Practical guidelines for the acute emergency sedation of the severely agitated older patient

Authors


  • Funding: None.

  • Conflict of interest: None.

Abstract

The vulnerability of older people to serious underlying medical illness and adverse effects of psychotropics means that the safe and effective treatment of severe agitation can be lifesaving, the primary management goals being to create a safe environment for the patient and others, and to facilitate assessment and treatment. We review the literature on acute sedation and provide practical guidelines for the management of this problem addressing a range of issues, including aetiology, assessment, pharmacological and non-pharmacological strategies, restraint and consent. The assessment of the agitated older patient must include concurrent assessment of the likely aetiology of, the risks posed by, and the risks/benefits of management options for, the agitation. A range of environmental modifications and non-pharmacological strategies might be implemented to maximize the safety of the patient and others. Physical restraints should only be considered after appropriate assessment and trial of alternative management and if the risk of restraint is less than the risk of the behaviour. Limited evidence supports a range of pharmacological options from traditional antipsychotics to atypical antipsychotics and benzodiazepines. It is advised to start low and go slow, using small increments of dose increase. Medical staff are frequently called to sedate agitated older patients in hospital settings, often after hours, with limited access to relevant medical information and history. Safe and effective management necessitates adequate assessment of the aetiology of the agitation, exhausting all non-pharmacological strategies, and resorting to pharmacological and/or physical restraint only when necessary, judiciously and for a short-term period, with frequent review and the obtaining of consent as soon as possible.

Introduction

Managing the acutely and severely agitated older patient is not easy. While delirium is a cause of agitation, there are significant other aetiologies that require consideration. Despite apparent frailty, older patients can still be extremely dangerous when aroused, posing significant risk to themselves and others, yet at the same time they can be extremely vulnerable to the adverse effects of sedation. Thus, the safe and effective treatment of an agitated older patient in the emergency department, general ward and occasionally, community setting, is critical. The two primary goals of management are to create a safe environment for the patient and others, and facilitate the assessment and treatment of the patient. Patients might be dehydrated, septic or in a metabolically altered state, and might have serious occult medical illnesses. Thus, rapid calming without excessive sedation can be lifesaving and facilitate medical and psychiatric evaluation and work-up.1 However, all agents currently used for the acute treatment of agitation have the potential for clinically important adverse events, including increased (‘paradoxical’) agitation. The challenge is to identify the cause of the agitation and to target management to the special needs of the older person. The following paper will provide practical guidelines for the management of this problem addressing a range of issues, including aetiology, assessment, pharmacological and non-pharmacological strategies, restraint and consent.

Common pitfalls: why is it important to get this right?

Common pitfalls in this situation include:

  • 1Treating the symptoms or behaviour and ignoring the underlying cause. Many of the underlying causes of severe agitation, such as delirium (see Aetiology), are associated with significant morbidity and mortality, particularly if left untreated. For example, delirium is associated with a two- to threefold increased risk of death.2
  • 2Automatic and unreviewed charting of as needed or ‘prn’ antipsychotic regimens for agitated patients. This can be problematic because in such circumstances control of the dosage is often left to staff who may be unfamiliar with the patient.
  • 3Over-sedation leading to serious adverse effects, such as dehydration, falls, respiratory depression, pneumonia and death.

Aetiology: what causes agitation in the older patient?

Management of the agitated older patient must commence with consideration of the likely aetiology (Fig. 1). Acute agitation is encountered in the context of a range of situations and disorders, most commonly in association with delirium and/or dementia. While the setting will influence the likelihood of particular aetiologies (e.g. mental health or palliative care wards), the presence of delirium must be considered in any patient who develops an acute agitated state and the diagnosis should be presumed until proven otherwise.4 Delirium may occur in the context of normal premorbid cognitive function, or complicate a dementia. Delirium has a range of common causes, including: (i) metabolic (e.g. dehydration, hypoxia, electrolyte abnormalities); (ii) infective; (iii) structural (e.g. stroke, pulmonary embolus, constipation); (iv) toxic (therapeutic and illicit drug use and withdrawal) and (v) environmental.5

Figure 1.

Individualized decision-making tree for severe agitation in older patients. BPSD, behavioural and psychological symptoms of dementia.

