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 relieved38% stated pain was somewhat relieved13% 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 foundWe underestimate painWe undertreat pain both in the ED and at D/CAnd, as a result, pt are dissatisfied

But, we are improvingFrom 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 roundsSee 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. As-needed 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

MOABind to specific receptors

Mu – Analgesia, RD, euphoria, physical dependenceKappa – Analgesia, sedation, RD, miosisSigma – Dysphoria, hallucinations, tachypnea, tachycardia

• 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 5-10 minutes• Duration of Action 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 5-10 min• Duration 2.5 to 4hrs

• Routes: IV, IM, PO

• Mediates histamine release, therefore can cause hypotension

• Prices between the two are relatively similar

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

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 MorphineIV Equiv

Peak Effect

Duration

Morphine 5 mg IV

10 mg IM

60 mg PO

5 mg IV 15-30 min

1 h

2 h

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 IV Equiv

Peak Effect

Duration

Oxy-codone

5 mg po 3 mg IV 1 h 2-3 h

Codeine 200 mg po

130 mg im

5 mg IV 1 – 1.5 hr

30-60 min

4h

Ibuprofen

APAP

400 mg po

650 mg po

2 mg IV

1 mg IV

30–60 min 4 –6 h

Ketolorac 30 mg IV 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)

two fx – 1) oppose the sedative features of codeine, 2) added analgesia – not well established, but amount of added analgesia varies from 0-40%

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 receptors10% 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.

LimitationsDon’t mention baseline pain scoresMany 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 doseMod-severe pain – likely not adequate and will likely

need more than one doseMany argue that a NNT of 9 for Tx of pain is sub-

optimal?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 sedationRecognize potential problems early and Intervene when necessary

Procedural Sedation

ObjectivesGoals of PSDefinitions Indications/Contra-indicationsApproachRxAddress 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. Sedation, Analgesia,+/-Anxiolysis, +/- Amnesia

2. Facilitation of procedure

3. While ensuring pt safety (and not making ourselves cushinoid from all the stress)

Definition

Procedural SedationRefers 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 2-hr rounds rather than 5 minutes.

General ApproachPre-Sedation1. 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)-NPOP/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

1. Pre-oxygenate?

2. MonitoringBP, HR, pulse oximetry, LOC- AVPU, +/- capnography,

3. ?O2 during PS

4. Rx-Procedural Sedation Drugs

Post-Sedation

1. Monitor

2. D/c criteria

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 Is this person a good candidate for PS?

How does one do this? 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

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”

Fasting Times11

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 all-comers 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 chart396 (44%) were appropriately fasted509 (56%) were did not meet ASA fasting criteria

Of the 396 that were fasted32 had an adverse event

Of the 509 that were not fasted35 had an adverse event

No statistical difference between the rates of a/e between the two groups

Conclusions

No significant difference in a/e between fasted -v- non-fastedDeeper 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. Objectives of Sedation

2. Benefits/Risks: • risk of dying from GA 1/160,000 (all comers), no #’s for PS

3. Limitations of the therapy

4. Alternatives

5. Duration of Post-sedation monitoring

6. What they can’t do post-sedation

Contra-Indications to PS

Absolute Lack of personnel experienced with airway

management or ALS/Unfamiliar with drugsLack of appropriate monitoring or resuscitative

equipmentAllergy or sensitivity to relevant Medications

Contra-Indications to PS

RelativeAirway abnormalities: facial/dental/anatomical

abnormalities that would make BVM/intubation difficult

Hemodynamically or neurologically unstable patientsHigh aspiration/Vomiting riskASA III/IV

Preparation

PersonnelPhysician and additional “qualified patient observer”

i.e. Nurse, Physician, RTAnother Physician?Their role is to observe pts airway patency, ventilation,

vital signs and monitoring devicesNo 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. Believe that pre-oxygenating the pt may mask hypoventilation and cause retention of CO2

