Rapid tranquilisation (Guidelines)

Warning

The goal of rapid tranquilisation is “to achieve a state of calmness without sedation, sleep or unconsciousness, thereby reducing the risk to self and/or others while maintaining the ability of the patient to respond to communication”(NICE, 2005) when appropriate psychological and behavioural approaches have failed to de-escalate acutely disturbed behaviour.

Quick reference guide (Rapid tranquilisation)

These quick reference algorithms are summaries for use in clinical settings and are to be used alongside the full guideline. 

The goal of rapid tranquillisation is “to achieve a state of calmness without sedation, sleep or unconsciousness, thereby reducing the risk to self and/or others while maintaining the ability of the patient to respond to communication”(NICE, 2005) when appropriate psychological and behavioural approaches have failed to de-escalate acutely disturbed behaviour.

A single as required dose of oral medication is not rapid tranquilisation.

Patient safety

The safety of the patient and others is the primary focus of this guideline. There are various considerations:

  • Non Pharmacological Approaches – can these methods be used to improve the situation?
  • Cumulative Antipsychotic Dose – Take into account regular prescriptions. If not it is possible to exceed maximum daily dose of antipsychotics placing the patient at increased risk of adverse events
  • Combinations – the use of two or more antipsychotics should be avoided where possible due to the risk of additive side effects including QT prolongation. This is a particularly important consideration in rapid tranquilisation where the patient’s physical state predisposes to cardiac arrhythmia. 
  • Age Specific Doses – there are important differences in the medication and doses in older adults and young people compared to in adults aged 18-65. This is covered in the age-specific algorithms.
  • Co-morbid neurological disorders – be aware of the risk of antipsychotics, especially in Parkinsons Disease and Lewy Body dementia where these medications should be avoided, and in epilepsy where the seizure threshold is reduced.

Key guideline updates

  • A benzodiazepine (lorazepam) is the first line drug of choice to achieve rapid tranquilisation.
  • Antipsychotic medication is considered a second line medication, but can be considered first line in exceptional circumstances.

The use of haloperidol has the following important updates:

  • Haloperidol can prolong the QTc and is contraindicated with other such medications (see Appendix 1 for a list of common medications that can prolong the QTc).
  • The use of haloperidol in such a combination renders treatment unlicensed and should be avoided where possible. If clinical circumstances make the use of such combinations unavoidable and all other options have been considered ensure the rationale for treatment is clearly documented. Consider increased monitoring of ECG and biochemical parameters.
  • The SPC for haloperidol requires a pre-treatment ECG. If circumstances make this impractical avoid haloperidol, or if use is unavoidable a clear justification must be documented.
  • The maximum cumulative dose of haloperidol over 24 hours (oral and/or IM)  in adults aged 18 years and above is now 20mg. The maximum cumulative dose in elderly patients is 5mg over 24 hours.

Please refer to the full policy (Section 9) if there is uncertainty about the legal status of the patient and the use of rapid tranquilisation.

The following three algorithms outline rapid tranquilisation options in the different patient age groups.

Algorithm 1: General adult aged 18 to 65 years

Algorithm 2: Older adult, typically over 65 years

Algorithm 3: Young people, 12 to 17 years

Appendix 1: QT prolongation and arrhythmia

Physiological risk factors for QTc prolongation and arrhythmia

  Symptom/sign
Cardiac
  • Long QT syndrome
  • Bradycardia
  • Ischaemic heart disease
  • Myocarditis
  • Myocardial infarction
  • Left ventricular hypertrophy
Metabolic
  • Hypokalaemia
  • Hypomagnesaemia
  • Hypocalcaemia
Others
  • Extreme physical exertion
  • Stress or shock
  • Anorexia nervosa
  • Extremes of age
  • Female gender

Drugs associated with QT prolongation.

This list is not exhaustive. Please refer to www.crediblemeds.org for more detailed information

Antipsychotic effect on QTc
Effect Medication
Nil
  • Brexpiprazole
  • Cariprazine
  • Lurasidone
Low
  • Aripiprazole
  • Asenapine
  • Clozapine
  • Flupentixol
  • Fluphenazine
  • Loxapine
  • Perphenazine
  • Prochlorperazine
  • Olanzapine
  • Paliperidone
  • Risperidone
  • Sulpiride
Moderate
  • Amiulpride
  • Chlorpromazine
  • Haloperidol
  • Iloperidone
  • Levomepromazine
  • Melperone
  • Quetiapine
  • Ziprasidone
High

Any IV antipsychotic

Pimozide

Sertindole

Any exceeding maximum dose
Unknown
  • Pipotiazine
  • Trifluoperazine
  • Zuclopenthixol

 

Non-psychotropics associated with QTc prolongation
Medication class Medication
Antibiotics
  • Erythromycin
  • Clarithromycin
  • Ampicillin
  • Co-trimoxazole
  • Pentamidine
  • (4 quinolones effect QTc – see manufacturers’ literature)
Antimalarials
  • Chloroquine
  • Mefloquine
  • Quinine
Antiarrhythmics
  • Quinidine
  • Disopyramide
  • Procainamide
  • Sotalol
  • Amiodarone
  • Bretylium
Others
  •  Amantadine
  • Cyclosporin
  • Diphenhydramine
  • Hydroxyzine
  • Methadone
  • Nicardipine
  • Tamoxifen
  • Citalopram
  • Escitalopram

General Principles

Aims of the guideline

The aims of this guideline are to:

Rapid Tranquilisation Definition

In this guideline, rapid tranquilisation is the administration of lorazepam and/or an antipsychotic via the parenteral route, or repeated oral administration within 60 minutes.

A single dose of ‘as required’ oral medication is not considered rapid tranquilisation.

