SedationSedation • Vicken Y. Totten MD, FACEP MS• With help from Drs. David Cheng,

Kelly Abbrescia, Tonya M. Thompson, and many others

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Historical notes Historical notes

• Alcohol probably the earliest analgesic– Lousy analgesic, poor therapeutic window

• Opiates x 1000s years–Highly valued, scarce

• Chloroform / Ether / Nitrous Oxide–Major step towards anesthesia, analgesia

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Early anesthesiaEarly anesthesia

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Procedural SedationProcedural Sedation

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ObjectivesObjectives

Review a few relevant definitions.Review goals of procedural sedationReview sedative agents

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DefinitionsDefinitionsPain: Noxious sensation transmitted by the

nervous system to the brain; influenced by cognition and emotion.

Sedation: a spectrum of reduced responsiveness to one’s environment

Anesthesia: “no sensation” -- No response to environment, sometimes including own body needs

Analgesia: “No pain” - relief of pain without anesthesia.

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• Dissociation (aka “dissociative sedation”). “The lights are on, and nobody’s home.”

• Disruption of perception with maintenance of neural activity

• Combines: i) sedation• ii) analgesia• iii) amnesia• iv) maintenance of muscle tone

More definitionsMore definitions

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• Anxiety: unpleasant emotional and physiological state of anticipating danger, pain, or distress.

• “Anxiolysis” – breaking anxiety. Reducing anxiety without producing sedation (ie. without reducing LOC)

More definitionsMore definitions

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Controlled sedation Controlled sedation • It’s a continuum!• Reassurance general anesthesia.• To the extent that you take control away

from the patient, be prepared to substitute for those functions

• Sedation is NOT analgesia

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Levels of sedationLevels of sedationMinimal sedation / anxiolysis only

no depression of consciousness Moderate sedation / moderately depressed LOC;

still responds purposefully to verbal commands or light touch

Deep sedation / markedly depressed LOC; responds purposefully only to intense or painful

stimuli airway and respiratory function may be

depressed

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General anesthesiaGeneral anesthesia• No purposeful response to any kind of stimuli.

May have unconscious awareness of very painful stimuli (ie. HR RR BP ICP)

• airway and respiratory function profoundly depressed; typically require airway and ventilation assistance

• Autonomic & cardiovascular functions may be depressed

• We don’t want to go here.

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RememberRemember, it’s a…, it’s a…

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The Ideal ED Procedural AgentThe Ideal ED Procedural Agent

No anxiety before event. (Anxiolysis)No pain during event. (Analgesia)No memory of event. (Amnesia)

And, complete function of all protective reflexes during the entire procedure

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What Other Characteristics What Other Characteristics Would ED Procedural Agents Ideally Possess?Would ED Procedural Agents Ideally Possess?

Rapid onsetShort duration of action.Rapid offset (ie. zero residual action).No hemodynamic effects.Easy to use and administerWide therapeutic windowMinimal contraindicationsWell tolerated (ie. minimal side-effects.)

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Doesn’t exist. So we settle for…Doesn’t exist. So we settle for…• Analgesia: Local or General• Sedation Anxiolysis, • +/- amnesia for the event• Protective reflexes usually

diminished. • How much diminution of reflexes is

tolerable?

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Goal: Moderately sedatedGoal: Moderately sedated

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The The moderately sedatedmoderately sedated state includes:state includes:

• marked anxiolysis• full amnesia• maintenance of airway, respiratory

function, and cardiovascular function

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Unfortunately,Unfortunately,• Easy to overshoot from moderate

sedation to deep sedation or to the anesthetic state.– loss of airway protection– marked respiratory depression– possible cardiovascular / autonomic

depression.• Sedation not always analgesic

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AMPLE Pre-Sedation Assessment-AMPLE Pre-Sedation Assessment-

A-Allergies- Foods, medications, latex, act.M-Medications, including prior sedations and how tolerated.P-Past medical historyL-Last PO intake E-Events leading to why patient is having

sedation

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ASA classesASA classes• ASA 1: Healthy• ASA 2: Mild controlled disease, 1

system; • ASA 3: Poorly controlled disease 1

major system• ASA 4: ≥ 1 system; severe disease,

constant threat to life• ASA 5: Moribund, imminent death, not

expected to live

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Get your team & PrepareGet your team & Prepare• Additional person• “SOAP-ME”:• Suction• Oxygen• Airways (BVM, oral, LMA, ETT)• Pharmacy (meds)• Monitors• Equipment (defibrillator, airway supplies,

etc)

