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Joint models linking longitudinal biomarkers or recurrent event processes with a terminal event, for example, mortality, have been studied extensively. Motivated by studies of recurrent delirium events in patients receiving care in an intensive care unit (ICU), we devise a joint model for a recurrent event process and multiple terminal events. Being discharged alive from the ICU or experiencing mortality may be associated with a patient's hazard of delirium, violating the assumption of independent censoring. Moreover, the direction of the association between the hazards of delirium and mortality may be opposite of the direction of association between the hazards of delirium and ICU discharge. Hence treating either terminal event as independent censoring may bias inferences. We propose a competing joint model that uses a latent frailty to link a patient's recurrent and competing terminal event processes. We fit our model to data from a completed placebo‐controlled clinical trial, which studied whether Haloperidol could prevent death and delirium among ICU patients. The clinical trial served as a foundation for a simulation study, in which we evaluate the properties, for example, bias and confidence interval coverage, of the competing joint model. As part of the simulation study, we demonstrate the shortcomings of using a joint model with a recurrent delirium process and a single terminal event to study delirium in the ICU. Lastly, we discuss limitations and possible extensions for the competing joint model. The competing joint model has been added to frailtypack, an R package for fitting an assortment of joint models. [ABSTRACT FROM AUTHOR]

Objective: ICU survivors suffer from long-lasting physical, mental, and cognitive health impairments, also called "postintensive care syndrome". However, an overview of the effectiveness of interventions to prevent or mitigate these impairments is lacking. The aim of this study is to assess the effectiveness of nonpharmacologic interventions.Data Sources: PubMed, CINAHL, PsycINFO, Embase, and Cochrane Library were systematically searched from inception until July 19, 2018.Study Selection: (Non)randomized clinical trials, controlled before-after studies, and interrupted time series were included. Outcomes of interest included patients physical, mental and cognitive outcomes, quality of life, and outcomes such as social functioning and functional status, measured after hospital discharge.Data Extraction: Two independent reviewers selected studies, extracted data, and assessed the risk of bias. Pooled mean differences and standardized mean differences were calculated using random-effect meta-analyses.Data Synthesis: After screening 17,008 articles, 36 studies, including 10 pilot studies, were included (n = 5,165 ICU patients). Interventions were subdivided into six categories: 1) exercise and physical rehabilitation programs; 2) follow-up services; 3) psychosocial programs; 4) diaries; 5) information and education; and 6) other interventions. Many outcomes favored the interventions, but significant differences were only found for diaries in reducing depression (two studies, n = 88; standardized mean difference, 0.68; 95% CI, 0.14-1.21) and anxiety (two studies, n = 88; standardized mean difference, 0.44; 95% CI, 0.01-0.87) and exercise programs in improving the Short Form Health Survey-36 Mental Component Score (seven studies, n = 664; mean difference, 2.62; 95% CI, 0.92-4.32).Conclusions: There is thin evidence that diaries and exercise programs have a positive effective on mental outcomes. Despite outcomes favoring the intervention group, other commonly used nonpharmacologic interventions in daily ICU practice are not supported by conclusive evidence from this meta-analysis. To improve recovery programs for ICU survivors, more evidence is needed from robust intervention studies using standardized outcomes. [ABSTRACT FROM AUTHOR]

Editorial The use of extracorporeal membrane oxygenation (ECMO) is associated with better survival rates among select critically ill patients such as those with acute respiratory failure due to COVID-19[[1], [3]] or cardiogenic shock.[4] However, approximately one-half of patients who receive ECMO will die, and severe complications often arise during treatment, including bleeding, ischemia, and neurological problems.[5] Consequently, the functional, cognitive, and mental outcomes after ECMO are extremely important, given that the overall goal of intensive care is survival with good or acceptable health. These patients were matched 1:6 with 3830 survivors of treatment in the intensive care unit (ICU) who had not been treated with ECMO. After propensity weighting, ICU survivorship following ECMO treatment, compared with ICU survivorship without ECMO treatment, was significantly associated with a higher risk of new mental health diagnoses (hazard ratio [HR], 1.24 [95% CI, 1.01-1.51]). [Extracted from the article]

Importance: Results of studies on use of prophylactic haloperidol in critically ill adults are inconclusive, especially in patients at high risk of delirium.Objective: To determine whether prophylactic use of haloperidol improves survival among critically ill adults at high risk of delirium, which was defined as an anticipated intensive care unit (ICU) stay of at least 2 days.Design, Setting, and Participants: Randomized, double-blind, placebo-controlled investigator-driven study involving 1789 critically ill adults treated at 21 ICUs, at which nonpharmacological interventions for delirium prevention are routinely used in the Netherlands. Patients without delirium whose expected ICU stay was at least a day were included. Recruitment was from July 2013 to December 2016 and follow-up was conducted at 90 days with the final follow-up on March 1, 2017.Interventions: Patients received prophylactic treatment 3 times daily intravenously either 1 mg (n = 350) or 2 mg (n = 732) of haloperidol or placebo (n = 707), consisting of 0.9% sodium chloride.Main Outcome and Measures: The primary outcome was the number of days that patients survived in 28 days. There were 15 secondary outcomes, including delirium incidence, 28-day delirium-free and coma-free days, duration of mechanical ventilation, and ICU and hospital length of stay.Results: All 1789 randomized patients (mean, age 66.6 years [SD, 12.6]; 1099 men [61.4%]) completed the study. The 1-mg haloperidol group was prematurely stopped because of futility. There was no difference in the median days patients survived in 28 days, 28 days in the 2-mg haloperidol group vs 28 days in the placebo group, for a difference of 0 days (95% CI, 0-0; P = .93) and a hazard ratio of 1.003 (95% CI, 0.78-1.30, P=.82). All of the 15 secondary outcomes were not statistically different. These included delirium incidence (mean difference, 1.5%, 95% CI, -3.6% to 6.7%), delirium-free and coma-free days (mean difference, 0 days, 95% CI, 0-0 days), and duration of mechanical ventilation, ICU, and hospital length of stay (mean difference, 0 days, 95% CI, 0-0 days for all 3 measures). The number of reported adverse effects did not differ between groups (2 [0.3%] for the 2-mg haloperidol group vs 1 [0.1%] for the placebo group).Conclusions and Relevance: Among critically ill adults at high risk of delirium, the use of prophylactic haloperidol compared with placebo did not improve survival at 28 days. These findings do not support the use of prophylactic haloperidol for reducing mortality in critically ill adults.Trial Registration: clinicaltrials.gov Identifier: NCT01785290. [ABSTRACT FROM AUTHOR]

Patients were evaluated for the presence of delirium twice daily using the CAM-ICU, however, for comparison of the delirium diagnosis, the CAM-ICU cannot serve as the gold standard. With interest we read the report on Natural Language Processing (NLP) diagnosed behavioral disturbance (NLP-Dx-Bd) in relation to delirium [[1]], but it left us also somewhat confused. [Extracted from the article]

Background: Delirium after cardiothoracic surgery is common and associated with impaired outcomes. Although several mechanisms have been proposed (including changes in cerebral perfusion), the pathophysiology of postoperative delirium remains unclear. Blood viscosity is related to cerebral perfusion and thereby might contribute to the development of delirium after cardiothoracic surgery. The aim of this study was to investigate whether whole blood viscosity differs between cardiothoracic surgery patients with and without delirium.Methods: In this observational study postoperative whole blood viscosity of patients that developed delirium (cases) were compared with non-delirious cardiothoracic surgery patients (controls). Cases were matched with the controls, yielding a 1:4 case-control study. Serial hematocrit, fibrinogen, and whole blood viscosity were determined pre-operatively and at each postoperative day. Delirium was assessed using the validated Confusion Assessment Method for the Intensive Care Unit or Delirium Screening Observation scale.Results: In total 80 cardiothoracic surgery patients were screened of whom 12 delirious and 48 matched non-delirious patients were included. No significant difference was found between both groups in fibrinogen (p = 0.36), hematocrit (p = 0.23) and the area under curve of the whole blood viscosity between shear rates 0.02 and 50 s(-1) (p = 0.80) or between shear rates 0.02 and 5 s(-1) (p = 0.78).Conclusion: In this case control study in cardiothoracic surgery patients changes in whole blood viscosity were not associated with the development of delirium. [ABSTRACT FROM AUTHOR]

