Christopher James Doig

Purpose We performed a secondary analysis of a prior systematic review and meta-analysis to examine the prevalence and incidence of ICU delirium and pain. Methods The original search examined MEDLINE, EMBASE, CINAHL, and the Cochrane Central Register of Controlled trials from inception to May 15, 2023 (PROSPERO ID: CRD42022367715). Articles eligible for the current study derived from those previously reviewed at full text review. Included in the current study were randomised or observational studies among critically ill adults, that reported delirium or pain incidence or prevalence. Proportion data was transformed using the Freeman-Tukey double arcsine method prior to pooling using a random effects meta-analysis model. Joanna Briggs’ Institute prevalence checklist was used for risk of bias. Results From 517 full-text articles, 213 original studies, 226 publications (183,285 patients) were included. The pooled delirium prevalence (173 studies) was 35.7% (95%CI 32.4–39.0%). The most common delirium subtype was hypoactive (16.5%, 95%CI 12.1–21.4%). The pooled delirium incidence (41 studies) was 28.8% (95%CI 23.2–34.8%). The pooled pain prevalence (11 studies) was 43.5% (95%CI 28.6–58.9%). Delirium prevalence but not incidence decreased since 2013 (before: 39.9%, 95%CI 34.7–45.3% vs. after: 32.3%, 95%CI 28.2–36.5%, p = 0.02). Pain prevalence decreased significantly since publication of pain, agitation and delirium guidelines in 2013 (before: 64.6%, 95%CI 41.6–84.6% vs. after: 35.8%, 95%CI 20.5–52.6%, p = 0.046). Conclusions Delirium and pain prevalence among adults admitted to ICUs have decreased since publication of pain, agitation and delirium guidelines. However, both remain common, occurring in up to one-half of patients.

Background: Untreated pain is associated with short-term and long-term consequences, including post-traumatic stress disorder and insomnia. Side effects of some analgesic medications include dysphoria, hallucinations and delirium. Therefore, both untreated pain and analgesic medications may be risk factors for delirium. Delirium is associated with longer length of stay or cognitive impairment. Our systematic review and meta-analysis will examine the relationship between pain or analgesic medications with delirium occurrence, duration and severity among critically ill adults.Methods and analysis: MEDLINE, EMBASE, CINAHL, the Cochrane Central Register of controlled trials and a review of recent conference abstracts will be searched without restriction from inception to 15 May 2023. Study inclusion criteria are: (1) age≥18 years admitted to intensive care; (2) report a measure of pain, analgesic medications and delirium; (3) study design—randomised controlled trial, quasiexperimental designs and observational cohort and case–control studies excluding case reports. Study exclusion criteria are: (1) alcohol withdrawal delirium or delirium tremens; or (2) general anaesthetic emergence delirium; or (3) lab or animal studies. Risk of bias will be assessed with the Risk of Bias V.2 and risk of bias in non-randomised studies tools. There is no language restriction. Occurrence estimates will be transformed using the Freeman-Tukey double arcsine. Point estimates will be pooled using Hartung-Knapp Sidik-Jonkman random effects meta-analysis to estimate a pooled risk ratio. Statistical heterogeneity will be estimated with the I²statistic. Risk of small study effects will be assessed using funnel plots and Egger test. Studies will be analysed for time-varying and unmeasured confounding using E values.Ethics and dissemination: Ethical approval is not required as this is an analysis of published aggregated data. We will share our findings at conferences and in peer-reviewed journals.PROSPERO registration number: The finalised protocol was submitted to the International Prospective Register of Systematic Reviews (PROSPERO ID: CRD42022367715).

