1. RSI Pharmacology New Hampshire
Division of Fire Standards & Training and
Emergency Medical Services

2. RSI Medications Protocol meds Oxygen Lidocaine Atropine Etomidate
Succinylcholine
Lorazepam
Fentanyl
Rocuronium
Vecuronium

3. Medication Information Parameters
Class
Pregnancy Risk Category
Preparation
Action
Onset
Duration
Drug Interactions
Side Effects
Reversal Agent(s)

4. 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
Onset: immediate
Duration: minutes
Mixed results regarding efficacy in decreasing ICP spike
Standardized therapy at present – primarily for patients with suspected traumatic brain injury
Also decreases the cough reflex and may decrease the incidence of post-laryngoscopy hypertension and tachycardia associated with intubation
May also be give directly squirted into the posterior pharynx and trachea – may produce as much ICP spike, etc. as direct laryngoscopy
Studies show ET suctioning and laryngeal manipulation cause an average ICP rise of 22 mmHg

5. Lidocaine
Antidysrhythmic with anesthetic properties that blunt transient increases in ICP that result from laryngoscopy.
Also blunts cough/gag reflex during laryngoscopy

6. 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
Atropine
Onset: Immediate
Duration: 4-6 hours

7. 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

8. 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.

9. 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

10. 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

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

12. 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

13. 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 – hours
75% excreted in urine within 24 hours
10% in bile and feces

14. Etomidate Drug Interactions Sedatives and Hypnotics – increased effect
Opiates – increased effect
No interaction with any neuromuscular blocker

15. Etomidate Side Effects Elderly patients sensitive
Hypotensive patients sensitive
Pain at injection site
Muscle twitching
30%
Myoclonic jerks
Variable, Facial

16. 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

17. Etomidate
Reversal Agents
NONE

18. Neuromuscular Blockers
HOW DO THEY WORK ????
WHAT DO THEY DO ?????

19. 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.

20. 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

21. 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

22. Motor Neuron
Dendrites
Neuron
Cell Body
Axon
Telondendria

23. 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

24. Anectine (Succinylcholine) SCh or “Succs”
The only depolarizing paralytic in clinical use
Benefits:
Rapid onset
Short duration
Will cause “fasciculations”
Succs attaches to the acetylcholine receptors of nerves and causes the nerves to depolarize – seen as muscle fasciculations. It remains until it is metabolized.

25. Succinylcholine Class Pregnancy Risk Category – C: Lactation - ?Safe
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

26. 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.
Bellise, Martha. “Chaz Higgs leaves jail”, Reno Gazette-Journal, March 27, 2007.

27. 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.
Bellise, Martha. “Chaz Higgs leaves jail”, Reno Gazette-Journal, March 27, 2007.

28. Succinylcholine Dose: 1.5mg/kg IV (maximum 150 mg)
When: Immediately after Etomidate
Onset: rapid, usually secs
Duration: short acting, 3-5 mins

29. Succinylcholine Action
Binds to nicotinic “M” receptors usually acted upon by Acetylcholine
Initial Depolarization of muscle membrane
Block further binding

30. Succinylcholine Drug interactions Potentiation of effects
Oxytocin, Beta Blockers, Organophosphate insecticides
Reduced duration of action
Diazepam
Other effects
Cardiac Glycosides – dysrhythmias

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

32. 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
Hyperkalemia
May precipitate fatal hyperkalemia!
K+ may rise up to 1mEq (Typical rise: ) {study: 46% increased, 46% decreased, 8% no change}
Increased risk in chronic disease states & acute injury SEVERAL DAYS after the insult (perists for several weeks)
Generally safe to administer within 24 hours of injury
High incidence of undiagnosed muscular dystrophy in peds makes Succs use “relatively contraindicated” in “elective” peds RSI (esp. males <8)

33. Succinylcholine Adverse Effects: Fasciculations Hyperkalemia
Bradycardia
Prolonged Neuromuscular Blockade
Malignant Hyperthermia

34. 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

35. 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

36. 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)

37. Succinylcholine Adverse Effects – Malignant Hyperthermia (MH)
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
Malignant hyperthermia is a rare complication with an autosomal dominant inheritance pattern. It occurs in approximately 1 in 15,000 children and 1 in 50,000 adults.
The clinical syndrome consists of high fever, tachypnea, tachycardia, cardiac arrhythmias, hypoxia, acidosis, myoglobinuria, and impaired coagulation. Unabated muscle contractions mediated by abnormal calcium channels are believed to be the physiologic basis for this condition. Treatment includes aggressive cooling measures, volume replacement, and correction of hypoxia and acid-base and electrolyte abnormalities. Dantrolene sodium, a direct-acting skeletal muscle relaxant, has been shown to be effective in reducing the muscle hypermetabolism that causes the fever.

38. 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

39. 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.