Background: The reference standard in studies on delirium assessment tools is usually based on the clinical judgment of only one delirium expert and may be concise, unstandardized, or not specified at all. This multicenter study investigated the performance of the Delirium Interview, a new reference standard for studies on delirium assessment tools allowing classification of delirium based on written reports. Methods: We tested the diagnostic accuracy of our standardized Delirium Interview by comparing delirium assessments of the reported results with live assessments. Our reference, the live assessment, was performed by two delirium experts and one well‐trained researcher who registered the results. Their delirium assessment was compared to the majority vote of three other independent delirium experts who judged the rapportage of the Delirium Interview. Our total pool consisted of 13 delirium experts with an average of 13 ± 8 years of experience. Results: We included 98 patients (62% male, mean age 69 ± 12 years), of whom 56 (57%) intensive care units (ICUs) patients, 22 (39%) patients with a Richmond Agitation Sedation Scale (RASS) < 0 and 26 (27%) non‐verbal assessments. The overall prevalence of delirium was 28%. The Delirium Interview had a sensitivity of 89% (95% confidence interval [CI]: 71%–98%) and specificity of 82% (95% CI: 71%–90%), compared to the diagnosis of an independent panel of two delirium experts and one researcher who examined the patients themselves. Negative and positive predictive values were 95% (95% CI: 86%–0.99%), respectively, 66% (95% CI: 49%–80%). Stratification into ICU and non‐ICU patients yielded similar results. Conclusion: The Delirium Interview is a feasible reference method for large study cohorts evaluating delirium assessment tools since experts could assess delirium with high accuracy without seeing the patient at the bedside. [ABSTRACT FROM AUTHOR]

Objective: Long-term health-related quality of life (HRQoL) was determined for patients admitted to the haematology ward who needed intensive care treatment (H-IC+) and compared with those who did not (H-IC−) as well as with that for patients admitted to the general ICU (nH-IC+). Methods: A cross-sectional study was carried out median 18 months after admission by employing the short form-36, checklist for individual strength, cognitive failure questionnaire and hospital anxiety and depression scale. Results: 27 (79%) of the 34 H-IC+ patients approached, and 93 (85%) of the 109 H-IC− patients approached replied. Data were adjusted for relevant covariates and matched with those of 149 patients in the general ICU. Apart from the lower role-physical functioning score for H-IC+ (P = 0.04) no other differences were found between H-IC+ and H-IC−. Groups H-IC+ and nH-IC+ evaluated their HRQoL on SF-36 similarly, except for the lower aggregated physical component summary (PCS) for H-IC+ (P<0.0001). After adjusting for PCS, no significant differences in CIS, CFQ and HADS were observed between the groups. Conclusions: Eighteen months after admission, patients treated for haematological malignancies reported similar HRQoL, whether or not they had received intensive care treatment, but reported a lower PCS than those of patients in the general ICU. Hence, there is no reason to assume that admission to the ICU has a negative impact on long-term HRQoL, so this should not affect the decision whether or not to transfer patients with haematological malignancies to the ICU. [ABSTRACT FROM AUTHOR]

Background Delirium is a frequent disorder in intensive care unit (ICU) patients with serious consequences. Therefore, preventive treatment for delirium may be beneficial. Worldwide, haloperidol is the first choice for pharmacological treatment of delirious patients. In daily clinical practice, a lower dose is sometimes used as prophylaxis. Some studies have shown the beneficial effects of prophylactic haloperidol on delirium incidence as well as on mortality, but evidence for effectiveness in ICU patients is limited. The primary objective of our study is to determine the effect of haloperidol prophylaxis on 28-day survival. Secondary objectives include the incidence of delirium and delirium-related outcome and the side effects of haloperidol prophylaxis. Methods This will be a multicenter three-armed randomized, double-blind, placebo-controlled, prophylactic intervention study in critically ill patients. We will include consecutive nonneurological ICU patients, aged ⩾18 years with an expected ICU length of stay ®1 day. To be able to demonstrate a 15% increase in 28-day survival time with a power of 80% and alpha of 0.05 in both intervention groups, a total of 2,145 patients will be randomized; 715 in each group. The anticipated mortality rate in the placebo group is 12%. The intervention groups will receive prophylactic treatment with intravenous haloperidol 1 mg/q8h or 2 mg/q8h, and patients in the control group will receive placebo (sodium chloride 0.9%), both for a maximum period of 28-days. In patients who develop delirium, study medication will be stopped and patients will subsequently receive open label treatment with a higher (therapeutic) dose of haloperidol. We will use descriptive summary statistics as well as Cox proportional hazard regression analyses, adjusted for covariates. Discussion This will be the first large-scale multicenter randomized controlled prevention study with haloperidol in ICU patients with a high risk of delirium, adequately powered to demonstrate an effect on 28-day survival. Trial registration Clinicaltrials.gov: NCT01785290. EudraCT number: 2012-004012-66. [ABSTRACT FROM AUTHOR]

Background Cardiac surgery-related acute kidney injury (CS-AKI) results in increased morbidity and mortality. Different models have been developed to identify patients at risk of CS-AKI. While models that predict dialysis and CS-AKI defined by the RIFLE criteria are available, their predictive power and clinical applicability have not been compared head to head. Methods Of 1388 consecutive adult cardiac surgery patients operated with cardiopulmonary bypass, risk scores of eight prediction models were calculated. Four models were only applicable to a subgroup of patients. The area under the receiver operating curve (AUROC) was calculated for all levels of CS-AKI and for need for dialysis (AKI-D) for each risk model and compared for the models applicable to the largest subgroup (n = 1243). Results The incidence of AKI-D was 1.9% and for CS-AKI 9.3%. The models of Rahmanian, Palomba and Aronson could not be used for preoperative risk assessment as postoperative data are necessary. The three best AUROCs for AKI-D were of the model of Thakar: 0.93 [95% confidence interval (CI) 0.91–0.94], Fortescue: 0.88 (95% CI 0.87–0.90) and Wijeysundera: 0.87 (95% CI 0.85–0.89). The three best AUROCs for CS-AKI-risk were 0.75 (95% CI 0.73–0.78), 0.74 (95% CI 0.71–0.76) and 0.70 (95% CI 0.73–0.78), for Thakar, Mehta and both Fortescue and Wijeysundera, respectively. The model of Thakar performed significantly better compared with the models of Mehta, Rahmanian, Fortescue and Wijeysundera (all P-values <0.01) at different levels of severity of CS-AKI. Conclusions The Thakar model offers the best discriminative value to predict CS-AKI and is applicable in a preoperative setting and for all patients undergoing cardiac surgery. [ABSTRACT FROM AUTHOR]

Background: Delirium is a serious and frequent psycho-organic disorder in critically ill patients. Reported incidence rates vary to a large extent and there is a paucity of data concerning delirium incidence rates for the different subgroups of intensive care unit (ICU) patients and their short-term health consequences. Objectives: To determine the overall incidence and duration of delirium, per delirium subtype and per ICU admission diagnosis. Furthermore, we determined the short-term consequences of delirium. Design: Prospective observational study. Participants and setting: All adult consecutive patients admitted in one year to the ICU of a university medical centre. Methods: Delirium was assessed using the Confusion Assessment Method-ICU three times a day. Delirium was divided in three subtypes: hyperactive, hypoactive and mixed subtype. As measures for short-term consequences we registered duration of mechanical ventilation, re-intubations, incidence of unplanned removal of tubes, length of (ICU) stay and in-hospital mortality. Results: 1613 patients were included of which 411 (26%) developed delirium. The incidence rate in the neurosurgical (10%) and cardiac surgery group (12%) was the lowest, incidence was intermediate in medical patients (40%), while patients with a neurological diagnosis had the highest incidence (64%). The mixed subtype occurred the most (53%), while the hyperactive subtype the least (10%). The median delirium duration was two days [IQR 1–7], but significantly longer (P <0.0001) for the mixed subtype. More delirious patients were mechanically ventilated and for a longer period of time, were more likely to remove their tube and catheters, stayed in the ICU and hospital for a longer time, and had a six times higher chance of dying compared to non-delirium ICU patients, even after adjusting for their severity of illness score. Delirium was associated with an extended duration of mechanical ventilation, length of stay in the ICU and in-hospital, as well as with in-hospital mortality. Conclusions: The delirium incidence in a mixed ICU population is high and differs importantly between ICU admission diagnoses and the subtypes of delirium. Patients with delirium had a significantly higher incidence of short-term health problems, independent from their severity of illness and this was most pronounced in the mixed subtype of delirium. Delirium is significantly associated with worse short-term outcome. [Copyright &y& Elsevier]