Background: Severe complicated intra-abdominal sepsis (SCIAS) has an increasing incidence with mortality rates over 80% in some settings. Mortality typically results from disruption of the gastrointestinal tract, progressive and self-perpetuating bio-mediator generation, systemic inflammation, and multiple organ failure. A further therapeutic option may be open abdomen (OA) management with negative peritoneal pressure therapy (NPPT) to remove inflammatory ascites and attenuate the systemic damage from SCIAS, although there are definite risks of leaving the abdomen open whenever it might possibly be closed. This potential therapeutic paradigm is the rationale being assessed in the Closed Or Open after Laparotomy (COOL trial) (https://clinicaltrials.gov/ct2/show/NCT03163095). Initially, the COOL trial received Industry sponsorship; however, this funding mandated the use of a specific trademarked and expensive NPPT device in half of the patients allocated to the intervention (open) arm. In August 2022, the 3 M/Acelity Corporation without consultation but within the terms of the contract canceled the financial support of the trial. Although creating financial difficulty, there is now no restriction on specific NPPT devices and removing a cost-prohibitive intervention creates an opportunity to expand the COOL trial to a truly global basis. This document describes the evolution of the COOL trial, with a focus on future opportunities for global growth of the study. Methods: The COOL trial is the largest prospective randomized controlled trial examining the random allocation of SCIAS patients intra-operatively to either formal closure of the fascia or the use of the OA with an application of an NPPT dressing. Patients are eligible if they have free uncontained intraperitoneal contamination and physiologic derangements exemplified by septic shock OR severely adverse predicted clinical outcomes. The primary outcome is intended to definitively inform global practice by conclusively evaluating 90-day survival. Initial recruitment has been lower than hoped but satisfactory, and the COOL steering committee and trial investigators intend with increased global support to continue enrollment until recruitment ensures a definitive answer. Discussion: OA is mandated in many cases of SCIAS such as the risk of abdominal compartment syndrome associated with closure, or a planned second look as for example part of “damage control”; however, improved source control (locally and systemically) is the most uncertain indication for an OA. The COOL trial seeks to expand potential sites and proceed with the evaluation of NPPT agnostic to device, to properly examine the hypothesis that this treatment attenuates systemic damage and improves survival. This approach will not affect internal validity and should improve the external validity of any observed results of the intervention. Trial registration: National Institutes of Health (https://clinicaltrials.gov/ct2/show/NCT03163095).

Critically ill patients in intensive care units experience profound alterations of their gut microbiota that have been linked to a high risk of hospital-acquired (nosocomial) infections and adverse outcomes through unclear mechanisms. Abundant mouse and limited human data suggest that the gut microbiota can contribute to maintenance of systemic immune homeostasis, and that intestinal dysbiosis may lead to defects in immune defense against infections. Here we use integrated systems-level analyses of fecal microbiota dynamics in rectal swabs and single-cell profiling of systemic immune and inflammatory responses in a prospective longitudinal cohort study of critically ill patients to show that the gut microbiota and systemic immunity function as an integrated metasystem, where intestinal dysbiosis is coupled to impaired host defense and increased frequency of nosocomial infections. Longitudinal microbiota analysis by 16s rRNA gene sequencing of rectal swabs and single-cell profiling of blood using mass cytometry revealed that microbiota and immune dynamics during acute critical illness were highly interconnected and dominated by Enterobacteriaceae enrichment, dysregulated myeloid cell responses and amplified systemic inflammation, with a lesser impact on adaptive mechanisms of host defense. Intestinal Enterobacteriaceae enrichment was coupled with impaired innate antimicrobial effector responses, including hypofunctional and immature neutrophils and was associated with an increased risk of infections by various bacterial and fungal pathogens. Collectively, our findings suggest that dysbiosis of an interconnected metasystem between the gut microbiota and systemic immune response may drive impaired host defense and susceptibility to nosocomial infections in critical illness.

Background: Family visitation in intensive care units (ICU) has been impacted by the severe acute respiratory syndrome coronavirus 2 (COVID-19) pandemic. While studies report on perceptions of families completely restricted from ICUs, little is known about the burden experienced by designated family caregivers allowed to visit their critically ill loved one. This study sought the perspectives of family caregivers of critically ill patients on the impact of one-person designated visitor policies mandated in ICUs during the COVID-19 pandemic.Methods: Throughout the study period a restricted visitation policy was mandated capturing the first (April 2020) and second (December 2020) waves of the pandemic that allowed one designated family caregiver (i.e., spouses or adult children) per patient to visit the ICU. Designated family caregivers of critically ill patients admitted to ICU September 2020 to November 2020 took part in individual 60-minute, semi-structured interviews at 6-months after discharge from the index ICU admission. Themes from family interviews were summarized with representative quotations.Results: Key themes identified following thematic analysis from six participants included: one visitor rule, patient advocate role, information needs, emotional distress, strategies for coping with challenges, practicing empathy, and appreciation of growth.Conclusion: Designated family caregivers of critically ill patients admitted to ICU during the COVID-19 pandemic perceived a complex and highly stressful experience. Support from ICU family liaisons and psychologists may help ameliorate the impact.

