Characterised by extreme agitation and aggression in a patient with an altered mental status, excited delirium syndrome is an increasingly common presentation resulting in a request for paramedic services (Ross, 2017). Excited delirium syndrome is a subcategory of delirium, although the symptoms are generally non-specific and there is no standardised definition of it (Li et al, 2019). Gonin et al (2018) concluded that attempts at defining excited delirium syndrome have generally been syndromic in nature and founded on clinically subjective criteria.
Patients presenting with excited delirium syndrome pose a significant risk, not only to themselves and the paramedics treating them but also to law enforcement and allied health professionals who may be involved.
The triggers for excited delirium syndrome are usually multifactorial in nature. Several medical conditions such as hypoxia, head injury and hypoglycaemia may mimic excited delirium syndrome, and these should not be overlooked because of the distracting nature of the presentation.
Evidence suggests that approximately 10% of excited delirium presentations end in cardiac arrest (Ordoobadi and Kivlehan, 2017).
The objectives of this article are to provide an understanding of this presentation, along with information on a safe and comprehensive approach to its management.
Pathophysiology
While the pathophysiology of excited delirium syndrome is complex and poorly understood (Li et al, 2019), it has two common potential triggers: acute drug use; and psychiatric illness (Ordoobadi and Kivlehan, 2017). Both triggers are reasonably common underlying causative factors that result in calls for paramedic service. Common triggers are shown in Table 1.
| Acute drug use | Methamphetamine |
| Psychiatric illness | Schizophrenia |
Acute use of stimulants or hallucinogenic drugs is most likely to trigger an episode of excited delirium, with the traditional triggers being methamphetamine, cocaine, phencyclidine (PCP) and lysergic acid diethylamide (LSD) (Mash et al, 2009). In addition, newer ‘designer’ drugs such as synthetic cathinones (‘bath salts’), which activate the sympathetic nervous system and produce psychotic behaviour, as well as synthetic marijuana, are all known to produce an agitated state reminiscent of excited delirium syndrome (Benzer et al, 2013; Kesha et al, 2013).
According to Li et al (2019), postmortem examination results have demonstrated the possibility of excessive dopamine stimulation in the striatum, along with an acute exposure to catecholaminergic psychoactive substances. However, Mash et al (2009) argue that the overall significance of this histopathologic finding in relation to excited delirium mortality is uncertain.
A history of schizophrenia or bipolar disorder is a known risk factor for excited delirium syndrome (Vilke et al, 2012; Proctor et al, 2019). Non-compliance with psychiatric medication—in particular a recent history of abrupt cessation of antipsychotic medication—is also thought to be a trigger for excited delirium syndrome in patients with a history of psychiatric illness (Ordoobadi and Kivlehan, 2017).
Cocaine-induced excited delirium syndrome was first recognised in the 1980s following a spike in presentations that have now been identified as excited delirium syndrome—the condition was unknown at the time (Ordoobadi and Kivlehan, 2017). Cocaine induces euphoria through increasing the amount of dopamine in the synapses between neurons in the central nervous system. As dopamine is the primary neurotransmitter in the reward pathways, euphoria results from any significant increase in the amount of dopamine available in the synapses. As a sympathomimetic drug, cocaine also activates the sympathetic nervous system, resulting in tachycardia, tachypnea, hypertension, dilated pupils and increased alertness (Gugelmann and Benowitz, 2018). The potential that cocaine can induce excited delirium syndrome is supported by histopathological findings which indicate excessive dopamine levels are apparent in the striatum (Mash et al, 2009).
Understanding the triggers for excited delirium syndrome and the pathophysiology behind them allow the paramedic to identify the likely signs and symptoms and formulate a clinical management plan.
Excessive dopamine signalling in the central nervous system is a key factor in this presentation, with dopamine affecting the brain’s ability to thermoregulate and maintain normothermia. Increases in dopamine could explain the presence of hyperthermia in excited delirium. However, recent research indicates that reactive oxygen species might be generated in excited delirium syndrome, with the resultant tissue damage being responsible for excited delirium syndrome (Schiavone et al, 2016).
