Scope
This article provides education regarding pharmacological strategies used in sedation of the agitated patient in Emergency Departments. Non-pharmacological strategies for managing agitated patients, not addressed here, should also always be employed, usually before sedation is considered.
For information regarding lawful rights to use restraint and sedation and when to consider the use of restrictive practices consult our Resources Regarding Restraint & Detention of Patients in Emergency Departments.
Please note that sedation of the agitated patient is completely different to procedural sedation which is covered separately in our Approach to Procedural Sedation.
Disclaimer
In addition to our standard disclaimer, note that sedation of the agitated patient is a very high risk clinical process. This article is provided for educational purposes and may be a useful refresher for clinicians who are already competent in sedation or valuable learning for clinicians embarking on the path to attain competency. However by itself, this article does not provide such competency. Alway consult local guidelines and policies and consult a senior clinician when seeking to apply information from this article.
Furthermore, the pharmacological properties and risks of the sedation agents are not discussed in detail – clinicians should consult alternative resources for full prescribing information about these medications before prescribing, including but not limited to, contraindications, precautions, adverse effects and interactions.
Consider the Risks & Resources
Consider the risks that require reduction
- Patient Self Harm
- Direct self harm or indirect harm through leaving the ED in a very unsafe state.
- Risk to Staff
- Sedation risks to patient from different drugs/routes of sedation given their clinical state, co-morbidities, likely co-ingestants
Balancing these risks will dictate the optimal speed of sedation required and partly inform the route and drugs used.
For example a highly agitated, physically violent, large individual may require rapid sedation to protect staff from imminent harm or to protect themselves from self-harm. This may favour the use of drugs or routes that provide rapid sedation.
By contrast an elderly individual with co-morbidities who presents a lower risk to staff and is more easily able to be contained, would favour that accepts a slower onset of sedation where sedation risks from the agents are minimised.
Consider your resources available
In settings with limited critical care skills/sedation experience or less available staff, they may favour an approach with theoretically lower sedation risks, particularly airway and breathing problems. For example, where parenteral sedation is required, some sources have suggested the use of a sole antipsychotic first line followed by ketamine as second line, avoiding the use of benzodiazepines entirely.
By contrast in EDs with high critical care/sedation experience they generally combine benzodiazepines with antipsychotics for parenteral sedation, before considering the use of ketamine. Indeed, safety fears regarding the addition of parenteral benzodiazepines do not appear supported by the evidence, when they are appropriately dose reduced and carefully titrated intravenously in combination with antipsychotics – see the Benefits of Combination Therapy section.
Patients often usually require physical restraint in order to deliver the first or first few doses of parenteral sedation. The number of available restraint-trained staff and their skills may indicate what type of routes that can be considered. For example if there are police or capable security guards available as part of the restraint team, and the patient’s upper limbs can be securely immobilised, the insertion of an IV cannula to titrate rapid onset sedation may be an optimally safe option (see Choosing the Route of Sedation Delivery) below).
Choosing the Route of Sedation Delivery
Choosing between the oral or parenteral route largely depends on the level of patient arousal and their cooperation with sedation medication.
The oral route is preferred for patients who are cooperative with taking oral sedation medication and whose assessment dictates slow onset of sedation is acceptable (see Consider Risks & Resources above). Parenteral sedation will generally be required in other patients.
Parenteral Sedation: IV (intravenous) versus IM (intra-muscular) Route
There is substantial controversy and practice variation regarding the choice of IV versus IM route. The choice of route requires nuance, tailored to the individual situation, considering several factors. The choice may be also be fluid as the clinician reacts to the circumstances and patient behaviour that presents itself as this evolves during sedation delivery and any associated restraint – an initial decision to use one route may require reassessment “on the fly”.
IV sedation:
- Provides faster sedation both because the medication is faster onset and because it can therefore be more rapidly titrated to the required dose at an acceptable sedation risk. This is because less time needs to elapse to observe most of the effect of that dose, before re-dosing.
