Search

Background To develop evidence-based clinical practice guidelines on venous thromboembolism (VTE) prevention in adults with trauma in inpatient settings. Methods The Saudi Critical Care Society (SCCS) sponsored guidelines development and included 22 multidisciplinary panel members who completed conflict-of-interest forms. The panel developed and answered structured guidelines questions. For each question, the literature was searched for relevant studies. To summarize treatment effects, meta-analyses were conducted or updated. Quality of evidence was assessed using the Grading Recommendations, Assessment, Development, and Evaluation (GRADE) approach, then the evidence-to-decision (EtD) framework was used to generate recommendations. Recommendations covered the following prioritized domains: timing of pharmacologic VTE prophylaxis initiation in non-operative blunt solid organ injuries; isolated blunt traumatic brain injury (TBI); isolated blunt spine trauma or fracture and/or spinal cord injury (SCI); type and dose of pharmacologic VTE prophylaxis; mechanical VTE prophylaxis; routine duplex ultrasonography (US) surveillance; and inferior vena cava filters (IVCFs). Results The panel issued 12 clinical practice recommendations—one, a strong recommendation, 10 weak, and one with no recommendation due to insufficient evidence. The panel suggests starting early pharmacologic VTE prophylaxis for non-operative blunt solid organ injuries, isolated blunt TBIs, and SCIs. The panel suggests using low molecular weight heparin (LMWH) over unfractionated heparin (UFH) and suggests either intermediate–high dose LMWH or conventional dosing LMWH. For adults with trauma who are not pharmacologic candidates, the panel strongly recommends using mechanical VTE prophylaxis with intermittent pneumatic compression (IPC). The panel suggests using either combined VTE prophylaxis with mechanical and pharmacologic methods or pharmacologic VTE prophylaxis alone. Additionally, the panel suggests routine bilateral lower extremity US in adults with trauma with elevated risk of VTE who are ineligible for pharmacologic VTE prophylaxis and suggests against the routine placement of prophylactic IVCFs. Because of insufficient evidence, the panel did not issue any recommendation on the use of early pharmacologic VTE prophylaxis in adults with isolated blunt TBI requiring neurosurgical intervention. Conclusion The SCCS guidelines for VTE prevention in adults with trauma were based on the best available evidence and identified areas for further research. The framework may facilitate adaptation of recommendations by national/international guideline policymakers.

Animal and human data indicate variable effects of interferons in treating coronavirus infections according to inflammatory status and timing of therapy. In this sub-study of the MIRACLE trial (MERS-CoV Infection Treated with a Combination of Lopinavir–Ritonavir and Interferon β-1b), we evaluated the heterogeneity of treatment effect of interferon-β1b and lopinavir–ritonavir versus placebo among hospitalized patients with MERS on 90-day mortality, according to cytokine levels and timing of therapy. We measured plasma levels of 17 cytokines at enrollment and tested the treatment effect on 90-day mortality according to cytokine levels (higher versus lower levels using the upper tertile (67%) as a cutoff point) and time to treatment (≤ 7 days versus > 7 days of symptom onset) using interaction tests. Among 70 included patients, 32 received interferon-β1b and lopinavir–ritonavir and 38 received placebo. Interferon-β1b and lopinavir–ritonavir reduced mortality in patients with lower IL-2, IL-8 and IL-13 plasma concentrations but not in patients with higher levels (p-value for interaction = 0.09, 0.07, and 0.05, respectively) and with early but not late therapy (p = 0.002). There was no statistically significant heterogeneity of treatment effect according to other cytokine levels. Further work is needed to evaluate whether the assessment of inflammatory status can help in identifying patients with MERS who may benefit from interferon-β1b and lopinavir–ritonavir. Trial registration: This is a sub-study of the MIRACLE trial (ClinicalTrials.gov number, NCT02845843).

Introduction Antiviral drugs have shown limited effectiveness in treating patients with coronavirus disease 2019 (COVID-19). We aimed to assess the effects of a favipiravir and hydroxychloroquine combination on treating moderate-to-severe COVID-19 patients. Methods An investigator-initiated, multicenter, open-label, randomized trial at nine hospitals. Eligible patients were adults with moderate-to-severe COVID-19 defined as oxygen saturation (SaO2) of ≤ 94% while breathing ambient air or significant clinical symptoms with chest x-ray changes requiring hospital admission. Randomization was in a 1:1 ratio to receive standard care (control group) or standard care plus favipiravir and hydroxychloroquine. The primary outcome was time to clinical improvement of two points (from the status at randomization) on a seven-category ordinal scale or live discharge from the hospital within 14 days. Analyses were done in an intention-to-treat population. Results From May 2020 to Jan 2021, 254 patients were enrolled; 129 were assigned to standard of care and 125 to the treatment. The mean age was 52 (± 13) years, and 103 (41%) were women. At randomization, six patients were on invasive mechanical ventilation, 229 (90.15%) were requiring supplemental oxygen only (with or without non-invasive ventilation), and 19 (7.48%) were receiving neither. The time to clinical improvement was not significantly different between the groups: median of 9 days in the treatment group and 7 days in the control group (HR: 0.845; 95% CI 0.617–1.157; p-value = 0.29). The 28-day mortality was not significantly different between the groups (7.63% treatment) vs. (10.32% control); p-value = 0.45. The most prevalent adverse events were headache, elevation in ALT, and the prolonged QTc interval in the treatment group. Conclusion The combination of favipiravir and hydroxychloroquine did not result in a statistically significant clinical benefit in patients with moderate-to-severe COVID-19. Clinical Trial Registration ClinicalTrials.gov (NCT04392973). Supplementary Information The online version contains supplementary material available at 10.1007/s40121-021-00496-6.