Safety
The main principle when managing excited delirium presentations must be ensuring the safety of the paramedics, law enforcement staff, other health professionals, the patient, carers and the public.
Patients with excited delirium syndrome display violent behaviour, increased pain tolerance and superhuman strength. These patients are difficult to physically restrain and will continue to struggle even once restrained, resulting in further risk of significant clinical harm to themselves, paramedics, law enforcement and allied health professionals involved in their management.
It is for this reason that it is paramount that a dual response is initiated in response to these presentations, with both paramedics and law enforcement officers working collaboratively to treat the patient safely. This dual response approach assists with paramedic safety in the initial stages of treatment, as law enforcement officers can physically control the patient.
To ensure the best possible outcome in the management of excited delirium presentations, consideration should be given to joint training exercises involving both paramedics and law enforcement officers. Multi-agency training exercises improve the understanding of each other’s role in the management of these presentations and ensure that the agencies are best placed to manage these presentations.
While all attempts at verbal de-escalation should be made by one person to avoid confusing an agitated patient, excited delirium patients typically do not respond to verbal de-escalation and will require physical control by law enforcement officers. Coordination with law enforcement officers before the application of physical restraint is important to ensure positive outcomes for patients with excited delirium syndrome, as expeditious access to a restrained patient reduces the time that they spend fighting against the restraints, reducing the risk of injury and the onset of acidosis.
SAFETY is a useful acronym to assist with remembering the main principles when managing a patient with excited delirium syndrome, and provides a structured and systematic approach to risk assessment in these cases (Box 1).
Given the potential for these presentations to escalate rapidly, it is imperative that a risk management and safety focus is adopted and continually re-assessed to minimise the risk of harm. Situational awareness is key to minimising the risks in the management of these presentations (Box 2). This is particularly important when working with new graduates and allied health professionals who may not be as familiar with the risks that are inherent in the provision of emergency, out-of-hospital care to patients with excited delirium syndrome.
Differential diagnosis
While the hallmarks of excited delirium syndrome are agitation and violent behaviour in a patient with an altered mental status, various other medical conditions can produce symptoms similar to it. Altered mental status can result from:
These need to be ruled out as causes for the patient presenting with altered mental status as opposed to assuming that the patient is experiencing an episode of acute behavioural disturbance.
There are several other potential causes for presenting with an altered mental status including:
These also need to be considered as differential diagnoses and are explored with other possible causes below.
| S | Safety: People, Object, Place (POP) threat assessment, constant assessment and reassessment of patient safety, the safety of paramedics and others |
| A | Aggression: be aware of the common triggers of aggression and violence |
| F | Fix: underlying organic illness; focus on de-escalation strategies |
| E | Evaluate: complete a vital signs survey, perfusion status assessment; respiratory status assessment; neurological status assessment; sedation assessment tool score; Signs and symptoms, Allergies, Medications, Past medical history, Last intake, Elimination (SAMPLE) |
| T | Tactical communication: use active listening, empathy, rapport, influence, and behaviour change |
| Y | Yes: I have the right resources: law enforcement, paramedics able to sedate the patient, other paramedic resources such as supervisors |
Anticholinergic toxidrome needs to be considered as overdose on a variety of over-the-counter and prescription medications can produce symptoms such as agitation and hot skin, effectively mimicking excited delirium syndrome.
Neuroleptic malignant syndrome is a neurological emergency associated with the use of antipsychotic medications, which causes altered mental status, hyperthermia, tachycardia, tachypnoea and muscle rigidity.
Serotonin syndrome produces similar presentations to neuroleptic malignant syndrome and needs to be considered while making a differential diagnosis in cases that could easily be misdiagnosed as excited delirium syndrome.
Thyroid storm is another presentation that can mimic excited delirium syndrome as this severe form of hyperthyroidism can produce delirium, tachycardia and hyperthermia.
Infections such as meningitis and encephalitis should be considered as a cause of altered mental status if other signs of infection are present.
Heat stroke should also be considered when ambient weather conditions are likely to cause this presentation, and a reliable history may suggest this to be the cause of the presentation.
