If you notice sudden changes in a loved one’s awareness, mood, attention, perception and thinking, they might be experiencing the symptom of delirium, especially if they are in the hospital or very ill.

Esther Oh, M.D., Ph.D., an associate professor of medicine, psychiatry and behavioral sciences and of pathology, specializes in memory disorders and co-directs Johns Hopkins’ Memory and Alzheimer’s Treatment Center. She provides insights on delirium, what it is, who’s at risk and how it can be prevented.

What is delirium?

Delirium is an altered state of consciousness, characterized by episodes of confusion, that can develop over hours or days. “Delirium is a syndrome, not a disease,” Oh clarifies, noting that it affects people of all ages, but especially older adults who are acutely ill. Many different health conditions are associated with it, including infection, reaction to sedating drugs, oxygen deprivation and organ failure.

A person with delirium may experience changes in their awareness of where they are. They may seem “out of it,” lethargic or uninterested in their surroundings. They may be confused, anxious, or see or hear things that are not there. Thinking and remembering are impaired, and anxiety, euphoria or fear may occur.

Delirium is common, especially in older adults and people who are very sick or in the hospital. Up to one-third of all patients staying in the hospital and 80% of patients in the intensive care unit (ICU) experience delirium.

“Health practitioners take delirium seriously,” says Oh. “Developing delirium is linked to worse outcomes in older people in the hospital, and it is associated with a higher risk of declining health and death.”

Types of Delirium

Hypoactive delirium is the most common type. It can cause subtle changes such as unusual drowsiness and lethargy. The person may not respond to caregivers or family and may seem dazed or “out of it.”

“This type of delirium can be difficult to diagnose, since many people who are very ill or who have just had major surgery are very sleepy,” Oh explains. “Doctors, nurses and family members may assume that the patient is just getting much needed rest.

“Screening for hypoactive delirium is important,” she stresses. “It can help for doctors, nurses and caregivers to rouse the patient and ask them a few questions to make sure they are aware of themselves and where they are.

“Catching and addressing hypoactive delirium as soon as possible is essential,” says Oh, who notes that an estimated 30% to 40% of cases can be prevented.

Hyperactive delirium is characterized by restlessness and agitation. A person with this type may wander or pace, experience hallucinations and mood swings, or refuse care due to delusions (persistent, unfounded beliefs) that they are not safe. Hyperactive delirium is easier to spot than the hypoactive type, but according to Oh, hyperactive delirium comprises only about 25% of cases.

Mixed delirium can cause hypoactive symptoms alternating with hyperactive symptoms in the same person.

COVID delirium can be hypoactive or hyperactive, and is associated with being on a respirator or breathing tube while being treated for infection with the SARS-CoV-2 coronavirus. It may result from the ICU experience itself, complicated by a lack of oxygen when COVID has resulted in pneumonia or heart damage.

Delirium Symptoms

A person with delirium may experience symptoms that come and go over the course of the day, including:

• Mental confusion (especially new confusion that develops over hours or days)
• Difficulty in paying attention, listening or absorbing information
• Lack of interest in one’s surroundings, seeming “out of it”
• Difficulty thinking or remembering
• Drowsiness or lethargy
• Feeling disoriented as to time and place
• Sensitivity to light and sounds
• Distortions in sensory perception: seeing or hearing things differently
• Hallucinations: seeing or hearing things that are not there. The person may pick at or brush their hands over their bedclothes to remove dirt or insects that are not present.
• Delusions: fixed ideas not based in reality. For instance, people with delirium may fear that providers or family members are trying to harm them.
• Euphoria, anxiety or agitation

Symptoms are often more pronounced in the evening and at night.

Delirium vs Dementia

Dementia and delirium can share some symptoms, such as problems with memory and reasoning, agitation and delusions, and there is a relationship between the two disorders:

• A person with dementia may experience episodes of delirium, especially in late stages of their disease.
• People who develop delirium may be at a higher risk for dementia.

However, the two diagnoses are different. Dementia describes any one of several long-term brain diseases that progress slowly over years. Dementia symptoms are consistent and progressive.

In contrast, delirium is acute: It develops relatively quickly, over the course of days or even hours. Unlike dementia, delirium symptoms tend to come and go: A person with delirium can be lucid in the morning and confused by late afternoon.

Can delirium “reveal” dementia?

Sometimes delirium can be a warning sign of dementia. For instance, Oh notes that older people hospitalized for broken bones associated with falls may show changes in cognition (thinking, reasoning and remembering) after hospitalization and treatment.

Oh says, “Older, hospitalized patients, especially those with falls, are likely to have a longer hospital stay and are at a higher-than-normal risk for readmission. They are also vulnerable to delirium, followed by dementia onset in recovery and rehabilitation.

“There is a significant rate of new dementia diagnoses after hospitalization and experiencing delirium. It may be that delirium is an event that unmasks dementia in people who have had declining cognition for some time, but who have up to that point been able to compensate for or hide their underlying illness.”

Causes of Delirium

The physical cause of delirium is not yet well understood. Delirium may be caused by several things working together, such as changes to the body due to illness and environmental factors. With delirium, tests may show a problem with the chemical messengers that help the brain and body communicate.

The Role of Acetylcholine and Adrenal Hormones

A naturally occurring blood chemical called acetylcholine may play a part in delirium. Acetylcholine is a neurotransmitter ― it conveys messages from nerve cells to the body ― and plays a role in attention, learning and memory. Low levels of acetylcholine can be seen in people with myasthenia gravis and some forms of dementia. Studies have revealed that people who take medications that interfere with the action of acetylcholine are at higher risk for delirium.

