Pharmacology for Endotracheal Intubation

• Pharmacology in Endotracheal Intubation will be discussed.

Objectives

• Application of nerve transmission principles to neuromuscular blocking agents pharmacology.
• Description of clinical applications of neuromuscular blocking drugs.
• Statement of medications' mechanisms of action that are hypnotic, sedative, or anxiolytic and their importance in respiratory care practices.
• Description of the mechanism and role of ventilatory stimulants.
• Explanation of the pain pathway (nociceptive pathway) and discuss the function of analgesic medications.
• Discussion of the role of medications for local and general anesthesia.
• Description of rapid sequence intubation in emergency airway management.

Complications of Intubation

• Failed intubation.
• Spinal cord and vertebral column injury.
• Corneal abrasion.
• Trauma to lips, teeth, tongue, and nose.
• Hyper/hypotension.
• Tachy/bradycardia.
• Arrhythmias.
• Increased ICP and IOP.
• Laryngospasm.
• Bronchospasm.
• Laryngeal trauma.
• Airway perforation.
• Tension pneumothorax.
• Esophageal intubation.
• Increased Raw.
• Gastric Aspiration.
• Residual muscle paralysis.
• Right main stem intubation.
• Impaired swallowing.
• Myocardial infarction.

Mechanisms Causing Hypotension

• Volume depletion.
• Positive pressure ventilation.
• PEEP and Autopeep.
• Medications.
• Myocardial Ischemia.

When to Intubate

• Intubation is required when patients have at least one of the following 5 indications:
• The Inability to maintain airway patency.
• The Inability to protect the airway against aspiration.
• Failure to ventilate.
• Failure to oxygenate.
• Anticipation of a deteriorating course that will eventually lead to respiratory failure.

Keys for Success and Safety in Intubation

• Assessment.
• Adequate Preparation.
• Proper Positioning.
• Creation of a Back-up plan (A, B, C.......Z).
• Early request for help.

Intubation During Cardiac Arrest

• Patients are apneic during a cardiac arrest.
• Breathing demonstrates Agonal breathing, an abnormal brainstem reflex characterized by gasping, labored breathing, accompanied by strange vocalizations and myoclonus (involuntary muscle jerks/twitches).
• Patients are unresponsive, flaccid, and areflexic Patients.
• Crash airway is easy to intubate, with no meds necessary.
• Steps include Preoxygenation, equipment preparation, and intubation.

Airway Management Includes

Awake Intubation

Rapid Sequence Intubation

Surgical Airway

• Cricothyrotomy

Awake Intubation

• Awake intubations are often performed when the patient has a known or suspected difficult airway, or history of difficult intubation or ventilation, in whom protective airway reflexes loss or frank apnea may have catastrophic effects.
• Local anesthesia with lidocaine spray is recommended.
• Preoxygenate with BVM or LMA.
• Prepare equipment prior to.
• The patient should be positioned in the sniffing position.
• Opioids can be used for pain, as they act on opioid receptors to produce morphine-like effects.
• Medically, opioids are primarily used for pain relief, including anesthesia.
• Benzodiazepines/IV anesthetics are prescribed for sedation.
• Benzodiazepines treat of anxiety, but they are also effective in treating several other conditions.
• Intubate.

Rapid Sequence Intubation (RSI)

• The implementation of RSI improved success and decreased complication rates for emergency intubations.
• RSI (rapid sequence intubation) describes a virtually simultaneous sedation (induction) administration and a neuromuscular blocking agent (paralytic) to render a patient rapidly unconscious and flaccid in order to facilitate emergent endotracheal intubation and to minimize aspiration risk.
• Endotracheal intubation using RSI is the cornerstone of emergency airway management outside the operating room.
• RSI assumes the patient is at aspiration risk of stomach contents, incorporating medications and techniques to minimize this risk.
• RSI helps mitigate the potential adverse effects of airway manipulation.
• Preoxygenation permits a longer period of apnea without clinically significant oxygen desaturation.
• Bag-mask ventilation is avoided during the interval between drug administration and endotracheal tube placement to minimize gastric insufflation and reducing the risk of aspiration.
• RSI is the standard of care in emergency airway management for intubations not anticipated to be difficult.
• The goal of RSI is to intubate the trachea without having to use BVM, which is often necessary when attempting to achieve intubating conditions with sedative agents alone (i.e., ketamine, etomidate, propofol).
• RSI is not indicated in unconscious and apneic patients.
• RSI should be approached with caution in patients with a suspected difficult airway with:
  • An unstable C-spine injury.
  • An Airway tumor.
  • Significant facial trauma.
  • Unfavorable anatomy.
  • Elevated ICP
  • Increased risk of ICH.
• When difficulty is anticipated, an awake technique or the use of airway adjuncts (i.e., fiberoptic intubation) is recommended.

