Clinical Pearls of Prehospital Agitation Management

Introduction

Prehospital medicine, by its very definition, occurs in an imperfect and potentially dangerous environment. While the vast majority of prehospital encounters occur without incident, some situations necessitate EMS providers gaining rapid control of patient behavior to protect the safety of the public and the patient. The decision to provide prehospital agitation management is not one to be taken lightly and involves heavy consideration between the patient’s rights, clinical status, and the necessity of prehospital intervention in the first place.

What is agitation, really?

Agitation is a catch-all term for any form of general uncooperative state or aggressive behavior by a patient. It is a broad spectrum and ranges from mere verbal aggression to physical violence refractory to de-escalation methods.

Examples of mild agitation include insults, verbal combativeness, elevated tone of voice, or excessive disagreement with providers. Mild agitation poses a hindrance to care but is generally resolvable through verbal coaching and de-escalation. In many instances, it requires no intervention at all. Some patients will not respond to verbal coaching regardless of what we say or do.

Moderate to severe agitation is most likely to require acute intervention by EMS providers. Agitation is most likely to require specific management when the patient’s behavior has begun posing a threat to themself, the community at large, or the EMS providers tasked with their care. Examples of moderate to severe agitation include verbal threats with demonstrated intention to carry them out, physical strikes toward EMS providers, self-injurious behavior, or repeated attempts to remove vital, life-sustaining equipment such as an ETT post-arrest.

Causes of Agitation

When addressing agitation, it is important to ask why the patient is agitated in the first place. Underlying medical issues are often the underlying reason for a patient’s agitation. For instance, patients who are delirious secondary to sepsis are unlikely to benefit from heavy sedatives and pharmacological intervention; rather, reversing their profound hypotension, hypovolemia, and the underlying infection will be the most beneficial. Providing interventions for agitation, especially pharmacological means, that are not tailored to the patient’s specific pathophysiology runs the risk of worsening their condition.

Sepsis

Sepsis is one of the most common causes of agitation and general delirium. Septic shock is a bodily overreaction to a systemic infection resulting in profound, widespread hypoperfusion. It is not a behavioral issue but is rather the result of accumulated toxins and poor blood flow to the areas that matter most. For further info on the pathophysiology of sepsis, check out our article HERE (link here).

Reversing sepsis delirium is focused on managing the patient’s hemodynamic status and providing pressure and oxygenation support. These patients require our medical management to support their vitals and maximize brain perfusion. If you can correct drops in brain perfusion, many sepsis patients will resume normal or near-normal mental status.

There are many secondary issues involved with sepsis management, including the presence of new-onset acute kidney injury (AKI).

Substance Use

Any psychoactive or intoxicating substance can produce mental status changes in high doses. For example, alcohol is one of the most commonly encountered intoxicants. Other common examples of intoxicating substances include opioids/heroin, cocaine, abused OTC medications, and even overdoses of prescribed antidepressants. We will detail some of the most common and clinically relevant cases below.

Opioids - Common opioids include hydromorphone, oxycontin, street heroin, oxycodone, and morphine. Opioids are potent analgesics that have sedative effects and produce life-threatening respiratory depression. While opioids do not commonly produce agitation and are much more likely to result in a lethargic, unresponsive state, patients can still have paradoxical excitation and agitation while under their effects.

Cocaine/Crack/Stimulants - Stimulants are potent agonists for the sympathetic nervous system. For many patients, stimulants can produce intense anxiety, hypertension, nausea/vomiting, intense focus, and a sensation of euphoria. Stimulants cause a surge of catecholamines. Patients on stimulants may experience a mental status resembling mania in which they exhibit increased strength/endurance and believed themselves to be capable of extraordinary tasks. Stimulants are often combined with other medications/substances to increase their effects, so be prepared for multiple toxidromes at play.

Alcohol - Alcohol is one of the most common reasons for delirium and works by as a CNS depressant hrough GABA agonism. Patients under the influence of alcohol often present with discoordinated muscle movements, decreased reaction time, reduced inhibitions, and poor cognition. While people react differently, patients under the influence of alcohol are prone to combativeness and general disorderly conduct. Alcohol can also be a respiratory depressant.

