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 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.
The debilitating and persistent effects of ICU-acquired delirium and weakness warrant testing of prevention strategies. The purpose of this study was to evaluate the effectiveness and safety of ...implementing the Awakening and Breathing Coordination, Delirium monitoring/management, and Early exercise/mobility bundle into everyday practice.
Eighteen-month, prospective, cohort, before-after study conducted between November 2010 and May 2012.
Five adult ICUs, one step-down unit, and one oncology/hematology special care unit located in a 624-bed tertiary medical center.
Two hundred ninety-six patients (146 prebundle and 150 postbundle implementation), who are 19 years old or older, managed by the institutions' medical or surgical critical care service.
Awakening and Breathing Coordination, Delirium monitoring/management, and Early exercise/mobility bundle.
For mechanically ventilated patients (n = 187), we examined the association between bundle implementation and ventilator-free days. For all patients, we used regression models to quantify the relationship between Awakening and Breathing Coordination, Delirium monitoring/management, and Early exercise/mobility bundle implementation and the prevalence/duration of delirium and coma, early mobilization, mortality, time to discharge, and change in residence. Safety outcomes and bundle adherence were monitored. Patients in the postimplementation period spent three more days breathing without mechanical assistance than did those in the preimplementation period (median interquartile range, 24 7-26 vs 21 0-25; p = 0.04). After adjusting for age, sex, severity of illness, comorbidity, and mechanical ventilation status, patients managed with the Awakening and Breathing Coordination, Delirium monitoring/management, and Early exercise/mobility bundle experienced a near halving of the odds of delirium (odds ratio, 0.55; 95% CI, 0.33-0.93; p = 0.03) and increased odds of mobilizing out of bed at least once during an ICU stay (odds ratio, 2.11; 95% CI, 1.29-3.45; p = 0.003). No significant differences were noted in self-extubation or reintubation rates.
Critically ill patients managed with the Awakening and Breathing Coordination, Delirium monitoring/management, and Early exercise/mobility bundle spent three more days breathing without assistance, experienced less delirium, and were more likely to be mobilized during their ICU stay than patients treated with usual care.
The optimum trough concentration of voriconazole for clinical response and safety is controversial. The objective of this review was to determine the optimum trough concentration of voriconazole and ...evaluate its relationship with efficacy and safety.
MEDLINE, EMBASE, ClinicalTrials.gov, the Cochrane Library and three Chinese literature databases were searched. Observational studies that compared clinical outcomes below and above the trough concentration cut-off value were included. We set the trough concentration cut-off value for efficacy as 0.5, 1.0, 1.5, 2.0 and 3.0 mg/L and for safety as 3.0, 4.0, 5.0, 5.5 and 6.0 mg/L. The efficacy outcomes were invasive fungal infection-related mortality, all-cause mortality, rate of successful treatment and rate of prophylaxis failure. The safety outcomes included incidents of hepatotoxicity, neurotoxicity and visual disorders.
A total of 21 studies involving 1158 patients were included. Compared with voriconazole trough concentrations of >0.5 mg/L, levels of <0.5 mg/L significantly decreased the rate of treatment success (risk ratio = 0.46, 95% CI 0.29-0.74). The incidence of hepatotoxicity was significantly increased with trough concentrations >3.0, >4.0, >5.5 and >6.0 mg/L. The incidence of neurotoxicity was significantly increased with trough concentrations >4.0 and >5.5 mg/L.
A voriconazole level of 0.5 mg/L should be considered the lower threshold associated with efficacy. A trough concentration >3.0 mg/L is associated with increased hepatotoxicity, particularly for the Asian population, and >4.0 mg/L is associated with increased neurotoxicity.