We examined the association between surveillance for deep vein thrombosis (DVT) among medical-surgical critically ill patients by twice-weekly ultrasonography and 90-day all-cause mortality. This was a pre-planned sub-study of the Pneumatic Compression for Preventing Venous Thromboembolism (PREVENT) trial (Clinicaltrials.gov: NCT02040103) that compared addition of intermittent pneumatic compression (IPC) to pharmacologic prophylaxis versus pharmacologic prophylaxis alone. The surveillance group included enrolled patients in the trial, while the non-surveillance group included eligible non-enrolled patients. Using logistic regression and Cox proportional hazards models, we examined the association of surveillance with the primary outcome of 90-day mortality. Secondary outcomes were DVT and pulmonary embolism (PE). The surveillance group consisted of 1682 patients and the non-surveillance group included 383 patients. Using Cox proportional hazards model with bootstrapping, surveillance was associated with a decrease in 90-day mortality (adjusted HR 0.75; 95% CI 0.57, 0.98). Surveillance was associated with earlier diagnosis of DVT [(median 4 days (IQR 2, 10) vs. 20 days (IQR 16, 22)] and PE [median 4 days (IQR 2.5, 5) vs. 7.5 days (IQR 6.1, 28.9)]. There was an increase in diagnosis of DVT (adjusted HR 5.49; 95% CI 2.92, 13.02) with no change in frequency in diagnosis of PE (adjusted HR 0.56; 95% CI 0.19, 1.91). Twice-weekly surveillance ultrasonography was associated with an increase in DVT detection, reduction in diagnostic testing for non-lower limb DVT and PE, earlier diagnosis of DVT and PE, and lower 90-day mortality. The PREVENT trial is registered at ClinicalTrials.gov, ID: NCT02040103. Registered on 3 November 2013; Current controlled trials, ID: ISRCTN44653506. Registered on 30 October 2013.

Background It is unclear whether screening for sepsis using an electronic alert in hospitalized ward patients improves outcomes. The objective of the Stepped-wedge Cluster Randomized Trial of Electronic Early Notification of Sepsis in Hospitalized Ward Patients (SCREEN) trial is to evaluate whether an electronic screening for sepsis compared to no screening among hospitalized ward patients reduces all-cause 90-day in-hospital mortality. Methods and design This study is designed as a stepped-wedge cluster randomized trial in which the unit of randomization or cluster is the hospital ward. An electronic alert for sepsis was developed in the electronic medical record (EMR), with the feature of being active (visible to treating team) or masked (inactive in EMR frontend for the treating team but active in the backend of the EMR). Forty-five clusters in 5 hospitals are randomized into 9 sequences of 5 clusters each to receive the intervention (active alert) over 10 periods, 2 months each, the first being the baseline period. Data are extracted from EMR and are compared between the intervention (active alert) and control group (masked alert). During the study period, some of the hospital wards were allocated to manage patients with COVID-19. The primary outcome of all-cause hospital mortality by day 90 will be compared using a generalized linear mixed model with a binary distribution and a log-link function to estimate the relative risk as a measure of effect. We will include two levels of random effects to account for nested clustering within wards and periods and two levels of fixed effects: hospitals and COVID-19 ward status in addition to the intervention. Results will be expressed as relative risk with a 95% confidence interval. Conclusion The SCREEN trial provides an opportunity for a novel trial design and analysis of routinely collected and entered data to evaluate the effectiveness of an intervention (alert) for a common medical problem (sepsis in ward patients). In this statistical analysis plan, we outline details of the planned analyses in advance of trial completion. Prior specification of the statistical methods and outcome analysis will facilitate unbiased analyses of these important clinical data. Trial registration ClinicalTrials.gov NCT04078594. Registered on September 6, 2019

Background Asia has more critically ill people than any other part of our planet. The aim of this article is to review the development of critical care as a specialty, critical care societies and education and research, the epidemiology of critical illness as well as epidemics and pandemics, accessibility and cost and quality of critical care, culture and end-of-life care, and future directions for critical care in Asia. Main body Although the first Asian intensive care units (ICUs) surfaced in the 1960s and the 1970s and specialisation started in the 1990s, multiple challenges still exist, including the lack of intensivists, critical care nurses, and respiratory therapists in many countries. This is aggravated by the brain drain of skilled ICU staff to high-income countries. Critical care societies have been integral to the development of the discipline and have increasingly contributed to critical care education, although critical care research is only just starting to take off through collaboration across groups. Sepsis, increasingly aggravated by multidrug resistance, contributes to a significant burden of critical illness, while epidemics and pandemics continue to haunt the continent intermittently. In particular, the coronavirus disease 2019 (COVID-19) has highlighted the central role of critical care in pandemic response. Accessibility to critical care is affected by lack of ICU beds and high costs, and quality of critical care is affected by limited capability for investigations and treatment in low- and middle-income countries. Meanwhile, there are clear cultural differences across countries, with considerable variations in end-of-life care. Demand for critical care will rise across the continent due to ageing populations and rising comorbidity burdens. Even as countries respond by increasing critical care capacity, the critical care community must continue to focus on training for ICU healthcare workers, processes anchored on evidence-based medicine, technology guided by feasibility and impact, research applicable to Asian and local settings, and rallying of governments for support for the specialty. Conclusions Critical care in Asia has progressed through the years, but multiple challenges remain. These challenges should be addressed through a collaborative approach across disciplines, ICUs, hospitals, societies, governments, and countries.

