Objective:To revise the “Clinical Practice Guidelines for the Sustained Use of Sedatives and Analgesics in the Critically Ill Adult” published in Critical Care Medicine in 2002.Methods:The American College of Critical Care Medicine assembled a 20-person, multidisciplinary, multi-institutional task f

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Clinical Practice Guidelines for the Management of Pain, Agitation, and Delirium in Adult Patients in the Intensive Care Unit

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(13)60688-1.pdf

Delirium in elderly people

Objective:To update and expand the 2013 Clinical Practice Guidelines for the Management of Pain, Agitation, and Delirium in Adult Patients in the ICU.Design:Thirty-two international experts, four methodologists, and four critical illness survivors met virtually at least monthly. All section groups g

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Clinical Practice Guidelines for the Prevention and Management of Pain, Agitation/Sedation, Delirium, Immobility, and Sleep Disruption in Adult Patients in the ICU

Following the severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV), another highly pathogenic coronavirus named SARS-CoV-2 (previously known as 2019-nCoV) emerged in December 2019 in Wuhan, China, and rapidly spreads around the world. This virus shares highly homological sequence with SARS-CoV, and causes acute, highly lethal pneumonia coronavirus disease 2019 (COVID-19) with clinical symptoms similar to those reported for SARS-CoV and MERS-CoV. The most characteristic symptom of patients with COVID-19 is respiratory distress, and most of the patients admitted to the intensive care could not breathe spontaneously. Additionally, some patients with COVID-19 also showed neurologic signs, such as headache, nausea, and vomiting. Increasing evidence shows that coronaviruses are not always confined to the respiratory tract and that they may also invade the central nervous system inducing neurological diseases. The infection of SARS-CoV has been reported in the brains from both patients and experimental animals, where the brainstem was heavily infected. Furthermore, some coronaviruses have been demonstrated able to spread via a synapse-connected route to the medullary cardiorespiratory center from the mechanoreceptors and chemoreceptors in the lung and lower respiratory airways. Considering the high similarity between SARS-CoV and SARS-CoV2, it remains to make clear whether the potential invasion of SARS-CoV2 is partially responsible for the acute respiratory failure of patients with COVID-19. Awareness of this may have a guiding significance for the prevention and treatment of the SARS-CoV-2-induced respiratory failure.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/jmv.25728

The neuroinvasive potential of SARS-CoV2 may play a role in the respiratory failure of COVID-19 patients

Context γ-Aminobutyric acid receptor agonist medications are the most commonly used sedatives for intensive care unit (ICU) patients, yet preliminary evidence indicates that the α 2 agonist dexmedetomidine may have distinct advantages Objective To compare the efficacy and safety of prolonged sedation with dexmedetomidine vs midazolam for mechanically ventilated patients Design, Setting, and Patients Prospective, double-blind, randomized trial conducted in 68 centers in 5 countries between March 2005 and August 2007 among 375 medical/surgical ICU patients with expected mechanical ventilation for more than 24 hours Sedation level and delirium were assessed using the Richmond Agitation-Sedation Scale (RASS) and the Confusion Assessment Method for the ICU Interventions Dexmedetomidine (02-14 μg/kg per hour [n = 244]) or midazolam (002-01 mg/kg per hour [n = 122]) titrated to achieve light sedation (RASS scores between −2 and +1) from enrollment until extubation or 30 days Main Outcome Measures Percentage of time within target RASS range Secondary end points included prevalence and duration of delirium, use of fentanyl and open-label midazolam, and nursing assessments Additional outcomes included duration of mechanical ventilation, ICU length of stay, and adverse events Results There was no difference in percentage of time within the target RASS range (773% for dexmedetomidine group vs 751% for midazolam group; difference, 22% [95% confidence interval {CI}, −32% to 75%]; P = 18) The prevalence of delirium during treatment was 54% (n = 132/244) in dexmedetomidine-treated patients vs 766% (n = 93/122) in midazolam-treated patients (difference, 226% [95% CI, 14% to 33%]; P  Conclusions There was no difference between dexmedetomidine and midazolam in time at targeted sedation level in mechanically ventilated ICU patients At comparable sedation levels, dexmedetomidine-treated patients spent less time on the ventilator, experienced less delirium, and developed less tachycardia and hypertension The most notable adverse effect of dexmedetomidine was bradycardia Trial Registration clinicaltrialsgov Identifier: NCT00216190Published online February 2, 2009 (doi:101001/jama200956)

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Dexmedetomidine vs midazolam for sedation of critically ill patients: a randomized trial.

