Monroe Community College - State University of New York

Public Safety Training Facility

Monroe Community College
Rochester, New York

Post Graduate Paramedic CME

Pharmacological Agents in Airway Management

by Bob Breese, EMT-P

Pharmacologic agents are important adjuncts to airway management. However, their use in the face of poor mechanical skills or judgment may negate any pharmacologic benefit derived from these agents. Proper airway management consists of adequate assessment, identification of non-patent and difficult airway situations, proper positioning, adequate suction and mastery of ventilatory skills. Endotracheal intubation should be performed by the most experienced responder present. Use of pharmacologic agents should only be undertaken when other means of airway patency have failed.

Certain situations are contraindications for the use of intravenous induction agents, while others are clearly indicated. Muscle relaxants must only be administered when there is a certainty of securing the airway.

Specific pharmacological agents are divided into: Sedative-Hypnotics, Anxiolytics, Paralytics (muscle relaxants), Anticholinergic drying agents and local anesthetics.

Review of basics regarding neuronal arousal mechanisms and physiologic action(s) of pharmacologic agents is essential for safe and efficacious application of airway adjuncts. The basic elements of anesthesia include unconsciousness, analgesia, inhibition of noxious reflexes and skeletal muscle relaxation.

Consciousness - Consciousness is a relative term which denotes a state of being aware, or perceiving physical facts or mental concepts; a state of general wakefulness and responsiveness to the environment. The body maintains arousal and neuronal homeostasis through selective activation of the hypothalamus, the limbic system and the cerebral cortex. This level of arousal varies from a state of excitement to sleep and coma. Arousal is controlled by chemical-mediated excitation and inhibition of neurons.

While acetylcholine and biogenic amines (dopa, dopamine, seratonin, etc...) are present in the central nervous system, they are found only in certain neurons. In contrast, there is a group of amino acids that are released as neurotransmitters and that also are universal cellular constituents. Glycine, glutamate and aspartate are three of the 20 common amino acids that are found in the proteins of all cells. g - aminobutyric acid (GABA) is an inhibitory neurotransmitter, synthesized from glutamate, while glutamate is an excitatory amino acid (EAA). Application of these neurotransmitters to the axons and glial cells of the central nervous system will cause either an increase or decrease of ion flux, which in turn will effect a stimulatory or inhibitory response. Stimulatory responses are generally caused by an increase in Na+ conductance or an increased level of Ca++ conductance. Conversely, inhibitory responses are generally caused by increases in K+ efflux or Cl- influx both resulting in hyperpolarization.

Specific Agents

Sedative-Hypnotics - Sedative-hypnotics are medications that inhibit the CNS, promoting drowsiness or unconsciousness. Rapid onset, short-acting sedative hypnotics are used in combination with other medications for rapid sequence induction of anesthesia (RSI).

Barbiturates - Barbiturates are a group of drugs which are derived from barbituric acid or the salts of barbituric acid, a substance which seems to inhibit the influx and efflux of Na+ and K+ from CNS neurons. This is accomplished by slowing the rate of GABA dissociation from its receptor. GABA receptors are linked to chloride ion channels. GABA stimulation causes the Cl- channels to remain open, increasing the intracellular influx of Cl-, which results in neuronal hyperpolarization and general inhibition of CNS neurons. Barbiturates, as with many sedative-hypnotics do not produce muscle relaxation or analgesia.

Generic Name -Thiopental Sodium

Trade Name -Pentathol

Dosing-2-5 mg/kg

Onset -rapid

Duration -ultra-short acting

Remarks -Thiobarbiturate 30 second onset 5 - 10 minute duration, increased venous capacitance, decreased preload, decreased CO, decreased BP. Reflex tachycardia No analgesia Hypovolemic patients and those with poor cardiac function are prone to hypotension at induction Respiratory significant Metabolism significantly slowed in hypothermia

Generic Name -Methohexitol

Trade Name -Brevital

Dose -1-2 mg/kg

Onset -rapid

Duration -ultra-short acting

Remarks -Oxybarbiturate 30 second onset, 5-10 minute duration. Similar effects as thiopental but shorter duration. No analgesia. May activate epileptic foci. May induce myoclonus. May be administered rectally with dosing of 30 mg/kg and extended duration of drowsiness 1-2 hours.

Imidazole derivatives - Imidazoles are a class of anti-fungal agents such as ketaconazole. However etomidate acts as an enhancer of GABA, which promotes cellular hypperpolarization.

Generic Name -Etomidate

Trade Name -Amidate

Dose -0.3 mg/kg

Onset -<1 min. onset

Duration -10 min. duration

Remarks -Cerebral effects very similar to those of thiopental. No analgesia. Cardiovascular effects minimal. Myoclonus noted. Pain on injection and thrombophlebitis - mixed in propylene glycol, Inhibits key enzymes in steroid production. Long-term use shows increased morbidity and mortality in ICU patients. Good choice in patients with ventricular dysfunction or ischemic heart disease. For short-term use.