Given that approximately 10% of excited delirium cases end in cardiac arrest (Ordoobadi and Kivlehan, 2017), it is imperative that these differential diagnoses/diseases are considered, and any reversible causes of the presentation are addressed as soon as it is safe to do so (Box 3).
Given the nature of these presentations, it is often not possible to address immediate life threats that would normally be identified at the primary survey stage of patient assessment because it may not be possible to complete the primary survey until the patient is physically restrained.
Negative sequelae
An awareness of the complications of excited delirium syndrome is essential to the safe and effective paramedic management of the patient to prevent them entering cardiac arrest.
Excited delirium is known to cause acidosis, rhabdomyolysis and secondary trauma, with approximately 10% of excited delirium patients going into cardiac arrest (Ordoobadi and Kivlehan, 2017).
The exact cause of acidosis remains unknown. However, there is evidence that suggests that extreme exertion beyond normal physiological limits and the resulting lactic acidosis may be a causative factor (Mash et al, 2009). The physiological response to metabolic acidosis is to increase the respiratory rate in an attempt to ‘blow off’ carbon dioxide, resulting in tachypnea. Metabolic acidosis could be further exacerbated by restraint, especially if the patient is restrained in a position that impedes ventilation, resulting in retention of carbon dioxide, subsequently leading to a hypercarbic state.
It is important to note that restraining the patient may cause a fight-or-flight response, even if the position in which the patient is restrained is not impeding ventilation thus exacerbating the metabolic acidosis as the patient exerts further energy struggling against the restraints. This resistance to the restraints will also cause a worsening of the hyperthermia experienced by the patient as the extreme exertion will further increase the generation of heat through the exertion of skeletal muscle.
Generally associated with crush syndrome in the out-of-hospital care setting, rhabdomyolysis is also observed in excited delirium syndrome cases, with the combination of hyperthermia, extreme exertion and agitation being the causative factors in this presentation (Mash et al, 2009). Rhabdomyolysis is likely to be caused by fighting against restraints and, as such, it should be considered in any patient who is restrained and has a history of doing this.
Rhabdomyolysis through the breakdown of as little as 150 g of skeletal muscle is sufficient to cause hyperkalaemia. Myoglobin is released into the bloodstream, secondary to rhabdomyolysis and has a direct effect on the nephrons in the kidneys, leading to acute renal injury. Another common sign of rhabdomyolysis in excited delirium syndrome is hypovolaemia, resulting from the extravasation of fluid into the injured muscle tissue.
Cardiac arrest in excited delirium syndrome presentations is often but not always preceded by a brief period of calm, where a previously violent and agitated patient suddenly becomes tranquil and lethargic. While the cause of cardiac arrest in these presentations is not well understood, it is likely to be multifactorial in nature. Evidence suggests that positional asphyxia is a likely factor because of the potential for respiration to be restricted during the restraint process (Chan et al, 1997). It is important to remember that these patients are already likely to be acidotic, and any restriction of respiration in these cases may precipitate a cardiac arrest.
In patients with excited delirium syndrome induced through acute cocaine use, it is possible that cardiotoxicity resulting from the toxic effects of cocaine on the myocardium may precipitate a cardiac arrest (Takeuchi et al, 2011).
Long QT syndrome has been observed in excited delirium presentations and there is a possibility that QT prolongation may be a factor in cardiac arrest in at least some of these presentations (Bozeman et al, 2013). The likely presence of QT prolongation needs to be considered if paramedics are contemplating the administration of haloperidol or droperidol because there is a risk of exacerbating this QT prolongation in susceptible individuals (Chase and Biros, 2002; Bozeman et al, 2013).
Treatment
The treatment for excited delirium syndrome is non-specific, with the focus being on the amelioration of symptoms and the management of agitation (Li et al, 2019). The management of agitation is key as physical struggle is a significant contributor to the catecholamine surge and metabolic acidosis that these patients experience. Physical restraint of a patient presenting with excited delirium syndrome is often required to minimise the risk of harm to the patient and paramedics.
