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 effect of computerised decision support alerts tailored to intensive care on the administration of high-risk drug combinations, and their monitoring: a cluster randomised stepped-wedge trial.

BACKGROUND: Drug-drug interactions (DDIs) can harm patients admitted to the intensive care unit (ICU). Yet, clinical decision support systems (CDSSs) aimed at helping physicians prevent DDIs are plagued by low-yield alerts, causing alert fatigue and compromising patient safety. The aim of this multicentre study was to evaluate the effect of tailoring potential DDI alerts to the ICU setting on the frequency of administered high-risk drug combinations. METHODS: We implemented a cluster randomised stepped-wedge trial in nine ICUs in the Netherlands. Five ICUs already used potential DDI alerts. Patients aged 18 years or older admitted to the ICU with at least two drugs administered were included. Our intervention was an adapted CDSS, only providing alerts for potential DDIs considered as high risk. The intervention was delivered at the ICU level and targeted physicians. We hypothesised that showing only relevant alerts would improve CDSS effectiveness and lead to a decreased number of administered high-risk drug combinations. The order in which the intervention was implemented in the ICUs was randomised by an independent researcher. The primary outcome was the number of administered high-risk drug combinations per 1000 drug administrations per patient and was assessed in all included patients. This trial was registered in the Netherlands Trial Register (identifier NL6762) on Nov 26, 2018, and is now closed. FINDINGS: In total, 10 423 patients admitted to the ICU between Sept 1, 2018, and Sept 1, 2019, were assessed and 9887 patients were included. The mean number of administered high-risk drug combinations per 1000 drug administrations per patient was 26·2 (SD 53·4) in the intervention group (n=5534), compared with 35·6 (65·0) in the control group (n=4353). Tailoring potential DDI alerts to the ICU led to a 12% decrease (95% CI 5-18%; p=0·0008) in the number of administered high-risk drug combinations per 1000 drug administrations per patient, after adjusting for clustering and prognostic factors. INTERPRETATION: This cluster randomised stepped-wedge trial showed that tailoring potential DDI alerts to the ICU setting significantly reduced the number of administered high-risk drug combinations. Our list of high-risk drug combinations can be used in other ICUs, and our strategy of tailoring alerts based on clinical relevance could be applied to other clinical settings. FUNDING: ZonMw.

Mental health-related quality of life is related to delirium in intensive care patients.

PURPOSE: Delirium during intensive care unit (ICU) stay may be related to premorbid mental illness. In addition, delirium during ICU stay may also negatively affect long-term health-related quality of life. The aim of our study was to investigate if delirium in the ICU is related to premorbid mental quality of life and affects long-term mental quality of life after ICU stay. METHODS: We performed a prospective cohort study in 1021 patients admitted for longer than 48 h in a medical-surgical ICU. We evaluated mental and physical quality of life using the Short-form-12 before ICU admission, at hospital discharge, and 3, 6 and 12 months after hospital discharge. Mixed model and logistic regression models were used to analyze the data. RESULTS: Patients who experienced a delirium during ICU stay reported a worse pre-admission mental quality of life than those without delirium (p < 0.001). Furthermore, patients who suffered from delirium during their ICU stay exhibited a significant decrease in mental quality of life over time relative to patients without delirium (p = 0.035). CONCLUSION: In this large follow-up study, we demonstrated that ICU survivors who experienced a delirium during ICU stay reported a significantly worse pre-admission mental health-related quality of life and a significant decrease in mental health-related quality of life in the year after hospital discharge compared with patients without delirium.

Dysphagia in Intensive Care Evaluation (DICE): An International Cross-Sectional Survey.

Dysphagia occurs commonly in the intensive care unit (ICU). Despite the clinical relevance, there is little worldwide research on prevention, assessment, evaluation, and/or treatment of dysphagia for ICU patients. We aimed to gain insight into this international knowledge gap. We conducted a multi-center, international online cross-sectional survey of adult ICUs. Local survey distribution champions were recruited through professional and personal networks. The survey was administered from November 2017 to June 2019 with three emails and a final telephone reminder. Responses were received from 746 ICUs (26 countries). In patients intubated > 48 h, 17% expected a > 50% chance that dysphagia would develop. This proportion increased to 43% in patients intubated > 7 days, and to 52% in tracheotomized patients. Speech-language pathologist (SLP) consultation was available in 66% of ICUs, only 4% reported a dedicated SLP. Although 66% considered a routine post-extubation dysphagia protocol important, most (67%) did not have a protocol. Few ICUs routinely assessed for dysphagia after 48 h of intubation (30%) or tracheostomy (41%). A large proportion (46%) used water swallow screening tests to determine aspiration, few (8%) used instrumental assessments (i.e., flexible endoscopic evaluation of swallowing). Swallowing exercises were used for dysphagia management by 30% of ICUs. There seems to be limited awareness among ICU practitioners that patients are at risk of dysphagia, particularly as ventilation persists, protocols, routine assessment, and instrumental assessments are generally not used. We recommend the development of a research agenda to increase the quality of evidence and ameliorate the implementation of evidence-based dysphagia protocols by dedicated SLPs.

