Sedation
• Vicken Y. Totten MD, FACEP MS
• With help from Drs. David Cheng,
Kelly Abbrescia, Tonya M.
Thompson, and many others
1
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
2
Early anesthesia
3
Procedural Sedation
4
Objectives
Review a few relevant definitions.
Review goals of procedural sedation
Review sedative agents
5
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.
6
More definitions
• 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
7
More definitions
• Anxiety: unpleasant emotional and
physiological state of anticipating
danger, pain, or distress.
• “Anxiolysis” – breaking anxiety.
Reducing anxiety without producing
sedation (ie. without reducing LOC)
8
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
9
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
10
General 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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Remember, it’s a…
12
The 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
13
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…
• Analgesia: Local or General
• Sedation Anxiolysis,
• +/- amnesia for the event
• Protective reflexes usually
diminished.
• How much diminution of reflexes is
tolerable?
15
Goal: Moderately sedated
16
The moderately sedated
state includes:
• marked anxiolysis
• full amnesia
• maintenance of airway, respiratory
function, and cardiovascular function
17
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
18
AMPLE Pre-Sedation Assessment-
A-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
20
Get your team & Prepare
• Additional person
• “SOAP-ME”:
• Suction
• Oxygen
• Airways (BVM, oral, LMA, ETT)
• Pharmacy (meds)
• Monitors
• Equipment (defibrillator, airway supplies,
etc)
21
Reversal Agents-
don’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
22
If you don’t
have it, you
will need it
23
Documentation & Monitoring
• Time out
• Record q5 minutes
• SPO2 & ETCO2 / HR / BP / LOC
• O2 given
• Medications
• Interventions
24
Remember for each drug…
The agent’s specific procedural
role
Its onset / duration / offset
Hemodynamic effects
Contraindications
Potential side-effects
25
Anxiolysis
26
Anxiolysis
• 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
27
Midazolam (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
28
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.
29
Midazolam, the good
• Has a wide therapeutic window.
• 1 mg -20 mg
• Reliably produces
• Anxiolysis
• Sedation
• Amnesia
30
Midazolam, the bad
In large doses, or with sedatives such as
alcohol, opioids, can produce…
Profound sedation
Respiratory depression
Hypotension
31
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
32
Side 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
33
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
34
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
35
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
36
Diprivan (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.
37
Diprivan (Propofol) the good
• anxiolytic/sedating effects
• Profoundly relaxing
• Amnestic properties
• Anticonvulsant properties
• Antiemetic properties
• Very short half-life
38
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
39
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
40
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
41
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.
42
43
Ketamine
• 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.
44
Dissociation
• 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”
45
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
46
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.
47
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
48
Metabolic inhibitors
Metabolism decreased (duration prolonged) by
• acute alcohol consumption
• macrolides (ie. erythromycin, Biaxin,
azithromycin)
• antifungals
• amiodarone
• cimetidine
• HIV protease inhibitors
• cyclosporine
• grapefruit juice
49
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
50
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
51
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
52
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.
53
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.
54
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
55
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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IV IM PO/PR
Dose 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
57
Idiot’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.
58
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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Opioids
• 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
• 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.
61
Fentanyl 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
62
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 profile
Low complication rate
63
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)
64
Idiot’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
65
Pitfalls 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!
66
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
67
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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