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Reversal Agents-Reversal Agents-don’t count on themdon’t count on them

• Naloxone– Competitively binds all 3 opiate

receptors– IV, IM, SC, SL, ETT– 0.1 mg/kg

• Flumazenil– Can terminate paradoxical reactions– 0.02 mg/kg– Lowers seizure threshold

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If you don’t If you don’t have it, you have it, you will need itwill need it

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Documentation & MonitoringDocumentation & Monitoring

• Time out • Record q5 minutes• SPO2 & ETCO2 / HR / BP / LOC

• O2 given• Medications• Interventions

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Remember for each drug…Remember for each drug…

The agent’s specific procedural role

Its onset / duration / offsetHemodynamic effectsContraindicationsPotential side-effects

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AnxiolysisAnxiolysis

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AnxiolysisAnxiolysis

• The standard: benzodiazepines• Benzos (BZP’s) bind to and potentiate

GABA (CNS inhibitory neurotransmitter)• in smaller doses: 1) anxiolysis• in larger doses: – 1) sedation – 2) amnesia– 3) respiratory and CV depression

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Midazolam (Versed) the standardMidazolam (Versed) the standard• Short acting, potent, reversible, safe.

Hydroxylated by the liver. 1 active & 2 inactive metabolites.

• Metabolites are conjugated and excreted in the urine.

• Chronic alcoholics: potentiated metabolism, shortened duration of action

• Cirrhosis or renal failure: decreased metabolism, prolonged duration of action

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Midazolam Midazolam • Highly lipid soluble at physiological pH

rapid CNS uptake• Peak effect within 1-5 minutes when

given IV• Duration of effect variable 30-60

minutes… • Longer in the obese because of

lipophilic distribution. • Activity sub-therapeutic after 7-15 mins.

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Midazolam, the good Midazolam, the good • Has a wide therapeutic window. • 1 mg -20 mg

• Reliably produces • Anxiolysis • Sedation • Amnesia

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Midazolam, the bad Midazolam, the bad In large doses, or with sedatives such as

alcohol, opioids, can produce…

Profound sedation Respiratory depression Hypotension

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Idiot’s Guide to Using Midazolam (Versed)Idiot’s Guide to Using Midazolam (Versed)

• Give initial dose & repeat q 3-5 minutes to desired effect

• Healthy adults: 1- 2 mg IV• Drunk, high, elderly, cirrhotic, or RF pts:

0.5- 1 mg IV• Chronic alcoholics — not currently

drunk: 2 – 4 mg IV initially, then 1 – 2 mg IV prn

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Side noteSide note::

• Remember, a variable amount of analgesic is going to be added.

• This may variably increase the level of sedation

• increase the potential for airway, respiratory, and cardiovascular compromise

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Idiot’s Guide to Midazolam Idiot’s Guide to Midazolam

• The role of midazolam is • Anxiolysis Sedation & Amnesia• NOT Analgesia• Just because they aren’t kicking and

screaming does not mean that they are pain free

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Diprivan (Propofol) Diprivan (Propofol)

• Highly-lipophilic • Unique class of drug (structure is 1,6-

diisopropylphenol)• Multifaceted mechanism of action:• GABA potentiation• reduced excitability of sensory and

motor neurons• inhibition of the acetylcholine receptor

channel

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Diprivan (Propofol)Diprivan (Propofol)• Emulsified in Protein-free soybean oil with

egg phosphatide• Painful on intravenous injection

(mechanism unclear) • No preservatives — must be refrigerated,

stored and handled properly• in theory, most egg-allergic patients

should tolerate this protein-free emulsion

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Diprivan (Propofol) metabolismDiprivan (Propofol) metabolism• Liver inactive conjugates.• Renal excretion • Interestingly, chronic hepatic or renal

failure has minimal effect on diprivan kinetics

• Propofol metabolism in the face of acute hepatic or renal failure has not been studied.

