Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study.

Background Traditional approaches to mechanical ventilation use tidal volumes of 10 to 15 ml per kilogram of body weight and may cause stretch-induced lung injury in patients with acute lung injury and the acute respiratory distress syndrome. We therefore conducted a trial to determine whether ventilation with lower tidal volumes would improve the clinical outcomes in these patients. Methods Patients with acute lung injury and the acute respiratory distress syndrome were enrolled in a multicenter, randomized trial. The trial compared traditional ventilation treatment, which involved an initial tidal volume of 12 ml per kilogram of predicted body weight and an airway pressure measured after a 0.5-second pause at the end of inspiration (plateau pressure) of 50 cm of water or less, with ventilation with a lower tidal volume, which involved an initial tidal volume of 6 ml per kilogram of predicted body weight and a plateau pressure of 30 cm of water or less. The primary outcomes were death before a patient was discharged home and was breathing without assistance and the number of days without ventilator use from day 1 to day 28. Results The trial was stopped after the enrollment of 861 patients because mortality was lower in the group treated with lower tidal volumes than in the group treated with traditional tidal volumes (31.0 percent vs. 39.8 percent, P=0.007), and the number of days without ventilator use during the first 28 days after randomization was greater in this group (mean [+/-SD], 12+/-11 vs. 10+/-11; P=0.007). The mean tidal volumes on days 1 to 3 were 6.2+/-0.8 and 11.8+/-0.8 ml per kilogram of predicted body weight (P Conclusions In patients with acute lung injury and the acute respiratory distress syndrome, mechanical ventilation with a lower tidal volume than is traditionally used results in decreased mortality and increases the number of days without ventilator use.

Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome.

XI. STRATEGIES FOR IMPROVING DIABETES CARE D iabetes is a chronic illness that requires continuing medical care and patient self-management education to prevent acute complications and to reduce the risk of long-term complications. Diabetes care is complex and requires that many issues, beyond glycemic control, be addressed. A large body of evidence exists that supports a range of interventions to improve diabetes outcomes. These standards of care are intended to provide clinicians, patients, researchers, payors, and other interested individuals with the components of diabetes care, treatment goals, and tools to evaluate the quality of care. While individual preferences, comorbidities, and other patient factors may require modification of goals, targets that are desirable for most patients with diabetes are provided. These standards are not intended to preclude more extensive evaluation and management of the patient by other specialists as needed. For more detailed information, refer to Bode (Ed.): Medical Management of Type 1 Diabetes (1), Burant (Ed): Medical Management of Type 2 Diabetes (2), and Klingensmith (Ed): Intensive Diabetes Management (3). The recommendations included are diagnostic and therapeutic actions that are known or believed to favorably affect health outcomes of patients with diabetes. A grading system (Table 1), developed by the American Diabetes Association (ADA) and modeled after existing methods, was utilized to clarify and codify the evidence that forms the basis for the recommendations. The level of evidence that supports each recommendation is listed after each recommendation using the letters A, B, C, or E.

Standards of Medical Care in Diabetes

Objective:To provide an update to the “Surviving Sepsis Campaign Guidelines for Management of Severe Sepsis and Septic Shock,” last published in 2008.Design:A consensus committee of 68 international experts representing 30 international organizations was convened. Nominal groups were assembled at ke

Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012.

Background Goal-directed therapy has been used for severe sepsis and septic shock in the intensive care unit. This approach involves adjustments of cardiac preload, afterload, and contractility to balance oxygen delivery with oxygen demand. The purpose of this study was to evaluate the efficacy of early goal-directed therapy before admission to the intensive care unit. Methods We randomly assigned patients who arrived at an urban emergency department with severe sepsis or septic shock to receive either six hours of early goal-directed therapy or standard therapy (as a control) before admission to the intensive care unit. Clinicians who subsequently assumed the care of the patients were blinded to the treatment assignment. In-hospital mortality (the primary efficacy outcome), end points with respect to resuscitation, and Acute Physiology and Chronic Health Evaluation (APACHE II) scores were obtained serially for 72 hours and compared between the study groups. Results Of the 263 enrolled patients, 130 were ...

Early Goal-Directed Therapy in the Treatment of Severe Sepsis and Septic Shock

Ethics and standard of care in clinical trials.

We examined the effects of intravenous sodium nitroprusside (NP) infusion on pulmonary arterial pressure (Ppa), pulmonary vascular resistance (PVR), dynamic compliance (Cdyn), resistance to airflow across the lungs (RL), and alveolar-arterial O2 pressure gradient (PAO2-PaO2) (room air) after endotoxemia in awake sheep. NP infused 2.5 h after endotoxin administration immediately reduced mean Ppa from 30 +/- 3 to 17 +/- 3 (SE) cmH2O, PVR from 6.3 +/- 0.7 to 4.8 +/- 0.5 cmH2O.l-1.min, and RL from 340 +/- 48 of base line to 205 +/- 73% and increased Cdyn from 54 +/- 5 of base line to 80 +/- 14% without affecting PAO2--PaO2. Ppa and lung mechanics returned immediately to preinfusion levels when NP was stopped. In vitro experiments with NP showed a dose-dependent relaxation of preconstricted pulmonary artery and vein, carbachol-preconstricted sheep tracheal strips, and bronchial rings. We conclude that NP reverses pulmonary hypertension and lung mechanics abnormalities after endotoxin and that this is due to effects of NP on airway and vascular smooth muscle. The return of these abnormalities after NP cessation suggests the continued presence of vascular and airway-constricting factors late after endotoxin. The lack of effect of NP on blood oxygenation suggests that deleterious effects on hypoxic vasoconstriction are offset by improved lung mechanics.

Effects of nitroprusside on lung mechanics and hemodynamics after endotoxemia in awake sheep.

The Measurement of Organ Dysfunction/Failure as an ICU Outcome

Rationale: Respiratory support (noninvasive ventilation or high-flow nasal cannula) applied at the time of extubation has been reported to reduce reintubation rates, but concerns regarding effectiv...

Protocolized Postextubation Respiratory Support to Prevent Reintubation: A Randomized Clinical Trial

The mechanisms involved in endotoxin-induced endothelial injury are not fully understood. Oxidant stress is thought to play a role in cell damage after endotoxin exposure. Glutathione may ameliorate these affects. Glutathione ethyl ester (GSE) was used in bovine pulmonary artery endothelial cell (BPAEC) cultures to determine the potential for attenuation of endotoxin-induced injury. GSE (0.05-25 mM) was preincubated with BPAEC for 4 h before endotoxin exposure. Fresh media containing GSE and Escherichia coli endotoxin (0.05 microgram/mL) were then placed on the BPAEC and incubated for 18 h. GSE, at doses of 5 and 25 mM, attenuated endotoxin-induced injury, as reflected by a significant reduction in lactate dehydrogenase release. This was paralleled by a significant increase in endotoxin-stimulated prostaglandin E2 and prostacyclin release. Thus, GSE attenuates endotoxin-induced injury of BPAEC in culture and alters BPAEC prostaglandin metabolism.

Gordon R. Bernard

Papers

Ethics and standard of care in clinical trials.

Effects of nitroprusside on lung mechanics and hemodynamics after endotoxemia in awake sheep.

The Measurement of Organ Dysfunction/Failure as an ICU Outcome

Protocolized Postextubation Respiratory Support to Prevent Reintubation: A Randomized Clinical Trial

Escherichia coli Endotoxin-Mediated Endothelial Injury Is Modulated by Glutathione Ethyl Ester