Advancing specificity in delirium: The delirium subtyping initiative.

BACKGROUND: Delirium, a common syndrome with heterogeneous etiologies and clinical presentations, is associated with poor long-term outcomes. Recording and analyzing all delirium equally could be hindering the field's understanding of pathophysiology and identification of targeted treatments. Current delirium subtyping methods reflect clinically evident features but likely do not account for underlying biology. METHODS: The Delirium Subtyping Initiative (DSI) held three sessions with an international panel of 25 experts. RESULTS: Meeting participants suggest further characterization of delirium features to complement the existing Diagnostic and Statistical Manual of Mental Disorders Fifth Edition Text Revision diagnostic criteria. These should span the range of delirium-spectrum syndromes and be measured consistently across studies. Clinical features should be recorded in conjunction with biospecimen collection, where feasible, in a standardized way, to determine temporal associations of biology coincident with clinical fluctuations. DISCUSSION: The DSI made recommendations spanning the breadth of delirium research including clinical features, study planning, data collection, and data analysis for characterization of candidate delirium subtypes. HIGHLIGHTS: Delirium features must be clearly defined, standardized, and operationalized. Large datasets incorporating both clinical and biomarker variables should be analyzed together. Delirium screening should incorporate communication and reasoning.

Enhancing European Management of Analgesia, Sedation, and Delirium: A Multinational, Prospective, Interventional Before-After Trial.

BACKGROUND: The objective of this study was to analyze the impact of a structured educational intervention on the implementation of guideline-recommended pain, agitation, and delirium (PAD) assessment. METHODS: This was a prospective, multinational, interventional before-after trial conducted at 12 intensive care units from 10 centers in Germany, Austria, Switzerland, and the UK. Intensive care units underwent a 6-week structured educational program, comprising online lectures, instructional videos, educational handouts, and bedside teaching. Patient-level PAD assessment data were collected in three 1-day point-prevalence assessments before (T1), 6 weeks after (T2), and 1 year after (T3) the educational program. RESULTS: A total of 430 patients were included. The rate of patients who received all three PAD assessments changed from 55% (107/195) at T1 to 53% (68/129) at T2, but increased to 73% (77/106) at T3 (p = 0.003). The delirium screening rate increased from 64% (124/195) at T1 to 65% (84/129) at T2 and 77% (82/106) at T3 (p = 0.041). The pain assessment rate increased from 87% (170/195) at T1 to 92% (119/129) at T2 and 98% (104/106) at T3 (p = 0.005). The rate of sedation assessment showed no signficiant change. The proportion of patients who received nonpharmacological delirium prevention measures increased from 58% (114/195) at T1 to 80% (103/129) at T2 and 91% (96/106) at T3 (p < 0.001). Multivariable regression revealed that at T3, patients were more likely to receive a delirium assessment (odds ratio [OR] 2.138, 95% confidence interval [CI] 1.206-3.790; p = 0.009), sedation assessment (OR 4.131, 95% CI 1.372-12.438; p = 0.012), or all three PAD assessments (OR 2.295, 95% CI 1.349-3.903; p = 0.002) compared with T1. CONCLUSIONS: In routine care, many patients were not assessed for PAD. Assessment rates increased significantly 1 year after the intervention. Clinical trial registration ClinicalTrials.gov: NCT03553719.

A core outcome set for studies evaluating interventions to prevent and/or treat delirium for adults requiring an acute care hospital admission: an international key stakeholder informed consensus study.

