Analgesia and Procedural Sedation Shawn Dowling Preceptor

Analgesia and Procedural
Sedation
Shawn Dowling
Preceptor
Dr. Ian Wishart
Analgesia Objectives
 Basic
Pain Pathophysiology
 Assessing Pain
 Management
 Rx
 Not
going to cover chronic pain, regional
anesthesia
Why do we need to talk pain…
1. Pain is the most common complaint of ED patients.
2. One of the most essential missions of all health care
providers should be the relief or prevention of pain and
suffering.
3. Patients judge physicians by how they treat pain.
4. We cause pain.
5. Unrelieved pain is associated with a long list of potential
negative physiologic and psychological outcomes.
Pain Pathophysiology
Black Box
Recognizing/Assessment of Pain

Patient report is primary method of pain assessment

Numeric scales can be used as a guide and as a reference for
evaluating analgesic effect, physician impression is junk
HR, BP, facial grimacing are poor indicators of pain
 Factors such as Ethnicity, Sex, Age, Cognitive functioning
affect our assessment of pain
 In the initial assessment – Ask what pain meds have
worked in the past

How good are we at recognizing and
managing Pain?
Study
 Convenience
cohort of 71 patients, tertiary ED
 >18 yrs of age
 Pts were asked to rate their pain w/VAS and NRS
@ arrival and at discharge
 These ratings were then compared to those given
by EP’s/Nurses
Results
# of pts who received Rx based on initial NRS
Results
Conclusions
 Physicians
and nurses consistently rated the pain
as less than the patient
 Pain:
 49%
stated pain was not relieved
 38% stated pain was somewhat relieved
 13% stated pain was relieved or completely relieved
 ONLY 30%
WERE SATISFIED WITH THEIR
PAIN CONTROL
 Pts
in mild-moderate pain were unlikely to receive
any analgesia
 Only 2/3 of those w/severe pain received any
analgesia & only 25% received opioids
 This
study supports what many prior studies had
found
 We
underestimate pain
 We undertreat pain both in the ED and at D/C
 And, as a result, pt are dissatisfied
 But,
we are improving
 From
1997-2001, use of analgesics in the ED increased
by 18%2
2McCaig.
National Hospital Ambulatory Medical Care Survey: 2001 ED Summary. National Center
for Health Statistics, 2003
Approach to Pain Control

Local/Regional

Will not cover today - see Bilal’s rounds
See this months CJEM for a review of hip # and femoral nerve block

Systemic
Anti-inflammatories (NSAID’s, APAP, COX-2) – see Dr.
Ukraintz’s Grand Rounds
 Opioids – This we will talk about
 Adjuvants

Rx: TCA’s, muscle relaxants, anti-convulsants
 Others: Music, distraction, etc.

The principles of pain control3
•In general, we chose if people are going to continue to have
pain, not because pain is unavoidable
•There is no reliable objective measure of pain
•Avoid the “squeaky-wheel-gets-the-oil” phenomenon of pain
control
•Pain control must be individualized
•Anticipate rather than react to pain
•When possible, let patient control his or her pain
3Ducharme
J. Acute pain and pain control:state of the art. Ann Emerg Med. June 2000;35:592-603
Opioids should be prescribed at fixed intervals to control
pain, with additional as-needed doses as required. Asneeded dosing by itself allows for gaps in pain control.
 Intramuscular or subcutaneous routes of opioids are
generally not indicated

Erratic absorption and do not allow titration
 No evidence supporting the idea that these routes are safer
 Onset of action is approximately the same as with oral
preparations

Opioids
 MOA
 Bind
to specific receptors
– Analgesia, RD, euphoria, physical dependence
 Kappa – Analgesia, sedation, RD, miosis
 Sigma – Dysphoria, hallucinations, tachypnea, tachycardia
 Mu
• Metabolized in the liver and excreted in the kidney
• In renal failure metabolites accumulate and result in prolonged
duration of action
Meperidine (Demerol)
• Onset of Action
• Duration of Action
5-10 minutes
2-3 hours
• CNS Toxicity secondary to metabolite normeperidine, a cerebral
irritant (anxiety, disorientation, tremors, seizures,
hallucinations,psychosis). These effects not antagonized by
naloxone.
• Care with Renal/Liver Disease (decreased excretion/metabolism –
leads to increased normeperidine), in the Elderly,
• Avoid in pts on MAOI’s – hypertensive emergency
• 1/8 the potency of IV Morphine with less benefits!
• More Nausea/dysphoria than morphine
• Poor ED analgesic choice!
Common Opioids

