Association Between Minimum Inhibitory Concentration, Beta-lactamase Genes and Mortality for Patients Treated With Piperacillin/Tazobactam or Meropenem From the MERINO Study.

INTRODUCTION: This study aims to assess the association of piperacillin/tazobactam and meropenem minimum inhibitory concentration (MIC) and beta-lactam resistance genes with mortality in the MERINO trial. METHODS: Blood culture isolates from enrolled patients were tested by broth microdilution and whole genome sequencing at a central laboratory. Multivariate logistic regression was performed to account for confounders. Absolute risk increase for 30-day mortality between treatment groups was calculated for the primary analysis (PA) and the microbiologic assessable (MA) populations. RESULTS: In total, 320 isolates from 379 enrolled patients were available with susceptibility to piperacillin/tazobactam 94% and meropenem 100%. The piperacillin/tazobactam nonsusceptible breakpoint (MIC >16 mg/L) best predicted 30-day mortality after accounting for confounders (odds ratio 14.9, 95% confidence interval [CI] 2.8-87.2). The absolute risk increase for 30-day mortality for patients treated with piperacillin/tazobactam compared with meropenem was 9% (95% CI 3%-15%) and 8% (95% CI 2%-15%) for the original PA population and the post hoc MA populations, which reduced to 5% (95% CI -1% to 10%) after excluding strains with piperacillin/tazobactam MIC values >16 mg/L. Isolates coharboring extended spectrum ß-lactamase (ESBL) and OXA-1 genes were associated with elevated piperacillin/tazobactam MICs and the highest risk increase in 30-day mortality of 14% (95% CI 2%-28%). CONCLUSIONS: After excluding nonsusceptible strains, the 30-day mortality difference from the MERINO trial was less pronounced for piperacillin/tazobactam. Poor reliability in susceptibility testing performance for piperacillin/tazobactam and the high prevalence of OXA coharboring ESBLs suggests that meropenem remains the preferred choice for definitive treatment of ceftriaxone nonsusceptible Escherichia coli and Klebsiella.

Neuromuscular blockade in patients with ARDS: a rapid practice guideline.

The aim of this Intensive Care Medicine Rapid Practice Guideline (ICM-RPG) is to formulate an evidence-based guidance for the use of neuromuscular blocking agents (NMBA) in adults with acute respiratory distress syndrome (ARDS). The panel comprised 20 international clinical experts from 12 countries, and 2 patient representatives. We adhered to the methodology for trustworthy clinical practice guidelines and followed a strict conflict of interest policy. We convened panelists through teleconferences and web-based discussions. Guideline experts from the guidelines in intensive care, development, and evaluation Group provided methodological support. Two content experts provided input and shared their expertise with the panel but did not participate in drafting the final recommendations. We followed the Grading of Recommendations Assessment, Development, and Evaluation approach to assess the certainty of evidence and grade recommendations and suggestions. We used the evidence to decision framework to generate recommendations. The panel provided input on guideline implementation and monitoring, and suggested future research priorities. The overall certainty in the evidence was low. The ICM-RPG panel issued one recommendation and two suggestions regarding the use of NMBAs in adults with ARDS. Current evidence does not support the early routine use of an NMBA infusion in adults with ARDS of any severity. It favours avoiding a continuous infusion of NMBA for patients who are ventilated using a lighter sedation strategy. However, for patients who require deep sedation to facilitate lung protective ventilation or prone positioning, and require neuromuscular blockade, an infusion of an NMBA for 48 h is a reasonable option.

Association of protein intake with the outcomes of critically ill patients: a post hoc analysis of the PermiT trial.

