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1.  Clinical monitoring of peripheral perfusion: there is more to learn 
Critical Care  2014;18(1):113.
Irrespective of initiating factors, the peripheral circulation shows two general phases during the development and treatment of shock. Most published reports support earlier knowledge that the peripheral circulation is among the first to deteriorate and the last to be restored. With the advent of new and old techniques that allow us to continuously monitor peripheral perfusion, we may further shift our focus from pressure-based to flow-based resuscitation. The persisting challenge is the validation (effect on outcome parameters) of peripheral perfusion monitoring tools that can be simple and readily available worldwide.
PMCID: PMC4014848  PMID: 24602404
3.  Incretins and the intensivist: what are they and what does an intensivist need to know about them? 
Critical Care  2014;18(1):205.
Hyperglycaemia occurs frequently in the critically ill, even in those patients without a history of diabetes. The mechanisms underlying hyperglycaemia in this group are complex and incompletely defined. In health, the gastrointestinal tract is an important modulator of postprandial glycaemic excursions and both the rate of gastric emptying and the so-called incretin hormones, glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide, are pivotal determinants of postprandial glycaemia. Incretin-based therapies (that is, glucagon-like peptide-1 agonists and dipeptidyl-peptidase-4 inhibitors) have recently been incorporated into standard algorithms for the management of hyperglycaemia in ambulant patients with type 2 diabetes and, inevitably, an increasing number of patients who were receiving these classes of drugs prior to their acute illness will present to ICUs. This paper summarises current knowledge of the incretin effect as well as the incretin-based therapies that are available for the management of type 2 diabetes, and provides suggestions for the potential relevance of these agents in the management of dysglycaemia in the critically ill, particularly to normalise elevated blood glucose levels.
PMCID: PMC4015118  PMID: 24602388
4.  Choosing wisely - when to mend a broken heart with ECMO? 
Critical Care  2014;18(1):112.
Refractory cardiac shock in the cardiac surgical intensive care unit confers significant morbidity and mortality. Extracorporeal membrane oxygenation (ECMO) has become a common intervention for refractory cardiogenic shock when other therapies have failed. However, it is difficult to predict who will benefit from this costly, resource-intensive, but potentially life-saving technology. Here, we discuss the utility of a novel biomarker, serum butylcholinesterase, in determining survival in patients supported with ECMO following cardiac surgery.
PMCID: PMC4059487  PMID: 24602370
5.  Transferring the critically ill patient: are we there yet? 
Critical Care  2015;19(1):62.
During the past few decades the numbers of ICUs and beds has increased significantly, but so too has the demand for intensive care. Currently large, and increasing, numbers of critically ill patients require transfer between critical care units. Inter-unit transfer poses significant risks to critically ill patients, particularly those requiring multiple organ support. While the safety and quality of inter-unit and hospital transfers appear to have improved over the years, the effectiveness of specific measures to improve safety have not been confirmed by randomized controlled trials. It is generally accepted that critically ill patients should be transferred by specialized retrieval teams, but the composition, training and assessment of these teams is still a matter of debate. Since it is likely that the numbers and complexity of these transfers will increase in the near future, further studies are warranted.
PMCID: PMC4335540
7.  Early hemodynamic resuscitation in septic shock: understanding and modifying oxygen delivery 
Critical Care  2014;18(1):111.
In a previous issue of Critical Care, researchers have focused on the venous-to-arterial carbon dioxide difference (Pv-aCO2) as a surrogate marker for systemic perfusion in patients with septic shock. Although the complex mechanisms responsible for an increased Pv-aCO2 in septic shock need to be further unraveled, the potential prognostic value of Pv-aCO2 seems clinically relevant and useful in daily practice in view of its easy availability.
PMCID: PMC4015123  PMID: 24602317
8.  Skeletal muscle mass and mortality - but what about functional outcome? 
Critical Care  2014;18(1):110.
