Effectiveness of Nebulized Tranexamic Acid in Patients with Moderate-to-Massive Hemoptysis at a Tertiary Academic Medical Center.

Introduction: The management of severe hemoptysis mainly consists of invasive interventional procedures, including angiographic bronchial artery embolization, various endobronchial interventions, and sometimes surgery. However, there are limited effective noninvasive medical therapies available. The objective of this analysis was to evaluate the effectiveness and safety of nebulized tranexamic acid (TXA) administration compared with conventional management in patients with hemoptysis. Methods: This Institutional Review Board-approved, single-center, retrospective matched cohort study was performed from January 1, 2018 to March 31, 2021. Electronic health record data were used to identify all adult inpatients with hemoptysis (International Classification of Diseases, Tenth Revision, code R04.2). All patients who received ≥1 dose of nebulized TXA were matched with up to five controls based on available severity criteria (hemoptysis severity, need for mechanical ventilation, and sequential organ failure assessment score at the time of hemoptysis diagnosis) with coarsened exact matching. The primary outcome was the need for invasive interventions for the management of hemoptysis. Secondary outcomes included time to hemoptysis resolution, duration of mechanical ventilation, hemoptysis recurrence, and hospital length of stay. Results: A total of 14 patients were treated with nebulized TXA; they were matched with 58 controls. Patients were 59.7% male, had a median age of 65.5 years, with airway disease (36.1%) being the major etiology of hemoptysis. There was no difference in the number of patients who required an invasive intervention between the TXA (35.7%) versus control group (56.9%), p = 0.344. Additionally, no difference was found in the time to hemoptysis resolution (p = 0.050), duration on mechanical ventilation (p = 0.128), hemoptysis recurrence (p = 1.000), or hospital length of stay (p = 0.139). Conclusions: In patients with hemoptysis, nebulized TXA may be considered as a noninvasive option for the management of hemoptysis. However, a larger analysis is warranted to determine the impact of nebulized TXA on invasive interventions for management.

Randomized Phase 2 Placebo-Controlled Trial of Nintedanib for the Treatment of Radiation Pneumonitis.

PURPOSE: Radiation pneumonitis (RP) is the most common dose-limiting toxicity for thoracic radiation therapy. Nintedanib is used for the treatment of idiopathic pulmonary fibrosis, which shares pathophysiological pathways with the subacute phase of RP. Our goal was to investigate the efficacy and safety of nintedanib added to a prednisone taper compared with a prednisone taper alone in reducing pulmonary exacerbations in patients with grade 2 or higher (G2+) RP. METHODS AND MATERIALS: In this phase 2, randomized, double-blinded, placebo-controlled trial, patients with newly diagnosed G2+ RP were randomized 1:1 to nintedanib or placebo in addition to a standard 8-week prednisone taper. The primary endpoint was freedom from pulmonary exacerbations at 1 year. Secondary endpoints included patient-reported outcomes and pulmonary function tests. Kaplan-Meier analysis was used to estimate the probability of freedom from pulmonary exacerbations. The study was closed early due to slow accrual. RESULTS: Thirty-four patients were enrolled between October 2015 and February 2020. Of 30 evaluable patients, 18 were randomized to the experimental Arm A (nintedanib + prednisone taper) and 12 to the control Arm B (placebo + prednisone taper). Freedom from exacerbation at 1 year was 72% (confidence interval, 54%-96%) in Arm A and 40% (confidence interval, 20%-82%) in Arm B (1-sided, P = .037). In Arm A, there were 16 G2+ adverse events possibly or probably related to treatment compared with 5 in the placebo arm. There were 3 deaths during the study period in Arm A due to cardiac failure, progressive respiratory failure, and pulmonary embolism. CONCLUSIONS: There was an improvement in pulmonary exacerbations by the addition of nintedanib to a prednisone taper. Further investigation is warranted for the use of nintedanib for the treatment of RP.

Cluster analysis of COVID-19 recovery center patients at a clinic in Boston, MA 2021-2022: impact on strategies for access and personalized care.

