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Many emergency medical services (EMS) providers become lulled into a false sense of security surrounding airway management through repetition and perceived proficiency. However, paramedic delivered airway management has become a hot-button issue in the medical community.1 While extensive education is conducted on the difficult airway, there is another element of difficult airway management which is often overlooked.2,3

The term “difficult airway” is often associated with an “anatomically” difficult airway, being an airway which the provider performing endotracheal intubation has difficulty obtaining an adequate view of the glottic opening. However, there is another component to difficult airway management in which paramedics often receive little training in recognition and management, termed the “physiologically difficult airway.”

Mosier and associates (2015) referenced the term “physiologically difficult airway” in the Western Journal of Emergency Medicine, noting, “physiologic derangements of the patient increase the risk of cardiovascular collapse from airway management.” They further noted specific areas of concern to include hypoxemia, hypotension, severe metabolic acidosis, and right ventricular failure.2 The focus of this article will be the preparation, planning, and treatment of the physiologically difficult airway.

HEAVEN Criteria

Researchers associated with the aeromedical provider Air Methods Corporation developed the “HEAVEN” criteria, published in the American Journal of Emergency Medicine in 2018 to assist in this component of airway management. Prior to this, difficult airway assessment tools were focused on identifying potentially anatomic difficult airways. The goal of this assessment tool was to identify patients who were at-risk of decompensation during rapid sequence induction (RSI).3

The HEAVEN criteria focus on patients who suffer from hypoxia, have either very small or very large body habitus, have anatomic challenges, have vomit, blood, or fluid in their airway, suffer from exsanguinating injuries, and have impaired neck mobility.3 By preparing for and correcting these conditions prior to intubation, patients will have a safer and more physiologically stable intubation attempt.

This article will focus on providing adequate pre-oxygenation and ensuring hemodynamic stability throughout the process of rapid sequence induction.


In preparing for the physiologically difficult airway, pre-oxygenation is a vital first step and should be performed in conjunction with preparation of equipment and evaluation of the airway. The goal of proper pre-oxygenation can also be viewed as the removal of nitrogen from the alveoli.

As nitrogen is normally more prevalent than oxygen at room air, providing an oxygen rich environment in the alveoli can aid in providing an ample reserve of oxygen for diffusion across the alveolar-capillary membrane. This diffusion will occur even during the period of apnea associated with intubation attempts.

When referencing the hemoglobin desaturation curve described by Farmery and Roe (1996),4 this can be a daunting and fear-provoking concept for many providers.

When viewing the diagram on the original source material, oxygen saturation is depicted on the vertical axis on the left, and time of apnea is depicted on the horizonal axis at the bottom. The model shows the time to oxygen desaturation at various oxygen saturations and physiologic states.

Observed at the top of the diagram, pre-oxygenating to 99% provides four minutes of safe apnea time prior to desaturation. In fact, a healthy adult will have nearly 10 minutes of apnea time prior to dangerous desaturation. Additionally, the time from desaturation from 99% to 90% is significantly higher than that of 90% to 60%.

Changes in metabolic demands through body composition or illness can alter this curve, as illustrated by the other oxygen desaturation curves in the model. However, it should be noted that with proper pre-oxygenation, there is still a reserve of oxygen available, and additional time of apnea prior to significant desaturation. These examples align well with Kuzmack and associates in the HEAVEN criteria, and their finding of hypoxia being a significant cause of deterioration during intubation attempts.3

One method to enhance pre-oxygenation is the utilization of apneic oxygenation. This includes the use of a nasal cannula running at high flow to provide a higher pressure of oxygenation to the alveoli. In addition to the high flow rates from a nasal cannula, oxygenation through either a non-rebreather mask or bag-valve mask is utilized to provide high flow oxygenation. Jarvis and associates (2018) utilized this measure as part of a bundle of care for patients undergoing delayed sequence intubation.5

As part of this bundle of care including proper patient positioning, apneic oxygenation, delayed sequence intubation, and a goal-directed pre-oxygenation of a SpO2 of at least 94%, lower rates of peri-intubation hypoxia were observed.5 By taking the time to properly pre-oxygenate patients, especially the critically ill patients encountered commonly in EMS, we provide a better chance at providing positive outcomes for patients undergoing advanced airway management outside of the hospital.

