Intubation Endotracheal Tube Medications

Mechanism of Action

Various medications and tube devices may be employed during rapid sequence intubation. The most commonly used of these are discussed here.

Etomidate

Etomidate is the most commonly used induction agent for rapid sequence intubation. This medication is a non-barbiturate sedative that depresses central nervous system function by activating gamma-aminobutyric acid (GABA) receptors. The advantages of etomidate therapy include a short onset of action (30 to 60 seconds) and a short half-life (3 to 5 minutes). Etomidate does not affect systemic blood pressure and demonstrates central nervous system (CNS) protective effects such as reduced cerebral blood flow and oxygen uptake.[5] This drug is usually preferable for patients with pre-existing hypotension and trauma.

Ketamine

Ketamine, a phencyclidine derivative, is a noncompetitive antagonist of the N-methyl-D-aspartate (NMDA) receptors, demonstrating analgesic, sympathomimetic, and amnestic properties. This drug has a short onset of action of 1 to 2 minutes and a half-life of 5 to 15 minutes.[6] Ketamine's effectiveness as a bronchodilator makes it a preferable agent for scenarios involving patients with acute severe asthma. 

Propofol

Propofol has multiple mechanisms of action but primarily potentiates GABA receptors. Because it is highly lipid-soluble, it induces sedation within 9 to 50 seconds and has a short half-life of 3 to 10 minutes. Propofol also has anti-convulsive and anti-emetic properties and reduces intracranial pressure, which is beneficial in patients with traumatic brain injury and status epilepticus. Because of such a quick onset of action and short half-life, it is also commonly used as a continuous titratable infusion for sedating mechanically ventilated patients.[7][8]

Neuromuscular Blocking Agents

Neuromuscular blocking agents (NMBAs) cause skeletal muscle paralysis and facilitate laryngoscopy and rapid endotracheal intubation. NMBAs must always be used along with an induction (sedating) agent to ensure the patient is unaware of their environment since they will be unable to respond after paralysis.

• Succinylcholine is a depolarizing NMBA and blocks acetylcholine receptor synaptic signaling at the motor endplate. The initial depolarization causes muscular fasciculation followed rapidly by flaccid paralysis because of persistent depolarization that exhausts the receptor's ability to respond. Succinylcholine has an onset of action of 30 to 60 seconds, lasts approximately 5 to 15 minutes, and is the most commonly used paralytic agent for rapid sequence intubation.
• Rocuronium is a non-depolarizing NMBA that competitively blocks acetylcholine receptors with an onset of action of 1 to 2 minutes but lasts for approximately 45 to 70 minutes. Because of this prolonged action, rocuronium is used only when succinylcholine is contraindicated or unavailable.[9][10]

Endotracheal Tubes

Standard endotracheal tubes (ETTs) are typically made of polyvinyl chloride (PVC); they can also be made from silicone, metal, or rubber, depending on the intended use. ETTs have internal diameters ranging from 2.0 mm to 12.0 mm depending on pediatric or adult patients and the estimate of what size would be appropriate for a given patient based on their anthropometry and the presence or absence of co-existing pulmonary or airway disease. Generally, tubes 7.5 mm to 8.5 mm in diameter are appropriate for average adult males; 7.0 mm to 7.5 mm are preferred for females. Providers should be prepared with multiple sizes of ETTs during intubation, as anatomic variations of the upper airway can be unpredictable. While un-cuffed ETTs are used in newborns, all other patients are given ETTs with an inflatable balloon at the distal end of the tube to form a seal when inflated against the tracheal wall that prevents air leaking around the tube to allow for adequate gas exchange. The cuff also maintains the ETT in the proper position and prevents oropharyngeal and gastrointestinal secretions from entering the lower respiratory tract. A pilot balloon is present on the proximal end of the ETT outside of the patient and has a one-way valve to allow for monitoring of the cuff pressure. A cuff pressure of 20 cm to 30 cm is usually recommended to provide an adequate seal without causing injury to the tracheal wall. Another key feature of standard ETTs includes a radiopaque marking all along the length of the tube to allow for tip identification and tube location on plain chest radiographs. During intubation, an indwelling stylet must be present within the ETT before inserting the ETT into the airway. Oral intubation is the recommended route for placing ETTs in emergent and rapid sequence intubation. Nasal intubation may only be considered for those with oral or mandibular trauma or facial deformities.[11][12]