Background: The optimal amount of protein intake in critically ill patients is uncertain. Objective: In this post hoc analysis of the PermiT (Permissive Underfeeding vs. Target Enteral Feeding in Adult Critically Ill Patients) trial, we tested the hypothesis that higher total protein intake was associated with lower 90-d mortality and improved protein biomarkers in critically ill patients. Design: In this post hoc analysis of the PermiT trial, we included patients who received enteral feeding for ≥3 consecutive days. Using the median protein intake of the cohort as a cutoff, patients were categorized into 2 groups: a higher-protein group (>0.80 g · kg-1 · d-1) and a lower-protein group (≤0.80 g · kg-1 · d-1). We developed a propensity score for receiving higher protein. Primary outcome was 90-d mortality. We also compared serial values of prealbumin, transferrin, 24-h urinary nitrogen, and 24-h nitrogen balance on days 1, 7, and 14. Results: Among the 729 patients included in this analysis, the average protein intake was 0.8 ± 0.3 g · kg-1 · d-1 [1.0 ± 0.2 g · kg-1 · d-1 in the higher-protein group (n = 365) and 0.6 ± 0.2 g · kg-1 · d-1 in the lower-protein group (n = 364); P < 0.0001]. There was no difference in 90-d mortality between the 2 groups [88/364 (24.2%) compared with 94/363 (25.9%), propensity score-adjusted OR: 0.80; 95% CI: 0.56, 1.16; P = 0.24]. Higher protein intake was associated with an increase in 24-h urea nitrogen excretion compared with lower protein intake, but without a significant change in prealbumin, transferrin, or 24-h nitrogen balance. Conclusions: In the PermiT trial, a moderate difference in protein intake was not associated with lower mortality. Higher protein intake was associated with increased nitrogen excretion in the urine without a corresponding change in prealbumin, transferrin, or nitrogen balance. Protein intake needs to be tested in adequately powered randomized controlled trials targeting larger differences in protein intake in high-risk populations.

Learning from defects using a comprehensive management system for incident reports in critical care.

Incident reporting systems are often used without a structured review process, limiting their utility to learn from defects and compromising their impact on improving the healthcare system. The objective of this study is to describe the experience of implementing a Comprehensive Management System (CMS) for incident reports in the ICU. A physician-led multidisciplinary Incident Report Committee was created to review, analyse and manage the department incident reports. New protocols, policies and procedures, and other patient safety interventions were developed as a result. Information was disseminated to staff through multiple avenues. We compared the pre- and post-intervention periods for the impact on the number of incident reports, level of harm, time needed to close reports and reporting individuals. A total of 1719 incidents were studied. ICU-related incident reports increased from 20 to 36 incidents per 1000 patient days (P=0.01). After implementing the CMS, there was an increase in reporting 'no harm' from 14.2 to 28.1 incidents per 1000 patient days (P<0.001). There was a significant decrease in the time needed to close incident report after implementing the CMS (median of 70 days [Q1-Q3: 26-212] versus 13 days [Q1-Q3: 6-25, P<0.001]). A physician-led multidisciplinary CMS resulted in significant improvement in the output of the incident reporting system. This may be important to enhance the effectiveness of incident reporting systems in highlighting system defects, increasing learning opportunities and improving patient safety.

Appropriate and timely antimicrobial therapy in cirrhotic patients with spontaneous bacterial peritonitis-associated septic shock: a retrospective cohort study.

BACKGROUND: Spontaneous bacterial peritonitis (SBP)-associated septic shock carries significant mortality in cirrhosis. AIM: To determine whether practice-related aspects of antimicrobial therapy contribute to high mortality. METHODS: Retrospective cohort study of all (n = 126) cirrhotics with spontaneous bacterial peritonitis (neutrophil count >250 or positive ascitic culture)-associated septic shock (1996-2011) from an international, multicenter database. Appropriate antimicrobial therapy implied either in vitro activity against a subsequently isolated pathogen (culture positive) or empiric management consistent with broadly accepted norms (culture negative). RESULTS: Overall hospital mortality was 81.8%. Comparing survivors (n = 23) with non-survivors (n = 103), survivors had lower Acute Physiology and Chronic Health Evaluation (APACHEII) (mean ± s.d.; 22 ± 7 vs. 32 ± 8) and model for end-stage liver disease (MELD) (24 ± 9 vs. 34 ± 11) scores and serum lactate on admission (4.9 ± 3.1 vs. 8.9  ± 5.3), P < 0.001 for all. Survivors were less likely to receive inappropriate initial antimicrobial therapy (0% vs. 25%, P = 0.013) and received appropriate antimicrobial therapy earlier [median 1.8 (1.1-5.2) vs. 9.5 (3.9-14.3) h, P < 0.001]. After adjusting for covariates, APACHEII [OR, odds ratio 1.45 (1.04-2.02) per 1 unit increment, P = 0.03], lactate [OR 2.34 (1.04-5.29) per unit increment, P = 0.04] and time delay to appropriate antimicrobials [OR 1.86 (1.10-3.14) per hour increment, P = 0.02] were significantly associated with increased mortality. CONCLUSIONS: Cirrhotic patients with septic shock secondary to spontaneous bacterial peritonitis have high mortality (>80%). Each hour of delay in appropriate antimicrobial therapy was associated with a 1.86 times increased hospital mortality. Admission APACHEII and serum lactate also significantly impacted hospital mortality. Earlier initiation of appropriate antimicrobial therapy could substantially improve outcome.

