Transcript RSI Pharmacology New Hampshire Division of Fire Standards & Training and

RSI Pharmacology
New Hampshire
Division of Fire Standards & Training and
Emergency Medical Services
RSI Medications
Protocol meds
 Oxygen
 Lidocaine
 Atropine
 Etomidate
 Succinylcholine
 Lorazepam
 Fentanyl
 Rocuronium
 Vecuronium

Medication Information Parameters
Class
 Pregnancy Risk Category
 Preparation
 Action
 Onset
 Duration
 Drug Interactions
 Side Effects
 Reversal Agent(s)
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Lidocaine
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Dose: 1.5 mg/kg IVP
When: At least 2 minutes
prior to intubation
Why: May prevent a rise in
ICP in TBI patients
Suspicion of increased ICP
Patient in respiratory
distress with reactive airway
disease or COPD
Lidocaine
Antidysrhythmic with anesthetic properties
that blunt transient increases in ICP that
result from laryngoscopy.
 Also blunts cough/gag reflex during
laryngoscopy
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Atropine
Dose: 0.5 mg IVP
 When: Prior to intubation for
bradycardic adults
 Why: Given to prevent
worsening bradycardia
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From Succs, vagal stimulation
during direct visualization, and
hypoxia
Etomidate
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Class – sedative/hypnotic used
for general anesthesia induction
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Dose dependent
Rapid onset/offset
Minimal hemodynamic and
respiratory effects compared to
other induction agents
Imidazole derivative unrelated to
any other agent
Etomidate
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Pregnancy Risk Category – C
No human studies and animal studies show
adverse effect
 Transmission to breast milk uncertain – likely –
but not a significant concern in an RSI
situation
Pediatrics – not approved for patients under 10 –
however RSI protocol only for age 12 and
above.
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Etomidate
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Preparation –
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2 mg/ml
20 and 40 mg vials (10 and 20 cc)
Propylene glycol 35%
Single use ampules
Abboject
Shelf life – 1 year
Does not need refrigeration
Etomidate
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Action
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Enhances GABA, the principal inhibitory
neurotransmitter
Action at the GABA-A receptor complex
Able to produce light sleep to deep coma
Dose dependent
EEG changes in anesthesia similar to
barbiturates
Etomidate
Indication: as an induction agent before
the administration of a neuromuscular
blockade agent.
 Contraindications: Known hypersensativity
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Etomidate
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Onset
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Rapid onset of loss of consciousness
Within one arm-brain circulation time
Rapid distribution to CNS
Then rapid clearance from the CNS and
redistribution
Etomidate
Dose: 0.3 mg/kg IV (maximum 40 mg)
 Duration of action
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With doses of 0.3 mg/kg
Duration of hypnosis is 3-5 minutes
Metabolized in liver to inactive metabolites
Then metabolite excreted through urine
Elimination half-life – 1.25-5 hours
75% excreted in urine within 24 hours
10% in bile and feces
Etomidate
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Drug Interactions
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Sedatives and Hypnotics – increased effect
Opiates – increased effect
No interaction with any neuromuscular blocker
Etomidate
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Side Effects
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Elderly patients sensitive
Hypotensive patients sensitive
Pain at injection site
Muscle twitching
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30%
Myoclonic jerks
Variable, Facial
Etomidate
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Side Effects
Decreased plasma cortisol concentrations
 Last up to 8 hours after injections
“Legal Laundry List” –
hyper and hypoventilaiton
apnea (5-90 seconds)
laryngospasm
hiccups / snoring
hyper and hypotension
Nausea / Vomiting after emergence
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Etomidate
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Reversal Agents
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NONE
Neuromuscular Blockers
HOW DO THEY WORK ????
WHAT DO THEY DO ?????
Neuromuscular Blockers
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Work by blocking the natural transmission of
nerve impulses to skeletal muscles.
No direct effect on: Heart, Digestive system,
Brain, Pupillary Response, Smooth Muscle or
other organ systems.
No effect on level of consciousness or pain
perception.
No direct effect on seizure activity.
Neuromuscular Blockers
Depolarizing Neuro Muscular Blockers
Succinylcholine (Anectine, Quelicin)
Non-Depolarizing Neuro Muscular
Blockers
Pancuronium (Pavulon),
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Vecuronium (Norcuron)
Classified depending upon the effect they have on
the neuromuscular endplate
Neural Transmission
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When a nerve impulse arrives at the synaptic
knob of the presynaptic neuron calcium flows in
and causes the release of neurotransmitters. The
neurotransmitters diffuse across the synaptic
cleft and attach to the dendrites of the
postsynaptic neuron. This allows the current to
flow from one neuron to the next.
More than 30 neurotransmitter in the human
body.
Neurotransmitter acetylcholine is essential to
understanding the function NMB
Motor Neuron
Dendrites
Neuron
Cell
Body
Axon
Telondendria
Acetylcholine
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–
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Produced within neurons by combining molecules
of acetylcoenzyme A and choline
Rapidly broken down in the synaptic cleft into
acetate and choline by the enzyme
acetylcholinesterase which is found on the outer
surface of the cell membranes.
