Discordance Between Invasive and NonInvasive Oxygen Saturation in Critically Ill COVID-19 Patients.

OBJECTIVES: To investigate discordance in oxy-hemoglobin saturation measured both by pulse oximetry (SpO2) and arterial blood gas (ABG, SaO2) among critically ill coronavirus disease 2019 (COVID-19(+)) patients compared to COVID-19(-) patients. METHODS: Paired SpO2 and SaO2 readings were collected retrospectively from consecutive adult admissions to four critical care units in the United States between March and May 2020. The primary outcome was the rate of discordance (|SaO2-SpO2|>4%) in COVID-19(+) versus COVID-19(-) patients. The odds each cohort could have been incorrectly categorized as having a PaO2/FiO2 above or below 150 by their SpO2: Fractional inhaled oxygen ratio (pulse oximetry-derived oxyhemoglobin saturation:fraction of inspired oxygen ratio [SF]) was examined. A multivariate regression analysis assessed confounding by clinical differences between cohorts including pH, body temperature, renal replacement therapy at time of blood draw, and self-identified race. RESULTS: There were 263 patients (173 COVID-19(+)) included. The rate of saturation discordance between SaO2 and SpO2 in COVID-19(+) patients was higher than in COVID-19(-) patients (27.9% vs 16.7%, odds ratio [OR] 1.94, 95% confidence interval [CI]: 1.11 to 2.27). The average difference between SaO2 and SpO2 for COVID-19(+) patients was -1.24% (limits of agreement, -13.6 to 11.1) versus -0.11 [-10.3 to 10.1] for COVID-19(-) patients. COVID-19(+) patients had higher odds (OR: 2.61, 95% CI: 1.14-5.98) of having an SF that misclassified that patient as having a PaO2:FiO2 ratio above or below 150. There was not an association between discordance and the confounders of pH, body temperature, or renal replacement therapy at time of blood draw. After controlling for self-identified race, the association between COVID-19 status and discordance was lost. CONCLUSIONS: Pulse oximetry was discordant with ABG more often in critically ill COVID-19(+) than COVID-19(-) patients. However, these findings appear to be driven by racial differences between cohorts.

Infective Endocarditis-Induced Lung Injury Mimicking Acute Vanishing Lung Syndrome.

Infective endocarditis is the infection of the endocardial surface of the heart valve. The right-sided endocarditis can be complicated by pulmonary injury. The pulmonary complications of infective endocarditis include pulmonary embolism, empyema, pleural effusion, lung abscess, and, in rare cases, pneumothorax. We present a case of bilateral pneumatoceles mimicking vanishing lung syndrome, a very rare pulmonary complication of right-sided infective endocarditis.

Computer clinical decision support that automates personalized clinical care: a challenging but needed healthcare delivery strategy.

How to deliver best care in various clinical settings remains a vexing problem. All pertinent healthcare-related questions have not, cannot, and will not be addressable with costly time- and resource-consuming controlled clinical trials. At present, evidence-based guidelines can address only a small fraction of the types of care that clinicians deliver. Furthermore, underserved areas rarely can access state-of-the-art evidence-based guidelines in real-time, and often lack the wherewithal to implement advanced guidelines. Care providers in such settings frequently do not have sufficient training to undertake advanced guideline implementation. Nevertheless, in advanced modern healthcare delivery environments, use of eActions (validated clinical decision support systems) could help overcome the cognitive limitations of overburdened clinicians. Widespread use of eActions will require surmounting current healthcare technical and cultural barriers and installing clinical evidence/data curation systems. The authors expect that increased numbers of evidence-based guidelines will result from future comparative effectiveness clinical research carried out during routine healthcare delivery within learning healthcare systems.

Implementation of a Longitudinal Critical Care Fellowship Ultrasound Curriculum.