Head Injuries

A patient that is agitated and confused following a significant mechanism of injury is likely experiencing profound shock or a head injury. These patients in particular require careful consideration when making the decision to deploy agitation management measures as almost all pharmacologic means will have an impact on assessment ability. Physical restraints will also worsen agitation and result in ICP increases in an already precarious patient. We will cover this more below.

Patients experiencing delirium secondary to a head injury often fight for a brief period of time before experiencing a rapid decline in mental status.

Alcohol Withdrawal

Patients experiencing alcohol withdrawal are at risk of the development of delirium tremens - or hallucinations associated with the withdrawal process. These patients will also experience severe discomfort including nausea/vomiting, diaphoresis, headache and myalgia, and photophobia. The withdrawal process is also accompanied by severe anxiety. Patients experiencing alcohol withdrawal require careful management to avoid exacerbating their anxiety.

Patients experiencing alcohol withdrawal often experience both auditory and visual hallucinations. Many of these patients will report seeing strange shapes or faces and abnormal tactile sensations. These patients are likely to be extremely fearful if experiencing hallucinations.

In the hospital, patients are given CIWA scoring to assess the severity of their withdrawal symptoms and guide medical management. Management for alcohol withdrawal is largely supportive. Patients experiencing moderate to severe withdrawal symptoms (as dictated by their CIWA scores) will be provided benzodiazepines including Ativan (lorazepam) and Versed (midazolam) for symptom management and seizure prevention.

Nonpharmacologic Methods of Agitation Management

As with all things, we should always exhaust non-invasive care measures before resorting to increasingly invasive measures. As healthcare clinicians, we must ensure that we remain patient advocates and balance the rights of the patient with the medical interests at play when making the decision to employ agitation management.

Verbal counselling and de-escalation is always the gold standard of agitation management. Healthcare clinicians have a variety of therapeutic communication techniques that can be employed to resolve the scenario and avoid further stress for all involved.

Agitation is reversible entirely in many patients if you are able to find the underlying reason for their agitation. For instance, many patients exhibit mild agitation and are verbally combative when they are attempting to refuse to care against medical wishes.

Verbal coaching of patients must be tailored to the specific patient and scenario that EMS clinicians are dealing with. A 20 year old male in college is likely to require different therapeutic communication measures than an 80 year old woman that is upset EMS is removing her from her nursing home room.

When employing verbal counselling, remember the patient is an individual with their own priorities and reasons for being agitated. If you are able to reverse the reason for their agitation and address their concerns, they are likely to be more cooperative.

When using verbal coaching, do:

• Be respectful, courteous, and empathetic to the patient’s condition.

  • Many patients are rational and have a reason for their agitation. Trying to understand the reason for their agitation may be the key to resolving it altogether.

• Be upfront and honest with patients to develop rapport.

  • Lying to patients about things like if the police are involved, if they will be forced to go to the hospital in the instance of suicidal ideation, or the severity of their condition will damage rapport and trust with the patient.

• Build rapport with the patient

  • Trust is a big part of ensuring that the patient continues to comply with treatment and transport. Avoid doing anything to risk damaging it.

  • Focus on commonalities with the patient while maintaining a professional relationship. Take the time to get to know the patient’s pertinent beliefs, goals of care, and frustrations. Understand the events that led up to the EMS encounter.

AVOID:

• Lying to patients

  • Lying to patients destroys rapport and may induce further agitation when the patient realizes they’ve been lied to.

• Making threats

  • Making a threat to a patient as a means of achieving compliance with treatment can constitute assault in many states. There are other more productive ways to achieve compliance.

  • It is against best practices to threaten a patient with law enforcement’s presence. If a scenario calls for law enforcement assistance, request it early. If not, avoid making mentions to law enforcement if not necessary. Many patients will be further agitated by the presence of law enforcement.

Physical Restraints

Physical restraints are indicated for both moderate and severe agitation. Physical restraints should only be used to ensure that the patient remains safely seated during transport and cannot physically strike providers or remove essential medical equipment. This article is not referring to safety measures such as stretcher belts or seatbelts when discussing physical restraints - this article is only discussing the use of restraints for combative or delirious patients.