There are limited U.S. data describing the risk factors for multidrug-resistant organism (MDRO) isolation in community-acquired pneumonia (CAP) and health care-associated pneumonia (HCAP). However, ...concern for the presence of these pathogens drives the prescribing of empiric broad-spectrum antibiotics for CAP and HCAP. A retrospective study of all adults hospitalized with community-onset pneumonia (CAP and HCAP) at a large U.S. medical center from January 2010 to December 2011 was conducted. The objective was to ascertain the rate of pneumonia caused by MDROs and to evaluate whether HCAP is a risk factor for MDRO pneumonia. Univariate and propensity score-adjusted multivariate analyses were performed. A total of 521 patients (50.5% CAP and 49.5% HCAP) were included. The most common etiologies of pneumonia were primary viral and Streptococcus pneumoniae. MDROs were isolated in 20 (3.8%) patients overall, and MDROs occurred in 5.9% and 1.9% of HCAP and CAP patients, respectively. The presence of an MDRO was not associated with HCAP classification (odds ratio OR=1.95; 95% confidence interval 95% CI, 0.66 to 5.80; P=0.23) or with most of its individual components (hemodialysis, home infusion, home wound care, and ≥48-h hospitalization in the last 90 days). Independent predictors of MDRO included the following: Pseudomonas aeruginosa colonization/infection in the previous year (OR=7.43; 95% CI, 2.24 to 24.61; P<0.001), antimicrobial use in the previous 90 days (OR=2.90; 95% CI, 1.13 to 7.45; P=0.027), admission from a nursing home (OR=4.19; 95% CI, 1.55 to 11.31; P=0.005), and duration of hospitalization in the previous 90 or 180 days (P=0.013 and P=0.002, respectively). MDROs were uncommon in HCAP and CAP. HCAP did not predict MDRO isolation. Local etiology of community onset pneumonia and specific MDRO risk factors should be integrated into therapeutic decisions to prevent empirical overprescribing of antibiotics for methicillin-resistant Staphylococcus aureus (MRSA) and P. aeruginosa.
Purpose
We set out to summarize the current knowledge on vasoactive drugs and their use in the management of shock to inform physicians’ practices.
Methods
This is a narrative review by a ...multidisciplinary, multinational—from six continents—panel of experts including physicians, a pharmacist, trialists, and scientists.
Results and conclusions
Vasoactive drugs are an essential part of shock management. Catecholamines are the most commonly used vasoactive agents in the intensive care unit, and among them norepinephrine is the first-line therapy in most clinical conditions. Inotropes are indicated when myocardial function is depressed and dobutamine remains the first-line therapy. Vasoactive drugs have a narrow therapeutic spectrum and expose the patients to potentially lethal complications. Thus, these agents require precise therapeutic targets, close monitoring with titration to the minimal efficacious dose and should be weaned as promptly as possible. Moreover, the use of vasoactive drugs in shock requires an individualized approach. Vasopressin and possibly angiotensin II may be useful owing to their norepinephrine-sparing effects.
The purpose of this study is to determine the rate of prolonged empiric antibiotic therapy in adult ICUs in the United States. Our secondary objective is to examine the relationship between the ...prolonged empiric antibiotic therapy rate and certain ICU characteristics.
Multicenter, prospective, observational, 72-hour snapshot study.
Sixty-seven ICUs from 32 hospitals in the United States.
Nine hundred ninety-eight patients admitted to the ICU between midnight on June 20, 2011, and June 21, 2011, were included in the study.
None.
Antibiotic orders were categorized as prophylactic, definitive, empiric, or prolonged empiric antibiotic therapy. Prolonged empiric antibiotic therapy was defined as empiric antibiotics that continued for at least 72 hours in the absence of adjudicated infection. Standard definitions from the Centers for Disease Control and Prevention were used to determine infection. Prolonged empiric antibiotic therapy rate was determined as the ratio of the total number of empiric antibiotics continued for at least 72 hours divided by the total number of empiric antibiotics. Univariate analysis of factors associated with the ICU prolonged empiric antibiotic therapy rate was conducted using Student t test. A total of 660 unique antibiotics were prescribed as empiric therapy to 364 patients. Of the empiric antibiotics, 333 of 660 (50%) were continued for at least 72 hours in instances where Centers for Disease Control and Prevention infection criteria were not met. Suspected pneumonia accounted for approximately 60% of empiric antibiotic use. The most frequently prescribed empiric antibiotics were vancomycin and piperacillin/tazobactam. ICUs that utilized invasive techniques for the diagnosis of ventilator-associated pneumonia had lower rates of prolonged empiric antibiotic therapy than those that did not, 45.1% versus 59.5% (p = 0.03). No other institutional factor was significantly associated with prolonged empiric antibiotic therapy rate.
Half of all empiric antibiotics ordered in critically ill patients are continued for at least 72 hours in absence of adjudicated infection. Additional studies are needed to confirm these findings and determine the risks and benefits of prolonged empiric therapy in the critically ill.
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