Rapid tranquilisation replaces the term emergency sedation in previous policies.

General Guidance

  • Management plans for individual patients should be made in advance with a view to minimising the risk of acutely disturbed behaviour occurring.
  • Consider non-pharmacological approaches
  • Optimise regular medication
  • If the patient requires oral “as required” psychotropic medication consider prescribing:
    • Benzodiazepines
    • Additional “as required” doses of the regular antipsychotic rather than introducing a second antipsychotic (being aware of the potential for this to trigger high dose antipsychotic therapy)
    • Promethazine
  • Early intervention is desirable as disturbed behaviour should be brought under control as soon as possible.
  • Initial attempts should be made to use a non-pharmacological approach rather than medication.
  • Consider and address physical causes for behaviour.

Patient Safety

The safety of the patient and others is the primary focus of this guideline. There are various considerations to ensure patient safety:

  • Non Pharmacological Approaches – first consider whether non pharmacological methods can be used to improve the situation.
  • Cumulative Antipsychotic Dose – When prescribing as required antipsychotic medication ensure that any regular medication is considered. If not it is possible to exceed the BNF maximum daily dose of antipsychotics, and place the patient at increased risk of adverse events.
  • Combinations – concomitant use of two or more antipsychotics should be avoided where possible due to the risk of additive side effects including QT prolongation. This is a particularly important consideration in rapid tranquilisation where the patient’s physical state predisposes to cardiac arrhythmia. 
  • Patient transfer – there are specific issues that relate to the transfer of patients who may require rapid tranquilisation during transport. Refer to 'community setting' for more details.
  • Intravenous (IV) medication – in very rare circumstances IV medication can be prescribed. Refer to 'general hospital setting' for more details.
  • Age Specific Doses – the core of this guideline discusses medication used for the general adult population (aged 18 – 65 years). For patients outside this age range there are important changes to the medication and doses. Refer to 'older adult population typically over 65 years' and 'young people 12-17 years' for more details.
  • Co-morbid neurological disorders – please be aware of the risk of antipsychotics, especially in Parkinsons Disease and Lewy Body dementia where these medications should be avoided, and in epilepsy where the seizure threshold is reduced.

Non Pharmacological Approaches

Whilst medication will continue to have a significant role to play in keeping the situation safe, non pharmacological approaches can significantly reduce the need for such medication. De-escalation techniques can be used where the situation is likely to involve anger, irritation, aggression or risk of violence. In such situations it is incumbent upon the service to provide staff training in de-escalation that enables them to:

  • Recognise the early signs of agitation, irritation, anger and aggression.
  • Understand the likely causes of aggression or violence, both generally and for each service user.
  • Use techniques for distraction and calming, and ways to encourage relaxation.
  • Recognise the importance of personal space.
  • Respond to a service user’s anger in an appropriate, measured and reasonable way and avoid provocation.
  • Re-enforce pre-existing de-escalation and emotional regulation skills.

Rapid Tranquilisation Medications

Route

The oral route should always be considered first and used if at all possible.
If oral medication is not possible then consider the intramuscular (IM) route.
The intravenous (IV) route should only be considered in very rare circumstances. Please refer to 'general hospital setting' for details.

Choice
  • A benzodiazepine (lorazepam) is the first line drug of choice to achieve rapid tranquilisation.
  • Antipsychotic medication is considered a second line medication, but can be considered first line in exceptional circumstances (see section on exceptional circumstances).
  • Avoid lorazepam in patients with compromised respiratory function.
  • Caution using lorazepam in combination with clozapine (respiratory depression in rare cases).
  • Assess risk factors for QTc prolongation  and avoid antipsychotics in patients with compromised cardiovascular function.
  • The prescribing of rapid tranquilisation should take into account the patient’s past response to medication, and any available advance statements.
  • If there is a risk of seizures (such as known epilepsy or alcohol withdrawal) use a benzodiazepine rather than an antipsychotic as the latter can lower the seizure threshold.
  • The use of haloperidol has the following important updates:

    • Haloperidol can prolong the QTc and is contraindicated with other such medications (see 'QTc Cautions and Contraindications' for a list of common medications that can prolong the QTc).
    • The use of haloperidol in such a combination renders treatment unlicensed and should be avoided where possible. If clinical circumstances make the use of such combinations unavoidable and all other options have been considered ensure the rationale for treatment is clearly documented. Consider increased monitoring of ECG and biochemical parameters.
    • The SPC for haloperidol requires a pre-treatment ECG. If circumstances make this impractical avoid haloperidol, or if use is unavoidable a clear justification must be documented.
  • IM aripiprazole or IM olanzapine (unlicensed in UK) are potential alternative antipsychotics that may be preferable to IM haloperidol, depending on individual clinical circumstances. A decision to use these alternatives should be made by a senior doctor.
  • IM olanzapine and an IM benzodiazepine must not be administered within 1 hour of each other.
Safety

Avoid

  • Do not mix lorazepam and an antipsychotic in the same syringe.

Ensure

  • Flumazenil is readily available.
  • Oral and IM procyclidine is readily available.

Specific Issues

Use of Flumazenil

  • Flumazenil is used to reverse the respiratory depression caused by benzodiazepines. It is anticipated that IM administration of benzodiazepines is unlikely to produce this effect. However the use of IM midazolam does increase this risk due to potential drug interactions involving midazolam but not lorazepam.
  • If required, flumazenil should be given by IV injection, 200 micrograms over 15 seconds, then 100 micrograms at 60 second intervals if required. Flumazenil has a short half-life and therefore subsequent doses may be necessary. Usual dose range 300 to 600 micrograms. Maximum total dose = 1mg in 24 hours (one initial dose and eight subsequent doses).