Background: The use of point-of-care ultrasound as a diagnostic and interventional tool is rapidly becoming standard of care in critical care medicine; a standardized training curriculum is needed to ensure provider proficiency. Objective: This study aimed to describe a longitudinal critical care ultrasound (CCUS) curriculum in a pulmonary critical care medicine (PCCM) fellowship training program. It evaluated the curriculum's impact on fellows' knowledge, skills, and self-reported confidence and retention of these attributes. Methods: We conducted a prospective observational study of a longitudinal CCUS training program within a single PCCM fellowship training program. Knowledge, skills, and confidence of 22 fellows were assessed at baseline; after initial training; and at 6, 12, and 18 months in five domains (ultrasound basics, vascular, lung/pleural, abdomen, and cardiac). We quantified changes in CCUS knowledge, confidence, and skills by fellowship class and assessed for longitudinal retention of these three attributes. The difference in scores between new first-year fellows undergoing formal training and second-year fellows with previous informal training was compared at matched time points. Results: After the initial formal training, there was a significant increase in knowledge, skills, and confidence scores, which were maintained or continued to increase up to 18 months. Fellows with 1 year of formal training also had a higher level of knowledge and skills than fellows with 1 year of informal training, although they had similar levels of self-reported confidence in their skills. Conclusion: A formal, longitudinal CCUS curriculum implemented in a PCCM fellowship program improves trainees' knowledge and skills in various ultrasound domains in addition to their confidence in using ultrasound for patient care. A longitudinal curriculum results in retention of all three attributes and appeared to be more effective than an informal training program based on teaching during rounds, but this needs to be replicated in a larger cohort.

Use of Handheld Ultrasound to Estimate Right Atrial Pressure in a Pulmonary Hypertension Clinic.

Rationale: Point-of-care ultrasonography is an invaluable asset for inpatient decision-making. Whether handheld ultrasound can be used in the outpatient management of pulmonary hypertension is unknown. Objectives: We investigated whether a handheld ultrasound estimate of right atrial pressure correlates with B-type natriuretic peptide (BNP) and clinical outcome over time in outpatients with pulmonary hypertension. Methods: This prospective study included outpatients in a Pulmonary Hypertension Comprehensive Care Center clinic who had a same-day BNP concentration. We used a handheld ultrasound to measure inferior vena cava size and collapsibility, which were used to estimate right atrial pressure (eRAP) and categorize it as normal, intermediate, or high. Correlation analysis was used to compare these ultrasound measurements with BNP at baseline and over time. Cox regression was used to determine whether these measurements were associated with time to clinical worsening. Results: Ninety patients (60% Group 1 pulmonary hypertension) were enrolled. Patients with an intermediate or high eRAP category at baseline had higher BNP concentrations than patients with normal eRAP. For every transition in eRAP category (e.g., from normal to intermediate) between clinic visits, BNP changed by an average of 155 pg/ml (95% confidence interval [CI], 84-227). Higher baseline eRAP category was independently associated with more than twofold increased risk for clinical worsening (hazard ratio, 2.44; 95% CI, 1.47-4.07). Conclusions: Right atrial pressure estimated by portable handheld ultrasound correlates with BNP at baseline and serially over time. Furthermore, eRAP is independently associated with clinical worsening. The use of portable handheld ultrasound to estimate right atrial pressure should be considered in pulmonary hypertension clinics. Clinical trial registered at clinicaltrials.gov (NCT02873039).

Acute effect of inhaled iloprost on exercise dynamic hyperinflation in COPD patients: A randomized crossover study.

