Delirium (Acute Confusional State): Causes, Identification, Assessment and Management

Introduction

Here is the definition of delirium from the shorter oxford textbook of psychiatry:

“delirium is a global impairment (clouding) of consciousness resulting in a reduced level of alertness, attention, perception of the environment, and thence cognitive performance.”

There are several terms used in this definition that can make it difficult to understand at first. It begins with a clouding of consciousness, which they say results in reduced alertness, attention, and perception, and these are cognitive or let's put it simply, mental abilities, so the overall mental abilities or cognitive performance is reduced. Now, let me quickly explain these and some other terms so you can fully comprehend this definition and the other signs and symptoms of delirium that we will be discussing.

Terminology

Perception

Perception occurs when the brain processes the raw sensory stimuli from the environment to generate meaningful information. For example, the light packets are the sensory data that, through the eyes and optic tract, reaches the visual cortex, which processes it to form an image. Similarly, sound waves are processed by the brain, so we hear voices that contain information. It is interesting and can be deceptive. Here, for example, we are seeing an apple, jumping, and rotating in a 3d space, even though the screen is flat. So, we are perceiving the light emitted from the screen which is the actual sensory data, as a 3d rotating apple. This apple is the final perception.

Attention 

Attention is our mental capacity to hold information actively in mind for processing, for example, mental manipulation, inference, making sense of information, deciding based on it etc. it has a limited capacity. On average, we can keep seven digits in mind at the same time.

Concentration

The ability to sustain attention is concentration. For example, if you count backwards from one thousand, how long can you do it without making a mistake.

Distractibility

Distractibility is a related term. It is simply like the inverse of our ability to filter out irrelevant stimuli and focus on the relevant ones.

Stupor

These are some cognitive functions, and these depend on the level of alertness. So, when a condition impairs alertness, these functions reduce and eventually pause. The patient appears in a sleep-like state, and we call this state stupor. These patients can still respond to at least some stimuli.

Coma

When they stop responding to stimuli, we say they are comatose. Please notice the perceptions and it may still reduce even responses to stimuli. Only when patients stop responding to stimuli, so we say they are in a coma.

Clouding of consciousness.

Any level of consciousness between complete alertness and stupor is what we call clouding of consciousness. 

So, now let's have a look at this definition again. 

“Delirium is a global impairment (couding) of consciousness resulting in a reduced level of alertness, attention, perception of the environment, and thence cognitive performance”.

I hope that now makes more sense. 

One key point about this definition is that it mentions no cause. Unlike conditions, for example, COVID-19, where we must find the evidence of its causative agent; the SARS-CoV-2, we define delirium by its clinical manifestations. So, let's discuss them.

Clinical Manifestations

Delirium has a wide range of manifestations, but there are some core features which are central to the diagnosis of delirium. And the course of these symptoms is also important.

These core features include a clouding or impairment of consciousness, visual misperceptions and hallucinations, reversal of sleep-wake cycle and variability of the symptoms over the day. Rapid onset is also important from the diagnostic point of view.

Clouding of consciousness 

Clouding of consciousness is the hallmark of delirium. They manifest it as drowsiness, decreased awareness of one’s surroundings, disorientation in time and place, and distractibility. At its most severe, the patient may be unresponsive (stuporous), but more commonly the impaired consciousness is quite subtle.

Rapid onset

Rapid onset is also one of its diagnostic characteristics. A further clue to the diagnosis is the onset has a temporal relationship with the cause. We'll describe it later. This rapid onset is most important to differentiate it from dementia. Most of the symptoms that occur in delirium also occur in dementia, but in which case, they arise over the years. In delirium, they begin within hours to a few days.

Variability

The symptoms of delirium change over the day, severity may intensify especially at night and then ease in the daytime, some symptoms may subside, new symptoms may arise. And this variability of the clinical picture is another diagnostic feature of delirium.

Reversal of Sleep-wake Cycle

Patients with delirium have a reversal of the sleep-wake cycle. They may sleep in the day and stay awake at night. And that could be one reason the symptoms appear to worsen at night. But a reversal for the sleep-wake cycle is also important.

