Delirium is a serious and complex problem facing critically ill patients, their families, and the health care system. When delirium develops, it is associated with prolonged hospital stays, increased ...costs, and long-term cognitive impairment in many patients. This article uses a clinical case to discuss our approach to delirium prevention and treatment in the ICU. We believe that an effective strategy to combat delirium requires implementation and adherence to a pain and sedation protocol as part of bundled care, use of a validated tool to detect delirium when present, and a focus on nonpharmacologic care strategies, including reorientation, early mobility, and incorporating family into care when possible. At present, the evidence does not support the routine administration of medications to prevent or treat delirium. A pharmacologic approach may be needed for agitated delirium, and we discuss our evaluation of the evidence for and against particular medications. Although delirium can be a distressing problem, there is evidence that it can be addressed through careful attention to prevention, detection, and minimizing the long-term impact on patients and their families.
Purpose
A causal biomarker for acute respiratory distress syndrome (ARDS) could fuel precision therapy options. Plasma angiopoietin-2 (ANG2), a vascular permeability marker, is a strong candidate on ...the basis of experimental and observational evidence. We used genetic causal inference methods—Mendelian randomization and mediation—to infer potential effects of plasma ANG2.
Methods
We genotyped 703 septic subjects, measured ICU admission plasma ANG2, and performed a quantitative trait loci (QTL) analysis to determine variants in the
ANGPT2
gene associated with plasma ANG2 (
p
< 0.005). We then used linear regression and post-estimation analysis to genetically predict plasma ANG2 and tested genetically predicted ANG2 for ARDS association using logistic regression. We estimated the proportion of the genetic effect explained by plasma ANG2 using mediation analysis.
Results
Plasma ANG2 was strongly associated with ARDS (OR 1.59 (95% CI 1.35, 1.88) per log). Five
ANGPT2
variants were associated with ANG2 in European ancestry subjects (
n
= 404). Rs2442608C, the most extreme
cis
QTL (coefficient 0.22, 95% CI 0.09–0.36,
p
= 0.001), was associated with higher ARDS risk: adjusted OR 1.38 (95% CI 1.01, 1.87)
, p
= 0.042. No significant QTL were identified in African ancestry subjects. Genetically predicted plasma ANG2 was associated with ARDS risk: adjusted OR 2.25 (95% CI 1.06–4.78),
p
= 0.035. Plasma ANG2 mediated 34% of the rs2442608C-related ARDS risk.
Conclusions
In septic European ancestry subjects, the strongest ANG2-determining
ANGPT2
genetic variant is associated with higher ARDS risk. Plasma ANG2 may be a causal factor in ARDS development. Strategies to reduce plasma ANG2 warrant testing to prevent or treat sepsis-associated ARDS.
A central tenet of caring for patients with ARDS is to treat the underlying cause, be it sepsis, pneumonia, or removal of an offending toxin. Identifying the risk factor for ARDS has even been ...proposed as essential to diagnosing ARDS. Not infrequently, however, the precipitant for acute hypoxemic respiratory failure is unclear, and this raises the question of whether a histologic lung diagnosis would benefit the patient. In this review, we consider the historic role of pathology in establishing a diagnosis of ARDS and the published experience of surgical and transbronchial lung biopsy in patients with ARDS. We reflect on which pathologic diagnoses influence treatment and suggest a patient-centric approach to weigh the risks and benefits of a lung biopsy for critically ill patients who may have ARDS.
Plasma interleukin-1 beta may influence sepsis mortality, yet recombinant human interleukin-1 receptor antagonist did not reduce mortality in randomized trials. We tested for heterogeneity in the ...treatment effect of recombinant human interleukin-1 receptor antagonist by baseline plasma interleukin-1 beta or interleukin-1 receptor antagonist concentration.
Retrospective subgroup analysis of randomized controlled trial.
Multicenter North American and European clinical trial.