Objectives The selected combination was based on limited evidence clinically and in vitro on the efficacy of the Favipiravir and Hydroxychloroquine in SARS-CoV-2. The two medications were listed in many guidelines as treatment options and ongoing trials assessing their efficacy and safety. Thus, we want to prove the clinical effectiveness of the combination as therapy. Trial design This is an Open label, multicenter, randomized controlled clinical trial to evaluate the safety and efficacy of novel therapeutic agents in hospitalized adults diagnosed with COVID-19. It is a multicenter trial that will compare Favipiravir plus Hydroxychloroquine combination (experimental arm) to a control arm. Participants All study procedures will be conducted in eight centres in Saudia Arabia: King Abdulaziz Medical City National Guard Health Affairs in Riyadh. King Abdulaziz Hospital - Al Ahsa, Saudi Arabia AlMadina General Hospital, Madnia, Saudi Arabia Al-Qatif Central Hospital, Saudi Arabia Imam Abdulrahman Al Faisal Hospital, Dammam, Saudi Arabia King Abdulaziz Medical City, Jeddah, Saudi Arabia King Abdulaziz Hospital, Makkah, Saudi Arabia Imam Abdulrahman Alfaisal Hospital, Riyadh, Saudi Arabia Inclusion Criteria • Should be at least 18 years of age, • Male or nonpregnant female, • Diagnosed with COVID-19 by PCR confirmed SARS-coV-2 viral infection. • Able to sign the consent form and agree to clinical samples collection (or their legal surrogates if subjects are or become unable to make informed decisions).. • Moderate or Severe COVID-19, defined as oxygen saturation (Sao2) of 94% or less while they were breathing ambient air or significant clinical symptoms that require hospital admission. • patients had to be enrolled within 10 days of disease onset. Exclusion Criteria • Patients who are pregnant or breastfeeding. • Will be transferred to a non-study site hospital or discharged from hospital within 72 hours. • Known sensitivity/allergy to hydroxychloroquine or Favipiravir • Current use of hydroxychloroquine for another indication • Prior diagnosis of retinopathy • Prior diagnosis of glucose-6-phosphate dehydrogenase (G6PD) deficiency • Major comorbidities increasing the risk of study drug including: i. Hematologic malignancy, ii. Advanced (stage 4-5) chronic kidney disease or dialysis therapy, iii. Known history of ventricular arrhythmias, iv. Current use of drugs that prolong the QT interval, Severe liver damage (Child-Pugh score ≥ C, AST> 5 times the upper limit), HIV. • The investigator believes that participating in the trial is not in the best interests of the patient, or the investigator considers unsuitable for enrollment (such as unpredictable risks or subject compliance issues). • Clinical prognostic non-survival, palliative care, or in deep coma and no have response to supportive treatment within three hours of admission • Patient with irregular rhythm • Patient with a history of heart attack (myocardial infarction) • Patient with a family history of sudden death from heart attack before the age of 50 • Take other drugs that can cause prolonged QT interval • Patient who is receiving immunosuppressive therapy (cyclosporin) which cannot be switched to another agent or adjusted while using the investigational drug • Gout/history of Gout or hyperuricemia (above the ULN), hereditary xanthinuria or xanthine calculi of the urinary tract. Intervention and comparator The treatment intervention would be for a maximum of 10 days from randomization and it would be as follows: Favipiravir for 10 days: Administer 1800 mg (9 tablets) by mouth twice daily for one day, followed by 800mg (4 tablets) twice daily (total days of therapy is 10 days) Hydroxychloroquine for 5 days: (400mg) twice daily on day 1; for days 2-5 (200mg) twice daily. Reference Comparator Therapy: Standard of care is defined as: Treatment that is accepted by medical experts as a proper treatment for Covid-19 disease. Standard care comprised of, as necessary, supplemental oxygen, noninvasive and invasive ventilation, antibiotic agents, vasopressor support, renal-replacement therapy, extracorporeal membrane oxygenation (ECMO), and antiviral therapy except Favipiravir. Also, it may include intravenous fluids and medications for symptoms relief . Main outcomes The primary endpoint is the time to clinical improvement, defined as the time from randomization to an improvement of two points (from the status at randomization) on a seven-category ordinal scale or live discharge from the hospital, whichever came first (14 days from Randomization). Randomisation Eligible participants will be randomized in a 1:1 ratio to either the combination group (Favipiravir and Hydroxychloroquine) or a control group. The patients will be randomized utilizing Web based data entry System with a stratification based on the centre and the ICU admission. Blinding (masking) This is an Open label study and only the analyst will be blinded during the study conduct. Numbers to be randomised (sample size) Under the classical two arm parallel design the total effective sample sizes needed is 472 subjects (236 subjects per group). Trial status Protocol version 3.1 (dated 11 Aug 2020), and currently recruitment is ongoing. The date recruitment started was May 21, 2020 and the investigators anticipate the trial will finish recruiting by the end of December 2020. Trial registration ClinicalTrials.gov Identifier: NCT04392973, 19 May 2020 Full protocol The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

With the expanding use of molecular assays, viral pathogens are increasingly recognized among critically ill adult patients with community-acquired severe respiratory illness; studies have detected respiratory viral infections (RVIs) in 17–53% of such patients. In addition, novel pathogens including zoonotic coronaviruses like the agents causing Severe Acute Respiratory Syndrome (SARS), Middle East Respiratory Syndrome (MERS) and the 2019 novel coronavirus (2019 nCoV) are still being identified. Patients with severe RVIs requiring ICU care present typically with hypoxemic respiratory failure. Oseltamivir is the most widely used neuraminidase inhibitor for treatment of influenza; data suggest that early use is associated with reduced mortality in critically ill patients with influenza. At present, there are no antiviral therapies of proven efficacy for other severe RVIs. Several adjunctive pharmacologic interventions have been studied for their immunomodulatory effects, including macrolides, corticosteroids, cyclooxygenase-2 inhibitors, sirolimus, statins, anti-influenza immune plasma, and vitamin C, but none is recommended at present in severe RVIs. Evidence-based supportive care is the mainstay for management of severe respiratory viral infection. Non-invasive ventilation in patients with severe RVI causing acute hypoxemic respiratory failure and pneumonia is associated with a high likelihood of transition to invasive ventilation. Limited existing knowledge highlights the need for data regarding supportive care and adjunctive pharmacologic therapy that is specific for critically ill patients with severe RVI. There is a need for more pragmatic and efficient designs to test different therapeutics both individually and in combination. Electronic supplementary material The online version of this article (10.1007/s00134-020-05943-5) contains supplementary material, which is available to authorized users.

Background Sepsis is a health problem of global importance; treatments focus on controlling infection and supporting failing organs. Recent clinical research suggests that intravenous vitamin C may decrease mortality in sepsis. We have designed a randomized controlled trial (RCT) to ascertain the effect of vitamin C on the composite endpoint of death or persistent organ dysfunction at 28 days in patients with sepsis. Methods LOVIT (Lessening Organ dysfunction with VITamin C) is a multicenter, parallel-group, blinded (participants, clinicians, study personnel, Steering Committee members, data analysts), superiority RCT (minimum n = 800). Eligible patients have sepsis as the diagnosis for admission to the intensive care unit (ICU) and are receiving vasopressors. Those admitted to the ICU for more than 24 h are excluded. Eligible patients are randomized to high-dose intravenous vitamin C (50 mg/kg every 6 h for 96 h) or placebo. The primary outcome is a composite of death or persistent organ dysfunction (need for vasopressors, invasive mechanical ventilation, or new and persisting renal replacement therapy) at day 28. Secondary outcomes include persistent organ dysfunction-free days to day 28, mortality and health-related quality of life at 6 months, biomarkers of dysoxia, inflammation, infection, endothelial function, and adverse effects (hemolysis, acute kidney injury, and hypoglycemia). Six subgroup analyses are planned. Discussion This RCT will provide evidence of the effect of high-dose intravenous vitamin C on patient-important outcomes in patients with sepsis. Trial registration clinicaltrials.gov, NCT03680274, first posted 21 September 2018.