BACKGROUND: There are known disparities in COVID-19 resource utilization that may persist during the recovery period for some patients. We sought to define subpopulations of patients seeking COVID-19 recovery care in terms of symptom reporting and care utilization to better personalize their care and to identify ways to improve access to subspecialty care. METHODS: Prospective study of adult patients with prior COVID-19 infection seen in an ambulatory COVID-19 recovery center (CRC) in Boston, Massachusetts from April 2021 to April 2022. Hierarchical clustering with complete linkage to differentiate subpopulations was done with four sociodemographic variables: sex, race, language, and insurance status. Outcomes included ICU admission, utilization of supplementary care, self-report of symptoms. RESULTS: We included 1285 COVID-19 patients referred to the CRC with a mean age of 47 years, of whom 71% were female and 78% White. We identified 3 unique clusters of patients. Cluster 1 and 3 patients were more likely to have had intensive care unit (ICU) admissions; Cluster 2 were more likely to be White with commercial insurance and a low percentage of ICU admission; Cluster 3 were more likely to be Black/African American or Latino/a and have commercial insurance. Compared to Cluster 2, Cluster 1 patients were more likely to report symptoms (ORs ranging 2.4-3.75) but less likely to use support groups, psychoeducation, or care coordination (all p < 0.05). Cluster 3 patients reported greater symptoms with similar levels of community resource utilization. CONCLUSIONS: Within a COVID-19 recovery center, there are distinct groups of patients with different clinical and socio-demographic profiles, which translates to differential resource utilization. These insights from different subpopulations of patients can inform targeted strategies which are tailored to specific patient needs.

Causes, Consequences, and Treatments of Sleep and Circadian Disruption in the ICU: An Official American Thoracic Society Research Statement.

Background: Sleep and circadian disruption (SCD) is common and severe in the ICU. On the basis of rigorous evidence in non-ICU populations and emerging evidence in ICU populations, SCD is likely to have a profound negative impact on patient outcomes. Thus, it is urgent that we establish research priorities to advance understanding of ICU SCD. Methods: We convened a multidisciplinary group with relevant expertise to participate in an American Thoracic Society Workshop. Workshop objectives included identifying ICU SCD subtopics of interest, key knowledge gaps, and research priorities. Members attended remote sessions from March to November 2021. Recorded presentations were prepared and viewed by members before Workshop sessions. Workshop discussion focused on key gaps and related research priorities. The priorities listed herein were selected on the basis of rank as established by a series of anonymous surveys. Results: We identified the following research priorities: establish an ICU SCD definition, further develop rigorous and feasible ICU SCD measures, test associations between ICU SCD domains and outcomes, promote the inclusion of mechanistic and patient-centered outcomes within large clinical studies, leverage implementation science strategies to maximize intervention fidelity and sustainability, and collaborate among investigators to harmonize methods and promote multisite investigation. Conclusions: ICU SCD is a complex and compelling potential target for improving ICU outcomes. Given the influence on all other research priorities, further development of rigorous, feasible ICU SCD measurement is a key next step in advancing the field.

Sleep Assessment in Critically Ill Adults: Established Methods and Emerging Strategies.

Sleep is a biological mandate with an integral role in optimizing functions that maintain psychological and physical health. During critical illness, however, sleep may be disrupted at best and elusive at worst. Sleep improvement efforts and research endeavors evaluating interventions to improve sleep in critically ill adults are hampered by limited methods available to measure sleep in this setting. This narrative review summarizes available modalities for sleep assessment in the ICU, describes new ICU sleep assessment methods under development, and highlights features of the ideal ICU sleep measurement tool. DATA SOURCES: The most relevant literature and author experiences were assessed for inclusion from PubMed and textbooks. STUDY SELECTION: The authors selected studies for inclusion by consensus. DATA EXTRACTION: The authors reviewed each study and selected appropriate data for inclusion by consensus. DATA SYNTHESIS: Currently available tools to measure sleep in critically ill adults have important flaws. Subjective measurements are limited by recall bias, the inability of many patients to communicate, and poorly correlate with objective measures when completed by surrogates. Actigraphy does not consider the effects of sedating medications or myopathy leading to an over estimation of sleep time. Polysomnography, the gold standard for sleep assessment, is limited by interpretation issues and practical application concerns. Single and multiple channel electroencephalogram devices offer real-time physiologic data and are more practical to use than polysomnography but are limited by the scope of sleep-specific information they can measure and poorly characterize the circadian system. CONCLUSIONS: A measurement tool that offers real-time sleep and circadian assessment and is practical for broad application in the ICU does not exist. Newer sleep assessment devices have shown promise in measuring physiologic data in real time; when used in combination with other assessment modalities, and analyzed by computational techniques, they may revolutionize sleep monitoring in the ICU.

