Heterogeneity in design and analysis of ICU delirium randomized trials: a systematic review

Abstract

Background There is a growing number of randomized controlled trials (RCTs) evaluating interventions to prevent or treat delirium in the intensive care unit (ICU). Efforts to improve the conduct of delirium RCTs are underway, but none address issues related to statistical analysis. The purpose of this review is to evaluate heterogeneity in the design and analysis of delirium outcomes and advance methodological recommendations for delirium RCTs in the ICU. Methods Relevant databases, including PubMed and Embase, were searched with no restrictions on language or publication date; the search was conducted on July 8, 2019. RCTs conducted on adult ICU patients with delirium as the primary outcome were included where trial results were available. Data on frequency and duration of delirium assessments, delirium outcome definitions, and statistical methods were independently extracted in duplicate. The review was registered with PROSPERO (CRD42020141204). Results Among 65 eligible RCTs, 44 (68%) targeted the prevention of delirium. The duration of follow-up varied, with 31 (48%) RCTs having ≤7 days of follow-up, and only 24 (37%) conducting delirium assessments after ICU discharge. The incidence of delirium was the most common outcome (50 RCTs, 77%) for which 8 unique statistical methods were applied. The most common method, applied to 51 of 56 (91%) delirium incidence outcomes, was the two-sample test comparing the proportion of patients who ever experienced delirium. In the presence of censoring of patients at ICU discharge or death, this test may be misleading. The impact of censoring was also not considered in most analyses of the duration of delirium, as evaluated in 24 RCTs, with 21 (88%) delirium duration outcomes analyzed using a non-parametric test or two-sample t test. Composite outcomes (e.g., rank-based delirium- and coma-free days), used in 11 (17%) RCTs, seldom explicitly defined how ICU discharge, and death were incorporated into the definition and were analyzed using non-parametric tests (11 of 13 (85%) composite outcomes). Conclusions To improve delirium RCTs, outcomes should be explicitly defined. To account for censoring due to ICU discharge or death, survival analysis methods should be considered for delirium incidence and duration outcomes; non-parametric tests are recommended for rank-based delirium composite outcomes. Trial registration PROSPERO CRD42020141204. Registration date: 7/3/2019.

Delirium management and current practice among Intensive Care Units Doctors, Khartoum

“…Delirium is common disorder among ICU patients. 3,6,8,11,12,15,16 Doctors and nurses are direct healthcare providers for critically ill patients. In addition to nurses, doctors are involved in delirium assessment and reporting, as mentioned by Pisani et al 5 Lack of knowledge among staff has been reported as one of the individual barriers 3 ; hence, our study tangled the knowledge of doctors.…”

“…Abbreviations CAM-ICU: Confusion Assessment Method for the Intensive Care Unit ICDSC: Intensive Care Delirium Screening Checklist ICU: Intensive Care Unit MV: Mechanical Ventilator Background Delirium is a state of brain dysfunction characterized by attention and cognition disturbances in a fluctuating pattern, [1][2][3][4][5][6][7] with an acute onset of confusion and decline in cognitive ability, often occurring in hospitalized patients. 8 Delirium is related to many factors, such as the pre-existing vulnerable state of patients or medication-induced delirium that occurs during hospital stay.…”

“…5,10 Critically ill patients who are complicated with delirium, in addition to their critical illness, have been associated with prolonged mechanical ventilation (MV), longer hospital and ICU stays, and increased mortality. 3,4,6,8,[11][12][13] The severity of adverse delirium outcomes was associated with the duration of delirium; the longer the duration, the worse the outcomes. 11 Prolonged delirium in the ICU is considered a risk factor for developing post-intensive care syndrome, which is characterized by worsened or new impairments in cognitive, physical, and mental health.…”

“…14 Its incidence varies widely; however, it has a high rate of 70-87%. 3,6,8,11,12,15,16 Although delirium is common, it is preventable. Prevention or early management of delirium is crucial to reverse the delirium state and minimize adverse clinical outcomes.…”

Timing errors and temporal uncertainty in clinical databases—A narrative review

“…Variability in standards and definitions can lead to inconsistencies in the documentation of clinical events. For example, the definitions of patient length of stay ( 177 , 178 ), ventilator free days ( 179 , 180 ) or time of onset of sepsis ( 181 ) may vary between different hospitals and jurisdictions. This variability can lead to later confusion about which definition was used for a particular event, making it difficult to compare results across different studies ( 182 ).…”