BACKGROUND AND OBJECTIVE: We tested whether the prostacyclin analog inhaled iloprost modulates dead space, dynamic hyperinflation (DH), and systemic inflammation/oxidative stress during maximal exercise in subjects with chronic obstructive pulmonary disease (COPD) who were not selected based on pulmonary hypertension (PH). METHODS: Twenty-four COPD patients with moderate-severe obstruction (age 59 ± 7 years, FEV1 53 ± 13% predicted) participated in a randomized, double-blind, placebo-controlled crossover trial. Each subject received a single nebulized dose of 5.0 µg iloprost or placebo on non-consecutive days followed by maximal cardiopulmonary exercise tests. The primary outcome was DH quantified by end-expiratory lung volume/total lung capacity ratio (EELV/TLC) at metabolic isotime. RESULTS: Inhaled iloprost was well-tolerated and reduced submaximal alveolar dead-space fraction but did not significantly reduce DH (0.70 ± 0.09 vs 0.69 ± 0.07 following placebo and iloprost, respectively, p = 0.38). Maximal exercise time (9.1 ± 2.3 vs 9.3 ± 2.2 min, p = 0.31) and peak oxygen uptake (17.4 ± 6.3 vs 17.9 ± 6.9 mL/kg/min, p = 0.30) were not significantly different following placebo versus iloprost. CONCLUSIONS: A single dose of inhaled iloprost was safe and reduced alveolar dead space fraction; however, it was not efficacious in modulating DH or improving exercise capacity in COPD patients who were not selected for the presence of PH.

Enabling a learning healthcare system with automated computer protocols that produce replicable and personalized clinician actions.

Clinical decision-making is based on knowledge, expertise, and authority, with clinicians approving almost every intervention-the starting point for delivery of "All the right care, but only the right care," an unachieved healthcare quality improvement goal. Unaided clinicians suffer from human cognitive limitations and biases when decisions are based only on their training, expertise, and experience. Electronic health records (EHRs) could improve healthcare with robust decision-support tools that reduce unwarranted variation of clinician decisions and actions. Current EHRs, focused on results review, documentation, and accounting, are awkward, time-consuming, and contribute to clinician stress and burnout. Decision-support tools could reduce clinician burden and enable replicable clinician decisions and actions that personalize patient care. Most current clinical decision-support tools or aids lack detail and neither reduce burden nor enable replicable actions. Clinicians must provide subjective interpretation and missing logic, thus introducing personal biases and mindless, unwarranted, variation from evidence-based practice. Replicability occurs when different clinicians, with the same patient information and context, come to the same decision and action. We propose a feasible subset of therapeutic decision-support tools based on credible clinical outcome evidence: computer protocols leading to replicable clinician actions (eActions). eActions enable different clinicians to make consistent decisions and actions when faced with the same patient input data. eActions embrace good everyday decision-making informed by evidence, experience, EHR data, and individual patient status. eActions can reduce unwarranted variation, increase quality of clinical care and research, reduce EHR noise, and could enable a learning healthcare system.

Care erosion in sedation assessment: A prospective comparison of usual care Richmond Agitation-Sedation Scale assessment with protocolized assessment for medical intensive care unit patients.

OBJECTIVES: To determine concordance between an explicit protocolized assessment of the Richmond Agitation-Sedation Scale and an assessment performed during usual care nursing practice. RESEARCH DESIGN: In an urban, safety-net hospital, intensive care nurses previously trained in sedation assessment recorded a bedside Richmond Agitation-Sedation Scale assessment, while study investigators used an explicit script to perform the assessment at a similar time point. Kappa indices determined concordance of the assessments. Bivariate analyses explored factors associated with discordance and unresponsiveness. RESULTS: Twenty-one subjects with 38 observations were analysed. Bedside nursing assessment was poorly concordant with protocolized assessment (ƙ = 0.21) with the former reporting significantly lighter sedation (median -2 vs. -5, p = .01). Bedside assessment was significantly less likely than protocolized assessment to categorize subjects as unresponsive (29 vs. 50%, p = .02). CONCLUSION: Methods used in usual clinical practice to assess adequacy of sedation frequently led to oversedation. We propose that care erosion, the deterioration of skills over time, may help explain this finding. IMPLICATIONS FOR NURSING MANAGEMENT: Results suggest sedation assessment may be particularly vulnerable to care erosion. Nurse managers should monitor for signs of care erosion and consider utilization of explicit scripts during sedation assessment and/or frequent education to ensure sedation assessment accuracy.