Background: Suitable biomarkers associated with the development of delirium are still not known. Urinary proteomics has successfully been applied to identify novel biomarkers associated with various disease states, but its value has not been investigated in delirium patients. Results: In a prospective explorative study hyperactive delirium patients after cardiac surgery were included for urinary proteomic analyses. Delirium patients were matched with non-delirium patients after cardiac surgery on age, gender, severity of illness score, LOS-ICU, Euro-score, C-reactive protein, renal function and aorta clamping time. Urine was collected within 24 hours after the onset of delirium. Matrix-assisted laser desorption/ionisationtime of flight mass spectrometry (MALDI-TOF MS) was applied to detect differences in the urinary proteome associated with delirium in these ICU patients. We included 10 hyperactive delirium and 10 meticulously matched non-delirium post-cardiac surgery patients. No relevant differences in the urinary excretion of proteins could be observed. Conclusions: We conclude that MALDI-TOF MS of urine does not reveal a clear hyperactive delirium proteome fingerprint in ICU patients. Trial Registration: Clinical Trial Register number: NCT00604773 [ABSTRACT FROM AUTHOR]

The objective of the study was to gain insight into the effectiveness of vacuum-assisted closure (VAC) therapy or, more particularly, topical negative pressure (TNP) in the treatment of pressure ulcers. We carried out a systematic search in Medline, Embase and Cinahl for Randomized Clinical Trials (RCTs) involving topical negative pressure in pressure ulcers over the period 1992–2007. Five RCTs were included. Two studies dealt exclusively with pressure ulcers. No significant differences in wound healing were found in these studies. Three other studies (mixed etiology of wounds) did show significant differences in wound healing, in the decrease of wound treatment time, and in the decrease in number of bacteria. The quality of these studies, both in terms of methodology and otherwise, did not always match with the scientific standard. Moreover, these studies lacked subgroup analyses. The analyzed studies described positive effects of TNP, although both the control treatment and the end points varied in these studies. On the basis of the systematic assessment of these five RCTs, the conclusion is that TNP has not proven to be more effective than various control interventions. The differences between and within the studies in terms of control interventions, the differences in randomization and a number of weaknesses in the analyses do not allow a good comparison. The main recommendations for follow-up studies include: randomization of patients rather than of wounds, a homogeneous patient population, the use of a single well-defined and procedurally documented control intervention, and prior calculation of the random sample size. [ABSTRACT FROM AUTHOR]

We advocate for the implementation of structured, multidisciplinary, rehabilitation programs, programs for ICU patients treated for COVID-19, just as for other ICU patients, to prevent or mitigate prolonged post-ICU related impairments. ICU patients treated for coronavirus disease 2019 (COVID-19) frequently experience symptoms of PICS 1 year after ICU treatment; however, their long-term outcomes beyond the first year are largely unknown [[2]]. [Extracted from the article]

OBJECTIVES: ICU survivors often suffer from long-lasting physical, mental, and cognitive health problems after hospital discharge. As several interventions that treat or prevent these problems already start during ICU stay, patients at high risk should be identified early. This study aimed to develop a model for early prediction of post-ICU health problems within 48 hours after ICU admission. DESIGN: Prospective cohort study in seven Dutch ICUs. SETTING/PATIENTS: ICU patients older than 16 years and admitted for greater than or equal to 12 hours between July 2016 and March 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Outcomes were physical problems (fatigue or ≥ 3 new physical symptoms), mental problems (anxiety, depression, or post-traumatic stress disorder), and cognitive impairment. Patient record data and questionnaire data were collected at ICU admission, and after 3 and 12 months, of 2,476 patients. Several models predicting physical, mental, or cognitive problems and a composite score at 3 and 12 months were developed using variables collected within 48 hours after ICU admission. Based on performance and clinical feasibility, a model, PROSPECT, predicting post-ICU health problems at 3 months was chosen, including the predictors of chronic obstructive pulmonary disease, admission type, expected length of ICU stay greater than or equal to 2 days, and preadmission anxiety and fatigue. Internal validation using bootstrapping on data of the largest hospital (n = 1,244) yielded a C-statistic of 0.73 (95% CI, 0.70-0.76). External validation was performed on data (n = 864) from the other six hospitals with a C-statistic of 0.77 (95% CI, 0.73-0.80). CONCLUSIONS: The developed and externally validated PROSPECT model can be used within 48 hours after ICU admission for identifying patients with an increased risk of post-ICU problems 3 months after ICU admission. Timely preventive interventions starting during ICU admission and follow-up care can prevent or mitigate post-ICU problems in these high-risk patients. [ABSTRACT FROM AUTHOR]

Background: Physical restraints remain to be commonly used in agitated intensive care unit (ICU) patients worldwide, despite a lack of evidence on efficacy and safety and reports of detrimental short and long-term consequences, such as prolonged delirium and a longer ICU length of stay. Physical restraint minimization approaches have focused mainly on educational strategies and other non-pharmacological interventions. Combining these interventions with goal-directed light sedation therapy if needed may play an important contributory role in further reducing the use of physical restraints. The aim of the study is to determine the effectiveness of a multicomponent intervention (MCI) program, combining person-centered non-pharmacological interventions with goal-directed light sedation, compared to physical restraints. Methods: A multicenter stepped-wedge cluster randomized controlled trial will be conducted in six Dutch ICUs. A power calculation based total of 480 (expected to become) agitated adult patients will be included in 26 months with a subsequent 2-year follow-up. Patients included in the control period will receive standard care with the current agitation management protocol including physical restraints. Patients included in the intervention period will be treated with the MCI program, consisting of four components, without physical restraints: education of ICU professionals, identification of patients at risk for agitation, formulation of a multidisciplinary person-centered care plan including non-pharmacological and medical interventions, and protocolized goal-directed light sedation using dexmedetomidine. Primary outcome is the number of days alive and outside of the ICU within 28 days after ICU admission. Secondary outcomes include length of hospital stay; 3-, 12-, and 24-month post-ICU quality of life; physical (fatigue, frailty, new physical problems), mental (anxiety, depression, and post-traumatic stress disorder), and cognitive health; and 1-year cost-effectiveness. A process evaluation will be conducted. Discussion: This will be the first multicenter randomized controlled trial determining the effect of a combination of non-pharmacological interventions and light sedation using dexmedetomidine compared to physical restraints in agitated ICU patients. The results of this study, including long-term patient-centered outcomes, will provide relevant insights to aid ICU professionals in the management of agitated patients. Trial registration: NCT05783505, registration date 23 March 2023. [ABSTRACT FROM AUTHOR]

Background: Delirium is a pathobiological brain process that is frequently observed in Intensive Care Unit (ICU) patients, and is associated with longer hospitalization as well as long-term cognitive impairment. In neurological ICU patients, delirium may be more treatment-resistant due to the initial brain injury. This study examined the effects of a multicomponent non-pharmacological nursing intervention program on delirium in neurological ICU patients. Methods: A single-center interrupted time series trial was conducted in adult neurological ICU patients at high risk for developing delirium who were non-delirious at admission. A multicomponent nursing intervention program focusing on modifiable risk factors for delirium, including the optimalization of vision, hearing, orientation and cognition, sleep and mobilization, was implemented as the standard of care, and its effects were studied. The primary outcome was the number of delirium-free and coma-free days alive at 28 days after ICU admission. The secondary outcomes included delirium incidence and duration, ICU and hospital length-of-stay and duration of mechanical ventilation. Results: Of 289 eligible patients admitted to the ICU, 130 patients were included, with a mean age of 68 ± 11 years, a mean APACHE-IV score of 79 ± 25 and a median predicted delirium risk (E-PRE-DELIRIC) score of 42 [IQR 38–50]). Of these, 73 were included in the intervention period and 57 in the control period. The median delirium- and coma-free days alive were 15 days [IQR 0–26] in the intervention group and 10 days [IQR 0–24] in the control group (level change −0.48 days, 95% confidence interval (95%CI) −7 to 6 days, p = 0.87; slope change −0.95 days, 95%CI −2.41 to 0.52 days, p = 0.18). Conclusions: In neurological ICU patients, our multicomponent non-pharmacological nursing intervention program did not change the number of delirium-free and coma-free days alive after 28 days. [ABSTRACT FROM AUTHOR]