Indications for RSI

• Failure to maintain airway tone
• Swelling of upper airway as in anaphylaxis or infection
• Facial or neck trauma with oropharyngeal bleeding or hematoma
• Decreased consciousness and loss of airway reflexes
• Failure to protect airway against aspiration - Decreased consciousness that leads to regurgitation of vomit, secretions, or blood
• Failure to ventilate
• Prolonged respiratory effort that results in fatigue or failure, as in status asthmaticus or severe COPD
• Failure to oxygenate
• Transport oxygen to pulmonary capillary blood
• Diffuse pulmonary edema
• ARDS
• Large pneumonia or airspace disease
• Pulmonary embolism
• Cyanide toxicity, carbon monoxide toxicity, methemoglobinemia
• Anticipated clinical course or deterioration
• Need for situation control, tests, procedures
• Uncooperative trauma patient with life-threatening injuries who needs procedures (i.e., chest tube) or immediate CT scanning
• Stab wound to neck with expanding hematoma
• Septic shock with high minute-ventilation and poor peripheral perfusion
• Intracranial hemorrhage with altered mental status and need for close blood pressure control
• Cervical spine fracture with concern for edema and loss of airway patency

Contraindications to RSI

• Absolute:
  • Total upper airway obstruction, which requires a surgical airway.
  • Total loss of facial/oropharyngeal landmarks, which requires a surgical airway.
• Relative:
  • Anticipated "difficult" airway, in which endotracheal intubation may be unsuccessful, resulting in reliance on successful bag-valve-mask (BVM) ventilation to keep an unconscious patient alive.
  • Techniques for awake intubation and difficult airway adjuncts can be used.
• Multiple methods can be used to evaluate the airway and the risk of difficult intubation (i.e., LEMON rule, 3-3-2, Mallampati class, McCormack and Lehane grade).
• the "crash" airway, in which the patient is in an arrest situation, unconscious and apneic.
  • Further, no time is available for preoxygenation, pretreatment, or induction and paralysis, as the patient is already unconscious and may be flaccid.
  • BVM ventilation, intubation, or both should be performed immediately without medications.

RSI Steps

1. Preparation
2. Preoxygenation
3. Pretreatment/Premedication
4. Paralysis with induction
5. Positioning and Protection (Sellick maneuver)
6. Placement of ETT with proof
7. Post-intubation care/management

Steps of RSI

• Assess the patient for difficult airway during Preparation
• Confirm that intubation equipment is functional
• Establish intravenous access
• Draw up essential drugs and determine sequence of administration (induction agent immediately followed by paralytic agent)
• Review possible medications contraindications
• Attach necessary monitoring equipment
• Preoxygenation is aimed at maximizing saturation levels and creating an O2 reservoir in the lungs to eliminate the need for BVM ventilation for the period of apnea after induction and paralysis to minimize the risk of stomach insufflation and aspiration (Most critical of all steps). --If needed, assist ventilation with bag-valve-mask (BVM) system only if needed to obtain an oxygen saturation =90%.
• Pretreatment/Premedication: ancillary meds administered to mitigate the adverse physiologic consequences of intubation:
  • Opioids for pain, HTN, CAD, ICP
  • Lidocaine spray at 4% and 1-2 mL of 2% jelly for local anesthesia of the hypopharynx
  • Lidocaine 1.5 mg/kg IV for ICP/asthma
  • Atropine 1 mg for decreasing secretions and bradycardia
  • Give pretreatment meds 3-5 minutes prior to sedation and paralysis
• Paralysis with Induction requires a rapidly-acting sedative induction agent via IV push to produce loss of consciousness, followed IMMEDIATELY by administration of a paralytic via IV push.
• Positioning and Protection
  • Position patient for optimal laryngoscopy (sniffing position)
  • Apply Sellick's maneuver on observing the beginning of unconsciousness
  • Firm pressure over the cricoid cartilage to prevent regurgitation of gastric contents
  • Maintain pressure throughout intubation sequence until the ET tube position is verified.
• Placement of ET tube with proof includes:
  • Visualize the ET tube passing through the vocal cords and confirm tube placement
    1. Condensation in tube
    2. Colorimetry (purple to yellow) or ETCO2
    3. Auscultation of bilateral breath sounds and equal chest rise. Triangle auscultation
    4. Increase in SPO2
    5. CXR
• Post intubation care/management includes:
  • Secure the ET tube into place.
  • Initiate mechanical ventilation.
  • Administer appropriate analgesic and sedative agents for patient comfort, to decrease O₂ demand, and to decrease ICP.