We have known for over a decade that critical illness survivors suffer from significant functional disability after hospital discharge. Muscle wasting is a major contributor to this disability, occurring early and rapidly during critical illness, with the subsequent weakness associated with delayed weaning and prolonged hospital stay. The scale of this long-term public health issue is concerning for two important reasons: increasing numbers of patients survive critical illness, and this is compounded by the lack of interventions to reduce skeletal muscle wasting to combat the functional disability. In the current issue of Critical Care, Weijs and colleagues demonstrate an indirect relationship between skeletal muscle mass on admission to the ICU and mortality. Observational data were obtained from 240 critically ill patients, all of whom received abdominal computer tomography scans for clinical reasons. Skeletal muscle volume was calculated for all visible skeletal muscle at the level of the third lumbar vertebra. In both continuous and categorical regression analysis, lower muscle volume on admission was associated with higher mortality, independent of Acute Physiology and Chronic Health Evaluation II score and gender. Interestingly, no association was observed between mortality and body mass index. These data also demonstrate that more than twice as many critical illness survivors with a low muscle mass on admission, compared to those with preserved muscle mass, were discharged to a nursing home. While this approach is novel and the results support the current clinical view in this area, one must regard these data with caution. Clinically relevant details, such as prior functional status, are not available. Despite these caveats, this study has two main messages. Firstly, muscle mass on admission to the ICU is a predictor of mortality and this physiological biomarker should therefore strongly be considered as an outcome measure in interventional studies. Secondly, low admission muscle mass is associated with increased disability and, in the case of this study, associated with an increased frequency of discharge to nursing homes. Further investigation is required to demonstrate the relationship between muscle mass, functional ability and discharge location.
PMCID: PMC4057190  PMID: 24528611
9.  Starling curves and central venous pressure 
Critical Care  2015;19(1):55.
Recent studies challenge the utility of central venous pressure monitoring as a surrogate for cardiac preload. Starting with Starling’s original studies on the regulation of cardiac output, this review traces the history of the experiments that elucidated the role of central venous pressure in circulatory physiology. Central venous pressure is an important physiologic parameter, but it is not an independent variable that determines cardiac output.
PMCID: PMC4329649
10.  Dose of colistin: a work in progress? 
Critical Care  2015;19(1):65.
PMCID: PMC4331303
13.  Fever in sepsis: is it cool to be hot? 
Critical Care  2014;18(1):109.
Changes in body temperature are a characteristic feature of sepsis. The study by Kushimoto and colleagues in a recent issue of Critical Care demonstrates that hypothermia is a very important manifestation of infection associated with very high mortality. Combined with recent data suggesting that febrile patients with infections have the lowest mortality risk, the study raises the question of whether inducing therapeutic hyperthermia might be beneficial in this patient group. Body temperature is easily measured and manipulated in the ICU, and interventional trials defining the most appropriate temperature targets in ICU patients with infections are urgently needed. One such study is in progress.
PMCID: PMC4056432  PMID: 24521542
15.  Predicting outcome in patients with sepsis: new biomarkers for old expectations 
Critical Care  2014;18(1):108.
Early prediction of the outcome of patients with sepsis could be helpful in guiding therapies but remains challenging. Presepsin, a new sepsis biomarker whose elevation as early as day 1 is well correlated with 28-day mortality, could be considered to this end.
PMCID: PMC4056609  PMID: 24517597
16.  Propofol, midazolam, vancomycin and cyclosporine therapeutic drug monitoring in extracorporeal membrane oxygenation circuits primed with whole human blood 
Critical Care  2015;19(1):40.
As a result of drug sequestration and increased volume of distribution, the extracorporeal membrane oxygenation (ECMO) procedure might lead to a decrease in drug concentrations during a patient’s treatment. The aim of this study was to evaluate sedative, antibiotic and immunosuppressive drug loss in ECMO circuit using ex-vivo and in-vitro experiments.
