15 minutes• Duration: 60 minutes
IV• Dose: 0.05-0.1mg/kg, max
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!
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
24
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
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
25
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
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
26
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
27
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
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
28
ketamine
COMPLICATIONS• Laryngospasm (1%)• Hypersalivation• Apnea• Vomiting• Agitation/Hallucinations/Emergence Reactions
Older aged population• Hypertension• Increased Intracranial and Intraocular Pressure• Myoclonus
29
Less common agents
Propofol Ketofol Brevital Etomidate Dexmedetomidine Nitrous oxide
30
propofol (Diprivan®)
Diprivan
31
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!
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
32
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
33
Why is propofol so restricted in the pediatric population, especially in the PICU settings?
34
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
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
36
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
37
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
+++ - - -
Ketamine AnalgesiaAmnesiaLittle respiratory/ CV depression
VomitingLaryngospasm
Propofol Reliable sedationAmnesticAnti-emetic
Respiratory & CV depressionBradycardiaNo analgesia
Dose: 1-3 mg/kg IV slow push, usually 1-1.5 mg/kgOnset: < 1 minDuration: 15-20 min
38
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
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
39
etomidate
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
40
etomidate
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, multi-
trauma 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.”
41
etomidate
Adrenal suppression Single induction dose
• ↓ cortisol & aldosterone levels (30 mins)
• transient < 24 hrs Inhibits conversion of
cholesterol to cortisol by a reversible & concentration- dependent blockade of 11ß-hydroxylase >> 17α-hydroxylase
42
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
43
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
44
dexmedetomidine (Precedexdexmedetomidine (Precedex®)®)
Relatively selective α2-adrenoceptor agonist with sedative properties
preserves cardiorespiratory function
maintained RR & oxygenation less concurrent opiate use not approved in children adverse effects
• hypotension• bradycardia
Dose: infusion 1 mcg/kg over 10 mininfusion 0.4 mcg/kg/h (0.2-0.7)
Onset: 6 mins t½ : 2 hrs
45
nitrous oxidenitrous oxide
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
46
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
47
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
48
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)
49
Hypoxemia
Is the airway patent?• Upper airway obstruction common, especially in
patients predisposed to obstructive sleep apnea (pre-existing obstruction, macroglossia, micrognathia, etc)
• Don’t merely give additional oxygen, but evaluate for obstruction, and intervene as needed…
50
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
52
BVM
53
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
54
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)
55
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…
56
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