Introduction Objective Methods Results Conclusion Physical therapists supporting patients in intensive care unit (ICU) rehabilitation can improve their clinical practice with insight in patients’ lived body experiences.To gain insight in patients’ lived body experiences during ICU stay and in recovery from critical illness.Through a comprehensive systematic literature search, 45 empirical phenomenological studies were identified. Patients’ lived body experiences were extracted from these studies and synthesized following the seven-phase interpretative approach as described by Noblit and Hare.Three lines of argument were illuminated: 1) “recovery from critical illness starts from a situation in which patients experience the lived body as unable;” 2) “patients experience progress in recovery from critical illness when the lived body is empowered;” and 3) “recovery from critical illness results in a lived body changed for life.” Eleven third-order constructs were formulated as different kinds of bodies: 1) “an intolerable body;” 2) “an alienated body;” 3) “a powerless body;” 4) “a dependent body;” 5) “a restricted body;” 6) “a muted body;” 7) “a touched body;” 8) “a transforming body;” 9) “a re-discovering body;” 10) “an unhomelike body;” and 11) “a remembering body.”Patients’ lived body experiences during ICU stay and in recovery from critical illness have richly been described in phenomenological studies and were synthesized in this meta-ethnography. [ABSTRACT FROM AUTHOR]

Background: This large-scale analysis pools individual data about the Clinical Frailty Scale (CFS) to predict outcome in the intensive care unit (ICU). Methods: A systematic search identified all clinical trials that used the CFS in the ICU (PubMed searched until 24th June 2020). All patients who were electively admitted were excluded. The primary outcome was ICU mortality. Regression models were estimated on the complete data set, and for missing data, multiple imputations were utilised. Cox models were adjusted for age, sex, and illness acuity score (SOFA, SAPS II or APACHE II). Results: 12 studies from 30 countries with anonymised individualised patient data were included (n = 23,989 patients). In the univariate analysis for all patients, being frail (CFS ≥ 5) was associated with an increased risk of ICU mortality, but not after adjustment. In older patients (≥ 65 years) there was an independent association with ICU mortality both in the complete case analysis (HR 1.34 (95% CI 1.25–1.44), p < 0.0001) and in the multiple imputation analysis (HR 1.35 (95% CI 1.26–1.45), p < 0.0001, adjusted for SOFA). In older patients, being vulnerable (CFS 4) alone did not significantly differ from being frail. After adjustment, a CFS of 4–5, 6, and ≥ 7 was associated with a significantly worse outcome compared to CFS of 1–3. Conclusions: Being frail is associated with a significantly increased risk for ICU mortality in older patients, while being vulnerable alone did not significantly differ. New Frailty categories might reflect its "continuum" better and predict ICU outcome more accurately. Trial registration: Open Science Framework (OSF: https://osf.io/8buwk/). [ABSTRACT FROM AUTHOR]

OBJECTIVES: To develop and externally validate a prediction model for ICU survivors' change in quality of life 1 year after ICU admission that can support ICU physicians in preparing patients for life after ICU and managing their expectations. DESIGN: Data from a prospective multicenter cohort study (MONITOR-IC) were used. SETTING: Seven hospitals in the Netherlands. PATIENTS: ICU survivors greater than or equal to 16 years old. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Outcome was defined as change in quality of life, measured using the EuroQol 5D questionnaire. The developed model was based on data from an academic hospital, using multivariable linear regression analysis. To assist usability, variables were selected using the least absolute shrinkage and selection operator method. External validation was executed using data of six nonacademic hospitals. Of 1,804 patients included in analysis, 1,057 patients (58.6%) were admitted to the academic hospital, and 747 patients (41.4%) were admitted to a nonacademic hospital. Forty-nine variables were entered into a linear regression model, resulting in an explained variance (R 2) of 56.6%. Only three variables, baseline quality of life, admission type, and Glasgow Coma Scale, were selected for the final model (R 2 = 52.5%). External validation showed good predictive power (R 2 = 53.2%). CONCLUSIONS: This study developed and externally validated a prediction model for change in quality of life 1 year after ICU admission. Due to the small number of predictors, the model is appealing for use in clinical practice, where it can be implemented to prepare patients for life after ICU. The next step is to evaluate the impact of this prediction model on outcomes and experiences of patients. [ABSTRACT FROM AUTHOR]

The document titled "The authors reply" is a response to a letter to the editor regarding the PROSPECT model, which predicts long-term physical, mental, and cognitive problems following critical illness. The authors address concerns about the low estimates of cognitive impairment in ICU survivors and inquire about plans to further refine the instrument through objective neuropsychologic tests. They also ask how clinicians should handle this limitation when discussing the risk of cognitive impairment with patients and families. The authors provide their affiliations and funding sources. The document includes references to related studies on cognitive impairment and post-intensive care syndrome. [Extracted from the article]

Ohbe and colleagues describe novel risk prediction models for new functional impairment in survivors of critical illness at hospital discharge using routinely collected predictors within 48 h of admission [[4]]. When a patient is admitted to the intensive care unit, the initial focus of clinicians and families is on survival. In an ideal world, we would be able to predict which patients are likely to have a good recovery after a period in the intensive care unit (ICU), and which patients will suffer ongoing functional impairment. [Extracted from the article]

Background: Delirium is a frequent disorder in intensive care unit (ICU) patients with serious consequences. Therefore, preventive treatment for delirium may be beneficial. Worldwide, haloperidol is the first choice for pharmacological treatment of delirious patients. In daily clinical practice, a lower dose is sometimes used as prophylaxis. Some studies have shown the beneficial effects of prophylactic haloperidol on delirium incidence as well as on mortality, but evidence for effectiveness in ICU patients is limited. The primary objective of our study is to determine the effect of haloperidol prophylaxis on 28-day survival. Secondary objectives include the incidence of delirium and delirium-related outcome and the side effects of haloperidol prophylaxis.Methods: This will be a multicenter three-armed randomized, double-blind, placebo-controlled, prophylactic intervention study in critically ill patients. We will include consecutive non-neurological ICU patients, aged ≥ 18 years with an expected ICU length of stay >1 day. To be able to demonstrate a 15% increase in 28-day survival time with a power of 80% and alpha of 0.05 in both intervention groups, a total of 2,145 patients will be randomized; 715 in each group. The anticipated mortality rate in the placebo group is 12%. The intervention groups will receive prophylactic treatment with intravenous haloperidol 1 mg/q8h or 2 mg/q8h, and patients in the control group will receive placebo (sodium chloride 0.9%), both for a maximum period of 28-days. In patients who develop delirium, study medication will be stopped and patients will subsequently receive open label treatment with a higher (therapeutic) dose of haloperidol. We will use descriptive summary statistics as well as Cox proportional hazard regression analyses, adjusted for covariates.Discussion: This will be the first large-scale multicenter randomized controlled prevention study with haloperidol in ICU patients with a high risk of delirium, adequately powered to demonstrate an effect on 28-day survival.Trial Registration: Clinicaltrials.gov: NCT01785290.EudraCT number: 2012-004012-66. [ABSTRACT FROM AUTHOR]