BACKGROUND: Trials of interventions to prevent or treat delirium in adults in an acute hospital setting report heterogeneous outcomes. Our objective was to develop international consensus among key stakeholders for a core outcome set (COS) for future trials of interventions to prevent and/or treat delirium in adults with an acute care hospital admission and not admitted to an intensive care unit. METHODS: A rigorous COS development process was used including a systematic review, qualitative interviews, modified Delphi consensus process, and in-person consensus using nominal group technique (registration http://www.comet - initiative.org/studies/details/796 ). Participants in qualitative interviews were delirium survivors or family members. Participants in consensus methods comprised international representatives from three stakeholder groups: researchers, clinicians, and delirium survivors and family members. RESULTS: Item generation identified 8 delirium-specific outcomes and 71 other outcomes from 183 studies, and 30 outcomes from 18 qualitative interviews, including 2 that were not extracted from the systematic review. De-duplication of outcomes and formal consensus processes involving 110 experts including researchers (N = 32), clinicians (N = 63), and delirium survivors and family members (N = 15) resulted in a COS comprising 6 outcomes: delirium occurrence and reoccurrence, delirium severity, delirium duration, cognition, emotional distress, and health-related quality of life. Study limitations included exclusion of non-English studies and stakeholders and small representation of delirium survivors/family at the in-person consensus meeting. CONCLUSIONS: This COS, endorsed by the American and Australian Delirium Societies and European Delirium Association, is recommended for future clinical trials evaluating delirium prevention or treatment interventions in adults presenting to an acute care hospital and not admitted to an intensive care unit.

A Core Outcome Set for Research Evaluating Interventions to Prevent and/or Treat Delirium in Critically Ill Adults: An International Consensus Study (Del-COrS).

OBJECTIVES: Delirium in critically ill adults is highly prevalent and has multiple negative consequences. To-date, trials of interventions to prevent or treat delirium report heterogenous outcomes. To develop international consensus among key stakeholders for a core outcome set for future trials of interventions to prevent and/or treat delirium in critically ill adults. DESIGN: Core outcome set development, as recommended by the Core Outcome Measures in Effectiveness Trials Handbook. Methods of generating items for the core outcome set included a systematic review and qualitative interviews with ICU survivors and family members. Consensus methods include a two-round web-based Delphi process and a face-to-face meeting using nominal group technique methods. SUBJECTS: International representatives from three stakeholder groups: 1) clinical researchers, 2) ICU interprofessional clinicians, and 3) ICU survivors and family members. SETTING: Telephone interviews, web-based surveys, and a face-to-face consensus meeting held at the 2019 European Delirium Association's annual meeting in Edinburgh, Scotland. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Qualitative interviews with 24 ICU survivors and family members identified 36 potential outcomes; six were additional to the 97 identified from the systematic review. After item reduction, 32 outcomes were presented in Delphi Round 1; 179 experts participated, 38 ICU survivors/family members (21%), 100 clinicians (56%), 41 researchers (23%). Three additional outcomes were added to Round 2; 134 Round 1 participants (75%) completed it. Upon conclusion of the consensus building processes, the final core outcome set comprised seven outcomes: delirium occurrence (including prevalence or incidence); delirium severity; time to delirium resolution; health-related quality of life; emotional distress (i.e., anxiety, depression, acute and posttraumatic stress); cognition (including memory); and mortality. CONCLUSIONS: This core outcome set, endorsed by the American and Australian Delirium Societies and European Delirium Association, is recommended for future clinical trials evaluating delirium prevention or treatment interventions in critically ill adults.

Phenotypes and subphenotypes of delirium: a review of current categorisations and suggestions for progression.

Delirium is a clinical syndrome occurring in heterogeneous patient populations. It affects 45-87% of critical care patients and is often associated with adverse outcomes including acquired dementia, institutionalisation, and death. Despite an exponential increase in delirium research in recent years, the pathophysiological mechanisms resulting in the clinical presentation of delirium are still hypotheses. Efforts have been made to categorise the delirium spectrum into clinically meaningful subgroups (subphenotypes), using psychomotor subtypes such as hypoactive, hyperactive, and mixed, for example, and also inflammatory and non-inflammatory delirium. Delirium remains, however, a constellation of symptoms resulting from a variety of risk factors and precipitants with currently no successful targeted pharmacological treatment. Identifying specific clinical and biological subphenotypes will greatly improve understanding of the relationship between the clinical symptoms and the putative pathways and thus risk factors, precipitants, natural history, and biological mechanism. This will facilitate risk factor mitigation, identification of potential methods for interventional studies, and informed patient and family counselling. Here, we review evidence to date and propose a framework to identify subphenotypes. Endotype identification may be done by clustering symptoms with their biological mechanism, which will facilitate research of targeted treatments. In order to achieve identification of delirium subphenotypes, the following steps must be taken: (1) robust records of symptoms must be kept at a clinical level. (2) Global collaboration must facilitate large, heterogeneous research cohorts. (3) Patients must be clustered for identification, validation, and mapping of subphenotype stability.