Hemodynamic Stability

Hypotension was specifically noted to be one of the key areas of concern noted by Mosier and associates.2 Specifically, patients who were hypotensive had difficulty tolerating the physiologic insult of RSI medications and intubation. This was further described by Yang and associates (2022) in the American Journal of Emergency Medicine, who found patients who were hypotensive prior to intubation have a higher risk of peri-intubation cardiac arrest.6

The term, “Resuscitation Before Intubation” has become favored in out-of-hospital RSI preparation. This favors aggressive management of hemodynamics, specifically heart rate and blood pressure control, prior to intubation attempts. The thought process in this phrase revolves around a known and expected drop in blood pressure following sedation, paralysis, and intubation. Ensuring the patient is stable enough to tolerate these physiologic changes is paramount to patient safety and long-term outcomes.

This need was highlighted by Spaite and associates (2017) who found in increase in long-term mortality among patients injured with traumatic brain injury (TBI) who experienced incidence of hypotension and hypoxia. Even more concerning, patients with TBI who experienced both hypoxia and hypotension suffered mortality two times greater than those experiencing only one factor.7

This finding highlights the profound impact EMS can have in the long-term mortality of injured patients. By properly defending against these variables early on in patient care with the use of proper pre-oxygenation, intravenous fluids, and potentially short-term vasoactive medications, patients can expect the potential for better survivability.

Induction Agents

The goal of all RSI induction agents is to facilitate a rapid loss of consciousness. However, with so many agents available and utilized, this can become confusing to many providers. Consequently, this is where many EMS providers begin to develop a one-size-fits-all approach. However, two areas of recall for providers are induction agents should always be given prior to paralytics, and the induction agent should be tailored to the patient and situation. Two agents are frequently encountered in the out-of-hospital environment, which will be discussed here.

Etomidate (Amidate) is a rapid onset, short acting hypnotic agent frequently utilized as the induction agent for RSI. With a duration of action of 3-5 minutes, and very rapid onset time, this is often a favored agent for induction. However, as with any medication, there are downsides, especially in the critically ill population. Etomidate can be associated with hypotension, especially exacerbating hypotension in critically ill patients. Additionally, concern should be given in patients with adrenal insufficiency and sepsis.8

Ketamine is an additional medication which has gained popularity for induction in the out-of-hospital environment. With a slightly longer duration of action than Etomidate, Ketamine is classified as a dissociative anesthetic. Interestingly, Ketamine has a dose-dependent relationship, with EMS providers seeking the “fully dissociative” dosing for induction of RSI. One additional benefit of Ketamine is a beta-2 agonist property, which can provide some level of bronchodilation as well.8

Providers utilizing Ketamine should be aware of the possibility of catecholamine release associated with this medication. This catecholamine release may cause harm in the presence of conditions where increases in blood pressure would be problematic. Examples of these conditions include congestive heart failure, acute myocardial infarction (MI), and aortic dissection. Additionally, Ketamine has been long warned against use in TBI. However, recent literature has shown no long-term increase in intercranial pressure associated with Ketamine use in TBI, making it safe to use in this patient population.9

It should be noted that while Ketamine is noted to exhibit a transient rise in blood pressure, this may not be the case in the profoundly unstable patient. This is thought to be due to the depletion in catecholamine reserves in the unstable patient through the compensation process prior to entering a shock state. Prior evidence has demonstrated Ketamine may cause a decrease in an already unstable patient’s blood pressure, which providers should be aware of in the dosing of induction agents in the critically ill patient.8, 10, 11

In determining the best agent to use, a risk/benefit analysis should be performed on the patient when weighing options for induction. Considerations such as active CHF exacerbation, concern for acute MI, or a suspicion of acute aortic dissection should give the provider pause surrounding Ketamine. However, patients with active bronchoconstriction or hypotension may raise concern with Etomidate and take advantage of the pharmacology of Ketamine.8


Chemical paralytics are utilized in RSI to provide muscle flaccidity and intentionally remove the patient’s gag reflex to facilitate intubation. There are many options available, however most fall into the categories of depolarizing or non-depolarizing neuromuscular blockage agents. Depolarizing agents create a widespread depolarization of multiple muscle fibers. During the refractory period following contraction, the muscle fibers are unable to be depolarized, and paralysis is achieved. As a result of paralysis occurring during the refractory period, the duration of paralysis is quite short.

