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Abstract. Unplanned transfers of patients from general medical-surgical wards to the intensive care unit (ICU) can occur as a result of unexpected patient deterioration. Such patients tend to have higher [...]

Byline: P. P. Pandharipande (1,8), A. Morandi (2,3,4), J. R. Adams (5), T. D. Girard (2,6,8), J. L. Thompson (7), A. K. Shintani (2,7), E. Wesley Ely (2,6,8) Keywords: Delirium; Amino acids; Tryptophan; Phenylalanine; Tyrosine; Large neutral amino acids; Blood brain barrier; LAT-1 transporter; Risk factor for delirium Abstract: Aim The pathophysiology of delirium remains elusive though neurotransmitters and their precursor large neutral amino acids (LNAAs) may play a role. This pilot study investigated whether alterations of tryptophan (Trp), phenylalanine (Phe), and tyrosine (Tyr) plasma levels were associated with a higher risk of transitioning to delirium in critically ill patients. Methods Plasma LNAA concentrations were determined on days 1 and 3 in mechanically ventilated (MV) patients from the MENDS randomized controlled trial (dexmedetomidine vs. lorazepam sedation). Three independent variables were calculated by dividing plasma concentrations of Trp, Phe, and Tyr by the sum of all other LNAA concentrations. Delirium was assessed daily using the confusion assessment method for the intensive care unit (CAM-ICU). Markov regression models were used to analyze independent associations between plasma LNAA ratios and transition to delirium after adjusting for covariates. Results The 97 patients included in the analysis had a high severity of illness (median APACHE II, 28 IQR, 24--32). After adjusting for confounders, only high or very low tryptophan/LNAA ratios (p = 0.0003), and tyrosine/LNAA ratios (p = 0.02) were associated with increased risk of transitioning to delirium, while phenylalanine levels were not (p = 0.27). Older age, higher APACHE II scores and increasing fentanyl exposure were also associated with higher probabilities of transitioning to delirium. Conclusions In this pilot study, plasma tryptophan/LNAA and tyrosine/LNAA ratios were associated with transition to delirium in MV patients, suggesting that alterations of amino acids may be important in the pathogenesis of ICU delirium. Future studies evaluating the role of amino acid precursors of neurotransmitters are warranted in critically ill patients. Author Affiliation: (1) Division of Critical Care Medicine, Department of Anesthesiology, Vanderbilt Medical Center, 526 MAB, 1211 21st Avenue South, Nashville, TN, 37212, USA (2) Center for Health Services Research, Vanderbilt Medical Center, Nashville, TN, USA (3) Department of Internal Medicine and Geriatrics, Poliambulanza Hospital, Brescia, Italy (4) Geriatric Research Group, Brescia, Italy (5) Vanderbilt University School of Medicine, Nashville, TN, USA (6) Division of Allergy/Pulmonary/Critical Care Medicine, Vanderbilt Medical Center, Nashville, TN, USA (7) Department of Biostatistics, Vanderbilt Medical Center, Nashville, TN, USA (8) VA Tennessee Valley Health System and Geriatric Research, Education and Clinical Center (GRECC), Nashville, TN, USA Article History: Registration Date: 24/06/2009 Received Date: 07/10/2008 Accepted Date: 23/06/2009 Online Date: 09/07/2009

Byline: Ulrike Holzinger (1), Joanna Warszawska (1), Reinhard Kitzberger (1), Harald Herkner (2), Philipp G. H. Metnitz (3), Christian Madl (1) Keywords: Glucose monitoring; Critical illness; Shock; Norepinephrine Abstract: Objective To evaluate the impact of circulatory shock requiring norepinephrine therapy on the accuracy and reliability of a subcutaneous continuous glucose monitoring system (CGMS) in critically ill patients. Design and setting A prospective, validation study of a medical intensive care unit at a university hospital was carried out. Methods Continuous glucose monitoring was performed subcutaneously in 50 consecutive patients on intensive insulin therapy (IIT), who were assessed according to the a priori strata of circulatory shock requiring norepinephrine therapy or not. Results A total of 736 pairs of sensor glucose (SG)/blood glucose (BG) values were analysed (502 without and 234 with norepinephrine therapy). For all values, repeated measures Bland--Altman analysis showed a mean difference of 0.08 mmol/l (limits of agreement: -1.26 and 1.43 mmol/l). Circulatory shock requiring norepinephrine therapy did not influence the relation of arterial BG with SG in a multivariable random effects linear regression analysis. The covariates norepinephrine dose, body mass index (BMI), glucose level and severity of illness also had no influence. Insulin titration grid analysis showed that 98.6% of the data points were in the acceptable treatment zone. No data were in the life-threatening zone. Conclusions Circulatory shock requiring norepinephrine therapy, as well as other covariates, had no influence on the accuracy and reliability of the CGMS in critically ill patients. Author Affiliation: (1) Intensive Care Unit 13H1, Department of Internal Medicine III, Medical University of Vienna, Waehringer Guertel 18--20, 1090, Vienna, Austria (2) Department of Emergency Medicine, Medical University of Vienna, Vienna, Austria (3) Department of Anaesthesiology and General Intensive Care, Medical University of Vienna, Vienna, Austria Article History: Registration Date: 23/03/2009 Received Date: 09/09/2008 Accepted Date: 12/02/2009 Online Date: 07/04/2009 Article note: http://clinicaltrials.gov/archive/NCT00494455