Five hundred twenty-nine subjects with sepsis and hypotension or hypoperfusion, representing 59% of the original trial population.
Random assignment of placebo or recombinant human interleukin-1 receptor antagonist × 72 hours.
We measured prerandomization plasma interleukin-1 beta and interleukin-1 receptor antagonist and tested for statistical interaction between recombinant human interleukin-1 receptor antagonist treatment and baseline plasma interleukin-1 receptor antagonist or interleukin-1 beta concentration on 28-day mortality. There was significant heterogeneity in the effect of recombinant human interleukin-1 receptor antagonist treatment by plasma interleukin-1 receptor antagonist concentration whether plasma interleukin-1 receptor antagonist was divided into deciles (interaction p = 0.046) or dichotomized (interaction p = 0.028). Interaction remained present across different predicted mortality levels. Among subjects with baseline plasma interleukin-1 receptor antagonist above 2,071 pg/mL (n = 283), recombinant human interleukin-1 receptor antagonist therapy reduced adjusted mortality from 45.4% to 34.3% (adjusted risk difference, -0.12; 95% CI, -0.23 to -0.01), p = 0.044. Mortality in subjects with plasma interleukin-1 receptor antagonist below 2,071 pg/mL was not reduced by recombinant human interleukin-1 receptor antagonist (adjusted risk difference, +0.07; 95% CI, -0.04 to +0.17), p = 0.230. Interaction between plasma interleukin-1 beta concentration and recombinant human interleukin-1 receptor antagonist treatment was not statistically significant.
We report a heterogeneous effect of recombinant human interleukin-1 receptor antagonist on 28-day sepsis mortality that is potentially predictable by plasma interleukin-1 receptor antagonist in one trial. A precision clinical trial of recombinant human interleukin-1 receptor antagonist targeted to septic patients with high plasma interleukin-1 receptor antagonist may be worthy of consideration.
Numerous prior opinion papers, administrative electronic health record data studies, and cross-sectional surveys of telehealth during the pandemic have been published, but none have combined ...assessments of video visit success monitoring with longitudinal assessments of perceived challenges to the rapid adoption of video visits during the pandemic.
This study aims to quantify (1) the use of video visits (compared with in-person and telephone visits) over time during the pandemic, (2) video visit successful connection rates, and (3) changes in perceived video visit challenges.
A web-based survey was developed for the dual purpose of monitoring and improving video visit implementation in our health care system during the COVID-19 pandemic. The survey included questions regarding rates of in-person, telephone, and video visits for clinician-patient encounters; the rate of successful connection for video visits; and perceived challenges to video visits (eg, software, hardware, bandwidth, and technology literacy). The survey was distributed via email to physicians, advanced practice professionals, and clinicians in May 2020. The survey was repeated in March 2021. Differences between the 2020 and 2021 responses were adjusted for within-respondent correlation across surveys and tested using generalized estimating equations.
A total of 1126 surveys were completed (511 surveys in 2020 and 615 surveys in 2021). In 2020, only 21.7% (73/336) of clinicians reported no difficulty connecting with patients during video visits and 28.6% (93/325) of clinicians reported no difficulty in 2021. The distribution of the percentage of successfully connected video visits ("Over the past two weeks of scheduled visits, what percentage did you successfully connect with patients by video?") was not significantly different between 2020 and 2021 (P=.74). Challenges in conducting video visits persisted over time. Poor connectivity was the most common challenge reported by clinicians. This response increased over time, with 30.5% (156/511) selecting it as a challenge in 2020 and 37.1% (228/615) in 2021 (P=.01). Patients not having access to their electronic health record portals was also a commonly reported challenge (109/511, 21.3% in 2020 and 137/615, 22.3% in 2021, P=.73).
During the pandemic, our health care delivery system rapidly adopted synchronous patient-clinician communication using video visits. As experience with video visits increased, the reported failure rate did not significantly decline, and clinicians continued to report challenges related to general network connectivity and patient access to technology.
