[Delirium, catatonia and substance withdrawal syndrome manifested as psychomotor agitation in COVID-19: a pharmacological management approach for the general hospital setting]. / Delirium, catatonía y síndrome de abstinencia manifestados como agitación psicomotora en COVID-19: una propuesta de manejo farmacológico en el hospital general.

BACKGROUND: Neuropsychiatric symptoms can be part of the clinical spectrum of COVID-19 infections. AIM: To devise an evidence based clinical algorithm as a guide for clinicians, to identify and treat underlying clinical syndromes of psychomotor agitation, such as delirium, catatonia or substance withdrawal in patients who are hospitalized and infected with SARS-CoV-2. MATERIAL AND METHODS: A review of the literature about the pharmacological management of neuropsychiatric manifestations of COVID-19 at the general hospital, to develop a clinical protocol based on a consensus from an interdisciplinary expert panel at a Clinical Hospital. RESULTS: A consensual clinical algorithm for the management of delirium, catatonia, and substance withdrawal, manifested as psychomotor agitation in patients hospitalized with COVID-19, was developed as a clinical proposal for physicians at different levels of complexity in health services. CONCLUSIONS: Cooperation among different clinical units in the general hospital facilitated the implementation of a clinical algorithm for clinicians for the management of psychomotor agitation in COVID-19 patients.

Study protocol to test the efficacy of self-administration of dexmedetomidine sedative therapy on anxiety, delirium, and ventilator days in critically ill mechanically ventilated patients: an open-label randomized clinical trial.

BACKGROUND: Administration of sedative and opioid medications to patients receiving mechanical ventilatory support in the intensive care unit is a common clinical practice. METHODS: A two-site randomized open-label clinical trial will test the efficacy of self-management of sedative therapy with dexmedetomidine compared to usual care on anxiety, delirium, and duration of ventilatory support after randomization. Secondary objectives are to compare self-management of sedative therapy to usual care on level of alertness, total aggregate sedative and opioid medication exposure, and ventilator-free days up to day 28 after study enrolment. Exploratory objectives of the study are to compare self-management of sedative therapy to usual care on 3- and 6-month post-discharge physical and functional status, psychological well-being (depression, symptoms of post-traumatic stress disorder), health-related quality of life, and recollections of ICU care. ICU patients (n = 190) who are alert enough to follow commands to self-manage sedative therapy are randomly assigned to self-management of sedative therapy or usual care. Patients remain in the ICU sedative medication study phase for up to 7 days as long as mechanically ventilated. DISCUSSION: The care of critically ill mechanically ventilated patients can change significantly over the course of a 5-year clinical trial. Changes in sedation and pain interventions, oxygenation approaches, and standards related to extubation have substantially impacted consistency in the number of eligible patients over time. In addition, the COVID-19 pandemic resulted in mandated extended pauses in trial enrolment as well as alterations in recruitment methods out of concern for study personnel safety and availability of protective equipment. Patient triaging among healthcare institutions due to COVID-19 cases also has resulted in inconsistent access to the eligible study population. This has made it even more imperative for the study team to be flexible and innovative to identify and enrol all eligible participants. Patient-controlled sedation is a novel approach to the management of patient symptoms that may be able to alleviate mechanical ventilation-induced distress without serious side effects. Findings from this study will provide insight into the efficacy of this approach on short- and long-term outcomes in a subset of mechanically ventilated patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT02819141. Registered on June 29, 2016.

A case for continuing statin medications in the intensive care unit: Reducing the risk for delirium.

PURPOSE: The objective of this review is to detail the utility of statin medications in the prevention and treatment of intensive care unit (ICU) delirium. SUMMARY: Delirium is a syndrome characterized by altered mental status, inattention, and disorganized thinking. It is particularly concerning in the ICU where specific risk factors are much more prevalent. Nonpharmacological therapy is the mainstay of treatment, aimed at increasing patient awareness; pharmacological therapies have also been explored with varying success. The utility of statin medications in this scenario has been investigated because of the numerous pleiotropic effects of these drugs. Although the benefits in terms of treating delirium are uncertain, statins may be good candidates for prevention. The peak anti-inflammatory effect of statins is delayed, so initiating a statin on admission will likely have little protective benefit, whereas continuation of a home regimen seems more likely to exert an effect. CONCLUSION: Statin medications are very commonly used, and, while their role in treating delirium is unclear, continuation of these medications from a home regimen is reasonable to decrease the odds of delirium in the intensive care population.

