ResearchPad - Critical Care and Intensive Care Medicine https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Early versus standard initiation of renal replacement therapy in furosemide stress test non-responsive acute kidney injury patients (the FST trial)]]> https://www.researchpad.co/product?articleinfo=5b58edae463d7e541411603f

Background

The timing of initiation of renal replacement therapy (RRT) in severe acute kidney injury (AKI) remains controversial, with early initiation resulting in unnecessary therapy for some patients while expectant therapy may delay RRT for other patients. The furosemide stress test (FST) has been shown to predict the need for RRT and therefore could be used to exclude low-risk patients from enrollment in trials of RRT timing. We conducted this multicenter pilot study to determine whether FST could be used to screen patients at high risk for RRT and to determine the feasibility of incorporating FST into a trial of early initiation of RRT.

Methods

FST was performed using intravenous furosemide (1 mg/kg in furosemide-naive patients or 1.5 mg/kg in previous furosemide users). FST-nonresponsive patients (urine output less than 200 mL in 2 h) were then randomized to early (initiation within 6 h) or standard (initiation by urgent indication) RRT.

Results

FST was completed in all patients (100%). Only 6/44 (13.6%) FST-responsive patients ultimately received RRT while 47/60 (78.3%) nonresponders randomized to standard RRT either received RRT or died (P <  0.001). Among 118 FST-nonresponsive patients, 98.3% in the early RRT arm and 75% in the standard RRT arm received RRT. The adherence to the protocol was 94.8% and 100% in the early and standard RRT group, respectively. We observed no differences in 28-day mortality (62.1 versus 58.3%, P = 0.68), 7-day fluid balance, or RRT dependence at day 28. However, hypophosphatemia occurred more frequently in the early RRT arm (P = 0.002).

Conclusion

The furosemide stress test appears to be feasible and effective in identifying patients for randomization to different RRT initiation times. Our findings should guide implementation of large-scale randomized controlled trials for the timing of RRT initiation.

Trial registration

clinicaltrials.gov, NCT02730117. Registered 6 April 2016.

Electronic supplementary material

The online version of this article (10.1186/s13054-018-2021-1) contains supplementary material, which is available to authorized users.

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<![CDATA[Population pharmacokinetics/pharmacodynamics of micafungin against Candida species in obese, critically ill, and morbidly obese critically ill patients]]> https://www.researchpad.co/product?articleinfo=5bfd958fd5eed0c484519c85

Background

Dosing in obese critically ill patients is challenging due to pathophysiological changes derived from obesity and/or critical illness, and it remains fully unexplored. This study estimated the micafungin probability of reaching adequate 24-h area under the curve (AUC0–24h)/minimum inhibitory concentration (MIC) values against Candida spp. for an obese/nonobese, critically ill/noncritically ill, large population.

Methods

Blood samples for pharmacokinetic analyses were collected from 10 critically ill nonobese patients, 10 noncritically ill obese patients, and 11 critically ill morbidly obese patients under empirical/directed micafungin treatment. Patients received once daily 100–150 mg micafungin at the discretion of the treating physician following the prescribing information and hospital guidelines. Total micafungin concentrations were determined by high-performance liquid chromatography (HPLC). Monte-Carlo simulations were performed and the probability of target attainment (PTA) was calculated using the AUC0–24/MIC cut-offs 285 (C. parapsilosis), 3000 (all Candida spp.), and 5000 (nonparapsilosis Candida spp.). Intravenous once-daily 100-mg, 150-mg, and 200-mg doses were simulated at different body weights (45, 80, 115, 150, and 185 kg) and age (30, 50, 70 and 90 years old). PTAs ≥ 90% were considered optimal. Fractional target attainment (FTA) was calculated using published MIC distributions. A dosing regimen was considered successful if the FTA was ≥ 90%.