Physical restraint
It is imperative that any restraints used are not applied in a manner that restricts the patient’s breathing and, as such, an excited delirium patient should never be hog-tied (Ordoobadi and Kivlehan, 2017), nor should they be placed in a prone position (Ordoobadi and Kivlehan, 2017; Gonin et al, 2018). Both approaches restrict the patient’s breathing and reduce the paramedic’s ability to assess airway and breathing, potentially contributing to poor outcomes for excited delirium syndrome patients. Compression of the neck and chest should also be avoided while restraint is required.
Application of four-point restraints, using the one hand up, one hand down position is an appropriate strategy that can be easily used in the emergency out-of-hospital care setting (Ordoobadi and Kivlehan, 2017). This requires the patient to be placed supine on the stretcher with soft restraints applied to all four extremities. Using the one arm up, one arm down position, the upper extremities can be restrained in such a way that the patient’s ability to struggle against the restraints is significantly reduced, thus reducing the development of rhabdomyolysis through a reduction in extreme exertion against the restraints (Ruttenber et al, 1999; Ordoobadi and Kivlehan, 2017). With the head of the stretcher raised to reduce the risk of aspiration, one arm can be secured to the head of the stretcher, while the other arm is secured to the stretcher’s side (Ordoobadi and Kivlehan, 2017).
Sedation
Takeuchi et al (2011) argue that the violent and unpredictable nature of patients presenting with excited delirium syndrome means rapid sedations should be considered to optimise patient outcomes.
Australian emergency services, the BC Emergency Health Services in Canada, the Regional Paramedic Program for Eastern Ontario and a few emergency service providers in the United States authorise paramedic administration of sedative agents for excited delirium syndrome presentations. However, Joint Royal Colleges Ambulance Liaison Committee (JRCALC) guidelines (Brown et al, 2019) for UK paramedics preclude the use of sedation by paramedics, instead emphasising a reliance on physical restraint. Requesting senior clinical staff for on-scene support and sedation should be an early consideration for all paramedics who are unable to administer sedation to manage these presentations.
In Australian emergency out-of-hospital care, sedation should be considered the primary treatment for excited delirium syndrome presentations, with a variety of options available ranging from benzodiazepines to ketamine (Gerold et al, 2015; Sekhon et al, 2021). If antipsychotics such as droperidol or haloperidol are available, these should be considered for use along with a benzodiazepine such as midazolam or lorazepam (Gerold et al, 2015; Sekhon et al, 2021).
When considering agents as a sedative for excited delirium syndrome, those with a short onset time which can be administered via the intramuscular (IM) or intranasal (IN) route should be the first choice.
Chase and Biros (2002) recommend caution in the use of haloperidol or droperidol in patients who have been prescribed psychiatric medication, or in cases where there may be electrolyte abnormalities, as there is a significant risk of QT prolongation and associated cardiac events.
Paramedics authorised to administer sedative agents should have a low threshold for the use of sedation in excited delirium presentations, with consideration for sedation as early as possible in the encounter (Ordoobadi and Kivlehan, 2017).
When deciding on the route of administration, it is important to consider the risks of needlestick injury if attempting IM injection with an agitated patient; the risk is likely less than attempting to insert an IV in the agitated patient but, nonetheless, this risk remains (Ordoobadi and Kivlehan, 2017). Similarly, the risk of bite injury associated with IN administration in an agitated patient needs to be considered (Ordoobadi and Kivlehan, 2017). If both IM and IN routes are available, the paramedic should weigh the risk of a needlestick injury from IM against the risk of bite injury from IN and select the lower-risk option.
The mainstay treatment for sedation in excited delirium syndrome is benzodiazepines as these are familiar to paramedics and widely used in the management of seizures in out-of-hospital care (Ordoobadi and Kivlehan, 2017; Sekhon et al, 2021).
IM administration of benzodiazepines, while effective for sedating patients, does have some disadvantages, including an onset time of up to 15 minutes and a long half-life. Administering multiple doses of midazolam or lorazepam in a short time frame can lead to dose stacking, with excessive sedation occurring many minutes after the initial doses have been administered (Ordoobadi and Kivlehan, 2017).