2. 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

In one study, 43% of men desated to <90% during sleep, 13% to <75%

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

CAEPNot mentioned in their guidelines

ACEPListed as an Option to be considered if patients

ventilatory effort cannot be visualized Not available in CHRA

Procedural Sedation ChecklistWhat 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 Airway Vent CVS

Light/

Moderate

Purposeful/Respond to verbal

normal normal normal

Deep Repeated

Painful

Possible

intervene

Possible

abnormal

Usually

normal

GA No

response

Often

intervene

Frequent

abnormal

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 PSRisk Assessment/Airway AssessmentPlan aheadTITRATION: Rapid IV boluses are more likely to

cause unexpected deteriorationThere 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

ChildrenHigher mg/kg dosingNarrower 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

Risk assessment and patient selection

2. Know How To Get To Where You Are Going Determine ideal depth of sedation/analgesia

3. Control the Environment

4. Choose the Right Rx, Dose and Route

5. Anticipate Complications

6. Recovery and Documentation

Ketamine Class

Dissociative agent – does not fall w/in the sedation classification

MOADisconnects 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

PharmacologyRoutes: IV/IM/PO/PR/INDose: IV - 1-2mg/kg IM - 4-5mg/kgOnset (min): IV – 1, IM – 5Duration: 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

LaryngospasmResult 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

intubationIn 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

KetamineHypersalivation

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/EResp events (apnea, laryngospasm, desats

<90%) – 4.5%Vomiting – 18.7%Emergence Phenomena* in the ED – 26.7%

-13.3% were considered significantEmergence Phenomena* at home – 22.4%*Defined a priori as agitation, dysphoria,

euphoria, active dreaming, nightmares, hallucinations

Significant if severe agitation, nightmares or hallucinations occurred

Significant Emergence PhenomenaKetamine – 7.1%Ketamine + Midaz group – 6.2%

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

ConclusionBoth groups had equally effective sedationMidaz 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 childrenMedian 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)

ConclusionsMidazolam does not decrease recovery agitationStudy noticed that presedation agitation increased

your risk of recovery sedation – subgroup analysis showed that they did not benefit either

Ketamine

Future QuestionsHow 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 PSBP 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

ClassSedative-hypnotic, alkyl phenol

Composed ofPurified eggSoyabean oil

PharmacologyHighly lipid soluble therefore it crosses BBB quickly

and has a large volume of distributionOnset of action: 1 min (one “arm-brain”)Duration of action: 8-10 min, but this can increase with

higher dosesClearance of the drug is not affected by renal or hepatic

dysfunction and levels do not accumulate

Route/DosingOnly available IV, 10 mg/mLDose

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 unstableElderly

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 2-2.5mg/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/peri-operative pts – may not be able to generalize to ED patients

Many decent studies in the procedural specialties (cardiology, GI) that have shown

Better patient satisfaction, Shorter recovery time, less vomiting

Few good ED studies for PS 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 studies did not have a max dose Some used adjuvant opioids (morphine or

fentanyl), others did not

Endpoint variable – Poorly defined“desired level of sedation”, Loss of lid reflexTolerating noxious stimuli w/o complaint

Pre-oxygenationVariable, study dependent

Study Type #’s Start Dose A/E

1. Swanson

2. Swanson

3. Havel

4. Guenther-Skokan

5. Miner

6. Godambe

(Adults)

Descr

Rand

Blind

Pros

Cases

Pros

Rand

4

20

43

40

21

59

0.14 mg/kg

0.21 mg/kg

1 mg/kg

1 mg/kg

Not stated

1 mg/kg

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/E7. Miner

8. Miner

9. Coll-Vincent

10. Bassett

11. Guenther

12. Pershad

Pros

Pros

Pros

Rand

Case

Series

Pros

Cons

Retro

Case

54

103

9

393

291

52

Not stated

1mg/kg

1.5mg/kg

1mg/kg

1mg/kg

1mg/kg

22 RD(41%)

5 hypoxia, 5 ass V

25 RD(49%)

5 hypoxia, 2 ass V

4 hypoxia,2 apnea

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 SedationOccurrences of RD/HypotensionProcedural SuccessPatient outcomes