Byline: Christiane Hartog (1), Konrad Reinhart (1) Keywords: Colloids; Crystalloids; Hydroxyethyl starch; Efficacy; Safety; Critically ill Abstract: Purpose To describe the risk--benefit profile of hydroxyethyl starch (HES). Methods Narrative review. Results (1) Efficacy: no single clinical study or systemic review has shown that administration of any HES solution confers a clinically relevant benefit compared to crystalloids in critically ill patients or surgical patients in need of volume replacement. Contrary to beliefs expecting a ratio of 4:1 or more for crystalloid to colloid volume need, recent studies of goal-directed resuscitation observed much lower ratios of between 1 and 1.6. (2) Safety: HES administration is associated with coagulopathy, nephrotoxicity, pruritus and increased long-term mortality. Clinical studies claiming that modern HES 130/0.4 is safe have serious methodological drawbacks and do not adequately address the safety concerns. Conclusions Given the complete lack of superiority in clinical utility studies and the wide spectrum of severe side effects, the use of HES in the ICU should be stopped. The belief that four times as much crystalloid as colloid fluid volume is needed for successful resuscitation is being seriously questioned. Author Affiliation: (1) Department of Anaesthesiology and Intensive Care Medicine, Friedrich Schiller University, Erlanger Allee 101, 07747, Jena, Germany Article History: Registration Date: 28/05/2009 Received Date: 15/12/2008 Accepted Date: 13/04/2009 Online Date: 17/06/2009 Article note: C. Hartog and K. Reinhart contributed equally to this work. The article arguing for this proposition is available at: doi: 10.1007/s00134-009-1520-6.

Byline: Valentin Fuhrmann (1), Nikolaus Kneidinger (1), Harald Herkner (2), Gottfried Heinz (3), Mariam Nikfardjam (3), Anja Bojic (4), Peter Schellongowski (4), Bernhard Angermayr (5), Reinhard Kitzberger (1), Joanna Warszawska (1), Ulrike Holzinger (1), Peter Schenk (1), Christian Madl (1) Keywords: Ischemic hepatitis; Shock liver; Risk factors; Hypoglycemia Abstract: Purpose Hypoxic hepatitis (HH) is a frequent cause of acute hepatocellular damage at the intensive care unit. Although mortality is reported to be high, risk factors for mortality in this population are unknown. Methods One-hundred and seventeen consecutive patients with HH were studied prospectively at three medical intensive care units of a university hospital. Results The main causes of hypoxic hepatitis were low cardiac output and septic shock, and most patients (74%) had more than one underlying factor. Peak aspartate transaminase (P = 0.02), lactate dehydrogenase (P = 0.03), INR (P < 0.001) and lactate (P < 0.01) were higher in non-survivors. Prolonged duration of HH caused higher overall mortality rate (P = 0.03). INR > 2 (P = 0.02), septic shock (P = 0.01) and SOFA score >10 (P = 0.04) were risk factors of mortality in the regression model. Conclusions Hypoxic hepatitis is the consequence of multiorgan injury. Outcome is influenced by the severity of liver impairment and the etiology and severity of the basic disease. Author Affiliation: (1) Intensive Care Unit 13H1, Department of Gastroenterology and Hepatology, Internal Medicine 3, Medical University of Vienna, Wahringer Gurtel 18-20, 1090, Vienna, Austria (2) Department of Emergency Medicine, Medical University of Vienna, Vienna, Austria (3) Intensive Care Unit 13H3, Department of Cardiology, Internal Medicine 2, Medical University of Vienna, Vienna, Austria (4) Intensive Care Unit 13I2, Internal Medicine 1, Medical University of Vienna, Vienna, Austria (5) Department of Gastroenterology and Hepatology, Internal Medicine 3, Medical University of Vienna, Vienna, Austria Article History: Registration Date: 18/05/2009 Received Date: 21/07/2008 Accepted Date: 30/04/2009 Online Date: 09/06/2009 Article note: The study was performed at the intensive care units 13H1, 13H3 and 13I2 of the Medical University of Vienna. Electronic supplementary material The online version of this article (doi: 10.1007/s00134-009-1508-2) contains supplementary material, which is available to authorized users.

