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 2 McCaig. 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 control

3

•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 3 Ducharme 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



MOA

 Bind to specific receptors  Mu – Analgesia, RD, euphoria, physical dependence  Kappa – Analgesia, sedation, RD, miosis  Sigma – 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 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 Mediates histamine release, therefore can cause hypotension Prices between the two are relatively similar 

Fentanyl

• • • • • • Onset of Action Duration 1-2min 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 Morphine Fentanyl

5 mg IV 10 mg IM 60 mg PO 50 ug IV

MorphineI V Equiv Peak Effect

5 mg IV 4 mg 15-30 min 1 h 2 h 2.5-10 min

Duration

2-4hr 4-5hr 4-5hr 30-75min

Demerol Hydro morphone

50 mg IV 75 mg IM 1 mg IV 1.5 mg IM 5 mg 5 mg 5-15 min 30 –60 min 3-4hr 15 min 30-60 min 2-3 hr 3-4 hr

Drug Oxy codone Dose

5 mg po

Morphine IV Equiv Peak Effect

3 mg IV 1 h

Duration

2-3 h

Codeine

200 mg po 130 mg im 5 mg IV

Ibuprofen APAP

400 mg po 650 mg po 2 mg IV 1 mg IV

Ketolorac

30 mg IV 1 – 1.5 hr 30-60 min 4h 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)  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 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 Review

4

   

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

effect (safety analysis).

: The sum pain intensity difference (efficacy analysis) and the proportion of patients reporting a side

4

Craen. 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 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 prescription 5  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 ED 6

5 Ngai 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

6 Petrack, 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. - unpublished 7

     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 Competence

8, 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” 8 Smithline 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 9 Vessey 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: 145-56 10 .



Clinical Policy for Procedural Sedation and Analgesia in the ED.

Annals of EM;

May 1998: 31, 663-677 11

PSA

 The practice formerly known as “conscious sedation”  Goals of PS 1.

Sedation, Analgesia,+/ Anxiolysis, +/- Amnesia 2.

3.

Facilitation of procedure While ensuring pt safety (and not making ourselves cushinoid from all the stress)

Definition



Procedural Sedation

 Refers 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 Approach

Pre-Sedation 1. 1 st 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

1

. Pre-oxygenate?

2

. Monitoring

BP, 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

Fasting Times

11   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 all comers peds sedation

12

Lots of controversy….

12 Cote, 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 had an adverse event  Of the 509 that were not fasted  35 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-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!!!

1.

Need to discuss Objectives of Sedation 2.

3.

4.

5.

6.

• Benefits/Risks: 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.

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

 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 Sedation Checklist

 What 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 Deep GA

Purposeful /Respond to verbal Repeated Painful No response normal Possible intervene Often intervene normal Possible abnormal Frequent abnormal normal 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

2.

3.

4.

5.

6.

Six Skills of Highly Effective

1.

Pediatric PSA (Adults as well)

Keep Your End Point and Goal in Mind

 Risk assessment and patient selection 

Know How To Get To Where You Are Going

Determine ideal depth of sedation/analgesia

Control the Environment Choose the Right Rx, Dose and Route Anticipate Complications Recovery and Documentation

Ketamine



Class

 Dissociative agent

–

classification does not fall w/in the sedation 

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 cases) (from a review of nearly 12,000  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 colonoscopy 13  13 Green. 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 2000

14

 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  Emergence 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 Phenomena

 Ketamine – 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 

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 2000 15 .

 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, alkyl phenol 

Composed of

 Purified egg  Soyabean oil



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 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 reflex  Tolerating noxious stimuli w/o complaint  Pre-oxygenation  Variable, study dependent

Study

1.

2.

3.

4.

5.

Swanson Swanson Havel Guenther Skokan Miner

Type #’s

4 Descr Rand Blind Pros 20 43 40 Cases Pros 21 6.

Godambe (Adults) Rand 59

Start Dose

0.14 mg/kg 0.21 mg/kg 1 mg/kg 1 mg/kg 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

7. Miner 8. Miner 9. Coll-Vincent 10. Bassett 11. Guenther

Type #’s

Pros Pros 54 103 9 Pros Rand Case Series Pros Cons 393 291 12. Pershad Retro Case 52

Start Dose A/E

Not stated 1mg/kg 1.5mg/kg 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;10:931-7 16

.

  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 Success  94% for methohexital, 98% for propofol  Patient Satisfaction/Recall/Pain  No 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 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



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



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 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 reports of seizures  After 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 have used many different outcomes  Resp: 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 (1 st 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. 1 st 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

1

. Pre-oxygenate?

2

Monitoring

BP, 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

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.