Beyond Ketamine: When to use Facilitated Intubation in the ED

Authors: Joshua Lowe, MD (EM Attending Physician, USAF); John Patrick, DO (EM Attending Physician, USAF); Michael Yoo, MD (EM Attending Physician, USAF); Rachel Bridwell, MD (EM Attending Physician, USA) // Reviewed by: Alex Koyfman, MD (@EMHighAK) and Brit Long (@long_brit)

Case:

A morbidly obese (BMI >60) 25-year-old male with a past medical history of sickle cell anemia and type 1 diabetes presents to the ED with chest pain and shortness of breath. The patient has one word dyspnea as a result and most of his history is obtained from his wife. She states that he tested positive for influenza three days prior and has been ill, but not unlike when he’s had the cold in the past. This morning when he woke up unable to breathe and with a sharp pain in the middle of his chest. Additionally, she states that he has not been able to eat for the last 2 days and has therefore not taken any of his insulin. Vital signs include BP 105/55 mm Hg, HR 117 beats per minute, RR 45 breaths per minute, SpO2 85% on 15L NRB, T 99.1 F, end tidal CO2 11 mm Hg.

Notable Physical Exam:

General: Tripoding, severe respiratory distress.

HEENT: mild nasal congestion, postnasal drip

Cardiac: tachycardic, regular rhythm, no murmurs, gallops, or rubs

Lungs: clear to auscultation bilaterally

ECG sinus tachycardia to 117 with rate related ST depressions

Bedside ABG shows pH: 7.29, PaCO2 27 mmHg, HCO3: 11 mmol/L, PaO2: 78 mmHg

You are currently concerned that this patient’s influenza and medication non-compliance caused him to go into diabetic ketoacidosis (DKA), in turn leading to an acute chest syndrome. This patient is hypoxic, acidemic, and has relative hypotension. These three parameters have repeatedly been associated with increased peri-intubation cardiac arrest (1-4). You place him on non-invasive  bilevel positive pressure ventilation and start him on an insulin infusion. After an hour, you notice the patient is becoming somnolent, and his respiratory efforts are tiring out despite NIPPV. You decide to intubate the patient. Realizing the risks of neuromuscular blocking agents (NMBAs), you decide to pursue a Ketamine-Only Breathing Intubation (KOBI). Unfortunately, as is all too frequently the case there is a national shortage, and ketamine is on back-order. Are you now forced into attempting a rapid sequence intubation (RSI), knowing the risks for this physiologically difficult patient?

Introduction:

Since the late 1990s, RSI has been the gold standard of emergency intubations (5). First described in 1970, RSI with the near-simultaneous administration of a sedative agent and NMBA has been shown to have increased first-pass success compared with intubation facilitated by a sedative alone (6,7). Also known as Facilitated intubation (FI), the use of intubating with only a sedative was an accepted alternative intubation technique prior to those definitive studies in the late 1990s but quickly was abandoned for RSI in all emergent endotracheal intubations (ETI) (8,9). However, emergency physicians have recently faced a multitude of patients requiring ETI with anatomically and physiologically difficult airways; these patients increase the risk of a can’t intubate/can’t oxygenate scenario or significant hypoxemia, hypercarbia, or acidemia. These clinically challenging intubations prompted emergency clinicians to turn to a KOBI technique and forgoing the use of an NMBA, which are not without risk. They increase the risks of hypoxia and acidosis during the apneic period as well as hypotension and hypoperfusion caused by the abrupt transition from negative-pressure to positive-pressure ventilation (10).  Additionally, many if not most emergency physicians do not receive adequate training on topical awake intubations (TAI) (11). The belief is that KOBI allows a patient to maintain their breathing and airway, while allowing the intubating provider to utilize the skills with which they are most comfortable. Given that KOBI is a sedative only intubation, it may represent a subset of FI with a similar first pass success rate (12).