When restraining patients, it may be best to avoid restraining all 4x extremities at once. Instead, clinicians can opt to leave one lower extremity free. This is done to avoid giving the patient excessive leverage when pulling against restraints. Use the least amount of restraint required to ensure patient and provider safet.y

Examples of restraint methods include cravats (triangular bandages) and commercial restraint devices. A rolled sheet can also be tied around the patient’s extremities as needed. Commercial restraint devices pose the least risk to the patient and are often the most simple to apply.

Current NAEMSP best practices dictate that EMS should avoid the use of rigid restraints such as QuickCuffs, zipties, or handcuffs. These restraints pose a higher risk of tissue ischemia and further injury to the patient (Kupas et al., 2021) and are often less effective than other restraint methods. The only use of hard restraints in EMS is when law enforcement applies them as part of an arrest.

In addition, it is critically important to avoid restraining patients in the prone position. Patients in the prone position are at severe risk of positional asphyxia. A 2021 study found that patients restrained in the prone position have decreased cardiac output in addition to a significantly, dangerously reduced tidal volume (Steinberg, 2021). Patients that are in prone positioning have to expend significant force to keep breathing and can fatigue quickly. Hogtying patients or bending the extremities backward is not an acceptable practice and risks harm to the patient.

Restraints are not without risk. Patients who are restrained by any means have a risk of tissue ischemia around the areas of restraint. In addition, excessively tight restraints pose the risk of neurovascular compromise and damage. Perform full CMS (circulation, motor, sensory) checks of each extremity prior to and following application of restraints. Current best practice is to allow for 2 finger breadths within each restraint to avoid compromising circulation (Kupas et al).

Avoid providing physical restraints as a punitive measure. Do not threaten to place a patient in restraints. This will damage rapport and likely worsen agitation to the point of needing more invasive measures.

Law Enforcement Interactions

EMS and law enforcement often work cooperatively when it comes to a combative patient. However, it is important to remember that EMS remains the medical authority and must be more considerate of the patient’s rights and clinical status. EMS has to toe the line of public safety and medicine whereas law enforcement largely only considers the threat that the patient poses to public safety.

It is never acceptable to sedate or restrain a patient based on law enforcement direction. Always perform your own comprehensive assessment of the patient’s status and weigh the benefits to the risks of sedation & restraint use. Law enforcement is not equipped to conduct assessments of a patient for EMS.

A patient who is handcuffed and under arrest must have law enforcement physically onboard the ambulance. Law enforcement must be readily available to release the patient’s handcuffs if the patient’s status declines.

Clinical Pearls of Physical Restraints

• Head injury victims are at increased risk for elevated intracranial pressure (ICP) concerns. The act of restraining them is likely to induce further agitation and confusion. In doing so, we risk elevating ICP further and exacerbating the issue. Use the least amount of force possible when restraining any patient, but especially patients with increased ICP.

  • It is especially important to sedate these patients if possible when making use of restraints to avoid exacerbating agitation and anxiety.

• Law enforcement must be onboard the ambulance during transports of arrested persons with handcuffs applied. Law enforcement must be available to quickly remove the handcuffs if the patient declines.

  • It is not acceptable for law enforcement to drive separately behind the ambulance in a separate vehicle. Law enforcement must be physically present in the back of the ambulance if the patient is handcuffed and in their custody. EMS providers run the risk of increased liability if transporting handcuffed patients without law enforcement onboard.

• Patients are often confused about why they are being restrained. Altered patients are likely to see EMS’ attempts at restraints as an assault and attempt to defend themselves.

  • Coach the patient on the reason for the restraints, the likely duration of their necessity, and the process of the restraint application. Many patients will be more cooperative if the process is explained rather than forced upon them.

Pharmacologic Management of Agitation

It is often in the best interest of both the crew and the patient to provide pharmacological adjuncts to physical restraints. Doing so decreases patient anxiety, promotes cooperation, and helps ensure a safer transport to definitive care. It can also allow for safe extrication from a scene such as inside a home or in public. We will review the important considerations for pharmacological restraint use, the most common adjunct medications, and clinical pearls below.

Clinical Pearls of Pharmacological Restraints

Chemical restraints are not without their risks. Anytime we provide sedative-hypnotic or mental status-altering medications in the field, we run the risk of CNS depression, respiratory depression, and adverse effects. As with all measures, it is important to balance the clinical status of the patient with the potential benefits of chemical restraints in each scenario.