Morphine
•
•
Onset of Action
Duration
•
Routes: IV, IM, PO
5-10 min
2.5 to 4hrs

Fentanyl
•
Onset of Action
1-2min
Duration
30-75min
Routes: IV, IM, TM
Chest wall rigidity: never any cases
in ED (occurs at high doses range of
10-15mcg/kg)
Not supposed to cause histamine
release
100 x more potent than morphine
•
•
•
•
Mediates histamine release,
therefore can cause hypotension
•
•
Prices between the two are
relatively similar
•
Percocet
• Onset of Action: 30 minutes, Peak 1 hr
• Duration: 2-3 hrs
• One Percocet contains 325mg Tylenol, 5 mg oxycodone
• Maximum dose is 12/day b/c of Tylenol component (should
not exceed 4gm/7)
• SE – same as codeine
• Abuse potential – HIGH, significant euphoria
Name
Dose
MorphineI Peak
V Equiv
Effect
Duration
Morphine
5 mg IV
10 mg IM
60 mg PO
5 mg IV
15-30 min
1h
2h
2-4hr
4-5hr
4-5hr
Fentanyl
50 ug IV
4 mg
2.5-10 min
30-75min
Demerol
50 mg IV
75 mg IM
5 mg
5-15 min
30 –60 min
3-4hr
Hydro morphone
1 mg IV
1.5 mg IM
5 mg
15 min
30-60 min
2-3 hr
3-4 hr
Drug
Dose
Morphine Peak
IV Equiv Effect
Duration
Oxycodone
5 mg po
3 mg IV
2-3 h
Codeine
200 mg po 5 mg IV
130 mg im
Ibuprofen 400 mg po 2 mg IV
APAP
650 mg po 1 mg IV
Ketolorac 30 mg IV
1h
1 – 1.5 hr 4h
30-60 min
30–60 min 4 –6 h
5-6 mg IV 60-75 min 6-8 hr
T#3’s
 What
are the three components of T#3’s
 Why
are these combined/amount?
 Tylenol (300mg) – we don’t really know (many
theories including CNS COX- inhibitor)
 Codeine (8, 15, 30 or 60mg)– we’ll review
 Caffeine (15 mg, except T#4 – no caffeine)
fx – 1) oppose the sedative features of codeine, 2) added
analgesia – not well established, but amount of added
analgesia varies from 0-40%
 two
Tylenol and Codeine
 Codeine
needs to be metabolized (specific CP450
enzyme in the liver) to morphine, which then acts
as an analgesic at the CNS opioid receptors
 10%
of caucasians lack this enzyme!!!
 May be one of the factors as to why some people find
they “don’t” respond to T#3’s
APAP vs T#3’s-Systematic Review4




OBJ: To assess whether adding codeine to tylenol has an additive
analgesic effect; to assess their safety.
Design: Systematic review with meta-analysis.
Trials: 24 of 29 trials met the inclusion criteria. Models studied in
the trials were postsurgical pain (21), postpartum pain (one),
osteoarthritic pain (one), and experimentally induced pain (one).
Dosages ranged from 400 to 1000 mg tylenol and 10 to 60 mg
codeine
Main outcome measures: The sum pain intensity difference
(efficacy analysis) and the proportion of patients reporting a side
effect (safety analysis).
4Craen. Et al. Analgesic efficacy and safety of paracetamol-codeine combinations versus paracetamol alone: a systematic review BMJ 1996;313:321-325 (10 August)
Results
Single dose pooled efficacy indicated that codeine + tylenol
provided a 5% increase in analgesia
 Incidence of side effects with each treatment was comparable in
the single dose trials. In the multidose studies a significantly
higher proportion of side effects occurred with tylenol-codeine
preparations.


Conclusion:
 The difference in analgesic effect between tylenol -codeine
combinations and tylenol alone was small but s.s.
 For occasional pain relief a tylenol -codeine combination might
be appropriate but repeated use increases the occurrence of side
effects.
Limitations
 Don’t
mention baseline pain scores
 Many argued that a 5% increase is not statistically
significant (5% of 15mm on a VAS is <1mm)
 Another group looked at RR and NNT. The RR was
1.25 (1.09-1.43).
 Number Needed to Treat: 9.1 people to get 50% pain
reduction with paracetamol plus 60 mg codeine
To Use or not to Use
?
Clinically significant benefit over tylenol alone, with
increasing s/e if used for >1 dose
 Mod-severe pain – likely not adequate and will likely
need more than one dose
 Many argue that a NNT of 9 for Tx of pain is suboptimal
 ?Consider in pts who state they respond well to T#3’s
Anti-emetic or not?





Opioid-induced emesis is multi-factorial: histamine release, direct
gastroparetic effect and stimulates central chemoreceptor
Occurs in approximately 20% of patients, somewhat dose-dpndt
Effective agents are antihistamines(gravol) or ondansetron
If pt has Hx of significant emesis/nausea, give anti-emetic 15
minutes before opioid
In general, do not need to pre-treat with anti-emetic
Other analgesia options
Music: variable success,
 Distraction is a well-known aid for decreasing pain.
 Immobilization of injured extremities often decreases pain
considerably
 Use of regional anaesthesia instead of systemic analgesia
should be considered.

Pediatric pain control
Children, including neonates, do feel pain and may suffer
adverse events if that pain is not properly controlled
 Pain management in children is as important as in adults

In one study no child with an extremity fracture was discharged
with an analgesic prescription5
 Only 37% of peds w/ LE # received analgesia while in the ED
 Only 24% of peds w/2 or 3 degree burns received analgesia
while in the ED6

5Ngai
B, Ducharme J. Documented use of analgesics in the emergency department and upon release of patients with extremity fractures
[letter]. Acad Emerg Med. 1997;4:1176-1178
6Petrack, E. Pain Management in the ED: Patterns of analgesic utilization. Pediatrics 1997;99(5):711-4.
Analgesia for Musculoskeletal Injuries in Children. A Blinded RCT Comparing
Acetaminophen, Ibuprofen and Codeine by Clark, Plint, et al. - unpublished7




298 patients aged 7-18, who suffered acute MSK injuries
VAS scales were measured at scheduled intervals
RESULTS: The study groups were similar
 At 1 hour, pain scores were lowered by 24.9mm in the ibuprofen group. This
was statistically better than improvement from codeine and acetaminophen
 At 4 hours, ibuprofen (30.9mm) and Codeine (23.3) both reached s.s.
 Tylenol did not s.s. decrease pain (13.3)
 By 4 hours 72.5% vs 60.4% vs 52.9% of the codeine, ibuprofen and
acetaminophen groups respectively has achieved adequate analgesia.
CONCLUSIONS:



