Transcript Sedation Controlled

Sedation
• 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
• 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 anesthesia
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Procedural Sedation
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Objectives
Review a few relevant definitions.
Review goals of procedural sedation
Review sedative agents
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Definitions
Pain: 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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More definitions
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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
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More 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)
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Controlled sedation
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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 sedation
Minimal 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 anesthesia
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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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Remember, it’s a…
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The Ideal ED Procedural Agent
No anxiety before event.
No pain during event.
No memory of event.
(Anxiolysis)
(Analgesia)
(Amnesia)
And, complete function of all protective
reflexes during the entire procedure
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What Other Characteristics
Would ED Procedural Agents Ideally Possess?
Rapid onset
Short duration of action.
Rapid offset (ie. zero residual action).
No hemodynamic effects.
Easy to use and administer
Wide therapeutic window
Minimal contraindications
Well tolerated (ie. minimal side-effects.)
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Doesn’t exist. So we settle for…
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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 sedated
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The moderately sedated
state includes:
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marked anxiolysis
full amnesia
maintenance of airway, respiratory
function, and cardiovascular function
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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 AssessmentA-Allergies- Foods, medications, latex, act.
M-Medications, including prior sedations
and how tolerated.
P-Past medical history
L-Last PO intake
E-Events leading to why patient is having
sedation
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ASA 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 & Prepare
• Additional person
• “SOAP-ME”:
• Suction
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Oxygen
Airways (BVM, oral, LMA, ETT)
Pharmacy (meds)
Monitors
Equipment (defibrillator, airway supplies,
etc)
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Reversal Agentsdon’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
have it, you
will need it
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Documentation & Monitoring
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Time out
Record q5 minutes
SPO2 & ETCO2 / HR / BP / LOC
O2 given
Medications
Interventions
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Remember for each drug…
The agent’s specific procedural role
Its onset / duration / offset
Hemodynamic effects
Contraindications
Potential side-effects
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Anxiolysis
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Anxiolysis
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The standard: benzodiazepines
Benzos (BZP’s) bind to and potentiate
GABA (CNS inhibitory neurotransmitter)
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in smaller doses: 1) anxiolysis
in larger doses:
– 1) sedation
– 2) amnesia
– 3) respiratory and CV depression
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Midazolam (Versed) the standard
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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
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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 
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Has a wide therapeutic window.
1 mg -20 mg
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Reliably produces
Anxiolysis
Sedation
Amnesia
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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)
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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 note:
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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
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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)
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Highly-lipophilic
Unique class of drug (structure is 1,6diisopropylphenol)
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)
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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) metabolism
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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 
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anxiolytic/sedating effects
Profoundly relaxing
Amnestic properties
Anticonvulsant properties
Antiemetic properties
Very short half-life
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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 
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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 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 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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Ketamine
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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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Dissociation
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neural discontinuity between the
cortico-thalamic system…
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responsible for higher-level functioning
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and the limbic system.
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responsible for emotions, motivations,
and memory
Return of coupling can be variable. This
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is turn is responsible for
“emergence phenomena”
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Dissociation effects include:
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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
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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 inducers
Metabolism increased (duration
reduced) with use of drugs that
induce Cytochrome P-450 3A4:
chronic alcohol consumption
- chronic INH use
- dexamethasone
- rifampin
- St. John’s Wort
Anticonvulsants: Tegretol, Dilantin,
Phenobarb
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Metabolic inhibitors
Metabolism 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  
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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  
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Typically indirect sympathetic stimulation
predominates ( HR BP)
If decreased sympathetic reserve, direct
effects predominate ( HR BP):
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patients in toxic, septic, or hemodynamic shock
cocaine users
pts on prolonged catecholamine infusions
tyrosine-depleted patients
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Additional effects:  
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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 
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Emergence is not rare. TOTAL7%
–Confusion
–Bad dreams
–Hallucinations
–Excitement/irrational
3%
2%
1%
1%
– Patients <10yrs old less likely; >16yrs old more likely,
to experience emergence.
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Emergence 
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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).
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Therefore, have patients recover from
Ketamine administration in a quiet, dark
room whenever possible.
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Idiot’s guide to using Ketamine.
Contraindications
Age < 3months
Upper respiratory infections
Procedures involving post. pharynx
Uncontrolled hypertension
Ischemic heart disease
CHF/pulmonary hypertension
Elevated ICP or IOP
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Doses
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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Dose
IV
IM
PO/PR
1-2 mg/kg 4-5 mg/kg 10 mg/kg
Lasts
6-60min
15-90min 25-120
min
Peds /
+Atropine +Atropine +Atropine
hyper
0.01 mg / 0.01 mg / 0.02 mg /
salivator kg
kg
kg
Adults + Versed
+ Versed + Versed
1mg
1mg
1mg
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Idiot’s guide to using Ketamine
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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
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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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Opioids
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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 is
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Semisynthetic, phenyl-piperidine
derivative.
Highly lipid soluble  rapid CNS
uptake
Rapidly redistributed from the CNS
into the adipose tissue
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Short duration of effect except… in Obese
patients, large doses  significant drugreservoir can be created in the adipose
tissue, leading to a greatly prolonged
(albeit mild) duration of effect.
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Fentanyl metabolism
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Dealkylated in the liver by our friend,
Cytochrome P-450 3A4  Norfentanyl
Urine excretion.
Once again:
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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 
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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 profile
Low complication rate
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Fentanyl Risks 
Itchy nose  quite common, quite inconsequential
Hypotension (low risk).
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Respiratory depression (low risk)
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Fentanyl, unlike Morphine, does not release histamine;
therefore the risk of  BP is low (unless combined with
sedatives or alcohol)
risk is once again low unless drug is combined with
sedatives or alcohol
Chest wall rigidity
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Rare <15 ug / kg (i.e. 7X the dose used for ED sedation)
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Idiot’s guide to using Fentanyl
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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)
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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 Sedation
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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
–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 / UH
–Back to baseline
–VS baseline
–Walk and Talk
–Drink, eat & Pee
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Or at least, pee…
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