Results

Overall, 100 mg of micafungin was once-daily administered for nonobese and obese patients with body mass index (BMI) ≤ 45 kg/m2 and 150 mg for morbidly obese patients with BMI > 45 kg/m2 (except two noncritically ill obese patients with BMI ~ 35 kg/m2 receiving 150 mg, and one critically ill patient with BMI > 45 kg/m2 receiving 100 mg). Micafungin concentrations in plasma were best described using a two-compartment model. Weight and age (but not severity score) were significant covariates and improved the model. FTAs > 90% were obtained against C. albicans with the 200 mg/24 h dose for all body weights (up to 185 kg), and with the 150 mg/24 h for body weights < 115 kg, and against C. glabrata with the 200 mg/24 h dose for body weights < 115 kg.

Conclusion

The lack of adequacy for the 100 mg/24 h dose suggested the need to increase the dose to 150 mg/24 h for C. albicans infections. Further pharmacokinetic/pharmacodynamic studies should address optimization of micafungin dosing for nonalbicans Candida infections.

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<![CDATA[Role of neomycin polymyxin sulfate solution bladder wash for prevention of catheter associated urinary tract infection in traumatic brain injury patient admitted to Intensive Care Unit: A prospective randomized study]]> https://www.researchpad.co/product?articleinfo=5b4ce857463d7e11b2f07590

Background:

Catheter - associated urinary tract infection (CAUTI) remains a critical threat for patients in intensive care unit especially in traumatic brain injury patients with low Glasgow coma score (GCS). Almost all patients in ICU receive antibiotic either prophylactic or therapeutic based on local antibiogram of particular ICU or hospital. For prophylaxis, systemic antibiotics are used. It will be helpful to avoid systemic side effects by introducing antibiotics locally through bladder irrigation. The indwelling urinary catheter is an essential part of modern medical care.

Aims and Objectives:

The primary objective was to study the effect of Neomycin and Polymyxin sulphate solution for bladder wash on CAUTI in traumatic brain injury patients. The secondary objectives was to study the various organisms causing CAUTI and their antibiotic sensitivity and resistance pattern.

Materials and Methods:

This was a prospective randomized controlled study performed on 100 patients who met the inclusion criteria at the trauma intensive care unit of Banaras Hindu University between September and February 2016. The patients were randomized into two groups – one was the study group which received Neomycin and Polymyxin Sulphate solution bladder wash, while the other was the control group that received Normal saline bladder wash. Urine samples were collected at certain days and sent for culture and sensitivity.

Results:

There was significant reduction in the incidence of CAUTI in neomycin/polymyxin test group in comparison to normal saline irrigated control group. Out of 50 patients in test group 8 patients and in control group 26 patients was identified as CAUTI positive and they were statistically significant. In our study pseudomonas aeruginosa (51%) was the commonest isolated pathogen.

Conclusions:

Neomycin and Polymyxin Sulphate bladder wash was effective in preventing CAUTI. It can thus decrease the antibiotic usage thereby preventing the emergence of antibiotic resistance.

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<![CDATA[Neuromuscular blockade is associated with the attenuation of biomarkers of epithelial and endothelial injury in patients with moderate-to-severe acute respiratory distress syndrome]]> https://www.researchpad.co/product?articleinfo=5b4bfdf9463d7e022037ff85

Background

Neuromuscular blockade (NMB) is a therapy for acute respiratory distress syndrome (ARDS). However, the mechanism by which NMB may improve outcome for ARDS patients remains unclear. We sought to determine whether NMB attenuates biomarkers of epithelial and endothelial lung injury and systemic inflammation in ARDS patients, and whether the association is dependent on tidal volume size and the initial degree of hypoxemia.