Blood concentrations of propofol, midazolam, cyclosporine and vancomycin were measured in an ex-vivo ECMO circuit primed with whole human blood, and compared to controls stored in polypropylene tubes. In vitro experiments were also conducted to further explore the role of temperature, oxygen exposure and polyvinylchloride surfaces on propofol loss in the ECMO circuit.
Propofol concentration decreased rapidly; 70% of its baseline concentration was lost after only 30 minutes, and only 11% remained after five hours (P <0.001 for the comparison with control polypropylene tube propofol concentration). Further experiments demonstrated that oxygen exposure and contact with polyvinylchloride tubing were respectively responsible for 70% and 85% of propofol loss after 45 minutes. Midazolam concentration also rapidly decreased in the ECMO circuit, with only 54% and 11% of baseline concentration being detected at 30 minutes and 24 hours respectively (P = 0.01 versus control). Alternatively, cyclosporine concentration remained stable for the five first hours, then decreased to 78% and 73% of the baseline value after 24 hours and 48 hours, (P = 0.35 versus control). Lastly, vancomycin concentration remained stable in the ECMO circuit for the 48-hour experimental protocol.
We observed important losses of propofol and midazolam, while cyclosporine concentration decreased slowly and moderately, and vancomycin concentration remained unchanged in the ex-vivo ECMO circuit primed with whole human blood. These data might help intensive care unit physicians planning clinical trials with a final objective to better adapt doses of these drugs while treating critically ill ECMO patients.
PMCID: PMC4335544
17.  Time to look beyond one-year mortality in critically ill hematological patients? 
Critical Care  2014;18(1):107.
The spectacular improvement in long-term prognosis of patients with hematological malignancies since the 1980s, coupled with the subsequent improvement over the past decade in short- and mid-term survival in cases of critical illness, resulted in an increasing referral of such patients to the ICU. A remaining question, however, is how these patients perform in the long term with regard to survival and quality of life. Here we discuss the present multicenter study on survival beyond 1 year in critically ill patients with hematological malignancies. We conclude with suggestions on how we can further improve the long-term outcome of these patients.
PMCID: PMC4056035  PMID: 24517551
18.  MicroRNAs: new biomarkers and therapeutic targets after cardiac arrest? 
Critical Care  2015;19(1):54.
Despite advances in resuscitation medicine, including target temperature management as part of post-cardiac arrest care, many patients will have a poor neurological outcome, most often resulting in death. It is a commonly held belief that the ability to prognosticate outcome at an early stage after cardiac arrest would allow subsequent health care delivery to be tailored to individual patients. However, currently available predictive methods and biomarkers lack sufficient accuracy and therefore cannot be generally recommended in clinical practice. MicroRNAs have recently emerged as potential biomarkers of cardiovascular diseases. While the biomarker value of microRNAs for myocardial infarction or heart failure has been extensively studied, less attention has been devoted to their prognostic value after cardiac arrest. This review highlights the recent discoveries suggesting that microRNAs may be useful both to predict outcome and to treat patients after cardiac arrest.
PMCID: PMC4324045
19.  The role of thoracic epidural anesthesia in severe acute pancreatitis 
Critical Care  2014;18(1):106.
In animal studies of severe acute pancreatitis, thoracic epidural anesthesia appears to enhance the splanchnic circulation, improve end-organ perfusion, and favorably influence mortality. The application of thoracic epidurals in the critically ill human patient is less clear. Methodological difficulties in reliably assessing mesenteric flow have hampered progress, and clinical concerns surrounding this potentially attractive therapeutic modality remain unanswered. Future research needs to focus on the impact of epidural anesthesia on basic human physiological pmeters to help direct further randomized studies in human disease.
PMCID: PMC4056351  PMID: 24502591
21.  Simplified lung ultrasound protocol shows excellent prediction of extravascular lung water in ventilated intensive care patients 
Critical Care  2015;19(1):36.