Severe neurologic syndrome associated with Middle East respiratory syndrome corona virus (MERS-CoV).

BACKGROUND: Since the identification of the first case of infection with the Middle East respiratory syndrome corona virus (MERS-CoV) in Saudi Arabia in June 2012, the number of laboratory-confirmed cases has exceeded 941 cases globally, of which 347 died. The disease presents as severe respiratory infection often with shock, acute kidney injury, and coagulopathy. Recently, we observed three cases who presented with neurologic symptoms. These are so far the first reported cases of neurologic injury associated with MERS-CoV infection. METHODS: Data was retrospectively collected from three patients admitted with MERS-CoV infection to Intensive Care unit (ICU) at King Abdulaziz Medical City, Riyadh. They were managed separately in three different wards prior to their admission to ICU. FINDING: The three patients presented with severe neurologic syndrome which included altered level of consciousness ranging from confusion to coma, ataxia, and focal motor deficit. Brain MRI revealed striking changes characterized by widespread, bilateral hyperintense lesions on T2-weighted imaging within the white matter and subcortical areas of the frontal, temporal, and parietal lobes, the basal ganglia, and corpus callosum. None of the lesions showed gadolinium enhancement. INTERPRETATION: CNS involvement should be considered in patients with MERS-CoV and progressive neurological disease, and further elucidation of the pathophysiology of this virus is needed.

Relationship between intracranial pressure monitoring and outcomes in severe traumatic brain injury patients.

Intracranial pressure (ICP) monitoring is recommended in patients with a severe traumatic brain injury (TBI) and an abnormal computed tomography (CT) scan. However, there is contradicting evidence about whether ICP monitoring improves outcome. The purpose of this study was to examine the relationship between ICP monitoring and outcomes in patients with severe TBI. From February 2001 to December 2008, a total of 477 consecutive adult (> or =18 years) patients with severe TBI were included retrospectively in the study. Patients who underwent ICP monitoring (n=52) were compared with those who did not (n=425). The primary outcome was hospital mortality. Secondary outcomes were ICU mortality, mechanical ventilation duration, the need for tracheostomy, and ICU and hospital length of stay (LOS). After adjustment for multiple potential confounding factors, ICP monitoring was not associated with significant difference in hospital or ICU mortality (odds ratio [OR] = 1.71, 95% confidence interval [CI] = 0.79 to 3.70, P = 0.17; OR = 1.01, 95% CI = 0.41 to 2.45, P = 0.99, respectively). ICP monitoring was associated with a significant increase in mechanical ventilation duration (coefficient = 5.66, 95% CI = 3.45 to 7.88, P < 0.0001), need for tracheostomy (OR = 2.02, 95% CI = 1.02 to 4.03, P = 0.04), and ICU LOS (coefficient = 5.62, 95% CI = 3.27 to 7.98, P < 0.0001), with no significant difference in hospital LOS (coefficient = 8.32, 95% CI = -82.6 to 99.25, P = 0.86). Stratified by the Glasgow Coma Scale score, ICP monitoring was associated with a significant increase in hospital mortality in the group of patients with Glasgow Coma Scale 7 to 8 (adjusted OR = 12.89, 95% CI = 3.14 to 52.95, P = 0.0004). In patients with severe TBI, ICP monitoring was not associated with reduced hospital mortality, however with a significant increase in mechanical ventilation duration, need for tracheostomy, and ICU LOS.