Methods

We performed a secondary analysis of patients enrolled in the ARDS network low tidal volume ventilation (ARMA) study. Our primary predictor variable was the number of days receiving NMB between study enrollment and day 3. Our primary outcome variables were the change in concentration of biomarkers of epithelial injury (serum surfactant protein-D (SP-D)), endothelial injury (von Willebrand factor (VWF)), and systemic inflammation (interleukin (IL)-8). Multivariable regression analysis was used to compare the change in biomarker concentration controlling for multiple covariates. Patients were stratified by treatment arm (12 versus 6 cm3/kg) and by an initial arterial oxygen tension (PaO2) to fractional inspired oxygen (FiO2) (P/F) ratio of 120.

Results

A total of 446 (49%) patients had complete SP-D, VWF, and IL-8 measurements on study enrollment and day 3. After adjusting for baseline differences, each day of NMB was associated with a decrease in SP-D (−23.7 ng/ml/day, p = 0.029), VWF (−33.5% of control/day, p = 0.015), and IL-8 (−362.6 pg/ml/day, p = 0.030) in patients with an initial P/F less than or equal to 120 and receiving low tidal volume ventilation. However, patients with a P/F ratio of greater than 120 or receiving high tidal volume ventilation had either no change or an increase in SP-D, WVF, or IL-8 concentrations.

Conclusion

NBM is associated with decreased biomarkers of epithelial and endothelial lung injury and systemic inflammation in ARDS patients receiving low tidal volume ventilation and those with a P/F ratio less than or equal to 120.

Electronic supplementary material

The online version of this article (10.1186/s13054-018-1974-4) contains supplementary material, which is available to authorized users.

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<![CDATA[Multicohort Analysis of Whole-Blood Gene Expression Data Does Not Form a Robust Diagnostic for Acute Respiratory Distress Syndrome]]> https://www.researchpad.co/product?articleinfo=5bf67e35d5eed0c484ca22be

Objectives:

To identify a novel, generalizable diagnostic for acute respiratory distress syndrome using whole-blood gene expression arrays from multiple acute respiratory distress syndrome cohorts of varying etiologies.

Data Sources:

We performed a systematic search for human whole-blood gene expression arrays of acute respiratory distress syndrome in National Institutes of Health Gene Expression Omnibus and ArrayExpress. We also included the Glue Grant gene expression cohorts.

Study Selection:

We included investigator-defined acute respiratory distress syndrome within 48 hours of diagnosis and compared these with relevant critically ill controls.

Data Extraction:

We used multicohort analysis of gene expression to identify genes significantly associated with acute respiratory distress syndrome, both with and without adjustment for clinical severity score. We performed gene ontology enrichment using Database for Annotation, Visualization and Integrated Discovery and cell type enrichment tests for both immune cells and pneumocyte gene expression. Finally, we selected a gene set optimized for diagnostic power across the datasets and used leave-one-dataset-out cross validation to assess robustness of the model.

Data Synthesis:

We identified datasets from three adult cohorts with sepsis, one pediatric cohort with acute respiratory failure, and two datasets of adult patients with trauma and burns, for a total of 148 acute respiratory distress syndrome cases and 268 critically ill controls. We identified 30 genes that were significantly associated with acute respiratory distress syndrome (false discovery rate < 20% and effect size >1.3), many of which had been previously associated with sepsis. When metaregression was used to adjust for clinical severity scores, none of these genes remained significant. Cell type enrichment was notable for bands and neutrophils, suggesting that the gene expression signature is one of acute inflammation rather than lung injury per se. Finally, an attempt to develop a generalizable diagnostic gene set for acute respiratory distress syndrome showed a mean area under the receiver-operating characteristic curve of only 0.63 on leave-one-dataset-out cross validation.

Conclusions:

The whole-blood gene expression signature across a wide clinical spectrum of acute respiratory distress syndrome is likely confounded by systemic inflammation, limiting the utility of whole-blood gene expression studies for uncovering a generalizable diagnostic gene signature.

