RSI Pharmacology New Hampshire Division of Fire Standards

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RSI Pharmacology
New Hampshire Division of Fire Standards
Training and Emergency Medical Services
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RSI Medications

• Protocol meds
• Oxygen
• Lidocaine
• Atropine
• Etomidate
• Succinylcholine
• Lorazepam
• Fentanyl
• Rocuronium
• Vecuronium

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Medication Information Parameters

• Class
• Pregnancy Risk Category
• Preparation
• Action
• Onset
• Duration
• Drug Interactions
• Side Effects
• Reversal Agent(s)

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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

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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
• From Succs, vagal stimulation during direct
  visualization, and hypoxia

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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

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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.

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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

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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

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Etomidate

• Indication as an induction agent before the
  administration of a neuromuscular blockade agent.
• Contraindications Known hypersensativity

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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

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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

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Etomidate

• Drug Interactions
• Sedatives and Hypnotics increased effect
• Opiates increased effect
• No interaction with any neuromuscular blocker

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Etomidate

• Side Effects
• Elderly patients sensitive
• Hypotensive patients sensitive
• Pain at injection site
• Muscle twitching
• 30
• Myoclonic jerks
• Variable, Facial

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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

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Etomidate

• Reversal Agents
• NONE

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Neuromuscular Blockers

• HOW DO THEY WORK ????
• WHAT DO THEY DO ?????

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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.

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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

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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

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Motor Neuron
Dendrites
Neuron
Cell Body
Axon
Telondendria
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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

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Anectine (Succinylcholine)SCh or Succs

• The only depolarizing paralytic in clinical use
• Benefits
• Rapid onset
• Short duration

Will cause fasciculations
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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

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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.

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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

• Action
• Binds to nicotinic M receptors usually acted
  upon by Acetylcholine
• Initial Depolarization of muscle membrane
• Block further binding

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Succinylcholine

• Drug interactions
• Potentiation of effects
• Oxytocin, Beta Blockers, Organophosphate
  insecticides
• Reduced duration of action
• Diazepam
• Other effects
• Cardiac Glycosides dysrhythmias

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Succinylcholine

• Indication Immediate severe airway compromise in
  the context of trauma, drug overdose, status
  epilepticus, etc. where respiratory arrest is
  imminent.

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Contraindications

• Severe burns
• gt 24 hours old
• Massive crush injuries
• gt8 hours old
• Spinal cord injury
• gt3 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!

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Succinylcholine

• Adverse Effects
• Fasciculations
• Hyperkalemia
• Bradycardia
• Prolonged Neuromuscular Blockade
• Malignant Hyperthermia

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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

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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

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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)

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Succinylcholine Adverse Effects Malignant
Hyperthermia (MH)

• Malignant Hyperthermia
• Very rare condition 115,000
• Patient experiences a rapid increase of
  temperature, metabolic acidosis, rhabdomyolysis,
  and DIC
• Treatment includes administration of Dantrolene
  and external means of temp. reduction

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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

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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/Slide
  Show_ENG_files/frame.htm

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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

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Succinylcholine

• Onset
• lt 1 Minute
• Slightly slower in hypotension

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Succinylcholine

• Duration
• 5-10 minutes
• Beware acetylcholinesterase deficiency
• Rare
• Prolonged action

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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

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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

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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 patients level of
consciousness. Signs/symptoms of discomfort may
include movement, increase heart rate, increased
blood pressure.
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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)
• Obese
• Geriatric
• CHF
• Hepatic or renal insufficiency

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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

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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 neuro-inhibitor
• Amnesia, anxiolysis, central muscle relaxation,
  anticonvulsant effects, hypnosis
• Doesnt 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)

• Dose 0.1mg/kg IVP
• Repeat/maintenance dose 0.01 mg/kg
• Onset 2-3 minutes
• Duration approx. 20-30 minutes

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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

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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
• (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)

• 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

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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