Objective
To update the 2008 consensus statements for the diagnosis and management of critical illness-related corticosteroid insufficiency (CIRCI) in adult and pediatric patients.
Participants
A ...multispecialty task force of 16 international experts in Critical Care Medicine, endocrinology, and guideline methods, all of them members of the Society of Critical Care Medicine and/or the European Society of Intensive Care Medicine.
Design/methods
The recommendations were based on the summarized evidence from the 2008 document in addition to more recent findings from an updated systematic review of relevant studies from 2008 to 2017 and were formulated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology. The strength of each recommendation was classified as strong or conditional, and the quality of evidence was rated from high to very low based on factors including the individual study design, the risk of bias, the consistency of the results, and the directness and precision of the evidence. Recommendation approval required the agreement of at least 80% of the task force members.
Results
The task force was unable to reach agreement on a single test that can reliably diagnose CIRCI, although delta cortisol (change in baseline cortisol at 60 min of <9 µg/dl) after cosyntropin (250 µg) administration and a random plasma cortisol of <10 µg/dl may be used by clinicians. We suggest against using plasma free cortisol or salivary cortisol level over plasma total cortisol (conditional, very low quality of evidence). For treatment of specific conditions, we suggest using intravenous (IV) hydrocortisone <400 mg/day for ≥3 days at full dose in patients with septic shock that is not responsive to fluid and moderate- to high-dose vasopressor therapy (conditional, low quality of evidence). We suggest not using corticosteroids in adult patients with sepsis without shock (conditional recommendation, moderate quality of evidence). We suggest the use of IV methylprednisolone 1 mg/kg/day in patients with early moderate to severe acute respiratory distress syndrome (PaO
2
/FiO
2
< 200 and within 14 days of onset) (conditional, moderate quality of evidence). Corticosteroids are not suggested for patients with major trauma (conditional, low quality of evidence).
Conclusions
Evidence-based recommendations for the use of corticosteroids in critically ill patients with sepsis and septic shock, acute respiratory distress syndrome, and major trauma have been developed by a multispecialty task force.
OBJECTIVE:To update the 2008 consensus statements for the diagnosis and management of critical illness-related corticosteroid insufficiency (CIRCI) in adult and pediatric patients.
PARTICIPANTS:A ...multispecialty task force of 16 international experts in critical care medicine, endocrinology, and guideline methods, all of them members of the Society of Critical Care Medicine and/or the European Society of Intensive Care Medicine.
DESIGN/METHODS:The recommendations were based on the summarized evidence from the 2008 document in addition to more recent findings from an updated systematic review of relevant studies from 2008 to 2017 and were formulated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology. The strength of each recommendation was classified as strong or conditional, and the quality of evidence was rated from high to very low based on factors including the individual study design, the risk of bias, the consistency of the results, and the directness and precision of the evidence. Recommendation approval required the agreement of at least 80% of the task force members.
RESULTS:The task force was unable to reach agreement on a single test that can reliably diagnose CIRCI, although delta cortisol (change in baseline cortisol at 60 min of < 9 μg/dL) after cosyntropin (250 μg) administration and a random plasma cortisol of < 10 μg/dL may be used by clinicians. We suggest against using plasma-free cortisol or salivary cortisol level over plasma total cortisol (conditional, very low quality of evidence). For treatment of specific conditions, we suggest using IV hydrocortisone < 400 mg/day for ≥ 3 days at full dose in patients with septic shock that is not responsive to fluid and moderate- to high-dose vasopressor therapy (conditional, low quality of evidence). We suggest not using corticosteroids in adult patients with sepsis without shock (conditional recommendation, moderate quality of evidence). We suggest the use of IV methylprednisolone 1 mg/kg/day in patients with early moderate to severe acute respiratory distress syndrome (PaO2/FiO2 < 200 and within 14 days of onset) (conditional, moderate quality of evidence). Corticosteroids are not suggested for patients with major trauma (conditional, low quality of evidence).
CONCLUSIONS:Evidence-based recommendations for the use of corticosteroids in critically ill patients with sepsis and septic shock, acute respiratory distress syndrome, and major trauma have been developed by a multispecialty task force.