Use of red cell distribution width in a population at high risk for pulmonary hypertension.

BACKGROUND: Pulmonary hypertension (PH) often presents with non-specific symptoms making early diagnosis difficult. Red cell distribution width (RDW) is a parameter routinely reported on an automated complete blood cell count that has been associated with numerous disease states. The purpose of this study was to further evaluate RDW as a biomarker for PH in at-risk populations. METHODS: In a retrospective, cross-sectional analysis of patients seen at a PH center over 1 year, we examined both patients with PH and patients at risk for but without PH (e.g. systemic sclerosis, [SSc]). We also studied a group of age-and sex-matched, non-diseased controls. Relevant characteristics were compared among the 3 groups using one-way ANOVA. Similar comparisons were made across World Health Organization (WHO) PH groups 1-4. RESULTS: RDW was highest in the PH patients (n = 181), intermediate in the at-risk for PH patients (n = 52), and lowest in matched controls (n = 100) (15.9 ±â€¯2.8 vs 14.8 ±â€¯2.8 vs 14.2 ±â€¯1.1%, respectively; p < 0.0001). There were no significant differences in RDW across WHO PH groups (p = 0.50). SSc patients with PH had significantly higher RDW values compared to SSc patients without PH (16.0 ±â€¯2.2 vs 14.4 ±â€¯1.9%, respectively; p = 0.03). CONCLUSIONS: RDW is significantly higher in PH patients, without regard to disease etiology, when compared to age- and sex-matched non-diseased controls. Importantly, RDW is also higher in PH patients compared to at-risk patients, particularly in the SSc cohort. The ease of obtaining RDW as a biomarker may help detect incident PH at earlier stages among patients who are at high risk for development of PH.

Microparticles in systemic sclerosis: Potential pro-inflammatory mediators and pulmonary hypertension biomarkers.

BACKGROUND AND OBJECTIVE: Endothelial microparticles (EMP) are submicron vesicles released from endothelial cells. We aimed to determine the utility of EMP as biomarkers of pulmonary arterial hypertension (PAH) in systemic sclerosis (SSc) patients and the pathogenic role of microparticles (MP) in vascular inflammation. METHODS: Levels of EMP (CD144+, CD31+, CD62E+ and CD143+) were compared between three groups (10 SSc patients with PAH, 10 SSc patients without pulmonary hypertension (no-PH) and 10 healthy age- and sex-matched controls). Human pulmonary artery endothelial cells (HPAEC) were exposed in vitro to MP obtained from SSc patients or healthy controls, and levels of cytokines and inflammatory adhesion molecules were compared. RESULTS: CD144+ EMP were significantly higher in the SSc-PAH group compared to either the SSc-no PH or healthy controls (diagnostic accuracy 80%, P = 0.02). Compared to controls, SSc patients had higher CD31+/CD62E+ ratios, indicating larger contributions of apoptosis to EMP release (P = 0.04). Patients with limited SSc had significantly higher levels of CD143+ EMP compared to those with diffuse subtype (P = 0.008). When HPAEC were exposed to MP from SSc patients, there was a significant increase in inflammatory cytokines and adhesion molecules. Interestingly, exposure to healthy control MP caused a reduction in inflammatory markers. CONCLUSION: EMP (particularly CD144+) are promising biomarkers of PAH in SSc but require further study. MP isolated from SSc patients induced an increase in endothelial cell inflammation and may be an important pathogenic factor in SSc.

Effect of Interhospital ICU Relocation on Patient Physiology and Clinical Outcomes.

