Throat and rectal swabs may have an important role in MRSA screening of critically ill patients.

OBJECTIVE: Methicillin-resistant Staphylococcus aureus (MRSA) is a major problem in intensive care units (ICU). International guidelines recommend screening patients for MRSA on admission, although consensus on sites required for optimum detection has not been reached. Our aim was to determine whether throat and rectal swabs identified a significant number of additional MRSA-colonised patients not captured by swabbing at keratinized skin carriage sites (anterior nares, perineum and axillae). DESIGN: Prospective cohort study. SETTING: 30-Bed medical and surgical ICU in a tertiary teaching hospital. PATIENTS: One thousand four hundred and eighty adult patients consecutively admitted over 15 months. MEASUREMENTS AND RESULTS: Swabs from carriage sites (anterior nares, perineum, axillae, throat and rectum), wounds and clinical samples taken within 48 h of ICU admission were analysed to identify patients admitted with MRSA. A complete set of carriage swabs were received from 1,470 patients. 105 (7%) patients were admitted with MRSA of which 63 (60%) were detected by a pooled keratinized skin swab (anterior nares, perineum, axillae). A further 36 (34%) patients were detected only by throat or rectal swabs. Indeed, throat and rectal swabs combined had a higher sensitivity than pooled keratinised skin swabs (76 vs. 60% P = 0.0247). Swabs from all carriage sites together detected 95% (100) of MRSA positive patients, with five patients being positive at wound sites only. CONCLUSIONS: The throat and rectum are important and potentially hidden sites of MRSA carriage in critically ill patients. These findings prompt the need for larger studies to determine the most cost-effective screening strategy for MRSA detection. DESCRIPTOR: Non-pulmonary nosocomial infections

Practical aspects of treatment with drotrecogin alfa (activated)

In November 2001, drotrecogin alfa (activated) was approved by the US Food and Drug Administration; in August 2002 it was approved by the European Medicines Agency. Since the approval of drotrecogin alfa (activated), however, critical care physicians have been faced with several challenges, namely its costs, selection of patients who are more likely to benefit from it, and the decision regarding when to start drotrecogin alfa (activated) treatment. There are also operational issues such as how to manage the infusion to deliver an effective treatment while minimizing the risk for bleeding, particularly in patients with deranged clotting, at around the time of surgery or during renal replacement therapy. While addressing these issues, this review remains practical but evidence based as much as possible

Activated protein C in severe acute pancreatitis without sepsis? Not just yet ...

Severe acute pancreatitis (SAP) is characterized by an unregulated systemic proinflammatory response secondary to activation of trypsin within the pancreatic tissue, resulting in multiple organ failure. This dysregulated inflammation leading to organ dysfunction also characterizes severe sepsis. Activated protein C (APC) has pleotropic effects on the immune, coagulation, inflammatory and apoptotic pathways, and has been postulated to benefit acute pancreatitis - although concerns of possible retroperitoneal bleeding remain. Currently, experimental studies and subgroup data on patients with pancreatitis from a randomized controlled trial of APC in severe sepsis form the literature on the possible role of APC in SAP. We review the first randomized controlled trial of APC in acute pancreatitis published in the present issue of Critical Care

Anaemia is not a risk factor for progression of acute kidney injury:A retrospective analysis

Background: In hospitalised patients, anaemia increases the risk of developing acute kidney injury (AKI). Our aim was to determine whether anaemia also has an impact on the risk of progression from early AKI to more severe AKI in critically ill patients. Methods: We retrospectively analysed the data of patients admitted to the adult intensive care unit between 2007 and 2009 who had AKI I as per the AKI Network classification, and who had undergone haemodynamic monitoring within 12 h of AKI I. We collected baseline characteristics, severity of illness, haemoglobin (Hb), and haemodynamic parameters in the first 12 h of AKI I and differentiated between patients who progressed to AKI III and those who did not. Univariate and multivariate logistic regression analyses were used to identify risk factors for progression. Associations between Hb, arterial oxygen saturation and cardiac index were explored by receiver operating characteristic curve analysis. Results: Two hundred and ten patients (median age 70 years, 68 % male) underwent haemodynamic monitoring within 12 h of AKI I; 85 (41.5 %) progressed to AKI III. The proportion of patients with underlying cardiac disease was significantly higher among progressors versus non-progressors (58 % vs 34 %, respectively; p = 0.001). On the first day of AKI I, progressors had a significantly higher Sequential Organ Failure Assessment score (9 vs 8; p &lt;0.001), lower cardiac index (median 2.6 vs 3.3 L/min/m2; p &lt;0.001), higher arterial lactate (2 vs 1.6 mmol/L; p &lt;0.001), higher central venous pressure (16 vs 13; p = 0.02), lower mean arterial blood pressure (median 71 vs 74 mmHg; p = 0.01) and significantly higher requirement for cardiovascular and respiratory support, but there was no difference in Hb concentration (median 96 g/L in both groups). Multivariable regression analysis showed that heart disease, need for mechanical ventilation, arterial lactate, Sequential Organ Failure Assessment score, central venous pressure and cardiac index on first day of AKI I were independently associated with progression to AKI III. There was no significant difference in the risk of progression between patients with Hb = or &gt; 80 g/L, and = or &gt; 100 g/L on day of AKI I. Conclusions: In critically ill patients with AKI stage 1, anaemia was not associated with an increased risk of progression to more severe AKI.</p