ECG

  • It is usually impractical to obtain an ECG from a patient who requires rapid tranquilisation. Therefore an ECG should be undertaken as soon as is practicable after admission to hospital.
  • Risk of ventricular arrhythmias increases significantly when the corrected QT interval (QTc) increases above normal limits. These limits are 440ms for men and 470ms for women.
  • Any medication which can prolong the QT interval should be stopped if the ECG shows a QTc of greater than 500ms.

Clopixol Acuphase

  • Clopixol Acuphase (zuclopenthixol acetate) is not recommended for rapid tranquilisation due to a long onset and duration of action. If considering its use please refer to 'exceptional circumstances'.

Midazolam (alternative to Lorazepam Injection when unavailable)

  • Midazolam injection is the recommended alternative to lorazepam injection, but this use is outside the product licence and should only be used in circumstances where lorazepam injection is not currently available. Under these circumstances use midazolam IM as an alternative when this guideline refers to lorazepam IM.
  • Please note the dosing is different. Consider a dose of midazolam IM 2·5mg to be equivalent to lorazepam IM 1mg.
  • Speed of onset of sedation with midazolam is around 15 minutes, which is two to three times more rapid than lorazepam. Note however that the duration of midazolam’s action is significantly shorter.
  • Midazolam has a number of significant interactions. Plasma midazolam concentrations may be markedly increased, up to fivefold, by co-administration of macrolide antibiotics (erythromycin, clarithromycin and quinupristin/dalfopristin), by azole antifungals (ketoconazole, itraconazole, and fluconazole) and by HIV protease inhibitors. Check BNF Appendix 1 or the manufacturer’s literature for a fuller list of interactions.

Antipsychotics in Rapid Tranquilisation, and the High Dose Protocol

Antipsychotics

Care should be taken to avoid combinations and high cumulative doses of antipsychotics where possible.
This guideline places an emphasis on lorazepam as the first line medication of choice. Antipsychotics are associated with a number of risks, including neuroleptic malignant syndrome, extrapyramidal side effects, seizures, and adverse cardiac events. There is little difference between antipsychotics and benzodiazepines in the effective management of acute psychotic behaviour (CR190), and given the above concerns, antipsychotic medication should not generally be considered as first line treatment of disturbed behaviour.

Antipsychotics could be considered in the following circumstances:

  • Where benzodiazepine prescription alone has been unsuccessful
  • Where benzodiazepines are contraindicated
  • In patients with a known positive response to antipsychotic medication
  • Where the patient indicates they would prefer antipsychotic medication (e.g. advanced statement).
  • In a patient with delirium

Before prescribing an antipsychotic, carefully consider the following:-

  • Is the patient antipsychotic-naïve?
  • Is there a risk of seizures (e.g. known epilepsy, alcohol withdrawal).
  • Does the patient have a history of adverse reactions to antipsychotics?
  • Are there any cardiac co-morbidities?
  • Is the patient currently prescribed other antipsychotic medication?
  • Does the patient have a co-morbid neurological disorder? - especially Parkinson’s disease or Lewy body dementia where antipsychotics should be avoided.

When an antipsychotic is prescribed, it is important to consider the total amount of different antipsychotic prescribed. This would include any regular antipsychotic (remember to include depot medication), as required medication, once only prescriptions and the dose of rapid tranquilisation you are planning. The purpose is to avoid triggering the high dose protocol where possible.

High Dose Protocol

The high dose protocol is triggered when the daily dose of antipsychotics prescribed exceeds 100% of the BNF maximum dose. This is calculated based on the maximum daily dosages of the various antipsychotics as recommended in the current edition of the BNF. As an example, a patient prescribed olanzapine 10mg regularly and 5mg as required is prescribed 75% of the maximum daily dose.
If this maximum limit is breached do not prescribe antipsychotics for rapid tranquilisation without senior review. The Royal College of Psychiatrists highlights that there is a lack of evidence supporting any benefit of high-dose antipsychotic prescription outweighing the risks, that this is not recommended for rapid tranquilisation, and that in the rare circumstances this occurs the decision should be on the advice of a consultant psychiatrist.
Please refer to the High Dose (Antipsychotic) Protocol for more information if needed.

The Prescribing of Rapid Tranquilisation

Refer to:

  • Algorthim 1 (aged 18-65)
  • Algorithm 2 for older adults (typically over 65 years) 
  • Algorithm 3 for young people (12-17 years)

The Rapid Tranquilisation Algorithms are a guide to the prescription, and monitoring of rapid tranquilisation.

Senior doctors/GPs are responsible for prescribing rapid tranquilisation, or advising that it be prescribed by a junior doctor or non-medical prescriber.

  • On admission the decision to prescribe rapid tranquilisation should be recorded in the Assessment/Admission booklet. Otherwise clearly document the reasons in the patient’s notes.
  • The review of this decision should be at the initial senior review, and at each ward round.

The patient is to be reviewed by a senior member of the medical team within 24 hours of the actual administration of rapid tranquilisation. This should occur on each occasion rapid tranquilisation is administered. The review may include: 

  • Alteration to the patient’s regular treatment.
  • Alteration to the prescribing of as required or rapid tranquilisation as a result of the patient’s response to the medication administered.

Prescribing Information (adults ages 18 to 65)

Lorazepam

Dose (oral, IM or IV) in patients aged 18-65 is 1mg to 2mg.
The bioavailability of the oral and intramuscular routes are similar. The speed of onset of sedation is similar for both routes. The maximum cumulative dose (oral and/or IM) is 8mg in 24 hours.  Also take into consideration any other benzodiazepines that the patient is prescribed.