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Diprivan (Propofol) the good Diprivan (Propofol) the good • anxiolytic/sedating effects• Profoundly relaxing• Amnestic properties• Anticonvulsant properties• Antiemetic properties• Very short half-life

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Diprivan (Propofol) the bad Diprivan (Propofol) the bad 3-5 minutes for effect (we’re impatient!)If dose overshoot Profound sedation /

respiratory depression and/or apnea Frequent hypotension (pre-hydrate!)Worse with alcohol, opioids, or other

sedatives; Caution: elderly or impaired

hemodynamic status

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Diprivan (Propofol) the Ugly Diprivan (Propofol) the Ugly

• Works better when injected slowly

• Need to give with lidocaine• Has no analgesic properties• Sedation potentiated by analgesia• Amnesia somewhat inconsistent

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Idiot’s Guide to Using DiprivanIdiot’s Guide to Using Diprivan

• Infusion dosing: slower, but safer• 0.3 mg / kg / min IV in adults (15 to

20 mg / min)• 0.5 mg / kg / min IV in children• Infuse at this rate until patient is

adequately sedated, and then continue at this rate until the procedure is nearing completion

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Idiot’s Guide to Using PropofolIdiot’s Guide to Using Propofol

• Bolus dosing: Faster. Greater risk of apnea, hypotension

• Bolus of 0.75 mg / kg IV in adults (40 to 65 mg) and 1 mg / kg IV in children

• If needed, give second ½ bolus in 2-3 mins• Q 2-4 min, give 10-20 mg in adults (0.5

mg / kg in children) to maintain sedation.

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KetamineKetamine

• A derivative of PCP (animal tranquilizer / general anesthetic)

• Drug of abuse (“Special K”)• Dissociative anesthetic• Decouples incoming sensation from

neurologic processing• The patient has only internal or no

stimuli to respond to.

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DissociationDissociation

• neural discontinuity between the cortico-thalamic system…

• responsible for higher-level functioning• and the limbic system.• responsible for emotions, motivations,

and memory • Return of coupling can be variable. This

is turn is responsible for “emergence phenomena”

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Dissociation effects include:Dissociation effects include:

• Sedation• Muscle tone and many reflexes

maintained (eg. breathing, coughing, swallowing, corneal reflexes)

• Analgesia. Possibly greater analgesia for somatic (ie. body wall) pain as opposed to visceral (ie. organ) pain

• Amnesia

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Ketamine metabolism Ketamine metabolism • P-450 cytochrome 3A4 to Norketamine• Mildly active 20-30% activity. Does not cross

Brain-Blood Barrier sufficiently to cause dissociation

• Metabolites conjugated and excreted in the urine

• Because the conjugated metabolites have so little activity, Ketamine’s duration of action is not greatly increased in renal failure.

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Metabolic inducersMetabolic inducersMetabolism increased (duration

reduced) with use of drugs that induce Cytochrome P-450 3A4:

chronic alcohol consumption- chronic INH use- dexamethasone- rifampin- St. John’s WortAnticonvulsants: Tegretol, Dilantin,

Phenobarb48

Metabolic inhibitorsMetabolic inhibitorsMetabolism decreased (duration prolonged) by • acute alcohol consumption• macrolides (ie. erythromycin, Biaxin,

azithromycin)• antifungals• amiodarone• cimetidine• HIV protease inhibitors• cyclosporine• grapefruit juice

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Ketamine Ketamine • Complex hemodynamic effects:• Direct myocardial depressant and systemic

vasodilator• Indirectly stimulates the sympathetic system

(possibly through inhibition of NE reuptake)• Overall, typically:• myocardial excitation O2 use, HR• systemic vasoconstriction BP

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Ketamine Ketamine • Typically indirect sympathetic stimulation

predominates ( HR BP)• If decreased sympathetic reserve, direct

effects predominate ( HR BP):• patients in toxic, septic, or hemodynamic shock• cocaine users• pts on prolonged catecholamine infusions• tyrosine-depleted patients

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Additional effects: Additional effects:

• bronchodilation (use in asthmatics)• laryngospasm (contraindicated in: children <3mo

old & respiratory illnesses (?)• salivation and bronchorrhea (pre-medicate

with Atropine)• cerebral vasodilation (increased ICP) • increased IOP • emergence

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Emergence Emergence • Emergence is not rare. TOTAL 7%–Confusion 3%–Bad dreams 2%–Hallucinations 1%–Excitement/irrational 1% – Patients <10yrs old less likely; >16yrs old more likely,

to experience emergence.

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Emergence Emergence

• Anecdotal evidence suggests that emergence reactions may be reduced by avoiding visual, verbal, or tactile stimulation during the recovery period (until the patient is fully conscious).– Therefore, have patients recover from

Ketamine administration in a quiet, dark room whenever possible.