Med Classes used in RSI

• Analgesics
• Induction agents
• Sedatives
• Neuromuscular Blocking Agents

Classes of Analgesics

• Medications decrease the patients perception of pain or pain intensity
• Analgesics include:
  • Opioids
  • Opioid Antagonist
  • Steroids
  • Nonsteroidal Anti-inflammatory

Analgesics

• Opioids (i.e., Morphine, Fentanyl)
  • Natural or synthetic chemical can bind to opioid receptors and exert an action.
  • They combine with pain receptor sites in the thalamus and limbic system to prevent the transmission of pain impulses.
  • Opioids can have varying potencies, actions onset and duration, chemical structures available administration routes, side effects, abuse potential, and differing costs.
• Side Effects:
  • Drowsiness and Euphoria
  • Depressed respiration and cough
  • Constricted pupils
  • Histamine release leading to vasodilation and bronchoconstriction
  • Nausea and vomiting
  • Urinary retention
  • Tolerance.
• Opioid Analgesics
  • Common Agents:
    • Morphine* - 2.5 – 5 mg IV push; onset 5-10 min; duration of action = 3-4 hrs.
    • Codeine
    • Hydromorphone (Dilaudid)
    • Fentanyl (Sublimaze)* - 1-2 mcg/kg IV push; immediate onset; duration of action = 30-60 min
    • Meperidine (Demerol)
    • Oxycodone
    • Nalbuphine (Nubain)
    • Methadone (Dolophine)
  • • Morphine or Fentanyl are commonly used opioids for the premedication phase of RSI.
• Analgesic Antagonists
  • Act to Reverse the CNS and ventilatory depression caused by opioids
  • They can be used in the event of a suspected narcotic overdose
  • Common Agents:
    • Naloxone (Narcan)

Induction

• The induction phase of rapid sequence intubation (RSI) is used produce anesthesia and rapid unresponsiveness.
• Etomidate is the most common agent used in the ED for this purpose, though today, numerous pharmacologic drug classes are used.
• The ideal drug to produce rapid unconsciousness has:
  • A short action duration
  • Causes minimal alterations in hemodynamics, respirations, and ICP (intracranial pressure).
• Most sedatives cause some degree of cardiovascular depression, with exaggerated effects in acutely ill, hypovolemic or hypotensive, patients.
• Factors to consider include altered hemodynamics, suspected ICP abnormalities, and reactive airway disease, thus the clinical status dictates which induction agent should be used.

Sedatives/Hypnotics/Anxiolytics

• A drug that reduces CNS arousal is a sedative that can induce sleep in larger doses.
• An hypnotic induces sleep.
• An Anxiolytic alleviates anxiety symptoms.
• Some drug classes, such as benzodiazepines, have all 3 characteristics and can be categorized as such.
• Anesthetics are frequently used in conjunction with analgesics to:
  • improve tolerance of ET tubes.
  • facilitate acceptance of mechanical ventilation.
  • suppress spont. ventilation.
  • prevent self-extubation.
• Cortex
  • Responsible for skeletal muscle control, sensations, senses, intellect and memory
  • Depression of the cortex can lead to slowed reflexes, slurred speech, and decreased mental ability
• Brain Stem
  • Responsible for Respiratory and Cardiovascular regulation
• Reticular activating system
  • Cells in the midbrain control sleep and wakefulness
  • Responsible for Sensory filtering
• Limbic system
  • Brain stem control of emotion
  • Disorders such as schizophrenia and manic depression
• Extrapyramidal system
  • Responsible for Balance and coordination

Benzodiazepines

• Most common drug class that enhances inhibitory effect on the receptor for the neurotransmitter GABA (Gamma aminobutyric acid)within the brain.
• GABA is the major inhibitory neurotransmitter, slowing or calming things down to increase efficiency (greater inhibition or calming).
• Common Agents:
  • (Xanax) Alprazolam
  • (Librium) Chlordiazepoxide
  • (Valium) Diazepam
  • (Versed) Midazolam
  • (Ativan) Lorazepam
• Benzodiazepine Reversal Medication:
  • (Romazicon) Flumazenil

Midazolam (Versed)

• Has the most rapid onset of all the BZD
• Major disadvantage: requires titration, which is far from feasible in RSI.
• Optimal effects: not observed for 3-5 min
• Is no longer recommended as a 1st line induction agent due to its slow onset and variable potency
• A mild respiratory depressant with overdose reversible with flumazenil

Anesthetics

• Anesthesia is the inability to perceive sensations, either local or general.
• Terminology
  • Induction is the timeframe to create level of anesthesia.
  • Maintenance is where the anesthetized state is continued.
  • Termination is the timeframe for the patient to recover from the anesthesia.

Mode of action:

• Local Anesthesia
  • Administration of an agent that acts locally to stop the transmission of that area sensations.
• General Anesthesia
  • Medication delivered by inhalation or IV
  • Induction of a total anesthetic state in which the patient does not respond to any stimuli.
  • Reserved for surgical procedures imposing substantial stresses on the patient.

Local Anesthesia

• "Caine" medications are divided chemically into amide and ester types.