@ 1 Hr only ibuprofen had reached clinically significant decrease in pain
@ 4 Hrs both ibuprofen and codeine had achieved clinically significant pain cont
In the pediatric ED, ibuprofen is the initial drug of choice for acute
analgesia.
Opioids and Competence8, 9
Some have argued that the use of opioids affects ones
competence and alters ones ability to give consent
 There have been at least two studies that have challenged
this dogma



Both show that patients retain their ability to give informed
consent despite receiving analgesics
One MD makes the arguments that “If pain meds are
withheld, patients may feel pressured to consent in order
to obtain medication to relieve their suffering”
8Smithline
HA, Mader TJ, Crenshaw BJ. Do patients with acute medical conditions have the capacity to give informed consent for emergency
medicine research? Acad Emerg Med. 1999;6:776-80
9Vessey W, Siriwardena A. Informed consent in patients with acute abdominal pain. Br J Surg. 1998;85:1278-80
Procedural Sedation and
Analgesia
In Skating over thin ice, our safety
is in our speed,
-Ralph Waldo Emerson
PS is w/i our Scope of Practice
 EP’s
are well trained to
 Monitor
patients during procedural sedation
 Recognize potential problems early and
 Intervene when necessary
Procedural Sedation
 Objectives
 Goals
of PS
 Definitions
 Indications/Contra-indications
 Approach
 Rx
 Address a few of the many controversies
I apologize in advance
 This
is an area of EM with lots of ongoing
controversy, debate and research
 Unfortunately, much of the research is conflicting
and less than optimal (not done in the ED setting,
very heterogeneous, “doctored”)…
 There are some guidelines to help us though
CONSENSUS Guidelines

Innes, Murphy, Nijseen-Jordan. Procedural Sedation and
Anaglesia in the ED. Canadian Consensus Guidelines. J of EM
vol 17: 145-5610.

Clinical Policy for Procedural Sedation and Analgesia in the ED.
Annals of EM; May 1998: 31, 663-67711
PSA


The practice formerly known
as “conscious sedation” Goals of PS
1.
2.
3.
Sedation, Analgesia,+/Anxiolysis, +/- Amnesia
Facilitation of procedure
While ensuring pt safety (and not
making ourselves cushinoid from
all the stress)
Definition
 Procedural
 Refers
Sedation
to a technique of administering sedatives or
dissociative agents +/- analgesia to induce a state that
allows the patient to tolerate unpleasant procedures
while maintaining cardio-respiratory function/reflexes.
Ideal Rx?
 Would
provide analgesia, sedation, amnesia, motor
control with a rapid onset and short duration
 While being safe, effective, simple to administer
and reversible
 Obviously
does not exist and therefore these are 2hr rounds rather than 5 minutes.
General Approach
Pre-Sedation
1. 1st question should I do PS?
-emergent
or
-ASA I/II
and -no concerns w/a.w.
Hx
-PMHx, Previous GA/sedation,
Meds/all (egg/soya)
-NPO
P/E
-VS
-ASSESS a.w.
-Establish baseline LOC
-Cardio-respiratory exam
2. Consent
-verbal or written
3.Preparation
-Equipment, Personel, monitors,
IV, Rx/reversal agents,
resucitative equipment
4.Documentation
Sedation
Post-Sedation
1. Pre-oxygenate?
1. Monitor
2. Monitoring
BP, HR, pulse oximetry, LOCAVPU, +/- capnography,
2. D/c criteria
3. ?O2 during PS
4. Rx
-Procedural Sedation Drugs
3. D/C instructions
Case #1
 38
yr guy has a Dislocated shoulder. Before you
reduce it, you plan on giving him some drugs.
 What
do you need to consider before procedural
sedation?

Need to Consider


How does one do this?


Is this person a good candidate for PS?
No ED evidence for this, mostly extrapolated from
anesthesia recommendations
All upcoming recommendations are based on
CAEP/ACEP PS consensus guidelines unless
otherwise stated
CAEP guidelines
 A Quick
Word…
 March
1996 EM committee convened (peds and adults)
 Initially Canadian Anesthesia Society was involved – in
the end they did not support the final product….
 Extensive
review of literature
 Recommendations are a combination of clinical
trials (few), case series (many) and expert opinion
(majority)
Pre-Sedation
 Hx:
 Recent
respiratory illnesses,
 PMHx,
 Prior
GA/PS,
 Meds,
 Allergies (Rx, foods-why),
 Last Oral Intake

P/E
VS
 Establish baseline LOC
 Cardiac exam
 Respiratory exam
 Airway

Look, Listen, Feel
 Evaluate with 1-2-3 (TMJ-mouth-thyro-omental distance)
 Mallampati
 Obstruction- Is there any indication of airway obstruction
 Neck Mobility

Fasting Times11
These pre-operative guidelines have very little evidence –
the statement from the ASA is “there is insufficient
published evidence to address the safety of any
preoperative fasting period.”
 Therefore their guidelines are “best guesses”

Why the ASA guidelines may not
Apply to ED PS?
 Majority
of our procedures are not elective
 Our goal is not to routinely achieve GA
 Logistically unrealistic
 ?Benefit (doing procedure) outweighs risk of
waiting (emotional, physical sequelae)
Fasting and Aspiration