Perceptual Abnormalities

We already described perception, and we said it reduces in delirium. Illusions and hallucinations are abnormalities of perception.

Illusion 

An illusion occurs when we misperceive a stimulus, in most cases a visual stimulus. For example, seeing a full-sized car sitting on a table when the car stands on the floor way behind the table. It is mostly a normal phenomenon. And note a stimulus is present but we misinterpret it. But sometimes, people perceive things without actual stimuli, like hearing voices or seeing something others can’t see.

We call them hallucinations:

Hallucinations

We can define hallucination simply as perception when there is no stimulus. It is frequently an abnormal phenomenon. Hallucinations occur principally in the visual and auditory modality; but uncommonly they can even be tactile, or olfactory, or gustatory.

• Tactile: the sense of touch
• Olfactory: the sense of smell
• Gustatory: sense of taste

Patients with delirium can experience illusions or visual misperceptions--like misinterpreting a stethoscope for a snake and hallucinations like seeing a giant scorpion hanging from the ceiling or some insects crawling on their skin. Patients with psychiatric disorders, like schizophrenia, experience auditory hallucinations. But patients with delirium experience visual hallucinations and visual misperceptions. These visual misperceptions are another diagnostic feature of delirium.

One link here is acetylcholine, which acts as a neurotransmitter in the brain and has a significant role in cognition. Its depletion is linked with visual hallucinations as well. And organic conditions with mental symptoms have impairments in this acetylcholine. Take, for example, delirium itself, Parkinson's disease, Dementia. Even anticholinergic medications can cause both visual hallucinations and cognitive impairment, and cholinergic medication is used to treat Parkinson's disease psychosis, which presents with visual hallucinations.

So, these are the core features of delirium. Patients with delirium may experience almost any psychiatric symptom; thought disturbances and mood symptoms are some other more common ones.

Other Symptoms of Delirium

Disturbances of thoughts

Thinking is slow and muddled, that is vague and confused. Patients may also exhibit delusions or ideas of reference.

Delusions

A delusion is an unshakeable belief (we cannot change it with logical explanations or evidence) that is held on inadequate grounds (they do not have a valid explanation or evidence for their belief, and that is not a conventional belief that the person might be expected to hold given their educational, cultural, and religious background. Previously we said illusions are mostly but not always normal. Hallucinations are mostly but not always abnormal. But a delusion is something that is always abnormal. So, someone who believes to be possessed by the supernatural is not delusional because it’s a cultural common belief. In the west, many young girls become convinced that they need to be thin and take extreme measures and their weight may reach life-threatening low levels and continue. And this is still not a delusion because they consider thinness socially desirable and that they educate most people about the risks of obesity is dangerous and the need for thinness.

Persecutory delusions are the most common ones, in which they develop a belief that someone wants to harm them.

Ideas of Reference

An idea of reference is a related term. It refers to an unnecessary tendency to link external events, things, or people to self. For example, someone enters the room, and the patient may think that he kills me. If this idea meets the criteria for delusion, we call a delusion of reference.

Epidemiology

What is epidemiology

Epidemiology deals with the distribution of diseases or health conditions in various ethnic, age groups, socio-economic groups, geographies. Some of these groups have higher rates, or we can say they have a higher predisposition for developing that condition.

These factors are not mutually exclusive, they can overlap. For example, delirium is more common in elderly, it is also more common in those who are hospitalized. So a hospitalized elderly is included in both these groups. Or, again we can say he has two predisposing risk factors for delirium. People with more of these risk factors are more likely to develop the condition.

Patients with certain medical conditions may also be predisposed to develop a condition. These are not epidemiological factors but I have included them here so you can learn the predisposing factors together.

Demographic Risk Factors

The most important demographic risk factor is old age. Alcohol users are also at an elevated risk as are people with functional impairment. Imagine an elderly woman in a wheelchair, who broke her leg and needs help from caretakers. If this elderly also had a long-term history of alcohol use, she would have all these demographic factors.

