BACKGROUND: Patients with severe coronavirus disease 2019 (COVID-19) have respiratory failure with hypoxemia and acute bilateral pulmonary infiltrates, consistent with ARDS. Respiratory failure in COVID-19 might represent a novel pathologic entity. RESEARCH QUESTION: How does the lung histopathology described in COVID-19 compare with the lung histopathology described in SARS and H1N1 influenza? STUDY DESIGN AND METHODS: We conducted a systematic review to characterize the lung histopathologic features of COVID-19 and compare them against findings of other recent viral pandemics, H1N1 influenza and SARS. We systematically searched MEDLINE and PubMed for studies published up to June 24, 2020, using search terms for COVID-19, H1N1 influenza, and SARS with keywords for pathology, biopsy, and autopsy. Using PRISMA-Individual Participant Data guidelines, our systematic review analysis included 26 articles representing 171 COVID-19 patients; 20 articles representing 287 H1N1 patients; and eight articles representing 64 SARS patients. RESULTS: In COVID-19, acute-phase diffuse alveolar damage (DAD) was reported in 88% of patients, which was similar to the proportion of cases with DAD in both H1N1 (90%) and SARS (98%). Pulmonary microthrombi were reported in 57% of COVID-19 and 58% of SARS patients, as compared with 24% of H1N1 influenza patients. INTERPRETATION: DAD, the histologic correlate of ARDS, is the predominant histopathologic pattern identified in lung pathology from patients with COVID-19, H1N1 influenza, and SARS. Microthrombi were reported more frequently in both patients with COVID-19 and SARS as compared with H1N1 influenza. Future work is needed to validate this histopathologic finding and, if confirmed, elucidate the mechanistic underpinnings and characterize any associations with clinically important outcomes.

Human infection by the novel viral pathogen SARS-CoV-2 results in a clinical syndrome termed Coronavirus Disease 2019 (COVID-19). Although the majority of COVID-19 cases are self-limiting, a substantial minority of patients develop disease severe enough to require intensive care. Features of critical illness associated with COVID-19 include hypoxemic respiratory failure, acute respiratory distress syndrome (ARDS), shock, and multiple organ dysfunction syndrome (MODS). In most (but not all) respects critically ill patients with COVID-19 resemble critically ill patients with ARDS due to other causes and are optimally managed with standard, evidence-based critical care protocols. However, there is naturally an intense interest in developing specific therapies for severe COVID-19. Here we synthesize the rapidly expanding literature around the pathophysiology, clinical presentation, and management of COVID-19 with a focus on those points most relevant for intensivists tasked with caring for these patients. We specifically highlight evidence-based approaches that we believe should guide the identification, triage, respiratory support, and general ICU care of critically ill patients infected with SARS-CoV-2. In addition, in light of the pressing need and growing enthusiasm for targeted COVID-19 therapies, we review the biological basis, plausibility, and clinical evidence underlying these novel treatment approaches.

The heterogeneity of critical illness complicates both clinical trial design and real-world management. This complexity has resulted in conflicting evidence and opinion regarding the optimal management in many intensive care scenarios. Understanding this heterogeneity is essential to tailoring management to individual patients. Hyperglycaemia is one such complication in the intensive care unit (ICU), accompanied by decades of conflicting evidence around management strategies. We hypothesized that analysis of highly-detailed electronic medical record (EMR) data would demonstrate that patients vary widely in their glycaemic response to critical illness and response to insulin therapy. Due to this variability, we believed that hyper- and hypoglycaemia would remain common in ICU care despite standardised approaches to management. We utilized the Medical Information Mart for Intensive Care III v1.4 (MIMIC) database. We identified 19,694 admissions between 2008 and 2012 with available glucose results and insulin administration data. We demonstrate that hyper- and hypoglycaemia are common at the time of admission and remain so 1 week into an ICU admission. Insulin treatment strategies vary significantly, irrespective of blood glucose level or diabetic status. We reveal a tremendous opportunity for EMR data to guide tailored management. Through this work, we have made available a highly-detailed data source for future investigation.

Rationale: The care of critically ill patients often involves complex discussions surrounding prognosis, goals, and end-of-life decision-making. Yet, physician and hospital practice patterns, rather than patient goals, remain a major determinant of the intensity of end-of-life care. For critically ill patients, palliative care may help promote treatments that are concordant with patients' goals, while minimizing the use of invasive and costly intensive care unit resources that may not be consistent with those goals.Objectives: To determine whether inpatient palliative care, delivered by specialist consultants or a primary medical team, is associated with reduced hospital length of stay and costs for older adults with septic shock at the end of life.Methods: This was a retrospective cohort using the National Inpatient Sample from 2013 to 2014, examining patients aged ≥65 years with septic shock who died during their hospitalization. The exposure of interest was inpatient palliative care encounter, including either generalist- or specialist-delivered palliative care. Outcomes were hospital length of stay, total cost for the hospitalization, and daily hospital cost. Patient and hospital-level confounders were used to derive inverse probability of treatment weights and estimate the association between palliative care and outcomes in a generalized linear model.Results: We studied 45,868 patients who died with a diagnosis of septic shock; 15,370 of these patients had a palliative care encounter. After inverse probability of treatment weighting, there were no appreciable differences between the population characteristics. Palliative care was associated with a shorter adjusted mean hospital length of stay (12.0 vs. 13.1 d; difference, -1.1 d; 95% confidence interval [CI], -1.4 to -0.9; P < 0.001), lower total hospital costs (69,700 vs. 76,800 U.S. dollars [USD]; difference, -7,100 USD; 95% CI, -8.5 to -5.2 thousand USD; P < 0.001), and lower daily hospital cost (5,900 vs. 6,200 USD; difference, -310 USD per day; 95% CI, -420 to -200 USD; P < 0.001) when compared with no palliative care.Conclusions: In a nationally representative sample of adults who died during a hospitalization with septic shock, receipt of palliative care was associated with shorter length of stay and lower total and daily hospital costs. This finding was robust to adjustment for patient- and hospital-level confounders, though unmeasured confounders still could be affecting these findings.