Pharmacological Treatment of Acute Psychiatric Symptoms in COVID-19 Patients: A Systematic Review and a Case Series.

Delirium and psychomotor agitation are relevant clinical conditions that may develop during COVID-19 infection, especially in intensive care unit (ICU) settings. The psychopharmacological management of these conditions is receiving increasing interest in psychiatry, considering hyperkinetic delirium as one of the most common neuropsychiatries acute consequences in COVID-19 recovery patients. However, there are no actual internationally validated guidelines about this topic, due to the relatively newly introduced clinical condition; in addition, a standardized psychopharmacologic treatment of these cases is a complex goal to achieve due to the risk of both drug-drug interactions and the vulnerable conditions of those patients. The aim of this systematic review and case series is to evaluate and gather the scientific evidence on pharmacologic handling during delirium in COVID-19 patients to provide practical recommendations on the optimal management of psychotropic medication in these kinds of patients. The electronic databases PubMed, Embase and Web of Science were reviewed to identify studies, in accordance with the PRISMA guidelines. At the end of the selection process, a total of 21 studies (n = 2063) were included. We also collected a case series of acute psychomotor agitation in COVID-19 patients hospitalized in ICU. Our results showed how the symptom-based choice of the psychotropic medication is crucial, and even most of the psychotropic drug classes showed good safety, one must not underestimate the possible drug interactions and also the possible decrease in vital functions which need to be strictly monitored especially during treatment with some kinds of molecules. We believe that the evidence-based recommendations highlighted in the present research will enhance the current knowledge and could provide better management of these patients.

The COVID-19 conundrum: Where both the virus and treatment contribute to delirium.

Whereas hospitalists and intensivists are treating the life-threatening respiratory conditions that often accompany COVID-19, delirium prevention, identification, and treatment may inadvertently be taking a backseat. However, delirium identification is important as it can serve as a key marker for hospital providers to identify COVID patients at risk for poor outcomes including ICU stay and death.2 COVID delirium has been difficult to manage because some COVID treatment methods are inherently deliriogenic and some medications traditionally used to manage delirium have been rendered ineffective among this population. Inpatient neurology and psychiatry practitioners are having to postulate new treatment techniques; one such medication algorithm can be found within this piece. It is important that delirium doesn't get lost in the chaos that is management of the COVID patient.

IL-6 Inhibition Reduces Neuronal Injury in a Murine Model of Ventilator-induced Lung Injury.

Mechanical ventilation is a known risk factor for delirium, a cognitive impairment characterized by dysfunction of the frontal cortex and hippocampus. Although IL-6 is upregulated in mechanical ventilation-induced lung injury (VILI) and may contribute to delirium, it is not known whether the inhibition of systemic IL-6 mitigates delirium-relevant neuropathology. To histologically define neuropathological effects of IL-6 inhibition in an experimental VILI model, VILI was simulated in anesthetized adult mice using a 35 cc/kg tidal volume mechanical ventilation model. There were two control groups, as follow: 1) spontaneously breathing or 2) anesthetized and mechanically ventilated with 10 cc/kg tidal volume to distinguish effects of anesthesia from VILI. Two hours before inducing VILI, mice were treated with either anti-IL-6 antibody, anti-IL-6 receptor antibody, or saline. Neuronal injury, stress, and inflammation were assessed using immunohistochemistry. CC3 (cleaved caspase-3), a neuronal apoptosis marker, was significantly increased in the frontal (P < 0.001) and hippocampal (P < 0.0001) brain regions and accompanied by significant increases in c-Fos and heat shock protein-90 in the frontal cortices of VILI mice compared with control mice (P < 0.001). These findings were not related to cerebral hypoxia, and there was no evidence of irreversible neuronal death. Frontal and hippocampal neuronal CC3 were significantly reduced with anti-IL-6 antibody (P < 0.01 and P < 0.0001, respectively) and anti-IL-6 receptor antibody (P < 0.05 and P < 0.0001, respectively) compared with saline VILI mice. In summary, VILI induces potentially reversible neuronal injury and inflammation in the frontal cortex and hippocampus, which is mitigated with systemic IL-6 inhibition. These data suggest a potentially novel neuroprotective role of systemic IL-6 inhibition that justifies further investigation.