SICQ Coping and the Health-Related Quality of Life and Recovery of Critically Ill ICU Patients: A Prospective Cohort Study.

BACKGROUND: The coping styles of the Sickness Insight in Coping Questionnaire (SICQ; positivism, redefinition, toughness, fighting spirit, nonacceptance) may affect the health and recovery of hospitalized critically ill patients. RESEARCH QUESTION: Do the SICQ coping styles of hospitalized critically ill patients relate to the patients health-related quality of life (HRQoL) and recovery? STUDY DESIGN AND METHODS: A prospective cohort study was conducted in a single university-affiliated Dutch hospital. Participants were critically ill adult patients admitted to a mixed medical-surgical ICU (start: n = 417; pre-ICU: n = 391; hospital discharge: n = 350; 3-month follow-up: n = 318; 6-month follow-up: n = 308; 12-month follow-up: n = 285). Coping was recorded with the SICQ pre-ICU and at discharge. HRQoL was measured with the SF-12 pre-ICU, at discharge, and 3, 6, and 12 months after discharge. Indicators of recovery were ICU and hospital length of stay, discharge disposition, and mortality. Correlation and regression analyses were used for data analysis. RESULTS: Positivism (r = 0.28-0.51), fighting spirit (r = 0.14-0.35), and redefinition (r = 0.12-0.23) associated significantly (P < .05) with mental HRQoL after discharge. Furthermore, positivism associated positively (P < .01) with physical HRQoL (r = 0.17-0.26) after discharge. Increase in positivism (r = 0.13), redefinition (r = 0.13), and toughness (r = 0.13) across the period of hospitalization associated positively (P ≤ .05) with mental HRQoL at discharge. Pre-ICU positivism associated with hospital length of stay (ρ = -.21, P ≤ .05) and hazard for death (HR = 0.57, P < .01) and had a unidirectional effect on mental HRQoL (ß = .30, P < .001). INTERPRETATION: SICQ coping is associated with long-term mental HRQoL, hospital length of stay, and hazard for death among hospitalized critically ill patients.

Health-related quality of life in ICU survivors-10 years later.

Many Intensive Care (ICU) survivors experience long lasting impairments in physical and psychological health as well as social functioning. The objective of our study was to evaluate these effects up to 10 years after ICU discharge. We performed a long-term prospective cohort study in patients admitted for longer than 48 h in a medical-surgical ICU. We evaluated health-related quality of life (HRQOL) before ICU admission using the Short-form-36 (SF-36), at ICU discharge, at hospital discharge and at 1, 2, 5 and 10 years follow up (all by patients). Changes in HRQOL were assessed based on linear mixed modeling. We included a total of 749 patients (from 2000 to 2008). During 10 years 475 (63.4%) patients had died, 125 (16.7%) patients were lost to follow up and 149 (19.9%) patients could be evaluated. The mean scores of four HRQOL dimensions (i.e., physical functioning (p < 0.001; mean 54, SD 32, effect size 0.77, 95% CI [0.54-1.0]), role-physical (p < 0.001; mean 44, SD 47, effect size 0.65, 95% CI [0.41-0.68] general health (p < 0.001; mean 52, SD 27, effect size 0.48; 95% CI 0.25-0.71) and social functioning (p < 0.001; mean 72, SD 32, effect size 0.41, 95% CI [0.19-0.64]) were still lower 10 years after ICU discharge compared with pre-admission levels (n = 149) and with an age reference population. Almost all SF-36 dimensions changed significantly over time from ICU discharge up to 10 years after ICU discharge. Over the 10 year follow up physical functioning of medical-surgical ICU survivors remains impaired compared with their pre-admission values and an age reference population. However, effect sizes showed no significant differences suggesting that surviving patients largely regained their age-specific HRQOL at 10 years.

Tailored modulation of the inflammatory balance in COVID-19 patients admitted to the ICU?-a viewpoint.

A growing consensus seems to be emerging that dexamethasone is a crucial component in the treatment of COVID-19-associated oxygen-dependent respiratory failure. Although dexamethasone has an undeniably beneficial effect on the inflammatory response in a subgroup of patients, the potential negative effects of corticosteroids must also be considered. In view of these negative effects, we argue that a one-size-fits-all dexamethasone approach may be potentially harmful in specific subsets of patients with COVID-19-associated ARDS. We propose a different individually tailored treatment strategy based on the patient's inflammatory response.