Paradigm Shift:

Instead of considering FI as RSI without paralytics, FI should be viewed as an awake intubation facilitated by a procedural sedation. In addition to avoiding the risks associated with NMBAs, FI allows the patient to maintain their own airway, thus removing the pressure from a time sensitive intubation as well as mitigating hypercarbia and hypoxemia from the apneic period. This is similar to a delayed sequence intubation (DSI), though no NMBA will be administered after endotracheal tube placement.  The trade off to using FI for these challenging airways is the consideration of an aspiration event, the initial indication for RSI. However, RSI has never been shown to reduce the risk of aspiration in the ED (13) or during emergent OR cases (14). First pass success (FPS) is key as increased attempts correlate to increased desaturation (>10%) events (~10% on first attempt, ~30% on second attempt, ~60% for 4+ attempts) (15). When accounting for the number of attempts, there were no differences in desaturation events between RSI and FI. This suggests that differences in FPS rate likely account for the observed differences in adverse events between RSI and FI (14,15). Still, there are those that believe that FPS is more of a physician-centered endpoint that does not fully reflect important patient-centric outcomes (16). This is because increased attempts have only been associated with transient desaturation events and have not been associated with cardiac arrest, hypotension, dysrhythmia, laryngospasm, dental trauma, mainstem intubation, extubation, or aspiration (5, 13, 15). Using FPS as a marker of success overshadows the clinically significant marker in these patients: hypoxemia, hypotension, and acidemia, especially in the spontaneously breathing patient. While RSI should remain the gold standard in the vast majority of patients in the ED, FI presents an additional technique to mitigate anatomic or physiologic risk.

FI has a long history of use in the prehospital world, as many agencies were/are reluctant to provide paralytics to paramedics. As a result, the data on FI are complicated by the fact that these were intubations that were performed by non-physician providers, with limited and infrequent repetitions, in challenging environments, without the support of other healthcare professionals, and frequently without a ventilator requiring prolonged bag valve masking. Despite this lack of generalizable data, the use of induction agent monotherapy is an emerging approach to these difficult intubations in the ED (12). To date, ketamine has been the agent of choice (12). However, since we are approaching FI as an intubation facilitated by a procedural sedation, other pharmacologic agents are available for the procedure of intubation.

Table 1. A Comparative Overview of Facilitate Intubation Medications

Ketamine:

Mechanism of Action: N-methyl-D-aspartate (NMDA) antagonist, partial mu receptor agonist, indirect brain-derived neurotrophic factor (BDNF) agonist through increasing glutamate.

Pros:

• Rapid onset of action.
• Excellent analgesic properties.
• Minimal respiratory depression, making it suitable for patients with compromised airways.

Cons:

• Laryngospasm, necessitating NMBA use.
• Emergence phenomena and dysphoria.
• Transient increase in blood pressure and heart rate.

Dexmedetomidine:

Mechanism of Action: Central alpha 2 adrenergic agonist.

Pros:

• Sedation and anxiolysis without significant respiratory depression.
• Minimal impact on airway reflexes.
• Suitable for awake procedures and prolonged sedation.
• Suitable for patients with respiratory diseases.
• Potential for rapid reversal by discontinuation.

Cons:

• Slower onset of action.
• Bradycardia and hypotension, especially with bolus loading doses.
• Cost.

Midazolam:

Mechanism of Action: GABA_A

Pros:

• Rapid onset of action.
• Anxiolytic and amnestic effects.
• Minimal cardiovascular effects.

Cons:

• Respiratory depression, particularly when combined with opioids.
• Paradoxical reactions (i.e., agitation or aggression).
• Comparatively slower onset and longer duration.

Etomidate:

Mechanism of Action: GABA_A

Pros:

• Rapid onset of action.
• Minimal cardiovascular depression.
• Cardiac stable.
• Minimal histamine release.

Cons:

• Short duration of action.
• Pain upon injection.
• Adrenal suppression, limiting its use in long procedures or critically ill patients.
• Contraindicated seizures or porphyria.

Propofol:

Mechanism of Action: GABA_A

Pros:

• Rapid onset and offset of action.
• Excellent amnestic and sedative properties.
• Can be titrated easily.

Cons:

• Significant respiratory depression, requiring careful monitoring.
• Hypotension and bradycardia, especially on induction.
• No intrinsic analgesic properties, necessitating analgesic administration and increasing the risk of respiratory depression, hypotension, and bradycardia.

Of these medications, ketamine has often been the agent of choice. Dexmedetomidine is another excellent agent but is relatively expensive and not quickly and readily available in all EDs (17). Midazolam has the profile of an acceptable alternative, though it carries the risk of respiratory depression (17,18). Etomidate is likely an agent of last resort for monotherapy due to the short duration of action (12). Despite the risk of hypotension and bradycardia, propofol has been shown in the ICU setting to be a safe and effective monotherapy intubation agent for hemodynamically unstable patients (19).

