A multicomponent intervention program to Prevent and Reduce AgItation and phySical rEstraint use in the ICU (PRAISE): study protocol for a multicenter, stepped-wedge, cluster randomized controlled trial.

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.

Differences in long-term outcomes between ICU patients with persistent delirium, non-persistent delirium and no delirium: A longitudinal cohort study.

PURPOSE: Determine differences in physical, mental and cognitive outcomes 1-year post-ICU between patients with persistent delirium (PD), non-persistent delirium (NPD) and no delirium (ND). MATERIALS AND METHODS: A longitudinal cohort study was performed in adult ICU patients of two hospitals admitted between July 2016-February 2020. Questionnaires on physical, mental and cognitive health, frailty and QoL were completed regarding patients' pre-ICU health status and 1-year post-ICU. Delirium data were from patients' total hospital stay. Patients were divided in PD (≥14 days delirium), NPD (<14 days delirium) or ND patients. RESULTS: 2400 patients completed both questionnaires, of whom 529 (22.0%) patients developed delirium; 35 (6.6%) patients had PD and 494 (93.4%) had NPD. Patients with delirium (PD or NPD) had worse outcomes in all domains compared to ND patients. Compared to NPD, more PD patients were frail (34.3% vs. 14.6%, p = 0.006) and fatigued (85.7% vs. 61.1%, p = 0.012). After adjustment, PD was significantly associated with long-term cognitive impairment only (aOR 3.90; 95%CI 1.31-11.63). CONCLUSIONS: Patients with PD had a higher likelihood to develop cognitive impairment 1-year post-ICU compared to NPD or ND. Patients with PD and NPD were more likely to experience impairment on all health domains (i.e. physical, mental and cognitive), compared to ND patients.

Baseline Anxiety and Depression and Risk for ICU Delirium: A Prospective Cohort Study.

OBJECTIVES: Anxiety and depression are common mental disorders in adults admitted to the ICU. Although depression increases postsurgical delirium and anxiety does not, their associations with ICU delirium in critically ill adults remain unclear. We evaluated the association between ICU baseline anxiety and depression and ICU delirium occurrence. DESIGN: Subgroup analysis of a prospective cohort study. SETTING: Single, 36-bed mixed ICU. PATIENTS: Nine-hundred ninety-one ICU patients admitted with or without delirium between July 2016 and February 2020; patients admitted after elective surgery or not assessed for anxiety/depression were excluded. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTs: The Hospital Anxiety and Depression Scale questionnaire was administered at ICU admission to determine baseline anxiety and depression. All patients were assessed with the Confusion Assessment Method for the ICU (CAM-ICU) q8h; greater than or equal to 1 +CAM-ICU assessment and/or scheduled antipsychotic use represented a delirium day. Multivariable logistic and Quasi-Poisson regression models, adjusted for ICU days and nine delirium risk variables ("Pre-ICU": age, Charlson Comorbidity Index, cognitive impairment; "ICU baseline": Acute Physiology and Chronic Health Evaluation-IV, admission type; "Daily ICU": opioid and/or benzodiazepine use, Sequential Organ Failure Assessment score, coma), were used to evaluate associations between baseline anxiety and/or depression and ICU delirium. Among the 991 patients, 145 (14.6%) had both anxiety and depression, 78 (7.9%) had anxiety only, 91 (9.2%) had depression only, and 677 (68.3%) had neither. Delirium occurred in 406 of 991 total cohort (41.0%) patients; in the baseline anxiety and depression group, it occurred in 78 of 145 (53.8%), in the anxiety only group, 37 of 78 (47.4%), in the depression only group, 39 of 91 (42.9%), and in the group with neither in 252 of 677 (37.2%). Presence of both baseline anxiety and depression was associated with greater delirium occurrence (adjusted odds ratio, 1.99; 95% CI, 1.10-3.53; p = 0.02) and duration (adjusted risk ratio, 1.62; 95% CI, 1.17-2.23; p < 0.01). CONCLUSIONS: Baseline anxiety and depression are associated with increased ICU delirium occurrence and should be considered when delirium risk reduction strategies are being formulated.

Exploring Ketamine Analgosedation Use and Its Effect on Incident Delirium in Critically Ill Adults.

