Noninvasive mechanical ventilation (NIV) is widely used in the acute care setting for acute respiratory failure (ARF) across a variety of aetiologies. This document provides European Respiratory ...Society/American Thoracic Society recommendations for the clinical application of NIV based on the most current literature.The guideline committee was composed of clinicians, methodologists and experts in the field of NIV. The committee developed recommendations based on the GRADE (Grading, Recommendation, Assessment, Development and Evaluation) methodology for each actionable question. The GRADE Evidence to Decision framework in the guideline development tool was used to generate recommendations. A number of topics were addressed using technical summaries without recommendations and these are discussed in the supplementary material.This guideline committee developed recommendations for 11 actionable questions in a PICO (population-intervention-comparison-outcome) format, all addressing the use of NIV for various aetiologies of ARF. The specific conditions where recommendations were made include exacerbation of chronic obstructive pulmonary disease, cardiogenic pulmonary oedema,
hypoxaemic respiratory failure, immunocompromised patients, chest trauma, palliation, post-operative care, weaning and post-extubation.This document summarises the current state of knowledge regarding the role of NIV in ARF. Evidence-based recommendations provide guidance to relevant stakeholders.
The coronavirus disease 2019 (COVID-19) pandemic has prompted expanded use of prone positioning for refractory hypoxemia. Clinical trials have demonstrated beneficial effects of early prone ...positioning for acute respiratory distress syndrome (ARDS), including decreased mortality. However, pregnant women were excluded from these trials. To address the need for low-cost, low-harm interventions in the face of a widespread viral syndrome wherein hypoxemia predominates, we developed an algorithm for prone positioning of both intubated and nonintubated pregnant women. This algorithm may be appropriate for a wide spectrum of hypoxemia severity among pregnant women. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus is responsible for the clinical manifestations of COVID-19. This syndrome can manifest as severe pneumonia complicated by hypoxemia and ARDS. Given the current global COVID-19 pandemic, with a large number of ARDS cases, there is renewed interest in the use of prone positioning to improve oxygenation in moderate or severe hypoxemia. Among the populations who can benefit from prone positioning are pregnant women experiencing severe respiratory distress, as long as the physiologic changes and risks of pregnancy are taken into account.
Guidelines currently recommend targeting light sedation with dexmedetomidine or propofol for adults receiving mechanical ventilation. Differences exist between these sedatives in arousability, ...immunity, and inflammation. Whether they affect outcomes differentially in mechanically ventilated adults with sepsis undergoing light sedation is unknown.
In a multicenter, double-blind trial, we randomly assigned mechanically ventilated adults with sepsis to receive dexmedetomidine (0.2 to 1.5 μg per kilogram of body weight per hour) or propofol (5 to 50 μg per kilogram per minute), with doses adjusted by bedside nurses to achieve target sedation goals set by clinicians according to the Richmond Agitation-Sedation Scale (RASS, on which scores range from -5 unresponsive to +4 combative). The primary end point was days alive without delirium or coma during the 14-day intervention period. Secondary end points were ventilator-free days at 28 days, death at 90 days, and age-adjusted total score on the Telephone Interview for Cognitive Status questionnaire (TICS-T; scores range from 0 to 100, with a mean of 50±10 and lower scores indicating worse cognition) at 6 months.
Of 432 patients who underwent randomization, 422 were assigned to receive a trial drug and were included in the analyses - 214 patients received dexmedetomidine at a median dose of 0.27 μg per kilogram per hour, and 208 received propofol at a median dose of 10.21 μg per kilogram per minute. The median duration of receipt of the trial drugs was 3.0 days (interquartile range, 2.0 to 6.0), and the median RASS score was -2.0 (interquartile range, -3.0 to -1.0). We found no difference between dexmedetomidine and propofol in the number of days alive without delirium or coma (adjusted median, 10.7 vs. 10.8 days; odds ratio, 0.96; 95% confidence interval CI, 0.74 to 1.26), ventilator-free days (adjusted median, 23.7 vs. 24.0 days; odds ratio, 0.98; 95% CI, 0.63 to 1.51), death at 90 days (38% vs. 39%; hazard ratio, 1.06; 95% CI, 0.74 to 1.52), or TICS-T score at 6 months (adjusted median score, 40.9 vs. 41.4; odds ratio, 0.94; 95% CI, 0.66 to 1.33). Safety end points were similar in the two groups.