Mitigation Strategies

1) Preoxygenation with non-invasive positive pressure ventilation (NIPPV)

Preoxygenation with Non-Invasive Positive Pressure Ventilation (NIPPV) has been shown to significantly improve intubation outcomes by increasing oxygen reserves in the lungs and reducing the risk of desaturation (a drop in oxygen saturation levels) during intubation.

Improved Oxygenation: Positive airway pressure provided by NIPPV can help re-expand collapsed alveoli or atelectatic lung parenchyma, increasing functional residual capacity (FRC), improving ventilation-perfusion matching, and increasing oxygenation (20,21). This additional lung volume can help maintain oxygenation for a longer period, even if the patient becomes apneic during intubation attempts. Patients additionally receive higher concentrations of oxygen, leading to improved oxygen reserves in the lungs (20,22).

Extended Safe Apnea Time: Preoxygenation with NIPPV can extend the duration of safe apnea by denitrogenating lungs (20-22). This oxygenation increases the margin of safety during intubation, especially when there are challenges or delays in securing the airway (20-22).

Reduced Risk of Desaturation: One of the primary goals of preoxygenation is to prevent or delay desaturation during intubation. Desaturation can lead to hypoxia and adverse events. NIPPV helps maintain oxygen saturation levels, reducing the risk of desaturation and its associated complications.

Calculation of Minute Ventilation: Most modern NIPPV machines display the patient’s real time minute ventilation. In acidemic patients, who’s compensatory tachypnea is to maintain homeostasis, the initial respiratory rate is often much higher than you would expect as we aim to keep their paCO2 at a stable range (23). The authors have found that this pre-intubation minute ventilation provides a great post intubation minute ventilation starting point to prevent immediate hypercapnea and decompensation, and thus allowing you time to evaluate the patient and the post intubation blood gas prior to making any changes. However, there are no data at this time to support it.

Improved Hemodynamic Stability at the Time of Intubation: NIPPV can enhance hemodynamic stability by increasing cardiac output and reducing the workload on the heart in particular patients (e.g., SCAPE). However, it increases intrathoracic pressure, decreasing preload which may result in hypotension in critically ill patients. By placing profoundly hypoxic patients on positive pressure ventilation prior to induction, this allows anticipated hypotension to be quantified and mitigated. Logistically, this further allows team members to address hemodynamics and airway sequentially, rather than simultaneously while attempting emergent ETI (20-22).

2) Video Laryngoscopy (VL)

VL offers many benefits that mitigate the risks of FI and help improve FPS (24).

Improved Visualization:

Video laryngoscopes allow for the use of standard or hyperangulated geometry, essentially allowing the operator to “look around the corner” on an anterior airway. Operators can manipulate the blade with less force to optimize the view, making it easier to identify and navigate the endotracheal tube into the trachea.

This allows the operator to see the glottic opening, vocal cords, and surrounding structures more directly and distinctly, even in difficult airway situations. By more easily visualizing the cords the operator is able to time the passage of the tube to coincide with the natural opening of the cords as the unparalyzed patient continues to spontaneously breathe.

Reduced Tissue Manipulation:

With video laryngoscopy, less force is required to achieve proper visualization, reducing the risk of activating the gag reflex, dental trauma, soft tissue injury, and bleeding during intubation attempts (25).

Better Management of Challenging Airways:

Video laryngoscopy is especially beneficial in cases of difficult or unexpected airways, including patients with limited mouth opening, cervical spine immobilization, or obesity (24, 25).

3) Semi-fowler/Ramped/sniffing position

The ramped or semi-fowlers position, also known as the “sniffing position,” is a patient positioning technique used to improve the first pass success during intubation, particularly in patients with challenging airways (figure 1). This position involves elevating the patient’s head and upper body to align the oral, pharyngeal, and tracheal axes, making it easier to visualize the glottic opening and navigate the endotracheal tube into the trachea (26). It is particularly useful in cases of physically difficult airway management, such as in patients with obesity, limited neck mobility, or cervical spine immobilization.

Specifically, the ramped position offers several benefits.