We present areas of uncertainty concerning intensive care unit-acquired weakness (ICUAW) and identify areas for future research. Age, pre-ICU functional and cognitive state, concurrent illness, frailty, and health trajectories impact outcomes and should be assessed to stratify patients. In the ICU, early assessment of limb and diaphragm muscle strength and function using nonvolitional tests may be useful, but comparison with established methods of global and specific muscle strength and physical function and determination of their reliability and normal values would be important to advance these techniques. Serial measurements of limb and respiratory muscle strength, and systematic screening for dysphagia, would be helpful to clarify if and how weakness of these muscle groups is independently associated with outcome. ICUAW, delirium, and sedatives and analgesics may interact with each other, amplifying the effects of each individual factor. Reduced mobility in patients with hypoactive delirium needs investigations into dysfunction of central and peripheral nervous system motor pathways. Interventional nutritional studies should include muscle mass, strength, and physical function as outcomes, and prioritize elucidation of mechanisms. At follow-up, ICU survivors may suffer from prolonged muscle weakness and wasting and other physical impairments, as well as fatigue without demonstrable weakness on examination. Further studies should evaluate the prevalence and severity of fatigue in ICU survivors and define its association with psychiatric disorders, pain, cognitive impairment, and axonal loss. Finally, methodological issues, including accounting for baseline status, handling of missing data, and inclusion of patient-centered outcome measures should be addressed in future studies.

PURPOSE: To analyze the relationship between hypercapnia developing within the first 48 h after the start of mechanical ventilation and outcome in patients with acute respiratory distress syndrome (ARDS). PATIENTS AND METHODS: We performed a secondary analysis of three prospective non-interventional cohort studies focusing on ARDS patients from 927 intensive care units (ICUs) in 40 countries. These patients received mechanical ventilation for more than 12 h during 1-month periods in 1998, 2004, and 2010. We used multivariable logistic regression and a propensity score analysis to examine the association between hypercapnia and ICU mortality. MAIN OUTCOMES: We included 1899 patients with ARDS in this study. The relationship between maximum PaCO2 in the first 48 h and mortality suggests higher mortality at or above PaCO2 of ≥50 mmHg. Patients with severe hypercapnia (PaCO2 ≥50 mmHg) had higher complication rates, more organ failures, and worse outcomes. After adjusting for age, SAPS II score, respiratory rate, positive end-expiratory pressure, PaO2/FiO2 ratio, driving pressure, pressure/volume limitation strategy (PLS), corrected minute ventilation, and presence of acidosis, severe hypercapnia was associated with increased risk of ICU mortality [odds ratio (OR) 1.93, 95% confidence interval (CI) 1.32 to 2.81; p = 0.001]. In patients with severe hypercapnia matched for all other variables, ventilation with PLS was associated with higher ICU mortality (OR 1.58, CI 95% 1.04-2.41; p = 0.032). CONCLUSIONS: Severe hypercapnia appears to be independently associated with higher ICU mortality in patients with ARDS. info:eu-repo/semantics/publishedVersion

To estimate the prevalence, risk factors, prophylactic treatment and impact on mortality for venous thromboembolism (VTE) in patients with moderate to severe traumatic brain injury (TBI) treated in the intensive care unit. A post hoc analysis of the erythropoietin in traumatic brain injury (EPO-TBI) trial that included twice-weekly lower limb ultrasound screening. Venous thrombotic events were defined as ultrasound-proven proximal deep venous thrombosis (DVT) or clinically detected pulmonary embolism (PE). Results are reported as events, percentages or medians and interquartile range (IQR). Cox regression analysis was used to calculate adjusted hazard ratios (HR) with 95% confidence intervals (CI) for time to VTE and death. Of 603 patients, 119 (19.7%) developed VTE, mostly comprising DVT (102 patients, 16.9%) with a smaller number of PE events (24 patients, 4.0%). Median time to DVT diagnosis was 6 days (IQR 2-11) and to PE diagnosis 6.5 days (IQR 2-16.5). Mechanical prophylaxis (MP) was used in 91% of patients on day 1, 97% of patients on day 3 and 98% of patients on day 7. Pharmacological prophylaxis was given in 5% of patients on day 1, 30% of patients on day 3 and 57% of patients on day 7. Factors associated with time to VTE were age (HR per year 1.02, 95% CI 1.01-1.03), patient weight (HR per kg 1.01, 95% CI 1-1.02) and TBI severity according to the International Mission for Prognosis and Analysis of Clinical Trials risk of poor outcome (HR per 10% increase 1.12, 95% CI 1.01-1.25). The development of VTE was not associated with mortality (HR 0.92, 95% CI 0.51-1.65). Despite mechanical and pharmacological prophylaxis, VTE occurs in one out of every five patients with TBI treated in the ICU. Higher age, greater weight and greater severity of TBI increase the risk. The development of VTE was not associated with excess mortality.

The effect of short-term caloric restriction on gene expression in critically ill patients has not been studied. In this sub-study of the PermiT trial (Permissive Underfeeding or Standard Enteral Feeding in Critically Ill Adults Trial- ISRCTN68144998), we examined gene expression patterns in peripheral white blood cells (buffy coat) associated with moderate caloric restriction (permissive underfeeding) in critically ill patients compared to standard feeding. Blood samples collected on study day 1 and 14 were subjected to total RNA extraction and gene expression using microarray analysis. We enrolled 50 patients, 25 in each group. Among 1751 tested genes, 332 genes in 12 pathways were found to be significantly upregulated or downregulated between study day 1 and 14 (global p value for the pathway ≤ 0.05). Using the heatmap, the differential expression of genes from day 1 to 14 in the permissive underfeeding group was compared to the standard feeding group. We further compared gene expression signal intensity in permissive underfeeding compared standard feeding by constructing univariate and multivariate linear regression models on individual patient data. We found differential expression of several genes with permissive underfeeding, most notably those related to metabolism, autophagy and other cellular functions, indicating that moderate differences in caloric intake trigger different cellular pathways.