[Delirium in the "young" covid-19 patient (<65 years): preliminary clinical indications]. / Il delirium nel paziente covid-19 "giovane" (<65 anni): indicazioni cliniche preliminari.

Delirium is a phenomenon classified within neuro-cognitive disorders in the DSM-5. It has several etiologies and it is often lethal. This contribute aims at analyzing clinical characteristics and diagnostic possibilities of delirium in patients affected by covid-19. Furthermore, some preliminary recommendations on the use of psychopharmacological treatment of delirium and their interactions with main drugs used to treat covid-19 are given, with a special attention to comorbidities like in immunocompromised patients, in those affected by diabetes and cancer, in pregnant women or in addicted clients.

Descriptive analysis of the unwarranted continuation of antipsychotics for the management of ICU delirium during transitions of care: A multicenter evaluation across New Jersey.

PURPOSE: Nearly half of intensive care unit (ICU) patients will develop delirium. Antipsychotics are used routinely for the management of ICU delirium despite limited reliable data supporting this approach. The unwarranted continuation of antipsychotics initiated for ICU delirium is an emerging transitions of care concern, especially considering the adverse event profile of these agents. We sought to evaluate the magnitude of this issue across 6 centers in New Jersey and describe risk factors for continuation. METHODS: This multicenter, retrospective study examined adult ICU patients who developed ICU delirium from June 2016 to June 2018. Patients were included in the study if they received at least 3 doses of antipsychotics while in the ICU with presence of either a clinical diagnosis of delirium or a positive Confusion Assessment Method score. Patients were excluded if they were on an antipsychotic before ICU admission. RESULTS: Of the 300 patients included and initiated on antipsychotics for ICU delirium, 157 (52.3%) were continued on therapy upon transfer from the ICU to another level of inpatient care. The number of patients continued on newly initiated antipsychotics further increased to 183 (61%) upon discharge from the hospital. CONCLUSION: The continuation of antipsychotics for the management of delirium during transitions of care was a common practice across ICUs in New Jersey. Several risk factors for continuation of antipsychotics were identified. Efforts to reduce unnecessary continuation of antipsychotics at transitions of care are warranted.

Management challenges in patients with comorbid COVID-19 associated delirium and serious mental illness - A case series.

BACKGROUND: There is still a lot unknown about the novel Coronavirus Disease 19 (COVID-19) and its effects in humans. This pandemic has posed several challenging clinical situations to healthcare providers. OBJECTIVE: We hope to highlight the distinctive challenges that COVID-19 presents in patients with serious mental illness and what steps primary medical teams can take to co-manage these patients with the psychiatry consultants. METHODS: We present a retrospective chart review of four patients who were on psychotropic polypharmacy and admitted to our hospital from the same long-term psychiatric facility with COVID-19 delirium and other associated medical complications. RESULTS: We illustrate how the primary medical teams and psychiatrists collaborated in clinical diagnosis, treatment, and management. CONCLUSIONS: Patients with serious mental illness and COVID-19 infection require active collaboration between primary medical teams and psychiatrists for diagnostic clarification, reduction of psychotropic polypharmacy to avoid adverse effects and drug-drug interactions, prevention of psychiatric decompensation, and active management of agitation while balancing staff and patient safety concerns.

Neurocovid: Pharmacological Recommendations for Delirium Associated With COVID-19.

