Long-term outcomes after treatment of delirium during critical illness with antipsychotics (MIND-USA): a randomised, placebo-controlled, phase 3 trial.

BACKGROUND: Delirium is common during critical illness and is associated with long-term cognitive impairment and disability. Antipsychotics are frequently used to treat delirium, but their effects on long-term outcomes are unknown. We aimed to investigate the effects of antipsychotic treatment of delirious, critically ill patients on long-term cognitive, functional, psychological, and quality-of-life outcomes. METHODS: This prespecified, long-term follow-up to the randomised, double-blind, placebo-controlled phase 3 MIND-USA Study was conducted in 16 hospitals throughout the USA. Adults (aged ≥18 years) who had been admitted to an intensive care unit with respiratory failure or septic or cardiogenic shock were eligible for inclusion in the study if they had delirium. Participants were randomly assigned-using a computer-generated, permuted-block randomisation scheme with stratification by trial site and age-in a 1:1:1 ratio to receive intravenous placebo, haloperidol, or ziprasidone for up to 14 days. Investigators and participants were masked to treatment group assignment. 3 months and 12 months after randomisation, we assessed survivors' cognitive, functional, psychological, quality-of-life, and employment outcomes using validated telephone-administered tests and questionnaires. This trial was registered with ClinicalTrials.gov, NCT01211522, and is complete. FINDINGS: Between Dec 7, 2011, and Aug 12, 2017, we screened 20 914 individuals, of whom 566 were eligible and consented or had consent provided to participate. Of these 566 patients, 184 were assigned to the placebo group, 192 to the haloperidol group, and 190 to the ziprasidone group. 1-year survival and follow-up rates were similar between groups. Cognitive impairment was common in all three treatment groups, with a third of survivors impaired at both 3-month and 12-month follow-up in all groups. More than half of the surveyed survivors in each group had cognitive or physical limitations (or both) that precluded employment at both 3-month and 12-month follow-up. At both 3 months and 12 months, neither haloperidol (adjusted odds ratio 1·22 [95% CI 0·73-2.04] at 3 months and 1·12 [0·60-2·11] at 12 months) nor ziprasidone (1·07 [0·59-1·96] at 3 months and 0·94 [0·62-1·44] at 12 months) significantly altered cognitive outcomes, as measured by the Telephone Interview for Cognitive Status T score, compared with placebo. We also found no evidence that functional, psychological, quality-of-life, or employment outcomes improved with haloperidol or ziprasidone compared with placebo. INTERPRETATION: In delirious, critically ill patients, neither haloperidol nor ziprasidone had a significant effect on cognitive, functional, psychological, or quality-of-life outcomes among survivors. Our findings, along with insufficient evidence of short-term benefit and frequent inappropriate continuation of antipsychotics at hospital discharge, indicate that antipsychotics should not be used routinely to treat delirium in critically ill adults. FUNDING: National Institutes of Health and the US Department of Veterans Affairs.

Racial Differences in Shared Decision-Making About Critical Illness.

Importance: Shared decision-making is the preferred method for evaluating complex tradeoffs in the care of patients with critical illness. However, it remains unknown whether critical care clinicians engage diverse patients and caregivers equitably in shared decision-making. Objective: To compare critical care clinicians' approaches to shared decision-making in recorded conversations with Black and White caregivers of patients with critical illness. Design, Setting, and Participants: This thematic analysis consisted of unstructured clinician-caregiver meetings audio-recorded during a randomized clinical trial of a decision aid about prolonged mechanical ventilation at 13 intensive care units in the US. Participants in meetings included critical care clinicians and Black or White caregivers of patients who underwent mechanical ventilation. The codebook included components of shared decision-making and known mechanisms of racial disparities in clinical communication. Analysts were blinded to caregiver race during coding. Patterns within and across racial groups were evaluated to identify themes. Data analysis was conducted between August 2021 and April 2023. Main Outcomes and Measures: The main outcomes were themes describing clinician behaviors varying by self-reported race of the caregivers. Results: The overall sample comprised 20 Black and 19 White caregivers for a total of 39 audio-recorded meetings with clinicians. The duration of meetings was similar for both Black and White caregivers (mean [SD], 23.9 [13.7] minutes vs 22.1 [11.2] minutes, respectively). Both Black and White caregivers were generally middle-aged (mean [SD] age, 47.6 [9.9] years vs 51.9 [8.8] years, respectively), female (15 [75.0%] vs 14 [73.7%], respectively), and possessed a high level of self-assessed health literacy, which was scored from 3 to 15 with lower scores indicating increasing health literacy (mean [SD], 5.8 [2.3] vs 5.3 [2.0], respectively). Clinicians conducting meetings with Black and White caregivers were generally young (mean [SD] age, 38.8 [6.6] years vs 37.9 [8.2] years, respectively), male (13 [72.2%] vs 12 [70.6%], respectively), and White (14 [77.8%] vs 17 [100%], respectively). Four variations in clinicians' shared decision-making behaviors by caregiver race were identified: (1) providing limited emotional support for Black caregivers, (2) failing to acknowledge trust and gratitude expressed by Black caregivers, (3) sharing limited medical information with Black caregivers, and (4) challenging Black caregivers' preferences for restorative care. These themes encompass both relational and informational aspects of shared decision-making. Conclusions and Relevance: The results of this thematic analysis showed that critical care clinicians missed opportunities to acknowledge emotions and value the knowledge of Black caregivers compared with White caregivers. These findings may inform future clinician-level interventions aimed at promoting equitable shared decision-making.