Byline: S. J. Thomson (1,2), M. L. Cowan (1), I. Johnston (1,2), S. Musa (1,2), M. Grounds (2), T. M. Rahman (1,2) Keywords: Liver function test; Critical care; Bilirubin; Alanine transaminase; Alkaline phosphatase; Gamma glutaryl transferase Abstract: Aims To evaluate the prevalence, patterns and significance of deranged liver function tests (LFT) in critically ill patients. Methods A prospective, observational data collection of the LFT [bilirubin, alanine aminotransferase (ALT), alkaline phosphatase (AKP), gamma glutaryl transferase (I3GT)] and critical care parameters in all admissions to the general intensive care unit (ICU) of our institution. Prevalence of abnormal LFT on the day of ITU admission is described and the relationship of abnormal LFT to clinical events and 30-day mortality analysed. Results Of 263 first admissions without hepatobiliary disease, 61% demonstrated an abnormal LFT at the point of admission. The majority of abnormalities were less than twice the upper limit of normal. Episodes of ventilation, haemofiltration and hypotension during the first 48 h were associated with an abnormal ALT on day 3. The presence of an abnormal ALT [odds ratio 2.7 (1.2--6.0)], AKP [OR 2.8 (1.1--7.3)] or I3GT [OR 3.9 (1.9--8.3)] was associated with an increased risk of death within 30 days of admission. When adjusted for APACHE II score, LFTs were not independent predictors of mortality. Discussion Low-grade abnormalities of LFT are a significant entity in critically ill patients and show an association with mortality outcomes and clinical events on ICU. They are likely to represent part of a spectrum of liver injury associated with critical illness and should not be disregarded. Author Affiliation: (1) Department of Gastroenterology and Hepatology, St George's Hospital, Blackshaw Rd, Tooting, London, SW17 0QT, UK (2) Department of Intensive Care Medicine, St George's Hospital, Blackshaw Rd, Tooting, London, SW17 0QT, UK Article History: Registration Date: 18/05/2009 Received Date: 25/11/2008 Accepted Date: 26/04/2009 Online Date: 10/06/2009

Byline: Marcio Manozzo Boniatti (1,2), Paulo Ricardo Cerveira Cardoso (1), Rodrigo Kappel Castilho (1), Silvia Regina Rios Vieira (1) Keywords: Acidosis; Acid base equilibrium; Strong ion gap; Outcomes; Prognosis Abstract: Purpose To determine whether Stewart's approach can improve our ability to diagnose acid--base disorders compared to the traditional model. Methods This prospective cohort study took place in a university-affiliated hospital during the period of February--May 2007. We recorded clinical data and acid--base variables from one hundred seventy-five patients at intensive care unit admission. Results Of the 68 patients with normal standard base excess (SBE) (SBE between -4.9 and +4.9), most (n = 59 86.8%) had a lower effective strong ion difference (SIDe), and of these, 15 (25.4%) had SIDe < 30 mEq/L. Thus, the evaluation according to Stewart's method would allow an additional diagnosis of metabolic disorder in 33.7% patients. Conclusions The Stewart approach, compared to the traditional evaluation, results in identification of more patients with major acid--base disturbances. Author Affiliation: (1) Critical Care Department, Hospital de Clinicas de Porto Alegre, Porto Alegre, Brazil (2) Rua Angelo Segalla, 622, CEP 95070-420, Caxias do Sul, RS, Brazil Article History: Registration Date: 01/04/2009 Received Date: 12/11/2008 Accepted Date: 23/03/2009 Online Date: 15/04/2009

