Advanced SedationFellows’ Conference

9-26-07

Thao M. Nguyen, MDPEM fellow

Emory UniversityChildren’s Healthcare of Atlanta

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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

< 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

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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

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

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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

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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

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

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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

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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

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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

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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

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

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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!

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

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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

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

+++ - - -

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

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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

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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

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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.”

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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

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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 (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

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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

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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

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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 (pre-existing 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