Relocation of large numbers of critically ill patients between hospitals is sometimes necessary and the risks associated with relocation may be high. In the setting of adherence to an interhospital intensive care unit (ICU) relocation protocol, we aimed to determine whether the interhospital relocation of all ICU patients in a single day is associated with changes in vital signs, device removal, and worse clinical outcomes. We conducted a prospective, observational, cohort study of all critically ill adults admitted to a tertiary medical center's ICUs on the day of a planned hospital relocation and exposed to interhospital ICU relocation compared with unexposed critically ill adults. Changes in vital signs were evaluated by the before-and-after interhospital relocation measurement of vital signs, and clinical outcomes were collected for all patients. A total of 699 patients were admitted to the ICU during the observation period, 24 of whom were exposed to interhospital ICU relocation on a single day. The median interhospital transport duration was 28 minutes (interquartile range: 24-35) and 29% of patients were receiving invasive mechanical ventilation. Patients exposed to interhospital ICU relocation had no significant change in any vital sign measurement and no devices were unintentionally removed. Inhospital mortality was similar (8.3%) to patients not exposed to interhospital ICU relocation (9.2%, P > .99). In the setting of adherence to an ICU relocation protocol, the interhospital ICU relocation of all critically ill adults during a single day is not associated with changes in vital signs, device removal, or worse clinical outcomes.

Liberal Versus Restrictive Intravenous Fluid Therapy for Early Septic Shock: Rationale for a Randomized Trial.

Prompt intravenous fluid therapy is a fundamental treatment for patients with septic shock. However, the optimal approach for administering intravenous fluid in septic shock resuscitation is unknown. Two competing strategies are emerging: a liberal fluids approach, consisting of a larger volume of initial fluid (50 to 75 mL/kg [4 to 6 L in an 80-kg adult] during the first 6 hours) and later use of vasopressors, versus a restrictive fluids approach, consisting of a smaller volume of initial fluid (≤30 mL/kg [≤2 to 3 L]), with earlier reliance on vasopressor infusions to maintain blood pressure and perfusion. Early fluid therapy may enhance or maintain tissue perfusion by increasing venous return and cardiac output. However, fluid administration may also have deleterious effects by causing edema within vital organs, leading to organ dysfunction and impairment of oxygen delivery. Conversely, a restrictive fluids approach primarily relies on vasopressors to reverse hypotension and maintain perfusion while limiting the administration of fluid. Both strategies have some evidence to support their use but lack robust data to confirm the benefit of one strategy over the other, creating clinical and scientific equipoise. As part of the National Heart, Lung, and Blood Institute Prevention and Early Treatment of Acute Lung Injury Network, we designed a randomized clinical trial to compare the liberal and restrictive fluids strategies, the Crystalloid Liberal or Vasopressor Early Resuscitation in Sepsis trial. The purpose of this article is to review the current literature on approaches to early fluid resuscitation in adults with septic shock and outline the rationale for the upcoming trial.

A Multicenter Randomized Trial of a Checklist for Endotracheal Intubation of Critically Ill Adults.

BACKGROUND: Hypoxemia and hypotension are common complications during endotracheal intubation of critically ill adults. Verbal performance of a written, preintubation checklist may prevent these complications. We compared a written, verbally performed, preintubation checklist with usual care regarding lowest arterial oxygen saturation or lowest systolic BP experienced by critically ill adults undergoing endotracheal intubation. METHODS: A multicenter trial in which 262 adults undergoing endotracheal intubation were randomized to a written, verbally performed, preintubation checklist (checklist) or no preintubation checklist (usual care). The coprimary outcomes were lowest arterial oxygen saturation and lowest systolic BP between the time of procedural medication administration and 2 min after endotracheal intubation. RESULTS: The median lowest arterial oxygen saturation was 92% (interquartile range [IQR], 79-98) in the checklist group vs 93% (IQR, 84-100) with usual care (P = .34). The median lowest systolic BP was 112 mm Hg (IQR, 94-133) in the checklist group vs 108 mm Hg (IQR, 90-132) in the usual care group (P = .61). There was no difference between the checklist and usual care in procedure duration (120 vs 118 s; P = .49), number of laryngoscopy attempts (one vs one attempt; P = .42), or severe life-threatening procedural complications (40.8% vs 32.6%; P = .20). CONCLUSIONS: The verbal performance of a written, preprocedure checklist does not increase the lowest arterial oxygen saturation or lowest systolic BP during endotracheal intubation of critically ill adults compared with usual care. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT02497729; URL: www.clinicaltrials.gov.