Byline: John McCaffrey (1), Clare Farrell (2), Paul Whiting (3), Arina Dan (1), Sean M. Bagshaw (4,5), Anthony P. Delaney (1,6) Keywords: Mechanical ventilation; Weaning; Peri-operative care; Artifical airways; Complications Abstract: Purpose To determine whether corticosteroids reduce the rate of extubation failure in intensive care patients of all age groups. Methods Medline, EMBASE, the Cochrane Central Register of Controlled Trials, bibliographies of relevant articles, selected conference abstracts and unpublished trial databases were searched. Randomised clinical trials (RCTs) evaluating corticosteroids for the purpose of preventing extubation failure in mechanically ventilated, critically ill patients of all ages were included. Two authors independently assessed the validity of included studies and extracted data regarding characteristics of the studies and the rates of reintubation and manifestations of laryngeal oedema. Results Fourteen RCTs including 2,600 participants were included. The mean duration of ventilation prior to attempted extubation ranged from 3 to 21 days. There was a reduction in reintubation with the use of corticosteroids, with a pooled odds ratio (OR) of 0.56 (95% CI 0.41--0.77, P < 0.0005). The effect of corticosteroids tended to be more pronounced in studies when used at least 12 h prior to attempted extubation (OR 0.41, 95% CI 0.26--0.64). The results were consistent across neonatal, paediatric and adult populations. There was also a reduction in laryngeal oedema in participants receiving corticosteroids, with a pooled OR of 0.36 (95% CI 0.27--0.49, P < 0.0005). Conclusions Corticosteroids reduce laryngeal oedema and importantly reduce the incidence of extubation failure in critically ill patients of all ages. Author Affiliation: (1) Intensive Care Unit, Royal North Shore Hospital, Pacific Highway, St. Leonards, Sydney, NSW, 2065, Australia (2) Department of Anaesthesia, Royal North Shore Hospital, St. Leonards, Sydney, NSW, Australia (3) Department of Anaesthesia and Critical Care, Sheffield Hospital Trust, Sheffield, UK (4) Division of Critical Care Medicine, University of Alberta Hospital, Edmonton, AB, Canada (5) Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada (6) Northern Clinical School, University of Sydney, St. Leonards, Sydney, NSW, Australia Article History: Registration Date: 23/03/2009 Received Date: 20/11/2008 Accepted Date: 28/02/2009 Online Date: 08/04/2009

Byline: Gerald Chanques (1,3), Jean-Michel Constantin (1), Magali Sauter (1), Boris Jung (1), Mustapha Sebbane (1), Daniel Verzilli (1), Jean-Yves Lefrant (2), Samir Jaber (1) Keywords: Respiratory insufficiency; Oxygen inhalation therapy; Mouth dryness; Pain; Intensive care equipment and supplies Abstract: Objective To measure (1) the discomfort in non-intubated patients under high-flow oxygen therapy (HFOT) humidified with bubble (BH) or heated humidifiers (HH), and (2) the hygrometric properties of oxygen with a BH and an HH. Design and setting This was a randomized cross-over study in critically ill patients during a 3-day period. The humidification device used at days 1 and 3 was changed for the other at day 2. (2) It was also an experimental bench study using the psychrometric method with five randomized flows (3, 6, 9, 12 and 15 l/min) and different humidification techniques. Methods Discomfort, particularly dryness of the mouth and throat, was measured for two humidification conditions (BH and HH) using a 0--10 numerical rating scale (NRS) by patients requiring HFOT with a face mask at a flow aY=5 l/min, in a double-blinded condition. Results (1) In this clinical study, 30 patients treated by HFOT at a median flow of 7.8 l/min (5.1--10.9) were included. The global incidence of moderate (NRS = 4--6) and severe discomfort (NRS = 7--10) was 25 and 29%, respectively. The median intensities of both mouth and throat dryness were significantly lower with the HH than with the BH [7.8 (5.0--9.4) vs. 5.0 (3.1--7.0), P = 0.001 and 5.8 (2.3--8.5) vs. 4.3 (2.0--5.0), P = 0.005, respectively]. (2) In the bench study, the mean absolute humidity measured at an ambient temperature of 26degC with the HH was two times greater than with the BH (30 +- 1 vs. 16 +- 2 mg/l, P < 0.05) regardless of the flow rate. Conclusions Compared to bubble humidifiers, the use of a heated-humidifier in patients with high-flow oxygen therapy is associated with a decrease of dryness symptoms mediated by increased humidity delivered to the patient. Author Affiliation: (1) Intensive Care and Anesthesiology Department 'B' (SAR B), Saint Eloi Hospital. Montpellier University Hospital, 80, Avenue Augustin Fliche, 34295, Montpellier Cedex 5, France (2) Intensive Care and Anesthesiology Department, Caremeau Hospital, Nimes University Hospital, Place Professeur Robert Debre, 30029, Nimes Cedex 9, France (3) Service d'Anesthesie et de Reanimation 'B' (SAR B), HOPITAL SAINT ELOI, CHU de Montpellier, 80 avenue Augustin Fliche, 34295, Montpellier Cedex 5, France Article History: Registration Date: 26/02/2009 Received Date: 04/04/2008 Accepted Date: 07/01/2009 Online Date: 18/03/2009 Article note: This article is discussed in the editorial available at: doi: 10.1007/s00134-009-1457-9. The authors declare that Fisher & Paykel Healthcare France (Courtaboeuf, France) provided technical assistance for the bench test study, including a financial aid of 3,000 [Euro], which was used to acquire technical equipment and to present results at scientific meetings. Respironics France (Carquefou, France) provided technical assistance for the bench test. Electronic supplementary material The online version of this article (doi: 10.1007/s00134-009-1456-x) contains supplementary material, which is available to authorized users.