Outcomes and measures of delirium interventional studies in palliative care to inform a core outcome set: A systematic review.

BACKGROUND: Trials of interventions for delirium in various patient populations report disparate outcomes and measures but little is known about those used in palliative care trials. A core outcome set promotes consistency of outcome selection and measurement. AIM: To inform core outcome set development by examining outcomes, their definitions, measures and time-points in published palliative care studies of delirium prevention or treatment delirium interventions. DESIGN: Prospectively registered systematic review adhering to Preferred Reporting Items for Systematic Reviews and Meta-Analyses. DATA SOURCES: We searched six electronic databases (1980-November 2020) for original studies, three for relevant reviews and the International Clinical Trials Registry Platform for unpublished studies and ongoing trials. We included randomised, quasi-randomised and non-randomised intervention studies of pharmacological and non-pharmacological delirium prevention and/or treatment interventions. RESULTS: From 13/3244 studies (2863 adult participants), we identified 9 delirium-specific and 13 non-delirium specific outcome domains within eight Core Outcome Measures in Effectiveness Trials (COMET) taxonomy categories. There were multiple and varied outcomes and time points in each domain. The commonest delirium specific outcome was delirium severity (n = 7), commonly using the Memorial Delirium Assessment Scale (6/8 studies, 75%). Four studies reported delirium incidence. Non-delirium specific outcomes included mortality, agitation, adverse events, other symptoms and quality of life. CONCLUSION: The review identified few delirium interventions with heterogeneity in outcomes, their definition and measurement, highlighting the need for a uniform approach. Findings will inform the next stage to develop consensus for a core outcome set to inform delirium interventional palliative care research.

Reporting of Outcomes and Outcome Measures in Studies of Interventions to Prevent and/or Treat Delirium in the Critically Ill: A Systematic Review.

OBJECTIVES: To inform development of a core outcome set, we evaluated the scope and variability of outcomes, definitions, measures, and measurement time-points in published clinical trials of pharmacologic or nonpharmacologic interventions, including quality improvement projects, to prevent and/or treat delirium in the critically ill. DATA SOURCES: We searched electronic databases, systematic review repositories, and trial registries (1980 to March 2019). STUDY SELECTION AND DATA EXTRACTION: We included randomized, quasi-randomized, and nonrandomized intervention studies of pharmacologic and nonpharmacologic interventions. We extracted data on study characteristics, verbatim descriptions of study outcomes, and measurement characteristics. We assessed quality of outcome reporting using the Management of Otitis Media with Effusion in Children with Cleft Palate study scoring system; risk of bias and study quality using the Cochrane tool and Scottish Intercollegiate Guidelines Network checklists. We categorized reported outcomes using Core Outcome Measures in Effectiveness Trials taxonomy. DATA SYNTHESIS: From 195 studies (1/195 pediatric) recruiting 74,632 participants and reporting a mean (SD) of 10 (6.2) outcome domains, we identified 12 delirium-specific outcome domains. Delirium incidence (147, 75% of studies), duration (67, 34%), and antipsychotic use (42, 22%) were most commonly reported. We identified a further 94 non-delirium-specific outcome domains within 19 Core Outcome Measures in Effectiveness Trials taxonomy categories. For both delirium-specific and nonspecific outcome domains, we found multiple outcomes in domains due to differing descriptions and time-points. The Confusion Assessment Method-ICU with Richmond Agitation-Sedation Scale to assess sedation was the most common measure used to ascertain delirium (51, 35%). Measurement generally began at randomization or ICU admission, and lasted from 1 to 30 days, ICU/hospital discharge. Frequency of measurement was highly variable with daily measurement and greater than daily measurement reported for 36% and 37% of studies, respectively. CONCLUSIONS: We identified substantial heterogeneity and multiplicity of outcome selection and measurement in published studies. These data will inform the consensus building stage of a core outcome set to inform delirium research in the critically ill.