Glycaemic fluctuation predicts mortality in critically ill patients.

Growing evidence suggests that glycaemic variability increases diabetic complications. However, the significance of glycaemic variability in critically ill patients remains unclear. We evaluated the predictors of glycaemic fluctuation and its association with critical care outcomes. This is a nested-cohort study within a clinical trial in which 523 patients at a medical surgical intensive care unit were randomised to either intensive insulin therapy (target glycaemic control: 4.4 to 6.1 mmol/l) or conventional insulin therapy (target control: 10.0 to 11.1 mmol/l). Glycaemic fluctuation was defined as the mean difference between the highest and lowest daily blood glucose. Patients were divided into wide and narrow fluctuation groups according to the median glycaemic fluctuation (6.0 mmol/l). The association between glycaemic fluctuation and different intensive care unit outcomes was studied. Predictors of glycaemic fluctuation were age (odds ratio for each year increment 1.03, 95% confidence interval 1.02 to 1.05), diabetes mellitus (odds ratio 3.00, 95% confidence interval 1.74 to 5.17), and daily insulin dose (odds ratio for each unit increment 1.04, 95% confidence interval 1.03 to 1.05). Similar levels of glucose fluctuation were observed in intensive insulin therapy and conventional insulin therapy patients. Wide glycaemic fluctuation was associated with higher mortality (22.2 vs. 8.4%, P < 0.001). Glycaemic fluctuation was identified as an independent predictor of intensive care unit mortality (odds ratio per mmol 1.08, 95% confidence interval 1.00 to 1.18) and hospital mortality (odds ratio per mmol 1.09, 95% confidence interval 1.02 to 1.17) using multivariate logistic regression analysis. In conclusion, wide glycaemic fluctuation is an independent predictor of mortality in critically ill patients. Whether reducing glycaemic fluctuation would lead to better outcomes needs further evaluation.

Safety of percutaneous tracheostomy in obese critically ill patients: a prospective cohort study.

Obesity has been described as a relative contraindication for percutaneous tracheostomy. The objective of our study was to examine the safety and complications of percutaneous tracheostomy in obese patients. We conducted a prospective cohort study of all consecutive patients who underwent percutaneous tracheostomy at a tertiary medical-surgical intensive care unit between May 2004 and October 2005. We compared percutaneous tracheostomy in obese patients (body mass index > or = 30 kg/m2) to non-obese patients. We documented the occurrence of the following complications: aborting the procedure, accidental extubation, conversion to surgical tracheostomy, paratracheal placement, the development of pneumothorax, major bleeding (requiring blood product transfusion or surgical intervention) or death. We also documented hypoxia, minor bleeding (requiring pressure dressing or suturing), subcutaneous emphysema and transient hypotension. During the study period, 227 percutaneous tracheostomies were performed. There were 50 percutaneous tracheostomies in the obese group and 177 in the non-obese group. In 45 obese patients, percutaneous tracheostomy was performed without bronchoscopic guidance. Major complications were significantly higher in obese patients (12% vs. 2%, P = 0.04), while the rate of minor complications was not significantly different between the two groups. There were no instances of death or pneumothorax, subcutaneous emphysema or need for surgical intervention during or in the postoperative period in either group. Our study suggests that percutaneous tracheostomy can be performed safely in the majority of obese patients.

The diagnostic yield and clinical impact of a chest X-ray after percutaneous dilatational tracheostomy: a prospective cohort study.