Novel Definitions of Wellness and Distress among Family Caregivers of Patients with Acute Cardiorespiratory Failure: A Qualitative Study.

Rationale: Family caregivers of patients with acute cardiorespiratory failure are at high risk for distress, which is typically defined as the presence of psychological symptoms such as anxiety, depression, or posttraumatic stress. Interventions to reduce caregiver distress and increase wellness have been largely ineffective to date. An incomplete understanding of caregiver wellness and distress may hinder efforts at developing effective support interventions. Objectives: To allow family caregivers to define their experiences of wellness and distress 6 months after patient intensive care unit (ICU) admission and to identify moderators that influence wellness and distress. Methods: Primary family caregivers of adult patients admitted to the medical ICU with acute cardiorespiratory failure were invited to participate in a semistructured interview 6 months after ICU admission as part of a larger prospective cohort study. Interview guides were used to assess caregiver perceptions of their own well-being, record caregiver descriptions of their experiences of family caregiving, and identify key stress events and moderators that influenced well-being during and after the ICU admission. This study was guided by the Chronic Traumatic Stress Framework conceptual model, and data were analyzed using the five-step framework approach. Results: Among 21 interviewees, the mean age was 58 years, 67% were female, and 76% were White. Nearly half of patients (47%) had died before the caregiver interview. At the time of the interview, 9 caregivers endorsed an overall sense of distress, 10 endorsed a sense of wellness, and 2 endorsed a mix of both. Caregivers defined their experiences of wellness and distress as multidimensional and composed of four main elements: 1) positive versus negative physical and psychological outcomes, 2) high versus low capacity for self-care, 3) thriving versus struggling in the caregiving role, and 4) a sense of normalcy versus ongoing life disruption. Postdischarge support from family, friends, and the community at large played a key role in moderating caregiver outcomes. Conclusions: Caregiver wellness and distress are multidimensional and extend beyond the absence or presence of psychological outcomes. Future intervention research should incorporate novel outcome measures that include elements of self-efficacy, preparedness, and adaptation and optimize postdischarge support for family caregivers.

Prevalence and predictors of shared decision-making in goals-of-care clinician-family meetings for critically ill neurologic patients: a multi-center mixed-methods study.

BACKGROUND: Shared decision-making is a joint process where patients, or their surrogates, and clinicians make health choices based on evidence and preferences. We aimed to determine the extent and predictors of shared decision-making for goals-of-care discussions for critically ill neurological patients, which is crucial for patient-goal-concordant care but currently unknown. METHODS: We analyzed 72 audio-recorded routine clinician-family meetings during which goals-of-care were discussed from seven US hospitals. These occurred for 67 patients with 72 surrogates and 29 clinicians; one hospital provided 49/72 (68%) of the recordings. Using a previously validated 10-element shared decision-making instrument, we quantified the extent of shared decision-making in each meeting. We measured clinicians' and surrogates' characteristics and prognostic estimates for the patient's hospital survival and 6-month independent function using post-meeting questionnaires. We calculated clinician-family prognostic discordance, defined as ≥ 20% absolute difference between the clinician's and surrogate's estimates. We applied mixed-effects regression to identify independent associations with greater shared decision-making. RESULTS: The median shared decision-making score was 7 (IQR 5-8). Only 6% of meetings contained all 10 shared decision-making elements. The most common elements were "discussing uncertainty"(89%) and "assessing family understanding"(86%); least frequent elements were "assessing the need for input from others"(36%) and "eliciting the context of the decision"(33%). Clinician-family prognostic discordance was present in 60% for hospital survival and 45% for 6-month independent function. Univariate analyses indicated associations between greater shared decision-making and younger clinician age, fewer years in practice, specialty (medical-surgical critical care > internal medicine > neurocritical care > other > trauma surgery), and higher clinician-family prognostic discordance for hospital survival. After adjustment, only higher clinician-family prognostic discordance for hospital survival remained independently associated with greater shared decision-making (p = 0.029). CONCLUSION: Fewer than 1 in 10 goals-of-care clinician-family meetings for critically ill neurological patients contained all shared decision-making elements. Our findings highlight gaps in shared decision-making. Interventions promoting shared decision-making for high-stakes decisions in these patients may increase patient-value congruent care; future studies should also examine whether they will affect decision quality and surrogates' health outcomes.