Use of Digital Pupillometry to Measure Sedative Response to Propofol.

BACKGROUND: Digital pupillometry (DP) accurately and precisely measures pupillary responses. Little is known about using DP to measure the sedative effect of isolated propofol administration. METHODS: We conducted a cross-sectional study of 19 adults undergoing moderate sedation with propofol during which we measured pupillary changes using DP. RESULTS: Maximum and minimum pupillary diameters decreased significantly with propofol (mean change from baseline to procedural termination -1.24 mm, standard error [SE] 0.25 and -0.79 mm, SE 0.13, respectively; P≤0.001 for both). Mean constriction velocity decreased by 0.84 mm/s between baseline and procedural termination (P=0.001). Pupillary latency increased significantly between baseline and induction (mean change 0.016 seconds, SE 0.007; P=0.04) but was not significantly different at other time points. CONCLUSION: We speculate that DP may be a useful tool to monitor propofol sedation.

Recommendations for the clinical management of patients receiving macitentan for pulmonary arterial hypertension (PAH): A Delphi consensus document.

In patients treated with macitentan (Opsumit®, Actelion Pharmaceuticals Ltd., Basel, Switzerland) for pulmonary arterial hypertension (PAH), prevention and/or effective management of treatment-related adverse events may improve adherence. However, management of these adverse events can be challenging and the base of evidence and clinical experience for macitentan is limited. In the absence of evidence, consensus recommendations from physicians experienced in using macitentan to treat PAH may benefit patients and physicians who are using macitentan. Consensus recommendations were developed by a panel of physicians experienced with macitentan and PAH using a modified Delphi process. Over three iterations, panelists developed and refined a series of statements on the use of macitentan in PAH and rated their agreement with each statement on a Likert scale. The panel of 18 physicians participated and developed a total of 118 statements on special populations, add-on therapy, drug-drug interactions, warnings and precautions, hospitalization and functional class, and adverse event management. The resulting consensus recommendations are intended to provide practical guidance on real-world issues in using macitentan to treat patients with PAH.

A Multicenter, Randomized Trial of Ramped Position vs Sniffing Position During Endotracheal Intubation of Critically Ill Adults.

BACKGROUND: Hypoxemia is the most common complication during endotracheal intubation of critically ill adults. Intubation in the ramped position has been hypothesized to prevent hypoxemia by increasing functional residual capacity and decreasing the duration of intubation, but has never been studied outside of the operating room. METHODS: Multicenter, randomized trial comparing the ramped position (head of the bed elevated to 25°) with the sniffing position (torso supine, neck flexed, and head extended) among 260 adults undergoing endotracheal intubation by pulmonary and critical care medicine fellows in four ICUs between July 22, 2015, and July 19, 2016. The primary outcome was lowest arterial oxygen saturation between induction and 2 minutes after intubation. Secondary outcomes included Cormack-Lehane grade of glottic view, difficulty of intubation, and number of laryngoscopy attempts. RESULTS: The median lowest arterial oxygen saturation was 93% (interquartile range [IQR], 84%-99%) with the ramped position vs 92% (IQR, 79%-98%) with the sniffing position (P = .27). The ramped position appeared to increase the incidence of grade III or IV view (25.4% vs 11.5%, P = .01), increase the incidence of difficult intubation (12.3% vs 4.6%, P = .04), and decrease the rate of intubation on the first attempt (76.2% vs 85.4%, P = .02), respectively. CONCLUSIONS: In this multicenter trial, the ramped position did not improve oxygenation during endotracheal intubation of critically ill adults compared with the sniffing position. The ramped position may worsen glottic view and increase the number of laryngoscopy attempts required for successful intubation. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT02497729; URL: www.clinicaltrials.gov.