Background: This study aimed to improve the PREPARE model, an existing linear regression prediction model for long‐term quality of life (QoL) of intensive care unit (ICU) survivors by incorporating additional ICU data from patients' electronic health record (EHR) and bedside monitors. Methods: The 1308 adult ICU patients, aged ≥16, admitted between July 2016 and January 2019 were included. Several regression‐based machine learning models were fitted on a combination of patient‐reported data and expert‐selected EHR variables and bedside monitor data to predict change in QoL 1 year after ICU admission. Predictive performance was compared to a five‐feature linear regression prediction model using only 24‐hour data (R2 = 0.54, mean square error (MSE) = 0.031, mean absolute error (MAE) = 0.128). Results: The 67.9% of the included ICU survivors was male and the median age was 65.0 [IQR: 57.0–71.0]. Median length of stay (LOS) was 1 day [IQR 1.0–2.0]. The incorporation of the additional data pertaining to the entire ICU stay did not improve the predictive performance of the original linear regression model. The best performing machine learning model used seven features (R2 = 0.52, MSE = 0.032, MAE = 0.125). Pre‐ICU QoL, the presence of a cerebro vascular accident (CVA) upon admission and the highest temperature measured during the ICU stay were the most important contributors to predictive performance. Pre‐ICU QoL's contribution to predictive performance far exceeded that of the other predictors. Conclusion: Pre‐ICU QoL was by far the most important predictor for change in QoL 1 year after ICU admission. The incorporation of the numerous additional features pertaining to the entire ICU stay did not improve predictive performance although the patients' LOS was relatively short. [ABSTRACT FROM AUTHOR]

Aims: To explore lived experiences of patients recovering from COVID‐19‐associated intensive care unit acquired weakness and to provide phenomenological descriptions of their recovery. Design: A qualitative study following hermeneutic phenomenology. Methods: Through purposeful sampling, 13 participants with COVID‐19‐associated intensive care unit acquired weakness were recruited with diversity in age, sex, duration of hospitalization and severity of muscle weakness. Semi‐structured in‐depth interviews were conducted from 4 to 8 months after hospital discharge, between July 2020 and January 2021. Interviews were transcribed verbatim and analysed using hermeneutic phenomenological analysis. Results: The analysis yielded five themes: 'waking up in alienation', 'valuing human contact in isolation', 'making progress by being challenged', 'coming home but still recovering' and 'finding a new balance'. The phenomenological descriptions reflect a recovery process that does not follow a linear build‐up, but comes with moments of success, setbacks, trying new steps and breakthrough moments of achieving mobilizing milestones. Conclusion: Recovery from COVID‐19‐associated intensive care unit acquired weakness starts from a situation of alienation. Patients long for familiarity, for security and for recognition. Patients want to return to the familiar situation, back to the old, balanced, bodily self. It seems possible for patients to feel homelike again, not only by changing their outer circumstances but also by changing the understanding of themselves and finding a new balance in the altered situation. Impact Muscle weakness impacts many different aspects of ICU recovery in critically ill patients with COVID‐19‐associated intensive care unit acquired weakness. Their narratives can help nurses and other healthcare professionals, both inside and outside of the intensive care unit, to empathize with patient experiences. When healthcare professionals connect to the lifeworld of patients, they will start to act and communicate differently. These insights could lead to optimized care delivery and meeting patients' needs in this pandemic or a possible next. [ABSTRACT FROM AUTHOR]

Purpose: To explore trends over time in admission prevalence and (risk-adjusted) mortality of critically ill haematological patients and compare these trends to those of several subgroups of patients admitted to the medical intensive care unit (medical ICU patients). Methods: A total of 1,741 haematological and 60,954 non-haematological patients admitted to the medical ICU were analysed. Trends over time and differences between two subgroups of haematological medical ICU patients and four subgroups of non-haematological medical ICU patients were assessed, as well as the influence of leukocytopenia. Results: The proportion of haematological patients among all medical ICU patients increased over time [odds ratio (OR) 1.06; 95 % confidence interval (CI) 1.03-1.10 per year; p < 0.001]. Risk-adjusted mortality was significantly higher for haematological patients admitted to the ICU with white blood cell (WBC) counts of <1.0 × 10/L (47 %; 95 % CI 41-54 %) and ≥1.0 × 10/L (45 %; 95 % CI 42-49 %), respectively, than for patients admitted with chronic heart failure (27 %; 95 % CI 26-28 %) and with chronic liver cirrhosis (38 %; 95 % CI 35-42 %), but was not significantly different from patients admitted with solid tumours (40 %; 95 % CI 36-45 %). Over the years, the risk-adjusted hospital mortality rate significantly decreased in both the haematological and non-haematological group with an OR of 0.93 (95 % CI 0.92-0.95) per year. After correction for case-mix using the APACHE-II score (with WBC omitted), a WBC <1.0 × 10/L was not a predictor of mortality in haematological patients (OR 0.86; 95 % CI 0.46-1.64; p = 0.65). We found no case-volume effect on mortality for haematological ICU patients. Conclusions: An increasing number of haematological patients are being admitted to Dutch ICUs. While mortality is significantly higher in this group of medical ICU patients than in subgroups of non-haematological ones, the former show a similar decrease in raw and risk-adjusted mortality rate over time, while leukocytopenia is not a predictor of mortality. These results suggest that haematological ICU patients have benefitted from improved intensive care support during the last decade. [ABSTRACT FROM AUTHOR]

Purpose: Long-term mental outcomes in family members of coronavirus disease 2019 (COVID-19) intensive care unit (ICU) survivors are unknown. Therefore, we assessed the prevalence of mental health symptoms, including associated risk factors, and quality of life (QoL) in family members of COVID-19 ICU survivors 3 and 12 months post-ICU. Methods: A prospective multicentre cohort study in ICUs of ten Dutch hospitals, including adult family members of COVID-19 ICU survivors admitted between March 1, and July 1, 2020. Symptom prevalence rates of anxiety, depression (Hospital Anxiety and Depression Scale) and Post-Traumatic Stress Disorder (Impact of Event Scale-6), and QoL (Short Form-12) before ICU admission (baseline), and after 3 and 12 months were measured. Additionally, associations between family and patient characteristics and mental health symptoms were calculated. Results: A total of 166 out of 197 (84.3%) included family members completed the 12-month follow-up of whom 46.1% and 38.3% had mental health symptoms 3 and 12 months post-ICU, respectively; both higher compared to baseline (22.4%) (p < 0.001). The mental component summary score of the SF-12 was lower at 12-month follow-up compared with baseline [mean difference mental component score: − 5.5 (95% confidence interval (CI) − 7.4 to − 3.6)]. Furthermore, 27.9% experienced work-related problems. Symptoms of anxiety (odds ratio (OR) 9.23; 95% CI 2.296–37.24; p = 0.002) and depression (OR 5.96; 95% CI 1.29–27.42; p = 0.02) prior to ICU admission were identified as risk factors for mental health symptoms after 12 months. Conclusion: A considerable proportion of family members of COVID-19 survivors reported mental health symptoms 3 and 12 months after ICU admission, disrupting QoL and creating work-related problems. [ABSTRACT FROM AUTHOR]

Importance: One-year outcomes in patients who have had COVID-19 and who received treatment in the intensive care unit (ICU) are unknown.Objective: To assess the occurrence of physical, mental, and cognitive symptoms among patients with COVID-19 at 1 year after ICU treatment.Design, Setting, and Participants: An exploratory prospective multicenter cohort study conducted in ICUs of 11 Dutch hospitals. Patients (N = 452) with COVID-19, aged 16 years and older, and alive after hospital discharge following admission to 1 of the 11 ICUs during the first COVID-19 surge (March 1, 2020, until July 1, 2020) were eligible for inclusion. Patients were followed up for 1 year, and the date of final follow-up was June 16, 2021.Exposures: Patients with COVID-19 who received ICU treatment and survived 1 year after ICU admission.Main Outcomes and Measures: The main outcomes were self-reported occurrence of physical symptoms (frailty [Clinical Frailty Scale score ≥5], fatigue [Checklist Individual Strength-fatigue subscale score ≥27], physical problems), mental symptoms (anxiety [Hospital Anxiety and Depression {HADS} subscale score ≥8], depression [HADS subscale score ≥8], posttraumatic stress disorder [mean Impact of Event Scale score ≥1.75]), and cognitive symptoms (Cognitive Failure Questionnaire-14 score ≥43) 1 year after ICU treatment and measured with validated questionnaires.Results: Of the 452 eligible patients, 301 (66.8%) patients could be included, and 246 (81.5%) patients (mean [SD] age, 61.2 [9.3] years; 176 men [71.5%]; median ICU stay, 18 days [IQR, 11 to 32]) completed the 1-year follow-up questionnaires. At 1 year after ICU treatment for COVID-19, physical symptoms were reported by 182 of 245 patients (74.3% [95% CI, 68.3% to 79.6%]), mental symptoms were reported by 64 of 244 patients (26.2% [95% CI, 20.8% to 32.2%]), and cognitive symptoms were reported by 39 of 241 patients (16.2% [95% CI, 11.8% to 21.5%]). The most frequently reported new physical problems were weakened condition (95/244 patients [38.9%]), joint stiffness (64/243 patients [26.3%]) joint pain (62/243 patients [25.5%]), muscle weakness (60/242 patients [24.8%]) and myalgia (52/244 patients [21.3%]).Conclusions and Relevance: In this exploratory study of patients in 11 Dutch hospitals who survived 1 year following ICU treatment for COVID-19, physical, mental, or cognitive symptoms were frequently reported. [ABSTRACT FROM AUTHOR]