- Faster sedation can minimise the risk to staff or patient self-harm in highly agitated violent patients.
- IV sedation can increase the sedation risk to the patient if the clinician is less experienced in IV sedation and chooses inappropriate doses/dose frequencies. By contrast, experienced hands can administer sedation with lower sedation risks through judicious rapid titration of appropriate doses.
- If an IV cannula is not already available, this requires a restraint team that has the skills and resources to immobilise a patient (especially upper limbs) for long enough in order to safely insert an IV cannula, or alternatively, a patient who decides to comply with IVC insertion once they realise restraint and sedation is inevitable.
- In addition if the patient is likely to be technically difficult to cannulate then the time taken to cannulate may outweigh any speed of onset benefits from the initial dose of IV sedation compared with the IM route.
- Where it is difficult to insert an IV cannula due to technical or patient compliance reasons, an initial IM dose followed by IV cannulation when the patient is more settled may be preferred.
IM sedation:
- Is slower onset and therefore requires longer periods between re-dosing for an acceptable sedation risk.
- Requires less restraint to deliver the first dose – the degree of patient restraint and immobility required to deliver an IM dose safely is substantially less than to insert an IV cannula. This may place both the staff and patient at less restraint-related risk of harm in delivering that first dose of medication.
- (Note, there are some patients who can not even be safely restrained well enough to deliver IM medication and alternative risk management strategies or resources called in to protect staff and/or the patient.)
- However, due to the slower onset, this may require a much longer period of physical restraint until the sedation takes effect. Longer periods of restraint increase restraint-related risk of harm to both the patient and staff.
- Highly agitated patients, if released from restraint before the sedation has taken effect, may seriously harm staff in attendance. This must be avoided.
- By contrast, there are some patients, whose risk of violence to staff is assessed to be very low and whose primary indication for sedation was to reduce their risk of self-harm (directly harming themselves or indirect harm by leaving the ED in a very unsafe state). Such patients may be well managed with an IM dose requiring only a brief restraint and then can be released from restraint with staff stepping away from the patient, out of reach, to contain them from a distance. Staff can then remain on standby, continually reassessing their risk of violence and self harm and reactive team restraint only if required.
- Even if the IM route has been chosen for initial ED sedation, it is may be advisable to follow up with IV cannula insertion when the patient is more settled to provide the option of sedation delivery by IV route later and to manage sedation related complications (e.g. hypotension).
Sedation Agent Choices
Introduction
Doses provided below are indicated for adults under 65 years of age. In elderly or frail, usually half of the recommended doses are used, especially initially. Lower doses may be used when sedation agents are combined or when patient co-ingestion of sedating drugs has already occurred e.g. alcohol, benzodiazepines.
Dose or dose frequency ranges are provided because different doses are often suitable for different patients depending on their size, arousal or co-morbidities/co-ingestants but also because different resources and guidelines recommend different doses.
Antipsychotics and/or Benzodiazepines are generally used first line as sedation agents either alone or in combination. Also some patients may require an antipsychotic not just for the sedation but also for the treatment of their condition (e.g. for psychosis).
The Benefits of Combination Therapy
Combination therapy can provide synergistic effects with regard to sedation.
With oral dosing the combination may provide a more effective sedation that can be more quick acting than sole agents, especially for patients with higher levels of arousal.
With parenteral dosing, the combination:
- Usually allows the use of lower doses of each agent compared with using each agent alone to achieve the same effective level of sedation.
- Can provide faster and more effective sedation than using either an antipsychotic or benzodiazepine alone.
For example for a moderate to severely agitated patient: a widely used, evidence-based IV combination dose of droperidol and midazolam is the famous “5 and 5” i.e. 5mg droperidol and 5mg midazolam.
- This was demonstrated to provide quicker and more effective sedation compared to 10mg droperidol IV with similar adverse events [Taylor 2017].
- This provides faster and more effective sedation compared to titrated IV midazolam starting with 5mg IV [Chan 2013]
As a result the combination therapy may be the most optimal solution in many situations, having considered your Risks & Resources and choice of delivery route.