Posttraumatic Stress Symptom Trajectories in Family Caregivers of Patients With Acute Cardiorespiratory Failure.

Importance: Overall, 1 in 3 family caregivers of patients who require intensive care unit (ICU) admission will experience significant posttraumatic stress symptoms (PTSSs), but little is known about how PTSSs evolve over time. Measuring PTSS trajectories could facilitate the development of targeted interventions to improve mental health outcomes for family caregivers of critically ill patients. Objective: To measure 6-month PTSS trajectories among caregivers of patients with acute cardiorespiratory failure. Design, Setting, and Participants: This prospective cohort study was conducted in the medical ICU of a large academic medical center among adult patients requiring (1) vasopressors for shock, (2) high-flow nasal cannula, (3) noninvasive positive pressure ventilation, or (4) invasive mechanical ventilation. Each patient was enrolled along with their primary caregiver, ie, the unpaid individual who provided the most physical, emotional, or financial support prior to ICU admission. Main Outcomes and Measures: Family caregiver PTSSs were assessed using the Impact of Events Scale-Revised within 48 hours of ICU admission, following ICU discharge, and 3 and 6 months after enrollment. Latent class growth analysis was used to measure PTSS trajectories. Preselected patient and caregiver characteristics measured at ICU admission were analyzed for association with trajectory membership. Six-month patient and caregiver outcomes were analyzed by caregiver trajectory. Results: Overall, 95 family caregivers were enrolled and provided baseline data; mean (SD) age was 54.2 (13.6) years, 72 (76%) were women, 22 (23%) were Black individuals, and 70 (74%) were White individuals. Three trajectories were identified: persistently low (51 caregivers [54%]), resolving (29 [31%]), and chronic (15 [16%]). Low caregiver resilience, prior caregiver trauma, high patient severity of illness, and good patient premorbid functional status were associated with the chronic trajectory. Caregivers with the chronic PTSS trajectory had worse 6-month health-related quality of life (mean [SD] total 36-item Short Form Survey score, persistently low trajectory: 104.7 [11.3]; resolving trajectory: 101.7 [10.4]; chronic trajectory: 84.0 [14.4]; P < .001) and reduced effectiveness at work (mean [SD] perceived effectiveness at work score, persistently low trajectory: 86.0 [24.2]; resolving trajectory: 59.1 [32.7]; chronic trajectory: 72.3 [18.4]; P = .009). Conclusions and Relevance: In this study, 3 distinct PTSS trajectories among ICU family caregivers were observed, with 16% of caregivers experiencing chronic PTSSs over the subsequent 6 months. Family caregivers with persistent PTSS had lower resilience, prior trauma, higher patient severity of illness, and higher baseline patient functional status compared with family caregivers with persistently low PTSS, with adverse effects on quality of life and work. Identifying these caregivers is an essential first step to develop interventions tailored to those with the greatest need for support.

Association Between Shared Decision-Making During Family Meetings and Surrogates' Trust in Their ICU Physician.