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Idiot’s guide to using Ketamine. Idiot’s guide to using Ketamine. Contraindications Contraindications

Age < 3monthsUpper respiratory infectionsProcedures involving post. pharynxUncontrolled hypertensionIschemic heart diseaseCHF/pulmonary hypertensionElevated ICP or IOP

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DosesDoses

Initial bolus below (peds & adults)Highly lipid solubility rapid

CNS uptake (eg. peak effect in 1-5mins IV)

Second ½ bolus PRN to maintain desired level of sedation.

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IV IM PO/PRDose 1-2 mg/kg 4-5 mg/kg 10 mg/kg

Lasts 6-60min 15-90min 25-120 min

Peds / hyper salivator

+Atropine 0.01 mg / kg

+Atropine 0.01 mg / kg

+Atropine 0.02 mg / kg

Adults + Versed 1mg

+ Versed 1mg

+ Versed 1mg

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Idiot’s guide to using KetamineIdiot’s guide to using Ketamine• Sedation + Analgesia + Amnesia• Can be sole agent for procedural sedation.• Typically, no need for additional analgesia.• ½ procedural dose can be used to provide

analgesia without sedation.• Consider theoretical need for additional

analgesia in procedures involving predominantly visceral (as opposed to somatic) painful stimuli.

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Analgesia. Opiods Analgesia. Opiods • 5 major opioid receptors: mu, kappa,

sigma, delta, epsilon• Opioid agonists (such as Morphine and

Fentanyl) operate predominantly at the mu (u) receptors

• perception of pain is mediated by u1- and u2-receptors, both:– centrally in the brain & supraspinally (by

inhibiting sensory dorsal horn pathways in the spinal cord)

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OpioidsOpioids• There are many different opioids (and

many different ways of classifying them), but for the purposes of procedural sedation in the ED, one opioid in particular has emerged as the agent of choice.

DEMEROL FENTANYL

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Fentanyl isFentanyl is• Semisynthetic, phenyl-piperidine

derivative.• Highly lipid soluble rapid CNS

uptake• Rapidly redistributed from the CNS

into the adipose tissue– Short duration of effect except… in Obese

patients, large doses significant drug-reservoir can be created in the adipose tissue, leading to a greatly prolonged (albeit mild) duration of effect.

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Fentanyl metabolismFentanyl metabolism• Dealkylated in the liver by our friend,

Cytochrome P-450 3A4 Norfentanyl• Urine excretion.• Once again:– Drug activity will be reduced by Cyt P-450

3A4 inducers– Drug activity will be prolonged by Cyt P-450

3A4 inhibitors

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Fentanyl Fentanyl

• Agent of choice for ED procedural sedation:Rapid onset: peak activity in 2-5 mins IV Short duration of action: sub-therapeutic within 10 mins

High potency (100 x Morphine)Favourable cardiovascular profileLow complication rate

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Fentanyl Risks Fentanyl Risks • Itchy nose quite common, quite inconsequential

• Hypotension (low risk). • Fentanyl, unlike Morphine, does not release histamine;

therefore the risk of BP is low (unless combined with sedatives or alcohol)

• Respiratory depression (low risk)• risk is once again low unless drug is combined with

sedatives or alcohol

• Chest wall rigidity• Rare <15 ug / kg (i.e. 7X the dose used for ED sedation)

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Idiot’s guide to using FentanylIdiot’s guide to using Fentanyl

• Only given IV (given over 30 secs)

• 1-2 ug / kg IV in adults, and 1-3 ug / kg IV in peds

• Use higher doses if patient:– has an induced P-450 (eg. boozer)

• Use lower doses if patient:– has an inhibited P-450 (eg. on Azithromycin)– If getting a sedative or is is <6 months old

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Pitfalls of ED SedationPitfalls of ED Sedation

• Never should take more than 30 min• If ED is too crazy• Patient not a good sedation candidate• If you can’t stay in the room with the

patient for the whole procedure• Remember this is elective!

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Discharge Criteria / ACH Discharge Criteria / ACH –Cardiovascular and Airway stability are

assured–VS are baseline and pulse Ox >97%–Easily arouseable, protective reflexes

intact–Talk, sit-up unaided, or ambulate with

minimal assistance–Patient at pre-sedation level of

responsiveness

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Discharge Criteria / Discharge Criteria / UH UH –Back to baseline–VS baseline–Walk and Talk–Drink, eat & Pee

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Or at least, pee…Or at least, pee…

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