Pediatric Procedural Sedation in the Emergency

Department

15 years later...... Are we there yet?

Bo Kennedy, MDPediatric Emergency Medicine

Urgent Painful Procedures in ED

• Fracture reductionFracture reduction

• Burn debriedmentBurn debriedment

• Abscess drainageAbscess drainage

• Laceration repairLaceration repair

• I.V. placement, I.V. placement, venipuncturevenipuncture

• Lumbar punctureLumbar puncture

• NG tube placementNG tube placement

15 years ago....

Kids were half as likely as adults to receive pain medications in the ED for painful conditions....

(fractures, burns, SS pain crises)

– 30% kids vs 60% adults got pain meds» Steve Selbst, Ann Emerg Med, 1990

15 years ago.... Undertreatment

Why?

1. Kids thought not to feel or remember pain

2. Kids expected to cry

3. Fear of adverse effects of opioids

4. Lack of training

5. Lack of consensus on meds, monitoring» Selbst, Drug Safety, 1992

» Schechter, Berde, Yaster, 1993

What we now know:

1. Kids thought not to feel pain

Infants have less maturation of their descending inhibitory pain pathways therefore they may actually experience pain more intensely compared to older children when exposed to the same stimulus.

What we now know:

1. Infants’ Memory for Procedural Pain

0

10

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60

70

80

Baseline Vaccination

Circumcised

Uncircumcised

• Distress in 87 infants during vaccination 4 to 6 months after circumcision vs. no circumcision

020406080

100120140160180200

Baseline Vaccination

Cry Duration Facial Action Score

Tadio, Lancet, 1997

seco

nds

What we now know:

1. Kids’ Memory for Procedural Pain

0

0.5

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1.5

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2.5

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3.5

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4.5

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Originalstudy

1 2 3 4

Placebo

Oral Fentanyl

Me a

n O

u ch e

r S

core

s• Children < 8 yrs with cancer

• L.P., bone marrow asp.

• self-report pain

Weisman, Arch Pediatr Adolesc Med, 1998

For ensuing procedures, all received oral fentanyl

Original study

Ensuing LPs and BMAs

1. Next steps....Impact of Memory?

Evaluation of Long term effects

• Post Traumatic Stress Disorder

• Conscious vs subconscious memory

What we now know:

2. Kids Are Expected to Cry

Difficulty in distinguishing pain from anxiety

No objective measures of pain

Parents and Healthcare Providers tend to underestimate children’s procedure related pain.

Schneider, CHC, 1992

“It hurts if I say it hurts!” David Kennedy, 5 yr old, while backpacking

2. Measures of Pain and AnxietyValidated Measures of Pain / Anxiety used for ED studies

When the patient is able to verbalize (self-report) Visual Analog Scales for Pain or Anxiety (5+ yrs of age) Oucher Score (Beyer, 3+ yrs)FACES scales (Bieri, 5+ years of age)

When the patient is too young or sedated to verbalize Measures of distress

OSBD-r information seeking verbal pain cry

(Jay, 1983) emotional support restraint flailverbal resistance scream

PBCL muscle tension pain verbalized cry (LeBaron, 1984) restraint used anxiety verbalized scream

verbal stalling physical resistance

CHEOPS Facial expression Torso position Cry (McGrath, 1985) Verbal expression Leg positionTouching wound

2. Measures of Pain and Anxiety

Needed

Practical measures developed and validated in ED for bedside assessment of pain or distress in verbal, pre-verbal, and sedated children.

3. Fear of Adverse Effects

Sedation Related Disasters Related to:

Sedations in non-hospital settings, w/o resuscitation equipment or trained personnel

Lack of use of pulse oximetry

Use of 3 or more sedating medications

Home administration of sedation meds or discharge before sufficient recovery

» Cote, Pediatrics, 2000

3. Frequency of Adverse Effects

Review of 1,022 ED procedural sedations with ketamine • No clinical evidence of pulmonary aspiration

Green, Ann Emerg Med, 1998

Review of 1,180 procedural sedations in pediatric ED• 2.3% experienced adverse events