BACKGROUND: Although trust is central to successful physician-family relationships in ICUs, little is known about how to promote surrogates' trust of ICU physicians in this setting. RESEARCH QUESTION: Does the conduct of family conferences and physicians' use of shared decision-making (SDM) within family conferences impact surrogates' trust in the physician? STUDY DESIGN AND METHODS: A mixed-methods secondary analysis was done of a multicenter prospective cohort study of 369 surrogate decision-makers of 204 decisionally incapacitated patients at high risk of death or severe functional impairment within 13 ICUs at six US medical centers between 2008 and 2012. Surrogates completed the Abbreviated Wake Forest Physician Trust Scale (range, 5-25) before and after an audio-recorded family conference conducted within 5 days of ICU admission. We qualitatively coded transcribed conferences to determine physicians' use of five SDM behaviors: discussing surrogate's role, explaining medical condition and prognosis, providing emotional support, assessing understanding, and eliciting patient's values and preferences. Using multivariable linear regression with adjustment for clustering, we assessed whether surrogates' trust in the physician increased after the family meeting; we also examined whether the number of SDM behaviors used by physicians during the family meeting impacted trust scores. RESULTS: In adjusted models, conduct of a family meeting was associated with increased trust (average change, pre- to post family meeting: 0.91 point [95% CI, 0.4-1.4; P < .01]). Every additional element of SDM used during the family meeting, including discussing surrogate's role, providing emotional support, assessing understanding, and eliciting patient's values and preferences, was associated with a 0.37-point increase in trust (95% CI, 0.08-0.67; P = .01). If all four elements were used, trust increased by 1.48 points. Explaining medical condition or prognosis was observed in nearly every conference (98.5%) and was excluded from the final model. INTERPRETATION: The conduct of family meetings and physicians' use of SDM behaviors during meetings were both associated with increases in surrogates' trust in the treating physician.

Creation and impact of containment units with high-risk zones during the coronavirus disease 2019 (COVID-19) pandemic.

BACKGROUND: The rapid spread of coronavirus disease 2019 (COVID-19) required swift preparation to protect healthcare personnel (HCP) and patients, especially considering shortages of personal protective equipment (PPE). Due to the lack of a pre-existing biocontainment unit, we needed to develop a novel approach to placing patients in isolation cohorts while working with the pre-existing physical space. OBJECTIVES: To prevent disease transmission to non-COVID-19 patients and HCP caring for COVID-19 patients, to optimize PPE usage, and to provide a comfortable and safe working environment. METHODS: An interdisciplinary workgroup developed a combination of approaches to convert existing spaces into COVID-19 containment units with high-risk zones (HRZs). We developed standard workflow and visual management in conjunction with updated staff training and workflows. The infection prevention team created PPE standard practices for ease of use, conservation, and staff safety. RESULTS: The interventions resulted in 1 possible case of patient-to-HCP transmission and zero cases of patient-to-patient transmission. PPE usage decreased with the HRZ model while maintaining a safe environment of care. Staff on the COVID-19 units were extremely satisfied with PPE availability (76.7%) and efforts to protect them from COVID-19 (72.7%). Moreover, 54.8% of HCP working in the COVID-19 unit agreed that PPE monitors played an essential role in staff safety. CONCLUSIONS: The HRZ model of containment unit is an effective method to prevent the spread of COVID-19 with several benefits. It is easily implemented and scaled to accommodate census changes. Our experience suggests that other institutions do not need to modify existing physical structures to create similarly protective spaces.

The Association of Selective Serotonin Reuptake Inhibitors With Delirium in Critically Ill Adults: A Secondary Analysis of the Bringing to Light the Risk Factors and Incidence of Neuropsychologic Dysfunction in ICU Survivors ICU Study.

OBJECTIVES: To assess the association between selective serotonin reuptake inhibitors (SSRI) and delirium in the subsequent 24 hours after drug administration in critically ill adults. DESIGN: Retrospective cohort study utilizing the Bringing to Light the Risk Factors and Incidence of Neuropsychologic Dysfunction in ICU Survivors dataset. SETTING: Two large U.S. ICUs. PATIENTS: Critically ill adults admitted to a medical or surgery ICU between March 2007 and May 2010 with respiratory failure or shock. INTERVENTIONS: Our primary outcome was the occurrence rate of delirium or coma during each day in the ICU. Our exposure variable was SSRI administration on the prior day in the ICU. As a secondary question, we assessed the association of SSRI administration and delirium the same day of SSRI administration in the ICU. MEASUREMENTS AND MAIN RESULTS: We analyzed 821 patients. The median age was 61.2 years old (interquartile range, 50.9-70.7), and 401 (48.8%) were female. A total of 233 patients (28.4%) received prescribed SSRIs at least once during their ICU admission. Delirium was present in 606 (74%) of the patients at some point during hospitalization in the ICU. Coma was present in 532 (64.8%) of the patients at some point during hospitalization in the ICU. After adjusting for multiple potential confounding factors, we found that SSRI administration in the ICU was associated with lower odds of delirium/coma (odds ratio [OR], 0.75; 95% CI, 0.57-1.00) the next day. An SSRI administered on the same day reduced the odds of delirium/coma as well (OR, 0.66; 95% CI, 0.50-0.87). CONCLUSIONS: SSRI administration is associated with decreased risk of delirium/coma in 24 hours and on the same day of administration in critically ill patients in a medical or surgical ICU.