Stress ulcer prophylaxis (SUP) using histamine-2-receptor antagonists has been a standard of care in intensive care units (ICUs) for four decades. Proton pump inhibitors (PPIs) are increasingly used despite apparently lower background rates of gastrointestinal bleeding and growing concerns about PPI-associated complications. Our objective was to understand the views and prescribing habits amongst Canadian physicians regarding SUP in the ICU and to gauge interest in a future randomized-controlled trial (RCT). We created a short self-administered survey about SUP for critically ill adults, evaluated its clinical sensibility, and pilot tested the instrument. We surveyed all physician members of the Canadian Critical Care Trials Group (CCCTG) by e-mail and sent reminders three and five weeks later. We received 94 of 111 (85%) surveys from the validated respondent pool between May and June, 2015. Respondents reported use of SUP most commonly in patients 1) receiving invasive mechanical ventilation (62, 66%), 2) expected to be ventilated for ≥ two days (25, 27%), or 3) receiving mechanical ventilation but nil per os (NPO) (20, 21%). Stress ulcer prophylaxis is discontinued when patients no longer receive mechanical ventilation (75%), no longer are NPO (22%), or are discharged from the ICU (19%). Stress ulcer prophylaxis involves PPIs in 68% of centres. Most respondents endorsed the need for a large rigorous RCT of PPI vs placebo to understand the risks and benefits of this practice. Stress ulcer prophylaxis is reportedly used primarily for the duration of mechanical ventilation. The CCCTG physicians believe that a placebo-controlled RCT is needed to evaluate the effectiveness and safety of contemporary SUP with PPIs.

Background It is recommended that critically ill patients undergo routine delirium monitoring with a valid and reliable tool such as the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU). However, the validity and reliability of the Arabic version of the CAM-ICU has not been investigated. Here, we test the validity and reliability of the Arabic CAM-ICU. Methods We conducted a psychometric study at ICUs in a tertiary-care hospital in Saudi Arabia. We recruited consecutive adult Arabic-speaking patients, who had stayed in the ICU for at least 24 hours, and had a Richmond Agitation-Sedation Scale (RASS) score ≥ − 2 at examination. Two well-trained examiners (ICU nurse and intensivist) independently assessed delirium in eligible patients with the Arabic CAM-ICU. Evaluations by the two examiners were compared with psychiatrist blind clinical assessment of delirium according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). Subgroup analyses were conducted for age, invasive mechanical ventilation, and gender. Results We included 108 patients (mean age: 62.6 ± 17.6; male: 51.9%), of whom 37% were on invasive mechanical ventilation. Delirium was diagnosed in 63% of enrolled patients as per the psychiatrist clinical assessment. The Arabic CAM-ICU sensitivity was 74% (95% confidence interval [CI] = 0.63–0.84) and 56% (95%CI = 0.44–0.68) for the ICU nurse and intensivist, respectively. Specificity was 98% (95%CI = 0.93–1.0) and 92% (95%CI = 0.84–1.0), respectively. Sensitivity was greater for mechanically-ventilated patients, women, and those aged ≥65 years. Specificity was greater for those aged

Background The demand for critical care beds is increasing out of proportion to bed availability. As a result, some critically ill patients are kept in the Emergency Department (ED boarding) awaiting bed availability. The aim of our study is to examine the impact of boarding in the ED on the outcome of patients admitted to the Intensive Care Unit(ICU). Methods This was a retrospective analysis of ICU data collected prospectively at King Abdulaziz Medical City, Riyadh from ED between January 2010 and December 2012 and all patients admitted during this time were evaluated for their duration of boarding. Patients were stratified into three groups according to the duration of boarding from ED. Those admitted less than 6 h were classified as Group I, between 6 and 24 h, Group II and more than 24 h as Group III. We carried out multivariate analysis to examine the independent association of boarding time with the outcome adjusting for variables like age, sex, APACHE, Mechanical ventilation, Creatinine, Platelets, INR. Results During the study period, 940 patients were admitted from the ED to ICU, amongst whom 227 (25%) were admitted to ICU within 6 h, 358 (39%) within 6–24 h and 355 (38%) after 24 h. Patients admitted to ICU within 6 h were younger [48.7 ± 22.2(group I) years, 50.6 ± 22.6 (group II), 58.2 ± 20.9 (group III) (P = 0.04)]with less mechanical ventilation duration[5.9 ± 8.9 days (Group I), 6.5 ± 8.1 (Group II) and 10.6 ± 10.5 (Group III), P = 0.04]. There was a significant increase in hospital mortality [51(22.5), 104(29.1), 132(37.2), P = 0.0006) and the ICU length of stay(LOS) [9.55 days (Group I), 9.8 (Group II) and 10.6 (Group III), (P = 0.002)] with increase in boarding duration. In addition, the delay in admission was an independent risk factor for ICU mortality(OR for group III vs group I is 1.90, P = 0.04) and hospital mortality(OR for group III vs Group I is 2.09, P = 0.007). Conclusion Boarding in the ED is associated with higher mortality. This data highlights the importance of this phenomenon and suggests the need for urgent measures to reduce boarding and to improve patient flow.

Background There is conflicting evidence about the relationship between the dose of enteral caloric intake and survival in critically ill patients. The objective of this systematic review and meta-analysis is to compare the effect of lower versus higher dose of enteral caloric intake in adult critically ill patients on outcome. Methods We reviewed MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus from inception through November 2015. We included randomized and quasi-randomized studies in which there was a significant difference in the caloric intake in adult critically ill patients, including trials in which caloric restriction was the primary intervention (caloric restriction trials) and those with other interventions (non-caloric restriction trials). Two reviewers independently extracted data on study characteristics, caloric intake, and outcomes with hospital mortality being the primary outcome. Results Twenty-one trials mostly with moderate bias risk were included (2365 patients in the lower caloric intake group and 2352 patients in the higher caloric group). Lower compared with higher caloric intake was not associated with difference in hospital mortality (risk ratio (RR) 0.953; 95 % confidence interval (CI) 0.838–1.083), ICU mortality (RR 0.885; 95 % CI 0.751–1.042), total nosocomial infections (RR 0.982; 95 % CI 0.878–1.077), mechanical ventilation duration, or length of ICU or hospital stay. Blood stream infections (11 trials; RR 0.718; 95 % CI 0.519–0.994) and incident renal replacement therapy (five trials; RR 0.711; 95 % CI 0.545–0.928) were lower with lower caloric intake. The associations between lower compared with higher caloric intake and primary and secondary outcomes, including pneumonia, were not different between caloric restriction and non-caloric restriction trials, except for the hospital stay which was lo nger with lower caloric intake in the c aloric restriction trials. Conclusions We found no association between the dose of caloric intake in adult critically ill patients and hospital mortality. Lower caloric intake was associated with lower risk of blood stream infections and incident renal replacement therapy (five trials only). The heterogeneity in the design, feeding route and timing and caloric dose among the included trials could limit our interpretation. Further studies are needed to clarify our findings. Electronic supplementary material The online version of this article (doi:10.1186/s13054-016-1539-3) contains supplementary material, which is available to authorized users.