In 27 years, no cases of aspiration in allcomers peds sedation12
Lots of controversy….
12Cote,
Notterman, et al. Adverse Sedation Effects in Pediatrics. Pediatrics, 2004.
 Prospective
Case Series of 1014 consecutive PS
pts from a PED
 905 had fasting data on chart
 396
(44%) were appropriately fasted
 509 (56%) were did not meet ASA fasting criteria
 Of
the 396 that were fasted
 32
 Of
the 509 that were not fasted
 35
 No
had an adverse event
had an adverse event
statistical difference between the rates of a/e
between the two groups
Conclusions
 No
significant difference in a/e between fasted -vnon-fasted
 Deeper
sedation and increasing age increased
likelihood of a/e
 Rates
of a/e were relatively low
Strengths of study
 Prospective,
ED based
 All PS was done by EP’s
 I think it’s generalizable to other PED’s
Limitations of study






Sample size/power calculations were based on rates of a/e,
not aspiration risk – therefore real potential for type II
error
Not a blinded study
Aspiration was not defined
Pediatric Population - ? Applicable to adults
Almost 50% of the drugs used were ketamine -?
Applicable to adults (no use of propofol or etomidate in
this study)
Fasting times were 9.6 hrs –v- 5.7 hrs (that’s pretty friggin
close to fasting, both groups were appropriately fasted for
liquids
So, you decide to proceed w/PSA
 What
do you need to get from pt?
 What stuff/people do you need/want to mobilize?
Consent


Verbal or written – document!!!
Need to discuss
1.
2.
Objectives of Sedation
Benefits/Risks:
•
3.
4.
5.
6.
risk of dying from GA 1/160,000 (all comers), no #’s for PS
Limitations of the therapy
Alternatives
Duration of Post-sedation monitoring
What they can’t do post-sedation
Contra-Indications to PS
 Absolute
 Lack
of personnel experienced with airway
management or ALS/Unfamiliar with drugs
 Lack of appropriate monitoring or resuscitative
equipment
 Allergy or sensitivity to relevant Medications
Contra-Indications to PS
 Relative
 Airway
abnormalities: facial/dental/anatomical
abnormalities that would make BVM/intubation
difficult
 Hemodynamically or neurologically unstable patients
 High aspiration/Vomiting risk
 ASA III/IV
Preparation
 Personnel
 Physician
and additional “qualified patient observer”
i.e. Nurse, Physician, RT
 Another Physician?
 Their role is to observe pts airway patency, ventilation,
vital signs and monitoring devices
 No clear evidence to support this
Patient Monitoring
Pre-sedation VS
 Frequent LOC assessment – AVPU good tool
 Observe ventilation and respiratory status
 Intermittent BP monitoring


If possibility or plan of sedating to the level of eyes
closing


Should have a pulse oximeter
+/- ECG for pts with CVD
 These
recommendations are based on consensus,
not evidence
 Although there is no evidence that
cardiopulmonary monitoring is of evidence – lack
of evidence shouldn’t preclude it’s use
Pre-oxygenate/supplemental 02?

Two camps
1.
2.

In one study, 43% of men desated to <90%
during sleep, 13% to <75%



Believe that pre-oxygenating the pt may mask
hypoventilation and cause retention of CO2
Others say, yeah, but if I pre-oxygenate well (5
minutes or 5-7 FVC breaths), I’m afforded a 5-8
minute apnea buffer if need be
Raises question of whether desats are significant?
Evidence: nothing conclusive
EMRAP – give them O2, especially with drugs
like propofol where short periods of apnea are
expected
Capnography?
Rationale is that capnography can identify inadequate
ventilation before desats occur
 Excellent correlation between ETCO2 and PaCO2,
 Correlation not as good when measured by nasal cannula
 No evidence to suggest that it will reduce complications
but may alert to subclinical respiratory depression
(defined as ETCO2 >50, increase >10 from baseline,
absent waveform)

Recommendations
 CAEP
 Not
mentioned in their guidelines
 ACEP
 Listed
as an Option to be considered if patients
ventilatory effort cannot be visualized
 Not
available in CHRA
 Procedural
 What
Sedation Checklist
would people have by the bedside?
 What would people want nearby?
Equipment

This stuff needs to be at the bedside
PS Rx
 Reversal Agents
 Pulse Ox, BP cuff
 O2 source, NC/BVM
 +/- IV


This equipment needs to be readily available
Cardiac monitoring
 Laryngoscope/tubes
 Crash cart

Equipment
Definitions
Sedation
Response
Light/
Purposeful
Moderate /Respond
to verbal
Deep
Repeated
Painful
GA
No
response
Airway
Vent
CVS
normal
normal
normal
Possible
intervene
Often
intervene
Possible
abnormal
Frequent
abnormal
Usually
normal
Maybe
abnormal
Unfortunately…
 Although
it’s broken up into convenient categories,
monitoring levels of sedation is inherently poor
and…
 The reality is that sedation is more of a continuum
with infinite possible endpoints rather than two
possible endpoints
 Before starting the procedure, you should have
pretty good idea of what your general endpoint is
Tips for smooth PS
 Risk Assessment/Airway Assessment
 Plan
ahead
 TITRATION: Rapid IV boluses are more likely to
cause unexpected deterioration
 There is a point during the PS that a patient is at highest
risk – depends on drug – be prepared !!
 GA should be viewed as an a/e and should be avoided
when possible

In moderate sedation,
Goal is 3-4, avoid 5-6
 Does not stay in level 4 for
greater than 15 minutes


In deep sedation

Pt are not to remain in 6 for
>15 minutes
Case #2
9
yr boy presents with complex facial laceration.
He’s very anxious and distressed. You decide to
sedate him for the procedure.
 Anything
particular with Pediatrics?
 What drugs do you want to use?
 Any
specific questions you need to ask?
 Any drugs to pre-treat with?