Byline: Stefan Rauch (1,3), Kristine Krueger (2), Alparslan Turan (1), Norbert Roewer (3), Daniel I. Sessler (4) Keywords: Critical care; Capsule endoscopy; Enteral nutrition; PillCam; Transit time Abstract: Purpose Gastrointestinal motility can be impaired by serious illness or medications, compromising enteral feeding in critical care patients. We compared small bowel transit time and morphology in neurosurgical critical care (ICU) patients with those in healthy subjects. Methods We evaluated small intestinal transit time, quality of visualization and intestinal morphology in 16 ICU patients (Glasgow Coma Scale score from 6 to 14) and 16 healthy ambulatory patients. Video data were obtained with PillCam SB capsules (Given Imaging Ltd., Yoqneam, Israel). Results Transit time was 5.1 h (3.9--7.7) (median [IQR]) in ICU and 4.3 (4.1--5.3 h) in ambulatory patients (P = 0.481). Six ICU patients (37%) and two ambulatory patients (12%) had pathological findings (ulcers, petechia, erosions) (P = 0.10). Conclusions Median small bowel transit times in critically ill neurosurgical patients were similar to those in ambulatory subjects, although transit times were more variable in the critically ill patients. Author Affiliation: (1) Department of Anesthesiology, University of Louisville, Louisville, KY, USA (2) Digestive Health Center, University of Louisville, Louisville, USA (3) Department of Anesthesiology, University of Wurzburg, Oberdurrbacher Str. 6, 97080, Wurzburg, Germany (4) Department of Outcomes Research, The Cleveland Clinic, Cleveland, OH, USA Article History: Registration Date: 16/01/2009 Received Date: 13/10/2008 Accepted Date: 11/12/2008 Online Date: 29/01/2009

Byline: Renata Rego Lins Fumis (1), Daniel Deheinzelin (1,2) Keywords: Anxiety; Depression; Intensive care unit; Hospital anxiety and depression scale; Cancer Abstract: Objective To determine prevalence and factors associated with symptoms of anxiety and depression in family members of critically ill cancer patients. Design Prospective cohort study. Setting A 23-bed intensive care unit in a tertiary cancer centre. Patients and Participants Three hundred consecutive families of cancer patients with length of stay >72 h in ICU. Intervention None. Measurements and main results The Hospital Anxiety and Depression Scale questionnaire and critical care family needs inventory were completed by family members. Prevalence of anxiety and depression in family members was 71 and 50.3%, respectively. Regarding the patients' disease, family depression was correlated with presence of metastasis, whereas hematological malignancies correlated with family' anxiety. Anxiety was independently associated with one patient-related factor (prolonged mechanical ventilation) and two family-related factors (catholic religion and gender). Factors associated with symptoms of depression included one patient-related factor (presence of metastasis) and one family-related factor (gender). Conclusions Present findings demonstrated a high prevalence of anxiety and depression in critically ill cancer patients' family members during an intensive care unit stay. Author Affiliation: (1) Unidade de Terapia Intensiva, Centro de Tratamento e Pesquisa Hospital A C Camargo, Rua Prof. Antonio Prudente, 211, Sao Paulo, SP, CEP 01509-900, Brazil (2) Nucleo Avancado de Torax, Hospital Sirio Libanes, Sao Paulo, SP, Brazil Article History: Registration Date: 13/01/2009 Received Date: 17/04/2008 Accepted Date: 01/12/2008 Online Date: 29/01/2009 Article note: Electronic supplementary material The online version of this article (doi: 10.1007/s00134-009-1406-7) contains supplementary material, which is available to authorized users.

