Fluid Management in Acute Respiratory Failure.

Fluid management in acute respiratory failure is an area of uncertainty requiring a delicate balance of resuscitation and fluid removal to manage hypoperfusion and avoidance of hypoxemia. Overall, a restrictive fluid strategy (minimizing fluid administration) and careful attention to overall fluid balance may be beneficial after initial resuscitation and does not have major side effects. Further studies are needed to improve our understanding of patients who will benefit from a restrictive or liberal fluid management strategy.

Nonimaging Diagnostic Tests for Pneumonia.

This article reviews the various nonimaging diagnostic tests available for the diagnosis of pneumonia including the methods by which specimens are obtained and the speed at which certain tests are available. Because tests results may be available at the time of radiologic image interpretation, it is important for the radiologist to be aware of the type of specimens and diagnostic tests to search for in the electronic medical record in order to provide a more refined imaging report. Diagnostic tests for the most common bacterial, fungal, viral, and parasitic infections are discussed.

Variation in Early Management Practices in Moderate-to-Severe ARDS in the United States: The Severe ARDS: Generating Evidence Study.

BACKGROUND: Although specific interventions previously demonstrated benefit in patients with ARDS, use of these interventions is inconsistent, and patient mortality remains high. The impact of variability in center management practices on ARDS mortality rates remains unknown. RESEARCH QUESTION: What is the impact of treatment variability on mortality in patients with moderate to severe ARDS in the United States? STUDY DESIGN AND METHODS: We conducted a multicenter, observational cohort study of mechanically ventilated adults with ARDS and Pao2 to Fio2 ratio of ≤ 150 with positive end-expiratory pressure of ≥ 5 cm H2O, who were admitted to 29 US centers between October 1, 2016, and April 30, 2017. The primary outcome was 28-day in-hospital mortality. Center variation in ventilator management, adjunctive therapy use, and mortality also were assessed. RESULTS: A total of 2,466 patients were enrolled. Median baseline Pao2 to Fio2 ratio was 105 (interquartile range, 78.0-129.0). In-hospital 28-day mortality was 40.7%. Initial adherence to lung protective ventilation (LPV; tidal volume, ≤ 6.5 mL/kg predicted body weight; plateau pressure, or when unavailable, peak inspiratory pressure, ≤ 30 mm H2O) was 31.4% and varied between centers (0%-65%), as did rates of adjunctive therapy use (27.1%-96.4%), methods used (neuromuscular blockade, prone positioning, systemic steroids, pulmonary vasodilators, and extracorporeal support), and mortality (16.7%-73.3%). Center standardized mortality ratios (SMRs), calculated using baseline patient-level characteristics to derive expected mortality rate, ranged from 0.33 to 1.98. Of the treatment-level factors explored, only center adherence to early LPV was correlated with SMR. INTERPRETATION: Substantial center-to-center variability exists in ARDS management, suggesting that further opportunities for improving ARDS outcomes exist. Early adherence to LPV was associated with lower center mortality and may be a surrogate for overall quality of care processes. Future collaboration is needed to identify additional treatment-level factors influencing center-level outcomes. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT03021824; URL: www.clinicaltrials.gov.

Promoting Evidence-Based Practice in Acute Respiratory Distress Syndrome: A Systematic Review.