BACKGROUND: The pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has emerged as one of the biggest health threats of our generation. A significant portion of patients are presenting with delirium and neuropsychiatric sequelae of the disease. Unique examination findings and responses to treatment have been identified. OBJECTIVE: In this article, we seek to provide pharmacologic and treatment recommendations specific to delirium in patients with COVID-19. METHODS: We performed a literature search reviewing the neuropsychiatric complications and treatments in prior coronavirus epidemics including Middle Eastern respiratory syndrome and severe acute respiratory syndrome coronaviruses, as well as the emerging literature regarding COVID-19. We also convened a work group of consultation-liaison psychiatrists actively managing patients with COVID-19 in our hospital. Finally, we synthesized these findings to provide preliminary pharmacologic recommendations for treating delirium in these patients. RESULTS: Delirium is frequently found in patients who test positive for COVID-19, even in the absence of respiratory symptoms. There appears to be a higher rate of agitation, myoclonus, abulia, and alogia. No data are currently available on the treatment of delirium in patients with COVID-19. Extrapolating from general delirium treatment, Middle Eastern respiratory syndrome/severe acute respiratory syndrome case reports, and our experience, preliminary recommendations for pharmacologic management have been assembled. CONCLUSIONS: COVID-19 is associated with neuropsychiatric symptoms. Low-potency neuroleptics and alpha-2 adrenergic agents may be especially useful in this setting. Further research into the pathophysiology of COVID-19 will be key in developing more targeted treatment guidelines.

An audit of end-of-life symptom control in patients with corona virus disease 2019 (COVID-19) dying in a hospital in the United Kingdom.

BACKGROUND: The literature contains limited information on the problems faced by dying patients with COVID-19 and the effectiveness of interventions to manage these. AIM: The aim of this audit was to assess the utility of our end-of-life care plan, and specifically the effectiveness of our standardised end-of-life care treatment algorithms, in dying patients with COVID-19. DESIGN: The audit primarily involved data extraction from the end-of-life care plan, which includes four hourly nursing (ward nurses) assessments of specific problems: patients with problems were managed according to standardised treatment algorithms, and the intervention was deemed to be effective if the problem was not present at subsequent assessments. SETTING/PARTICIPANTS: This audit was undertaken at a general hospital in England, covered the 8 weeks from 16 March to 11 May 2020 and included all inpatients with COVID-19 who had an end-of-life care plan (and died). RESULTS: Sixty-one patients met the audit criteria: the commonest problem was shortness of breath (57.5%), which was generally controlled with conservative doses of morphine (10-20 mg/24 h via a syringe pump). Cough and audible respiratory secretions were relatively uncommon. The second most common problem was agitation/delirium (55.5%), which was generally controlled with standard pharmacological interventions. The cumulative number of patients with shortness of breath, agitation and audible respiratory secretions increased over the last 72 h of life, but most patients were symptom controlled at the point of death. CONCLUSION: Patients dying of COVID-19 experience similar end-of-life problems to other groups of patients. Moreover, they generally respond to standard interventions for these end-of-life problems.

End-of-life care in COVID-19: An audit of pharmacological management in hospital inpatients.

BACKGROUND: Hospital clinicians have had to rapidly develop expertise in managing the clinical manifestations of COVID-19 including symptoms common at the end of life, such as breathlessness and agitation. There is limited evidence exploring whether end-of-life symptom control in this group requires new or adapted guidance. AIM: To review whether prescribing for symptom control in patients dying with COVID-19 adhered to existing local guidance or whether there was deviation which may represent a need for revised guidance or specialist support in particular patient groups. DESIGN/SETTING: A retrospective review of the electronic patient record of 61 hospital inpatients referred to the specialist palliative care team with swab-confirmed COVID-19 who subsequently died over a 1-month period. Intubated patients were excluded. RESULTS: In all, 83% (40/48) of patients were prescribed opioids at a starting dose consistent with existing local guidelines. In seven of eight patients where higher doses were prescribed, this was on specialist palliative care team advice. Mean total opioid dose required in the last 24 h of life was 14 mg morphine subcutaneous equivalent, and mean total midazolam dose was 9.5 mg. For three patients in whom non-invasive ventilation was in place higher doses were used. CONCLUSION: Prescription of end-of-life symptom control drugs for COVID-19 fell within the existing guidance when supported by specialist palliative care advice. While some patients may require increased doses, routine prescription of higher starting opioid and benzodiazepine doses beyond existing local guidance was not observed.