The Newark–Hartford astrochronostratigraphic polarity timescale (APTS) was developed using a theoretically constant 405-kiloyear eccentricity cycle linked to gravitational interactions with ...Jupiter–Venus as a tuning target and provides a major timing calibration for about 30 million years of Late Triassic and earliest Jurassic time. While the 405-ky cycle is both unimodal and the most metronomic of the major orbital cycles thought to pace Earth’s climate in numerical solutions, there has been little empirical confirmation of that behavior, especially back before the limits of orbital solutions at about 50 million years before present. Moreover, the APTS is anchored only at its younger end by U–Pb zircon dates at 201.6 million years before present and could even be missing a number of 405-ky cycles. To test the validity of the dangling APTS and orbital periodicities, we recovered a diagnostic magnetic polarity sequence in the volcaniclastic-bearing Chinle Formation in a scientific drill core fromPetrified Forest National Park (Arizona) that provides an unambiguous correlation to the APTS. New high precision U–Pb detrital zircon dates from the core are indistinguishable from ages predicted by the APTS back to 215 million years before present. The agreement shows that the APTS is continuous and supports a stable 405-kiloyear cycle well beyond theoretical solutions. The validated Newark–Hartford APTS can be used as a robust framework to help differentiate provinciality from global temporal patterns in the ecological rise of early dinosaurs in the Late Triassic, amongst other problems.
A leading hypothesis explaining Phanerozoic mass extinctions and associated carbon isotopic anomalies is the emission of greenhouse, other gases, and aerosols caused by eruptions of continental flood ...basalt provinces. However, the necessary serial relationship between these eruptions, isotopic excursions, and extinctions has never been tested in geological sections preserving all three records. The end-Triassic extinction (ETE) at 201.4 Ma is among the largest of these extinctions and is tied to a large negative carbon isotope excursion, reflecting perturbations of the carbon cycle including a transient increase in CO₂. The cause of the ETE has been inferred to be the eruption of the giant Central Atlantic magmatic province (CAMP). Here, we show that carbon isotopes of leaf wax derived lipids (n-alkanes), wood, and total organic carbon from two orbitally paced lacustrine sections interbedded with the CAMP in eastern North America show similar excursions to those seen in the mostly marine St. Audrie's Bay section in England. Based on these results, the ETE began synchronously in marine and terrestrial environments slightly before the oldest basalts in eastern North America but simultaneous with the eruption of the oldest flows in Morocco, a CO₂ super greenhouse, and marine biocalcification crisis. Because the temporal relationship between CAMP eruptions, mass extinction, and the carbon isotopic excursions are shown in the same place, this is the strongest case for a volcanic cause of a mass extinction to date.
Objective
To provide a narrative review of the latest concepts and understanding of the pathophysiology of critical illness-related corticosteroid insufficiency (CIRCI).
Participants
A multispecialty ...task force of international experts in critical care medicine and endocrinology and members of the Society of Critical Care Medicine (SCCM) and the European Society of Intensive Care Medicine (ESICM).
Data sources
Medline, Database of Abstracts of Reviews of Effects (DARE), Cochrane Central Register of Controlled Trials (CENTRAL) and the Cochrane Database of Systematic Reviews.
Results
Three major pathophysiologic events were considered to constitute CIRCI: dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis, altered cortisol metabolism, and tissue resistance to glucocorticoids. The dysregulation of the HPA axis is complex, involving multidirectional crosstalk between the CRH/ACTH pathways, autonomic nervous system, vasopressinergic system, and immune system. Recent studies have demonstrated that plasma clearance of cortisol is markedly reduced during critical illness, explained by suppressed expression and activity of the primary cortisol-metabolizing enzymes in the liver and kidney. Despite the elevated cortisol levels during critical illness, tissue resistance to glucocorticoids is believed to occur due to insufficient glucocorticoid alpha-mediated anti-inflammatory activity.
Conclusions
Novel insights into the pathophysiology of CIRCI add to the limitations of the current diagnostic tools to identify at-risk patients and may also impact how corticosteroids are used in patients with CIRCI.