O2 sats < 90% requiring intervention Emesis

Paradoxical reactions Apnea

Laryngospasm Bradycardia

Pena, Ann Emerg Med, 1999

3. Frequency of Adverse Effects

• 260 children

• ASA-PS I, II • Displaced

fractures

• Randomized to F/M or K/M

0

5

10

15

20

25

30

Hypoxia AirwayManeuver

BreathingCues

Oxygen Vomiting Dysphoria

F/M K/M

%

Kennedy, Ped, 1998

3. Adverse Event Timing

1,367 procedural sedations

Adverse Event: (% total) Potential life-threats:

hypoxia (84%)stridor (2%)hypotension (1%)

Other:Emesis (6%)Agitation (3%)Rash (3%)

Regimens

F/M: 108 / 660 (16%)K/M: 31 / 326 (10%)

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70

-120-110-100-90 -80 -70 -60 -50 -40 -30 -20 -10 0 10 20 30 40 50 60 70 80 90 100110120

F/M

K/M

Minutes from final PSA medications

Num

ber

Newman, Ann Emerg Med, 2003

3. Adverse Effects / Events…Next?Needed Uniform definitions, e.g.,

– Hypoxia (< __% O2 sat. on Rm Air x __ seconds)

– Hypercarbia (> __ rise in mm CO2 x __ seconds)

– Bradycardia

– Hypotension

– Airway maneuvers

Frequency/Type for specific clinical scenarios – Procedure type

– Patient type

4. Lack of Training Development of Pediatric Emergency

Medicine

Incorporation of sedation training in EM

programs

Training guided by Procedural

Sedation/Analgesia research

Next.....Uniform training standards?

4. Effect of Training

Survey: Would you sedate for reduction of a 40 angulated radius fracture in a 3 or 8 year old?

Yes 57% general EDs100% children’s hospital EDs

Krauss, Ped Emerg Care, 1998

5. Lack of Consensus ...monitoring

Monitoring Guidelines

AAP, 1989, 1992, 2002ASA, 1996, 2002 ACEP, 1998JCAHO, 2002

5. Consensus: Goals of Sedation

• Patient safety and welfare

• Minimize pain

• Minimize negative psychological response

• Maximize amnesia

• Behavior control

AAP Committee on Drugs, 1992

5. Consensus Guidelines

Definitions1. Minimal

2. Moderate

3. Deep

4. General Anesthesia

AAP, ASA, JCAHO, 2002

– Dissociative sedation ? (Ketamine)

Conscious sedation

5. Consensus Guidelines

Monitoring (Deep Sedation)1. Dedicated observer of pt’s

cardiopulmonary function

2. Pulse oximetry

3. HR, ECG AAP, ASA, JCAHO, 2002

Next ?– End-tidal CO2

5. Consensus GuidelinesNeeded

Standardization of stimulus or means to objectively determine depth of sedation, including when patient stimulation is undesirable, e.g., MRI scan.

• BIS ?• Standardized stimulus, command ?

Development of means to assess reactivity of protective airway reflexes

• different agents • different depths of sedation

5. Consensus Guidelines....NPO? Currently recommended fasting periods for

elective sedations are based more upon long-standing practice than careful study.

ASA Taskforce, Pre-op Fasting, Anesthesiology 1999

ASA/AAP NPO Guidelines for Elective SedationAge Time

Clear Liquids All Ages 2 hours

Breast milk Newborn - 6 months 4 hours

Infant formula All Ages 6 hours

Solids (light meal) > 6 Months 6 hours

5. Consensus Guidelines....NPO?

Many sedations performed in the ED do not meet elective NPO recommendations, especially for solids.

– e.g., 56% of 905 sedated children in Boston Children’s ED did not meet fasting guidelines for elective sedations.

» Agrawal, Ann Emerg Med, 2003

5. NPO......... Does it matter? Painful injuries and narcotic pain medications may

delay gastric emptying.

Correlation of fasting time with emesis is unclear in children sedated for urgent procedures.

(905 patients)Fasting time (hours)

Solids Clear Liquids

No emesis 6.8 6.0

Emesis 6.8 5.8 Agrawal, Ann Emerg Med, 2003

Pulmonary Aspiration in Children with General Anesthesia

63,180 cases - 24 with aspiration (Mayo Clinic) 1 / 373 in emergency cases

• 1 / 4,544 in elective cases

• 9 / 24 who aspirated developed respiratory symptomsWarner, Anesth, 1999

50,880 cases – 52 with aspiration (CHIP)• 21 / 52 active vomiting during induction

• 15 / 52 required intervention Risk doubled if emergency case

Borland, J Clin Anesth, 1998

3&5. Risk of Pulmonary Aspiration and other Adverse Events?