Functional Impairment 

To help you precisely understand, impairment is used in medical terms for a pathological defect or disease. The loss of function as a result of this defect, is the functional impairment. A broken leg is an impairment and the inability to walk, the need for a wheelchair, or help with self-care needs is functional impairment.

Medical Risk Factors

Now, let's assume, she develops delirium and comes to your for assessment, and you find that she also has developed dementia due to long-term alcohol use. And as you assess her further, you discover that she broke her leg because she fell due to a brain stroke. And as a result of the brain stroke, she also lost her eyesight. So that makes her more likely to experience another episode. Because if she had delirium once, she could have it again. Her cerebral reserve is reduced because dementia reduces brain volume, then she lost part of her cerebral cortex because of the stroke which also took away her eyesight. These are the medical predisposing factors for delirium.

So, so now that the patient is at even higher risk for delirium, let's assume she comes to you with the third episode of delirium while you are working in the emergency department. After the emergency management, you admit her to the medical unit. And when the patient improves, you send her to a residential home instead. So, now she is even at even higher risk for a third episode. The Elderly in the community are at risk of delirium, but the risk in residential homes is 4-8 times higher. A higher than one in patients who present to the emergency department have delirium. Patients who are admitted to the hospital are even more likely to have delirium. This makes sense because we admit only those patients who are more seriously ill. Especially those admitted to medical units. Because medical conditions are some more common causes, compared to for example those with psychiatric conditions, diseases of the eyes, nose etc. there is no mention but patients in the ICU are highly likely to have delirium as well.

We already mentioned delirium has a prevalence of around 1-2% In the community sample of elderly. People presenting to the emergency department have about as high as 20% rates of delirium (8—17%)

Up to 35% of people on admission to the hospital may have delirium. Hospitalised patients in medical units may have up to 64% rates, but all these rates are the highest values of the expected ranges that we have found in epidemiological studies. The actual values could be much lower than these.

Aetiology

Aetiology refers to all the factors and processes that eventually lead to the disease. Every condition is caused by multiple risk factors. Let's take COVID-19, for example. Is it the virus? Or is it pathogenicity? What about the lack of our immunity to it? And now that the entire world knows how to protect, why is the virus still spreading? Do you think there may be a role for our risky behaviours that we keep exposing ourselves or faulty ways of thinking like I will not get it?

Aetiology and related concepts on delirium

So, the virus is the causative factor, its pathogenicity is part of the pathophysiology, our lack of immunity is the predisposing factor. faulty ways of thinking and risky behaviours are risk factors which can predispose but when they eventually trigger the disease, so we know them as precipitating. And we collectively know these factors as aetiological factors.

With delirium, causative factors are especially diverse, as we will see.

For the individual cases, the aetiology involves multiple factors most of the time, for example, you admit an elderly man with uncontrolled diabetes suffers cardiac failure to the CCU where he is started on steroids and digoxin. But note that some cases may even be idiopathic — that is, we don’t know what caused the delirium. These cases require the most careful workup. Because treatment of the underlying cause is most important for the outcome.

In the elderly admitted to the hospital, drugs and infection are the most frequent cause of delirium.

Substances of abuse

Some of the most common drugs of abuse include alcohol, benzodiazepines, and opioids. Alcohol and benzodiazepine withdrawal cause a special type of delirium that we call delirium tremens.

Delirium Tremens

Apart from the general symptoms of delirium, delirium tremens is characterised by an autonomic instability like irregular heart rate. Epileptic fits may also occur. The prognosis of delirium tremens is even worse. Many people use benzodiazepines as their regular sleeping pills, and they may attempt to withdraw from them on their own because they don’t see it as a serious risk to their health. These patients could then present as idiopathic cases of delirium. So, it is important to ask about benzodiazepine use in such cases.

Medications

An extensive list of medications can cause delirium, but the most common ones are sedatives, medications with anticholinergic properties, steroids, and digoxin. While evaluating delirium, always look at whether the patient is receiving these medications. But since the list is extensive, always aim to cut down on the doses and number of medications to a bare minimum

Medical Conditions

Again, many conditions can cause delirium but septicaemia, high degree fever and organ failures like renal or liver failure, or even cardiac failure are among the common ones. Of thumb, delirium has a temporal relation with its cause. So, if someone develops a medical condition and then they develop delirium, we might assume that as a cause.