Byline: Jose A. Martinez (1), Esther Delgado (2), Sara Marti (3), Francesc Marco (3), Jordi Vila (3), Josep Mensa (1), Antoni Torres (4), Carles Codina (5), Antoni Trilla (6), Alex Soriano (1), Aitor Alquezar (2), Pedro Castro (2), Jose M. Nicolas (2) Keywords: Intensive care unit; Pseudomonas aeruginosa; Antipseudomonal agents; Antimicrobial resistance; Emergence of resistance; Nosocomial infection Abstract: Objective To assess the role of antipseudomonal agents on Pseudomonas aeruginosa colonization and acquisition of resistance. Design Prospective cohort study. Setting Two medical intensive care units. Patients and participants 346 patients admitted for aY= 48 h. Intervention Analysis of data from an 8-month study comparing a mixing versus a cycling strategy of antibiotic use. Measurements and results Surveillance cultures from nares, pharynx, rectum, and respiratory secretions were obtained thrice weekly. Acquisition of resistance was defined as the isolation, after 48 h of ICU stay, of an isolate resistant to a given antibiotic if culture of admission samples were either negative or positive for a susceptible isolate. Emergence of resistance refers to the conversion of a defined pulsotype from susceptible to non-susceptible. Forty-four (13%) patients acquired 52 strains of P. aeruginosa. Administration of piperacillin-tazobactam for aY= 3 days (OR 2.6, 95% CI 1.09--6.27) and use of amikacin for aY= 3 days (OR 2.6, 95% CI 1.04--6.7) were positively associated with acquisition of P. aeruginosa, whereas use of quinolones (OR 0.27, 95% CI 0.1--0.7) and antipseudomonal cephalosporins (OR 0.27, 95% CI 0.08--0.9) was protective. Exposure to quinolones and cephalosporins was not associated with the acquisition of resistance, whereas it was linked with usage of all other agents. Neither quinolones nor cephalosporins were a major determinant on the emergence of resistance to themselves, as resistance to these antibiotics developed at a similar frequency in non-exposed patients. Conclusions In critically ill patients, quinolones and antipseudomonal cephalosporins may prevent the acquisition of P. aeruginosa and may have a negligible influence on the acquisition and emergence of resistance. Author Affiliation: (1) Department of Infectious Diseases, Hospital Clinic, IDIBAPS, University of Barcelona, Villarroel 170, 08036, Barcelona, Spain (2) Medical Intensive Care Unit, Hospital Clinic, IDIBAPS, University of Barcelona, Barcelona, Spain (3) Microbiology Laboratory, Hospital Clinic, IDIBAPS, University of Barcelona, Barcelona, Spain (4) Respiratory Intensive Care Unit-ICPTC, Hospital Clinic, IDIBAPS, University of Barcelona, Barcelona, Spain (5) Department of Pharmacy, Hospital Clinic, IDIBAPS, University of Barcelona, Barcelona, Spain (6) Unit for Evaluation, Supporting and Prevention, Hospital Clinic, IDIBAPS, University of Barcelona, Barcelona, Spain Article History: Registration Date: 02/10/2008 Received Date: 29/10/2007 Accepted Date: 09/09/2008 Online Date: 21/10/2008

Byline: M. Cecconi (1), D. Dawson (1), R. M. Grounds (1), A. Rhodes (1) Keywords: Cardiovascular monitoring; Statistics; Methodology Abstract: Background Lithium dilution cardiac output by LiDCO[TM]plus (LiDCO, Cambridge, UK) is a validated methodology for measuring cardiac output. It is used to calibrate a pulse pressure analysis algorithm (PulseCO) for the continuous measurement of subsequent changes in this variable. The variability of measurements, or precision, within patients of lithium dilution cardiac output has not previously been described. Material and methods Thirty-five hemodynamically stable patients in intensive care, with no significant variability in heart rate, mean arterial pressure or central venous pressure, were recruited. Fifty-three determinations of cardiac output were made, each using four lithium dilution measurement curves performed consecutively within a maximum period of 10 min. The coefficient of variation of the measurements was determined and used to derive the least significant change in cardiac output that this technique could reliably detect. Results For a single measurement, the coefficient of variation was 8%. This equates to the technique being able to detect a change (least significant change) between two measurements of 24%. Averaging two lithium dilution measurements improved the coefficient of variation to 6% with a least significant change of 17%. Using the average of three curves reduced the coefficient of variation to 5% with a least significant change of 14%. Conclusions To achieve a good precision with this technique, three lithium dilution measurements should be averaged. This will allow changes in cardiac output of more than 14% to be reliably detected. The understanding of the precision of this technique allows the user to know when a real change has happened to their patient. Author Affiliation: (1) Department of Intensive Care Medicine, St George's Hospital, London, SW17 0QT, UK Article History: Registration Date: 01/09/2008 Received Date: 28/10/2007 Accepted Date: 10/08/2008 Online Date: 18/09/2008 Article note: Preliminary data was presented at the Bruxelles ISICEM conference in 2007. Electronic supplementary material The online version of this article (doi: 10.1007/s00134-008-1292-4) contains supplementary material, which is available to authorized users.