Delirium is a neurobehavioral syndrome caused by dysregulation of neuronal activity secondary to systemic disturbances. Over time, a number of theories have been proposed in an attempt to explain the processes leading to the development of delirium. Each proposed theory has focused on a specific mechanism or pathologic process (e.g., dopamine excess or acetylcholine deficiency theories), observational and experiential evidence (e.g., sleep deprivation, aging), or empirical data (e.g., specific pharmacologic agents' association with postoperative delirium, intraoperative hypoxia). This article represents a review of published literature and summarizes the top seven proposed theories and their interrelation. This review includes the "neuroinflammatory," "neuronal aging," "oxidative stress," "neurotransmitter deficiency," "neuroendocrine," "diurnal dysregulation," and "network disconnectivity" hypotheses. Most of these theories are complementary, rather than competing, with many areas of intersection and reciprocal influence. The literature suggests that many factors or mechanisms included in these theories lead to a final common outcome associated with an alteration in neurotransmitter synthesis, function, and/or availability that mediates the complex behavioral and cognitive changes observed in delirium. In general, the most commonly described neurotransmitter changes associated with delirium include deficiencies in acetylcholine and/or melatonin availability; excess in dopamine, norepinephrine, and/or glutamate release; and variable alterations (e.g., either a decreased or increased activity, depending on delirium presentation and cause) in serotonin, histamine, and/or γ-aminobutyric acid. In the end, it is unlikely that any one of these theories is fully capable of explaining the etiology or phenomenologic manifestations of delirium but rather that two or more of these, if not all, act together to lead to the biochemical derangement and, ultimately, to the complex cognitive and behavioral changes characteristic of delirium.

Neuropathogenesis of delirium: review of current etiologic theories and common pathways.

https://www.westicu.cn/UpFile/201406/2014062170671361.pdf

Dexmedetomidine and the reduction of postoperative delirium after cardiac surgery.

Background Delirium is the most common neuropsychiatric syndrome encountered by clinicians dealing with older adults and the medically ill and is best characterized by 5 core domains: cognitive deficits, attentional deficits, circadian rhythm dysregulation, emotional dysregulation, and alteration in psychomotor functioning. Design An extensive literature review and consolidation of published data into a novel interpretation of known pathophysiological causes of delirium. Results Available data suggest that numerous pathological factors may serve as precipitants for delirium, each having differential effects depending on patient-specific patient physiological characteristics (substrate). On the basis of an extensive literature search, a newly proposed theory, the systems integration failure hypothesis, was developed to bring together the most salient previously described theories, by describing the various contributions from each into a complex web of pathways-highlighting areas of intersection and commonalities and explaining how the variable contribution of these may lead to the development of various cognitive and behavioral dysfunctions characteristic of delirium. The specific cognitive and behavioral manifestations of the specific delirium picture result from a combination of neurotransmitter function and availability, variability in integration and processing of sensory information, motor responses to both external and internal cues, and the degree of breakdown in neuronal network connectivity, hence the term acute brain failure. Conclusions The systems integration failure hypothesis attempts to explain how the various proposed delirium pathophysiologic theories interact with each other, causing various clinically observed delirium phenotypes. A better understanding of the underlying pathophysiology of delirium may eventually assist in designing better prevention and management approaches.

Delirium pathophysiology: An updated hypothesis of the etiology of acute brain failure.

https://www.criticalcare.theclinics.com/article/S0749-0704(08)00055-9/pdf

Pathoetiological model of delirium: a comprehensive understanding of the neurobiology of delirium and an evidence-based approach to prevention and treatment.

José R. Maldonado

Papers

Neuropathogenesis of delirium: review of current etiologic theories and common pathways.

Dexmedetomidine and the reduction of postoperative delirium after cardiac surgery.

Delirium pathophysiology: An updated hypothesis of the etiology of acute brain failure.

Pathoetiological model of delirium: a comprehensive understanding of the neurobiology of delirium and an evidence-based approach to prevention and treatment.

The Stanford Integrated Psychosocial Assessment for Transplantation (SIPAT): A New Tool for the Psychosocial Evaluation of Pre-Transplant Candidates