These are some interesting causes, especially important for the idiopathic delirium where no cause is evident. Sleep deprivation, for example, may not be revealed unless we enquire about it. Similarly, keep constipation and dehydration in mind. Sometimes, mental trauma and extreme physical pain may also induce delirium.

So, these were the common causes of delirium. But remember that the list is extensive.

Pathophysiology of delirium

The pathophysiology of delirium is less well understood but,

This slowing of activity correlates with the severity of the clinical picture. The more severe the clinical picture, the slower the activity on the EEG. Dopamine and acetylcholine are involved in the final common pathway. We already explained the role of acetylcholine. Dopamine is also a central nervous system stimulant neurotransmitter and has a role in cognition and hallucinations. This time auditory hallucinations, but also in delusions.

You can help remember this with the d of the dopamine for the d in the delusions and the d in the auditory hallucinations. You'll learn more about it in another lesson on schizophrenia, where it has a more significant role.

Studies implicate a range of other factors which include inflammatory, metabolic, and genetic factors. We will not discuss these. This is the end of the aetiology section. Now the assessment where we discuss the clinical and laboratory assessment.

Assessment

Clinical assessment

Clinical assessment includes the general history and bedside testing, including a physical and neurological examination.

History

In history, we enquire about the major symptoms of delirium that we discussed. For example, whether they experience visual symptoms. And we also elicit the course, to confirm its rapid onset and its temporal association with its cause, identify the fluctuation in symptoms and whether the symptoms worsen at night. Reversal of the sleep-wake cycle is also relevant here.

Bed-side testing

During history taking, we already develop an impression of whether the patient appears drowsy. So, we begin by testing orientation to time, place, and person. Simply assess whether the patient is aware of the location, the date and time, and whether they can recognise the people around.

That was bedside testing. Now, two investigations can help us in the diagnosis. Again, it’s a clinical diagnosis, but these investigations can help when we are in doubt.

We already explained the inverse relationship between the severity of clinical presentation and background activity on EEG. So, this can aid the diagnosis. But it is not too sensitive or specific.

The most sensitive and specific test is the Confusion Assessment Method. It is a clinical tool that can test patients on the bedside, and it takes only two minutes to apply. It is not much different from clinical assessment, but it has standardised the entire process. So, it can be especially useful for learning. When you practice a few times on it, you can then do the same. You can download it from that link.

This was about the diagnostic assessment of delirium. The assessment of underlying causes must be even more careful. Particularly in those cases in whom the cause is unknown. A thorough medical history, physical history, and investigations. This assessment varies case by case. Just as in most cases, we tailor our physical examination based on the history and the lab investigations based on both. Then we can go back and forth until we find the exact cause.

Patients with idiopathic delirium require the most attention. And in those cases, it is wise to start with causes that we are likely to overlook, for example, look whether the patient is on Catheter, which widespread practice twice in medical units. Using physical restraints is not common but keep them in mind. Enquire about constipation, whether they have been sleeping well, again an easily missed cause. Patients are frequently secretive about their drug use, or in case of benzodiazepines, they may not consider it serious, look for the other signs of drug withdrawal in such cases. Pain can also cause delirium, so to keep that in mind. Check for dehydration with a skin pinch. But the assessment should not stop here. We keep assessing until we know the cause. So, this concludes the assessment section, which we regard as a part of the management.

But in this next section, we discuss the rest of the management, focused on the preventive and therapeutic interventions.

Management

Treating the underlying cause is the most important treatment. Because the outcome depends on it.

But preventive therapies are even more important because no delirium is preferable to delirium, but also, preventive therapies are more effective than therapeutic. We have some non-pharmacological and pharmacological interventions to prevent delirium.

Non-pharmacological Treatment Options

HELP and eliminating the risk factors are among the nonpharmacological interventions.