Ketamine is increasingly being used for analgosedation, but its effect on delirium remains unclear. We compared delirium risk variables and ketamine analgosedation use between adults who developed incident delirium and those who did not, evaluated whether ketamine analgosedation increases delirium risk, and compared ICU delirium characteristics, treatments, and outcomes between ketamine and nonketamine patients with delirium. DESIGN: Secondary, subgroup analysis of a cohort study. SETTING: Single, 36-bed mixed medical-surgical ICU in the Netherlands from July 2016 to February 2020. PATIENTS: Consecutive adults were included. Patients admitted after elective surgery, not expected to survive greater than or equal to 48 hours, admitted with delirium, or where delirium occurred prior to ketamine use were excluded. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Trained ICU nurses evaluated patients without coma (Richmond Agitation Sedation Scale. -4/-5) every 8 hours with the Confusion Assessment Method ICU; a delirium day was defined by greater than or equal to1 + Confusion Assessment Method ICU and/or scheduled antipsychotic use. Among 11 variables compared between the delirium and nondelirium groups (Baseline: age, Charlson Comorbidity score, cognitive impairment, admission type, and Acute Physiology and Chronic Health Evaluation-IV score, daily ICU [until delirium occurrence or discharge]: Sequential Organ Failure Assessment score, coma, benzodiazepine, opioid, and ketamine use) and total ICU days, 7 (age, Charlson score, Sequential Organ Failure Assessment score, coma, benzodiazepine, opioid, and ketamine use) were significantly different and were entered, along with delirium occurrence, in a logistic regression model. A total of 332 of 925 of patients (36%) developed delirium. Ketamine use was greater in patients with delirium (54 [16%] vs 4 [0.7%]; p < 0.01). Ketamine use (adjusted odds ratio, 5.60; 95% CI, 1.09-29.15), age (adjusted odds ratio, 1.03; 95% CI, 1.01-1.06), coma (adjusted odds ratio, 2.10; 95% CI, 1.15-3.78), opioid use (adjusted odds ratio, 171.17; 95% CI, 66.45-553.68), and benzodiazepine use (adjusted odds ratio, 34.07; 95% CI, 8.12-235.34) were each independently and significantly associated with increased delirium. Delirium duration, motoric subtype, delirium treatments, and outcomes were not different between the ketamine and nonketamine groups. CONCLUSIONS: Ketamine analgosedation may contribute to increased ICU delirium. The characteristics of ketamine and nonketamine delirium are similar. Further prospective research is required to evaluate the magnitude of risk for delirium with ketamine use.

Social Determinants of Health and Delirium Occurrence and Duration in Critically Ill Adults.

Social determinants of health may affect ICU outcome, but the association between social determinants of health and delirium remains unclear. We evaluated the association between three social determinants of health and delirium occurrence and duration in critically ill adults. DESIGN: Secondary, subgroup analysis of a cohort study. SETTING: Single, 36-bed mixed medical-surgical ICU in the Netherlands. PATIENTS: Nine hundred fifty-six adults consecutively admitted from July 2016 to February 2020. Patients admitted after elective surgery, residing in a nursing home, or not expected to survive greater than or equal to 48 hours were excluded. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Four factors related to three Center for Disease Control social determinants of health domains (social/community context [ethnicity], education access/quality [educational level], and economic stability [employment status and monthly income]) were collected at ICU admission from patients (or families). Well-trained ICU nurses evaluated patients without coma (Richmond Agitation Sedation Scale, -4, -5) and with the Confusion Assessment Method-ICU and/or a delirium day was defined by greater than or equal to 1 + Confusion Assessment Method-ICU and/or scheduled antipsychotic use. Multivariable logistic regression models controlling for ICU days and 10 delirium risk variables (before-ICU: age, Charlson, cognitive impairment, any antidepressant, antipsychotic, or benzodiazepine use; ICU baseline: Acute Physiology and Chronic Health Evaluation IV and admission type; daily ICU: Sequential Organ Failure Assessment, restraint use, coma, benzodiazepine, or opioid use) evaluated associations between each social determinant of health factor and both ICU delirium occurrence and duration. Delirium occurred in 393/956 patients (45.4%) for 2 days (1-5 d). Patients with low (vs high) income had more ICU delirium (p = 0.05). Multivariate analyses revealed no social determinants of health to be significantly associated with increased delirium occurrence or duration. Low (vs high) income was weakly associated with increased delirium occurrence (adjusted odds ratio, 1.83; 95% CI, 0.91-3.89). Low (vs high) education (adjusted relative risk, 1.21; 95% CI, 0.97-1.53) was weakly associated with a longer delirium duration. CONCLUSIONS: Social determinants of health did not affect ICU delirium in one Dutch region. Additional research across different countries/regions and where additional social determinants of health are considered is needed to define the association between social determinants of health and ICU delirium.

Factors associated with a persistent delirium in the intensive care unit: A retrospective cohort study.

PURPOSE: To explore differences between ICU patients with persistent delirium (PD), non-persistent delirium (NPD) and no delirium (ND), and to determine factors associated with PD. MATERIALS AND METHODS: Retrospective cohort study including all ICU adults admitted for ≥12 h (January 2015-February 2020), assessable for delirium and followed during their entire hospitalization. PD was defined as ≥14 days of delirium. Factors associated with PD were determined using multivariable logistic regression analysis. RESULTS: Out of 10,295 patients, 3138 (30.5%) had delirium, and 284 (2.8%) had PD. As compared to NPD (n = 2854, 27.7%) and ND (n = 7157, 69.5%), PD patients were older, sicker, more physically restrained, longer comatose and mechanically ventilated, had a longer ICU and hospital stay, more ICU readmissions and a higher mortality rate. Factors associated with PD were age (adjusted odds ratio [aOR] 1.03; 95% confidence interval [CI] 1.02-1.04); emergency surgical (aOR 1.84; 95%CI 1.26-2.68) and medical (aOR 1.57; 95%CI 1.12-2.21) referral, mean Sequential Organ Failure Assessment (SOFA) score before delirium onset (aOR 1.18; 95%CI 1.13-1.24) and use of physical restraints (aOR 5.02; 95%CI 3.09-8.15). CONCLUSIONS: Patients with persistent delirium differ in several characteristics and had worse short-term outcomes. Physical restraints were the most strongly associated with PD.