With the increasing prevalence of COVID-19 in hospitalised populations, the management of aggression is likely to be a significant issue because of:

• patient factors: patient vulnerability characteristics: e.g. difficulty comprehending and adhering to infection control principles ^{[1, 2]})
• environmental factors: difficulties maintaining physical distancing in these settings, factors to do with staffing and layout, e.g. communal living spaces, shared bedrooms and bathrooms
• disease factors: delirium – most commonly due to hypoxia - with associated aggression a common presentation of COVID-19 ^[3]
• treatment factors: Some potential treatments for COVID-19 (e.g. chloroquine) can have psychiatric adverse effects ^[4]

Assessment

Management of acute severe behavioural disturbance (ASBD) should be based on local protocols with emphasis on de-escalation strategies and oral medication to reduce the need for restraint and parenteral sedation. Different protocols exist for patients under 18 and over 65. NSW Health - Guideline for the management of patients with Acute Severe Behavioural Disturbance (ASBD) in Emergency Departments is available as a companion to local protocols.

Out-of-hospital treatment of a mental health patients with a respiratory illness, possibly COVID-19, is a challenging situation. Local organisation-specific procedures and policies should be observed throughout the treatment, transport and handover of the patient to the receiving facility. Caring for adults with COVID-19 in the Community outlines guidance to assist staff with triage, monitoring and escalation.

These protocols should be augmented by the following specific considerations in patients with known or suspected COVID-19:

Before restraint and pharmacological management

• Restraint and involuntary administration of sedation is a potentially traumatising experience for the patient and is likely to be even more distressing during the pandemic with a generally increased levels of anxiety and the potentially confronting nature of staff PPE.
• All efforts should be made to reassure and de-escalate the situation, ideally by a clinician known to the patient.
• All staff members involved in sedation should be dressed as for contact and droplet and airborne precautions.
• There should be sufficient staff available for physical restraint and ensure patient and staff safety including during medication administration.
• It is essential to obtain baseline physical observations prior to pharmacological intervention or as immediately as possible following sedation, especially oxygen saturation and ECG.
• The aim in management of ASBD is conscious sedation. Deeper sedation should only be undertaken in settings where staff have advanced airway management skills and equipment and have appropriate PPE (airborne precautions).

Pharmacological considerations in safe sedation for people with suspected, probable or confirmed COVID-19

Considerations for early pharmacological treatment

• Restraint is a high risk for clinical staff and patients and should be avoided if possible. The aim should be to reduce the length of each episode of restraint and need for recurrent episodes of restraint as far as possible.
• To reduce recurrent restraint, careful consideration should be given to early pharmacological treatment, preferably administered by the oral route, to address the underlying cause of ASBD, with a focus on agitation.
• This may lead to the decision to treat with antipsychotic medication early and not rely on sedating agents alone.
• Be aware of time to action of commonly used medications.

Dosing considerations

• Ensure the medication used for acute disturbance is an effective dose, as ineffective dosing may lead to repeated injections.
• Consider risk of over-sedation and assess patients for history or signs of intoxication with alcohol or substances.
• Caution is especially required in those who are antipsychotic naïve as the risk of over-sedation increases with increasing doses. Over-sedation can lead to loss of protective airway reflexes. If over-sedated, use continuous pulse oximetry (if available) and visual observation until rousable. Then continue the usual monitoring protocol.
• Always consider COVID-19 Drug Interactions. The NSW Therapeutic Advisory Group website includes up-to-date information about medicines use in the treatment of COVID-19. Some medications that are currently being trialled or utilised for COVID-19 treatment may have clinically significant interactions with psychotropic medications used in sedation.
• Always consider concurrent medications and relevant comorbidities when prescribing sedating agents.

Identifying and managing adverse effects

• Be prepared for management of serious dystonic reactions (laryngeal spasm) - it is often a confusing presentation. Administration of benztropine or alternate anticholinergic should be parenteral, MET or Code Blue should be called, and anticholinergics should be administered for at least the following 48 hours.
• Extrapyramidal side effects are more likely in the elderly.
• Neuroleptic Malignant Syndrome (NMS) is also possible and may present as high fever (that is also common in COVID-19) without additional clinical manifestations of NMS.