Note: Refer to 'Older Adult Population (Typically over 65 years)' section for older adult dosing, refer to 'Young People (12-17)' section for young people dosing.
Note: IV lorazepam should only be considered under the general hospital setting. Refer to 'general hospital setting' section for information.
Note: Ensure the dilution of lorazepam IM with an equal volume of water for injection prior to administration

Lorazepam

Maximum Adult Dose

Speed of onset of sedation

Duration of sedation

Time to peak

Oral

8mg in 24 hours

30 to 45 minutes

4 to 6 hours

2  hours

IM

8mg in 24 hours

30 to 45 minutes

4 to 6 hours

1 to 1.5 hours

IV

4mg in 24 hours

5 to 10 minutes

4 to 6 hours

about 5 minutes

Haloperidol

Dose (oral or IM) in patients aged 18-65 is 5mg.
The maximum cumulative dose (oral and/or IM) is 20mg in 24 hours. It is anticipated that most patients will not require more than 15mg cumulatively in 24 hours. The speed of onset of action between the oral and IM route is different.

Note: Refer to 'Older Adult Population (Typically over 65 years)' section for older adult dosing, refer to 'Young People (12-17)' section for young people dosing.
Note: There is a requirement for a baseline ECG prior to treatment with haloperidol, and the need to consider ongoing ECG monitoring. If a pre-ECG is not possible, there needs to be careful consideration given to haloperidol as an appropriate treatment choice. See 'choice' section in 'rapid tranquilisation medications' 
Note: The use of haloperidol is contraindicated in combination with other medicines that prolong the QTc. Refer to 'QTc Cautions and Contraindications.'

Haloperidol

Maximum Adult Dose

Speed of onset of sedation

Duration of sedation

Time to peak

Oral

20mg in 24 hours

1 to 2 hours

4 to 8 hours

2  to 6 hours

IM

20mg in 24 hours

20 to 40 minutes

4 to 8 hours

20 to 40 minutes

Note: Ensure a prescription of procyclidine (oral or IM) alongside haloperidol (as there is a risk of dystonia, especially in young males).

Alternative IM antipsychotics

If the use of haloperidol is inappropriate, and IM antipsychotic medication is considered necessary, then aripiprazole or olanzapine could be considered as alternatives.

Aripiprazole
A single dose of short acting IM aripiprazole is 9.75mg. A repeat dose if needed can be administered after a minimum of two hours.

Aripiprazole

Maximum Adult Dose

Time to peak

IM

30mg in 24 hours

1 to 3 hours

Olanzapine (unlicenced in the UK)
A single dose of short acting IM olanzapine in patients aged 18-65 is 10mg. A repeat dose if needed can be administered after a minimum of two hours.
Note: IM olanzapine as a short acting injection should not be administered within an hour of administering an IM benzodiazepine, especially if alcohol has been consumed.

Olanzapine

Maximum Adult Dose

Time to peak

IM

20mg in 24 hours

15 to 45 minutes

Further prescribing information

It is important to prescribe different routes of administration (oral, IM, IV) on separate lines of the kardex. When prescribing IM or IV medication it is important to cross reference with the oral route, stating ‘if oral route inappropriate’ . The risk of an error in administration is minimised if the routes of administration of a single medication are written on the kardex one below the other.

See: Algorithm 1

Older Adult Population (Typically over 65 years)

Although the rapid tranquilisation guidelines have different recommendations for different age groups, the age ranges are intended as a guide not an absolute.  Overall frailty, the presence of co-morbidities, polypharmacy and previous psychotropic use/response should be considered when deciding what subsection to use.

Aim

 To highlight the specific areas and risks inherent in the rapid tranquilisation of older patients.

This guideline does not cover the treatment of delirium. Please refer to the national guidance on this topic: SIGN guideline 157: Risk reduction and management of delirium (see annex 4)

General principles

Over sedation or unconsciousness is particularly dangerous in frail adults and should not be considered a successful outcome.

  • Consider and address physical causes for behaviour.
  • Older adults may respond to lower doses and may take longer to respond.
  • Start with the lowest appropriate dose and titrate slowly upwards if necessary.
  • If the oral route (preferable) is unavailable use intramuscular (IM) route with caution.
  • Avoid the intravenous (IV) route.
  • Patients with renal or hepatic insufficiency may require a lower initial dose, with subsequent adjustments at smaller increments and at longer intervals.
  • Consider the risk of falls when using sedative medication in this population.
  • Avoid procyclidine use where possible.
  • If in doubt seek advice from psychiatry.
Prescribing Information

A benzodiazepine (lorazepam) is the drug of choice to achieve rapid tranquilisation.
Antipsychotic medication can be considered an alternative in exceptional circumstances (see main policy section and algorithm for older adults)

Lorazepam

  • Benzodiazepines are best avoided if delirium is diagnosed or suspected.
  • Lorazepam is contra-indicated in patients with respiratory depression or severe hepatic insufficiency.
  • Paradoxical reactions to benzodiazepines occur in less than 1% of patients however older adults may be more predisposed to these reactions.

Lorazepam

Initial dose

Maximum Older Adult Dose*

Speed of onset of sedation

Duration of sedation

Time to peak

Oral

0.5mg to 1mg

2mg in 24 hours

30 to 45 minutes

4 to 6 hours

2 hours

IM

0.5mg to 1mg

2mg in 24 hours

30 to 45 minutes

4 to 6 hours

1 to 1.5 hours

  • The bioavailability and speed of onset of sedation is similar for both oral and IM routes

Haloperidol

  • Haloperidol is contra-indicated in the lewy body dementias and Parkinson’s disease.
  • As highlighted in the 'General principles' section of the guideline, there are specific considerations with haloperidol, QTc prolongation, and ECG monitoring.
  • Avoid use in patients with compromised cardiovascular function or at risk of seizure.
  • The IM route generally has significantly greater bioavailabilty than the oral route.
  • The speed of onset of action between the oral and IM route is different.