Among mechanically ventilated adults with sepsis who were being treated with recommended light-sedation approaches, outcomes in patients who received dexmedetomidine did not differ from outcomes in those who received propofol. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT01739933.).
Arginine has vasodilatory effects, via its conversion by NO synthase into NO, and immunomodulatory actions which play important roles in sepsis. Protein breakdown affects arginine availability and ...the release of asymmetric dimethylarginine, an inhibitor of NO synthase, may therefore affect NO synthesis in patients with sepsis. The objective of the present study was to investigate whole-body in vivo arginine and citrulline metabolism and NO synthesis rates, and their relationship to protein breakdown in patients with sepsis or septic shock and in healthy volunteers. Endogenous leucine flux, an index of whole-body protein breakdown rate, was measured in 13 critically ill patients with sepsis or septic shock and seven healthy controls using an intravenous infusion of 1-13Cleucine. Arginine flux, citrulline flux and the rate of conversion of arginine into citrulline (an index of NO synthesis) were measured with intravenous infusions of 15N2guanidino-arginine and 5,5-2H2citrulline. Plasma concentrations of nitrite plus nitrate, arginine, citrulline and asymmetric dimethylarginine were measured. Compared with controls, patients had a higher leucine flux and higher NO metabolites, but arginine flux, plasma asymmetric dimethylarginine concentration and the rate of NO synthesis were not different. Citrulline flux and plasma arginine and citrulline were lower in patients than in controls. Arginine production was positively correlated with the protein breakdown rate. Whole-body arginine production and NO synthesis were similar in patients with sepsis and septic shock and healthy controls. Despite increased proteolysis in sepsis, there is a decreased arginine plasma concentration, suggesting inadequate de novo synthesis secondary to decreased citrulline production.
Managing critically ill obstetric patients in the ICU is a challenge because of their altered physiology, different normal ranges for laboratory and clinical parameters in pregnancy, and potentially ...harmful effects of drugs and interventions on the fetus. About 200 to 700 women per 100,000 deliveries require ICU admission. A systematic five-step approach is recommended to enhance maternal and fetal outcomes: (1) differentiate between medical and obstetric disorders with similar manifestations, (2) identify and treat organ dysfunction, (3) assess maternal and fetal risk from continuing pregnancy and decide if delivery/termination of pregnancy will improve outcome, (4) choose an appropriate mode of delivery if necessary, and (5) optimize organ functions for safe delivery. A multidisciplinary team including the intensivist, obstetrician, maternal-fetal medicine specialist, anesthesiologist, neonatologist, nursing specialist, and transfusion medicine expert is key to optimize outcomes. Severe preeclampsia and its complications, HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome, and amniotic fluid embolism, which cause significant organ failure, are reviewed. Obstetric conditions that were not so common in the past are increasingly seen in the ICU. Thrombotic thrombocytopenic purpura of pregnancy is being diagnosed more frequently. Massive hemorrhage from adherent placenta is increasing because of the large number of pregnant women with scars from previous cesarean section. With more complex fetal surgical interventions being performed for congenital disorders, maternal complications are increasing. Ovarian hyperstimulation syndrome is also becoming common because of treatment of infertility with assisted reproduction techniques. Part II will deal with common medical disorders and their management in critically ill pregnant women.
Mortality related to severe-moderate and severe ARDS remains high. We searched the literature to update this topic. We defined severe hypoxemic respiratory failure as Pao2/Fio2 < 150 mm Hg (ie, ...severe-moderate and severe ARDS). For these patients, we support setting the ventilator to a tidal volume of 4 to 8 mL/kg predicted body weight (PBW), with plateau pressure (Pplat) ≤ 30 cm H2O, and initial positive end-expiratory pressure (PEEP) of 10 to 12 cm H2O. To promote alveolar recruitment, we propose increasing PEEP in increments of 2 to 3 cm provided that Pplat remains ≤ 30 cm H2O and driving pressure does not increase. A fluid-restricted strategy is recommended, and nonrespiratory causes of hypoxemia should be considered. For patients who remain hypoxemic after PEEP optimization, neuromuscular blockade and prone positioning should be considered. Profound refractory hypoxemia (Pao2/Fio2 < 80 mm Hg) after PEEP titration is an indication to consider extracorporeal life support. This may necessitate early transfer to a center with expertise in these techniques. Inhaled vasodilators and nontraditional ventilator modes may improve oxygenation, but evidence for improved outcomes is weak.