Administration

Rapid sequence intubation involves sequential steps that lead to successful endotracheal intubation. These steps allow for adequate choice, dose, timing, and sequence of administration of sedatives, analgesics, and paralytics while ensuring that all equipment and the patient are prepared. Rapid sequence intubation using NMBAs is the standard of care and is associated with reduced complications compared to sedatives alone. Rapid sequence intubation comprises the following steps: preparation, pre-oxygenation, pretreatment, paralysis and induction, positioning, placement and confirmation, and post-intubation management. These steps are often called the "7 Ps" of rapid sequence intubation.[13]

Preparation

Preparation includes assessing the difficulty of a patient and establishing adequate intravenous access and continuous monitoring (telemetry, blood pressure, and pulse oximetry). As mentioned previously, ETTs of multiple sizes should be available and tested for cuff leaks. Laryngoscopes, both curved and straight, should be available in various sizes. All laryngoscopes should be checked for a functioning light source. Bedside suction devices should be easily accessible. A backup plan should be readily available even if an airway assessment does not reveal obvious evidence of difficulty. Adequate nursing staff and respiratory therapists must be present to assist with intubation, monitoring, administering drugs, and preparing the ventilator.[14]

Pre-oxygenation

Pre-oxygenation involves providing the highest possible oxygen concentration at high flows for 3 to 5 minutes. This allows the patient to tolerate more prolonged periods of apnea without causing hypoxia during rapid sequence intubation. The upper airway patency must be maintained with chin lift or jaw thrust maneuvers facilitating oxygen entry into the airways. For patients in whom achieving high oxygen saturation is not possible, pre-oxygenation can be performed with non-invasive positive pressure ventilation masks or positive end-expiratory pressure (PEEP) valves that can be added to the bag-valve mask.[15]

Pretreatment

Pretreatment is an additional step involving administering medications that may optimize the patient for intubation. For example, intravenous fluids, anxiolysis with benzodiazepines, or opioid medications may be used before administrating sedatives and NMBAs. Typically, a short-acting opioid, such as intravenous fentanyl, is administered for pretreatment. In patients with reactive airway disease, a short-acting β-agonist (albuterol) may be administered during this step to minimize airway resistance. Rarely, pretreatment with α-adrenergic inotropic agents in patients with shock may circumvent further reduction in mean arterial pressure following intubation due to loss of sympathetic tone from using specific induction agents.

Paralysis and induction

Paralysis with induction involves the simultaneous administration of the medications for sedation and paralysis that have been decided earlier in the preparation phase based on clinical status, allergies, and potential contraindications. During rapid sequence intubation, the dose of these drugs should be pre-calculated and administered intravenously as a bolus and never titrated. The onset and duration of action should all be taken into consideration. Etomidate should be administered intravenously at 0.15 mg/kg to 0.3 mg/kg, depending on the patient's difficulty. Ketamine should be given in a dose of 2 mg/kg intravenously. Propofol is given in doses of 0.5 mg/kg to 2 mg/kg intravenously, depending on hemodynamic stability. Immediately after the induction agent, the paralytic agent of choice is administered intravenously. Succinylcholine is given in a 1.5 mg/kg dose, whereas rocuronium is given in a 1 mg/kg dose.

Positioning

The protection and positioning phase is vital, as the patient is now paralyzed, and the airway must be protected from aspiration. Minimal bag-mask ventilation should be used to keep oxygen saturations adequate; this will be possible only if pre-oxygenation is sufficient. Clinicians can perform the Sellick maneuver by applying pressure over the cricoid cartilage to occlude the esophagus if necessary.

Placement

Placement should occur once adequate sedation and paralysis have been obtained. Direct laryngoscopy should be performed, and once the glottis is visualized definitively, an appropriately sized endotracheal tube with stylet should be placed through the vocal cords under direct visualization. After that, the endotracheal tube cuff is inflated with 10 mL of air, and the stylet is removed. Placement should be confirmed by end-tidal carbon dioxide detection and quantitative or colorimetric methods. Auscultation over both lung fields and the epigastric region should also be performed to ensure equal breath sounds on both sides of the chest are absent in the epigastric region. A chest radiograph should be performed to determine the depth of airway intubation. The endotracheal tube tip should be located 2 cm to 5 cm from the carina on chest radiography.

Management

Post-intubation management involves securing the endotracheal tube, connecting to a mechanical ventilator, and evaluating and managing potential complications. As discussed earlier, appropriate sedation agents should be initiated. Most induction agents have short half-lives.

