RSI PharmacologyRSI Pharmacology

New HampshireNew Hampshire

Division of Fire Standards & Training andDivision of Fire Standards & Training andEmergency Medical ServicesEmergency 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 situationPediatrics – 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 hypoventilaitonapnea (5-90 seconds)laryngospasmhiccups / snoringhyper 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

Axon

Dendrites

Cell Body

Telondendria

Neuron

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.

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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

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

SummaryR a p id S e qu en ce In tu b a tion

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V e curo n ium O RR e cu ro m ium

P e r M e d ica l C o n tro l O n ly

IN T U B A T E !

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S e llic ks M a n e u ver - B U R P

E to m id a te IV

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