Background: Fluctuating course of delirium and complexities of ICU care mean delirium symptoms are hard to identify or commonly confused with other disorders. Delirium is difficult to diagnose, and clinicians and researchers may combine assessments from multiple tools. We evaluated diagnostic accuracy of different combinations of delirium assessments performed in each enrolled patient.Methods: Data were obtained from a previously conducted cross-sectional study. Eligible adult patients who remained admitted to ICU for >24 hours with at least one family member present were consecutively enrolled as patient-family dyads. Clinical delirium assessments (Intensive Care Delirium Screening Checklist [ICSDC] and Confusion Assessment Method-ICU [CAM-ICU]) were completed twice daily by bedside nurse or trained research assistant, respectively. Family delirium assessments (Family Confusion Assessment Method and Sour Seven) were completed once daily by family members. We pooled all delirium assessment tools in a single two-class latent model and pairwise (i.e., combined, clinical or family assessments) Bayesian analyses.Results: Seventy-three patient-family dyads were included. Among clinical delirium assessments, the ICDSC had lower sensitivity (0.72; 95% Bayesian Credible [BC] interval 0.54–0.92) and higher specificity (0.90; 95%BC, 0.82–0.97) using Bayesian analyses compared to pooled latent class analysis and CAM-ICU had higher sensitivity (0.90; 95%BC, 0.70–1.00) and higher specificity (0.94; 95%BC, 0.80–1.00). Among family delirium assessments, the Family Confusion Assessment Method had higher sensitivity (0.83; 95%BC, 0.71–0.92) and higher specificity (0.93; 95%BC, 0.84–0.98) using Bayesian analyses compared to pooled latent class analysis and the Sour Seven had higher specificity (0.85; 95%BC, 0.67–0.99) but lower sensitivity (0.64; 95%BC 0.47–0.82).Conclusions: Results from delirium assessment tools are often combined owing to imperfect reference standards for delirium measurement. Pairwise Bayesian analyses that explicitly accounted for each tool’s (performed within same patient) prior sensitivity and specificity indicate that two combined clinical or two combined family delirium assessment tools have fair diagnostic accuracy.

Introduction Flexible visitation policies in hospitals are an important component of care that contributes to reduced stress and increased satisfaction among patients and their family members. Early evidence suggests restricted visitation policies enacted in hospitals during the COVID-19 pandemic are having unintended consequences on patients, family members and healthcare providers. There is a need for a comprehensive summary of the impacts of restricted visitation policies on key stakeholders and approaches to mitigate that impact. Methods and analysis We will conduct a scoping review as per the Arksey-O’Malley 5-stage scoping review method and the Scoping Review Methods Manual by the Joanna Briggs Institute. We will search relevant electronic databases (eg, CINAHL, MEDLINE, PsycINFO), grey literature and preprint repositories. We will include all study designs including qualitative and quantitative methodologies (excluding protocols) as well as reports, opinions and editorials, to identify the broad impact of restricted hospital visitation policies due to the COVID-19 pandemic on patients, family members or healthcare providers of hospitalised patients, and approaches taken or proposed to mitigate this impact. Two reviewers will calibrate the screening criteria and data abstraction form and will independently screen studies and abstract the data. Narrative synthesis with thematic analysis will be performed. Ethics and dissemination Ethical approval is not applicable as this review will be conducted on published literature only. This scoping review will identify, describe and categorise impacts of restricted hospital visitation policies due to the COVID-19 pandemic on patients, family members and healthcare providers of hospitalised patients, and approaches that have been taken to mitigate impact. We will provide a comprehensive synthesis by developing a framework of restricted visitation policies and associated impacts. Our results will inform the development of consensus statements on restricted visitation policies to be implemented in future pandemics. PROSPERO registration number CRD42020221662.