**13. Delirium**

Delirium is a complex neurocognitive and behavioral syndrome, characterized by alterations in the level of consciousness and attention, associated with cognitive and perception alterations [48]. It has an abrupt onset and a fluctuating course.

Although its presence is very frequent, it is highly underdiagnosed. In patients with oncological and terminal pathology, its frequency varies between 26 and 44% and in recent days up to 80–90% [49].

Predisposing and precipitating factors of delirium have been described that we must consider for an early diagnosis. As described by Rolfson D, a powerful model that encourages clinicians to delineate multiple predisposing factors or vulnerability aspects and also to clearly list the acute triggers [50].

As predisposing factors, we have advanced age, male, visual disturbances, dementia, depression, physical dependence, immobility, fractured femur, alcoholism, serious physical illness, and stroke [51].

As acute triggers, we have drugs, organic involvement of the central nervous system, severe acute illness; cardiac, renal, respiratory or hepatic failure, infections, metabolic disorders such as hyponatremia, hyperkalemia, hypomagnesemia, and hypoglycemia; dehydration, anemia, disseminated intravascular coagulation and major surgery [49, 51, 52].

Opioid and nonopioid psychoactive drugs have been identified as clear precipitating factors. Also, dehydration is associated with reversible delirium [53].

Knowing its high incidence, it is necessary to always have the suspicion of being faced with this pathology, even more so when there is a reversibility chance in 50% of the cases [49] and in the ones that are not reversible, symptomatic treatment can always be carried out. Hence the importance of making a correct diagnosis and a prompt treatment that help us avoid early deaths and reduce the suffering of the patient and their families.

The diagnosis is clinical, for which we have The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM 5), (DSM 5) criteria described in **Table 2** [54, 55]. A differential diagnosis must be made with depressive episodes, psychotic events, and dementias.

#### DSM-5


DSM-5 Diagnosis and Statistical Manual of Mental Disorders, fifth edition.

#### **Table 2.**

*DSM-5 delirium diagnosis criteria.*

Once the delirium has been diagnosed, an evaluation of the causes must be initiated, provided that the patient is not in a state of agony. All tests must be consistent with the patient's clinical status and with the expected benefit of their practice [48, 49, 56].

Among the complementary tests to request we have hemogram, coagulation, blood biochemistry (ions), kidney function, liver function, urine sediment and culture, oxygen saturation, chest X-ray, and brain CT [57].

Regarding the pathophysiology of delirium, we know that there is a wide range of causes, ranging from pharmacological to alteration of cerebral metabolism [57].

Pharmacological as a consequence of exceeding the therapeutic margin, especially with those with anticholinergic action. Opioids can cause delirium by increasing dopamine and glutamate activity and decreasing acetylcholine activity. Corticosteroids have been related to the appearance of delirium due to alteration of the hypothalamic-pituitary-adrenal axis. The neurotransmitter Gamma-aminobutyric acid (GABA), activity is decreased in delirium due to benzodiazepine and alcohol deprivation, while in hepatic encephalopathy its levels are increased by the increase in ammonia that induces the elevation of glutamate and glutamine [58, 59].

Alteration of cerebral metabolism due to a deficiency of the substances required to maintain it (mainly glucose and oxygen), toxins, or excessive metabolic demand as occurs in fever.

Likewise, cytokines also seem to be involved in the appearance of some types of delirium.

Lesions on diffuse structures composed of the thalamus and bilateral hemispheric pathways have been related to the appearance of delirium. Other structures composed of the frontal and parietal cortex of the right hemisphere and damaged by infarction of the middle cerebral artery and the right cerebral artery have also been related [60, 61].


## **14. Clinical manifestations of delirium**

Three types of delirium have been established according to their clinical manifestations: hyperactive, hypoactive, and mixed [51, 62].

We must take special care when facing a hypoactive type of delirium, since it is often difficult to diagnose, leading to a misdiagnosis and thus inadequate treatment.

The consciousness alteration usually fluctuates throughout the day. Alertness can be both increased and decreased. There is an attention deficit, the patient does not usually follow the dialog and responds with answers that do not correspond to the questions. The thinking process is usually incoherent or disorganized. It can also be accompanied by a language disorder that can range from dysarthria to mutism: the patient has difficulty finding the right word (dysnomia) or confuses some words with others (paraphasias). There is an alteration in immediate, short-term, or long-term memory. Disorientation, paranoid ideas, or hallucinations can also be present. The

sleep-wake cycle is also usually altered. The patient may manifest an increase in pain with increases in analgesic requirements, and constructive visual apraxia (inability to copy geometric figures or more complex drawings) [49, 51, 56].

The hyperactive type predominates a psychomotor agitation, hallucinations, delusions, and a state of hyperalertness and agitation. While in the hypoactive type, a state of hypoalertness, lethargy, drowsiness, decay, and bradypsychia predominates. The mixed type is the most frequent, representing 66% of cases, characterized by alternating periods of lethargy and agitation [51, 56].