Previously, we showed that acute encephalopathy without delirium is associated with a significantly higher Delirium Rating Scale-Revised-98 (DRS-R-98) score than no acute encephalopathy and no delirium.[5] We speculate that acute encephalopathy without delirium indicates subsyndromal delirium with the potential to deteriorate to delirium. Single-channel electroencephalography (EEG) can detect postoperative delirium based on increased relative delta power.[[1]] However, relative delta power can be nonspecific since noise, such as eye movements and glossokinetic artifacts, also manifest predominantly within this low-frequency range. [Extracted from the article]

We thank Barreto et al ([1]) for their interest in our systematic review and meta-analysis regarding nonpharmacologic interventions to prevent or mitigate adverse long-term outcomes among ICU survivors, from our recent article ([2]) published in I Critical Care Medicine i . As a consequence, standardized mean difference (SMD) instead of the mean difference (MD) were calculated while the same scale was used in most, but not all, of the interventions. 1 Barreto BB, Luz M, Gusmao-Flores D. Nonpharmacologic Interventions to Prevent or Mitigate Adverse Long-Term Outcomes Among ICU Survivors: Is the ICU Diary Really Important?. [Extracted from the article]

Background Long-term health sequelae of coronavirus disease 2019 (COVID-19) may be multiple but have thus far not been systematically studied. Methods All patients discharged after COVID-19 from the Radboud University Medical Center, Nijmegen, the Netherlands, were consecutively invited to a multidisciplinary outpatient facility. Also, nonadmitted patients with mild disease but with symptoms persisting >6 weeks could be referred by general practitioners. Patients underwent a standardized assessment including measurements of lung function, chest computed tomography (CT)/X-ray, 6-minute walking test, body composition, and questionnaires on mental, cognitive, health status, and quality of life (QoL). Results 124 patients (59 ± 14 years, 60% male) were included: 27 with mild, 51 with moderate, 26 with severe, and 20 with critical disease. Lung diffusion capacity was below the lower limit of normal in 42% of discharged patients. 99% of discharged patients had reduced ground-glass opacification on repeat CT imaging, and normal chest X-rays were found in 93% of patients with mild disease. Residual pulmonary parenchymal abnormalities were present in 91% of discharged patients and correlated with reduced lung diffusion capacity. Twenty-two percent had low exercise capacity, 19% low fat-free mass index, and problems in mental and/or cognitive function were found in 36% of patients. Health status was generally poor, particularly in the domains functional impairment (64%), fatigue (69%), and QoL (72%). Conclusions This comprehensive health assessment revealed severe problems in several health domains in a substantial number of ex–COVID-19 patients. Longer follow-up studies are warranted to elucidate natural trajectories and to find predictors of complicated long-term trajectories of recovery. [ABSTRACT FROM AUTHOR]

Background: Delirium occurs frequently following cardiothoracic surgery, and infectious disease is an important risk factor for delirium. Surgery and cardiopulmonary bypass induce suppression of the immune response known as immunoparalysis. We aimed to investigate whether delirious patients had more pronounced immunoparalysis following cardiothoracic surgery than patients without delirium, to explain this delirium-infection association.Methods: A prospective matched case-control study was performed in two university hospitals. Cytokine production (tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-8 and IL-10) of ex vivo lipopolysaccharide (LPS)-stimulated whole blood was analyzed in on-pump cardiothoracic surgery patients preoperatively, and at 5 timepoints up to 3 days after cardiothoracic surgery. Delirium was assessed by trained staff using two validated delirium scales and chart review.Results: A total of 89 patients were screened of whom 14 delirious and 52 non-delirious patients were included. Ex vivo-stimulated production of TNF-α, IL-6, IL-8, and IL-10 was severely suppressed following cardiothoracic surgery compared to pre-surgery. Postoperative release of cytokines in non-delirious patients was attenuated by 84% [IQR: 13-93] for TNF-α, 95% [IQR: 78-98] for IL-6, and 69% [IQR: 55-81] for IL-10. The attenuation in ex vivo-stimulated production of these cytokines was not significantly different in patients with delirium compared to non-delirious patients (p > 0.10 for all cytokines).Conclusions: The post-operative attenuation of ex vivo-stimulated production of pro- and anti-inflammatory cytokines was comparable between patients that developed delirium and those who remained delirium-free after on-pump cardiothoracic surgery. This finding suggests that immunoparalysis is not more common in cardiothoracic surgery patients with delirium compared to those without. [ABSTRACT FROM AUTHOR]

Objectives: Haloperidol is commonly administered in the ICU to reduce the burden of delirium and its related symptoms despite no clear evidence showing haloperidol helps to resolve delirium or improve survival. We evaluated the association between haloperidol, when used to treat incident ICU delirium and its symptoms, and mortality.Design: Post hoc cohort analysis of a randomized, double-blind, placebo-controlled, delirium prevention trial.Setting: Fourteen Dutch ICUs between July 2013 and December 2016.Patients: One-thousand four-hundred ninety-five critically ill adults free from delirium at ICU admission having an expected ICU stay greater than or equal to 2 days.Interventions: Patients received preventive haloperidol or placebo for up to 28 days until delirium occurrence, death, or ICU discharge. If delirium occurred, treatment with open-label IV haloperidol 2 mg tid (up to 5 mg tid per delirium symptoms) was administered at clinician discretion.Measurements and Main Results: Patients were evaluated tid for delirium and coma for 28 days. Time-varying Cox hazards models were constructed for 28-day and 90-day mortality, controlling for study-arm, delirium and coma days, age, Acute Physiology and Chronic Health Evaluation-II score, sepsis, mechanical ventilation, and ICU length of stay. Among the 1,495 patients, 542 (36%) developed delirium within 28 days (median [interquartile range] with delirium 4 d [2-7 d]). A total of 477 of 542 (88%) received treatment haloperidol (2.1 mg [1.0-3.8 mg] daily) for 6 days (3-11 d). Each milligram of treatment haloperidol administered daily was associated with decreased mortality at 28 days (hazard ratio, 0.93; 95% CI, 0.91-0.95) and 90 days (hazard ratio, 0.97; 95% CI, 0.96-0.98). Treatment haloperidol administered later in the ICU course was less protective of death. Results were stable by prevention study-arm, predelirium haloperidol exposure, and haloperidol treatment protocol adherence.Conclusions: Treatment of incident delirium and its symptoms with haloperidol may be associated with a dose-dependent improvement in survival. Future randomized trials need to confirm these results. [ABSTRACT FROM AUTHOR]

Dear Editor, In the intensive care unit (ICU), ethical dilemmas regarding decision-making occur every day, as ICU professionals strive to provide care that is proportional and in line with patients' preferences. Of the 400 invited ICU professionals, 37 out of 74 physicians (50%) and 157 out of 326 nurses (48.2%) completed the survey. A good ethical climate, in which ICU professionals are encouraged to share their personal views, protects ICU professionals from moral distress, and may improve staff retention [[2]]. [Extracted from the article]