Surrogates of Patients With Severe Acute Brain Injury Experience Persistent Anxiety and Depression Over the 6 Months After ICU Admission.

CONTEXT: Severe Acute Brain Injury (SABI) is neurologically devastating, and surrogates for these patients may struggle with particularly complex decisions due to substantial prognostic uncertainty. OBJECTIVES: To compare anxiety and depression symptoms over time between SABI surrogates and non-SABI surrogates for patients requiring prolonged mechanical ventilation (PMV). METHODS: We conducted a secondary analysis of the data from a multicenter randomized trial of a decision aid intervention for surrogates of adults experiencing PMV. Eligible patients were enrolled from medical, surgical, trauma, cardiac, and neurologic intensive care units (ICUs). ICU admitting diagnoses were used to identify patients experiencing SABI. We compared anxiety and depression symptoms as measured by the Hospital Anxiety and Depression Scale score 6 months after trial enrollment between surrogates of patients with SABI and surrogates of patients experiencing PMV for other reasons. RESULTS: Our analysis included 206 patients, 60 (29%) with SABI and 146 (71%) without SABI, and their primary surrogate decision makers. After adjusting for potential confounders including surrogate demographics, surrogate financial distress, patient severity of illness baseline GCS, and patient health status at 6 months, we found that surrogates of patients experiencing SABI had higher symptoms of anxiety and depression than surrogates of non-SABI patients (adjusted mean difference 3.6, 95% CI 1.2-6.0). CONCLUSION: Surrogates of PMV patients with SABI experience persistently elevated anxiety and depression symptoms over 6 months compared to surrogates of PMV patients without SABI. Further work is needed to understand contributors to prolonged distress in this higher risk population.

Evolution of Investigating Informed Assent Discussions about CPR in Seriously Ill Patients.

CONTEXT: Outcomes after cardiopulmonary resuscitation (CPR) remain poor. We have spent 10 years investigating an "informed assent" (IA) approach to discussing CPR with chronically ill patients/families. IA is a discussion framework whereby patients extremely unlikely to benefit from CPR are informed that unless they disagree, CPR will not be performed because it will not help achieve their goals, thus removing the burden of decision-making from the patient/family, while they retain an opportunity to disagree. OBJECTIVES: Determine the acceptability and efficacy of IA discussions about CPR with older chronically ill patients/families. METHODS: This multi-site research occurred in three stages. Stage I determined acceptability of the intervention through focus groups of patients with advanced COPD or malignancy, family members, and physicians. Stage II was an ambulatory pilot randomized controlled trial (RCT) of the IA discussion. Stage III is an ongoing phase 2 RCT of IA versus attention control in in patients with advanced chronic illness. RESULTS: Our qualitative work found the IA approach was acceptable to most patients, families, and physicians. The pilot RCT demonstrated feasibility and showed an increase in participants in the intervention group changing from "full code" to "do not resuscitate" within two weeks after the intervention. However, Stages I and II found that IA is best suited to inpatients. Our phase 2 RCT in older hospitalized seriously ill patients is ongoing; results are pending. CONCLUSIONS: IA is a feasible and reasonable approach to CPR discussions in selected patient populations.

Evaluation of Physicians' Electronic Health Records Experience Using Actual and Perceived Measures.

Background: Inadequate electronic health record (EHR) interface design hinders the physician-EHR experience, which may lead to increase physician frustration and fatigue levels. Objectives: The objective of this study was to examine the physician EHR experience by evaluating the congruency between actual and perceived measures among physicians with different EHR expertise and utilization levels. Methods: We conducted a cross-sectional EHR usability study of intensive care unit (ICU) physicians at a major Southeastern medical center. We used eye-tracking glasses to measure provider EHR-related fatigue and three surveys to measure the perceived EHR experience. Results: Of the 25 ICU physicians, 11 were residents, nine were fellows, and five were attending physicians. No significant differences were found between actual fatigue levels and their perceived EHR usability (p=0.159), workload (p=0.753), and satisfaction (p=0.773). Conclusion: We found that there was low congruency between physicians' EHR-related fatigue and the perceived ratings for usability, satisfaction, and workload, which suggests using actual and perceived measures for a comprehensive assessment of the user experience. EHR-related fatigue may not be instantly felt by some physicians, hence the similar rating of perceived EHR experience among physicians.

Posttraumatic Stress Disorder Symptom Clusters in Surrogate Decision Makers of Patients Experiencing Chronic Critical Illness.