Succinylcholine is an extremely prevalent depolarizing neuromuscular blockade agent. With a very rapid onset and short duration of action, this agent has been very popular for decades for RSI neuromuscular blockade. However, this agent does not come without risk. Due to the widespread muscle contraction, there is also a resulting increase in oxygen consumption and increase in serum potassium levels associated with Succinylcholine. For this reason, Succinylcholine should be avoided in conditions where a rise in potassium should be avoided, such as renal failure and suspected rhabdomyolysis.12

Additionally, malignant hyperthermia is a rare condition associated Succinylcholine. This is a true life-threatening condition associated with significant rises in body temperature, skeletal muscle rigidity, tachycardia, tachypnea, and acidosis. Early recognition by EMS and early hospital treatment are essential for survival in this condition.

Conversely, non-depolarizing paralytics function to block the actions of acetylcholine at the synapses in neurons. This can be thought of as a “lock and key” function, where the non-depolarizing paralytic sits on the acetylcholine receptor site, preventing acetylcholine from binding. As a result of this blockade, the duration of action of non-depolarizing significantly longer than that of their depolarizing counterparts.

Non-depolarizing neuromuscular blockage agents such as Rocuronium and Vecuronium boast significantly longer duration of actions. However, the risks of hyperkalemia and malignant hyperthermia are significantly less. In situations where providers have a high index of suspicion for these conditions, a non-depolarizing neuromuscular blockage agent should be considered.

However, providers should be cognizant of the extended period or muscle paralysis associated with these medications. Early re-sedation is required to ensure the patient is not paralyzed without adequate sedation.

When deciding on the best agent for the presenting patient, multiple factors must be weighed to ensure a safe decision is made for the patient. Patients undergoing dialysis or presenting with other symptoms of hyperkalemia should avoid the use of Succinylcholine. Additionally, the same should be considered for patients with an unknown down-time or who are chronically wheelchair bound due to concerns for rhabdomyolysis.

Post-Intubation Management

While so much of our focus is on the steps to successfully place the endotracheal tube, post-intubation patient management can be just as tenuous. Due to changes in intrathoracic pressure associated with positive pressure ventilation, changes to hemodynamics can be noted following intubation. This can be exacerbated by the effects of the medications utilized to facilitate RSI.

When considering hemodynamic management, hypotension is a common post-intubation concern. This is often a self-limiting condition, however intravenous fluids and short-term vasopressor therapies may assist in stabilizing the patient during this time. Recent literature found no difference in patient outcome between patients receiving push-dose Phenylephrine and Norepinephrine infusion. The recommendations of this research were to tailor vasopressors to patient pathology needs.13

Post-intubation sedation and analgesia must also be on the forefront of provider’s minds. Keeping in mind this is a painful procedure, adequate sedation and analgesia not only allows for easier ventilation, but also aids in blunting the hemodynamic responses to pain. In the normotensive patient, benzodiazepines such as Midazolam are prevalent in the out-of-hospital setting and have been shown to be useful in providing adequate sedation.

Additionally, using benzodiazepines in conjunction with opioids can be beneficial to providing greater levels of sedation and analgesia. For the patient who is hypotensive or near-hypotensive, lower-dose Ketamine may prove useful in preventing as significant of hypotension from forming.


While out-of-hospital care providers receive significant training surrounding safe airway management and recognition of the anatomically difficult airway, often little attention is paid to the physiologically unstable patients and special considerations which must be undertaken with this patient population.

Recent evidence surrounding this issue shows a population who is at-risk for serious complications during intubation attempts. Further education and training should be developed and undertaken regarding this population of patients to ensure patient remain safe and well cared for throughout the procedure. Out-of-hospital care providers should develop a tailor-made approach for each patient to ensure a safe and physiologically stable environment throughout the procedure.