Needed

Large collaborative data bases (50-100,000+ cases) in which adverse events can be tracked to help elucidate the overall risks of adverse sedation event.

5. Lack of Consensus ...

Medications

5. 15 years later.... D.P.T. Prospective study of 63 children• mean age 3.6 years

• 29% were only mildly sedated

• Mean times to:– deepest sedation 45 minutes– discharge 4.7 hours– eating/drinking 11 + 8 hours– “ normal ” 19 + 15 hours

Terndrup, Ann Emerg Med, 1991

5. D.P.T.

• Not easily titrated

• Delayed onset of action

• Protracted sedation

• No anxiolysis or amnesia

• High rate of therapeutic failure

• High rate of serious adverse effects

• Alternative sedatives/analgesics should be considered

AAP Committee on Drugs, 1995

5. 15 years later....Consensus...meds

Medication Regimens

Opioids

Ketamine

Midazolam (0.11-0.15 mg/kg)*

Fentanyl (1.6 ± .66 mcg)*

Glycopyrollate

Fentanyl / Midazolam vs. Ketamine / Midazolam

260 children, 5-15 years of age, ASA-PS I or II

Displaced fractureRandomized

* Mean 1st reduction dose, titrated to effect

Kennedy, Peds, 1998

Ketamine (1.1 ±.52 mg/kg)*

5. F/M vs K/M: Results

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60

80

100

Deep Sedation CompleteAmnesia

Successful First Attempt

F/M

K/M

%

Kennedy, Peds,. 1998

5. F/M vs K/M: Effectiveness

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1.5

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2.5

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Pre-sedation Procedure Discharge

F/M

K/M

P< .0001

OSBD-R

(distress)

Kennedy, Peds,. 1998

F/M vs K/M : Adverse Events

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5

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15

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25

30

Hypoxia AirwayManeuver

BreathingCues

Oxygen Vomiting Dysphoria

F/M

K/M

%

P= .001

P= .001

P= .04

Kennedy, Peds,. 1998

Ketamine and Midazolam 266 children undergoing PSA in ED

Ketamine (1 mg/kg) +

PlaceboKetamine (1 mg/kg) + Midazolam (0.1 mg/kg)

Wathen, Ann Emerg Med, 2000

in single syringe

Randomized

Distress (OSBD-r)

O2 sat <90

(%)

Vomiting

(%)

Sedation

Time* (min)

Significant

Emergence (%)

Ketamine <1 1.6 19 78 7

Ket / Midaz <1 7.3 10 75 6 Agitation in > 10 yr olds: 36% w/ Midazolam vs. 6% w/ Placebo

Next...Ketamine & Schizophrenia?

Olney, J, Science, 1991

Newcomer JW, Neuropsychopharmacology. 1999

NMDA-glutamate receptor hypofunction model of schizophrenia

Next...Ketamine & Schizophrenia?

Newcomer JW, Neuropsychopharmacology. 1999

Next...Ketamine & Schizophrenia?

Newcomer JW, Neuropsychopharmacology. 1999

Next...Ketamine & Schizophrenia?

Newcomer JW, Neuropsychopharmacology. 1999

5. Next...Ketamine & 2- Adrenergic Agonists?

40 young adults undergoing elective superficial surgery

Midazolam (0.07 mg/kg IM)

Dexmedetomidine (2.5 mcg/kg IM)

Ketamine anesthesia

Levanen, J, Anesthesiology, 1995

Recovery: Hallucinations, Confusion

Unrealistic Dreams, Nightmares

Midazolam 55 %

Dexmedetomidine 5 %

5. Next steps......KetamineNeeded

– Use of validated measures of psychotomimetic effects

– Further evaluation of modulation of dysphoria by adjunctive GABA, alpha adrenergic agents (midazolam, dexmedetomidine, barbiturates)

– Avoidance of use in patients of families with history of psychosis?

– Variance across puberty?

15 years later....