Symptoms of posttraumatic stress disorder (PTSD) are common among surrogate decision makers of patients with chronic critical illness (CCI). PTSD symptoms can be categorized into clusters including intrusion, avoidance, and hyperarousal, each of which has been associated with distinct outcomes and treatment responses. Our objective was to determine which symptom cluster was predominant among surrogates of patients with CCI. DESIGN: Secondary analysis of data from a clinical trial of a communication intervention. SETTING: The original trial was conducted in medical intensive care units at three tertiary-care centers and one community hospital. PATIENTS: Patients with CCI (≥7 d of mechanical ventilation and not expected to die or to be weaned from the ventilator in the subsequent 72 hr) and their surrogates. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Surrogate PTSD symptoms were measured 90 days after onset of patient CCI using the Impact of Events Scale-Revised (IES-R). The IES-R includes a total score (range, 0-88, higher scores indicate severe symptoms) as well as three subscales that assess intrusion, avoidance, and hyperarousal (range of intrusion and avoidance scores 0-32 and range of hyperarousal score 0-24). Intrusion symptoms were most severe (mean score, 10.3; 95% CI, 9.3-11.2), followed by avoidance (mean score, 8.0; 95% CI, 7.2-8.8). Hyperarousal symptoms were lowest (mean score, 5.1; 95% CI, 4.5-5.7). In a multivariable linear regression model, we found that surrogates of patients who died had higher odds of intrusion (ß, 5.52; p < 0.0001) and avoidance (ß, 3.29; p = 0.001) symptoms than surrogates of patients who lived, even after adjusting for baseline symptoms of anxiety and depression. Patient death was not associated with hyperarousal symptoms. CONCLUSIONS: Intrusive thoughts are the most severe PTSD symptom in surrogates of patients experiencing CCI, with intensified symptoms among surrogates of patients who died. These results have the potential to inform tailored treatment strategies to reduce PTSD symptoms in this population.

Variability of Prognostic Communication in Critically Ill Neurologic Patients: A Pilot Multicenter Mixed-Methods Study.

IMPORTANCE: Withdrawal-of-life-sustaining treatments (WOLST) rates vary widely among critically ill neurologic patients (CINPs) and cannot be solely attributed to patient and family characteristics. Research in general critical care has shown that clinicians prognosticate to families with high variability. Little is known about how clinicians disclose prognosis to families of CINPs, and whether any associations exist with WOLST. OBJECTIVES: Primary: to demonstrate feasibility of audio-recording clinician-family meetings for CINPs at multiple centers and characterize how clinicians communicate prognosis during these meetings. Secondary: to explore associations of 1) clinician, family, or patient characteristics with clinicians' prognostication approaches and 2) prognostication approach and WOLST. DESIGN SETTING AND PARTICIPANTS: Forty-three audio-recorded clinician-family meetings during which prognosis was discussed from seven U.S. centers for 39 CINPs with 88 family members and 27 clinicians. MAIN OUTCOMES AND MEASURES: Two investigators qualitatively coded transcripts using inductive methods (inter-rater reliability > 80%) to characterize how clinicians prognosticate. We then applied univariate and multivariable multinomial and binomial logistic regression. RESULTS: Clinicians used four distinct prognostication approaches: Authoritative (21%; recommending treatments without discussing values and preferences); Informational (23%; disclosing just the prognosis without further discussions); advisory (42%; disclosing prognosis followed by discussion of values and preferences); and responsive (14%; eliciting values and preferences, then disclosing prognosis). Before adjustment, prognostication approach was associated with center (p < 0.001), clinician specialty (neurointensivists vs non-neurointensivists; p = 0.001), patient age (p = 0.08), diagnosis (p = 0.059), and meeting length (p = 0.03). After adjustment, only clinician specialty independently predicted prognostication approach (p = 0.027). WOLST decisions occurred in 41% of patients and were most common under the advisory approach (56%). WOLST was more likely in older patients (p = 0.059) and with more experienced clinicians (p = 0.07). Prognostication approach was not independently associated with WOLST (p = 0.198). CONCLUSIONS AND RELEVANCE: It is feasible to audio-record sensitive clinician-family meetings about CINPs in multiple ICUs. We found that clinicians prognosticate with high variability. Our data suggest that larger studies are warranted in CINPs to examine the role of clinicians' variable prognostication in WOLST decisions.

Effects of a National Quality Improvement Collaborative on ABCDEF Bundle Implementation.