Acute respiratory distress syndrome (ARDS) is associated with long-term impairments in brain and muscle function that significantly impact the quality of life of those who survive the acute illness. ...The mechanisms underlying these impairments are not yet well understood, and evidence-based interventions to minimize the burden on patients remain unproved. The NHLBI of the NIH assembled a workshop in April 2023 to review the state of the science regarding ARDS-associated brain and muscle dysfunction, to identify gaps in current knowledge, and to determine priorities for future investigation. The workshop included presentations by scientific leaders across the translational science spectrum and was open to the public as well as the scientific community. This report describes the themes discussed at the workshop as well as recommendations to advance the field toward the goal of improving the health and well-being of ARDS survivors.
Abstract Purpose Neuron specific enolase (NSE) concentrations are prognostic following traumatic and anoxic brain injury, and may provide a method to quantify neuronal injury in other populations. We ...determined the association of admission plasma NSE concentrations with mortality and delirium in critically ill septic patients. Methods Retrospective analysis of 124 patients from a larger sepsis cohort. Plasma NSE was measured in the earliest blood draw at intensive care unit (ICU) admission. Primary outcomes were 30-day mortality and ICU delirium determined by chart review. Results Sixty-one patients (49.2%) died within 30 days and delirium developed in 34 (31.5%) of the 108 patients who survived at least 24 hours and were not persistently comatose. Each doubling of the NSE concentration was associated with a 7.3% (95% CI 2.5–12.0, P = .003) increased risk of 30-day mortality and a 5.2% (95% CI 3.2–7.2, P < .001) increased risk of delirium. An NSE concentration > 12.5ug/L was independently associated with a 23.3% (95% CI 6.7–39.9, P = .006) increased risk of 30-day mortality and a 29.3% (95% CI 8.8–49.8, P = .005) increased risk of delirium. Conclusions Higher plasma NSE concentrations were associated with mortality and delirium in critically ill septic patients, suggesting NSE may have utility as a marker of neuronal injury in sepsis.
The objective of this study is to describe the relationship between two quantitative muscle ultrasound measures, the rectus femoris cross-sectional area (RF-CSA) and quadriceps muscle thickness, with ...volitional measures of strength and function in critically ill patients with sepsis.
We performed a prospective study of patients admitted to a medical ICU with sepsis and shock or respiratory failure. We examined the association of two ultrasound measurements – the RF-CSA and quadriceps muscle thickness – with strength and function at day 7. Strength was determined using the Medical Research Council Score and function using Physical Function in the ICU Test, scored.
Twenty-nine patients were enrolled; 19 patients had outcome testing performed. Over 7days, RF-CSA and thickness decreased by an average of 23.2% and 17.9%, respectively. The rate of change per day of RF-CSA displayed a moderate correlation with strength (ρ 0.51, p-value 0.03) on day 7. Baseline and day 7 RF-CSA did not show a significant correlation with either outcome. Quadriceps muscle thickness did not significantly correlate with either outcome.
Muscle atrophy as detected by the rate of change in RF-CSA moderately correlated with strength one week after sepsis admission.
•Muscle atrophy occurs early in sepsis and can be detected by peripheral muscle ultrasound.•Change in rectus femoris cross-sectional area detected by ultrasound over the first week of sepsis moderately correlates with strength.•Quantitative muscle ultrasound complements volitional measures of strength and function in describing skeletal muscle dysfunction in sepsis.
Survivors of acute respiratory distress syndrome (ARDS) experience challenges that persist well beyond the time of hospital discharge. Impairment in physical function, cognitive function, and mental ...health are common and may last for years. The current coronavirus disease 2019 pandemic is drastically increasing the incidence of ARDS worldwide, and long-term impairments will remain lasting effects of the pandemic. Evaluation of the ARDS survivor should be comprehensive, and common domains of impairment that have emerged from long-term outcomes research over the past 2 decades should be systematically evaluated.
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