Patients with dementia may develop acute agitation due to frank delirium, but additionally, agitation in dementia may communicate a range of possible physical or emotional discomforts, commonly fear, pain, disorientation, constipation, overstimulation or other unmet needs.6

Other important aetiologies to consider include alcohol or benzodiazepine intoxication or withdrawal, agitated depression, primary psychotic illness, brain injury and an acute response to stressful events.

Assessment

The assessment of the agitated older patient must include concurrent assessment of:

  • The likely aetiology of the agitation
  • The risks posed by the agitation
  • The risks and benefits of agitation management options for the individual patient

In distinguishing the aetiology of the agitation, it is important that a thorough history (particularly a collateral history) is taken, particularly to distinguish between delirium and dementia, where the duration of the symptoms is crucial to the diagnosis. Ascertaining presence of symptoms suggestive of dementia with Lewy bodies will necessitate particular caution in choice of pharmacological agents (see Fig. 1) and finally, past history of primary psychiatric illness will also influence management.

Medical evaluation and stabilization with full physical examination and organic screen (including, but not limited to full blood count and profile including electrolytes, blood sugar levels, C-reactive protein and urine examination) should occur in parallel with psychiatric assessment and management (Fig. 1). Pain assessment charts based on patient observation, rather than self-report, may aid detection of pain in non-verbal patients. A mental status evaluation documenting levels of consciousness and attention, extent of cognitive dysfunction and signs of psychosis is crucial in the diagnosis of delirium. The content of any delusions will impact upon the risk assessment, such that very frightened, paranoid patients may pose a particular risk to staff. It is important to note that while organic work-up for delirium is an essential part of the management plan, there is rarely time to carry this out in the setting of a behavioural emergency. Initial management may have to commence prior to completion of assessment, and must be associated with repeated reassessment. While it is essential that no presumptions are made regarding the implications of past presentations upon a current presentation, it is also essential to consider their relevance to assessment, risk assessment and management strategies. For example, if it is known that a particular patient has a past history of schizophrenia with severe psychotic relapses associated with aggressive behaviour, responding to particular doses of antipsychotic medications, then this might guide treatment choices. Conversely, such patients may still present with delirium, so that past history should not prejudice clinical management and lead to premature diagnostic closure.

Management

Prevention of delirium

The incidence of delirium can be decreased in hospital patients by multicomponent interventions which target immobility, dehydration, sleep deprivation and sensory impairments.7,8 Orthogeriatric services commencing prior to surgery have been shown to reduce delirium in older patients with hip fracture by addressing psychoactive drug use, fluid and electrolyte imbalance, immobility, hypoxia, pain and bowel and bladder function.9

Consent issues

The principle or doctrine of necessity upholds the actions of doctors who are unable to get instructions from patients who are likely to be incapable only for a short period because, for example, they were unconscious or delirious and, with care and treatment, would soon regain capacity. In such circumstances, doctors can treat such patients by doing no more than is reasonably required. It is then incumbent upon the doctor who is continuing to treat the patient to obtain consent from the patient, or if they are incapable, from the patient's proxy, as soon as is practical. In regards to patients unable to give consent, obtaining valid consent from either a person responsible, guardian or tribunal (depending on the state or jurisdiction and whether the patient is objecting or not) is particularly important for agents acting on the central nervous system and substances used to ‘control behaviour’.

Non-pharmacological strategies

Environmental modifications

A range of environmental modifications may be implemented to maximize the safety of patient and others, including: (i) involvement of family members in care or supervision of the patient (familiar faces can be reassuring to those who are very frightened or agitated); (ii) movement to a position of best observation, or placement in a purpose-built secure unit; (iii) preventing access to means of self-harm, such as open windows, balconies, internal stairwells, hand hoists over beds, cords and coat hangers; (iv) falls injury prevention strategies; (v) distraction devices or inaccessible placement (e.g. between scapulae) of cannulae to prevent removal of catheters or cannulae and (vi) consideration of one to one nursing. Such strategies can be useful regardless of the aetiology of the agitation (see references for reviews of delirium management5,10–13). In particular, use of specialized units, or ‘delirium rooms’, for patients with acute agitation associated with hyperactive delirium, with access to both geriatric and psychiatric input and specialized, trained nursing staff, may be associated with lower physical and chemical restraint and improved function.14,15

Physical restraint

Physical restraint is the intentional restriction of a person's voluntary movement or behaviour by the use of a device and includes use of limb, wrist and vest restraints, mittens, bedrails, tray chairs and bucket chairs. Restraints may be used in the management of severe agitation, but care needs to be taken as their use can actually result in an increase in agitation and aggression, as well as abrasions, pressure areas and compressive neuropathies.16 Their use should only be considered after appropriate assessment and trial of alternative management methods and if the risk of restraint use is less than the risk of the behaviour. They should never be used as a replacement for nursing care or patient supervision, and consent must always be sought for their use.