  1. Crewdson, K., Lockey, D. J., Røislien, J., Lossius, H. M., & Rehn, M. (2017). The success of pre-hospital tracheal intubation by different pre-hospital providers: a systematic literature review and meta-analysis. Critical care (London, England), 21(1), 31. DOI: 10.1186/s13054-017-1603-7
  2. Mosier, J. M., Joshi, R., Hypes, C., Pacheco, G., Valenzuela, T., & Sakles, J. C. (2015). The Physiologically Difficult Airway. The western journal of emergency medicine, 16(7), 1109–1117. DOI: 10.5811/westjem.2015.8.27467
  4. Farmery, A. D., & Roe, P. G. (1996). A model to describe the rate of oxyhaemoglobin desaturation during apnoea. British journal of anaesthesia, 76(2), 284–291. DOI: 10.1093/bja/76.2.284
  5. Jarvis, J. L., Gonzales, J., Johns, D., & Sager, L. (2018). Implementation of a Clinical Bundle to Reduce Out-of-Hospital Peri-intubation Hypoxia. Annals of emergency medicine, 72(3), 272–279.e1. DOI: 10.1016/j.annemergmed.2018.01.044
  6. Yang, T. H., Chen, K. F., Gao, S. Y., & Lin, C. C. (2022). Risk factors associated with peri-intubation cardiac arrest in the emergency department. The American journal of emergency medicine, 58, 229–234. DOI: 10.1016/j.ajem.2022.06.013
  7. Spaite, D. W., Hu, C., Bobrow, B. J., Chikani, V., Barnhart, B., Gaither, J. B., Denninghoff, K. R., Adelson, P. D., Keim, S. M., Viscusi, C., Mullins, T., & Sherrill, D. (2017). The Effect of Combined Out-of-Hospital Hypotension and Hypoxia on Mortality in Major Traumatic Brain Injury. Annals of emergency medicine, 69(1), 62–72. DOI: 10.1016/j.annemergmed.2016.08.007
  8. Stollings, J. L., Diedrich, D. A., Oyen, L. J., & Brown, D. R. (2014). Rapid-sequence intubation: a review of the process and considerations when choosing medications. The Annals of pharmacotherapy, 48(1), 62–76. DOI: 10.1177/1060028013510488
  9. Godoy, D. A., Badenes, R., Pelosi, P., & Robba, C. (2021). Ketamine in acute phase of severe traumatic brain injury “an old drug for new uses?”. Critical care (London, England), 25(1), 19. DOI: 10.1186/s13054-020-03452-x
  10. Kim, J., Jung, K., Moon, J., et al. Ketamine versus etomidate for rapid sequence intubation in patients with trauma: a retrospective study in a level 1 trauma center in Korea. BMC Emerg Med 23, 57 (2023). DOI: 10.1186/s12873-023-00833-7
  11. Krebs, W., Werman, H., Jackson, J., Swecker, K. A., Hutchison, H., Rodgers, M., et al. (2021). Prehospital Ketamine Use for Rapid Sequence Intubation: Are Higher Doses Associated With Adverse Events?. Air medical journal, 40(1), 36–40. DOI: 10.1016/j.amj.2020.11.007
  12. Hamilton LA, Watts CS, Crain MR. (2013). Hyperkalemia and Rhabdomyolysis With Succinylcholine Used for Rapid Sequence Intubation: A Case Report. Journal of Pharmacy Technology, 29(6):247-249. DOI:10.1177/8755122513500907
  13. Schmitt, C. J., Mattson, A. E., Brown, C. S., Mara, K. C., Cabrera, D., Sandefur, B. J., & Wieruszewski, E. D. (2023). The incidence of cardiovascular instability in patients receiving various vasopressor strategies for peri-intubation hypotension. The American journal of emergency medicine, 65, 104–108. DOI: 10.1016/j.ajem.2022.12.020

Aaron is a clinical instructor in Creighton University’s Department of Paramedicine. He has over fifteen years of experience in various levels of emergency medicine. Aaron’s research and professional interests include prehospital airway management, bringing critical care level care to the prehospital environment and first responder mental health.

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