Haloperidol

Initial dose

Maximum

Older Adult Dose**

Speed of onset of sedation

Duration of sedation

Time to peak

Oral

0.5mg to 1mg

2.5mg in 24 hours

1 to 2 hours

4 to 8 hours

2 to 6 hours

IM

0.5mg to 1mg

2.5mg in 24 hours

20 to 40 minutes

4 to 8 hours

20 to 40 minutes

**doses above 2.5 mg daily should only be considered in patients who have tolerated higher doses and after reassessment of the individual benefit-risk.

Alternative IM antipsychotics

If the use of haloperidol is inappropriate or contra-indicated, and IM antipsychotic medication is considered necessary, then aripiprazole or olanzapine can be considered as alternatives.

Aripiprazole

Aripiprazole

Initial dose

Maximum Older Adult Dose

Time to peak

IM

5.25mg (0.7ml)

30mg in 24 hours

1 to 3 hours

A repeat dose if needed can be administered after a minimum of two hours and up to three injections per 24 hour period.

Olanzapine

Olanzapine

Initial dose

Maximum Older Adult Dose

Time to peak

IM

2.5 to 5mg

20mg in 24 hours

15 to 45 minutes

IM olanzapine as a short acting injection should not be administered within an hour of administering an IM benzodiazepine, especially if alcohol has been consumed.

A repeat dose if needed can be administered after a minimum of two hours; up to three injections per 24 hour period.

See: Algorithm 2

Young people (12 to 17 years)

Age range is intended as a guide and is not absolute; there is wide variation in the weight, height and stage of development of young people between age 12 and 17. Clinical judgement is required in determining the most appropriate dose of medication and caution should be used especially in psychotropic naive individuals.

Aim

 To highlight the specific areas and risks inherent in the rapid tranquilisation of young people.

General principles

This policy is for rapid tranquilisation and is not to guide managing general agitation or distress in young people.

  • Ensure physical causes for acute behavioural disturbance are assessed and treated as appropriate – consider the impact of any physical co-morbidities, developmental disorders and substance use on presentation.
  • Consider the young person’s age and weight when prescribing – in general lower doses will be required in those < 40kg and / or < 16 years of age.
  • Start with the lowest appropriate dose and titrate slowly upwards if necessary.
  • If the oral route (preferable) is unavailable use intramuscular (IM) route with caution.
  • Avoid the intravenous (IV) route where possible.
  • If able discuss use of rapid tranquilisation with Child and Adolescent Psychiatrist prior to use. Where this is not possible use caution and discuss at the next available opportunity. The Phoenix Centre operates Monday – Friday, 9am – 5pm (Tel. 01463 705597) and provides Child and Adolescent Mental Health Services (CAMHS) in Highland.
Prescribing Information

A benzodiazepine (lorazepam) is the drug of choice to achieve rapid tranquilisation. Antipsychotic medication can be considered – atypical antipsychotic by oral route is preferred where possible (see main policy section and algorithm for young people age 12 - 17).
Maximum daily doses includes both oral and intramuscular doses.

Lorazepam

  • Lorazepam is contra-indicated in patients with respiratory depression
  • Paradoxical reactions to benzodiazepines occur in less than 1% of patients however young people may be more predisposed to these reactions.
  • The bioavailability and speed of onset of sedation is similar for both oral and IM routes.

Lorazepam

Initial dose

Maximum Young Person Dose*

Speed of onset of sedation

Duration of sedation

Oral

0.5mg to 2mg

4mg in 24 hours

30 to 45 minutes

4 to 6 hours

IM

0.5mg to 2mg

4mg in 24 hours

30 to 45 minutes

4 to 6 hours

*Higher doses may be used in exceptional circumstances in discussion with senior psychiatrist

Risperidone

  • There is reduced risk of extra-pyramidal side-effects with risperidone compared to haloperidol and use should be considered in antipsychotic naive patents where oral route is available.
  • There is no IM preparation available that is suitable for rapid tranquilisation.

Risperidone

Initial dose

Maximum Young Person Dose

Time to peak

Oral

0.5 to 2 mg

6mg in 24 hours

1 to 2 hours

Haloperidol

  • As highlighted in the 'General principles' section of the guideline there are specific considerations with haloperidol, QTc prolongation, and ECG monitoring.
  • Caution is advised in antipsychotic naive young people as extra-pyramidal side-effects are more common – parenteral anticholingerics e.g. procyclidine must be available.
  • Avoid use in patients with compromised cardiovascular function or at risk of seizure.
  • The IM route generally has significantly greater bioavailabilty than the oral route.
  • The speed of onset of action between the oral and IM route is different.

Haloperidol

Initial dose

Maximum

Young Person Dose**

Speed of onset of sedation

Duration of sedation

Oral

2.5mg

15mg in 24 hours

1 to 2 hours

4 to 8 hours

IM

1 to 2.5mg

7.5mg in 24 hours

20 to 40 minutes

4 to 8 hours

**doses above 15 mg daily should only be considered in patients who have tolerated higher doses and after reassessment of the individual benefit-risk.

Alternative antipsychotics

If the use of haloperidol is inappropriate or contra-indicated, and IM antipsychotic medication is considered necessary, then aripiprazole or olanzapine can be considered as alternatives.

Aripiprazole

Aripiprazole

Initial dose

Maximum Young Person Dose

Time to peak

IM

5.25mg (0.7ml)

30mg in 24 hours

1 to 3 hours

A repeat dose if needed can be administered after a minimum of two hours and up to three injections per 24 hour period.

Olanzapine

Olanzapine

Initial dose

Maximum Young Person Dose

Time to peak

IM

2.5 to 5mg

20mg in 24 hours

15 to 45 minutes

IM olanzapine as a short acting injection should not be administered within an hour of administering an IM benzodiazepine, especially if alcohol has been consumed.