Alignment of Airway Axis: The primary benefit of the ramped position is that it aligns the axis of the airway, specifically the oral, pharyngeal, and tracheal axis (26). The oral axis runs from the lips to the base of the tongue, the pharyngeal axis extends from the base of the tongue to the glottic opening, and the tracheal axis continues from the glottic opening into the trachea (figures 2,3). When these axes are properly aligned, glottic structures are more easily visualized during laryngoscopy.

Improved Visualization: Elevating the patient’s head and upper body in the ramped position creates a more favorable angle for laryngoscopy. It promotes the natural curvature of the spine, aligning the axes and lifting the patient’s head slightly forward. This alignment results in a “sniffing” posture, which extends the neck and positions the head in a way that straightens the airway, allowing for better visualization of the vocal cords and glottis.

Reduced Soft Tissue Obstruction: In some patients, especially those with obesity, myxedema coma, or limited neck mobility, the base of the tongue and other soft tissues can obstruct the view of the glottic opening (23). The ramped position helps displace these soft tissues anteriorly, reducing the risk of obstruction during laryngoscopy.

A well-aligned airway and improved visualization of the glottic opening make it easier for the intubator to pass the endotracheal tube through the vocal cords and into the trachea. This has been shown to increase the first pass success rate in these challenging scenarios, reducing the risk of complications and optimizing patient safety (23).

Case Resolution:

The patient was placed on NIPPV. His minute ventilation was calculated at 41 Lpm, and the ventilator was preset to match. The patient was placed in a semi-fowler’s position and given 0.4mg/kg of midazolam. Once the patient was sedated, the VL blade was inserted, and his vocal cords were visualized. The ET tube was placed in time with the natural opening of his vocal cords, and the patient was moved over to the vent which had been pre-set to match the title volume he was pulling on the NIPPV machine without issue.

Personal take:

While discussing this approach with many EM physicians whom we respect, one recurring critique was “We fought so hard to get the right to use paralytics in the ED, why would you want to go backwards.” We don’t want to go backwards! What we want is to use the right tool/approach for the right patient. We have progressed over the last 2 decades to become masters of RSI in the emergency airway. It’s time to expand that toolbox to be able to utilize old techniques, mitigated by new technology and preparation, to use the best, tailored approach for the physiologic and anatomic features of the patient in front of you. We feel that FI, in conjunction with NIPPV pre-oxygenation, semi-fowler/ramped positioning with their head in the sniffing position, and the use of VL, often provides the best approach for physiologically and anatomically difficult airways, especially in EDs where TAI is frequently not an option.

References:

