Delirium reveals itself in an acute and fluctuating clinical presentation whose most important characteristic is inattention accompanied by disorganized thinking or an altered level of consciousness. It can be hyperactive, hypoactive (the most common one) or else have a mixed clinical presentation. The prevalence of delirium in the intensive care setting (ICS) is extremely variable: it affects 30%–80% of critically ill patients and its presence is associated independently—according to some authors—with a higher mortality rate, higher healthcare costs, and an extended length of stay. Also, these patients have a long-term higher risk of cognitive impairment, and a higher incidence rate of mental state disorders like anxiety and depression.1

Advanced age, the existence of high severity scores, and prolonged mechanical ventilation are among the risk factors associated with the development of delirium especially in patients with acute respiratory distress syndrome (ARDS), deep sedation, and use of benzodiacepines.2

The COVID-19 pandemic caused by SARS-CoV-2 has been associated with an extremely high prevalence of delirium especially in patients with ARDS on mechanical ventilation who have been affected in up to 80% of the cases.1

The type of predominant delirium in these patients was the hyperactive type characterized by a state of unusual agitation after the withdrawal of sedatives that is difficult to control and sometimes has serious repercussions like self-extubations.

The biggest prevalence of delirium in these patients with COVID-19 is due to a confluence of factors that have traditionally been associated with the development of delirium and other aspects that are very present in this group of patients like pain, fear, anxiety, familial isolation, sleeplessness, and prolonged immobilization.3 This adds to the damage caused to the central nervous system by SARS-CoV-2 or direct neural damage4,5 or immonulogical mechanisms. Therefore, all these patients should be considered high-risk patients for the development of delirium, which leads to having to implement early on measures for identification, prevention, and treatment purposes.6

Identifying delirium in the critically ill patient can be done fast and easy using validated scales like the CAM-ICU (Confusion Assessment Method for ICU) or the ICDSC (Intensive Care Delirium Screening Checklist). Despite of these scales, in general, the search for delirium is a rare practice in the ICS,7 something that has probably exacerbated during the COVID-19 pandemic due to, among other factors, issues with prioritizing and isolating patients, the collapse of the healthcare system, the hiring of untrained personnel, and the use of personal protection equipment.8 Therefore, it is likely that the prevalence of delirium in critically ill patients infected with SARS-COV-2 may have been higher than previously thought, meaning that its long-term consequences can also be significant.1

Although, to this date, no pharmacological treatment has proven effective to prevent delirium in patients with SARS-CoV-2, the implementation of general non-pharmacological measures—recommended both for prevention and treatment purposes—can be effective (Fig. 1)3 paying special attention to a few distinctive aspects of this pandemic.

Figure 1.

Treatment of delirium. Non-pharmacological recommendations and pharmacological approach.

* Rule out organic causes of delirium such as hypoxemia, hypercapnia, kidney or liver failure, shock, sepsis, metabolic acidosis or hiydroelectrolytic alterations. Dose of dexmedetomidine for the management of hyperactive delirium: between 0.2 mcg/kg and 1.4 mcg/kg per hour. Dose of haloperidol: 2.5 mg–5 mg IV. It can be repeated every 10 min–30 min up to a cumulative dose of 30 mg. Early dose of quetiapine: 25 mg/8−12 h PO increasing by 25 mg per dose on a daily basis. Early dose of olanzapine: 5 mg/24 h PO. Early dose of risperidone: 1 mg/24 h PO. Dose of valproic acid: 1200–1600 mg/day IV throughout 3–4 takes that can be preceded by a 28 mg/kg load. Dose of melatonin: starting from 2 to 4 mg PO administered 1 to 2 h before night rest.

BDZ, benzodiazepines; RASS, Richmond Agitation Sedation Scale.

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Regarding the traditional package of ABCDEF measures that has been associated with less delirium in critically ill patients on mechanical ventilation,9 its implementation poses multiple barriers in patients with COVID-19.3 Among them the need for deep sedation and neuromuscular blockade, patients being spread out across different units, the hiring of new and untrained personnel, the heavier workloads sustained, and the use of personal protection equipment. It all adds to the fact that family visits were absolutely restricted.3,4 Therefore, it is necessary to adequate the ABCDEF measures to the special characteristics of patients with SARS-CoV-2 by incorporating a new letter (R) that refers to how important adaptation to mechanical ventilation is in these patients to avoid asynchronies (ABCDEF-R, Table 1).10

Also, there are few specific recommendations on the management of delirium (Fig. 1) for patients with COVID-19 admitted to the ICS.3,5 Same as it happens with its prevention, non-pharmacological strategies with multicomponent interventions can be useful to control delirium.

Before initiating pharmacological treatment, other organic causes or trigger factors of delirium should be ruled out such as pain, fear, anxiety (more common in patients with hyperactive delirium) or oversedation (more prevalent in cases of hypoactive delirium). If delirium persists after solving and ruling all these aspects of delirium out pharmacological treatment should be initiated based on the existing recommendations for the management of delirium in critically ill patients.5

In case of hyperactive delirium, the use of IV dexmedetomidine especially in patients whose delirium becomes complicated or delays the process of weaning from mechanical ventilation. Typical (haloperidol) or atypical (quetiapine, olanzapine) antipsychotic drugs should be spared for patients with hyperactive delirium as bailout drugs in situations of agitation, anxiety or hallucinations, and only as long as these symptoms persist.5 Valproic acid can be an option for patients with refractory symptoms to the usual antipsychotic drugs while melatonin can be useful in patients with COVID-19 and cytokine storm thanks to its immunomodulatory, neuroprotective, and sleep-regulatory properties, especially in elderly patients with low levels of melatonin, something that contributes to the appearance of delirium.3

Regarding the pharmacological treatment of hypoactive delirium, the best therapeutic options available are dexmedetomidine, quetiapine or risperidone to treat persistent symptoms plus adjusted analgosedation.

In conclusion, delirium is a common problem in the ICS, and it is even more common in patients with COVID-19. This added to the difficulties associated with this disease require a great effort regarding the prevention, diagnosis, and early management of delirium. Since, for the time being, we don’t know of any specific measures for the management of delirium in patients with SARS-CoV-2 the existing general recommendations should be implemented in critically ill patients while making a few adaptations based on the individual characteristics of each individual patient.