Ultrasound of the lung and quantification of B lines was recently introduced as a novel tool to detect overhydration. In the present study, we aimed to evaluate a four-region protocol of lung ultrasound to determine the pulmonary fluid status in ventilated patients in the intensive care unit.
Fifty patients underwent both lung ultrasound and transpulmonary thermodilution measurement with the PiCCO system. An ultrasound score based on number of single and confluent B lines per intercostal space was used to quantify pulmonary overhydration. To check for reproducibility, two different intensivists who were blinded as to the ultrasound pictures reassessed and classified them using the same scoring system. The results were compared with those obtained using other methods of evaluating hydration status, including extravascular lung water index (EVLWI) and intrathoracic blood volume index calculated with data from transpulmonary thermodilution measurements. Moreover, chest radiographs were assessed regarding signs of pulmonary overhydration and categorized based on a numeric rating scale.
Lung water assessment by ultrasound using a simplified protocol showed excellent correlation with EVLWI over a broad range of lung hydration grades and ventilator settings. Correlation of chest radiography and EVLWI was less accurate. No correlation whatsoever was found with central venous pressure measurement.
Lung ultrasound is a useful, non-invasive tool in predicting hydration status in mechanically ventilated patients. The four-region protocol that we used is time-saving, correlates well with transpulmonary thermodilution measurements and performs markedly better than chest radiography.
PMCID: PMC4335373  PMID: 25656060
22.  Prothrombin complex concentrates and a specific antidote to dabigatran are effective ex-vivo in reversing the effects of dabigatran in an anticoagulation/liver trauma experimental model 
Critical Care  2014;18(1):R27.
New oral anticoagulants are effective alternatives to warfarin. However, no specific reversal agents are available for life-threatening bleeding or emergency surgery. Using a porcine model of trauma, this study assessed the ability of prothrombin complex concentrate (PCC), activated PCC (aPCC), recombinant FVIIa (rFVIIa) and a specific antidote to dabigatran (aDabi-Fab) to reverse the anticoagulant effects of dabigatran.
Dabigatran etexilate (DE) was given orally for 3 days (30 mg/kg bid) and intravenously on day 4 to achieve consistent, supratherapeutic concentrations of dabigatran. Blood samples were collected at baseline, after oral DE, after intravenous dabigatran, and 60 minutes post-injury. PCC (30 and 60 U/kg), aPCC (30 and 60 U/kg), rFVIIa (90 and 180 μg/kg) and antidote (60 and 120 mg/kg) were added to blood samples ex-vivo. Coagulation was assessed by thromboelastometry, global coagulation assays and diluted thrombin time.
Plasma concentrations of dabigatran were 380 ± 106 ng/ml and 1423 ± 432 ng/ml after oral and intravenous administration, respectively, and all coagulation parameters were affected by dabigatran. Both PCCs and aDabi-Fab, but not rFVIIa, reversed the effects of dabigatran on thromboelastometry parameters and prothrombin time. In contrast, aPTT was only normalised by aDabi-Fab. Plasma concentration (activity) of dabigatran remained elevated after PCC and rFVIIa therapy, but was not measureable after aDabi-Fab.
In conclusion, PCC and aPCC were effective in reducing the anticoagulant effects of dabigatran under different conditions, while aDabi-Fab fully corrected all coagulation measures and decreased the plasma concentration of dabigatran below the limit of detection. No significant effects were observed with rFVIIa.
PMCID: PMC4059479  PMID: 24499559
23.  Pharmacokinetic variability and exposures of fluconazole, anidulafungin, and caspofungin in intensive care unit patients: Data from multinational Defining Antibiotic Levels in Intensive care unit (DALI) patients Study 
Critical Care  2015;19(1):33.
The objective of the study was to describe the pharmacokinetics (PK) of fluconazole, anidulafungin, and caspofungin in critically ill patients and to compare with previously published data. We also sought to determine whether contemporary fluconazole doses achieved PK/pharmacodynamic (PD; PK/PD) targets in this cohort of intensive care unit patients.