BACKGROUND: The ABCDEF bundle (Assess, prevent, and manage pain and Delirium; Both spontaneous awakening and breathing trials; Choice of analgesia/sedation; Early mobility; and Family engagement) improves intensive care unit outcomes, but adoption into practice is poor. OBJECTIVE: To assess the effect of quality improvement collaborative participation on ABCDEF bundle performance. METHODS: This interrupted time series analysis included 20 months of bundle performance data from 15 226 adults admitted to 68 US intensive care units. Segmented regression models were used to quantify complete and individual bundle element performance changes over time and compare performance patterns before (6 months) and after (14 months) collaborative initiation. RESULTS: Complete bundle performance rates were very low at baseline (<4%) but increased to 12% by the end. Complete bundle performance increased by 2 percentage points (SE, 0.9; P = .06) immediately after collaborative initiation. Each subsequent month was associated with an increase of 0.6 percentage points (SE, 0.2; P = .04). Performance rates increased significantly immediately after initiation for pain assessment (7.6% [SE, 2.0%], P = .002), sedation assessment (9.1% [SE, 3.7%], P = .02), and family engagement (7.8% [SE, 3%], P = .02) and then increased monthly at the same speed as the trend in the baseline period. Performance rates were lowest for spontaneous awakening/breathing trials and early mobility. CONCLUSIONS: Quality improvement collaborative participation resulted in clinically meaningful, but small and variable, improvements in bundle performance. Opportunities remain to improve adoption of sedation, mechanical ventilation, and early mobility practices.

Rapid analysis of local data to inform off-label tocilizumab use early in the COVID-19 pandemic.

The interleukin-6 receptor antagonist tocilizumab became widely used early in the coronavirus disease 2019 (COVID-19) pandemic based on small observational studies that suggested clinical benefit in COVID-19 patients with a hyperinflammatory state. To inform our local treatment algorithms in the absence of randomized clinical trial results, we performed a rapid analysis of the first 11 hospitalized COVID-19 patients treated with tocilizumab at our academic medical center. We report their early clinical outcomes and describe the process by which we assembled a team of diverse trainees and stakeholders to extract, analyze, and disseminate data during a time of clinical uncertainty.

The Association between Patient Health Status and Surrogate Decision Maker Post-Traumatic Stress Disorder Symptoms in Chronic Critical Illness.

Rationale: Surrogate decision-makers of patients with chronic critical illness (CCI) are at high risk for symptoms of post-traumatic stress disorder (PTSD). Whether patient health status after hospital discharge is a risk factor for surrogate PTSD symptoms is not known. Objectives: To determine the association between patient health status 90 days after the onset of CCI and surrogate symptoms of PTSD. Methods: We performed a secondary analysis of the data from a multicenter randomized trial of a communication intervention for adult patients with CCI and their surrogate decision-makers. Results: Surrogate PTSD symptoms were measured at 90 days using the Impact of Events Scale-Revised. For patients who were alive at 90 days, location was used as a marker of health status and included the following categories: 1) home (relatively good health and low acuity), 2) acute rehabilitation (moderate care needs and impairments, generally expected to improve), 3) skilled nursing facility (moderate care needs and impairments, generally not expected to improve significantly or quickly), 4) long-term acute care facility (persistently high acute care needs and functional impairment), and 5) readmission to an acute care hospital (suggesting the highest acuity of illness and care needs of the cohort). Patients who died before 90 days were categorized as deceased. In the analyses, 365 surrogates and 256 patients were included. Among patients, 49% were female, and the mean age was 59 years. Among surrogates, 71% were female, and the mean age was 51 years. A directed acyclic graph was constructed to identify covariates to be included in the model. Compared with symptoms seen among surrogates of patients living at home, heightened PTSD symptoms were seen among surrogates of patients who were readmitted to an acute care hospital (ß coefficient, 15.9; 95% confidence interval [CI], 4.5 to 27.3) or had died (ß coefficient, 14.8; 95% CI, 8.8 to 20.9) at 90 days. Conclusions: Surrogates of patients with CCI who have died or have been readmitted to an acute care hospital at 90 days experience increased PTSD symptoms as compared with surrogates of patients who are living at home. These patients and surrogates represent a readily identifiable group who may benefit from enhanced emotional support.

Physician experiences of screen-level features in a prominent electronic health record: Design recommendations from a qualitative study.