Adverse Effects

Rapid sequence intubation aims to intubate the trachea safely and as quickly as possible without compromising oxygenation and hemodynamics.[16] During rapid sequence intubation, many complications can arise, some related to the clinical condition, some from adverse effects of medications, and others from the endotracheal tube placement or incorrect confirmation.[17]

Tube size selection is important during the preparation phase of rapid sequence intubation. Attempting intubation with an endotracheal tube that is too large can cause vocal cord injury and laryngeal edema. 

Aspiration of gastric contents is a potential risk in all patients undergoing this procedure. Fasting is encouraged if clinical suspicion for anticipated intubation is high, but this cannot always be achieved in emergencies. Although cricoid pressure can be employed, at times, it can disrupt the laryngoscopy view and lead to esophageal rupture if active vomiting occurs. An aspiration event often results in a new infiltrate following endotracheal intubation on chest radiography.[18]

Esophageal intubation can result in severe hypoxemia, ultimately leading to cardiac arrest and death. Hence, end-tidal carbon dioxide detection (colorimetric or waveform capnography) is recommended to confirm tracheal placement. Pneumothorax is a rare but potentially severe risk with endotracheal intubation; it usually results from a right or left mainstem intubation and can also occur in patients with severe reactive airway disease. Chest radiography following intubation is necessary to identify the tube placement depth and check for pneumothorax.[18]

A key component of successful rapid sequence intubation is adequate sedation. Due to the many available drugs, the adverse effects of each sedative medication must be weighed against its potential benefits. Potential adverse effects of etomidate include myoclonus, nausea/vomiting, and adrenal suppression. A single induction dose of etomidate may cause reversible adrenocortical suppression by reversibly inhibiting 11-β-hydroxylase, a key enzyme in cortisol synthesis. When it occurs, it generally does not last more than 24 hours, and the cortisol level usually does not fall below normal physiologic levels. Etomidate can also lower the seizure threshold in patients who have a known seizure disorder.[19]

Ketamine is known to cause disturbing dreams, hallucinations, and emotional distress as its sedative properties wear off. This is often referred to as the re-emergence phenomenon. This effect can be limited if concurrent benzodiazepine medications are used for sedation. As it increases cerebral blood flow, it should be avoided in patients with elevated intracranial pressures.[6]

Propofol is contraindicated in patients with soybean or egg allergies, as current formulations may contain these products, resulting in a potential allergic reaction. As it decreases sympathetic activity, peripheral vasodilation and myocardial depression occur, leading to hypotension. This often resolves rapidly by replenishing intravascular volume by administering intravenous fluid bolus and sometimes with the transient use of inotropic agents. Propofol may also lead to the potential worsening of an existing neurological injury by reducing cerebral perfusion pressure.[7]

Contraindications

Etomidate can lower the seizure threshold in patients with a seizure disorder and can also cause nausea and vomiting. Etomidate can cause dose-dependent inhibition of adrenal cortisol production for up to 12 hours. Hence, clinicians should exercise caution for patients with known adrenal insufficiency or seizure disorder.[19]

Ketamine’s sympathomimetic effects can lead to an increased cardiac output and blood pressure, which can precipitate cardiac ischemia in patients with known coronary artery disease. Ketamine is also a cerebral vasodilator, which can cause increased intracranial pressures. Due to these side effects, ketamine is contraindicated in patients with closed intracranial trauma, raised intraocular pressures, coronary artery disease, and hypertension.[6]

Propofol most commonly causes hypotension by reducing systemic vascular resistance, which is treated with a bolus of intravenous fluids. Additionally, some patients may have hypersensitivity reactions if allergic to eggs or soy products. Propofol should be used cautiously or avoided in those patients with pre-existing hypotension.[7]

A personal or family history of malignant hyperthermia and conditions predisposing to life-threatening hyperkalemia are absolute contraindications for using succinylcholine.[9]

Enhancing Healthcare Team Outcomes

There are many medications used during endotracheal intubation. While the procedure is performed by nurse anesthetists, anesthesiologists, emergency department physicians, intensivists, and many others, everyone on the interprofessional team must know about the potential adverse effects of these medications. Additionally, it is important to have resuscitative equipment in the room before the procedure. During an emergency intubation, a dedicated nurse must monitor the vital signs. With appropriate collaborative teamwork, vigilant monitoring, and open communication, using appropriate medications for endotracheal administration can successfully help the patient achieve better outcomes.