Statin use and risk of delirium in the critically ill.

RATIONALE: Delirium is common in intensive care unit (ICU) patients and is a predictor of worse outcomes and neuroinflammation is a possible mechanism. The antiinflammatory actions of statins may reduce delirium. OBJECTIVES: To determine whether critically ill patients receiving statin therapy had a reduced risk of delirium than those not on statins. METHODS: A prospective cohort analysis of data from consecutive ICU patients admitted to a UK mixed medical and surgical critical care unit between August 2011 and February 2012; the Confusion Assessment Method for ICU was used to determine the days each patient was assessed as being free of delirium during ICU admission. MEASUREMENTS AND MAIN RESULTS: Delirium-free days, daily administration of statins, and serum C-reactive protein (CRP) were recorded. Four hundred and seventy consecutive critical care patients were followed, of whom 151 patients received statins. Using random-effects multivariable logistic regression, statin administration the previous evening was associated with the patient being assessed as free of delirium (odds ratio, 2.28; confidence interval, 1.01-5.13; P < 0.05) and with lower CRP (ß = -0.52; P < 0.01) the following day. When the association between statin and being assessed as free of delirium was controlled for CRP, the effect size became nonsignificant (odds ratio, 1.56; confidence interval, 0.64-3.79; P = 0.32). CONCLUSIONS: Ongoing statin therapy is associated with a lower daily risk of delirium in critically ill patients. An ongoing clinical trial, informed by this study, is investigating if statins are a potential therapy for delirium in the critically ill.

Sedation/drugs used in intensive care sedation.

PURPOSE OF REVIEW: There is recognition that the use of sedative drugs in critically ill patients is potentially harmful, particularly in relation to ICU delirium and clinical outcomes. In that context, there is an increasing interest in maintaining light sedation, the use of non-gamma-aminobutyric acid agonist agents and antipsychotics. RECENT FINDINGS: The sedative drugs currently available have limitations relating to duration of action, cost or variability in response. Recent reviews and meta-analyses comparing sedatives in ICU patients differ in their findings depending on whether trials in elective cardiac surgical patients are included. Dexmedetomidine does appear to reduce the number of ventilator days in the less sick critically ill patient. There is currently no evidence to support the routine use of antipsychotics in ICU patients to prevent or treat delirium, although they will reduce agitation and they appear to be well tolerated when used in the critically ill patient. Sedation protocols and early mobilization reduce the use of sedative drugs and improve some outcomes but are challenging to implement in practice. SUMMARY: The bedside clinician needs to balance the need to sedate the patient and maintain life-saving support, while keeping their patient responsive, cooperative and pain free.

Missing link or not, mobilise against delirium.

Delirium is known to be a predictor of adverse outcomes. In a prospective study Abelha and colleagues showed that postoperative delirium was an independent risk factor for deterioration in functional capacity following discharge. While evidence for causality remains elusive, there is no doubt that patients who develop delirium are left with new functional and cognitive impairment. Finding a pharmacological treatment for the prevention and treatment of delirium is a priority in delirium research and the results of ongoing trials are awaited. Early mobilisation of ICU patients has been demonstrated to decrease delirium and improve functional outcomes. Resources should be directed to appropriate, progressive mobilisation of all critically ill patients as a priority.

Whole blood thiamine, intravenous thiamine supplementation and delirium occurrence in the intensive care unit: retrospective cohort analyses.