What is the rationale for these?
Pediatrics
 Children
 Higher
mg/kg dosing
 Narrower safety margin
 <6 mo – slower drug clearance, increased BBB
penetration, decreased Lean Body Mass
Good article for peds inclined
 Attempted to prospectively look at the AAP/ASA
guidelines in PS and see outcomes (a/e, sedation depth,
sedation failure)
 Attempted to tease out some of the factors that influenced
complication rates
 Not just ED (includes all PS done in this hospital)


Hoffman. Risk Reduction in Pediatric Sedation in Application of an AAP/ASA Process Model.
Pediatrics, Feb 2002; 109:236-43
Six Skills of Highly Effective
Pediatric PSA (Adults as well)
1.
Keep Your End Point and Goal in Mind

2.
Know How To Get To Where You Are Going

3.
4.
5.
6.
Risk assessment and patient selection
Determine ideal depth of sedation/analgesia
Control the Environment
Choose the Right Rx, Dose and Route
Anticipate Complications
Recovery and Documentation
Ketamine
 Class
agent – does not fall w/in the sedation
classification
 Dissociative
 MOA
 Disconnects
the thalamus from the limbic system via
simultaneously depressing cortical function while
stimulating limbic system
 Creates trancelike state characterized by potent
analgesia, sedation, amnesia
Ketamine
 Pharmacology
 Routes:
IV/IM/PO/PR/IN
 Dose: IV - 1-2mg/kg IM - 4-5mg/kg
 Onset (min): IV – 1, IM – 5
 Duration: IV – 15 min, IM – 15-30 min
 IV:
Given as a bolus over 60 seconds, with titration
doses given (not frequently needed)
Ketamine

Indications:
Any brief painful or
emotionally disturbing
procedure in children
 Generally not
recommended for imaging
since only require
anxiolysis/ involuntary
movements may interfere
with imaging

Only Absolute CI’s are < 3 mths, >45 yrs, CAD and prior psychiatric illness
Ketamine

Advantages
Rapid onset/Short Duration
 Maintain CVS and Resp reflexes
 Minimal Resp depression



Minimal apnea and when it occurs is usually at around 1 minute
after dose and resolves rapidly
Bronchodilation – what’s the mechanism of this
Ketamine
 A/E
 Laryngospasm
 Result
of “hypersensitive” laryngeal reflex
 IR approx 0.4%1 (from a review of nearly 12,000
cases)
 And only a small fraction (2 in 12,000) required
intubation
 In one study of endoscopy – 9.4% IR with upper
endoscopy and 0% with colonoscopy13

13Green.
Ketamine Sedation for pediatric gastroenterology Procedures. J Peds Gastro. 2001
Ketamine
 Hypersalivation
 Thought
to maybe increase risk of laryngospasm secondary to
laryngeal irritation
 Brown et al (unpublished data) looked at 297 children and
found similar salivation scores between those receiving
ketamine + atropine and those receiving only ketamine
Don’t know much about study, validity, etc
 ?Significance

 Increase
muscular tone/purposeful movements
Ketamine

?Increase in ICP
1974-2003 small prospective randomized studies done with
intravenous ketamine for sedation on ventilated head injured
patients
 No change or significant improvement in ICP
 No change in cerebral perfusion pressure
 Maintains cerebral autoregulation

Vomiting
 HTN/Tachycardia


Usually not clinically significant
Emergence Phenomena - Thought to be due
to re-connection of thalamus and cortex
 Wathen.
Does Midazolam alter the clinical
effects of IV ketamine sedation in children?
Annals of EM, December 200014
RCT/double blinded: ketamine IV (1mg/kg) + glycopyrrolate
(5micrograms/kg) +/-midazolam (0.1mg/kg)
 266 pts
 Median age 6.2 yrs (4.5 mths to 16 yrs)
 Looked specifically at emergence phenomena, but also looked at
all a/e

 A/E
 Resp
events (apnea, laryngospasm, desats
<90%) – 4.5%
 Vomiting – 18.7%
 Emergence Phenomena* in the ED – 26.7%
-13.3% were considered significant
Phenomena* at home – 22.4%
 *Defined a priori as agitation, dysphoria,
euphoria, active dreaming, nightmares,
hallucinations
 Emergence
 Significant
if severe agitation, nightmares or
hallucinations occurred
 Significant
Emergence Phenomena
– 7.1%
 Ketamine + Midaz group – 6.2%
 Ketamine
 Not
statistically significant (sample and power
calculations were done)
 PLUS,
Midaz group had (statistically signific)
 More
agitation (prior studies have also shown this)
 More oxygen desats
 Conclusion
 Both
groups had equally effective sedation
 Midaz did not decrease emergence, but
increased agitation and incidence of desats
Ketamine
 Post-Recovery Agitation