• Local anesthesia Creates insensitivity to specific body area pain, with no loss of consciousness given topically on mucous membranes or by agent injection into the site.

• Local Ester Anesthetics:

  • Procaine (Novocain)
  • Benzocaine (Anbesol)
  • Tetracaine (Pontocaine)
  • Cocaine

• Local Amide Anesthetics:

  • Lidocaine (Xylocaine)
  • Mepivacaine (Carbocaine)
  • Bupivacaine (Marcaine)

IV Anesthetics

• Used as adjuncts to inhaled anesthesia, or as a primary agent state of anesthesia maintenance:
  • Rapid onset and short duration.
  • Highly lipid-soluble, crossing the blood-brain barrier and placenta.
  • Excreted by the kidneys.
  • Classified as barbiturate, benzodiazepine or miscellaneous.

IV Anesthetics: Common Agents

• Thiopental (Pentothal)
• Methohexital (Brevital)
• Propofol (Diprivan)
• Etomidate (Amidate)*
• Ketamine (Ketalar) – induction agent of choice in patients with reactive airway disease (bronchospasm)
• Midazolam (Versed)

Etomidate

0.3 mg/kg IV

• Onset: 10-15 sec. and Duration of action: 4-10 min.
• Considered the ideal sedative for RSI due to rapidity of onset, short action duration, minimal cardio-depressant effects, and its safety for patients with head injury, and minimal adverse effects.
• Etomidate lacks analgesic effects and has no absolute contraindications to its use in RSI.

Propofol

1-2.5 mg/kg IV

• Onset: 15-45 sec. and a Duration: 5-10 min.
• Produces a dose-dependent and potent depression of consciousness ranging from light sedation to a comatose state.
• Lacks any analgesic activity.
• Possesses amnesic properties.
• Characterized as ultrashort onset, brief duration of action, and extreme potency
• Can cause Hypotension, bradycardia, and tachycardia to occur.

Neuromuscular Blocking Agents (Paralytics)

• History
  • Curare, used by South American Indians
• Clinical Use:
  • Muscle paralysis during surgery
  • In conjunction with anesthesia, prior to endotracheal intubation
  • Muscle paralysis for mechanical ventilation
• Two Classifications:
  • Non-depolarizing
  • Depolarizing

Neuromuscular Blocking Agents

Non-depolarizing Agents:

• Action Mode:
  • Competitive inhibition of ACh at nerve-muscle receptor sites
  • Depolarization does not occur
  • Blockade can be reversed by cholinesterase inhibitors with Ach, while preventing Cholinesterase from breaking down Ach
  • “Indirect Acting” parasympathomimetics as Neostigmine and Pyridostigmine

Specific Non-depolarizing Agents:

• Pancuronium (Pavulon)
• Vecuronium (Norcuron)
• Atracurium (Tracrium)
• Rocuronium (Zemuron) – rapid onset; duration 30-40 min.
• Mivacurium (Mivacron)
• Cisatracurium (Nimbex)
• Doxacurium (Nuromax)

Side Effects of Non-Depolarizing Agents

• Hypotension
• Prolonged apnea
• Tachycardia
• Histamine release: bronchoconstriction

Depolarizing Agents

• Action Mode:
  • Depolarization does occur, with muscle membrane remaining in a refractory state and fasciculations occur.
  • Results in Further contraction is not possible until drug is metabolized, and no action antidote for reversing blockade exists.
  • Characterized as short acting, 2 to 4 minutes, and metabolized by cholinesterase.

Specific Depolarizing Agents

• Succinylcholine (Anectine) – 1.5 mg/kg IV
  • Onset: 45 sec and Duration: 6-10 min.
• Considered the “Gold standard” quick action intubation because it works quickly at vocal cords.
• Rapid onset and short duration product can be given as bolus or infusion.
• Associated to Multiple side effects: cardiovascular, hyperkalemia, malignant hyperthermia, fasciculations, rise in ICP, IOP, IGP, histamine release.

Contraindications to Succinylcholine:

• Major burns within the past year
• Crush injuries
• Stroke/spinal cord injury with extensive denervation
• Malignant hyperthermia, a disease that causes a fast rise in body temperature and severe muscle contractions when someone with the disease gets general anesthesia that passes down through families.
• Hyperkalemia
• Elevated ICP
• Side Effects of depolarizing agents:
  • Histamine release
  • Muscle soreness
  • Prolonged duration of action
  • Inherited abnormality
  • Cholinesterase of an atypical molecular structure with supported ventilation required for hours

Sedation and Paralysis

• Sedation MUST precede use of paralytics
  • Sedation: benzodiazepines, intravenous anesthetic agents
  • Paralysis:
  • depolarizing NMBA (succinylcholine)
  • Non-depolarizing NMBA – gantacurium, rocuronium, cisatracurium, vecuronium, pancuronium