Perceived PainRecall of the ProcedureSatisfaction 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 Success94% for methohexital, 98% for propofol

Patient Satisfaction/Recall/PainNo statistically significant differences

WeaknessesDon’t mention the procedural sedation endpointState BIS score <70 increases RD, avg score was 65Not BLINDEDNo significant decline in BP conflicts with most other

propofol studiesNegative 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 hospitals200 Cases

Propofol: # 1 Rx, 100% success rate for procedures. No reports of patients needing to be BVM.

What 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 this an urgent/emergent procedure?

If not, do you have options? NEED TO CONSIDER HOW IT WOULD LOOK

IF SOMETHING WENT WRONG!!!

Elderly and PSA

ElderlyMore prone to cardiopulmonary decompensationProlonged duration

Less fat/muscleCrappy kidneysRx-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

ClassNon-barbituate sedative-hypnotic

MOAWorks thru the GABA receptorSedationNo analgesia

PharmacologyDose IV: 0.1-0.2mg/kgOnset of Action: 1 minDuration of Action: 10-15 min

Contra-Indications3P’sPregnantPoor adrenal fxPrior Seizure

AdvantagesLess CVS effects b/c no histamine releaseFavorable reduction in ICP?Less RD than other agents (propofol, thiopental)

A/E & DisadvantagesRDVomitingMyoclonus 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

ClassShort acting BZD

MOAProvides anxiolysis, amnesia, sedationFacilitates action of GABA (inhibitory NT) via

inhibiting glycine

PharmacologyRoutes: IV/IM/PO/TM/PROnset: IV/IN 1-5 m, IM 5-15 m, PO >30mPeak: IV 1-2m, IM 15-60 m, IN 10m, Duration: Up to 2 hoursDose: 0.05-0.1mg/kg

Usually start w/1-2 mg titrating up to effect

Hepatic metabolism, renal clearance

AdvantagesShort half-lifeGood sedation/Amnesia/AnxiolysisReversibleMultiple administration routes

CI: Allergy to midazolam (?other BZD’s) Disadvantages/Cautions

Resp: Potent Respiratory depression b/c of increased sensitivity to CO2 (amplified by use of opioid)

CVS: Hypotension and bradycardiaCNS: Agitation, involuntary mvmt, paradoxical

hyperactivity, nystagmus, slurred speechBe very careful with elderly!!

Use smaller doses (start with 0.5, titrate by 0.25-0.50mg)

Reversal Agents

FlumazenilBZD receptor antagonistPharmacology

Onset: IV 1-2mPeak: 5-10mDuration: 45-90mDose: 0.1mg (0.01mg/kg) titrating up to a max of 2mg

CIAllergyUse of BZD for seizuresChronic BZD use – risk of ppt withdrawal seizureNot recommended in serious TCA overdose

Case reports of seizures

After administration, should monitor x 120 to monitor for rebound RD

Narcan

MOAOpioid receptor antagonistPharmacology

Onset: IV 1-2mPeak: 5-10mDuration: 1-4 hrsDose: 2.0 mg or 0.1mg to 0.2 mg (10-100mics/kg) titrated to

response up to a max of 10 mg

CI - AllergyCautious 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 have used many different outcomesResp: desats<90%, ETCOs >50, Increase >10 from

baseline, absent waveform, aspirationGI: 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 suturedLikely 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

Pre-Sedation1. 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)-NPOP/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

1. Pre-oxygenate? 2MonitoringBP, HR, pulse oximetry, LOC- AVPU, +/- capnography,

3. ?O2 during PS

4. Rx-Procedural Sedation Drugs

Post-Sedation

1. Monitor

2. D/c criteria

3. D/C instructions

General Approach: Pre-Sedation, Sedation, Post-sedation

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.