Dissociative anesthetics - Dissociative anesthesia resembles a cataleptic state in which the eyes remain open and although non-responsive, the patient may appear wakeful. Varying degrees of muscle tone and spontaneous limb movements are present. Emergence delirium may be a problem. Ketamine, a phencyclidine derivative, is the primary dissociative agent used today, causing a dissociation between the thalamoneocortical and limbic systems . Ketamine effects in the CNS that appear to be responsible for anesthetic effects include interference with the EAA neurotransmitter glumtamate by blocking the NMDA (N--methyl-D-aspartate) receptor Ketamine may also bind to peripheral opioid receptors. and may explain its analgesic effects.

Generic Name -Ketamine

Trade Name -Ketalar

Dose -1-3 mg/kg IV, 4-6 mg/kg IM

Onset -1 minute IV, 5 minutes IM

Duration -15 minutes

Remarks -Potent analgesic. Adrenergic activation. Minimal respiratory effect with some bronchodilation. Salivation and increased secretions. Emergence reactions and hallucinations. Rarely used alone.

Other induction agents:

Propofol is an isopropyl alkylphenol formulated as a 1% solution in a lipid base (hence it's nickname - milk of anesthesia or milk of analgesia). Propofol acts on the GABA receptor. Propofol is unrelated to barbiturates, eugenols, or steroid anesthetics. It produces rapid induction and rapid recovery with little cumulative effect.

Generic Name -Propofol

Trade Name -Diprivan

Dose -10 mg (1ml) every 10 seconds until induction

Onset -rapid (< 60 seconds)

Remarks -More rapid and complete awakening than barbiturates. Reduces blood pressure more than thiopental. Exaggerated hemodynamic effects in hypovolemia. Pain with injection into non-antecubital, small vein. Prolonged exposure to heat may promote bacterial contamination.

Antianxiety agents- Amnestic, anticonvulsant, hypnotic, and sedative effects. Useful sedation for procedures and tolerance of mechanical ventilation. These include benzodiazepines and antihistamines. Because antihistamines have longer duration, only benzodiazepines will be discussed here.

Benzodiazepines - Benzodiazepines are a large family of medication of which diazepam is the model. Benzodiazepines are stimulators of the GABA receptor, increasing the intracellular influx of Cl- ions. This causes neuronal hypperpolarization. Additionally, benzodiazepines may increase the availability of the inhibitory amino acid (IAA) glycine, which may explain the skeletal muscle relaxant and antianxiety effects.

Generic Name -Diazepam

Trade Name -Valium

Dose -2 - 20 mg

Onset -1 - 2 min

Duration -2 - 4 hour

Remarks -Mild sedation. Anticonvulsant action. Seldom used since introduction of midazolam for sedation.

Generic Name -Midazolam

Trade Name -Versed

Dose -0.15- 0.35 mg/kg until induction or sedation level achieved

Onset -1 - 2 min.

Duration -45 minutes.

Remarks -More retrograde amnesia. Increased incidence respiratory depression in elderly when given with narcotics.

Generic Name -Lorazepam

Trade Name -Ativan

Dose -0.5 - 2 mg

Onset -1 - 2 min.

Duration -45 min.

Remarks -Mild sedation. Anticonvulsant.

Opiates - Derivatives of Morphine act at opiate receptors present in multiple forms at multiple sites. Opiates are potent analgesics. Alfentanyl is 5 times more potent than Fentanyl. Sufentanyl is 10 times more potent than Fentanyl. Fentanyl is 3 times more potent than Morphine.

Generic Name -Morphine

Trade Name -same

Dose -2 - 15 mg

Onset -10 minutes

Remarks -Respiratory depression, Nausea and vomiting. Dysphoria, Muscle rigidity. Hypotension from histamine release.

Muscle relaxants (paralytics) -- In the context of RSI muscle relaxation is synonymous with paralysis. Muscle relaxants block the nicotinic acetylcholine receptor motor end-plate, thereby inhibiting neuromuscular transmission and leading to muscle flaccidity. Inactivation of the receptor can be attained in two ways: by depolarizing the receptor continuously, which leads to complex form of desensitization (depolarizing muscle relaxants); or by competitively antagonizing the receptor (non-depolarizing agents). Depolarizing agents are non-reversible. Non-depolarizing agents may be reversed. Neostigmine, pyridostigmine, and edrophonium are used clinically to reverse the competitive antagonism of non-depolarizing agents.

Paralytics

Generic Name -Succinylcholine

Trade Name -Annectine

Type -depolarizing agent

Dose -(1 mg/kg adult) (2mg/kg peds)

Onset -60 seconds

Duration -3 - 10 minutes.

Remarks -Cardiac dysrhythmias, Histamine release, Hyperkalemia in trauma/burn patients, increased intraocular and intracranial pressure, Fasciculation common, Malignant hyperthermia possible.

Generic Name -Rocuronium

Trade Name -Zemuron

Type -non depolarizing

Dose -0.6 - 1 mg/kg

Onset -60 - 90 seconds

Duration - < 20 minute duration

Remarks -increased heart rate, Useful in patients with contraindication to sux.

Generic Name -Vecuronium

Trade Name -Norcuron

Type -non depolarizing

Dose -0.08 - 1mg/kg

Onset -3 minutes