Low tidal volume ventilation and prone positioning are recommended therapies yet underused in acute respiratory distress syndrome. We aimed to assess the role of interventions focused on implementation of low tidal volume ventilation and prone positioning in mechanically ventilated adult patients with acute respiratory distress syndrome. DATA SOURCES: PubMed, Excerpta Medica Database, Cumulative Index to Nursing and Allied Health Literature, and Cochrane Central Register of Controlled Trials. STUDY SELECTION: We searched the four databases from January 1, 2001, to January 28, 2021, for studies that met the predefined search criteria. Selected studies focused on interventions to improve implementation of low tidal volume ventilation and prone positioning in mechanically ventilated patients with acute respiratory distress syndrome. DATA EXTRACTION: Two authors independently performed study selection and data extraction using a standardized form. DATA SYNTHESIS: Due to methodological heterogeneity of included studies, meta-analysis was not feasible; thus, we provided a narrative summary and assessment of the literature. Eight nonrandomized studies met our eligibility criteria. Most studies looked at interventions to improve adherence to low tidal volume ventilation. Most interventions focused on education for providers. Studies were primarily conducted in the ICU and involved trainees, intensivists, respiratory therapists, and critical care nurses. Although overall quality of the studies was very low, the primary outcomes of interest suggest that interventions could improve adherence to or implementation of low tidal volume ventilation and prone positioning in acute respiratory distress syndrome. MEASUREMENTS AND MAIN RESULTS: Two authors independently performed study selection and data extraction using a standardized form. Due to methodologic heterogeneity of included studies, meta-analysis was not feasible; thus, we provided a narrative summary and assessment of the literature. Eight nonrandomized studies met our eligibility criteria. Most studies looked at interventions to improve adherence to low tidal volume ventilation. Most interventions focused on education for providers. Studies were primarily conducted in the ICU and involved trainees, intensivists, respiratory therapists, and critical care nurses. Although overall quality of the studies was very low, the primary outcomes of interest suggest that interventions could improve adherence to or implementation of low tidal volume ventilation and prone positioning in acute respiratory distress syndrome. CONCLUSIONS: There is a dearth of literature addressing interventions to improve implementation of evidence-based practices in acute respiratory distress syndrome. Existing interventions to improve clinician knowledge and facilitate application of low tidal volume ventilation and prone positioning may be effective, but supporting studies have significant limitations.

Should the CIWA-Ar be the standard monitoring strategy for alcohol withdrawal syndrome in the intensive care unit?

BACKGROUND: The Clinical Institute Withdrawal Assessment for Alcohol-Revised (CIWA-Ar) is commonly used in hospitals to titrate medications for alcohol withdrawal syndrome (AWS), but may be difficult to apply to intensive care unit (ICU) patients who are too sick or otherwise unable to communicate. OBJECTIVES: To evaluate the frequency of CIWA-Ar monitoring among ICU patients with AWS and variation in CIWA-Ar monitoring across patient demographic and clinical characteristics. METHODS: The study included all adults admitted to an ICU in 2017 after treatment for AWS in the Emergency Department of an academic hospital that standardly uses the CIWA-Ar to assess AWS severity and response to treatment. Demographic and clinical data, including Richmond Agitation-Sedation Scale (RASS) assessments (an alternative measure of agitation/sedation), were obtained via chart review. Associations between patient characteristics and CIWA-Ar monitoring were tested using logistic regression. RESULTS: After treatment for AWS, only 56% (n = 54/97) of ICU patients were evaluated using the CIWA-Ar; 94% of patients had a documented RASS assessment (n = 91/97). Patients were significantly less likely to receive CIWA-Ar monitoring if they were intubated or identified as Black. CONCLUSIONS: CIWA-Ar monitoring was used inconsistently in ICU patients with AWS and completed less often in those who were intubated or identified as Black. These hypothesis-generating findings raise questions about the utility of the CIWA-Ar in ICU settings. Future studies should assess alternative measures for titrating AWS medications in the ICU that do not require verbal responses from patients and further explore the association of race with AWS monitoring.

Hyperammonemia syndrome due to Ureaplasma infection after liver-kidney transplant.

Hyperammonemia syndrome, with high levels of ammonia and neurologic dysfunction, is a syndrome with historically high mortality that may occur after solid organ transplantation. Recently, this has been associated with infection due to Ureaplasma, mostly following lung transplantation. We describe the first case of hyperammonemia syndrome due to Ureaplasma infection after liver-kidney transplantation. Our patient rapidly recovered after specific antibiotic treatment. It is important to consider these infections in the differential diagnosis for encephalopathy post-transplant, as these organisms often do not grow using routine culture methods and polymerase chain reaction testing is typically required for their detection. This is particularly critical after liver transplantation, where a number of other etiologies may be considered as a cause of hyperammonemia syndrome.

