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)
Lidocaine
 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
Atropine
 Dose: 0.5 mg IVP
 When: Prior to intubation for
bradycardic adults
 Why: Given to prevent
worsening bradycardia
 From Succs, vagal stimulation
during direct visualization, and
hypoxia
Etomidate
 Class – sedative/hypnotic used
for general anesthesia induction
 Dose dependent
 Rapid onset/offset
 Minimal hemodynamic and
respiratory effects compared to
other induction agents
 Imidazole derivative unrelated to
any other agent
Etomidate
 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.
Etomidate
 Preparation –
 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
 Action
 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
Etomidate
 Onset
 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
 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
 Drug Interactions
 Sedatives and Hypnotics – increased effect
 Opiates – increased effect
 No interaction with any neuromuscular blocker
Etomidate
 Side Effects
 Elderly patients sensitive
 Hypotensive patients sensitive
 Pain at injection site
 Muscle twitching
 30%
 Myoclonic jerks
 Variable, Facial
Etomidate
 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
Etomidate
 Reversal Agents
 NONE
Neuromuscular Blockers

 HOW DO THEY WORK ????

 WHAT DO THEY DO ?????

Neuromuscular Blockers
 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), Vecuronium (Norcuron)
 Classified depending upon the effect they have on
the neuromuscular endplate
 Neural Transmission
 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
– 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:
 Rapid onset
 Short duration

Will cause “fasciculations”

Succinylcholine
 Class
 Depolarizing Neuromuscular Blocker
 Pregnancy Risk Category – C:
 “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
Succinylcholine Effect
 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.
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
Succinylcholine
 Action
 Binds to nicotinic “M” receptors usually acted
upon by Acetylcholine
 Initial Depolarization of muscle membrane
 Block further binding
Succinylcholine
 Drug interactions
 Potentiation of effects
 Oxytocin, Beta Blockers, Organophosphate
insecticides
 Reduced duration of action
 Diazepam
 Other effects
 Cardiac Glycosides – dysrhythmias
Succinylcholine
 Indication: Immediate severe airway
compromise in the context of trauma,
drug overdose, status epilepticus, etc.
where respiratory arrest is imminent.
Contraindications
 Severe burns
 > 24 hours old
 Massive crush injuries
 >8 hours old
 Spinal cord injury
 >3 days old
 Penetrating eye injuries
 Narrow angle glaucoma
 Hx of malignant
hyperthermia
 patient or family
 Pseudocholinesterase
deficiency
 Neuromuscular disease
 patient or family
 Hyperkalemia
 May precipitate fatal
hyperkalemia!
Succinylcholine
 Adverse Effects:
 Fasciculations

 Hyperkalemia

 Bradycardia

 Prolonged Neuromuscular Blockade

 Malignant Hyperthermia
Succinylcholine – Adverse Effects
 Fasciculations:
 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 –
 Rocuronium 0.06 mg/kg
Succinylcholine – Adverse Effects
 Hyperkalemia
 Normal rise in serum K+ is up to 0.5 meq/L
 Pathological rise may occur in
 Rhabdomyolysis
 Receptor upregulation
 May be life-threatening
 4-5 days post injury most critical
 Any ongoing neuro/muscular process is at risk
Succinylcholine
Adverse Effects - Hyperkalemia

 Receptor upregulation in
 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)

 Malignant Hyperthermia
 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
 Absolute contraindication
 Acute loss of intracellular calcium control
 Results in:
 Muscular rigidity (masseter)
 Autonomic instability
 Hypoxia
 Hypotension
 Hyperkalemia
 Myoglobinemeia
 DIC
 Elevated temperature a late finding
MH - Treatment
 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.
 www.mhaus.org
 http://medical.mhaus.org/NonFB/
Slideshow_eng/SlideShow_ENG_files/frame.htm
Succinylcholine
 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
 Onset
 < 1 Minute
 Slightly slower in hypotension
Succinylcholine
 Duration
 5-10 minutes
 Beware acetylcholinesterase deficiency
 Rare
 Prolonged action
Succinylcholine
 Reversal Agent
 Neostigmine 0.5-2 mg IV
 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
 Special Considerations
 Consider atropine in bradycardic adults
 Pre-medicate with Lidocaine because
fasciculations can lead to increased ICP
 LETHAL in the wrong hands
 Constant attendance
 Have BVM ready to go before administering drug
 Has no effect on consciousness
Midazolam & Lorazepam
 Benzodiazepines
 Provide sedation, amnesia, and
anticonvulsant properties
 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
Midazolam
 Duration: 1-4 hours
 Hepatic clearance
 Decreased dose needed (longer half life)
 Obese
 Geriatric
 CHF
 Hepatic or renal insufficiency
Lorazepam
 Class – Benzodiazepine II
 (Intermediate Acting)
 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
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
Lorazepam
 Enhances GABA – the primary neuro-
inhibitor
 Amnesia, anxiolysis, central muscle
relaxation, anticonvulsant effects,
hypnosis
 Doesn’t release histamine
 Allergic reactions rare
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

Vecuronium & Rocuronium
 Non-Depolarizing Paralytics
 Provide paralysis, but NO sedation,
amnesia, or analgesia properties
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
Vecuronium (Norcuron)
 Dose: 0.1mg/kg IVP
 Repeat/maintenance dose: 0.01 mg/kg
 Onset: 2-3 minutes
 Duration: approx. 20-30 minutes
Vecuronium (Norcuron)
 Metabolized by the liver and kidneys
 Use with caution in patients with liver
failure
 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
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
Rocuronium (Zemuron)
 Competitive blockade of ACH
 Reversed by ACHesterase inhibitors
 Degradation, liver metabolism and
bile/kidney excretion
 Reversed by neostigmine
Rocuronium (Zemuron)
 No known contraindications
 Pregnancy class B
 (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.
Rocuronium (Zemuron)
 Onset: 30-60 seconds
 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
Prolonged Seizure Activity
 Neuromuscular Blockers cease motor
activity but DO NOT stop seizure
 Anticonvulsant (diazepam) administration
should precede neuromuscular blockers
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
Summary R a pid S e qu e n c e In tu b atio n

P re -o x yg e na te p a tie nt
1 0 0 % O 2 for 5 m in u tes
N R M a sk o r B V M

L id oc a ine IV if in d ica ted

E to m id ate IV

S e llic k s M a n e u v er - B U R P

S u c cin ylc h o line

IN T U B A T E !

L o ra z e p am IV O R V e c uro n iu m O R
M id a z o lam R e c u ro m ium
P e r M e dic a l C o n tro l O n ly