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<![CDATA[Doctor—your septic patients have scurvy!]]> https://www.researchpad.co/product?articleinfo=5b4a90c2463d7e67a7d90ac9 ]]> <![CDATA[Supplemental parenteral nutrition versus usual care in critically ill adults: a pilot randomized controlled study]]> https://www.researchpad.co/product?articleinfo=5bf57e09d5eed0c48498f2fd

Background

In the critically ill, energy delivery from enteral nutrition (EN) is often less than the estimated energy requirement. Parenteral nutrition (PN) as a supplement to EN may increase energy delivery. We aimed to determine if an individually titrated supplemental PN strategy commenced 48–72 hours following ICU admission and continued for up to 7 days would increase energy delivery to critically ill adults compared to usual care EN delivery.

Methods

This study was a prospective, parallel group, phase II pilot trial conducted in six intensive care units in Australia and New Zealand. Mechanically ventilated adults with at least one organ failure and EN delivery below 80% of estimated energy requirement in the previous 24 hours received either a supplemental PN strategy (intervention group) or usual care EN delivery. EN in the usual care group could be supplemented with PN if EN remained insufficient after usual methods to optimise delivery were attempted.

Results

There were 100 patients included in the study and 99 analysed. Overall, 71% of the study population were male, with a mean (SD) age of 59 (17) years, Acute Physiology and Chronic Health Evaluation II score of 18.2 (6.7) and body mass index of 29.6 (5.8) kg/m2. Significantly greater energy (mean (SD) 1712 (511) calories vs. 1130 (601) calories, p < 0.0001) and proportion of estimated energy requirement (mean (SD) 83 (25) % vs. 53 (29) %, p < 0.0001) from EN and/or PN was delivered to the intervention group compared to usual care. Delivery of protein and proportion of estimated protein requirements were also greater in the intervention group (mean (SD) 86 (25) g, 86 (23) %) compared to usual care (mean (SD) 53 (29) g, 51 (25) %, p < 0.0001). Antibiotic use, ICU and hospital length of stay, mortality and functional outcomes were similar between the two groups.

Conclusions

This individually titrated supplemental PN strategy applied over 7 days significantly increased energy delivery when compared to usual care delivery. Clinical and functional outcomes were similar between the two patient groups.

Trial registration

Clinical Trial registry details: NCT01847534 (First registered 22 April 2013, last updated 31 July 2016)

Electronic supplementary material

The online version of this article (10.1186/s13054-018-1939-7) contains supplementary material, which is available to authorized users.

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<![CDATA[Extracorporeal membrane oxygenation for severe Middle East respiratory syndrome coronavirus]]> https://www.researchpad.co/product?articleinfo=5bf4ec67d5eed0c484817b04

Background

Middle East respiratory syndrome (MERS) is caused by a coronavirus (MERS‐CoV) and is characterized by hypoxemic respiratory failure. The objective of this study is to compare the outcomes of MERS-CoV patients before and after the availability of extracorporeal membrane oxygenation (ECMO) as a rescue therapy in severely hypoxemic patients who failed conventional strategies.

Methods

We collected data retrospectively on MERS-CoV patients with refractory respiratory failure from April 2014 to December 2015 in 5 intensive care units (ICUs) in Saudi Arabia. Patients were classified into two groups: ECMO versus conventional therapy. Our primary outcome was in-hospital mortality; secondary outcomes included ICU and hospital length of stay.

Results

Thirty-five patients were included; 17 received ECMO and 18 received conventional therapy. Both groups had similar baseline characteristics. The ECMO group had lower in-hospital mortality (65 vs. 100%, P = 0.02), longer ICU stay (median 25 vs. 8 days, respectively, P < 0.01), and similar hospital stay (median 41 vs. 31 days, P = 0.421). In addition, patients in the ECMO group had better PaO2/FiO2 at days 7 and 14 of admission to the ICU (124 vs. 63, and 138 vs. 36, P < 0.05), and less use of norepinephrine at days 1 and 14 (29 vs. 80%; and 36 vs. 93%, P < 0.05).