The protein C pathway: implications for the design of the RESPOND study

The predictive value of plasma protein C level in sepsis has been demonstrated in a number of studies in which depressed protein C levels were associated with increased likelihood of negative outcome. Data from the PROWESS (Recombinant Human Activated Protein C Worldwide Evaluation in Severe Sepsis) trial indicate that administration of drotrecogin alfa (activated; DrotAA) leads to an increase in endogenous protein C levels in severe sepsis patients. In a group as heterogeneous as sepsis patients, the currently approved dose and duration of administration (24 μg/kg per hour for 96 hours) might not be optimal in some individuals. The RESPOND (Research Evaluating Serial Protein C levels in severe sepsis patients ON Drotrecogin alfa [activated]) trial is a phase II study being conducted to explore the use of endogenous protein C level as both a biomarker and a steering parameter for administration of DrotAA. Eligible patients will receive DrotAA either at the normal, currently approved dose and duration of administration ('standard therapy') or at a higher dose with variable infusion duration or variable infusion duration only ('alternative therapy'). The duration of DrotAA infusion in the alternative therapy arm depends on the individual response in terms of sustained increase in endogenous protein C. The ultimate aims of this and potential following studies are as follows: to establish serial plasma protein C measurement as a biomarker that will aid in the identification of severe sepsis patients who are most likely to benefit from DrotAA therapy, to enable adjustment of DrotAA therapy in individual patients (specifically, the possibility to use a higher dose and to adjust the infusion duration), and to provide guidance to the clinician regarding whether the patient is responding to DrotAA

Randomized trial evaluating serial protein C levels in severe sepsis patients treated with variable doses of drotrecogin alfa (activated)

International audienceINTRODUCTION: Serial alterations in protein C levels appear to correlate with disease severity in patients with severe sepsis, and it may be possible to tailor severe sepsis therapy with the use of this biomarker. The purpose of this study was to evaluate the dose and duration of drotrecogin alfa (activated) treatment using serial measurements of protein C compared to standard therapy in patients with severe sepsis. METHODS: This was a phase 2 multicenter, randomized, double-blind, controlled study. Adult patients with two or more sepsis-induced organ dysfunctions were enrolled. Protein C deficient patients were randomized to standard therapy (24 μg/kg/hr infusion for 96 hours) or alternative therapy (higher dose and/or variable duration; 24/30/36 μg/kg/hr for 48 to 168 hours). The primary outcome was a change in protein C level in the alternative therapy group, between study Day 1 and Day 7, compared to standard therapy. RESULTS: Of 557 patients enrolled, 433 patients received randomized therapy; 206 alternative, and 227 standard. Baseline characteristics of the groups were largely similar. The difference in absolute change in protein C from Day 1 to Day 7 between the two therapy groups was 7% (P = 0.011). Higher doses and longer infusions were associated with a more pronounced increase in protein C level, with no serious bleeding events. The same doses and longer infusions were associated with a larger increase in protein C level; higher rates of serious bleeding when groups received the same treatment; but no clear increased risk of bleeding during the longer infusion. This group also experienced a higher mortality rate; however, there was no clear link to infusion duration. CONCLUSIONS: The study met its primary objective of increased protein C levels in patients receiving alternative therapy demonstrating that variable doses and/or duration of drotrecogin alfa (activated) can improve protein C levels, and also provides valuable information for incorporation into potential future studies. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00386425