BACKGROUND: Thiamine di-phosphate is an essential cofactor in glucose metabolism, glutamate transformation and acetylcholinesterase activity, pathways associated with delirium occurrence. We hypothesised that a deficiency in whole blood thiamine and intravenous thiamine supplementation could impact delirium occurrence. AIM: To establish whether a deficiency in whole blood thiamine and/or intravenous thiamine supplementation within 72 h of intensive care admission is associated with delirium occurrence. METHOD: The first dataset was secondary analysis of a previous study in an intensive care unit in the Netherlands, reported in 2017. The second dataset contained consecutive intensive care admissions 2 years before (period 1: October 2014 to October 2016) and after (period 2: April 2017 to April 2019) routine thiamine supplementation was introduced within 72 h of admission. Delirium was defined as a positive Confusion Assessment Method-Intensive Care Unit score(s) in 24 h. RESULTS: Analysis of the first dataset (n = 57) using logistic regression showed no relationship between delirium and sepsis or whole blood thiamine, but a significant association with age (p = 0.014). In the second dataset (n = 3074), 15.1% received IV thiamine in period 1 and 62.6% during period 2. Hierarchical regression analysis reported reduction in delirium occurrence in the second period; this did not reach statistical significance, OR = 0.81 (95% CI 0.652-1.002); p = 0.052. CONCLUSION: No relationship was detected between whole blood thiamine and delirium occurrence on admission, at 24 and 48 h. It remains unclear whether routine intravenous thiamine supplementation during intensive care admission impacts delirium occurrence. Further prospective randomised clinical trials are needed.

The Delphi Delirium Management Algorithms. A practical tool for clinicians, the result of a modified Delphi expert consensus approach.

Delirium is common in hospitalised patients, and there is currently no specific treatment. Identifying and treating underlying somatic causes of delirium is the first priority once delirium is diagnosed. Several international guidelines provide clinicians with an evidence-based approach to screening, diagnosis and symptomatic treatment. However, current guidelines do not offer a structured approach to identification of underlying causes. A panel of 37 internationally recognised delirium experts from diverse medical backgrounds worked together in a modified Delphi approach via an online platform. Consensus was reached after five voting rounds. The final product of this project is a set of three delirium management algorithms (the Delirium Delphi Algorithms), one for ward patients, one for patients after cardiac surgery and one for patients in the intensive care unit.

Alpha 2 agonists for sedation to produce better outcomes from critical illness (A2B Trial): protocol for a multicentre phase 3 pragmatic clinical and cost-effectiveness randomised trial in the UK.

INTRODUCTION: Almost all patients receiving mechanical ventilation (MV) in intensive care units (ICUs) require analgesia and sedation. The most widely used sedative drug is propofol, but there is uncertainty whether alpha2-agonists are superior. The alpha 2 agonists for sedation to produce better outcomes from critical illness (A2B) trial aims to determine whether clonidine or dexmedetomidine (or both) are clinically and cost-effective in MV ICU patients compared with usual care. METHODS AND ANALYSIS: Adult ICU patients within 48 hours of starting MV, expected to require at least 24 hours further MV, are randomised in an open-label three arm trial to receive propofol (usual care) or clonidine or dexmedetomidine as primary sedative, plus analgesia according to local practice. Exclusions include patients with primary brain injury; postcardiac arrest; other neurological conditions; or bradycardia. Unless clinically contraindicated, sedation is titrated using weight-based dosing guidance to achieve a Richmond-Agitation-Sedation score of -2 or greater as early as considered safe by clinicians. The primary outcome is time to successful extubation. Secondary ICU outcomes include delirium and coma incidence/duration, sedation quality, predefined adverse events, mortality and ICU length of stay. Post-ICU outcomes include mortality, anxiety and depression, post-traumatic stress, cognitive function and health-related quality of life at 6-month follow-up. A process evaluation and health economic evaluation are embedded in the trial.The analytic framework uses a hierarchical approach to maximise efficiency and control type I error. Stage 1 tests whether each alpha2-agonist is superior to propofol. If either/both interventions are superior, stages 2 and 3 testing explores which alpha2-agonist is more effective. To detect a mean difference of 2 days in MV duration, we aim to recruit 1437 patients (479 per group) in 40-50 UK ICUs. ETHICS AND DISSEMINATION: The Scotland A REC approved the trial (18/SS/0085). We use a surrogate decision-maker or deferred consent model consistent with UK law. Dissemination will be via publications, presentations and updated guidelines. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT03653832.