A repeat dose if needed can be administered after a minimum of two hours; up to three injections per 24 hour period.

See: Algorithm 3

The Administration of Rapid Tranquilisation

Administration of medication

Nursing staff may use their professional judgement to administer lorazepam and/or antipsychotic for rapid tranquilisation when this is prescribed.
This decision requires two registered nurses (New Craigs).

Lorazepam
Calculate the total amount of lorazepam that has been administered to the patient in the last 24 hours on all areas of the Kardex. This includes the “as required”,  “once only”, regular prescription and rapid tranquilisation supplementary sheet. Ensure that the total dose administered in 24 hours from all routes does not exceed the maximum dose stated in the rapid tranquilisation prescription. If maximum cumulative dose has been reached you cannot administer any more lorazepam and would need a medical review.

Antipsychotic
The decision to prescribe an antipsychotic for rapid tranquilisation should be made by a senior doctor/GP and the rapid tranquilisation dose should be clearly prescribed. The administration of rapid tranquilisation antipsychotic does not require dose calculation by nursing staff. 

Recording What Has Been Administered via Rapid Tranquilisation and Follow-up

For the administration of rapid tranquilisation, two nurses’ initials should be recorded on the kardex along with the dose administered (New Craigs).

  • All entries for rapid tranquilisation should be recorded in red pen (New Craigs).
  • Any incident requiring rapid tranquilisation and the effect of rapid tranquilisation should be recorded in the case notes (consider using the red sticker system – currently applicable only to New Craigs Hospital).
  • Contact the patient’s consultant/duty consultant requesting that the patient be reviewed within 24 hours of administration of the rapid tranquilisation medication. See section on 'The Prescribing of Rapid Tranquilisation.'
  • A post incident review should take place as soon as possible after the administration of rapid tranquilisation if restraint has been required.

Observation and Monitoring

Basic monitoring uses the ACVPU score, to highlight if the patient is Alert, Confused, responding to Voice or Pain, or Unresponsive.
Nursing observation of mental state, and as necessary, monitoring of vital signs, should be undertaken as per guidance outlined below.
If restraint is required in order to administer via the parenteral route, then a member of the team should take responsibility for protecting and supporting the head and neck, and for ensuring that the airway and breathing are not compromised and that colour and respiration are constantly monitored until restraint ceases.
Check the patient every 15 minutes for 90 minutes following the administration of rapid tranquilisation. This period can be extended if there are concerns, and restarted if further rapid tranquilisation is administered.
The level of checks will depend on the sedation of the patient and the route of administration. For this purpose the ‘ACVPU’ scale is used to assess a patient’s level of consciousness. Patients are defined either as ‘alert’ (A on ACVPU) or ‘sedated’ (C,V,P or U on ACVPU). The levels of checks are outlined below.

Alert Patient

IM Medication administered or sedated patient

  • Talking
  • ACVPU score

If the patient’s consciousness level reduces and becomes sedated the monitoring switches across to the sedated patient.

  • Temperature
  • Pulse
  • Blood Pressure
  • Oxygen saturation
  • Respiratory rate
  • ACVPU Score
  • Record the NEWS score on an observation chart.
  • If the patient refuses NEWS monitoring this should be written along the length of the column for that monitoring episode on the NEWS chart. Record what you can e.g. awake, good colour, respiratory rate.
  • The frequency and duration of checking/monitoring are based on when rapid tranquilisation medication is at its maximum plasma level and overall duration of action.
  • For vital sign monitoring, consider a wrist measurement device such as Omron r5.
  • The ‘Red Sticker’ for monitoring response to rapid tranquilisation should be used in the patient’s notes to identify the time, medication, reason and response to rapid tranquilisation (New Craig only).

Nursing staff who have a concern about a patient who has received rapid tranquilisation medication should seek medical advice at any time. See the table below for triggers for concern and the required remedial action.

Observations and Monitoring: Triggers for concern and how to act

Problem/Change to Baseline

Remedial Action

Respiratory rate reduction to <10 breaths/minute

or

Oxygen Saturation <94% on pulse oximeter

Maintain a patent airway
Give oxygen (caution in patients with COPD)
Give IV flumazenil if benzodiazepine induced respiratory depression.
If induced by any other sedative agent may require mechanical ventilation and transfer to medical care.

Increased temperature

Withhold antipsychotics if above 38oC (risk of neuroleptic malignant syndrome and arrhythmia). Check creatinine kinase urgently.

Pulse increased >100 beats per minutes

Refer to medical care

Pulse decreased <60 beats per minutes

Refer to medical care

Fall in blood pressure of >20mmHg orthostatic drop, or systolic blood pressure <90mmHg, or diastolic blood pressure <50mmHg

Lie patient flat.
Tilt bed towards head.
Monitor closely.

Acute dystonia (including oculogyric crisis)

Give procyclidine 5mg to 10mg IM.
Repeat after 20 minutes if necessary to maximum of 20mg/24 hours.

Legislation relating to Rapid Tranquilisation

Common Law

In medical and psychiatric emergencies in non-detained patients, common law allows treatment to protect a patient’s life and/or the well-being of others. No certification is needed beyond the documentation of an accurate description of the actions taken within the patient’s notes. However any patient who has the capacity to make or withhold consent cannot be given medical treatment without that consent. While the use of common law is acceptable in certain emergency situations, judicious application of the Adults with Incapacity (Scotland) Act 2000, and the Mental Health (Care and Treatment)(Scotland) Act 2003, provide a framework for patients deemed incapable to consent to treatment because of a mental disorder.