Conclusions

ECMO use, as a rescue therapy, was associated with lower mortality in MERS patients with refractory hypoxemia. The results of this, largest to date, support the use of ECMO as a rescue therapy in patients with severe MERS-CoV.

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<![CDATA[Tailoring nutrition therapy to illness and recovery]]> https://www.researchpad.co/product?articleinfo=5b47481f463d7e6d853626cc

Without doubt, in medicine as in life, one size does not fit all. We do not administer the same drug or dose to every patient at all times, so why then would we live under the illusion that we should give the same nutrition at all times in the continuum of critical illness? We have long lived under the assumption that critical illness and trauma lead to a consistent early increase in metabolic/caloric need, the so-called “hypermetabolism” of critical illness. What if this is incorrect? Recent data indicate that early underfeeding of calories (trophic feeding) may have benefits and may require consideration in well-nourished patients. However, we must confront the reality that currently ICU nutrition delivery worldwide is actually leading to “starvation” of our patients and is likely a major contributor to poor long-term quality of life outcomes. To begin to ascertain the actual calorie and protein delivery required for optimal ICU recovery, an understanding of “starvation” and recovery from starvation and lean body mass (LBM) loss is needed. To begin to answer this question, we must look to the landmark Minnesota Starvation Study from 1945. This trial defines much of the world’s knowledge about starvation, and most importantly what is required for recovery from starvation and massive LBM loss as occurs in the ICU. Recent and historic data indicate that critical illness is characterized by early massive catabolism, LBM loss, and escalating hypermetabolism that can persist for months or years. Early enteral nutrition during the acute phase should attempt to correct micronutrient/vitamin deficiencies, deliver adequate protein, and moderate nonprotein calories in well-nourished patients, as in the acute phase they are capable of generating significant endogenous energy. Post resuscitation, increasing protein (1.5–2.0 g/kg/day) and calories are needed to attenuate LBM loss and promote recovery. Malnutrition screening is essential and parenteral nutrition can be safely added following resuscitation when enteral nutrition is failing based on pre-illness malnutrition and LBM status. Following the ICU stay, significant protein/calorie delivery for months or years is required to facilitate functional and LBM recovery, with high-protein oral supplements being essential to achieve adequate nutrition.

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<![CDATA[Attempting to validate the overtriage/undertriage matrix at a Level I trauma center]]> https://www.researchpad.co/product?articleinfo=5bf1b0cfd5eed0c484d2902d <![CDATA[Sepsis 2016 Paris]]> https://www.researchpad.co/product?articleinfo=5989db59ab0ee8fa60bdefc5 ]]> <![CDATA[The System-Wide Effect of Real-Time Audiovisual Feedback and Postevent Debriefing for In-Hospital Cardiac Arrest: The Cardiopulmonary Resuscitation Quality Improvement Initiative*]]> https://www.researchpad.co/product?articleinfo=5bc36d8940307c2291144851

Supplemental Digital Content is available in the text.

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<![CDATA[Heparin-Binding Protein Measurement Improves the Prediction of Severe Infection With Organ Dysfunction in the Emergency Department]]> https://www.researchpad.co/product?articleinfo=5bc36d8c40307c2291144852

Supplemental Digital Content is available in the text.

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<![CDATA[Asphyxia by Drowning Induces Massive Bleeding Due To Hyperfibrinolytic Disseminated Intravascular Coagulation]]> https://www.researchpad.co/product?articleinfo=5bc36d8e40307c2291144853

Supplemental Digital Content is available in the text.

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<![CDATA[Rapid Diagnosis of Infection in the Critically Ill, a Multicenter Study of Molecular Detection in Bloodstream Infections, Pneumonia, and Sterile Site Infections*]]> https://www.researchpad.co/product?articleinfo=5bc36d8540307c2291144850

Supplemental Digital Content is available in the text.