A chest X-ray (CXR) is routinely performed after percutaneous dilatational tracheostomy (PDT). The purpose of this study was to evaluate the diagnostic yield of routine CXR following PDT and its impact on patient management and to identify predictors of post-PDT CXR changes. Two-hundred-and-thirty-nine patients who underwent PDT in a 21-bed intensive care unit were included prospectively in the study. The following data were collected: patient demographics, APACHE III scores, pre-PDT FiO2 and PEEP, PDT technique, perioperative complications and the use of bronchoscopic guidance. We compared post-PDT CXR with the last pre-PDT CXR. We documented any post-PDT new radiographic findings including atelectasis, pneumothorax, pneumomediastinum, surgical emphysema, pulmonary infiltrates or tracheostomy tube malposition. We also recorded management modifications based on post-PDT radiographic changes, including increased PEEP, chest physiotherapy, therapeutic bronchoscopy or chest tube insertion. Atelectasis was the only new finding detected on post-PDT CXRs of 24 (10%) patients. The new radiographic findings resulted in a total of 14 modifications of management in 10 (4%) patients including increased PEEP in six, chest physiotherapy in six and bronchoscopy in two patients. Trauma and pre-PDT PEEP >5 cmH2O were independent predictors of post-PDT CXR changes. Routine CXR following PDT has a low diagnostic yield, detecting mainly atelectasis and leading to a change in the management in only a minority ofpatients. Routine CXR after apparently uncomplicated PDT performed by an experienced operator may not be necessary and selective use may improve its diagnostic yield. Further studies are required to validate the safety of selective versus routine post-PDT CXR.

Microbiology of community-acquired pneumonia in the Gulf Corporation Council states.

In spite of advances in microbiological and serological investigations over the last two decades, etiological attribution remains difficult in community-acquired pneumonia (CAP). Even after exhaustive investigation, the etiology of CAP remains unknown in up to 50% of patients. Common pathogens include Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis. In addition, several investigators document the importance of atypical pathogens including Mycoplasma pneumoniae, Chlamydophila pneumoniae and Legionella pneumophila in the etiology of CAP in the GCC region. Increasingly, other etiologies, particularly influenza viruses, varicella zoster virus and Mycobacterium tuberculosis, have been recognized as causative pathogens of CAP within the region. Rates of antimicrobial resistance of S. pneumoniae and other pathogens are rising in the Gulf Corporation Council (GCC) region and susceptibility profiles of antibiotics against intracellular pathogens such as Chlamydophila pneumoniae and Mycoplasma pneumoniae are not routinely performed. Injudicious prescribing and over-use of antibiotics drive much resistance. The GCC CAPWG calls for urgent governmental regulations to limit and monitor antibiotic prescription in the GCC region.

Clinical presentation and diagnostic workup for community-acquired pneumonia: the Gulf Corporation Council CAP Working Group consensus statement.

Community-acquired pneumonia (CAP) is diagnosed on the basis of a suggestive history and compatible physical findings and new infiltrates on a chest radiograph. No criteria or combination of criteria based on history and physical examination have been found to be gold standard. With the rise in elderly Gulf Cooperation Council (GCC) residents, CAP is likely to present with non-classical manifestations such as somnolence, new anorexia, and confusion and carries a worse outcome than CAP in their younger counterparts. Tuberculosis should be considered in the differential diagnosis of unresolving CAP in the GCC region. Diagnostic work up depends on severity of CAP, clinical course and underlying risk factors.

Management and prevention strategies for community-acquired pneumonia in the Gulf Corporation Council.

Risk factors identify likelihood and severity of community-acquired pneumonia (CAP) and may allow prognostication. Prognostic factors can focus resources and efforts on those who may need special observation. Several risk assessment tools are used to estimate the severity of CAP and whether these tools can be used to predict outcomes, to determine disposition or even used to determine ICU level of care is hotly under debate. Treating CAP depends on age and comorbidities, as well as local epidemiology and disease severity. The current guidelines for managing CAP categorize patients with CAP into the healthy outpatient, the outpatient with modifying factors or comorbidities, the inpatient with CAP and patients requiring intensive care unit admission. These guidelines took into account regional bacteriology, antibiotic resistance data and available antibiotics to formulate recommendations. Preventive strategies for CAP include the administration of pneumococcal and influenza vaccine in selected populations at risk.