Adults with Incapacity (Scotland) Act 2000

Under section 47 of this act, a patient who is incapable of making decisions about medical treatment can be given “any procedure or treatment designed to safeguard or promote physical or mental health” without their consent, subject to the principles of the Act. These are that the treatment must be of benefit, be the least-restrictive, take account of the wishes of the person, consult with relevant others, and encourage the person to use existing skills and develop new skills. The medical practitioner primarily responsible for the medical treatment of the adult must issue a Section 47 Certificate of Incapacity.
This act prohibits the use of force or detention, unless it is immediately necessary and only for so long as is necessary in the circumstances. Therefore if an adult shows continued resistance to treatment for mental disorder consideration should be given to making use of the mental health act.

Mental Health (Care and Treatment) (Scotland) Act 2003

The Act allows for the administration of medication to treat mental disorder (including acutely disturbed behaviour secondary to delirium and dementia) without and/or against the patient’s consent. It does not allow the administration of non-psychiatric treatment without their consent.
Where a treatment plan exists (T2 or T3) which does not permit the administration of medication necessary for rapid tranquilisation of the patient, then a T4 must be completed.
In medical emergencies for any detained patient, Section 243 of the Mental Health (Care and Treatment) (Scotland) Act 2003 allows the administration of medical treatment without consent to:

  • Save a patient’s life.
  • Prevent serious deterioration in the patient’s condition.
  • Alleviate serious suffering on the part of the patient.
  • Prevent the patient behaving violently and/or being a danger to themselves or others.

Following this action the prescribing doctor has a responsibility to inform the Mental Welfare Commission of their action within seven days, and to inform the patient’s Responsible Medical Officer.

Exceptional Circumstances

In exceptional circumstances, based on clinical judgement, there may be good reasons for not following the above guidelines. This section considers these exceptional circumstances. Clearly document in the patient notes why this is the case.

Exceeding Maximum dosing

When the first two stages of the rapid tranquilisation algorithm have failed, or if the maximum amount of prescribed medication has been used and there is a further need for rapid tranquilisation within a 24 hour period, then it is possible to exceed the maximum dosing recommended in the algorithm.
This decision needs to be made by a senior doctor/GP, who can instruct the junior doctor. This is because of the associated increased risks with high dose antipsychotics and benzodiazepines which are outlined elsewhere in this guideline. Every effort should be made to obtain an ECG before exceeding maximum dosing.

First line use of antipsychotic

Occasionally there may be a need to prescribe an antipsychotic as the first line medication for rapid tranquilisation. Whilst this is not the preferred medication, there would need to be justification as to its use with lorazepam or on its own. This may include patient preference in an advanced statement, a history of paradoxical agitation with benzodiazepines, or a positive response previously to this medication.
This decision should be made by a senior doctor/GP, with consideration to the various risks, including the risk of haloperidol in combination with other medications, and the recommendation to have an ECG. See 'choice' section in 'Rapid tranquilisation medications'.

Clopixol Acuphase

Clopixol Acuphase (zuclopenthixol acetate) is not recommended for rapid tranquilisation due to a long onset and duration of action, but may be considered as an option when:

  • The patient is liable to be disturbed over an extended time period.
  • There is a past history of good/timely response.
  • There is a past history of repeated parenteral administration.
  • Cited in an advance statement.

The use of Clopixol Acuphase should be a consultant decision.
Never administer to patients who are neuroleptic naïve.

General Hospital Setting

Intravenous (IV) medication

This sub-section specifically relates to the use of (IV) medication for general adult patients (18-65 years).
Rapid tranquilisation for general adults using the oral or intramuscular route is covered in the 'Prescribing Information (adults ages 18-65)' section of this guideline.

Choice

The oral and IM routes should be considered first. The use of IV lorazepam should only be considered:

  • If rapid tranquilisation is essential.
  • If a peripheral venous cannula is already in situ.
  • If an anaesthetist is available on site, or a member of staff is available who is competent in advanced airways techniques.
  • Following discussion with a senior member of the medical team.
  • After ensuring flumazenil is prescribed.

Avoid where possible in young people (12-17 years) and avoid in older adults (typically over 65 years).
IV haloperidol is not licensed for rapid tranquilisation. Given the serious potential side effects and interactions of haloperidol it is not considered first line choice for rapid tranquilisation, and is not for use through the IV route.
If using the IV route, lorazepam is the first line medication to consider, and the only medication covered in this guideline.

Dose

The dose and speed of action for IV lorazepam varies compared to the oral and IM routes. The maximum single dose is 2mg, the maximum daily dose is 4mg/24 hours and the speed of onset of sedation is 5 to 10 minutes following administration. 
The following flow diagram should be considered when prescribing and administering IV lorazepam.

Community Setting

Occasionally patients in the community setting will require rapid tranquilisation. This may take place in a variety of scenarios, such as at the patient’s home, at a nursing home, or during transport. The assessing senior doctor/GP is responsible for recommending rapid tranquilisation and prescribing this on the kardex if indicated.
At the time of initial assessment it may be that rapid tranquilisation is not considered necessary.
If the patient's mental health subsequently deteriorates then the senior doctor/GP should return to reassess and, if indicted, prescribe rapid tranquilisation. In exceptional circumstances, when this is not possible, the advice of the senior doctor/GP should be sought. They can advise on the prescribing of rapid tranquilisation by a junior doctor or non-medical prescriber who has reviewed the patient.

Lorazepam

There is a risk with lorazepam of respiratory depression. This should be managed with attention to airway and breathing, with oxygen if required, and can be reversed with IV flumazenil.
IV flumazenil should be prescribed as an “as required” medication alongside IM lorazepam. (see 'specific issues').
If there are no signs of deteriorating consciousness or respiratory depression an hour following rapid tranquilisation, the risk of developing this is considered low.