Few-Shot Object Detection: Application to Medieval Musicological Studies.

Detecting objects with a small representation in images is a challenging task, especially when the style of the images is very different from recent photos, which is the case for cultural heritage datasets. This problem is commonly known as few-shot object detection and is still a new field of research. This article presents a simple and effective method for black box few-shot object detection that works with all the current state-of-the-art object detection models. We also present a new dataset called MMSD for medieval musicological studies that contains five classes and 693 samples, manually annotated by a group of musicology experts. Due to the significant diversity of styles and considerable disparities between the artistic representations of the objects, our dataset is more challenging than the current standards. We evaluate our method on YOLOv4 (m/s), (Mask/Faster) RCNN, and ViT/Swin-t. We present two methods of benchmarking these models based on the overall data size and the worst-case scenario for object detection. The experimental results show that our method always improves object detector results compared to traditional transfer learning, regardless of the underlying architecture.

Plasma neurofilament light chain protein as a predictor of days in delirium and deep sedation, mortality and length of stay in critically ill patients.

BACKGROUND: Delirium predicts poor outcomes, however identifying patients with the worst outcomes is challenging. Plasma neurofilament light protein (NfL) is a sensitive indicator of neuronal damage. We undertook an exploratory observational study to determine the association between plasma NfL and delirium in the critically ill. METHODS: MoDUS was a randomised placebo-controlled delirium trial of simvastatin done in an UK adult general ICU. We measured NfL levels in plasma samples using a Single molecule array (Simoa) platform. We explored associations between patient's plasma NfL levels and number of delirium days, and clinical outcomes. The control group for baseline NfL were preoperative patients undergoing major surgery. FINDINGS: The majority of critically ill patients already had a high NfL level on admission. Patients with higher plasma NfL levels at days one and three spent more days in delirium or deep sedation. Patients with zero or one day in delirium or deep sedation had day one mean concentrations of 37.8 pg/ml (SD 32.6) compared with 96.5 pg/ml (SD 106.1)) for patients with two days or more, p-value 0.002 linear mixed effects model. Survivors discharged before 14 days had lower mean plasma NfL concentrations compared to those with longer hospital stays and/or who died within six months. The area under ROC curve for predicting death within six months using day one NfL was 0.81 (0.7,0.9). INTERPRETATION: Measurement of plasma NfL within three days of admission may be useful to identify those patients with worse clinical outcomes, and as an enrichment strategy for future delirium interventional trials in the critically ill. FUNDING: Alzheimer's Society UK, UK Dementia Research Institute.

Sedation in the Intensive Care Unit.

PURPOSE OF REVIEW: This narrative review illustrates literature over the last 5 years relating to sedation delivery to mechanically ventilated adult patients in intensive care units. RECENT FINDINGS: There has been an increase in dexmedetomidine-related publications but although systematic reviews suggest dexmedetomidine reduces delirium, agitation, and length of stay, clinical trials have not supported these findings. It is likely to be useful for the managing patients with persisting agitation. Guidelines continue to recommend lightly sedating patients but considerable variation remains in clinical practice and in research trials. Protocols with no sedative infusions and morphine boluses as needed are feasible and safe, while educational interventions can decrease sedation-related adverse events. SUMMARY: Research trials have mainly focused on individual drugs rather than practice. Given evidence is slow to translate into practice; work is needed to understand and respond to the concerns of clinicians regarding deep sedation and agitation.

Parenteral thiamine for prevention and treatment of delirium in critically ill adults: a systematic review protocol.