Awake Proning as an Adjunctive Therapy for Refractory Hypoxemia in Non-Intubated Patients with COVID-19 Acute Respiratory Failure: Guidance from an International Group of Healthcare Workers.

Non-intubated patients with acute respiratory failure due to COVID-19 could benefit from awake proning. Awake proning is an attractive intervention in settings with limited resources, as it comes with no additional costs. However, awake proning remains poorly used probably because of unfamiliarity and uncertainties regarding potential benefits and practical application. To summarize evidence for benefit and to develop a set of pragmatic recommendations for awake proning in patients with COVID-19 pneumonia, focusing on settings where resources are limited, international healthcare professionals from high and low- and middle-income countries (LMICs) with known expertise in awake proning were invited to contribute expert advice. A growing number of observational studies describe the effects of awake proning in patients with COVID-19 pneumonia in whom hypoxemia is refractory to simple measures of supplementary oxygen. Awake proning improves oxygenation in most patients, usually within minutes, and reduces dyspnea and work of breathing. The effects are maintained for up to 1 hour after turning back to supine, and mostly disappear after 6-12 hours. In available studies, awake proning was not associated with a reduction in the rate of intubation for invasive ventilation. Awake proning comes with little complications if properly implemented and monitored. Pragmatic recommendations including indications and contraindications were formulated and adjusted for resource-limited settings. Awake proning, an adjunctive treatment for hypoxemia refractory to supplemental oxygen, seems safe in non-intubated patients with COVID-19 acute respiratory failure. We provide pragmatic recommendations including indications and contraindications for the use of awake proning in LMICs.

SURvival PRediction In SEverely Ill Patients Study-The Prediction of Survival in Critically Ill Patients by ICU Physicians.

The surprise question, "Would I be surprised if this patient died in the next 12 months?" is a tool to identify patients at high risk of death in the next year. Especially in the situation of an ICU admission, it is important to recognize patients who could and could not have the benefits of an intensive treatment in the ICU department. DESIGN AND SETTING: A single-center, prospective, observational cohort study was conducted between April 2013 and April 2018, in ICU Gelre hospitals, location Apeldoorn. PATIENTS: A total of 3,140 patients were included (57% male) with a mean age of 63.5 years. Seven-hundred thirteen patients (23%) died within 1 year. INTERVENTIONS: The physician answered three different surprise question's with either "yes" or "no": "I expect that the patient is going to survive the ICU admission" (surprise question 1), "I expect that the patient is going to survive the hospital stay" (surprise question 2), and "I expect that the patient is going to survive one year after ICU admission" (surprise question 3). We tested positive and negative predicted values of the surprise questions, the mean accuracy of the surprise questions, and kappa statistics. MEASUREMENTS AND MAIN RESULTS: The positive and negative predictive values of the surprise questions for ICU admission, hospital admission, and 1-year survival were, respectively, 64%/94%, 59%/92%, and 60%/86%. Accordingly, the mean accuracy and kappa statistics were 93% (95% CI, 92-94%), κ equals to 0.43, 89% (95% CI, 88-90%), κ equals to 0.40, and 81% (95% CI, 80-82%), κ equals to 0.43. CONCLUSIONS: The frequently overlooked simple and cheap surprise question is probably an useful tool to evaluate the prognosis of acutely admitted critically ill patients.

Effect of a Lower vs Higher Positive End-Expiratory Pressure Strategy on Ventilator-Free Days in ICU Patients Without ARDS: A Randomized Clinical Trial.