Specific Environments

Patient’s Home
If IM lorazepam is administered at the patient’s home, the clinician should remain on site for an hour, or until replaced by ambulance crew or nursing staff.  Emphasis is on early identification of deteriorating respiratory function by monitoring closely (see 'observation and monitoring' section) and responding to a deterioration in respiratory function by calling an ambulance and supporting and maintaining an airway until an ambulance arrives.

 Stability/Storage
The manufacturer does not guarantee stability out of the fridge for longer than a period of 30 minutes. Beyond that its use would be "off licence". However, data indicates that lorazepam injection remains stable for a period of up to 6 months at ambient temperatures (fluctuating between 10 to 30 degrees centigrade).

Transport

Escort or place of safety teams should establish that appropriate medication has been prescribed. 

An ambulance with oxygen and airway/breathing adjuncts is required for transport due to the possible risk of respiratory depression in patients who have had, or may require, rapid tranquilisation. 
In the event of respiratory depression the crew should manage the patient’s airway and oxygenation, and seek the quickest way for the patient to receive IV flumazenil (carried by the escort team along with equipment for cannulation).  This would be via a GP or local A&E department.

Antipsychotics

The likelihood of being able to arrange an ECG for patients in the community is low. This highlights the risks associated with the prescription of antipsychotics discussed in the body of this guideline. Therefore any prescription should be carefully considered and the rationale for treatment clearly documented.

Equipment

Medical, escort or place of safety bags should have available all the equipment required for safe administration and monitoring of rapid tranquilisation. This includes:

Medication (inc. Flumazenil)Thermometer
Equipment for IM injection  Pulse oximeter
Equipment for cannulation Sphygmomanometer
Kardex and NEWS chart Sharps box

QTc Cautions and Contraindications (Taylor et al, 2012, p.114-115)

Physiological Risk Factors for QTc Prolongation and Arrhythmia

Symptom/Sign

Cardiac

Long QT syndrome
Bradycardia
Ischaemic heart disease
Myocarditis
Myocardial infarction
Left ventricular hypertrophy

Metabolic

Hypokalaemia
Hypomagnesaemia
Hypocalcaemia

Others

Extreme physical exertion
Stress or shock
Anorexia nervosa
Extremes of age
Female gender

Drugs Associated with QT prolongation – this list is not exhaustive. Please refer to www.crediblemeds.org for more detailed information

Antipsychotic effect on QTc

Non-psychotropics associated with QTc prolongation

Effect

Medication

Medication Class

Medication

Nil

Brexpiprazole
Cariprazine
Lurasidone

Antibiotics

Erythromycin
Clarithromycin
Ampicillin
Co-trimoxazole
Pentamidine
(4 quinolones effect QTc – see manufacturers’ literature)

Low

Aripiprazole
Asenapine
Clozapine
Flupentixol
Fluphenazine
Loxapine
Perphenazine
Prochlorperazine
Olanzapine
Paliperidone
Risperidone
Sulpiride

Antimalarials

Chloroquine
Mefloquine
Quinine

Antiarrhythmics

Quinidine
Disopyramide
Procainamide
Sotalol
Amiodarone
Bretylium

Moderate

Amiulpride
Chlorpromazine
Haloperidol
Iloperidone
Levomepromazine
Melperone
Quetiapine
Ziprasidone

Others

Amantadine
Cyclosporin
Diphenhydramine
Hydroxyzine
Methadone
Nicardipine
Tamoxifen
Citalopram
Escitalopram

High

Any IV antipsychotic
Pimozide
Sertindole
Any exceeding maximum dose

Unknown

Pipotiazine
Trifluoperazine
Zuclopenthixol

Bibliography

  • BNF 76 - September 2018- March 2019, 2018, BMJ group and Pharmaceutical Press, UK. Available at: https://www.medicinescomplete.com/#/browse/bnf [accessed 23 October 2018]
  • Electronic Medicines Compendium summary of product characteristics [online]. Available at: http://www.medicines.org.uk [accessed 23 October 2018]
  • NICE Guideline NG10: Violence and Aggression, Short-term management in mental health, health and community settings, May 2015 [online]. Available at: https://www.nice.org.uk/guidance/ng10 [accessed 23 October 2018]
  • Patel et al, 2018, Joint BAP NAPICU evidence-based consensus guidelines for the clinical management of acute disturbance: De-escalation and rapid tranquillisation, Journal of Psychopharmacology, pages 1-40. Available at: https://www.bap.org.uk/pdfs/BAP_Guidelines-RapidTranquillisation.pdf [accessed 23 October 2018]
  • Royal College of psychiatrists CR190 Consensus statement on high dose antipsychotic medication, November 2014 [online]. Available at: https://www.rcpsych.ac.uk/files/pdfversion/CR190.pdf [accessed 23 October 2018]
  • Taylor D. et al, 2018, The Maudsley Prescribing Guidelines in Psychiatry, 13th edition, Wiley Blackwell, UK.  The Adults with Incapacity (Scotland) Act 2000. Available at: http://www.legislation.gov.uk/asp/2000/4/contents [accessed 16 April 2019]
  • The Mental Health (Care and Treatment) (Scotland) Act 2003. Available at: http://www.legislation.gov.uk/asp/2003/13/contents [accessed 16 April 2019]

Abbreviations

AbbreviationMeaning
ECGElectrocardiogram
QTQ and T are points on an electrocardiogram
QTcCorrected QT Interval (QTc)
SPCManufacturer's summary of product characteristics

Editorial Information

Last reviewed: 06/02/2020

Next review date: 28/02/2023

Author(s): Mental Health Services .

Approved By: TAM Subgroup of ADTC

Reviewer name(s): Principal Pharmacist.

Document Id: TAM442

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