Finally, as benzodiazepines have a respiratory depressant effect, paramedics must ensure that the patient’s respirations are adequate and should be prepared to manage the patient’s airway and breathing.
Ketamine is a dissociative anaesthetic agent that provides analgesia, amnesia and sedation while preserving airway reflexes and breathing. Because of its wide therapeutic index and minimal side effects, ketamine is increasingly used in the sedation of agitated or violent patients with a recommended dosage of 0.25–2 mg/kg in the intravenous (IV) route or 4–5 mg/kg IM.
With an onset time of 3–5 minutes for an IM dose, its onset of action is much quicker than for benzodiazepines. The duration of action is 20–30 minutes IM (Ordoobadi and Kivlehan, 2017).
While the use of ketamine appears to be promising in the management of excited delirium syndrome, caution is required because a large number of patients with excited delirium syndrome require intubation following the administration of ketamine (Ordoobadi and Kivlehan, 2017; Sekhon et al, 2021). Intubation appears to be higher in patients who received benzodiazepines before ketamine (Scheppke et al, 2014; Olives et al, 2016). Sekhon et al (2021) have reported an increase in adverse outcomes following ketamine administration in older adults. Takeuchi et al (2011) further caution that the evidence base supporting the use of ketamine for emergent sedation in the agitated patient is limited and more structured research is needed to establish its safety and efficacy.
Care for sequelae of the syndrome
The treatment goals for excited delirium presentations change to managing the syndrome’s sequelae once adequate sedation has been achieved.
A key supportive treatment for these patients is fluid resuscitation as extreme exertion and hyperthermia are likely to have led to dehydration because of diaphoresis (Vilke et al, 2012). Hyperthermia should be suspected in these presentations and can be determined by temperature checks. External cooling should be administered in these cases, with consideration given to the use of cooled IV fluids (Takeuchi et al, 2011; Gonin et al, 2018). Administration of fluids at a rate of 20 ml/kg is appropriate as an initial bolus, with a low threshold for additional boluses as required to correct dehydration and to treat rhabdomyolysis (Takeuchi et al, 2011; Ordoobadi and Kivlehan, 2017).
Acidosis is common in excited delirium syndrome presentations and should be a management consideration. While the administration of sodium bicarbonate by the IV route is not authorised in the JRCALC guidelines (Brown et al, 2019), this should be considered in the in-hospital setting as this will treat the acidosis and also start to treat any rhabdomyolysis that may be present through limiting the toxicity of the by-products of skeletal muscle breakdown (Gonin et al, 2018).
In jurisdictions where paramedics are authorised to administer sodium bicarbonate, this should be a consideration where metabolic acidosis is evidenced empirically or based on blood chemistry, with an aggressive reversal of the metabolic acidosis likely to improve patient outcome (Takeuchi et al, 2011; Gonin et al, 2018).
Respiration should be carefully monitored in these cases as patients compensate for metabolic acidosis by increasing their respiratory rate. Measures that may inhibit compensatory hyperventilation should be avoided (Gonin et al, 2018).
Conclusion
While a definitive definition of excited delirium syndrome has not yet emerged, and existing definitions tend to be syndromic and based on clinically subjective findings, these presentations often require treatment that is non-specific and symptomatic.
Safety should be a paramount consideration in the management of these patients, and this can be achieved in part using a dual response where paramedics and law enforcement officers work collaboratively to provide treatment to the patient.
From a patient safety perspective, it is imperative that physical restraints do not restrict the patient’s ability to breathe, with the use of the four-point restraint approach using the one arm up, one arm down position recommended.
Sedation is the primary management approach for excited delirium syndrome, with the use of ketamine and a benzodiazepine recommended. Paramedics who are not authorised to administer sedation should consider making an early request for support from higher-level clinicians who may have this authority.
Following sedation, treatment goals should shift to managing the syndrome’s negative sequelae such as hyperthermia, acidosis and rhabdomyolysis.