Byline: Daniel G. Ezra (1), Michelle P. Y. Chan (2), Lola Solebo (2), Aeesha P. Malik (2), Elizabeth Crane (3), Andrew Coombes (2), Marie Healy (4) Keywords: Cornea; Exposure; Intensive care; Eye lubricant Abstract: Purpose To compare the cost and effectiveness of the two most popular forms of eye care in intensive care, ocular lubricant (Lacrilube) and polyacrylamide hydrogel dressings (Geliperm) for the prevention of exposure keratopathy in the critically ill. Methods A prospective randomised contralateral eye study was conducted at the Intensive Care Unit (ICU), Royal London Hospital, London, UK. Eighty eyes of 40 patients were recruited. Each patient received both Lacrilube and Geliperm allocated at random to different sides. A daily ophthalmology ward round was conducted. The outcome measures included the greatest palpebral aperture length, conjunctival oedema, and any exposure keratopathy. Results There was no statistically significant difference in the maximum corneal exposure score between the eyes treated with Lacrilube and Geliperm (P = 0.38). No significant difference in degree of chemosis or palpebral aperture was identified. Conclusions Our data suggest that Geliperm is as effective as Lacrilube in the prevention of exposure keratopathy in the critically ill. We also note that nursing staff must be fully trained in its application for eye care. Author Affiliation: (1) Moorfields Eye Hospital, London, EC1V 2PD, UK (2) Department of Ophthalmology, Royal London Hospital, London, E1 1BB, UK (3) Centre for Environmental and Preventive Medicine, Wolfson Institute of Preventive Medicine, Queen Mary School of Medicine and Dentistry, London, EC1M 6BQ, UK (4) Department of Intensive Care, Royal London Hospital, London, E1 1BB, UK Article History: Registration Date: 01/09/2008 Received Date: 22/03/2008 Accepted Date: 28/08/2008 Online Date: 23/09/2008 Article note: An erratum to this article can be found at http://dx.doi.org/10.1007/s00134-008-1349-4

Byline: Vincent Peigne (1), KateAina Rusinova (1), Lionel Karlin (2), Michael Darmon (1), Jean-Paul Fermand (2), Benoit Schlemmer (1), Elie Azoulay (1,3) Keywords: Bone marrow transplantation; Acute respiratory failure; Noninvasive mechanical ventilation; Sepsis; Early admission Abstract: Objective Therapeutic advances have improved survival in patients with myeloma (MM) over the past decade. We investigated whether survival has also improved in critically ill myeloma patients. Design Retrospective study. Setting Intensive care unit. Patient Consecutive myeloma patients admitted to a teaching hospital ICU between 1990 and 2006. We compared three year-of-admission groups (1990--1995, 1996--2001, and 2002--2006) that matched changes in myeloma treatment (chemotherapy only, stem cell transplantation, and new molecules, respectively). Intervention None. Measurements and main results We included 196 patients. Reasons for ICU admission and patient characteristics were similar across groups however, less use of conventional chemotherapy and radiotherapy and greater use of steroids were noted in the more recent periods. Over time, vasopressors and invasive mechanical ventilation were used decreasingly, and noninvasive ventilation increasingly, to treat acute respiratory failure. Hospital mortality decreased from 75% in 1990--1995 to 49% in 1996--2001 and 40% in 2002--2006 (P = 0.0007). Mortality was associated with poor performance status [OR 2.27, 95% CI (1.04--4.99)], need for mechanical ventilation [OR 4.33, 95% CI (1.86--10.10)], need for vasopressors [OR 2.57, 95% CI (1.12--5.86)], and admission for an event related to myeloma progression [OR 2.77, 95% CI (1.13--6.79)]. ICU admission within 48 h after hospital admission was associated with lower mortality [OR 0.28, 95% CI (0.19--0.89)]. Conclusion Hospital mortality decreased significantly over the last 15 years in myeloma patients admitted to the ICU. Risk factors for death were organ failure and poor chronic health status. Early ICU admission was associated with lower mortality, suggesting opportunities for further improving survival. Author Affiliation: (1) Medical ICU, AP-HP, Hopital Saint-Louis, 75010, Paris, France (2) Department of Immunology, AP-HP, Hopital Saint-Louis, 75010, Paris, France (3) Service de Reanimation Medicale, Hopital Saint-Louis et Universite Paris 7, 1 rue Claude Vellefaux, 75010, Paris, France Article History: Registration Date: 02/10/2008 Received Date: 01/05/2008 Accepted Date: 08/09/2008 Online Date: 14/10/2008

