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
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) Ù 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 2 nd 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: 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 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 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.
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) 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 1 st trimester studies not available/ do not confirm. No evidence of 2 nd or 3 rd 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