Diffuse optical tomography for mapping cerebral hemodynamics and functional connectivity in delirium.

INTRODUCTION: Delirium is associated with mortality and new onset dementia, yet the underlying pathophysiology remains poorly understood. Development of imaging biomarkers has been difficult given the challenging nature of imaging delirious patients. Diffuse optical tomography (DOT) offers a promising approach for investigating delirium given its portability and three-dimensional capabilities. METHODS: Twenty-five delirious and matched non-delirious patients (n = 50) were examined using DOT, comparing cerebral oxygenation and functional connectivity in the prefrontal cortex during and after an episode of delirium. RESULTS: Total hemoglobin values were significantly decreased in the delirium group, even after delirium resolution. Functional connectivity between the dorsolateral prefrontal cortex and dorsomedial prefrontal cortex was strengthened post-resolution compared to during an episode; however, this relationship was still significantly weaker compared to controls. DISCUSSION: These findings highlight DOT's potential as an imaging biomarker to measure impaired cerebral oxygenation and functional dysconnectivity during and after delirium. Future studies should focus on the role of cerebral oxygenation in delirium pathogenesis and exploring the etiological link between delirium and dementias. HIGHLIGHTS: We developed a portable diffuse optical tomography (DOT) system for bedside three-dimensional functional neuroimaging to study delirium in the hospital. We implemented a novel DOT task-focused seed-based correlation analysis. DOT revealed decreased cerebral oxygenation and functional connectivity strength in the delirium group, even after resolution of delirium.

A Retrospective Analysis of Guanfacine for the Pharmacological Management of Delirium.

Background Delirium is a syndrome of acute brain failure that represents a change from an individual's baseline cognitive functioning characterized by deficits in attention and multiple aspects of cognition that fluctuate in severity over time. The symptomatic management of delirium's behavioral manifestations remains difficult. The alpha-2 agonists, dexmedetomidine and clonidine, are efficacious, but their potential cardiovascular adverse effects limit their utilization. Guanfacine is an oral alpha-2 agonist with a lower potential for such adverse outcomes; however, its use in delirium has not been studied. Methods A retrospective descriptive analysis of guanfacine for managing hyperactive or mixed delirium at Tampa General Hospital from January 2020 to October 2020 was conducted. The primary outcome was the time reduction in acute sedative administration. Secondary outcomes included renewed participation in physical therapy or occupational therapy (PT/OT), decreased opioid use, and an incidence of cardiovascular adverse effects. Results One hundred forty-nine patients were identified as having received guanfacine for managing delirium during the study period. All experienced a reduction in acute sedative use after the initiation of guanfacine. In 93 patients receiving PT/OT and no longer participating due to behavioral agitation, 74% had a documented renewal of services within four days. Of 112 patients on opioids, 70% experienced a 25% reduction in opioid administration within four days. No patients experienced consecutive episodes of hypotension that required a change in their clinical care. Two patients experienced a single episode of consecutive bradycardia that led to the discontinuation of guanfacine.  Conclusions Based on our retrospective study, guanfacine is a well-tolerated medication for the management of delirium. Even in medically and critically ill patients, cardiovascular adverse events were rare with guanfacine. Patients treated with guanfacine experienced decreased acute sedative use for behavioral agitation. Additionally, patients treated with guanfacine received fewer opioids and were better able to participate in PT/OT. Future studies with prospective, randomized, placebo-controlled designs are warranted to evaluate this promising intervention for delirium further.

Intravenous haloperidol: A systematic review of side effects and recommendations for clinical use.

INTRODUCTION: Though not approved by the United States Food and Drug Administration, intravenous haloperidol (IVH) is widely used off-label to manage agitation and psychosis in patients with delirium in the hospital setting. Over the years, concerns have emerged regarding side effects of IVH, particularly its potential to cause QT prolongation, torsades de pointes (TdP), extrapyramidal symptoms and catatonia. METHODS: We conducted a systematic review of literature of published literature related to side effects of IVH in PubMed in accordance with PRISMA guidelines. RESULTS: 77 of 196 identified manuscripts met inclusion criteria, including 34 clinical trials and 34 case reports or series. DISCUSSION: Extrapyramidal symptoms, catatonia and neuroleptic malignant syndrome appears to be relatively rare with IVH. In most prospective studies, IVH did not cause greater QT prolongation than placebo, and rates of TdP with IVH appear to be low. There is not clear evidence to suggest that IVH carries greater risk for QT prolongation or TdP than other antipsychotics. CONCLUSIONS: Based on the available literature, we provide modified evidence-based monitoring recommendations for clinicians prescribing IVH in hospital settings. Specifically, we recommend electrocardiogram monitoring only when using doses >5 mg of IVH and telemetry only for high-risk patients receiving cumulative doses of at least 100 mg or with accurately corrected QTc >500 ms.

The need to expand access to electroconvulsive therapy: a retrospective analysis of a new academic service.

BACKGROUND: Studies have long described the efficacy of electroconvulsive therapy (ECT); however, access to care continues to be an obstacle to treatment. Despite national trends resulting in declining availability of ECT, a new academic service was created to serve the needs of an area with limited resources. In this study, the characteristics and outcomes of patients receiving treatment during the first year of a new ECT program were assessed. The goals were to analyze treatment outcomes in this population and to identify associations between patient characteristics, treatment parameters, and clinical response. METHODS: Medical charts from the first 49 patients undergoing ECT between October 2010 and September 2011 were retrospectively reviewed. Patient characteristics, indications for ECT, and treatment parameters were compared with clinical improvement as defined by the Montgomery-Asberg Depression Rating Scale (MADRS). RESULTS: Of the 46 patients included in this study, the majority were female (63%), Caucasian (89%), and diagnosed with major depressive disorder (63%). The acute series duration ranged from 3 to 29 treatments (median of 13), with 50% (n=23) of patients achieving remission (MADRS<10) and 78% (n=36) achieving response (MADRS reduction > 50%) at the completion of the acute series. Positive outcomes were found to be associated with a history of medication-resistant conditions. CONCLUSIONS: ECT is a highly effective intervention for the treatment of depression and continues to be a sought-after therapy. Efficacy rates in the first year of this service were comparable to what has been reported in the general population and emphasize the need for the continued availability of ECT as a treatment option.

Charles Bonnet syndrome: are medications necessary?

Charles Bonnet syndrome (CBS) is a clinical entity in which patients develop vivid visual hallucinations in the absence of psychiatric illness. In the great majority of cases, a decline in visual acuity precedes the development of CBS. The patient maintains intact reality testing and recognizes that the hallucinations are not real. There is no definitive cure for CBS, although various pharmacologic agents, behavioral strategies, and ophthalmologic interventions have been used in an attempt to reduce or relieve symptoms. We present the case of a 79-year-old man who presented with the onset of vivid visual hallucinations after developing cataracts. We also review previous case reports of CBS and discuss treatment options.