Other neurotransmitters — such as epinephrine and norepinephrine, hormones secreted by the adrenal glands — are also the subject of research into how delirium develops.

Neurofilament Light Protein: A Link to Delirium

When brain cells are damaged, they release a protein called neurofilament light (NFL) protein. Recent technology advancements have helped researchers develop tests that can detect this protein in the blood.

“NFL can be a biomarker for head trauma, dementia and other conditions where damage to brain cells is occurring,” Oh says. “Research shows that more severe delirium symptoms are associated with higher levels of NFL protein in the blood, so delirium may be caused by some process that physically injures the brain.”

Challenges in Delirium Research

Scientific studies are still trying to unlock the mystery of how and why delirium develops.

“There is a lot of research in this area,” says Oh. “One thing that complicates research is that we don’t have a good animal model for delirium. We’ve been able to create animal models for other diseases, but symptoms of delirium, particularly inattention, are hard to gauge in a mouse.”

Risk Factors for Delirium

A range of conditions are associated with a higher chance of developing delirium, including:

• Being hospitalized, especially in the intensive care unit
• Older age, especially people age 80 and up
• Dehydration
• Malnutrition
• Dementia
• Parkinson’s disease
• Infection, including meningitis, sepsis and others
• Organ failure
• Difficulty seeing or hearing
• Multiple medications with mental or emotional side effects
• Complex surgery with anesthesia, such as an open cardiac procedure
• Hip fracture
• Drug intoxication or withdrawal (including alcohol withdrawal)
• Being on a ventilator or experiencing oxygen deprivation from any cause, including lung disease, opioid drugs or pneumonia
• Low blood sugar or other metabolic disease

The Impact of Staying in the Hospital

Along with the physical impact of serious illness, injury or surgery, a hospital stay is stressful for patients and interrupts their sense of time and routine. Some examples of environmental factors in the hospital that may contribute to delirium:

• Medications, especially opioids for pain, can cause side effects such as sedation.
• Lights and noise from machines can interrupt sleep, as can technologists awakening patients for tests such as vital signs and blood draws that continue through the night.
• Practitioners wear similar professional garb, with or without masks covering their faces, so patients may find it harder to keep track of who is caring for them.
• Separation from family and home can make a person feel anxious or sad.

Delirium Diagnosis

Doctors diagnose delirium by observing a patient’s symptoms. This can be challenging since many delirium symptoms may be due to other causes.

One clue that a person’s mental status change is due to delirium is how abruptly the problem starts. Symptoms that appear relatively quickly ― over hours or days ― suggest delirium. A fast onset is less likely in other problems such as a dementia or psychiatric illness.

Tests for Delirium

In the rare case that a person develops signs of delirium without a clear underlying cause, the doctor may recommend one or more tests.

• Urine and blood tests. Testing for infection, metabolic imbalances, abnormal blood gas levels, liver function and drug intoxication in blood and urine can identify some causes of delirium.
• Electroencephalogram, or EEG. This is a test that records electrical activity in the brain. It can identify certain seizure disorders, which sometimes have delirium-like symptoms.
• Imaging. In most cases of delirium, imaging tests are not necessary. A brain CT may be recommended if the delirium has no underlying cause and does not improve. MRI of the brain may help the doctor spot inflammation or a minor stroke, which may explain symptoms in some rare cases.

Older adults with meningitis, an infection of the central nervous system, may have different symptoms than a younger person, and these can look like delirium. If meningitis is expected, a lumbar puncture can help diagnose it or rule it out.

Treatment for Delirium

There is not a specific medicine or treatment that gets rid of delirium. Treatment for delirium starts with addressing the underlying cause.

• Medications. A person who is in the hospital and experiencing delirium may get sleep or calming medications to help them rest if they are fearful or agitated. But some sedating drugs can make delirium worse.
• Supporting sleep. Steps to regulate sleep-and-wake cycles can help. For instance, the family or care team can provide a darker, quieter environment at night for sleeping and natural light during the day.
• Presence of loved ones. Family members can help orient a person with delirium to time and place. Having family and friends nearby can help a person with delirium feel safer.
• Hospital care. In the hospital, a patient’s care team may take these steps to help minimize the risk and impact of delirium:
• Check the patient’s mental status regularly and be alert for changes.
• Change medications that may be making delirium worse, or give the patient a temporary break from those medications.
• Encourage mobility, including physical therapy and occupational therapy, as soon as the patient can respond and participate.
• Ensure the patient’s glasses and hearing aid are available and in use during the day so they can see and hear.
• Watch for and manage wandering or aggressive behaviors that could cause falls or otherwise endanger the person or others.
• Reassure patients that they are safe in the hospital receiving care.

Delirium Recovery and Prognosis

Delirium can be serious, and it is associated with severe illness and physical stress. Managing the underlying cause can help resolve delirium. The outlook is best for patients who are younger, have fewer medical problems and can fully recover from illness or surgery and return home to more familiar surroundings.

For others, delirium continues and may complicate care. Delirium can cause a person to forget medical instructions, such as when and how to take medications. The person may not be able to care for themselves and may need time in a rehabilitation facility or a transition to assisted living.

Family and Friends: Speak Up if You Suspect Delirium

Family members or caregivers may be the first to notice that the person is acting abnormally. Signs of delirium can be distressing to patients and their family. Calmly reassuring your loved one that he or she is safe and receiving care in the hospital can ease fear or confusion.

Oh stresses the importance of loved ones in identifying and managing delirium. “No one knows the patient better than friends and family members,” she notes. “If you notice something not quite right about your loved one, telling the nurse or doctor is very important.

“The sooner delirium is identified, the sooner the team can address it.”