Sherwin. Does Adjunctive Midazolam reduce recovery agitation after
ketamine for pediatric procedures? Annals of EM, March 200015.
 RCT/double
blinded: atropine + ketamine 1.5mg/kg +/midazolam (0.5mg/kg, max 2g)
 104 children
 Median age 6 years (12mth – 15 yrs)
 Used VAS to determine whether “not agitated” to
“worst possible agitation” – not a validated tool
 Pre-sedation
– VAS 7 midaz group, 6 in
placebo
 Recovery agitation – 5 in midaz group, 6.5 in
placebo
 Not
statistically significant, (power and sample sizes
were calculated)
 Conclusions
 Midazolam
does not decrease recovery agitation
 Study noticed that presedation agitation increased
your risk of recovery sedation – subgroup analysis
showed that they did not benefit either
Ketamine
 Future
Questions
 How
safe is it in adults?
 Is there a specific subset of people that would benefit
from pre-treatment with a BZD?
 i.e.
those that are agitated pre-sedation?
 Is
there a benefit to adding atropine?
 Is ketamine S(+) enantiomer better?
 Current
studies on-going in Europe
Case #3
 Your
working at the PLC and a 15 yr guy presents
with a dislocated patella. PMHx – nil.
 You
decide to give him some PSA.
 Senior
guys: What are your options?
 What combination are you going to use?
Case #4
 51
yr male w/ stable, new onset a-fib.
 No
Contra-Indications to PS
 BP 160/80
 What
Drug do you want to use?
 Any specific history questions based on drug?
 Why?
 How are you going to give it?
Propofol
 Class
 Sedative-hypnotic,
 Composed
 Purified
of
egg
 Soyabean oil
alkyl phenol
 Pharmacology
 Highly
lipid soluble therefore it crosses BBB quickly
and has a large volume of distribution
 Onset of action: 1 min (one “arm-brain”)
 Duration of action: 8-10 min, but this can increase with
higher doses
 Clearance of the drug is not affected by renal or hepatic
dysfunction and levels do not accumulate
 Route/Dosing
 Only
available IV, 10 mg/mL
 Dose
 As
a bolus: start low and go slow, but go
20 mg bolus, then 10-20 mg/45-60 seconds until desired effect
 Ducharme (EP in New Brunswick) suggests titrating until pt has a
verbal response to being shaken
 State no cases of apnea or serious 02 desats with this technique
(unpublished data) and propofol doses range from 40-160 mg

Propofol

Indications
 Not clear guidelines but…
 Short, intensely painful procedures
 i.e. cardioversion, hip/shoulder reduction

CI’s
 Absolute
 Egg/Soya Allergy
 Relative
 Hemodynamically unstable
 Elderly

Advantages
 Quick onset, short duration/recovery
 Anti-emetic properties
 Minimal anesthetic hangover
 Increases seizure threshold
 Good amnestic properties
 High patient satisfaction

Disadvantages and A/E

Respiratory depression/Apnea
Mechanism is via increase sensitivity to CO2 (same mechanism
as opioids and BZD, so be careful if using together)
 10-60% depending on study (typically dose dependent)


CVS: myocardial depressant
Anesthesia literature states 25-40% decrease in MAP with 22.5mg/kg
 Multiple studies have shown that it drops BP more than
thiopental or etomidate

No analgesic properties
 Pain at injection site – from protein component


Can decrease by combining with 1-2 mL lido
Propofol for PS - Adults

Numerous studies
Many of the studies are done in stable, elective, pre/perioperative pts – may not be able to generalize to ED patients
 Many decent studies in the procedural specialties (cardiology,
GI) that have shown



Few good ED studies for PS


Better patient satisfaction, Shorter recovery time, less vomiting
Most are for RSI
Many studies done for Cardioversion

Not ED setting, Use much higher doses of propofol – most use
2.5/kg,
Propofol studies in the ED
 12
studies done in the ED
6
were in Peds (n=878)
 6 were in Adults (n=114)
 Incidence
of RD: 0-50%
 Dosing variable
 Most
 Some
studies did not have a max dose
used adjuvant opioids (morphine or
fentanyl), others did not
 Endpoint
variable – Poorly defined
 “desired
level of sedation”,
 Loss of lid reflex
 Tolerating noxious stimuli w/o complaint
 Pre-oxygenation
 Variable,
study dependent
Type #’s
4
Descr 20
Rand 43
Blind
Guenther- Pros 40
Skokan
Cases
Miner
Pros 21
Study
1. Swanson
2. Swanson
3. Havel
Start Dose
0.14 mg/kg
0.21 mg/kg
1 mg/kg
4.
1 mg/kg
5.
Godambe Rand 59
(Adults)
6.
Not stated
1 mg/kg
A/E
None
2 apnea, 1 assisted
vent
5 hypoxia (12%)
14 oversedated
12 hypoxia (30%)
22 RD (41%)
5 hypoxia, 5 ass V
18 hypoxia (31%)
No apnea
Study
Type #’s
Start Dose A/E
7. Miner
8. Miner
Pros
Pros
54
Not stated
103
9
1mg/kg
1.5mg/kg
9. Coll-Vincent
10. Bassett
11. Guenther
12. Pershad
Pros
Rand
Case 393
Series
Pros
291
Cons
Retro
Case
52
22 RD(41%)
5 hypoxia, 5 ass V
25 RD(49%)
5 hypoxia, 2 ass V
4 hypoxia,2 apnea
1mg/kg
1mg/kg
1mg/kg
19 hypoxia (5%)
3 apnea w/ass V
15 hypoxia (5%)
12 partial obstr
3 apnea w/ass V
3 RD (6%)
One of the Propofol studies

Miner, et al. Randomized Clinical Trial of Propofol versus
Methohexital for PS during Fracture and Dislocation Reduction
in the ED. Acad EM, Sept 2003;10:931-716.