Impact of Vasoactive Medications on ICU-Acquired Weakness in Mechanically Ventilated Patients.

BACKGROUND: Vasoactive medications are commonly used in the treatment of critically ill patients, but their impact on the development of ICU-acquired weakness is not well described. The objective of this study is to evaluate the relationship between vasoactive medication use and the outcome of ICU-acquired weakness. METHODS: This is a secondary analysis of mechanically ventilated patients (N = 172) enrolled in a randomized clinical trial of early occupational and physical therapy vs conventional therapy, which evaluated the end point of ICU-acquired weakness on hospital discharge. Patients underwent bedside muscle strength testing by a therapist blinded to study allocation to evaluate for ICU-acquired weakness. The effects of vasoactive medication use on the incidence of ICU-acquired weakness in this population were assessed. RESULTS: On logistic regression analysis, the use of vasoactive medications increased the odds of developing ICU-acquired weakness (odds ratio [OR], 3.2; P = .01) independent of all other established risk factors for weakness. Duration of vasoactive medication use (in days) (OR, 1.35; P = .004) and cumulative norepinephrine dose (µg/kg/d) (OR, 1.01; P = .02) (but not vasopressin or phenylephrine) were also independently associated with the outcome of ICU-acquired weakness. CONCLUSIONS: In mechanically ventilated patients enrolled in a randomized clinical trial of early mobilization, the use of vasoactive medications was independently associated with the development of ICU-acquired weakness. Prospective trials to further evaluate this relationship are merited. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01777035; URL: www.clinicaltrials.gov.

Molecular Screen Identifies Cardiac Myosin-Binding Protein-C as a Protein Kinase G-Iα Substrate.

BACKGROUND: Pharmacological activation of cGMP-dependent protein kinase G I (PKGI) has emerged as a therapeutic strategy for humans with heart failure. However, PKG-activating drugs have been limited by hypotension arising from PKG-induced vasodilation. PKGIα antiremodeling substrates specific to the myocardium might provide targets to circumvent this limitation, but currently remain poorly understood. METHODS AND RESULTS: We performed a screen for myocardial proteins interacting with the PKGIα leucine zipper (LZ)-binding domain to identify myocardial-specific PKGI antiremodeling substrates. Our screen identified cardiac myosin-binding protein-C (cMyBP-C), a cardiac myocyte-specific protein, which has been demonstrated to inhibit cardiac remodeling in the phosphorylated state, and when mutated leads to hypertrophic cardiomyopathy in humans. GST pulldowns and precipitations with cGMP-conjugated beads confirmed the PKGIα-cMyBP-C interaction in myocardial lysates. In vitro studies demonstrated that purified PKGIα phosphorylates the cMyBP-C M-domain at Ser-273, Ser-282, and Ser-302. cGMP induced cMyBP-C phosphorylation at these residues in COS cells transfected with PKGIα, but not in cells transfected with LZ mutant PKGIα, containing mutations to disrupt LZ substrate binding. In mice subjected to left ventricular pressure overload, PKGI activation with sildenafil increased cMyBP-C phosphorylation at Ser-273 compared with untreated mice. cGMP also induced cMyBP-C phosphorylation in isolated cardiac myocytes. CONCLUSIONS: Taken together, these data support that PKGIα and cMyBP-C interact in the heart and that cMyBP-C is an anti remodeling PKGIα kinase substrate. This study provides the first identification of a myocardial-specific PKGIα LZ-dependent antiremodeling substrate and supports further exploration of PKGIα myocardial LZ substrates as potential therapeutic targets for heart failure.