Characterization of Nocturnal Neuroactive Medication Use and Related Sleep Documentation in Critically Ill Adults.

We retrospectively characterized scheduled, newly initiated, nocturnal neuroactive medication use, and related clinician documentation, in a cohort of consecutive adults admitted greater than or equal to 24 hours to seven different medical/surgical ICUs at two academic centers who had not received a scheduled nocturnal neuroactive medication prior to admission, over a 5-month period (April 1, 2017, to August 31, 2017). A total of 207 different newly initiated, scheduled nocturnal neuroactive medication orders were written (melatonin agonist 101 [48.8%], antipsychotic 80 [38.6%], antidepressant 17 [8.2%], benzodiazepine 9 [4.3%]) in 189 (9.7%) of the 1,955 patients. Among the 1,553 nights, the 189 patients spent in the ICU, a scheduled nocturnal neuroactive medication was administered on 1,103 (71%), an "as needed" nocturnal neuroactive medication was solely administered on 183 (11.8%), delirium occurred on 736 (47.4%), and nurses were twice as likely as physicians (28.8% vs 11.4%; p < 0.0001) to document a note about sleep quality. Among the 69.8% of patients discharged to the floor, and the 64.5% from the hospital, the scheduled nocturnal neuroactive medication was continued in 85.6% and 87.3%, respectively. Scheduled nocturnal neuroactive medication initiation is common, often continued beyond hospital discharge, and poorly documented.

Lessons from Pharmacovigilance: Pulmonary Immune-Related Adverse Events After Immune Checkpoint Inhibitor Therapy.

PURPOSE: To characterize pulmonary toxicities associated with the use of novel immune checkpoint inhibitors METHODS: Adverse event reports from immune checkpoint inhibitors targeting PD-1/L1 and CTLA-4 were captured from the W.H.O pharmacovigilance database (VigiBase) up until Dec. 31st 2019 and were analyzed to evaluate for measures of association between the use of immune checkpoint inhibitors and pulmonary toxicities. Disproportionality analysis using both frequentist and Bayesian approaches were used to detect signals between pulmonary immune-related adverse events and the use of these agents. RESULTS: A total of 9202 adverse pulmonary immune checkpoint inhibitor-related events were captured up until 2019. Adverse pulmonary events were compromised of 1305 airway, 18 alveolar, 5491 interstitial, 898 pleural, 560 vascular and 939 non-specific pulmonary events. We found a common association between all immune checkpoint inhibitors studied and pneumonitis, interstitial lung disease, pulmonary embolism and respiratory failure. We also noted other associations between immune checkpoint inhibitors, however not as uniformly across agents. Most of these immune-related adverse drug reactions were noted to be severe and accounted for a significant source of mortality in the reported cases. CONCLUSION: Immune checkpoint inhibitors are associated with a spectrum of inflammatory pulmonary toxicities. The breadth of pulmonary complications and prevalence may be underappreciated with the use of these agents.

Impact of COVID-19 on Patients with Cancer Receiving Immune Checkpoint Inhibitors.

Introduction: To evaluate the impact of Sars-Cov-2 infection on mortality and immune checkpoint inhibitor (ICI) toxicity in patients with cancer receiving ICIs compared to those not receiving ICIs. Methods: We conducted a retrospective matched cohort study of 25 patients receiving ICIs within 1 year of coronavirus disease 2019 (COVID-19) diagnosis between March 20, 2020, and June 3, 2020, at the Dana-Farber Cancer Institute/Mass General Brigham. Cases were matched 1:1 with controls based on age, sex, and anticancer therapy within the prior 6 months. Results: Seven of 25 (28%) patients receiving ICIs died from COVID-19 as compared with nine of 25 (36%) controls. Through multivariable analysis adjusting for age, sex, and anticancer therapy, ICI use was not associated with increased risk for COVID-19 death (OR [odds ratio] 0.36, 95% CI 0.07-1.87). Determinants of mortality included age (OR 1.14, 95% CI 1.03-1.27) and chronic obstructive pulmonary disease (OR 12.26, 95% CI 1.76-85.14). Statin use was protective against mortality (OR 0.08, 95% CI 0.01-0.63). Two patients experienced persistent immune-related adverse events (irAEs) (hypophysitis); one had new-onset irAE (hypothyroidism) during their COVID-19 course. Patients with ICIs had significantly higher platelet (p = 0.017) and D-dimer (p = 0.037) levels. Elevated troponin levels (p = 0.01) were associated with COVID-19 death in patients using ICI. Conclusion: There is insufficient evidence to conclude COVID-19-related outcomes are associated with ICIs, and we did not observe an increased risk of COVID-19-related death associated with ICIs. The potential protective effect of statin therapy and role of laboratory biomarkers warrant further investigation.