Pharmacological strategies: what is the evidence?

Traditional antipsychotics

Acute sedation with traditional high-potency neuroleptics (e.g. haloperidol) can have significant side-effects, particularly dystonia and extrapyramidal symptoms. However, they have the potential benefit of reducing arousal with less sedation and have less impact on blood pressure and muscarinic receptors than some of the lower potency antipsychotics (e.g. chlorpromazine), which should not be used in older persons.

A recent Cochrane review of antipsychotic use in delirium found equal efficacy of low-dose haloperidol to the atypical antipsychotics olanzapine and risperidone and no greater frequency of adverse drug effects.17 The efficacy and safety of haloperidol in treating agitation in dementia have also been evaluated in a Cochrane Systematic Review of five randomized placebo-controlled trials that showed that demented subjects receiving haloperidol showed no significant improvement in overall agitation scores but an improvement in aggression compared with controls.18

One of the major issues with regards to the use of traditional antipsychotics in acutely agitated patients with dementia is the neuroleptic hypersensitivity associated with dementia with Lewy bodies.19 Extreme caution is thus advised with using traditional antipsychotics to acutely sedate any patient with a history of dementia, parkinsonism, visual hallucinations and fluctuating consciousness.

Atypical antipsychotics

There are some limited data to support the use of olanzapine in the management of acute agitation in older people. In a meta-analysis of three studies, Battaglia et al.1 found that acute agitation in patients with dementia (n= 206) in an emergency department setting was significantly reduced by intramuscular (IM) olanzapine (2.5 mg) (1–3 injections/24 h) when compared with placebo with no more sedation than lorazepam (1.0 mg). Similarly, in a double-blind randomized trial comparing the efficacy and safety of rapid-acting IM olanzapine (dosages of 2.5 and 5.0 mg) with lorazepam (1.0 mg) or placebo in 272 patients with agitation associated with Alzheimer's disease and vascular dementia, Meehan et al.20 found that at 2 h, both olanzapine and lorazepam showed superiority over placebo in terms of reduced agitation. This was maintained at 24 h in the olanzapine, but not the lorazepam group. There were no significant differences in sedation, adverse events, extrapyramidal symptoms, QT interval or vital signs among all groups.

IM olanzapine reaches mean maximum plasma concentration 15–45 min after injection (vs 3–6 h for an equivalent oral dose) while maintaining a similar pharmacokinetic profile to oral olanzapine (half-life, clearance and volume of distribution) such that dose adjustments are not necessary when equating the two modes of administration. Hypotension and bradycardia have been observed during IM administration of olanzapine.21

Risperidone has been studied for the longer-term management of agitation in the elderly, specifically for the management of psychosis and behavioural disturbances in patients with dementia;22,23 and to control agitation in delirium, where it has been found to have equal efficacy to haloperidol.24 However, the use of risperidone to control acute agitation immediately has not been studied. The only currently available parenteral formulation is an extended-acting slow release formulation that is dosed every 2 weeks and therefore not suitable for use in acute agitation. However, there is an available rapidly dissolving oral tablet (‘quicklet’), which may have practical advantages in this context.

Ziprasidone, another atypical antipsychotic available in rapid-acting IM formulation, might have a role in treating acutely agitated older patients. A retrospective study of the safety of IM ziprasidone in agitated elderly patients admitted to a neuropsychiatric service found no significant differences in QTc intervals of treated patients;3 and a study of older patients admitted to a psychiatric emergency service found equal efficacy to haloperidol and no adverse effects on electrocardiogram, heart rate or blood pressure, nor adverse cardiac events.25 A case series of five patients with Parkinson's disease demonstrated no deterioration of motor function or other relevant side-effects in patients treated with IM ziprasidone for acute agitation.26

Although there is no evidence supporting or refuting the use of quetiapine in the acute emergency sedation of older patients, patients with delirium treated with quetiapine improved more rapidly than a placebo group on a delirium severity scale.27

Benzodiazepines

Equally efficacious to neuroleptics in producing sedation, benzodiazepines (e.g. lorazepam) are not associated with extrapyramidal symptoms and can be better tolerated in the rapid treatment of agitation. However, respiratory depression, excessive sedation (greater than seen with high-potency neuroleptics), and, rarely paradoxical disinhibition and increased agitation, can pose significant problems, particularly with agents such as midazolam and diazepam. There is a preference for benzodiazepines with shorter half-lives given the risk of accumulation and over-sedation, particularly in older people.