Objectives: Although patient's health status before ICU admission is the most important predictor for long-term outcomes, it is often not taken into account, potentially overestimating the attributable effects of critical illness. Studies that did assess the pre-ICU health status often included specific patient groups or assessed one specific health domain. Our aim was to explore patient's physical, mental, and cognitive functioning, as well as their quality of life before ICU admission.Design: Baseline data were used from the longitudinal prospective MONITOR-IC cohort study.Setting: ICUs of four Dutch hospitals.Patients: Adult ICU survivors (n = 2,467) admitted between July 2016 and December 2018.Interventions: None.Measurements and Main Results: Patients, or their proxy, rated their level of frailty (Clinical Frailty Scale), fatigue (Checklist Individual Strength-8), anxiety and depression (Hospital Anxiety and Depression Scale), cognitive functioning (Cognitive Failure Questionnaire-14), and quality of life (Short Form-36) before ICU admission. Unplanned patients rated their pre-ICU health status retrospectively after ICU admission. Before ICU admission, 13% of all patients was frail, 65% suffered from fatigue, 28% and 26% from symptoms of anxiety and depression, respectively, and 6% from cognitive problems. Unplanned patients were significantly more frail and depressed. Patients with a poor pre-ICU health status were more often likely to be female, older, lower educated, divorced or widowed, living in a healthcare facility, and suffering from a chronic condition.Conclusions: In an era with increasing attention for health problems after ICU admission, the results of this study indicate that a part of the ICU survivors already experience serious impairments in their physical, mental, and cognitive functioning before ICU admission. Substantial differences were seen between patient subgroups. These findings underline the importance of accounting for pre-ICU health status when studying long-term outcomes. [ABSTRACT FROM AUTHOR]

Background: Methods to identify patients at risk for incomplete physical recovery after intensive care unit (ICU) stay are lacking. Our aim was to develop a method for prediction of new-onset physical disability at ICU discharge.Methods: Multinational prospective cohort study in 10 general ICUs in Sweden, Denmark, and the Netherlands. Adult patients with an ICU stay ≥12 hours were eligible for inclusion. Sixteen candidate predictors were analyzed with logistic regression for associations with the primary outcome; new-onset physical disability 3 months post-ICU, defined as a ≥10 score reduction in the Barthel Index (BI) compared to baseline.Results: Of the 572 included patients, follow-up data are available on 78% of patients alive at follow-up. The incidence of new-onset physical disability was 19%. Univariable and multivariable modeling rendered one sole predictor for the outcome: physical status at ICU discharge, assessed with the five first items of the Chelsea critical care physical assessment tool (CPAx) (odds ratio 0.87, 95% confidence interval (CI) 0.81-0.93), a higher score indicating a lower risk, with an area under the receiver operating characteristics curve of 0.68 (95% CI 0.61-0.76). Negative predictive value for a low-risk group (CPAx score >18) was 0.88, and positive predictive value for a high-risk group (CPAx score ≤18) was 0.32.Conclusion: The ICU discharge assessment described in this study had a moderate AUC but may be useful to rule out patients unlikely to need physical interventions post-ICU. For high-risk patients, research to determine post-ICU risk factors for an incomplete rehabilitation is mandated. [ABSTRACT FROM AUTHOR]

Objectives: To externally validate two delirium prediction models (early prediction model for ICU delirium and recalibrated prediction model for ICU delirium) using either the Confusion Assessment Method-ICU or the Intensive Care Delirium Screening Checklist for delirium assessment.Design: Prospective, multinational cohort study.Setting: Eleven ICUs from seven countries in three continents.Patients: Consecutive, delirium-free adults admitted to the ICU for greater than or equal to 6 hours in whom delirium could be reliably assessed.Interventions: None.Measurements and Main Results: The predictors included in each model were collected at the time of ICU admission (early prediction model for ICU delirium) or within 24 hours of ICU admission (recalibrated prediction model for ICU delirium). Delirium was assessed using the Confusion Assessment Method-ICU or the Intensive Care Delirium Screening Checklist. Discrimination was determined using the area under the receiver operating characteristic curve. The predictive performance was determined for the Confusion Assessment Method-ICU and Intensive Care Delirium Screening Checklist cohort, and compared with both prediction models' original reported performance. A total of 1,286 Confusion Assessment Method-ICU-assessed patients and 892 Intensive Care Delirium Screening Checklist-assessed patients were included. Compared with the area under the receiver operating characteristic curve of 0.75 (95% CI, 0.71-0.79) in the original study, the area under the receiver operating characteristic curve of the early prediction model for ICU delirium was 0.67 (95% CI, 0.64-0.71) for delirium as assessed using the Confusion Assessment Method-ICU and 0.70 (95% CI, 0.66-0.74) using the Intensive Care Delirium Screening Checklist. Compared with the original area under the receiver operating characteristic curve of 0.77 (95% CI, 0.74-0.79), the area under the receiver operating characteristic curve of the recalibrated prediction model for ICU delirium was 0.75 (95% CI, 0.72-0.78) for assessing delirium using the Confusion Assessment Method-ICU and 0.71 (95% CI, 0.67-0.75) using the Intensive Care Delirium Screening Checklist.Conclusions: Both the early prediction model for ICU delirium and recalibrated prediction model for ICU delirium are externally validated using either the Confusion Assessment Method-ICU or the Intensive Care Delirium Screening Checklist for delirium assessment. Per delirium prediction model, both assessment tools showed a similar moderate-to-good statistical performance. These results support the use of either the early prediction model for ICU delirium or recalibrated prediction model for ICU delirium in ICUs around the world regardless of whether delirium is evaluated with the Confusion Assessment Method-ICU or Intensive Care Delirium Screening Checklist. [ABSTRACT FROM AUTHOR]

Background: Delirium incidence in intensive care unit patients is high and associated with impaired long-term outcomes. The use of prophylactic haloperidol did not improve short-term outcome among critically ill adults at high risk of delirium. This study evaluated the effects of prophylactic haloperidol use on long-term quality of life in this group of patients and explored which factors are associated with change in quality of life.Methods: A preplanned secondary analysis of long-term outcomes of the pRophylactic haloperidol usE for DeliriUm in iCu patients at high risk for dElirium (REDUCE) study was conducted. In this multicenter randomized clinical trial, nondelirious intensive care unit patients were assigned to prophylactic haloperidol (1 or 2 mg) or placebo (0.9% sodium chloride). In all groups, patients finally received study medication for median duration of 3 days [interquartile range, 2 to 6] until onset of delirium or until intensive care unit discharge. Long-term outcomes were assessed using the Short Form-12 questionnaire at intensive care unit admission (baseline) and after 1 and 6 months. Quality of life was summarized in the physical component summary and mental component summary scores. Differences between the haloperidol and placebo group and factors associated with changes in quality of life were analyzed.Results: Of 1,789 study patients, 1,245 intensive care unit patients were approached, of which 887 (71%) responded. Long-term quality of life did not differ between the haloperidol and placebo group (physical component summary mean score of 39 ± 11 and 39 ± 11, respectively, and P = 0.350; and mental component summary score of 50 ± 10 and 51 ± 10, respectively, and P = 0.678). Age, medical and trauma admission, quality of life score at baseline, risk for delirium (PRE-DELIRIC) score, and the number of sedation-induced coma days were significantly associated with a decline in long-term quality of life.Conclusions: Prophylactic haloperidol use does not affect long-term quality of life in critically ill patients at high risk for delirium. Several factors, including the modifiable factor number of sedation-induced coma days, are associated with decline in long-term outcomes. [ABSTRACT FROM AUTHOR]

The article provides an executive summary of the 2018 Pain, Agitation/sedation, Delirium, Immobility (rehabilitation/mobilization), and Sleep (disruption) (PADIS) clinical practice guidelines, and it mentions updates to the 2013 pain, agitation, and delirium prevention and management guidelines. Medical protocols are examined, along with opioid therapy and the therapeutic use of drugs such as acetaminophen, nefopam, and ketamine.