To analyze the frequency, rationale and determinants of attending physicians requesting that their eligible patients not be approached for participation in a thromboprophylaxis trial. Research personnel in 67 centers prospectively documented eligible non-randomized patients due to physicians declining to allow their patients to be approached. In 67 centers, 3,764 patients were enrolled, but 1,460 eligible patients had no consent encounter. For 218 (14.9 %) of these, attending physicians requested that their patients not be approached. The most common reasons included a high risk of bleeding (31.2 %) related to fear of heparin bioaccumulation in renal failure, the presence of an epidural catheter, peri-operative status or other factors; specific preferences for thromboprophylaxis (12.4 %); morbid obesity (9.6 %); uncertain prognosis (6.4 %); general discomfort with research (3.7 %) and unclear reasons (17.0 %). Physicians were more likely to decline when approached by less experienced research personnel; considering those with >10 years of experience as the reference category, the odds ratios (OR) for physician refusals to personnel without trial experience was 10.47 [95 % confidence interval (CI) 2.19–50.02] and those with less than 10 years experience was 1.72 (95 % CI 0.61–4.84). Physicians in open rather than closed units were more likely to decline (OR 4.26; 95 % CI 1.27–14.34). Refusals decreased each year of enrollment compared to the pilot phase. Tracking, analyzing, interpreting and reporting the rates and reasons for physicians declining to allow their patients to be approached for enrollment provides insights into clinicians’ concerns and attitudes to trials. This information can encourage physician communication and education, and potentially enhance efficient recruitment.

Background Older age is associated with chronic illnesses and disability, which contribute to increased admission to the intensive care unit (ICU). Our primary objective was to compare the characteristics, ICU management and outcomes of critically ill patients ≥ 80 year-old with those of younger patients. Methods This was a retrospective cohort study of patients admitted to a tertiary-care ICU from 1999 to 2011. The characteristics, ICU management and outcomes of patients ≥ 80 year-old were compared with those 50–64.9 and 65–79.9 year-old. Multivariate analysis was performed to determine the adjusted risk of Do-Not-Resuscitate orders and hospital mortality in patients ≥ 80 year-old compared with the younger groups. Results During the study period, patients aged ≥ 80 years (N = 748) represented 7.9% of all ICU admissions and 12.8% of patients aged ≥ 50 years. Chronic cardiac (32.2%) and respiratory (21.8%) diseases were more prevalent in them than the younger groups (p

Background The objective of this study was to examine the outcomes of critically ill patients who were transferred from other hospitals to a tertiary care center in Saudi Arabia as a quality improvement project. Methods This was a retrospective study of adult patients admitted to the medical-surgical intensive care unit (ICU) of a tertiary care hospital. Patients were divided according to the source of referral into three groups: transfers from other hospitals, and direct admissions from emergency department (ED) and from hospital wards. Standardized mortality ratio (SMR) was calculated. Multivariate analysis was performed to determine the independent predictors of mortality. Results Of the 7,654 patients admitted to the ICU, 611 patients (8%) were transferred from other hospitals, 2,703 (35.3%) were direct admissions from ED and 4,340 (56.7%) from hospital wards. Hospital mortality for patients transferred from other hospitals was not significantly different from those who were directly admitted from ED (35% vs. 33.1%, p = 0.37) but was lower than those who were directly admitted from hospital wards (35% vs. 51.2%, p < 0.0001). SMRs did not differ significantly across the three groups. Conclusions Critically ill patients who were transferred from other hospitals constituted 8% of all ICU admissions. Mortality of these patients was similar to patients with direct admission from the ED and lower than that of patients with direct admission from hospital wards. However, risk-adjusted mortality was not different from the other two groups.

Daily sedation interruption and protocol implementation have been recommended to reduce excessive sedation; however, their use has been inconsistent. We hypothesized that the use of an age, kidney and liver function adjusted sedation protocol would be associated with reduced doses and improved outcomes compared with a standard protocol.

Background Nutritional support is an essential part of the management of critically ill patients. However, optimal caloric intake has not been systematically evaluated. We aim to compare two strategies of enteral feeding: permissive underfeeding versus target feeding. Method/Design This is an international multi-center randomized controlled trial in critically ill medical- surgical adult patients. Using a centralized allocation, 862 patients will be randomized to permissive underfeeding or target feeding. Patients in the permissive group receive 50% (acceptable range is 40% to 60%) of the calculated caloric requirement, while those in the targeted group receive 100% (acceptable range 70% to 100%) of the calculated caloric requirement. The primary outcome is 90-day all-cause mortality. Secondary outcomes include ICU and hospital mortality, 28-day, and 180-day mortality as well as health care-associated infections, organ failure, and length of stay in the ICU and hospital. The trial has 80% power to detect an 8% absolute reduction in 90-day mortality assuming a baseline risk of death of 25% at an alpha level of 0.05. Discussion Patient recruitment started in November 2009 and is currently active in five centers. The Data Monitoring Committee advised continuation of the trial after the first interim analysis. The study is expected to finish by November 2013. Trial registration Current Controlled Trials ISRCTN68144998