Respiratory depression

• Avoid medication which may lead to respiratory depression ^[5].
• Risk of respiratory depression from benzodiazepine use is unlikely when used as monotherapy but may increase when combined with other respiratory depressants.
• Parenteral midazolam has the advantage of early onset of action which may allow for earlier release of restraint but has increased risk of respiratory depression and need for airway support. Oral or parenteral lorazepam may be a preferred option due to reduced risk of needing airway support and longer action. Avoid diazepam or clonazepam if possible ^[6] and ensure ready availability of flumazenil. ^{[7, 8, 9]}
• Flumazenil should only be used when the prescriber is confident that the patient does not have a history of long-term benzodiazepine abuse.
• Ensure awareness that respiratory status can deteriorate precipitously with COVID-19. Therefore, long-acting medicines, which may have respiratory depressant activity such as diazepam should be avoided, unless there are clinical grounds for suspecting alcohol or benzodiazepine withdrawal.

Zuclopenthixol acetate (Acuphase®)

• Consider Zuclopenthixol acetate (Acuphase®), particularly in the group of patients with a clear diagnosis and previous exposure to antipsychotic medication.
• Avoid use in antipsychotic naïve patients.
• An ECG should be performed prior to administration of Acuphase®.
• Sedative effects peak 12 hours, but effects may last 72 hours. Acuphase® does not provide rapid tranquilisation and a faster-acting sedative may need to be co-administered. Peak plasma concentrations occur at 24 to 36 hours.
• Reduced doses are recommended in the elderly (max 100 mg per dose).
• Dystonic reactions requiring anticholinergics will need repeat dosing for the duration of action of zuclopenthixol acetate. This may have implications for any delirium.

Ketamine

• Ketamine has been associated with an increase in psychotic symptoms.
• If possible, ketamine should be avoided in patients with a history of a psychosis as it may lead to the increased need for subsequent and parenteral sedation.

Post-sedation considerations

• Monitoring of vital signs, especially of oxygen saturation, should be especially stringent.
• If not practicable, continuous observation of the patient's colour, respiratory rate and level of consciousness and agitation with escalation of safe monitoring of other parameters.
• If a patient is over sedated (not rousable to verbal stimuli) continuous visual observation should be maintained until rousable. Note, protective airway reflexes are lost when patients are over sedated.
• Monitor for emergent central nervous system difficulties, seen in 25% of COVID- 19 patients in one series, although these were mostly mild and transient ^[11].

References

1. Zhu Y Chen L et al. The Risk and Prevention of Novel Coronavirus Pneumonia Infections Among Inpatients in Psychiatric Hospitals. Neurosci Bull. 2020;36(3):299-302.
2. Yao H Chen JH Xu YF. Patients with mental health disorders in the COVID-19 epidemic. Lancet Psychiatry. 2020;7(4):e21.
3. Kotfis K Roberson W et al. COVID-19: ICU delirium management during SARS-CoV- 2 pandemic. Critical Care. 2020;24(1):1-9.
4. Sato Kenichiro et al. Neuropsychiatric adverse events of chloroquine: a real-world pharmacovigilance study using the FDA Adverse Event Reporting System (FAERS) database. Neuroscience Trends. 2020.
5. Tahir T Watkins A et al. Liaison psychiatry services in Wales. British Journal of Psychiatry Bulletin. 2019;43(1):17-20.
6. Patel M X Sethi F Barnes T et al. Joint BAP NAPICU evidence-based consensus guidelines for the clinical management of acute disturbance: de-escalation and rapid tranquillisation. Journal of Psychiatric Intensive Care. 2018;14(2):89-132.
7. Baldacara L Sanches M Cordeiro D Jackoswski A. Rapid tranquilization for agitated patients in emergency psychiatric rooms: a randomized trial of olanzapine, ziprasidone, haloperidol plus promethazine, haloperidol plus midazolam and haloperidol alone. Revista brasileira de psiquiatria. 2011;33(1):30-9.
8. Huf G Alexander J Allen M Raveendran N. Haloperidol plus promethazine for psychosis-induced aggression. Cochrane Database of Systematic Reviews. 2011(11).
9. Knott JC, Taylor DM, Castle DJ. Randomized clinical trial comparing intravenous midazolam and droperidol for sedation of the acutely agitated patient in the emergency department. Annals of Emergency Medicine. 2006;47(1):61-7.
10. Grampian N. Medication use for acute behavioural disturbance during the COVID-19 pandemic. NHS Grampian; 2020. p. 1-5.
11. Rogers JP Chesney E et al. Psychiatric and neuropsychiatric presentations associated with severe coronavirus infections: a systematic review and meta-analysis with comparison to the COVID-19 pandemic. Lancet Psychiatry. 2020:1-17.

Return to COVID‐19 Acute Severe Behavioural Disturbance Risk Formulation Framework.​