103 patients randomized: 52 received methohexital (brevatil)
1mg/kg followed by 0.5mg/kg Q3-5m, 51 received propofol 1mg/kg followed by 0.5mg/kg Q3-5m
All Pts received adjuvant morphine
Cont Monitoring: VS, ETCO2, Pulse oximetry, BIS scores




Incl: >18 yrs, reduction of # or dislocation
Excl: unable to give consent, allergy to either drug, intoxicated
Baseline patient characteristics were the same
 Outcomes
 Depth of Sedation
 Occurrences of RD/Hypotension
 Procedural Success
 Patient outcomes
 Perceived Pain
 Recall of the Procedure
 Satisfaction with the Procedure

 Supplemental
O2 was given at discretion of EP
 RD: defined as
 Loss
of ETCO2 waveform, >10 increase in ETCO2
from baseline, desat<90%
 Hypotension:
 Drop
>20% from baseline

Outcomes
No significant difference in depth of sedation
 RD

48% w/methohexital
 49% w/propofol
 More pts in the propofol group received suppl O2
 Those who received only 1 dose of propofol had significantly less RD –
subgroup analysis

Six pts required BVM (2 propofol, 4 methohexital), none
required BVM for >1 minute, none had sats <90% for greater
than 1 minute
 No significant declines in BP were detected

 Procedural
 94%
 Patient
 No
Success
for methohexital, 98% for propofol
Satisfaction/Recall/Pain
statistically significant differences
 Weaknesses
 Don’t
mention the procedural sedation endpoint
 State BIS score <70 increases RD, avg score was 65
 Not BLINDED
 No significant decline in BP conflicts with most other
propofol studies
 Negative study
 ???others
Unpublished Data

Be skeptical but…

EMRAP guy (Al Sacchetti) suggests:
Pre-oxygenate w/100% NRB: gives you a buffer in case pt has apneic
period
 Pre-Treat with Lido (1-2mL)
 Bolus (0.75-1.0 mg/kg), given slowly
 Perform procedure
 Followed by small bolus PRN
 With 10 yrs experience at their hospital – no complications, no BVM conveniently never described was they consider complications

 PS
registry from 6 hospitals
 200

 What
Cases
Propofol: # 1 Rx, 100% success rate for procedures. No reports of
patients needing to be BVM.
this data means???
Propofol- The arguments for and
against

PROpofol
Don’t need ED evidence
 RD is real, but very transient
 Pts go deep, but transiently
 Short recovery
 High pt satisfaction
 Low Aspiration IR
 Great anti-emetic/less V


Against Propofol







Not enough ED evidence
RD is underestimated
Low BP is underestimated
Pts go too deep-?monitoring
?doctored studies
Potency makes it difficult to
titrate
?Aspiration risk-?fasted, type II
errors
Case # 5
87 yr old man, with Distal
radius # from a FOOSH
injury.
 Ortho asks you to give
him a little sedation so
they can push on his wrist.

PMHx: COPD (on home
O2), Aortic Stenosis
 MEDS: A bunch
 All – none
 P/E – BP 100/50,
 Obese, bearded guy

What do you do?
 Do
you want to give him PSA?
 Is
 If
this an urgent/emergent procedure?
not, do you have options?
 NEED TO CONSIDER HOW IT WOULD LOOK
IF SOMETHING WENT WRONG!!!
Elderly and PSA
 Elderly
 More
prone to cardiopulmonary decompensation
 Prolonged duration
 Less
fat/muscle
 Crappy kidneys
 Rx-Rx Interactions
 More
Co-morbidities
Controversies
 Should
we use opioids with it?
 Recognize
that adding another drug increases incidence
of a/e.
 Morphine or fentanyl?
 Will
it make it’s way into the peds ED’s?
 Patient-controlled sedation?
 Is the RD clinically significant?
Etomidate
 Class
 Non-barbituate
sedative-hypnotic
 MOA
 Works
thru the GABA receptor
 Sedation
 No analgesia
 Pharmacology
 Dose
IV: 0.1-0.2mg/kg
 Onset of Action: 1 min
 Duration of Action: 10-15 min
 Contra-Indications
 3P’s
 Pregnant
 Poor
adrenal fx
 Prior Seizure
 Advantages
 Less
CVS effects b/c no histamine release
 Favorable reduction in ICP
 ?Less RD than other agents (propofol, thiopental)
 A/E
& Disadvantages
 RD
 Vomiting
 Myoclonus
 Inhibits
corticosteroid sxn, probably not an issue with
single dose/PS
Etomidate – studies
 Falk,
Zed. Etomidate for PS in the ED. Annals of
Pharmacotherapy. July-Aug 2004.
 Schenarts, Burton. Adrenocortical Dysfunction.
Academic Emergency Medicine. Jan 2001, vol 8.
 Ruth, Burton. IV Etomidate for PS in ED patients.
Academic Emergency Medicine. Jan 2001, vol 8.
Midazolam
 Class
 Short
acting BZD
 MOA
 Provides
anxiolysis, amnesia, sedation
 Facilitates action of GABA (inhibitory NT) via
inhibiting glycine
 Pharmacology
 Routes:
IV/IM/PO/TM/PR
 Onset: IV/IN 1-5 m, IM 5-15 m, PO >30m
 Peak: IV 1-2m, IM 15-60 m, IN 10m,
 Duration: Up to 2 hours
 Dose: 0.05-0.1mg/kg
Usually start w/1-2 mg titrating up to effect
Hepatic
metabolism, renal clearance
 Advantages
 Short
half-life
 Good sedation/Amnesia/Anxiolysis
 Reversible
 Multiple administration routes
Allergy to midazolam (?other BZD’s)
 Disadvantages/Cautions
 CI:
 Resp:
Potent Respiratory depression b/c of increased
sensitivity to CO2 (amplified by use of opioid)
 CVS: Hypotension and bradycardia
 CNS: Agitation, involuntary mvmt, paradoxical
hyperactivity, nystagmus, slurred speech
 Be very careful with elderly!!
 Use
smaller doses (start with 0.5, titrate by 0.25-0.50mg)
Reversal Agents
 Flumazenil
 BZD
receptor antagonist
 Pharmacology
 Onset:
IV 1-2m
 Peak: 5-10m
 Duration: 45-90m
 Dose: 0.1mg (0.01mg/kg) titrating up to a max of 2mg
 CI
 Allergy
 Use
of BZD for seizures
 Chronic BZD use – risk of ppt withdrawal seizure
 Not recommended in serious TCA overdose
 Case
 After
reports of seizures
administration, should monitor x 120 to
monitor for rebound RD
Narcan
 MOA
 Opioid
receptor antagonist
 Pharmacology
 Onset:
IV 1-2m
 Peak: 5-10m
 Duration: 1-4 hrs
 Dose: 2.0 mg or 0.1mg to 0.2 mg (10-100mics/kg) titrated to
response up to a max of 10 mg
 CI
-
 Allergy
 Cautious
use in those w/physical dependence on
opioids or
 Agitated abusive pts(?prophylactic restraints)
 After administration, should monitor x 120 to monitor for
rebound RD
What constitutes an a/e?
 Studies
 Resp:
have used many different outcomes
desats<90%, ETCOs >50, Increase >10 from
baseline, absent waveform, aspiration
 GI: vomiting,
 CVS: sBP <20%,
 Admission to higher level of care than was expected
D/C criteria