Combination treatment, such as haloperidol with lorazepam, appears superior in efficacy to either agent alone; however, sedative effects are at least as great as with benzodiazepines used as a single agent..28,29 In particular, combinations of olanzapine with parenteral benzodiazepine have not been studied, and it is recommended that parenteral benzodiazepine not be given until at least 2 h after olanzapine administration due to risk of respiratory depression.30 Parenteral benzodiazepines available in Australia include lorazepam,30 midazolam (used often to treat acute agitation in adult patients presenting to Australian emergency departments)31 and clonazepam, although, with the exception of lorazepam,20 there is no randomized controlled trial evidence for their use in older patients. IM diazepam is not recommended for use for acute sedation. Intravenous sedation is also best avoided in older patients with agitation.

General principles for pharmacological treatment

As with all antipsychotic use, start low and go slow, using small increments of dose increase (Table 1). Following oral or parenteral sedation, it is essential that appropriate advice is given to staff regarding appropriate levels of supervision, observation and frequency of review. This should be based on both the medication used and individual clinical situation, but should include consideration of the risks of falls, increased confusion, over-sedation and increased confusion. It should also aim to initiate strategies to reduce the risk of further episodes of agitation.

Table 1. Medication options for acute sedation of older patients in general hospital wards
RouteDrug classMedicationsInitial dose (mg)Maximum dose in 24 hCaution
  1. Adapted from Mental Health and Drug and Alcohol Office.30 Individual clinical scenarios may require use of doses outside these ranges, or alternative medications, but this should only be with the supervision of a senior clinician with appropriate experience. If parkinsonism or suspicion of Lewy Body Dementia avoid antipsychotics initially and DO NOT use haloperidol. All antipsychotics, including both first-generation typical and second-generation atypical antipsychotics, have been associated with increased mortality. Pharmaceutical Benefits Scheme-approved indications of antipsychotic use are for schizophrenia and bipolar disorder; with the exception of risperidone which has PBS approval for use in dementia. IMI, intramuscular injection.

OralBenzodiazepineLorazapem (can be swallowed or used sublingually)0.5–1.255 mgRespiratory depression, confusion, ataxia
  Diazepam for alcohol or benzodiazepine withdrawal2–5Three times daily as per Alcohol Withdrawal ScaleRespiratory depression, confusion, ataxia
 AntipsychoticOlanzapine wafer2.5–510 mgConfusion hypotension, bradycardia, ataxia
  Risperidone quicklet0.5–12 mgHypotension sedation, ataxia
IMIAntipsychoticOlanzapine2.52.5 mg increments to max dose of 7.5 mg, at no closer than 30 min intervalsConfusion hypotension, bradycardia, ataxia
  Haloperidol0.25–0.52 mg dailyDystonia, extrapyramidal signs

Use of ‘prn’ (or as needed) medications should be used with caution. They should not be prescribed routinely, but can be helpful when titrating medication dosages to meet clinical needs, thus intended as a short-term solution. They should be prescribed at a specific dose (rather than range of doses) and preferably by the usual treating team, for a specific indication or symptom and reviewed daily. It has been found that a significant reduction in the percentage of patients receiving psychotropic prn medications (53.4% to 23.1%) in an acute care geriatric psychiatry setting was achieved following the introduction of a multidisciplinary educational approach involving documentation of the indications for using prn medication and the steps that were taken before the prn medications were utilized (A. Burhan, unpubl. data).

Conclusion

Medical staff are frequently called to sedate agitated older patients in hospital settings, often after hours, sometimes with limited access to relevant medical information and history. The vulnerability of older people to serious underlying medical illness and adverse effects of psychotropics means that safe and effective management necessitates adequate assessment and clarification of the aetiology of the agitation, exhausting all non-pharmacological strategies, resorting to pharmacological and/or physical restraint only when necessary, and doing so judiciously and for a short-term period, with frequent review and the obtaining of consent as soon as possible.

Ancillary