Patients' and Their Caregivers' Interest in Learning About Post-ICU Syndrome and Seeking Help for It.

Critical Illness Recovery Programs report low attendance. We aimed to provide information about postintensive care syndrome and to learn which patients would pursue help in a Critical Illness Recovery Clinic. All patients who checked in to our Lung Center were given a survey regarding their ICU experience and offered information about postintensive care syndrome and an appointment in the clinic. Nine hundred and twenty respondents reported having had an ICU experience: 37% of former ICU patients reported difficulty returning to their normal lives afterward compared with 21% who were family or close friends of a former ICU patient. Only 5% requested information and less than 1% requested a dedicated appointment. More than one of three former ICU patients and one in five close friends or relatives of former ICU patients reported difficulty returning to their normal lives after their ICU experience. Very few pursued the opportunity to learn more about it or seek help.

Evaluation of the Efficacy and Safety of Inhaled Epoprostenol and Inhaled Nitric Oxide for Refractory Hypoxemia in Patients With Coronavirus Disease 2019.

OBJECTIVES: The objectives of this study were to evaluate the efficacy and safety of inhaled epoprostenol and inhaled nitric oxide in patients with refractory hypoxemia secondary to coronavirus disease 2019. DESIGN: Retrospective single-center study. SETTING: ICUs at a large academic medical center in the United States. PATIENTS: Thirty-eight adult critically ill patients with coronavirus disease 2019 and refractory hypoxemia treated with either inhaled epoprostenol or inhaled nitric oxide for at least 1 hour between March 1, 2020, and June 30, 2020. INTERVENTIONS: Electronic chart review. MEASUREMENTS AND MAIN RESULTS: Of 93 patients screened, 38 were included in the analysis, with mild (4, 10.5%), moderate (24, 63.2%), or severe (10, 26.3%), with acute respiratory distress syndrome. All patients were initiated on inhaled epoprostenol as the initial pulmonary vasodilator and the median time from intubation to initiation was 137 hours (68-228 h). The median change in Pao2/Fio2 was 0 (-12.8 to 31.6) immediately following administration of inhaled epoprostenol. Sixteen patients were classified as responders (increase Pao2/Fio2 > 10%) to inhaled epoprostenol, with a median increase in Pao2/Fio2 of 34.1 (24.3-53.9). The mean change in Pao2 and Spo2 was -0.55 ± 41.8 and -0.6 ± 4.7, respectively. Eleven patients transitioned to inhaled nitric oxide with a median change of 11 (3.6-24.8) in Pao2/Fio2. A logistic regression analysis did not identify any differences in outcomes or characteristics between the responders and the nonresponders. Minimal adverse events were seen in patients who received either inhaled epoprostenol or inhaled nitric oxide. CONCLUSIONS: We found that the initiation of inhaled epoprostenol and inhaled nitric oxide in patients with refractory hypoxemia secondary to coronavirus disease 2019, on average, did not produce significant increases in oxygenation metrics. However, a group of patients had significant improvement with inhaled epoprostenol and inhaled nitric oxide. Administration of inhaled epoprostenol or inhaled nitric oxide may be considered in patients with severe respiratory failure secondary to coronavirus disease 2019.

A Systematic Review of Risk Factors for Sleep Disruption in Critically Ill Adults.

OBJECTIVES: Numerous risk factors for sleep disruption in critically ill adults have been described. We performed a systematic review of all risk factors associated with sleep disruption in the ICU setting. DATA SOURCES: PubMed, EMBASE, CINAHL, Web of Science, Cochrane Central Register for Controlled Trials, and Cochrane Database of Systematic Reviews. STUDY SELECTION: English-language studies of any design published between 1990 and April 2018 that evaluated sleep in greater than or equal to 10 critically ill adults (> 18 yr old) and investigated greater than or equal to 1 potential risk factor for sleep disruption during ICU stay. We assessed study quality using Newcastle-Ottawa Scale or Cochrane Risk of Bias tool. DATA EXTRACTION: We abstracted all data independently and in duplicate. Potential ICU sleep disruption risk factors were categorized into three categories based on how data were reported: 1) patient-reported reasons for sleep disruption, 2) patient-reported ratings of potential factors affecting sleep quality, and 3) studies reporting a statistical or temporal association between potential risk factors and disrupted sleep. DATA SYNTHESIS: Of 5,148 citations, we included 62 studies. Pain, discomfort, anxiety/fear, noise, light, and ICU care-related activities are the most common and widely studied patient-reported factors causing sleep disruption. Patients rated noise and light as the most sleep-disruptive factors. Higher number of comorbidities, poor home sleep quality, home sleep aid use, and delirium were factors associated with sleep disruption identified in available studies. CONCLUSIONS: This systematic review summarizes all premorbid, illness-related, and ICU-related factors associated with sleep disruption in the ICU. These findings will inform sleep promotion efforts in the ICU and guide further research in this field.