1. Heffner AC et al. Incidence and factors associated with cardiac arrest complicating emergency airway management. Resuscitation 2013; 84(11): 1500 – 4. PMID: 23911630
2. Kim WY et al. actors Associated with the Occurrence of Cardiac Arrest after Emergency Tracheal Intubation in the Emergency Department. PLoS One 2014; 9(11): e112779. PMID: 25402500
3. Forsythe SM et al. Sodium Bicarbonate for the Treatment of Lactic Acidosis. Chest 2000; 117(1): 260 – 7. PMID: 10631227
4. Mosier JM et al. The Physiologically Difficult Airway. WJEM 2015; 16(7): 1109 – 17. PMID: 26759664
5. Li J, Murphy-Lavoie H, Bugas C, Martinez J, Preston C. Complications of emergency intubation with and without paralysis. Am J Emerg Med. 1999 Mar;17(2):141-3. doi: 10.1016/s0735-6757(99)90046-3. PMID: 10102312.
6. Stept WJ, Safar P. Rapid induction-intubation for prevention of gastric-content aspiration. Anesth Analg. 1970 Jul-Aug;49(4):633-6.
7. Okubo M, Gibo K, Hagiwara Y, Nakayama Y, Hasegawa K; Japanese Emergency Medicine Network Investigators. The effectiveness of rapid sequence intubation (RSI) versus non-RSI in emergency department: an analysis of multicenter prospective observational study. Int J Emerg Med. 2017 Dec;10(1):1. doi: 10.1186/s12245-017-0129-8. Epub 2017 Jan 25.
8. Wang HE, O’Connor RE, Megargel RE, Bitner M, Stuart R, Bratton-Heck B, Lamborn M, Tan L. The utilization of midazolam as a pharmacologic adjunct to endotracheal intubation by paramedics. Prehosp Emerg Care. 2000 Jan-Mar;4(1):14-8.
9. Dickinson ET, Cohen JE, Mechem CC. The effectiveness of midazolam as a single pharmacologic agent to facilitate endotracheal intubation by paramedics. Prehosp Emerg Care. 1999 Jul-Sep;3(3):191-3.
10. Naguib M, Magboul MM. Adverse effects of neuromuscular blockers and their antagonists. Drug Saf. 1998, 18:99-116. 10.2165/00002018-199818020-00002
11. Kaisler, Maria C., et al. “Awake intubations in the emergency department: A report from the National Emergency Airway Registry.” The American Journal of Emergency Medicine 49 (2021): 48-51.
12. Driver BE, Prekker ME, Reardon RF, Sandefur BJ, April MD, Walls RM, Brown CA 3rd. Success and Complications of the Ketamine-Only Intubation Method in the Emergency Department. J Emerg Med. 2021 Mar;60(3):265-272. doi: 10.1016/j.jemermed.2020.10.042. Epub 2020 Dec 9. PMID: 33308912
13. Neilipovitz, David T., and Edward T. Crosby. “No evidence for decreased incidence of aspiration after rapid sequence induction.” Canadian Journal of Anesthesia 54.9 (2007): 748.
14. Wallace C, McGuire B. Rapid sequence induction: its place in modern anaesthesia. Continuing Educ Anaesth Crit Care Pain. 2013;14(3):130–5.
15. Sakles, John C., et al. “The importance of first pass success when performing orotracheal intubation in the emergency department.” Academic Emergency Medicine 20.1 (2013): 71-78.
16. Perlmutter MC, Merelman AH, Strayer RJ. Response to “Success and Complications of the Ketamine-Only Intubation Method in the Emergency Department”. J Emerg Med. 2021 Jun;60(6):816-817. doi: 10.1016/j.jemermed.2021.01.010. PMID: 34147233.
17. Riker RR, Shehabi Y, Bokesch PM, et al. Dexmedetomidine vs Midazolam for Sedation of Critically Ill Patients: A Randomized Trial. JAMA. 2009;301(5):489–499. doi:10.1001/jama.2009.56
18. Lowe J B, Yoo M J, Patrick J O, et al. (August 12, 2023) Facilitated Intubation: Time to Re-examine an Old Technique With Its Associated Risks Mitigated by New Technology. Cureus 15(8): e43364. doi:10.7759/cureus.43364
19. Koenig SJ, Lakticova V, Narasimhan M, Doelken P, Mayo PH. Safety of Propofol as an Induction Agent for Urgent Endotracheal Intubation in the Medical Intensive Care Unit. J Intensive Care Med. 2015 Dec;30(8):499-504. doi: 10.1177/0885066614523100. Epub 2014 Feb 17. PMID: 24536033.
20. Mosier JM, Hypes CD, Sakles JC. Understanding preoxygenation and apneic oxygenation during intubation in the critically ill. Intensive Care Med. 2017, 43:226-8. 10.1007/s00134-016-4426-0
21. Chen FH. Hemodynamic effects of positive pressure ventilation: vena caval pressure in patients without injuries to the inferior vena cava. J Trauma. 1985, 25:347-9. 10.1097/00005373-198504000-00013
22. MacIntyre NR. Physiologic effects of noninvasive ventilation. Respir Care. 2019, 64:617-28. 10.4187/respcare.06635
23. Lellouche F, Delorme M, Brochard L. Impact of Respiratory Rate and Dead Space in the Current Era of Lung Protective Mechanical Ventilation. Chest. 2020 Jul;158(1):45-47. doi: 10.1016/j.chest.2020.02.033. Epub 2020 Jul 2. PMID: 32654726.
24. Li, Timmy, et al. “Video laryngoscopy is associated with improved first‐pass intubation success compared with direct laryngoscopy in emergency department trauma patients.” Journal of the American College of Emergency Physicians Open 2.1 (2021): e12373.
25. Kelly FE, Cook TM. Seeing is believing: getting the best out of videolaryngoscopy. Br J Anaesth. 2016 Sep;117 Suppl 1:i9-i13.
26. Chanthawatthanarak, Sivit, et al. “First-Pass Success Rates of Endotracheal Intubation Using Ramped versus Supine Positioning in the Emergency Department.” Journal of the Medical Association of Thailand 103 (2020).