The Defining Antibiotic Levels in Intensive care unit patients (DALI) study was a prospective, multicenter point-prevalence PK study. Sixty-eight intensive care units across Europe participated. Inclusion criteria were met by critically ill patients administered fluconazole (n = 15), anidulafungin (n = 9), and caspofungin (n = 7). Three blood samples (peak, mid-dose, and trough) were collected for PK/PD analysis. PK analysis was performed by using a noncompartmental approach.
The mean age, weight, and Acute Physiology and Chronic Health Evaluation (APACHE) II scores of the included patients were 58 years, 84 kg, and 22, respectively. Fluconazole, caspofungin, and anidulafungin showed large interindividual variability in this study. In patients receiving fluconazole, 33% did not attain the PK/PD target, ratio of free drug area under the concentration-time curve from 0 to 24 hours to minimum inhibitory concentration (fAUC0–24/MIC) ≥100. The fluconazole dose, described in milligrams per kilogram, was found to be significantly associated with achievement of fAUC0–24/MIC ≥100 (P = 0.0003).
Considerable interindividual variability was observed for fluconazole, anidulafungin, and caspofungin. A large proportion of the patients (33%) receiving fluconazole did not attain the PK/PD target, which might be related to inadequate dosing. For anidulafungin and caspofungin, dose optimization also appears necessary to minimize variability.
Electronic supplementary material
The online version of this article (doi:10.1186/s13054-015-0758-3) contains supplementary material, which is available to authorized users.
PMCID: PMC4335513
25.  Efficiency of hydrogen peroxide in improving disinfection of ICU rooms 
Critical Care  2015;19(1):30.
The primary objective of this study was to determine the efficiency of hydrogen peroxide (H2O2) techniques in disinfection of ICU rooms contaminated with multidrug-resistant organisms (MDRO) after patient discharge. Secondary objectives included comparison of the efficiency of a vaporizator (HPV, Bioquell®) and an aerosolizer using H2O2, and peracetic acid (aHPP, Anios®) in MDRO environmental disinfection, and assessment of toxicity of these techniques.
This prospective cross-over study was conducted in five medical and surgical ICUs located in one University hospital, during a 12-week period. Routine terminal cleaning was followed by H2O2 disinfection. A total of 24 environmental bacteriological samplings were collected per room, from eight frequently touched surfaces, at three time-points: after patient discharge (T0), after terminal cleaning (T1) and after H2O2 disinfection (T2).
In total 182 rooms were studied, including 89 (49%) disinfected with aHPP and 93 (51%) with HPV. At T0, 15/182 (8%) rooms were contaminated with at least 1 MDRO (extended spectrum β–lactamase-producing Gram-negative bacilli 50%, imipenem resistant Acinetobacter baumannii 29%, methicillin-resistant Staphylococcus aureus 17%, and Pseudomonas aeruginosa resistant to ceftazidime or imipenem 4%). Routine terminal cleaning reduced environmental bacterial load (P <0.001) without efficiency on MDRO (15/182 (8%) rooms at T0 versus 11/182 (6%) at T1; P = 0.371). H2O2 technologies were efficient for environmental MDRO decontamination (6% of rooms contaminated with MDRO at T1 versus 0.5% at T2, P = 0.004). Patient characteristics were similar in aHPP and HPV groups. No significant difference was found between aHPP and HPV regarding the rate of rooms contaminated with MDRO at T2 (P = 0.313). 42% of room occupants were MDRO carriers. The highest rate of rooms contaminated with MDRO was found in rooms where patients stayed for a longer period of time, and where a patient with MDRO was hospitalized. The residual concentration of H2O2 appears to be higher using aHPP, compared with HPV.
H2O2 treatment is efficient in reducing MDRO contaminated rooms in the ICU. No significant difference was found between aHPP and HPV regarding their disinfection efficiency.
PMCID: PMC4335785  PMID: 25641219

Results 1-25 (13521)