The broken down choline is taken up by the axon
terminal and used in the synthesis of new
acetylcholine
Anectine (Succinylcholine)
SCh or “Succs”
The only depolarizing paralytic in clinical
use
 Benefits:
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Rapid onset
Short duration
Will cause “fasciculations”
Succinylcholine
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Class
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Depolarizing Neuromuscular Blocker
Pregnancy Risk Category – C:
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“Risk cannot be ruled out – Human studies are lacking and
animal studies are either positive for fetal risk or lacking as well.
However potential benefits may justify the potential risk.”
Lactation - ?Safe
 Metabolism – in plasma
 Excretion - kidney
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Succinylcholine Effect
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2 phases to blocking
The first block is due to the prolonged stimulation
of the acetylcholine receptor results first in
disorganized muscle contractions (fasciclations),
as the acetylcholine receptors are stimulated. On
stimulation, the acetylcholine receptors becomes
a general ion channel, so there is a high flux of
potassium out of the cell, and of sodium into the
cell, resulting in an endplate potential less than
the action potential. So, after the initial firing,
the celll remains refractory.
Succinylcholine Effect - continued
The 2nd Block Phase
 On continued stimulation, the
acetylcholine receptors become
desensitized and close. This means that
new acetylcholine signals do not cause an
action potential; and the continued
binding of sux is ignored. This is the
principal paralytic effect of sux, and wears
off as the sux is degraded and the
acetylcholine receptors return to their
normal configuration.
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Succinylcholine
Dose: 1.5mg/kg IV (maximum 150 mg)
 When: Immediately after Etomidate
 Onset: rapid, usually 30-90 secs
 Duration: short acting, 3-5 mins
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Succinylcholine
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Action
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Binds to nicotinic “M” receptors usually acted
upon by Acetylcholine
Initial Depolarization of muscle membrane
Block further binding
Succinylcholine
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Drug interactions
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Potentiation of effects
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Reduced duration of action
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Oxytocin, Beta Blockers, Organophosphate
insecticides
Diazepam
Other effects
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Cardiac Glycosides – dysrhythmias
Succinylcholine
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Indication: Immediate severe airway
compromise in the context of trauma,
drug overdose, status epilepticus, etc.
where respiratory arrest is imminent.
Contraindications
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Severe burns
 > 24 hours old
Massive crush injuries
 >8 hours old
Spinal cord injury
 >3 days old
Penetrating eye injuries
Narrow angle glaucoma
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Hx of malignant
hyperthermia
 patient or family
Pseudocholinesterase
deficiency
Neuromuscular disease
 patient or family
Hyperkalemia
 May precipitate fatal
hyperkalemia!
Succinylcholine
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Adverse Effects:
 Fasciculations
 Hyperkalemia
 Bradycardia
 Prolonged
Neuromuscular Blockade
 Malignant Hyperthermia
Succinylcholine – Adverse Effects
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Fasciculations:
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Associated with increased ICP, IOP, IGP
ICP only clinically important
Cause and Effect – unknown
If needed pre-treat with Lidocaine, and a
defasciculating dose of a non-depolarizing
neuromuscular blocker –
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Rocuronium 0.06 mg/kg
Succinylcholine – Adverse Effects
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Hyperkalemia
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Normal rise in serum K+ is up to 0.5 meq/L
Pathological rise may occur in
 Rhabdomyolysis
 Receptor upregulation
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May be life-threatening
4-5 days post injury most critical
Any ongoing neuro/muscular process is at risk
Succinylcholine
Adverse Effects - Hyperkalemia
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Receptor upregulation in
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Burns – especially 5 days post burn
Denervation or neuromuscular disorders
Crush injuries
Intra-abdominal infections
Myopathies
Renal failure – controversial
Use a non-depolarizer instead (Roc)
Succinylcholine
Adverse Effects – Malignant Hyperthermia (MH)
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Malignant Hyperthermia
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Very rare condition – 1:15,000
Patient experiences a rapid increase of
temperature, metabolic acidosis,
rhabdomyolysis, and DIC
Treatment includes administration of
Dantrolene and external means of temp.
reduction
Succinylcholine
Adverse Effects - MH
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Absolute contraindication
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Acute loss of intracellular calcium control
Results in:
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Muscular rigidity (masseter)
Autonomic instability
Hypoxia
Hypotension
Hyperkalemia
Myoglobinemeia
DIC
Elevated temperature a late finding
MH - Treatment
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If the diagnosis of MH is seriously being
considered – Contact medical control immediately
and divert to the CLOSEST facility
Once in the hospital Dantrolen 2.5 mg/kg IV q 5
minutes until muscle relaxation or maximum
dose of 10mg/kg.
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Succinylcholine
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Dose: 1.5 mg/kg IV (maximum 150 mg),
following Emotidate
Administration of a neuromuscular blocker does
not alter mentation or the ability to feel pain
Succinylcholine
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Onset
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< 1 Minute
Slightly slower in hypotension
Succinylcholine
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Duration
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5-10 minutes
Beware acetylcholinesterase deficiency
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Rare
Prolonged action
Succinylcholine
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Reversal Agent
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Neostigmine 0.5-2 mg IV
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This is given if the patient does not loose their
paralysis. This would not be given pre-hospital.