Hematite is the most abundant surficial iron oxide on Earth resulting from near-surface processes that make it important for addressing numerous geologic problems. While red beds have proved to be ...excellent paleomagnetic recorders, the early diagenetic origin of hematite in these units is often questioned. Here, we validate pigmentary hematite ("pigmentite") as a proxy indicator for the Late Triassic environment and its penecontemporaneous origin by analyzing spectrophotometric measurements of a 14.5-My-long red bed sequence in scientific drill core CPCP-PFNP13-1A of the Chinle Formation, Arizona. Pigmentite concentrations in the red beds track the evolving pattern of the Late Triassic monsoon and indicate a long-term rise in aridity beginning at ∼215 Ma followed by increased oscillatory climate change at ∼213 Ma. These monsoonal changes are attributed to the northward drift of the Colorado Plateau as part of Laurentia into the arid subtropics during a time of fluctuating CO
Our results refine the record of the Late Triassic monsoon and indicate significant changes in rainfall proximal to the Adamanian-Revueltian biotic transition that thus may have contributed to apparent faunal and floral events at 216 to 213 Ma.
Analysis of sleep for the diagnosis of sleep disorders such as Type-1 Narcolepsy (T1N) currently requires visual inspection of polysomnography records by trained scoring technicians. Here, we used ...neural networks in approximately 3,000 normal and abnormal sleep recordings to automate sleep stage scoring, producing a hypnodensity graph-a probability distribution conveying more information than classical hypnograms. Accuracy of sleep stage scoring was validated in 70 subjects assessed by six scorers. The best model performed better than any individual scorer (87% versus consensus). It also reliably scores sleep down to 5 s instead of 30 s scoring epochs. A T1N marker based on unusual sleep stage overlaps achieved a specificity of 96% and a sensitivity of 91%, validated in independent datasets. Addition of HLA-DQB1*06:02 typing increased specificity to 99%. Our method can reduce time spent in sleep clinics and automates T1N diagnosis. It also opens the possibility of diagnosing T1N using home sleep studies.
The negative organic carbon isotope excursion (CIE) associated with the end-Triassic mass extinction (ETE) is conventionally interpreted as the result of a massive flux of isotopically light carbon ...from exogenous sources into the atmosphere (e.g., thermogenic methane and/or methane clathrate dissociation linked to the Central Atlantic Magmatic Province CAMP). Instead, we demonstrate that at its type locality in the Bristol Channel Basin (UK), the CIE was caused by a marine to nonmarine transition resulting from an abrupt relative sea level drop. Our biomarker and compound-specific carbon isotopic data show that the emergence of microbial mats, influenced by an influx of fresh to brackish water, provided isotopically light carbon to both organic and inorganic carbon pools in centimeter-scale water depths, leading to the negative CIE. Thus, the iconic CIE and the disappearance of marine biota at the type locality are the result of local environmental change and do not mark either the global extinction event or input of exogenous light carbon into the atmosphere. Instead, the main extinction phase occurs slightly later in marine strata, where it is coeval with terrestrial extinctions and ocean acidification driven by CAMP-induced increases in PCO₂; these effects should not be conflated with the CIE. An abrupt sea-level fall observed in the Central European basins reflects the tectonic consequences of the initial CAMP emplacement, with broad implications for all extinction events related to large igneous provinces.
The end-Triassic extinction is characterized by major losses in both terrestrial and marine diversity, setting the stage for dinosaurs to dominate Earth for the next 136 million years. Despite the ...approximate coincidence between this extinction and flood basalt volcanism, existing geochronologic dates have insufficient resolution to confirm eruptive rates required to induce major climate perturbations. Here, we present new zircon uranium-lead (U-Pb) geochronologic constraints on the age and duration of flood basalt volcanism within the Central Atlantic Magmatic Province. This chronology demonstrates synchroneity between the earliest volcanism and extinction, tests and corroborates the existing astrochronologic time scale, and shows that the release of magma and associated atmospheric flux occurred in four pulses over about 600,000 years, indicating expansive volcanism even as the biologic recovery was under way.
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