The goal of this qualitative study was to assess physicians' perceptions around features of key screens within a prominent commercial EHR, and to solicit end-user recommendations for improved retrieval of high-priority clinical information. We conducted a qualitative, descriptive study of 25 physicians in a medical ICU setting. at a tertiary academic medical center. An in-depth, semi-structured interview guide was developed to elicit physician perceptions on information retrieval as well as favorable and unfavorable features of specific EHR screens. Transcripts were independently coded in a qualitative software management tool by at least two trained coders using a common code book. We successfully obtained vendor permission to map physicians perception's on full Epic© screenshots. Among the 25 physician participants (13 female; 5 attending physicians, 9 fellows, 11 residents), the majority of participants reported experiencing challenges finding clinical information in the EHR. We present the most favorable and unfavorable screen-level features for four central EHR screens: Flowsheet, Notes/Chart Review, Results Review, and Vital Signs. We also compiled participants' recommendations for a comprehensive EHR dashboard screen to better support clinical workflow and information retrieval in the medical ICU through User-Centered Design. ICU physicians demonstrated a mix of positive and negative attitudes toward specific screen-level features in a major vendor-based EHR system. Physician perceptions of information overload emerged as a theme across multiple EHR screens. Our findings underscore the importance of qualitative research and end-user feedback in EHR software design and interface optimization at both the vendor and institutional level.

Randomized, Placebo-controlled Trial of Inhaled Treprostinil for Patients at Risk for Acute Respiratory Distress Syndrome.

Rationale: Inhaled treprostinil may improve oxygenation and have additional antiinflammatory effects in early acute hypoxemic respiratory failure, potentially preventing or reducing the severity of acute respiratory distress syndrome (ARDS).Objectives: To determine whether administration of inhaled treprostinil to patients at risk for ARDS is feasible, safe, and efficacious.Methods: We performed a double-blind, placebo-controlled, single-center randomized pilot trial at a quaternary care academic medical center. Patients with acute hypoxemia due to pneumonia or signs of low-pressure pulmonary edema with a unilateral or bilateral infiltrate on chest imaging and a 4 L/min supplemental oxygen requirement not requiring positive pressure ventilation were evaluated. Randomized patients received study drug or placebo (2:1 ratio). Treatment was initiated at 6 breaths every 4 hours and titrated up to 12 breaths. Subjects were maintained on treatment for 7 days and then tapered off over a period of 4 days. Study drug was stopped if positive pressure ventilation was required (invasive or noninvasive).Results: Fourteen patients were enrolled over a period of 31 months. Baseline characteristics were not significantly different between treatment groups with respect to age, sex, race, Acute Physiologic Assessment and Chronic Health Evaluation score, lung injury prediction score, or baseline mean oxygen saturation as measured by pulse oximetry (SpO2):fraction of inspired oxygen (FiO2) ratio. Trends in daily baseline and 30-minute postdose SpO2:FiO2 ratio for all treatment points were not significantly different between placebo and treprostinil. Four patients required positive pressure ventilation in the treprostinil group versus one in the placebo group.Conclusions: Inhaled treprostinil administration is feasible in patients at risk for ARDS but was not associated with improvement in the SpO2:FiO2 ratio relative to placebo. Drug-associated adverse events were not severe nor unexpected based on the known adverse effect profile of inhaled treprostinil. The clinical benefit of this intervention is unclear at this time in the absence of larger studies.Clinical trial registered with Clinicaltrials.gov (NCT02370095).

Bronchoalveolar Tregs are associated with duration of mechanical ventilation in acute respiratory distress syndrome.

BACKGROUND: Foxp3+ regulatory T cells (Tregs) play essential roles in immune homeostasis and repair of damaged lung tissue. We hypothesized that patients whose lung injury resolves quickly, as measured by time to liberation from mechanical ventilation, have a higher percentage of Tregs amongst CD4+ T cells in either airway, bronchoalveolar lavage (BAL) or peripheral blood samples. METHODS: We prospectively enrolled patients with ARDS requiring mechanical ventilation and collected serial samples, the first within 72 h of ARDS diagnosis (day 0) and the second 48-96 h later (day 3). We analyzed immune cell populations and cytokines in BAL, tracheal aspirates and peripheral blood, as well as cytokines in plasma, obtained at the time of bronchoscopy. The study cohort was divided into fast resolvers (FR; n = 8) and slow resolvers (SR; n = 5), based on the median number of days until first extubation for all participants (n = 13). The primary measure was the percentage of CD4+ T cells that were Tregs. RESULTS: The BAL of FR contained more Tregs than SR. This finding did not extend to Tregs in tracheal aspirates or blood. BAL Tregs expressed more of the full-length FOXP3 than a splice variant missing exon 2 compared to Tregs in simultaneously obtained peripheral blood. CONCLUSION: Tregs are present in the bronchoalveolar space during ARDS. A greater percentage of CD4+ cells were Tregs in the BAL of FR than SR. Tregs may play a role in the resolution of ARDS, and enhancing their numbers or functions may be a therapeutic target.