•
•
•
•
•
•
CAEP
Satisfactory a.w. patency, V,
CVS fx and hydration
LOC back to baseline
Pt can sit unassisted (if age
appropriate)
Tolerates PO intake
Pt or responsible adult
understands d/c instructions
Monitor x 2 hrs if given
reversal agent

ACEP
•
Pain and d/c are addressed
No new S/Sx
Minimal nausea
VS are w/i N range
Pt is conscious and
responds appropriately
Resp Status is @ baseline
•
•
•
•
•
 Prospective,
data collection
 1341 pts included, standardized data collection by
nurse, telephone f/u at 24 hrs
 Classified a/e as 1. Serious (life-threatening or
requiring medical intervention) and 2. Other
 Referred to a/e as Primary (1st a/e) or Secondary (if
they occurred any pt after Primary)
Results

Timing of a/e
92% during the procedure
 Serious a/e: Median time 2 m (range –104 to +40 m??)


Three a/e occurred relatively late (all hypoxia)
All were secondary a/e
 At 26m, 30m, 40m
 No pts required hospitalization based a/e from PS


No Primary a/e > 25 minutes after final medication
Weaknesses

Poor f/u – only 64%

15% of these reported an a/e
Vomiting (76%)
 Unspecified (4%)
 Ataxia (3%)
 Facial swelling, rash, AP, fatigue, nightmares, hives, confusion, HA (each
had 1 patient)

Rx of choice was versed +/- fentanyl
 One pt desated to 87% w/stridor 60 minutes after final
drug, BUT excluded b/c insufficient documentation
 No power/sample size calculations

 Looked
specifically at a/e from PS, but not
necessarily from abnormal neuromuscular dysfx –
i.e. did the kid fall walking out the ED and need
his head sutured
 Likely
an issue if we want to try to generalize this to
older kids and adults
D/C Criteria
CAEP
 Baseline physical status/mental status
 Sit and talk appropriately
 Responsible caregiver present
 Verbal instructions – return if…
 Written d/c instructions
 Minimal 2 hr observation if reversal agents used
 Document discharge condition

D/C instructions (CAEP)
 Avoid
dangerous activities (biking, swimming,
driving, etc…) until the effects of the medications
have passed
 You may feel dizzy, nauseated – start with fluids
and progress as tolerated
 Avoid EtOH, sleeping pills or any meds that can
cause drowsiness x 24 hrs
General Approach: Pre-Sedation, Sedation, Post-sedation
Pre-Sedation
1. 1st question should I do PS?
-emergent
or
-ASA I/II (include table)
and -no concerns w/a.w.
Hx
-PMHx, Previous GA/sedation,
Meds/all (egg/soya)
-NPO
P/E
-VS
-ASSESS a.w.
-Establish baseline LOC
-Cardio-respiratory exam
2. Consent
-verbal or written
3.Preparation
-Equipment, Personel, monitors,
IV, Rx/reversal agents,
resucitative equipment
4.Documentation
Sedation
Post-Sedation
1. Pre-oxygenate?
1. Monitor
2Monitoring
BP, HR, pulse oximetry, LOCAVPU, +/- capnography,
2. D/c criteria
3. ?O2 during PS
4. Rx
-Procedural Sedation Drugs
3. D/C instructions
The END
References - General








Pain Management in the ED. Emergency Medicine Reports. Feb 2002.
Pediatric Pain Control. Pediatric Emergency Medicine Reports. Aug 1999.
Acute Pain Management in the ED. EMR. July 26, 2004.
Procedural Sedation: Part 1. EMR. Oct 7, 2002.
Procedural Sedation: Part 1. EMR. Oct 21, 2002.
Pediatric Procedural Sedation: Keeping it Safe and Simple. PEMR. Feb 1, 2001.
The Six Skills of Highly Effective Pediatric Sedation. PEMR. Aug 1997.
Procedural Sedation: EMRAP, July 2004.