Recommendation of a practical guideline for safe tracheostomy during the COVID-19 pandemic

PurposeThe COVID-19 pandemic is placing unprecedented demand upon critical care services for invasive mechanical ventilation. There is current uncertainty regarding the role of tracheostomy for weaning ventilated patients with COVID-19 pneumonia. This is due to a number of factors including prognosis, optimal healthcare resource utilisation, and safety of healthcare workers when performing such a high-risk aerosol-generating procedure.MethodsLiterature review and proposed practical guideline based on the experience of a tertiary healthcare institution with 195 critical care admissions for COVID-19 up until 4th April 2020.ResultsA synthesis of the current international literature and reported experience is presented with respect to prognosis, viral load and staff safety, thus leading to a pragmatic recommendation that tracheostomy is not performed until at least 14 days after endotracheal intubation in COVID-19 patients. Practical steps to minimise aerosol generation in percutaneous tracheostomy are outlined and we describe the process and framework for setting up a dedicated tracheostomy team.ConclusionIn selected COVID-19 patients, there is a role for tracheostomy to aid in weaning and optimise healthcare resource utilisation. Both percutaneous and open techniques can be performed safely with careful modifications to technique and appropriate enhanced personal protective equipment. ORL-HNS surgeons can play a valuable role in forming tracheostomy teams to support critical care teams during this global pandemic

Improved Outcome of Severe Acute Pancreatitis in the Intensive Care Unit

Background. Severe acute pancreatitis (SAP) is associated with serious morbidity and mortality. Our objective was to describe the case mix, management, and outcome of patients with SAP receiving modern critical care in the Intensive Care Unit (ICU). Methods. Retrospective analysis of patients with SAP admitted to the ICU in a single tertiary care centre in the UK between January 2005 and December 2010. Results. Fifty SAP patients were admitted to ICU (62% male, mean age 51.7 (SD 14.8)). The most common aetiologies were alcohol (40%) and gallstones (30%). On admission to ICU, the median Acute Physiology and Chronic Health Evaluation (APACHE) II score was 17, the pancreatitis outcome prediction score was 8, and the median Computed Tomography Severity Index (CTSI) was 4. Forty patients (80%) tolerated enteral nutrition, and 46% received antibiotics for non-SAP reasons. Acute kidney injury was significantly more common among hospital nonsurvivors compared to survivors (100% versus 42%, = 0.0001). ICU mortality and hospital mortality were 16% and 20%, respectively, and median lengths of stay in ICU and hospital were 13.5 and 30 days, respectively. Among hospital survivors, 27.5% developed diabetes mellitus and 5% needed long-term renal replacement therapy. Conclusions. The outcome of patients with SAP in ICU was better than previously reported but associated with a resource demanding hospital stay and long-term morbidity

Healthcare-associated bloodstream infections in critically ill patients: descriptive cross-sectional database study evaluating concordance with clinical site isolates

Abstract Background Healthcare-associated bloodstream infections are related to both increased antibiotic use and risk of adverse outcomes. An in-depth understanding of their epidemiology is essential to reduce occurrence and to improve outcomes by targeted prevention strategies. The objectives of the study were to determine the epidemiology, source and concordance of healthcare-associated bloodstream infections with clinical site isolates. Methods We conducted a descriptive cross-sectional study in critically ill adults admitted to a tertiary semi-closed intensive care unit in England to determine the epidemiology, source and concordance of healthcare-associated bloodstream infections with clinical site isolates. All nosocomial positive blood cultures over a 4-year study period were identified. Pathogens detected and concordances with clinical site are reported as proportions. Results Contaminant pathogens accounted for half of the isolates. The most common non-contaminant pathogens cultured were Pseudomonas spp. (8.0%), Enterococcus spp. (7.3%) and Escherichia coli (5.6%). Central venous catheter-linked bloodstream infections represent only 6.0% of the positive blood cultures. Excluding contaminants and central venous line infections, in only 39.5% of the bloodstream infections could a concordant clinical site source be identified, the respiratory and urinary tracts being the most common. Conclusions Clinical practice should focus on a) improving blood culture techniques to reduce detection of contaminant pathogens and b) ensuring paired clinical site cultures are performed alongside all blood cultures to better understand the epidemiology and potential implications of primary and secondary discordant health-care associated bloodstream infections. </jats:sec