A bronchial-airway gene-expression classifier to improve the diagnosis of lung cancer: Clinical outcomes and cost-effectiveness analysis.

Bronchoscopy is the safest procedure for lung cancer diagnosis when an invasive evaluation is required after imaging procedures. However, its sensitivity is relatively low, especially for small and peripheral lesions. We assessed benefits and costs of introducing a bronchial gene-expression classifier (BGC) to improve the performance of bronchoscopy and the overall diagnostic process for early detection of lung cancer. We used discrete-event simulation to compare clinical and economic outcomes of two different strategies with the standard practice in former and current smokers with indeterminate nodules: (i) location-based strategy-integrated the BGC to the bronchoscopy indication; (ii) simplified strategy-extended use of bronchoscopy plus BGC also on small and peripheral lesions. Outcomes modeled were rate of invasive procedures, quality-adjusted-life-years (QALYs), costs and incremental cost-effectiveness ratios. Compared to the standard practice, the location-based strategy (i) reduced absolute rate of invasive procedures by 3.3% without increasing costs at the current BGC market price. It resulted in savings when the BGC price was less than $3,000. The simplified strategy (ii) reduced absolute rate of invasive procedures by 10% and improved quality-adjusted life expectancy, producing an incremental cost-effectiveness ratio of $10,109 per QALY. In patients with indeterminate nodules, both BGC strategies reduced unnecessary invasive procedures at high risk of adverse events. Moreover, compared to the standard practice, the simplified use of BGC for central and peripheral lesions resulted in larger QALYs gains at acceptable cost. The location-based is cost-saving if the price of classifier declines.

Enablers and Barriers to Implementing ICU Follow-Up Clinics and Peer Support Groups Following Critical Illness: The Thrive Collaboratives.

OBJECTIVES: Data are lacking regarding implementation of novel strategies such as follow-up clinics and peer support groups, to reduce the burden of postintensive care syndrome. We sought to discover enablers that helped hospital-based clinicians establish post-ICU clinics and peer support programs, and identify barriers that challenged them. DESIGN: Qualitative inquiry. The Consolidated Framework for Implementation Research was used to organize and analyze data. SETTING: Two learning collaboratives (ICU follow-up clinics and peer support groups), representing 21 sites, across three continents. SUBJECTS: Clinicians from 21 sites. MEASUREMENT AND MAIN RESULTS: Ten enablers and nine barriers to implementation of "ICU follow-up clinics" were described. A key enabler to generate support for clinics was providing insight into the human experience of survivorship, to obtain interest from hospital administrators. Significant barriers included patient and family lack of access to clinics and clinic funding. Nine enablers and five barriers to the implementation of "peer support groups" were identified. Key enablers included developing infrastructure to support successful operationalization of this complex intervention, flexibility about when peer support should be offered, belonging to the international learning collaborative. Significant barriers related to limited attendance by patients and families due to challenges in creating awareness, and uncertainty about who might be appropriate to attend and target in advertising. CONCLUSIONS: Several enablers and barriers to implementing ICU follow-up clinics and peer support groups should be taken into account and leveraged to improve ICU recovery. Among the most important enablers are motivated clinician leaders who persist to find a path forward despite obstacles.

Key mechanisms by which post-ICU activities can improve in-ICU care: results of the international THRIVE collaboratives.