Oral Agents
Benzodiazepines
- Lorazepam 1-2mg (max 6-8mg in 24hrs)
- Diazepam 5-10mg (max 60mg in 24hrs), though some sources state 5-20mg.
Can be repeated every 30-60min.
Antipsychotics
- Olanzapine is generally first line due to formulations that are more rapidly absorbed than tablets such as the wafer.
- 5-10mg (max 30mg in 24hrs)
- Different sources recommend different frequencies – eTG states can be repeated every 30min whereas some resources recommend slower repeat dosing (e.g. every 2hrs)
Parenteral Agents
Antipsychotics
- Droperidol is first line
- IV/IM 5-10mg (max 20mg in 24hrs)
- If sole agent, usually 10mg is given, whereas if combined with midazolam usually 5mg is given.
- Redosing: IV every 5-10min, IM every 10-15min
- Olanzapine is an alternative if droperidol can’t be used (e.g. allergy)
- 10mg IM (max 30mg in 24hrs)
- Redosing: repeat every 30min.
- IV use is not officially licensed in Australia but some research supports its IV use at same doses.
Benzodiazepines
- Midazolam
- Most common choice due to rapid onset and ability to use both IV and IM
- IV: 5mg every 3-5 minutes
- IM 5-10mg every 15 minutes
- Ideally obtain IV access after 1st dose for subsequent carefully titrated dosing
- If 20mg cumulative delivered dose over time is insufficient – seek expert advice.
- Duration of action is often only 1-2 hours, so often is not the optimal choice when extended periods of sedation are required.
- Diazepam
- Can only be given parenterally IV (not IM), preferably through a decent sized vein to minimise stinging sensation
- 5-10mg IV doses every 5-10minutes.
- Preferred over midazolam when longer periods of sedation are required.
- So this may be used first line instead of midazolam if suitable IV line available and rapidity of onset not crucial.
- Alternatively it can be used for subsequent dosing after an effective initial sedation with midazolam, when the patient rouses and still requires extension of duration of sedation.
- It is first line in the provision of sedation during Toxidromes such as sympathomimetic, serotenergic and anticholinergic – see Sedation for Toxidromes section.
Options for Patients Resistant to 1st Line Sedation Agents
Occasionally some patients can be very difficult to either initially sedate or keep sedated effectively, despite significant combined antipsyshotic and benzodiazepine delivery.
Other Agents
- Ketamine
- IV 1-1.5mg/kg total dose may be needed if sole agent but less (0.5mg/kg) may be sufficient in combination with other sedatives.
- Alternative methods of delivery
- Given slow IV bolus of total expected dose over 1-2min
- Given 0.5mg/kg doses titrated every 60 seconds
- IM: 4-5mg/kg
- no clear max dose is known though some sources cite 400mg.
- Safety
- Relative safety compared with other sedation agents from an airway and breathing point of view (rare risks of laryngospasm) because it creates a dissociative state rather than deep level of traditional sedation.
- However large IV doses (e.g 1-1.5mg/kg) given as rapid bolus can occasionally cause periods of apnoea – hence dosing recommendations above
- Can create behavioural problems on descent or emergence into/from the dissociative state. This is why this is not usually used 1st line but is an excellent “rescue” option.
- Central sympathetic inhibitors (alpha 2 agonists)
- Provide sedation (and a degree of analgesia) via sympathetic inhibition
- Beware bradycardia, blood pressure instability (initial brief hypertension followed by prolonged hypotension), medication interactions (e.g. with beta blockers) and consider the patient’s physiologic need for preserved sympathetic drive (e.g. sepsis, shock states)
- Closely monitor HR and BP
- Clonidine
- Dose: 100mcg in 10ml saline given slowly IV over 5-10min; can repeat after 15min to a maximum of 200mg
- Oral dosing regimens suggest 50-200mcg QID
- Dexmedetomidine:
- Similar to clonidine with probably better sedation and a little less haemodynamic issues.
