Chemical sedation of excited delirium in the pre-hospital setting

A 30-year-old male presents to emergency medical services profoundly combative with a Richmond Agitation–Sedation Scale of +4 after reported use of intravenous methamphetamines. A preliminary diagnosis of excited delirium syndrome is made based on the history obtained and the decision is made to chemically sedate the patient. While preparing for sedation, you wonder which pharmacological agent will produce the fastest and safest sedation in this patient population.


Comment
Despite the challenges which patients suffering from ExDS will present to practitioners, literature examining the management of these patients in the pre-hospital environment is exclusively from the United States or founded in the setting of an emergency department with regional variations in the optimal sedative recommended for use in this patient population. Although the pre-hospital and emergency department settings share a number of features, the pre-hospital environment is an unpredictable, profoundly resource-poor setting without consistent access to anaesthesia and advanced medical therapies potentially required for management of deteriorating patients with ExDS. This is of particular importance when considering not simply the efficacy, but the safety of pharmacological management of patients presenting with ExDS.

Clinical bottom line
There is insufficient evidence to recommend one pharmacological agent in the management of ExDS within the pre-hospital environment generally, and no evidence specific to specialist paramedic practice in the United Kingdom. Although ketamine is associated with the most rapid onset of adequate sedation in patients with ExDS, it is also associated with the highest rate of adverse events and its use is frequently reported to result in the requirement for endotracheal intubation. However, it is unclear whether the requirement for intubation is driven by clinical need or provider discomfort, given the number of intubations performed by single providers within multiple studies. Antipsychotic agents such as haloperidol and droperidol appear to have a superior safety profile when compared against ketamine and midazolam, although they are associated with a protracted time to adequate sedation, which is of particular relevance in the setting of an ExDS patient and in the setting of the resource-poor pre-hospital environment.
The choice of pharmacological agent for sedation of the patient with ExDS will depend on the local legality of paramedic-led administration of scheduled medications, availability, clinician comfort and available resources to manage unexpected complications. Further high-quality controlled trials of benzodiazepines, antipsychotics and ketamine are required before any recommendation for widespread use of any agent can be made.

Conflict of interest
None declared.

Funding
None.

Clinical scenario
A 30-year-old male presents to emergency medical services (EMS) profoundly combative with a Richmond Agitation-Sedation Scale of +4 after reported use of intravenous methamphetamines. A preliminary diagnosis of excited delirium syndrome (ExDS) is made based on the history obtained and the decision is made to chemically sedate the patient. While preparing for sedation, you wonder which pharmacological agent will produce the fastest and safest sedation in this patient population.

Clinical question
In patients presenting with ExDS in the pre-hospital environment, is the use of benzodiazepines, antipsychotics or ketamine superior in producing rapid and uncomplicated sedation? TX (paramedic or ems or emergency medical service or prehospital or pre-hospital or ambulance or emergency medical technician or emt) AND TX (excited delirium syndrome OR ExDS OR agitation OR acute behavioural disturbance)

Search strategy
Literature was considered relevant if it described a piece of primary research in the pre-hospital setting, with a focus on the pharmacological management of ExDS. Literature was excluded if the research was undertaken in a hospitalbased setting, or if it was non-interventional in nature.

United States of America National Library of Medicine:
90 results, of which nine were considered relevant.

Cumulative Index to Nursing and Allied Health Literature:
145 results, of which eight were considered relevant. None in addition to those identified previously.

Relevant literature
See Table 1 for relevant literature. Single-blind, randomised controlled trial Reduction in agitation 71% reduction in agitation at 10 mins (p < 0.001) in intervention group • Convenience sample with illogical inclusion and exclusion criteria, particularly considering the small volume system the trial was undertaken in.
• Unvalidated sedation scale used to assess level of agitation.
• Over half of the patients in the placebo group never required sedation, bringing the internal validity into question.
• Unclear whether outcome assessors were blind to allocation. Retrospective case series Time-to-sedation 4 mins and 3 mins respectively • No comparator population.

Requirement
• Poorly described objectives from the case series.
• Unclear why ketamine was chosen over standard therapies for the EMS agency (enrolment bias).
• Significant protocol deviation, not all patients received the prescribed subsequent dosage of midazolam with no sub-group analysis performed.
• Significant amount of missing data from patient records, with total reliance on this incomplete data for recording of adverse events (interpretation bias).
• No indication of how records were identified within the EMS system, leading to potential inclusion bias. • Paramedics were not blinded to allocation, as it was known to paramedics that patients were allocated according to day of the month.
• Single-centre trial with small volume of patients, never likely to enrol required numbers.
• Although patients were assessed with the RASS score, they were enrolled based on protocol definitions, limiting external validity.
• Five additional patients excluded by the EMS agency medical control with no reason given. • No objective measurement of agitation or combativeness, making it difficult to analyse requirements and improvement with sedation.

Requirement
• During ketamine period, haloperidol and midazolam remained available for use and 27 patients received this in place of ketamine, potentially suggesting selection bias.
• 55% of intubations were performed by a single provider, with potential for provider discomfort with ketamine influencing intubation rate.
• Staff injury not uniformly documented and may be influenced by reporting bias.