OBJECTIVE: To identify the key mechanisms that clinicians perceive improve care in the intensive care unit (ICU), as a result of their involvement in post-ICU programs. METHODS: Qualitative inquiry via focus groups and interviews with members of the Society of Critical Care Medicine's THRIVE collaborative sites (follow-up clinics and peer support). Framework analysis was used to synthesize and interpret the data. RESULTS: Five key mechanisms were identified as drivers of improvement back into the ICU: (1) identifying otherwise unseen targets for ICU quality improvement or education programs-new ideas for quality improvement were generated and greater attention paid to detail in clinical care. (2) Creating a new role for survivors in the ICU-former patients and family members adopted an advocacy or peer volunteer role. (3) Inviting critical care providers to the post-ICU program to educate, sensitize, and motivate them-clinician peers and trainees were invited to attend as a helpful learning strategy to gain insights into post-ICU care requirements. (4) Changing clinician's own understanding of patient experience-there appeared to be a direct individual benefit from working in post-ICU programs. (5) Improving morale and meaningfulness of ICU work-this was achieved by closing the feedback loop to ICU clinicians regarding patient and family outcomes. CONCLUSIONS: The follow-up of patients and families in post-ICU care settings is perceived to improve care within the ICU via five key mechanisms. Further research is required in this novel area.

Models of Peer Support to Remediate Post-Intensive Care Syndrome: A Report Developed by the Society of Critical Care Medicine Thrive International Peer Support Collaborative.

OBJECTIVES: Patients and caregivers can experience a range of physical, psychologic, and cognitive problems following critical care discharge. The use of peer support has been proposed as an innovative support mechanism. DESIGN: We sought to identify technical, safety, and procedural aspects of existing operational models of peer support, among the Society of Critical Care Medicine Thrive Peer Support Collaborative. We also sought to categorize key distinctions between these models and elucidate barriers and facilitators to implementation. SUBJECTS AND SETTING: Seventeen Thrive sites from the United States, United Kingdom, and Australia were represented by a range of healthcare professionals. MEASUREMENTS AND MAIN RESULTS: Via an iterative process of in-person and email/conference calls, members of the Collaborative defined the key areas on which peer support models could be defined and compared, collected detailed self-reports from all sites, reviewed the information, and identified clusters of models. Barriers and challenges to implementation of peer support models were also documented. Within the Thrive Collaborative, six general models of peer support were identified: community based, psychologist-led outpatient, models-based within ICU follow-up clinics, online, groups based within ICU, and peer mentor models. The most common barriers to implementation were recruitment to groups, personnel input and training, sustainability and funding, risk management, and measuring success. CONCLUSIONS: A number of different models of peer support are currently being developed to help patients and families recover and grow in the postcritical care setting.

Clinical Practice Guidelines for the Prevention and Management of Pain, Agitation/Sedation, Delirium, Immobility, and Sleep Disruption in Adult Patients in the ICU.

OBJECTIVE: To update and expand the 2013 Clinical Practice Guidelines for the Management of Pain, Agitation, and Delirium in Adult Patients in the ICU. DESIGN: Thirty-two international experts, four methodologists, and four critical illness survivors met virtually at least monthly. All section groups gathered face-to-face at annual Society of Critical Care Medicine congresses; virtual connections included those unable to attend. A formal conflict of interest policy was developed a priori and enforced throughout the process. Teleconferences and electronic discussions among subgroups and whole panel were part of the guidelines' development. A general content review was completed face-to-face by all panel members in January 2017. METHODS: Content experts, methodologists, and ICU survivors were represented in each of the five sections of the guidelines: Pain, Agitation/sedation, Delirium, Immobility (mobilization/rehabilitation), and Sleep (disruption). Each section created Population, Intervention, Comparison, and Outcome, and nonactionable, descriptive questions based on perceived clinical relevance. The guideline group then voted their ranking, and patients prioritized their importance. For each Population, Intervention, Comparison, and Outcome question, sections searched the best available evidence, determined its quality, and formulated recommendations as "strong," "conditional," or "good" practice statements based on Grading of Recommendations Assessment, Development and Evaluation principles. In addition, evidence gaps and clinical caveats were explicitly identified. RESULTS: The Pain, Agitation/Sedation, Delirium, Immobility (mobilization/rehabilitation), and Sleep (disruption) panel issued 37 recommendations (three strong and 34 conditional), two good practice statements, and 32 ungraded, nonactionable statements. Three questions from the patient-centered prioritized question list remained without recommendation. CONCLUSIONS: We found substantial agreement among a large, interdisciplinary cohort of international experts regarding evidence supporting recommendations, and the remaining literature gaps in the assessment, prevention, and treatment of Pain, Agitation/sedation, Delirium, Immobility (mobilization/rehabilitation), and Sleep (disruption) in critically ill adults. Highlighting this evidence and the research needs will improve Pain, Agitation/sedation, Delirium, Immobility (mobilization/rehabilitation), and Sleep (disruption) management and provide the foundation for improved outcomes and science in this vulnerable population.