Medication Regimens

N2O

N20 vs Midazolam: Suturing

Standard Care (L.E.T. + comforting)

50% N2O Oral Midazolam

N2O + Midazolam

204 children, 2-6 yrs old with facial lacerations

Luhmann, Ann Emerg Med, Jan 2001

N2O SELF-ADMINISTRATION by a 3 yr old

N20 vs Midazolam: Suturing

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6

SC M N MN SC M N MN SC M N MN

OS

BD

-R(d

istr

ess)

Luhmann, Ann Emerg Med, 2001

p=.0002

p=.003

Injection Cleaning Suturing

% Adverse Effects

Ataxia Vomiting

Std. Care 0 0

Midazolam 24 0

N2O 2 10

Midazolam + N2O

28 2

K/M vs N2O/HB

Enrollment

Oxycodone (0.2mg/kg)

Midazolam (2mg)

andKetamine (1 mg/kg)

Nitrous Oxide (50%)

& Hematoma Block (2.5 mg/kg 1% lidocaine)

Radiographs

102 children, 5-15 yrs, mid to distal forearm fractures

Luhmann, APA, SAEM 2004

K/M vs N2O/HB Efficacy: PBCL Scores

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Baseline FractureReduction

Recovery

KetamineNitrous Oxide

PBCL Score ( mean) p = 0.3

p = 0.2

p = 0.4

PBCL muscle tension pain verbalized cry restraint used anxiety verbalized scream verbal stalling physical resistance

Recovery time: K / M = 83 32 min N2O/HB = 16 10 min

(p< 0.0001)

Luhmann, APA, SAEM 2004

15 years later....

Medication Regimens:

Pentobarbital

• Long track record of safety and efficacy• However, prolonged recovery and dysphoria • New ultra-fast CT scans dramatically reduce

need for sedation

15 years later....

Medication Regimens:

Propofol

Propofol Sedative anesthetic with no analgesic but some

anti-emetic and amnestic effects.

– Used for painless diagnostic procedures,

e.g., MRI or CT scans.

– For painful procedures, frequently combined with an opioid, e.g., fentanyl, morphine

– Rapid and gentle recovery makes it an attractive agent for brief procedures.

Propofol For I.V. induction of general anesthesia:

1-3 mg/kg then continuous infusion of 75-300 mcg/kg/min.

For I.V. induction of deep sedation:1-2 mg/kg, repeated prn and/or continuous

infusion of 60-100 mcg/kg/min.

• Rapid onset: 0.5-1 minute, • Short duration of sedation: 5-10 minutes• Elimination half-life: 6-7 hours

Propofol 89 ASA I and II fasted children 2-18 years old Undergoing fracture reduction

Propofol (1 mg/kg/2 min) +67-100 mcg/kg/min*

Midazolam (0.16 mg/kg)

Morphine (0.24 mg/kg)

* Additional 1 mg/kg bolus in 81%

Results Ramsey (mean)

Amnesia (%)

Recovery (min)

Hypoxemia (%)(< 93% on RA)

Midazolam 4/6 91 76 11.6

Propofol 5/6 80 15 10.9

Havel, Acad Emerg Med, 1999

Propofol 113 children ASA-PS Class I or II, 3-18 years

old, undergoing fracture reduction

Propofol0.5-1 mg/kg (mean 4.6 mg/kg) +

Fentanyl 1-2 mcg/kg (mean 1.2 mcg/kg)

Ketamine 1-2 mg/kg (mean 2 mg/kg) +

Midazolam (0.05 mg/kg, max 2 mg)

Results OSBD-r

(mean)

Recovery time (mean) (min)

Hypoxia (%<90%)

Emesis

Propofol / Fentanyl 0.278 21 31 0

Midazolam / Ketamine 0.084 54 7 2

Godambe, Peds, 2003

Propofol 393 sedations in children, ASA-PS I/II,

94% with fractures

• Fasted minimum of 3 hrs• Pre-emptive oxygenation• 3-member sedation team, in addition to

procedure team:1. Emergency physician2. RN documenter3. ED technician to assist with airway mgt

Bassett, Ann Emerg Med, 2003

PropofolMedication protocol

• Morphine 0.1mg/kg if initially in pain, 11% of pts, mean dose 0.08

• Fentanyl 1-2 mcg/kg prior to procedure 72% of pts, mean dose 1.2 mcg/kg

• Propofol 1 mg/kg+ 0.5 mg/kg prn mean dose 2.7 mg/kg

92% with hypotension, usually transient 5% with hypoxia (< 90% sat), despite supplemental O2

– Duration 1-3 minutes

Capnography not measured No measure of procedure-related distress

Bassett, Ann Emerg Med, 2003

Propofol for ED PSA

Concerns• Difficult to titrate to desired sedation endpoints

without overshooting to apnea and hypotension.