Importance: It is uncertain whether invasive ventilation can use lower positive end-expiratory pressure (PEEP) in critically ill patients without acute respiratory distress syndrome (ARDS). Objective: To determine whether a lower PEEP strategy is noninferior to a higher PEEP strategy regarding duration of mechanical ventilation at 28 days. Design, Setting, and Participants: Noninferiority randomized clinical trial conducted from October 26, 2017, through December 17, 2019, in 8 intensive care units (ICUs) in the Netherlands among 980 patients without ARDS expected not to be extubated within 24 hours after start of ventilation. Final follow-up was conducted in March 2020. Interventions: Participants were randomized to receive invasive ventilation using either lower PEEP, consisting of the lowest PEEP level between 0 and 5 cm H2O (n = 476), or higher PEEP, consisting of a PEEP level of 8 cm H2O (n = 493). Main Outcomes and Measures: The primary outcome was the number of ventilator-free days at day 28, with a noninferiority margin for the difference in ventilator-free days at day 28 of -10%. Secondary outcomes included ICU and hospital lengths of stay; ICU, hospital, and 28- and 90-day mortality; development of ARDS, pneumonia, pneumothorax, severe atelectasis, severe hypoxemia, or need for rescue therapies for hypoxemia; and days with use of vasopressors or sedation. Results: Among 980 patients who were randomized, 969 (99%) completed the trial (median age, 66 [interquartile range {IQR}, 56-74] years; 246 [36%] women). At day 28, 476 patients in the lower PEEP group had a median of 18 ventilator-free days (IQR, 0-27 days) and 493 patients in the higher PEEP group had a median of 17 ventilator-free days (IQR, 0-27 days) (mean ratio, 1.04; 95% CI, 0.95-∞; P = .007 for noninferiority), and the lower boundary of the 95% CI was within the noninferiority margin. Occurrence of severe hypoxemia was 20.6% vs 17.6% (risk ratio, 1.17; 95% CI, 0.90-1.51; P = .99) and need for rescue strategy was 19.7% vs 14.6% (risk ratio, 1.35; 95% CI, 1.02-1.79; adjusted P = .54) in patients in the lower and higher PEEP groups, respectively. Mortality at 28 days was 38.4% vs 42.0% (hazard ratio, 0.89; 95% CI, 0.73-1.09; P = .99) in patients in the lower and higher PEEP groups, respectively. There were no statistically significant differences in other secondary outcomes. Conclusions and Relevance: Among patients in the ICU without ARDS who were expected not to be extubated within 24 hours, a lower PEEP strategy was noninferior to a higher PEEP strategy with regard to the number of ventilator-free days at day 28. These findings support the use of lower PEEP in patients without ARDS. Trial Registration: ClinicalTrials.gov Identifier: NCT03167580.

Developing and testing a nurse-led intervention to support bereavement in relatives in the intensive care (BRIC study): a protocol of a pre-post intervention study.

BACKGROUND: When a patient is approaching death in the intensive care unit (ICU), patients' relatives must make a rapid transition from focusing on their beloved one's recovery to preparation for their unavoidable death. Bereaved relatives may develop complicated grief as a consequence of this burdensome situation; however, little is known about appropriate options in quality care supporting bereaved relatives and the prevalence and predictors of complicated grief in bereaved relatives of deceased ICU patients in the Netherlands. The aim of this study is to develop and implement a multicomponent bereavement support intervention for relatives of deceased ICU patients and to evaluate the effectiveness of this intervention on complicated grief, anxiety, depression and posttraumatic stress in bereaved relatives. METHODS: The study will use a cross-sectional pre-post design in a 38-bed ICU in a university hospital in the Netherlands. Cohort 1 includes all reported first and second contact persons of patients who died in the ICU in 2018, which will serve as a pre-intervention baseline measurement. Based on existing policies, facilities and evidence-based practices, a nurse-led intervention will be developed and implemented during the study period. This intervention is expected to use 1) communication strategies, 2) materials to make a keepsake, and 3) a nurse-led follow-up service. Cohort 2, including all bereaved relatives in the ICU from October 2019 until March 2020, will serve as a post-intervention follow-up measurement. Both cohorts will be performed in study samples of 200 relatives per group, all participants will be invited to complete questionnaires measuring complicated grief, anxiety, depression and posttraumatic stress. Differences between the baseline and follow-up measurements will be calculated and adjusted using regression analyses. Exploratory subgroup analyses (e.g., gender, ethnicity, risk profiles, relationship with patient, length of stay) and exploratory dose response analyses will be conducted. DISCUSSION: The newly developed intervention has the potential to improve the bereavement process of the relatives of deceased ICU patients. Therefore, symptoms of grief and mental health problems such as depression, anxiety and posttraumatic stress, might decrease. TRIAL REGISTRATION: Netherlands Trial Register Registered on 27/07/2019 as NL 7875, www.trialregister.nl.

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.

Prevalence, Pathophysiology, Diagnostic Modalities, and Treatment Options for Dysphagia in Critically Ill Patients.

Postextubation dysphagia may impose a substantial burden on intensive care unit patients and healthcare systems. Approximately 517,000 patients survive mechanical ventilation during critical care annually. Reports of postextubation dysphagia prevalence are highly variable ranging between 3% and 93%. Of great concern is aspiration leading to the development of aspiration pneumonia when patients resume oral feeding. Screening for aspiration with a water swallow test has been reported to be positive for 12% of patients in the intensive care unit after extubation. This review aims to increase awareness of postextubation dysphagia and provide an updated overview of the current knowledge regarding prevalence, pathophysiology, diagnostic modalities, and treatment options.