RSI Pharmacology

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

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

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 – 1.25-5 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”

25. 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

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.

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.

28. 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

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. 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! Contraindications

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) • 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

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. • www.mhaus.org • http://medical.mhaus.org/NonFB/Slideshow_eng/SlideShow_ENG_files/frame.htm

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 05.-1 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 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: 15-20 minutes

47. Midazolam • Duration: 1-4 hours • Hepatic clearance • Decreased dose needed (longer half life) • Obese • Geriatric • CHF • Hepatic or renal insufficiency

48. 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

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

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