Advanced airway equipment and cardiac monitoring must be available if a patient is to be given chemical restraints. Many of the common agitation medications carry a significant risk of respiratory depression. If a patient’s respiratory status declines, ALS providers must be able and willing to take over the airway to prevent hypoxia. Providing sedative medications without proper monitoring is dangerous and against best practices.

End tidal CO2 monitoring (ETCO2) is especially important for monitoring sedated patients. ETCO2 allows providers to see a real-time waveform of the patient’s respirations and assess their rate, quality, and the presence of carbon dioxide retention. Sedated patients are at increased risk for hypoventilation, which will in turn induce carbon dioxide retention and potentially lead to respiratory acidosis. If this occurs, the patient may require ventilatory support.

Pulse oximetry is another important vital sign to assess but often has a delay when showing changes in patient status. A patient may be hypoxic by the time that the SpO2 updates to show changes. It is also significantly less reliable for patients with darker skin complexions (Al-Halawani et al., 2023).

Image sourced from Adobe Stock images. Photo of capnography waveform above.

Common Pharmacologic Restraints

• Versed (midazolam)

  Versed, also known as midazolam, is a potent benzodiazepine that is commonly used for emergent sedation, preoperative anxiolysis and sedation, and procedural sedation. Its main mechanism of action is through GABA agonism. It is a potent sedative-hypnotic medication. It is unique in that it induces anterograde amnesia, making it a feasible tool for EMS interventions such as synchronized cardioversion. It is the first-line medication for terminating seizures in many EMS protocols.

  Avoid using midazolam in any patients with a known HX of acute angle-closure glaucoma or in active shock. Midazolam does have vasodilatory effects and reduces sympathetic nervous system drive (Lingamchetty et al., 2023).

  Midazolam (and all benzodiazepines) can induce paradoxical excitation. Signs of paradoxical excitation include agitation, increased aggression, and stereotyped, erratic muscular movements. While no RCT is available exploring paradoxical excitation with midazolam use, a 2004 study on pediatrics found that 3.4 percent of the studied patient population receiving midazolam required ketamine as a second, adjunctive therapy after experiencing paradoxical excitation (Golparvar et al., 2004).

  Exercise caution when using midazolam in a patient who has already ingested high levels of alcohol or other CNS depressants. Stacking the medications can worsen CNS depression and prompt respiratory depression (Lingamchetty et al., 2023).

  What is GABA? Gamma amino-butyric acid (GABA) is an inhibitory neurotransmitter that plays a large role in anxiety, sleep regulation, and stress levels. Alcohol actually has a similar mechanism of action as midazolam - by increasing GABA, alcohol drops stress levels and induces relaxation.

  Major side effects include hypotension, weakness, fatigue, dizziness, altered mental status, poor cognition, and uncoordinated muscle movements.

  Routes: IV/IM/IN

• Ativan (Lorazepam)

  Lorazepam is another benzodiazepine that is similar in mechanism to midazolam. However, lorazepam does have a longer duration of action and may be less optimal than midazolam for prehospital sedation.

  Routes: IV/IM/IN

• Haloperidol

  Haloperidol is a 1st-generation typical antipsychotic that is used for both long-term control of psychotic conditions such as schizophrenia and acute agitation management. It is a dopamine (D2 receptor) competitive antagonist. It is commonly used in EMS protocols for the management of psychiatric disorder-related agitation and psychosis.

  Haloperidol should not be used in elderly patients, especially those with dementia, or those with dopamine-deficient conditions such as Parkinson’s disease. There is an increased risk of mortality with haloperidol use in the elderly (Rahman & Marwaha, 2023). Haloperidol can also result in a drug-induced form of Parkinsonism due to its dopamine-blocking effects.

  Haloperidol is a QT-prolonging medication and should be used with caution. Many patients with diagnosed psychiatric disorders are already on some form of psychiatric medication that can be QT-prolonging. Stacking these medications runs the risk of ventricular dysrhythmia development.

  Dystonia is a significant side effect of antipsychotic use characterized by involuntary, spasmodic muscle contractions (Rahman & Marwaha, 2023). It is extremely unpleasant and sometimes painful for the patient. Tardive dyskinesia is also a concern with antipsychotic use.