Methodologic Innovation in Creating Clinical Practice Guidelines: Insights From the 2018 Society of Critical Care Medicine Pain, Agitation/Sedation, Delirium, Immobility, and Sleep Disruption Guideline Effort.

OBJECTIVES: To describe novel guideline development strategies created and implemented as part of the Society of Critical Care Medicine's 2018 clinical practice guidelines for pain, agitation (sedation), delirium, immobility (rehabilitation/mobility), and sleep (disruption) in critically ill adults. DESIGN: We involved critical illness survivors from start to finish, used and expanded upon Grading of Recommendations, Assessment, Development and Evaluation methodology for making recommendations, identified evidence gaps, and developed communication strategies to mitigate challenges. SETTING/SUBJECTS: Thirty-two experts from five countries, across five topic-specific sections; four methodologists, two medical librarians, four critical illness survivors, and two Society of Critical Care Medicine support staff. INTERVENTIONS: Unique approaches included the following: 1) critical illness survivor involvement to help ensure patient-centered questions and recommendations; 2) qualitative and semiquantitative approaches for developing descriptive statements; 3) operationalizing a three-step approach to generating final recommendations; and 4) systematic identification of evidence gaps. MEASUREMENTS AND MAIN RESULTS: Critical illness survivors contributed to prioritizing topics, questions, and outcomes, evidence interpretation, recommendation formulation, and article review to ensure that their values and preferences were considered in the guidelines. Qualitative and semiquantitative approaches supported formulating descriptive statements using comprehensive literature reviews, summaries, and large-group discussion. Experts (including the methodologists and guideline chairs) developed and refined guideline recommendations through monthly topic-specific section conference calls. Recommendations were precirculated to all members, presented to, and vetted by, most members at a live meeting. Final electronic voting provided links to all forest plots, evidence summaries, and "evidence to decision" frameworks. Written comments during voting captured dissenting views and were integrated into evidence to decision frameworks and the guideline article. Evidence gaps, reflecting clinical uncertainty in the literature, were identified during the evidence to decision process, live meeting, and voting and formally incorporated into all written recommendation rationales. Frequent scheduled "check-ins" mitigated communication gaps. CONCLUSIONS: Our multifaceted, interdisciplinary approach and novel methodologic strategies can help inform the development of future critical care clinical practice guidelines.

Laboratory Tests and X-ray Imaging in a Surgical Intensive Care Unit: Checking the Checklist.

CONTEXT: Patients in the surgical intensive care unit (ICU) frequently undergo laboratory and imaging testing. These tests can lead to iatrogenic anemia and radiation exposure. Many of these tests may be unnecessary for the management of a patient's illness in the surgical ICU, and their ordering may be a reflex rather than in response to a clinical question. Checklists have been used in critical care to identify and address patient care strategies. OBJECTIVE: To examine whether adding a "diagnostic testing" section to a daily checklist used for patient rounds in a surgical ICU would decrease the amount of laboratory tests and chest x-ray imaging ordered. METHODS: An additional section was added to an established ICU daily checklist, which included the following 2 questions: "Is a [chest x-ray] needed for clinical management tomorrow?" and "What laboratory tests are medically necessary for tomorrow?" Comparison was made between 3-month preintervention (control group) and intervention (intervention group) periods. Medical records of hospitalized patients during the preintervention and intervention periods were compared to determine differences in the number of tests ordered per day during each period. RESULTS: A total of 307 adult patients at a single institution were included in the analysis: 155 in the control group and 152 in the intervention group. The patients in each group were similar in terms of sex, age, Sequential Organ Failure scores, Charlson Comorbidity Index scores, elective admission status, surgical procedures, number of days of mechanical ventilation, ICU length of stay, and in-hospital death. No statistical reductions in laboratory tests or chest x-ray imaging ordered per day from the preintervention to intervention period were found. CONCLUSION: The addition of the diagnostic testing section to the daily checklist did not result in a reduction of the amount of tests ordered per day. Further research on test appropriateness and the possible addition of a clinician decision-making tool could be studied in the future to assist with reduction of tests ordered in the surgical ICU.