Hospital Elderly Life Program

HELP is a structured program, which studies have shown effective in preventing delirium. It is a commercial product from the American College of Geriatrics that costs five thousand dollars for a 2-year subscription. Eliminating risk factors is the most workable option. 

Eliminating risk factors 

Target those who are highly predisposed, think about an elderly, who lost his eyesight, and broke his leg because of a fall is now hospitalised with multiple pathologies and receiving multiple medications, including anti-dementia treatment. So, find a list and think about what they can avoid.

Pharmacological Treatments

Effective pharmacological treatments include antipsychotics in low doses, gabapentin, and melatonin. Several antipsychotics have anticholinergic and sedative properties, haloperidol is a good option. Gabapentin is an antiepileptic, which also helps.

You can remember melatonin because this is the hormone that regulates the sleep-wake cycle. Remember the sleep-wake cycle reversal in delirium.

The world health organisation has classified delirium as mental and behavioural disorder. So, they do not recognise it as a medical condition. But it’s a medical emergency. Because the underlying causes are organic.

The mortality is high. It needs urgent medical attention. Because the prognosis depends on the treatment of the underlying cause. So, we require careful workup patients to identify them, especially when they are not clear.

Psychiatric management aims to relieve distress, control agitation, and prevent exhaustion that can occur because of this agitated behaviour.

We have some pharmacological and nonpharmacological treatment options. The nonpharmacological treatments are the mainstay, while we reserve the pharmacological treatments for those with severe agitation and hallucinations.

Now we know clouding of consciousness is the hallmark of delirium which results in poor cognition, disorientation to time and place, confusion. So, imagine you do not know where you are. Everyone seems a stranger, you are not aware of the time, and add to that the experience of frightening hallucinations, like seeing scorpions and snakes. So that’s more like a nightmare. And patients become anxious and agitated. Which is the best indication for psychiatric treatment? So, the most effective known way to treat it is to target the core manifestations. Confused patients may ask questions, you give them frequent explanations; they do not know where the who, so we orient, Ideally, we should nurse them in a single quiet room, and if possible, the same staff, the same clinician should take care of them. We should encourage relatives to visit more frequently and at night the lighting should be enough to allow orientation but not too much to impair sleep. Finally, for hallucinations, if for example, they see snakes; we reassure them that they can see them, but they are not real, they are part of your illness.

Antipsychotics are the first-line pharmacological treatment, but their use is limited by their side effects, especially sedation and anticholinergic effects. So, they are only used to control severe agitation and improve sleep. Haloperidol at a slight dose is most used for this purpose because it has a suitable effect and side-effect profile for delirium.

Prognosis

Many cases recover quickly. But the mortality is considerable. Prognosis relates to the underlying cause.

Regarding mortality, around one in 4 patients may die over the following three months. Just to be clear, mortality differs from case fatality. We always express mortality with a period, in a specific population. Here, it is also a crude death rate because the actual causes are always multiple. Case fatality is cause-specific mortality, so we can never relate it to delirium because delirium never causes death. The risk of death doubles over the next two years after an episode of delirium. Again, this is the standardised mortality ratio. The rate of death in patients with delirium compared to its rate of the population over two years.

Delirium has a complex relationship with dementia. Dementia predisposes to delirium. Similarly, delirium increases the risk of dementia. It also acts synergistically with the underlying neuropathology to increase the risk of cognitive decline.

Now, the elderly, people with dementia or physical illness, have a poor outcome. Which makes sense. Because, in old age, people have already become physically weak. Similarly, we just said delirium speeds up the rate of dementia so we can understand that. People with a pre-existing physical illness, for example, asthma, are more likely to die from the condition that caused delirium.

Causes of Delirium

Mnemonic: "COLD-PATHES"

• Constipation, cerebral haemorrhage
• Opiates, organ failure (liver, heart, kidney)
• Lithium
• Digoxin, diuretics, dehydration
• Pain, postoperative hypoxia
• Alcohol (intoxication, withdrawal), anticholinergics
• Thiamine deficiency
• Hypo/hyperglycaemia
• Encephalitis, epileptic fits
• Steroids, sedatives, septicaemia, space-occupying lesion, sensory deprivation