Background The importance of intra-abdominal pressure (IAP) and abdominal perfusion pressure (APP) in cirrhotic patients with septic shock is not well studied. We evaluated the relationship between IAP and APP and outcomes of cirrhotic septic patients, and assessed the ability of these measures compared to other common resuscitative endpoints to differentiate survivors from nonsurvivors. Methods This study was a post hoc analysis of a randomized double-blind placebo-controlled trial in which mean arterial pressure (MAP), central venous oxygen saturation (ScvO2) and IAP were measured every 6 h in 61 cirrhotic septic patients admitted to the intensive care unit. APP was calculated as MAP - IAP. Intra-abdominal hypertension (IAH) was defined as mean IAP ≥ 12 mmHg, and abdominal hypoperfusion as mean APP < 60 mmHg. Measured outcomes included ICU and hospital mortality, need for renal replacement therapy (RRT) and ventilator- and vasopressor-free days. Results IAH prevalence on the first ICU day was 82%, and incidence in the first 7 days was 97%. Compared to patients with normal IAP, IAH patients had significantly higher ICU mortality (74.0% vs. 27.3%, p = 0.005), required more RRT (78.0% vs. 45.5%, p = 0.06) and had lower ventilator- and vasopressor-free days. On a multivariate logistic regression analysis, IAH was an independent predictor of both ICU mortality (odds ratio (OR), 12.20; 95% confidence interval (CI), 1.92 to 77.31, p = 0.008) and need for RRT (OR, 6.78; 95% CI, 1.29 to 35.70, p = 0.02). Using receiver operating characteristic curves, IAP (area under the curve (AUC) = 0.74, p = 0.004), APP (AUC = 0.71, p = 0.01), Acute Physiology and Chronic Health Evaluation II score (AUC = 0.71, p = 0.02), but not MAP, differentiated survivors from nonsurvivors. Conclusions IAH is highly prevalent in cirrhotic patients with septic shock and is associated with increased ICU morbidity and mortality.

The objective of this study was to evaluate the impact of CHF on severe sepsis and septic shock survivor outcomes after 1 year of hospital discharge.

Background The effect of statin therapy on mortality in critically ill patients is controversial, with some studies suggesting a benefit and others suggesting no benefit or even potential harm. The objective of this study was to evaluate the association between statin therapy during intensive care unit (ICU) admission and all-cause mortality in critically ill patients. Methods This was a nested cohort study within two randomised controlled trials conducted in a tertiary care ICU. All 763 patients who participated in the two trials were included in this study. Of these, 107 patients (14%) received statins during their ICU stay. The primary endpoint was all-cause ICU and hospital mortality. Secondary endpoints included the development of sepsis and severe sepsis during the ICU stay, the ICU length of stay, the hospital length of stay, and the duration of mechanical ventilation. Multivariate logistic regression was used to adjust for clinically and statistically relevant variables. Results Statin therapy was associated with a reduction in hospital mortality (adjusted odds ratio [aOR] = 0.60, 95% confidence interval [CI] 0.36-0.99). Statin therapy was associated with lower hospital mortality in the following groups: patients >58 years of age (aOR = 0.58, 95% CI 0.35-0.97), those with an acute physiology and chronic health evaluation (APACHE II) score >22 (aOR = 0.54, 95% CI 0.31-0.96), diabetic patients (aOR = 0.52, 95% CI 0.30-0.90), patients on vasopressor therapy (aOR = 0.53, 95% CI 0.29-0.97), those admitted with severe sepsis (aOR = 0.22, 95% CI 0.07-0.66), patients with creatinine ≤100 μmol/L (aOR = 0.14, 95% CI 0.04-0.51), and patients with GCS ≤9 (aOR = 0.34, 95% CI 0.17-0.71). When stratified by statin dose, the mortality reduction was mainly observed with statin equipotent doses ≥40 mg of simvastatin (aOR = 0.53, 95% CI 0.28-1.00). Mortality reduction was observed with simvastatin (aOR = 0.37, 95% CI 0.17-0.81) but not with atorvastatin (aOR = 0.80, 95% CI 0.84-1.46). Statin therapy was not associated with a difference in any of the secondary outcomes. Conclusion Statin therapy during ICU stay was associated with a reduction in all-cause hospital mortality. This association was especially noted in high-risk subgroups. This potential benefit needs to be validated in a randomised, controlled trial.

Traumatic brain injury studies predominantly use an assessment of neurological function some time after hospital discharge as the primary endpoint. Recent studies have followed up patients at 6 months after injury with very variable loss to follow up [1,2]. We have established an outcome process that minimises loss to follow up and maximises the quality of the outcome assessment.

Staphylococcus aureus including MRSA (15.3%), Klebsiella spp. (6.8%), Haemophilus spp. (6.1%), and Enterobacter spp. (5.0%). Acinetobacterspp. and MRSA were significantly associated with late-onset VAP while Haemophilus spp. and Streptococcus pneumoniae were significantly associated with early-onset VAP. Acinetobacter spp. was the only pathogen associated with recurrent VAP and its incidence showed a significant increasing trend during the study period. Acinetobacter spp. was significantly associated with prolonged ventilation, sedation, and nasogastric intubation.

Central Line Associated Bloodstream Infection (CLABSI) is a major source of morbidity, mortality and increased medical costs among adult patients admitted to ICU. Risk factors for CLABSI include inappropriate central line insertion practices and catheter care.

Introduction Hyperglycemia represents an independent prognostic factor in critically ill non-diabetic patients but not in those with diabetes. In this context, there is an ongoing debate on the benefit of an intensive insulin therapy, particularly in diabetic patients. We tested the hypothesis that expression of the receptor for advanced glycation end-products (RAGE), an important signal transduction receptor that elicits long-lasting nuclear factor kappa B (NF-κB) activation, may underlie this difference. RAGE expression is regulated by multiple ligands, including high mobility group box-1 (HMGB-1), and is reflected by its released soluble form (sRAGE). Methods A predesigned analysis was conducted of prospectively collected samples from 76 hyperglycemic critically ill patients (33 type-2 diabetes, 43 non-diabetes) aged ≥18 years with blood glucose of > 6.1 mmol/L enrolled in a randomized controlled trial comparing intensive insulin therapy with conventional insulin therapy. sRAGE and its ligand HMGB-1 together with IL-6, and soluble thrombomodulin (as markers of inflammation and endothelial cell injury, respectively) were evaluated in ICU, at Days 1, 3, 5 and 7. Plasma samples from 18 healthy subjects were used as controls. Results Both diabetic and non-diabetic hyperglycemic patients showed increased plasma sRAGE, HMGB-1 and soluble thrombomodulin levels at the time of admission to ICU. Plasma IL-6 concentration was only increased in non-diabetic patients. Plasma levels of sRAGE were higher in diabetic compared with non-diabetic patients. Intensive insulin therapy resulted in a significant decrease of sRAGE and thrombomodulin at Day 7, in diabetic but not in non-diabetic patients. Circulating sRAGE levels correlated positively with IL-6 and soluble thrombomodulin levels and inversely with HMGB-1. Multivariate regression analysis demonstrated that sRAGE remains independently correlated with HMGB-1 only in diabetic patients. Neither sRAGE nor any inflammatory markers are associated with mortality. Conclusions These findings support the hypothesis that sRAGE release, time-course and response to intensive insulin therapy differ between hyperglycemic diabetic and non-diabetic critically ill patients. Whether this difference underlies the dissimilarity in clinical outcome of hyperglycemia in these two conditions warrants further studies.