40. 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

41. Succinylcholine
Onset
< 1 Minute
Slightly slower in hypotension

42. Succinylcholine Duration 5-10 minutes
Beware acetylcholinesterase deficiency
Rare
Prolonged action

43. 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 mg IV to prevent side effects such as bradycardia

44. 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

45. 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
Midazolam: 2x as potent as diazepam
*Induction dose: benzo of choice. In the well-premedicated, healthy patient, 0.2 mg/kg over 5-15 seconds – induction occurs in 28 seconds
The stresses of intubation are not blocked by midazolam – so adjuvant anesthetics, usually opioids, are often combined with benzos
(but combo of versed + fentanyl or sufentanyl produces greater decreases in systemic BP than each drug alone)
(there is evidence that midazolam and diazepam decrease catecholamine – use with caution in certain pt populations who are surviving on catecholamines…)
Decrease in SVR results in a slight decrease in arterial BP (12-26% reduction in MAP)
More than the other benzos
“despite the hypotension, midazolam, even in doses as high as 0.2 mg/kg, is safe and effective for induction of anesthesia…” – Miller, anesthesia book
In pts with elevated left ventricular filling pressures, midazolam produces a “NTG-like” effect by lowering the filling pressure and increasing CO.
Study: 0.1 mg/kg v. 0.1 mg/kg with a max of 5mg for RSI. 219 patients. Results: statistically significant relationship between versed use and hypotension and SBP decrease following RSI
Sign/symptoms: Movement, Increase in heart rate
Pay close attention to the patient’s level of consciousness. Signs/symptoms of discomfort may include movement, increase heart rate, increased blood pressure.

46. Midazolam (Versed) Dose: 0.05-0.1 mg/kg IVP Rapid onset – 1-2 minutes
Single dose duration: minutes
In the prehospital setting, hypotension with midazolam was found to be dose related and thus should be used cautiously in patients with hypovolemia or traumatic brain injury, or both.

47. Midazolam Duration: 1-4 hours Hepatic clearance
Decreased dose needed (longer half life)
Obese
Geriatric
CHF
Hepatic or renal insufficiency
Midazolam HCl should only be administered IV or IM.
Also available as versed syrup for PO use
Don’t use in pregnancy – increased congenital malformations

48. Lorazepam Class – Benzodiazepine II Pregnancy Risk Category – D
(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

49. 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
Don’t use in pregnancy – increased congenital malformations

50. Lorazepam Enhances GABA – the primary neuro-inhibitor
Amnesia, anxiolysis, central muscle relaxation, anticonvulsant effects, hypnosis
Doesn’t release histamine
Allergic reactions rare

51. Lorazepam - Metabolism
Similar for all BNZ
Lipid soluble – brain penetration
Rapid onset – sec
t ½  min
t ½  hours – 5 active metabolites

52. Vecuronium & Rocuronium
Non-Depolarizing Paralytics
Provide paralysis, but NO sedation, amnesia, or analgesia properties

53. 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
Vial: 10 mg/10 ml
Structural analog to pavulon – but not vagolytic

54. Vecuronium (Norcuron)
Dose: 0.1mg/kg IVP
Repeat/maintenance dose: 0.01 mg/kg
Onset: 2-3 minutes
Duration: approx minutes
Repeat dose not part of NH EMS protocol
Vec may be given with on-line medical consultation for continued paralysis

55. 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
Associated with prolonged blockade after med is DC’d –
All steroid-based NMBAs have been associated with prolonged recovery time and myopathy – undergo extensive hepatic metabolism, producing active drug metabolites
Vec produces 3 active metabolites – one as 80% as strong as Vec. Accumulates in pts with renal failure (hepatic elimination is decreased in pts with uremia)
So, lessening in popularity in the ICU

56. 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

57. Rocuronium (Zemuron) Competitive blockade of ACH
Reversed by ACHesterase inhibitors
Degradation, liver metabolism and bile/kidney excretion
Reversed by neostigmine

58. 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.

59. Rocuronium (Zemuron) Onset: 30-60 seconds Dose: 1 mg/kg IVP
Fastest onset of all non-depolarizing NMBs
Dose related
Dose: 1 mg/kg IVP
Duration: minutes
Repeat/maintenance dose is the same as the initial dose
Vial: 10mg/ml vials of 50 mg (or 10mg/ml vials of 100 mg)
Repeat dose not part of NH EMS protocol
Roc may be given with on-line medical consultation for continued paralysis
*Raising the dose of Roc from 0.6 to 0.9 mg/kg nearly halves the time for suitable intubating conditions, but it also increases the duration. Nevertheless, most studies concur Roc 0.9 mg/kg or higher should be used for “crash” RSI conditions.

60. Prolonged Seizure Activity
Neuromuscular Blockers cease motor activity but DO NOT stop seizure
Anticonvulsant (diazepam) administration should precede neuromuscular blockers

61. 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
Review complications to be anticipated with pregant patients.

62. Summary