Purpose: We assessed the prevalence and variables associated with haloperidol use for delirium in ICU patients and explored any associations of haloperidol use with 90-day mortality.Methods: All acutely admitted, adult ICU patients were screened during a 2-week inception period. We followed the patient throughout their ICU stay and assessed 90-day mortality. We assessed patients and their variables in the first 24 and 72 h in ICU and studied their association together with that of ICU characteristics with haloperidol use.Results: We included 1260 patients from 99 ICUs in 13 countries. Delirium occurred in 314/1260 patients [25% (95% confidence interval 23-27)] of whom 145 received haloperidol [46% (41-52)]. Other interventions for delirium were benzodiazepines in 36% (31-42), dexmedetomidine in 21% (17-26), quetiapine in 19% (14-23) and olanzapine in 9% (6-12) of the patients with delirium. In the first 24 h in the ICU, all subtypes of delirium [hyperactive, adjusted odds ratio (aOR) 29.7 (12.9-74.5); mixed 10.0 (5.0-20.2); hypoactive 3.0 (1.2-6.7)] and circulatory support 2.7 (1.7-4.3) were associated with haloperidol use. At 72 h after ICU admission, circulatory support remained associated with subsequent use of haloperidol, aOR 2.6 (1.1-6.9). Haloperidol use within 0-24 h and within 0-72 h of ICU admission was not associated with 90-day mortality [aOR 1.2 (0.5-2.5); p = 0.66] and [aOR 1.9 (1.0-3.9); p = 0.07], respectively.Conclusions: In our study, haloperidol was the main pharmacological agent used for delirium in adult patients regardless of delirium subtype. Benzodiazepines, other anti-psychotics and dexmedetomidine were other frequently used agents. Haloperidol use was not statistically significantly associated with increased 90-day mortality. [ABSTRACT FROM AUTHOR]

Objectives: To develop and validate an abbreviated version of the Cognitive Failure Questionnaire that can be used by patients as part of self-assessment to measure functional cognitive outcome in ICU survivors.Design: A retrospective multicenter observational study.Setting: The ICUs of two Dutch university hospitals.Patients: Adult ICU survivors.Interventions: None.Measurements and Main Results: Cognitive functioning was evaluated between 12 and 24 months after ICU discharge using the full 25-item Cognitive Failure Questionnaire (CFQ-25). Incomplete CFQ-25 questionnaires were excluded from analysis. Forward selection in a linear regression model was used in hospital A to assess which of the CFQ-25 items should be included to prevent a significant loss of correlation between an abbreviated and the full CFQ-25. Subsequently, the performance of an abbreviated Cognitive Failure Questionnaire was determined in hospital B using Pearson's correlation. A Bland-Altman plot was used to examine whether the reduced-item outcome scores of an abbreviated Cognitive Failure Questionnaire were a replacement for the full CFQ-25 outcome scores. Among 1,934 ICU survivors, 1,737 were included, 819 in hospital A, 918 in hospital B. The Pearson's correlation between the abbreviated 14-item Cognitive Failure Questionnaire (CFQ-14) and the CFQ-25 was 0.99. The mean of the difference scores was -0.26, and 95% of the difference scores fell within +5 and -5.5 on a 100-point maximum score.Conclusions: It is feasible to use the abbreviated CFQ-14 to measure self-reported cognitive failure in ICU survivors as this questionnaire has a similar performance as the full CFQ-25. [ABSTRACT FROM AUTHOR]

Introduction: Medical and nursing protocols in perioperative care for pancreaticoduodenectomy are mainly mono-disciplinary, limiting their integration and transparency in a continuous health care system. The aims of this study were to evaluate adherence to a multidisciplinary clinical pathway for all pancreaticoduodenectomy patients during their entire hospital stay and to determine if the use of this clinical pathway is associated with beneficial effects on clinical end points.Materials and Methods: A prospective cohort study was conducted in 95 pancreaticoduodenectomy patients treated according to a clinical pathway, including a variance report, compared to a historical control group (n = 52) with a traditional treatment regime.Results: Process evaluation of the clinical pathway group revealed that protocol adherence throughout all units was above 80%. Major complications according to Clavien-Dindo classification grade ≥3 decreased from 27 to 13%; p = 0.02. Hospital length of stay was significantly shorter in the clinical pathway group, median 10 days [IQR 8-15], compared with the control group, median 13 days [IQR 10-18]; p = 0.02.Conclusion: The use of a clinical pathway in pancreaticoduodenectomy patients was associated with high protocol adherence, improved outcome and shorter hospital length of stay. Variance report analysis and protocol adherence with a Prepare-Act-Reflect Cycle are essential in surveillance of outcome. [ABSTRACT FROM AUTHOR]

Background Delirium is a common disorder in Intensive Care Unit (ICU) patients and is associated with serious short- and long-term consequences, including re-intubations, ICU readmissions, prolonged ICU and hospital stay, persistent cognitive problems, and higher mortality rates. Considering the high incidence of delirium and its consequences, prevention of delirium is imperative. This study focuses on a program of standardized nursing and physical therapy interventions to prevent delirium in the ICU, called UNDERPIN-ICU (nUrsiNg DEliRium Preventive INterventions in the ICU). Objective : To determine the effect of the UNDERPIN-ICU program on the number of delirium-coma-free days in 28 days and several secondary outcomes, such as delirium incidence, the number of days of survival in 28 and 90 days and delirium-related outcomes. Design and setting A multicenter stepped wedge cluster randomized controlled trial. Methods Eight to ten Dutch ICUs will implement the UNDERPIN-ICU program in a randomized order. Every two months the UNDERPIN-ICU program will be implemented in an additional ICU following a two months period of staff training. UNDERPIN-ICU consists of standardized protocols focusing on several modifiable risk factors for delirium, including cognitive impairment, sleep deprivation, immobility and visual and hearing impairment. Participants ICU patients aged ≥18 years (surgical, medical, or trauma) and at high risk for delirium, E-PRE-DELIRIC ≥35%, will be included, unless delirium was detected prior ICU admission, expected length of ICU stay is less then one day or when delirium assessment is not possible. Discussion For every intervention the balance between putative benefit and potential unwanted side effects needs to be considered. In non-ICU patients, it has been shown that a similar program resulted in a significant reduction of delirium incidence and duration. Recent small studies using multi component interventions to prevent delirium in ICU patients have also shown beneficial effect, without unwanted side effects. We therefore feel that the proportionality of potential positive effects of the UNDERPIN-ICU program, weighed against potential unwanted side effects is favourable. Since this has not been rigorously proven in ICU patients, we will study the effects of this program in ICU patients using a stepped wedge design. Trial registration The study is registered in the clinical trials registry: https://clinicaltrials.gov/ . Reporting method Standard Protocol Items: Recommendations for Interventional Trails (SPIRIT). [ABSTRACT FROM AUTHOR]

Delirium frequently occurs in intensive care unit patients and is associated with worse outcomes. Recently, a multicomponent non-pharmacological nursing intervention program called UNDERPIN-ICU, was implemented in ten Dutch intensive care units. The program was aimed at delirium reduction by optimizing four modifiable risk factors: visual and hearing impairment, cognitive impairment, immobility, and sleep deprivation. Despite its scientific fundament and extensive implementation, this program showed no effect on delirium outcomes. To explore factors that hindered or facilitated the application of the UNDERPIN-ICU delirium program in daily practice as experienced by healthcare professionals. Semi-structured focus group interviews were conducted in all participating centers between April and June of 2019. Directed content and thematic analyses were applied. Interviews were coded. Codes were grouped into categories based on factors that hindered or facilitated program application. In total, 22 ICU nurses, 3 ICU physicians, 5 local delirium group members and one research manager participated in 10 focus group interviews. We found 41 factors that hindered or facilitated program application, grouped into five categories: interventions; individual healthcare professional; patient; implementation process; capacity for change, incentives and resources. Among the factors identified in this study, the facilitating factors included standardized interventions, a structured implementation, interactive educational meetings and, feedback and support. The hindering factors included doubts about usefulness, feasibility, the extensive number of program components, limited knowledge about the program and a focus on physical care. Factors that hindered program application may explain why the UNDERPIN-ICU program did not have positive effects on delirium outcomes. Factors that facilitated application should be strengthened in future non-pharmacological nursing interventions to prevent or reduce delirium in intensive care. ClinicalTrials.gov Identifier: NCT03002701 ; registration date December 26, 2016. [ABSTRACT FROM AUTHOR]

Similarly, a significantly lower delirium severity score was found for cases classified as "no acute encephalopathy" but "delirium", compared to a positive classification by both expert panels. Studies on delirium detection tools usually have a delirium expert as a reference rater. Interestingly, if "acute encephalopathy" was present without clinical delirium, a significantly higher severity of delirium score (DRS-R-98) was observed, compared to a negative classification by both expert panels. [Extracted from the article]