  Routes: IV/IM/Long-acting IM/PO

• Benadryl (diphenhydramine)

  Diphenhydramine is a 1st-generation antihistamine medication that is available over the counter. It works via H1 histamine receptor antagonism, preventing the action of histamine. While not a mainline sedative in and of itself, it does still play a role in many EMS protocols nationwide in addition to ER sedation use.

  Diphenhydramine crosses the blood-brain barrier and is a potent CNS depressant (Sicari & Zabbo, 2023). It has anticholinergic properties which make it suboptimal and potentially dangerous when stacking with other anticholinergic substances. For instance, monoamine oxidase A inhibitors, tricyclic antidepressants, and diazepam are all anticholinergic medications.

  Diphenhydramine is useful in reversing the effects of dystonia following sedation with antipsychotics (Sicari & Zabbo, 2023).

  Routes: IM, IV, PO,

• Ketamine

  Ketamine is a dissociative-anesthetic medication with a wide variety of uses. It is commonly used for general sedation, procedural sedation, rapid sequence induction (RSI), and even as a rescue medication in severe bronchospasm. It is less of an overall CNS depressant than the other listed medications.

  Ketamine has a dose range that allows for a variety of effects. At lower dose ranges, it produces analgesia with some dissociation. At higher ranges, it can produce total anesthesia and an unconscious state. It is important that clinicians properly dose the patient for the scenario at hand to avoid over or undersedation.

  Ketamine is known to induce episodes of tachycardia and hypertension that are often transient (Rosenbaum et al., 2024). There is some debate in the medical community about its use in patients where hypertension would be a concern such as patients with head injuries/increased intracranial pressure and known vasculopathies (Rosenbaum et al., 2024).

  Routes: IM/IV/IN

Conclusion

Deciding to provide invasive agitation management methods should be made with care and consideration. EMS clinicians have a unique role in public safety and medicine as first responders tasked with pharmacological sedation. EMS clinicians should exercise significant caution and tact when providing sedation and physical restraints.

References

Al-Halawani, R., Charlton, P., Qassem, M., & Kyriacou, P. A. (2023). A review of the effect of skin pigmentation on pulse oximeter accuracy. Physiological Measurement, 44(5), 05TR01. https://doi.org/10.1088/1361-6579/acd51a

Golparvar, M., Saghaei, M., Sajedi, P., & Razavi, S. S. (2004). Paradoxical reaction following intravenous midazolam premedication in pediatric patients - a randomized placebo controlled trial of ketamine for rapid tranquilization. Paediatric Anaesthesia, 14(11), 924–930. https://doi.org/10.1111/j.1460-9592.2004.01349.x

Kupas, D. F., Wydro, G. C., Tan, D. K., Kamin, R., Harrell, A. J., & Wang, A. (2021). Clinical care and restraint of agitated or combative patients by emergency medical services practitioners. Prehospital Emergency Care, 25(5), 721–723. https://doi.org/10.1080/10903127.2021.1917736

Lingamchetty, T. N., Hosseini, S. A., & Saadabadi, A. (2023, June 5). Midazolam. StatPearls - NCBI Bookshelf. https://www.ncbi.nlm.nih.gov/books/NBK537321/

Olejarczyk, J. P., & Young, M. (2022, November 28). Patient rights and ethics. StatPearls - NCBI Bookshelf. https://www.ncbi.nlm.nih.gov/portal/utils/pageresolver.fcgi?recordid=660f5efd72b48f442b428a43

Rahman, S., & Marwaha, R. (2023, September 1). Haloperidol. StatPearls - NCBI Bookshelf. https://www.ncbi.nlm.nih.gov/books/NBK560892/

Rosenbaum, S. B., Gupta, V., Patel, P., & Palacios, J. L. (2024, January 30). Ketamine. StatPearls - NCBI Bookshelf. https://www.ncbi.nlm.nih.gov/books/NBK470357/

Sicari, V., & Zabbo, C. P. (2023, July 10). Diphenhydramine. StatPearls - NCBI Bookshelf. https://www.ncbi.nlm.nih.gov/books/NBK526010/

Steinberg, A. (2021). Prone restraint cardiac arrest: A comprehensive review of the scientific literature and an explanation of the physiology. Medicine, Science and the Law/Medicine, Science and the Law, 61(3), 215–226. https://doi.org/10.1177/0025802420988370