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<![CDATA[Delirium diagnosis, screening and management]]> https://www.researchpad.co/product?articleinfo=5ba6fb5b40307c4d1c2820a5

Purpose of review

Our review focuses on recent developments across many settings regarding the diagnosis, screening and management of delirium, so as to inform these aspects in the context of palliative and supportive care.

Recent findings

Delirium diagnostic criteria have been updated in the long-awaited Diagnostic Statistical Manual of Mental Disorders, fifth edition. Studies suggest that poor recognition of delirium relates to its clinical characteristics, inadequate interprofessional communication and lack of systematic screening. Validation studies are published for cognitive and observational tools to screen for delirium. Formal guidelines for delirium screening and management have been rigorously developed for intensive care, and may serve as a model for other settings. Given that palliative sedation is often required for the management of refractory delirium at the end of life, a version of the Richmond Agitation-Sedation Scale, modified for palliative care, has undergone preliminary validation.

Summary

Although formal systematic delirium screening with brief but sensitive tools is strongly advocated for patients in palliative and supportive care, it requires critical evaluation in terms of clinical outcomes, including patient comfort. Randomized controlled trials are needed to inform the development of guidelines for the management of delirium in this setting.

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<![CDATA[Peripheral Neural Detection of Danger–Associated and Pathogen–Associated Molecular Patterns]]> https://www.researchpad.co/product?articleinfo=5ba6ea0640307c4ae697c738

Objective:

Bidirectional links between the nervous and immune systems modulate inflammation. The cellular mechanisms underlying the detection of danger-associated molecular patterns and pathogen-associated molecular patterns by the nervous system are not well understood. We hypothesized that the carotid body, a tissue of neural crest origin, detect pathogen associated molecular patterns and danger associated molecular patterns via an inflammasome-dependent mechanism similar to that described in immune cells.

Design:

Randomized, controlled laboratory investigation.

Setting:

University laboratory.

Subjects:

C57Bl/6J mice; juvenile Sprague-Dawley rats, primary human neutrophils.

Interventions:

Rat carotid body chemosensitive cells, and human neutrophils, were treated with TLR agonists to activate inflammasome-dependent pathways. In mice, systemic inflammation was induced by the pathogen associated molecular pattern zymosan (intraperitoneal injection; 500 mg/kg). Isolated carotid body/carotid sinus nerve preparations were used to assess peripheral chemoafferent activity. Ventilation was measured by whole-body plethysmography.

Measurements and Main Results:

Chemosensitive carotid body glomus cells exhibited toll-like receptor (TLR-2 and TLR-4), NLRP1, and NLRP3 inflammasome immunoreactivities. Zymosan increased NLRP3 inflammasome and interleukin-1β expression in glomus cells (p < 0.01). Human neutrophils demonstrated similar LPS-induced changes in inflammasome expression. Carotid body glomus cells also expressed IL-1 receptor and responded to application of IL-1β with increases in intracellular [Ca2+]. Four hours after injection of zymosan carotid sinus nerve chemoafferent discharge assessed in vitro (i.e., in the absence of acidosis/circulating inflammatory mediators) was increased five-fold (p < 0.001). Accordingly, zymosan-induced systemic inflammation was accompanied by enhanced respiratory activity.

Conclusions:

In carotid body chemosensitive glomus cells, activation of toll-like receptors increases NLRP3 inflammasome expression, and enhances IL-1β production, which is capable of acting in an autocrine manner to enhance peripheral chemoreceptor drive.

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<![CDATA[trauma.org – moulage]]> https://www.researchpad.co/product?articleinfo=5ba5301840307c1f94d43bbb ]]> <![CDATA[Isabel]]> https://www.researchpad.co/product?articleinfo=5ba5302040307c1f94d43bbd ]]> <![CDATA[ICU-USA]]> https://www.researchpad.co/product?articleinfo=5ba5302240307c1f94d43bbe ]]>