+/- atropine 05.-1 mg IV to prevent side
effects such as bradycardia
Succinylcholine
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Special Considerations
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Consider atropine in bradycardic adults
Pre-medicate with Lidocaine because
fasciculations can lead to increased ICP
LETHAL in the wrong hands
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Constant attendance
Have BVM ready to go before administering drug
Has no effect on consciousness
Midazolam & Lorazepam
Benzodiazepines
 Provide sedation, amnesia, and
anticonvulsant properties
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No analgesia
•Midazolam: Faster onset, shorter duration than lorazepam
•Lorazepam: may be the preferred agent due to its longer
action duration
Pay close attention to the patient’s level of
consciousness. Signs/symptoms of discomfort may
include movement, increase heart rate, increased
blood pressure.
Midazolam (Versed)
Dose: 0.05-0.1 mg/kg IVP
 Rapid onset – 1-2 minutes
 Single dose duration: 15-20 minutes
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Midazolam
Duration: 1-4 hours
 Hepatic clearance
 Decreased dose needed (longer half life)
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Obese
Geriatric
CHF
Hepatic or renal insufficiency
Lorazepam
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Class – Benzodiazepine II
 (Intermediate Acting)
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Pregnancy Risk Category – D
 (Positive evidence of human fetal risk. Maternal benefit
may outweigh fetal risk in serious or life-threatening
situations)
Metabolism – liver
 Excretion - urine
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Lorazepam (Ativan)
Dose: 1-2 mg IV every 15 minutes as
needed for sedation (maximum 10 mg)
 Onset: 5 minutes
 Duration: 6-8 hours, dose dependant
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Lorazepam
Enhances GABA – the primary neuroinhibitor
 Amnesia, anxiolysis, central muscle
relaxation, anticonvulsant effects,
hypnosis
 Doesn’t release histamine
 Allergic reactions rare
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Lorazepam - Metabolism
Similar for all BNZ
 Lipid soluble – brain penetration
 Rapid onset – 60-120 sec
 t ½  - 3-10 min
 t ½  - 10-20 hours – 5 active metabolites
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Vecuronium & Rocuronium
Non-Depolarizing Paralytics
 Provide paralysis, but NO sedation,
amnesia, or analgesia properties
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Vecuronium (Norcuron)
Considered safe without many
contraindications
 May be used in most patients
including cardiovascular,
pulmonary, and neurological
emergencies
 Must be reconstituted from
powdered form
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Vecuronium (Norcuron)
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Dose: 0.1mg/kg IVP
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Repeat/maintenance dose: 0.01 mg/kg
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Onset: 2-3 minutes
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Duration: approx. 20-30 minutes
Vecuronium (Norcuron)
Metabolized by the liver and kidneys
 Use with caution in patients with liver
failure
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May have 2x the recovery time
Patients with renal or hepatic failure will
need less medication to maintain paralysis
 Does not cause hypotension or
tachycardia
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Rocuronium (Zemuron)
Very similar properties to Vecuronium
 Does not need to be mixed, can be stored
at room temp for 60 days
 Less vagolytic properties
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Rocuronium (Zemuron)
Competitive blockade of ACH
 Reversed by ACHesterase inhibitors
 Degradation, liver metabolism and
bile/kidney excretion
 Reversed by neostigmine
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Rocuronium (Zemuron)
No known contraindications
 Pregnancy class B
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 (Animal Studies show no risk or adverse fetal effects
but controlled human 1st trimester studies not
available/ do not confirm. No evidence of 2nd or 3rd
trimester risk. Fetal harm possible but unlikely)
Lactation ?Safe
 “Back-up” paralytic agent.
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Rocuronium (Zemuron)
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Onset: 30-60 seconds
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Fastest onset of all non-depolarizing NMBs
Dose related
Dose: 1 mg/kg IVP
 Duration: 20-75 minutes
 Repeat/maintenance dose is the same as
the initial dose
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Prolonged Seizure Activity
Neuromuscular Blockers cease motor
activity but DO NOT stop seizure
 Anticonvulsant (diazepam) administration
should precede neuromuscular blockers
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Pregnant Patients and Neuromuscular Blockers
Pregnancy = weight gain
 Larger breast may increase resistance
during BVM
 Toxemia may cause edemotous airway
 Desaturate more rapidly due to reduced
functional residual capacity and increased
oxygen consumption
 Regurgitation more likely
 Decreased cardiac output
 Supine Hypotensive Syndrome
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Summary
Rapid Sequence Intubation
Pre-oxygenate patient
100% O2 for 5 minutes
NR Mask or BVM
Lidocaine IV if indicated
Etomidate IV
Sellicks Maneuver - BURP
Succinylcholine
INTUBATE !
Lorazepam IV OR
Midazolam
Vecuronium OR
Recuromium
Per Medical Control Only