• Loss of protective airway reflexes during apneic periods likely places patients at increased risk of pulmonary aspiration, especially if positive pressure ventilation administered. Gastric insufflation likely induces passive regurgitation.

Propofol for ED PSAConcerns (cont.)

• Patients must be carefully screened for “full stomachs” and difficult airways.

• Propofol should only be used by providers with in-depth knowledge of its adverse effects and skilled in airway assessments and positive pressure ventilation.

• When propofol is administered, an experienced provider must be dedicated to administering the sedation and managing the airway and cardiorespiratory status of the patient and not involved with the procedure being performed.

Propofol for ED PSANeeded

Large, thorough studies of patientsundergoing procedural sedation with propofol in the ED to better clarify:

1. Risks of adverse events,

1. Effectiveness of distress reduction, amnesia, and

1. Recovery and post-recovery experiences.

15 years later....

Medication Regimens:

Etomidate

Etomidate• Hypnotic anesthetic- no analgesia • Little hemodynamic effect• Frequently used in the emergency setting to induce

unconsciousness during endotracheal intubation (RSI)

When using a dose of 0.2-0.3 mg/kg • Onset of sedation: 15-45 seconds• Duration of sedation: 3-12 minutes• Rapid recovery of consciousness due to redistribution• Clearance half-life of 1-3 hours Rapid administration may result in transient apnea.

Etomidate [3 reports on non-RSI ED use] 53 children (mean age 9.7 years, range 2-17 years)

retrospective series, fracture reduction

– Mean initial dose 0.2 mg/kg (range 0.1-0.4 mg/kg)• 17% required second dose

– Morphine (mean 0.21 mg/kg) as adjunct – 83% procedural success rate

Adverse Effects / Events– No desaturation below 94% on supplemental O2

(End-tidal CO2 not measured)– No apnea, or positive pressure ventilation – No vomiting– Transient hypotension in 1 pt

Dickinson: Acad Emerg Med,2001

Etomidate 51 sedations in 48 patients - 18 were 1-25 years old

(most children underwent fracture reduction) • prospective feasibility study of adverse events

– Dose 0.1 mg/kg, repeated in 60%– Morphine or Fentanyl as adjuncts– “Adequate” sedation in 98%, Procedural success in 94%– Amnesia in 69%

Adverse Effects / Events– Face mask O2 needed in 10% (max desaturation 31%)– Bradycardia for < 30 seconds in 1 pt– Mean drop in B.P. 12 mm (max. 48 mm in 6 yr old)– Myoclonus in 8% – vomiting in 2% Ruth: Acad Emerg Med, 2001

Etomidate 150 procedures, 15 in patients 6 to 17 years of age

• retrospective, observational

– Mean initial dose 0.2 mg/kg, 2nd dose in 9%

– Adjunctive meds (opiates, benzodiazepines) in 23%

– Sedation (Aldrete Recovery Score)• Moderate 32%, • Deep 68%

Adverse Effects / Events– O2 desaturation in 5 adults-- 4 received BVM (3%)– Emesis in 2 (1.3%)

Vinson, Ann Emerg Med. 2002

Etomidate 101 patients < 19 yrs old, undergoing oncological

procedures• Retrospective chart review

– Etomidate 0.3 mg/kg

– Fentanyl 1 mcg/kg as adjunct

Adverse events/effects– Myoclonus in 18% – Vomiting in 10%, – Agitation in 4%– Hypoxemia in 2%.

McDowell: J Clin Anesth. 1995

EtomidateNeeded

Prospective study of use in ED in Children • Standardized protocol

– Dose (titrated to effect?) – Analgesic adjunct – Procedure specific– Impact of myoclonus on CT scans, suturing?

Elucidation of risk of apnea, aspiration

Next steps......• Comparative trials to determine safety and

efficacy of procedure specific sedation techniques

• Use of regional anesthesia– Fracture HB blocks

• Forearm, Ankle

– Regional Blocks• FNB

• Personalization of sedation techniques– Preferences: some don’t want to be ‘put to sleep’

Non-pharmacological strategies: Positions of Comfort

Next steps Building Bridges

Collaborative multidisciplinary studies– EM Physicians and Nurses

– Anesthesiologists

– Psychologists / Psychiatrists

– Pharmacists

– Child Life Specialists

SAFETY