You are appointed director of a new large multi-discipline intensive care unit in an academic center. The hospital is affiliated with a medical school and as such there will be an adequate number of medical students, residents, and fellows (specializing in critical care) rotating through the unit. The unit will be a 'closed' (intensivist-led) model. In setting up the call schedule for the intensivists, you need to decide whether the mandate will be for the intensivists to provide 24/7 in-house coverage as opposed to off-hour coverage from home. You wonder about the sustainability of each model.

Whether it is the primary reason for admission or a complication of critical illness, upper gastrointestinal bleeding is commonly encountered in the intensive care unit. In this setting, in the absence of endoscopy, intensivists generally provide supportive care (transfusion of blood products) and acid suppression (such as proton pump inhibitors). More recently, octreotide (a somatostatin analogue) has been used in such patients. However, its precise role in patients with upper gastrointestinal bleeding is not necessarily clear and the drug is associated with significant costs. In this issue of Critical Care, two expert teams debate the merits of using octreotide in non-variceal upper gastrointestinal bleeding.

Early tracheostomy has been associated with improved outcome in patients with high likelihood of death or ventilator dependency. While a significant number of patients with acute lung injury (ALI) require prolonged mechanical ventilation and could potentially benefit from early tracheostomy, lack of an accurate prediction limits its utilization in this group of patients.

A significant proportion of trauma patients require tracheostomy during intensive care unit stay. The timing of this procedure remains a subject of debate. The decision for tracheostomy should take into consideration the risks and benefits of prolonged endotracheal intubation versus tracheostomy. Timing of tracheostomy is also influenced by the indications for the procedure, which include relief of upper airway obstruction, airway access in patients with cervical spine injury, management of retained airway secretions, maintenance of patent airway and airway access for prolonged mechanical ventilation. This review summarizes the potential advantages of tracheostomy versus endotracheal intubation, the different indications for tracheostomy in trauma patients and studies examining early versus late tracheostomy. It also reviews the predictors of prolonged mechanical ventilation, which may guide the decision regarding the timing of tracheostomy.

Despite the integral role played by tracheostomy in the management of trauma patients admitted to intensive care units (ICUs), its timing remains subject to considerable practice variation. The purpose of this study is to examine the impact of early tracheostomy on the duration of mechanical ventilation, ICU length of stay, and outcomes in trauma ICU patients. The following data were obtained from a prospective ICU database containing information on all trauma patients who received tracheostomy over a 5-year period: demographics, Acute Physiology and Chronic Health Evaluation II score, Simplified Acute Physiology Score II, Glasgow Coma Scale score, Injury Severity Score, type of injuries, ICU and hospital outcomes, ICU and hospital length of stay (LOS), and the type of tracheostomy procedure (percutaneous versus surgical). Tracheostomy was considered early if it was performed by day 7 of mechanical ventilation. We compared the duration of mechanical ventilation, ICU LOS and outcome between early and late tracheostomy patients. Multivariate analysis was performed to assess the impact of tracheostomy timing on ICU stay. Of 653 trauma ICU patients, 136 (21%) required tracheostomies, 29 of whom were early and 107 were late. Age, sex, Acute Physiology and Chronic Health Evaluation II score, Simplified Acute Physiology Score II and Injury Severity Score were not different between the two groups. Patients with early tracheostomy were more likely to have maxillofacial injuries and to have lower Glasgow Coma Scale score. Duration of mechanical ventilation was significantly shorter with early tracheostomy (mean ± standard error: 9.6 ± 1.2 days versus 18.7 ± 1.3 days; P 14 days). Early tracheostomy in trauma ICU patients is associated with shorter duration of mechanical ventilation and ICU LOS, without affecting ICU or hospital outcome. Adopting a standardized strategy of early tracheostomy in appropriately selected patients may help in reducing unnecessary resource utilization.

Introduction We conducted the present study to assess the validity of mortality prediction systems in patients admitted to the intensive care unit (ICU) with severe sepsis and septic shock. We included Acute Physiology and Health Evaluation (APACHE) II, Simplified Acute Physiology Score (SAPS) II, Mortality Probability Model (MPM) II0 and MPM II24 in our evaluation. In addition, SAPS II and MPM II24 were customized for septic patients in a previous study, and the customized versions were included in this evaluation. Materials and method This cohort, prospective, observational study was conducted in a tertiary care medical/surgical ICU. Consecutive patients meeting the diagnostic criteria for severe sepsis and septic shock during the first 24 hours of ICU admission between March 1999 and August 2001 were included. The data necessary for mortality prediction were collected prospectively as part of the ongoing ICU database. Predicted and actual mortality rates, and standardized mortality ratio were calculated. Calibration was assessed using Lemeshow-Hosmer goodness of fit C-statistic. Discrimination was assessed using receiver operating characteristic curves. Results The overall mortality prediction was adequate for all six systems because none of the standardized mortality ratios differed significantly from 1. Calibration was inadequate for APACHE II, SAPS II, MPM II0 and MPM II24. However, the customized version of SAPS II exhibited significantly improved calibration (C-statistic for SAPS II 23.6 (P = 0.003) and for customized SAPS II 11.5 (P = 0.18)). Discrimination was best for customized MPM II24 (area under the receiver operating characteristic curve 0.826), followed by MPM II 24 and customized SAPS II. Conclusion Although general ICU mortality system models had accurate overall mortality prediction, they had poor calibration. Customization of SAPS II and, to a lesser extent, MPM II 24 improved calibration. The customized model may be a useful tool when evaluating outcomes in patients with sepsis.