The first of this two-part series on critical illness in pregnancy dealt with obstetric disorders. In Part II, medical conditions that commonly affect pregnant women or worsen during pregnancy are ...discussed. ARDS occurs more frequently in pregnancy. Strategies commonly used in nonpregnant patients, including permissive hypercapnia, limits for plateau pressure, and prone positioning, may not be acceptable, especially in late pregnancy. Genital tract infections unique to pregnancy include chorioamnionitis, group A streptococcal infection causing toxic shock syndrome, and polymicrobial infection with streptococci, staphylococci, and Clostridium perfringens causing necrotizing vulvitis or fasciitis. Pregnancy predisposes to VTE; D-dimer levels have low specificity in pregnancy. A ventilation-perfusion scan is preferred over CT pulmonary angiography in some situations to reduce radiation to the mother's breasts. Low-molecular-weight or unfractionated heparins form the mainstay of treatment; vitamin K antagonists, oral factor Xa inhibitors, and direct thrombin inhibitors are not recommended in pregnancy. The physiologic hyperdynamic circulation in pregnancy worsens many cardiovascular disorders. It increases risk of pulmonary edema or arrhythmias in mitral stenosis, heart failure in pulmonary hypertension or aortic stenosis, aortic dissection in Marfan syndrome, or valve thrombosis in mechanical heart valves. Common neurologic problems in pregnancy include seizures, altered mental status, visual symptoms, and strokes. Other common conditions discussed are aspiration of gastric contents, OSA, thyroid disorders, diabetic ketoacidosis, and cardiopulmonary arrest in pregnancy. Studies confined to pregnant women are available for only a few of these conditions. We have, therefore, reviewed pregnancy-specific adjustments in the management of these disorders.
Coronavirus disease 2019 (COVID-19) is primarily an infection of the respiratory tract, but it can have multisystem manifestations. Cardiac complications of COVID-19 can range from acute myocardial ...injury, cardiac arrhythmias, or heart failure, amongst others. Heart failure (HF) in COVID-19 can be a de novo process or due to worsening of pre-existing cardiovascular ailment. HF in a patient with COVID-19 not only poses challenges in clinical presentation and management of COVID-19 but also affect prognosis of the patient. This article aims to succinctly revisit the implications of this pandemic regarding pre-existing HF or new-onset HF based on prevailing data. It also focuses on the management and special recommendations from prior studies and guidelines.
Anti- N -methyl-d-aspartate receptor encephalitis (NMDARE) is characterized by a constellation of psychiatric, neurologic, autonomic, and cardiopulmonary manifestations. Although patients typically ...recover with appropriate treatment, they commonly require weeks to months of inpatient care, including prolonged stays in critical care units. This case series not only advocates for consideration of the disease in the appropriate context but also specifically highlights the distinct challenges intensivists encounter caring for patients with NMDARE. With a greater knowledge of the nuances and sequelae of NMDARE, critical care specialists will be better equipped to anticipate and manage the potentially life-threatening complications of the disease.
Remodeling of the airway wall occurs in adults with asthma, and reticular basement membrane (RBM) thickening is pathognomonic of the asthma process. To investigate whether RBM thickening is present ...in children with difficult asthma and comparable to that seen in adults with asthma, we used light microscopy to measure RBM thickness in plastic-embedded endobronchial biopsy sections from 19 children with difficult asthma who were prescribed 1,600 microg/day or more of inhaled steroids (age range, 6-16 years), 10 children without asthma (7-16 years), and three adult groups: 8 healthy control subjects (21-42 years), 10 mild steroid-naive subjects with asthma (18-41 years), and 6 adults (3 steroid naive and 3 on inhaled steroids) intubated after a life-threatening attack of asthma (20-64 years). RBM thickness in the children with asthma was similar to that in adults with either mild or life-threatening asthma (median 8.2 range 5.4-11.1 versus 8.1 5.8-10.0 and 7.2 2.8-10.0 microm, respectively) and greater than either adult or pediatric control subjects (8.2 5.4-11.1 versus 4.4 3.2-6.3 microm, p < 0.01, and 4.9 3.7-8.3 microm, p < 0.01). We conclude that RBM thickening is already present in children with difficult asthma and to a similar extent to that seen in adults with asthma. In addition, we find no association with age, symptom duration, lung function, or concurrent eosinophilic airway inflammation.
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