- Not typically available in EDs, more commonly in ICU.
- Loading dose infusion: 1 mcg/kg over 10 minutes.
- Maintenance infusion: 0.2-1.0 mcg/kg/hr, starting at 0.4mcg/kg/hr and titrating to effect or side effects.
Other Strategies
- Ensure you have optimised the use of non-pharmacological strategies (beyond the scope of this article).
- Ensure you have assessed, investigated and treated any primary or exacerbating causes of agitation.
- Treat concurrent contributory pathophysiology (e.g. hypoxia, hypercapnia, BSL/metabolic, hypotension, sepsis, CNS infections, seizure activity etc)
- Treat pain
- Untreated pain may not be easily recognised in agitated patients and can contribute to their sedation-resistant agitation
- Aside from usual non-opioid agents, carefully titrated doses of IV opioids may have dramatic effects. If other sedatives such as benzodiazepines have been used, be careful and “go low and go slow” e.g. 2.5mg morphine or 25mcg fentanyl titrated doses and have naloxone available to reverse if needed.
- Bladder care:
- Urinary retention can commonly exacerbate agitation, especially in toxidromes such as anticholinergic syndrome
- A bladder scan, repeated every 4 hours is advisable in agitated and sedated patients along with the insertion of an indwelling urinary catheter as required.
Sedation for Toxidromes
Sedation is often required in toxidromes such as sympathomimetic, seroternergic and anticholinergic syndromes.
Benzodiazepines, usually titrated IV diazepam are generally first line because:
- The extended duration of action with slow offset is appropriate to the extended duration of toxidrome
- It co-targets the suppression of severe physiological autonomic excitation such as severe hypertension, tachycardia, hyperreflexia and clonus.
Addition of an antipsychotic is required if physiological targets have been met and additional sedation is required or because agitation is so severe more rapid and effective sedation is required.
Antipsychotics are generally avoided if anticholinergic syndrome is suspected as the additional anticholinergic load can worse the clinical presentation and delirium.
Monitoring for the Sedated Patient
Monitoring will depend on the type and route of sedation delivered, patient specific concerns and co-morbidities and available resources and skill mix.
In general, in the ED it is essential to have:
- More intensive nursing ratios to observe sedated patients
- Continuous saturations
- Regular blood pressure monitoring
It can be desirable to additionally have:
- CO2 monitoring (usually but not exclusively via a nasal prong detector)
- Continuous cardiac monitoring (if available)
If the patient’s arousal changes and consciousness improves, reassess their decision-making capacity and risks that require reduction. See Resources Regarding Restraint and Detention of ED Patients for more information about this.
References
Guidelines
- eTG (electronic Therapeutic Guidelines, Australia) – Pharmacological management for acute behavioural disturbance in adults (accessed 6/10/24)
- MIMS online drug resource (accessed 6/10/24)
- Royal Perth Hospital – Pharmaceutical Management of Acute Agitation and Arousal in Patients Under 65 (Nov 2021)
- Fiona Stanley Hospital – Acute Severe Behavioural Disturbance (ASBD), Management in the Emergency Department
- WA Country Health Service – Acute Behavioural Disturbance in Emergency Departments (May 24)
- The Acutely Agitated Patient in a Remote Location: Assessment & Management Guidelines – a consensus statement by Australian aeromedical retrieval services (Alice Springs Hospital Retrieval Services, medStar, CareFlight, Royal Flying Doctor Service), 2015
- St Johns Ambulance WA Clinical Practice Guidelines
- Disturbed & Abnormal Behaviour (Oct 2022)
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- Droperidol (March 2023), Ketamine (Oct 2022).
- Queensland Ambulance Service Guidelines
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- Clinical Practice Procedures: Behavioural Disturbances/Emergency sedation – acute behavioural disturbance (Sept 2022)
- Drug Therapy Protocols: Droperidol (Sept 2024), Midazolam (Sept 2022) and Ketamine (July 2022)
Studies