BACKGROUND: Delirium is an acute confusional state, common in critical illness and associated with cognitive decline. There is no effective pharmacotherapy to prevent or treat delirium, although it is scientifically plausible that thiamine could be effective. Thiamine studies in dementia patients are inconclusive. Aside from small numbers, all used oral administration: bioavailability of thiamine is poor; parenteral thiamine bypasses this. In the UK, parenteral thiamine is administered as a compound vitamin B and C solution (Pabrinex®). The aim of this review is to evaluate the effectiveness of parenteral thiamine (alone or in a compound solution) in preventing or treating delirium in critical illness. METHODS: We will search for studies in electronic databases (MEDLINE (Pro-Quest), EMBASE, CINAHL, LILACS, CNKI, AMED, and Cochrane CENTRAL), clinical trials registries (WHO International Clinical Trials Registry, ClinicalTrials.gov, and Controlled-trials.com), and grey literature (Google Scholar, conference proceedings, and Index to Theses). We will perform complementary searches of reference lists of included studies, relevant reviews, clinical practice guidelines, or other pertinent documents (e.g. official documents and government reports). We will consider quasi-randomised or randomised controlled trials in critically ill adults. We will include studies that evaluate parenteral thiamine versus standard of care, placebo, or any other non-pharmacological or pharmacological interventions. The primary outcomes will be the delirium core outcome set, including incidence and severity of delirium and cognition. Secondary outcomes are adapted from the ventilation core outcome set: duration of mechanical ventilation, length of stay, and adverse events incidence. Screening, data extraction, and risk of bias assessment will be undertaken independently by two reviewers. If data permits, we will conduct meta-analyses using a random effects model and, where appropriate, sensitivity and subgroup analyses to explore sources of heterogeneity. DISCUSSION: This review will provide evidence for the effectiveness of parental thiamine in the prevention or treatment of delirium in critical care. Findings will contribute to establishing the need for a multicentre study of parenteral thiamine in the prevention and treatment of critical care delirium. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42019118808.

The association between post-cardiac arrest cerebral oxygenation and survival with favorable neurological outcomes: A multicenter study.

OBJECTIVE: Cerebral oximetry is a non-invasive system that uses near infrared spectroscopy to measure regional cerebral oxygenation (rSO2) in the frontal lobe of the brain. Post-cardiac arrest rSO2 may be associated with survival and neurological outcomes in out-of-hospital cardiac arrest patients; however, no studies have examined relationships between rSO2 and neurological outcomes following in-hospital cardiac arrest (IHCA). We tested the hypothesis that rSO2 following IHCA is associated with survival and favorable neurological outcomes. DESIGN: Prospective study from nine acute care hospital in the United States and United Kingdom. PATIENTS: Convenience sample of IHCA patients admitted to the intensive care unit with post-cardiac arrest syndrome. INTERVENTIONS: Cerebral oximetry monitoring (Equanox 7600, Nonin Medical, MN, USA) during the first 48 h after IHCA. MEASUREMENTS AND MAIN RESULTS: Subject's rSO2 was calculated as the mean of collected data at different time intervals: hourly between 1-6 h, 6-12 h, 12-18 h, 18-24 h and 24-48 h. Demographic data pertaining to possible confounding variables for rSO2 and primary outcome were collected. The primary outcome was survival with favorable neurological outcomes (cerebral performance scale [CPC] 1-2) vs severe neurological injury or death (CPC 3-5) at hospital discharge. Univariate and multivariate statistical analyses were performed to correlate cerebral oximetry values and other variables with the primary outcome. Among 87 studied patients, 26 (29.9%) achieved CPC 1-2. A significant difference in mean rSO2 was observed during hours 1-2 after IHCA in CPC 1-2 vs CPC 3-5 (73.08 vs. 66.59, p = 0.031) but not at other time intervals. There were no differences in age, Charlson comorbidity index, APACHE II scores, CPR duration, mean arterial pressure, PaO2, PaCO2, and hemoglobin levels between two groups. CONCLUSIONS: There may be a significant physiological difference in rSO2 in the first two hours after ROSC in IHCA patients who achieve favorable neurological outcomes, however, this difference may not be clinically significant.