Byline: Benoit P. Guery (1), Maiken C. Arendrup (2), Georg Auzinger (3), Elie Azoulay (4), Marcio Borges Sa (5), Elizabeth M. Johnson (6), Eckhard Muller (7), Christian Putensen (8), Coleman Rotstein (9), Gabriele Sganga (10), Mario Venditti (11), Rafael Zaragoza Crespo (12), Bart Jan Kullberg (13) Keywords: Antifungal; Azole; Candida; Candidiasis; Echinocandins; Invasive candidiasis; Intensive care; Polyenes Abstract: Background Invasive candidiasis and candidemia are frequently encountered in the nosocomial setting particularly in the intensive care unit (ICU). Objective and methods To review the current management of invasive candidiasis and candidemia in non-neutropenic adult ICU patients based on a review of the literature and an European expert panel discussion. Results and conclusions Empiric and directed treatment for invasive candidiasis are predicated on the hemodynamic status of the patient. Unstable patients may benefit from broad-spectrum antifungal agents, which can be narrowed once the patient has stabilized and the identity of the infecting species is established. In stable patients, a more classical approach using fluconazole may be satisfactory provided that the patient is not colonized with fluconazole resistant strains or there has been recent past exposure to an azole ( Author Affiliation: (1) Infectious Diseases, SGRIVI, Hopital Huriez, CHRU Lille, 59045, Lille Cedex, France (2) Unit of Mycology, Department Bacteriology, Mycology and Parasitology, Statens Serum Institut, Building 43/117, 2300, Copenhagen, Denmark (3) Liver Intensive Care, Institute of Liver Studies, King's College Hospital, Denmark Hill, London, SE5 9RS, UK (4) Service de Reanimation Medicale, Hopital Saint-Louis, 1, avenue Claude-Bellefaux, 75010, Paris, France (5) Sepsis Unit, Intensive Care Department, Hospital Son Llatzer, Palma de Mallorca, Spain (6) Mycology Reference Laboratory, National Collection of Pathogenic Fungi, The HPA Centre for Infections, HPA South West Laboratory, Myrtle Road, Kingsdown, Bristol, BS2 8EL, UK (7) Universitatsklinik fur Anasthesiologie, Intensivmedizin und Schmerztherapie, Knappschaftskrankenhaus Bochum, Langendreer, Klinikum der Ruhr-Universitat, In der Schornau 23--25, 44892, Bochum, Germany (8) Operative Intensivmedizin, Klinik und Poliklinik fur Anasthesiologie und Operative Intensivmedizin, Rheinische-Friedrich-Wilhelms Universitat Bonn, Sigmund-Freud Str. 25, 53127, Bonn, Germany (9) Division of Infectious Diseases, University Health Network, Toronto General Hospital, NCSB 11-1212, 200 Elizabeth Street, Toronto, ON, M5G 2C4, Canada (10) Department of Surgery, Division of General Surgery and Organ Transplantation, Policlinico 'A Gemelli', Catholic University, Largo Gemelli, 8, 00168, Rome, Italy (11) Internal Medicine, Clinical Medicine Department, 'La Sapienza' University, Rome, Viale dell' Universita, 37, 00185, Rome, Italy (12) Secretario GTEI-SEMICYUC, Medicina Intensiva, Hospital Universitario Dr. Peset, Avenida Gaspa Aguilar, 90, 46107, Valencia, Spain (13) Department of Medicine (463), Nijmegen Institute for Infection, Inflammation, and Immunity (N4i), Radboud University Nijmegen Medical Centre, PO Box 9101, 6500 HB, Nijmegen, The Netherlands Article History: Registration Date: 10/10/2008 Received Date: 09/10/2008 Accepted Date: 09/10/2008 Online Date: 30/10/2008 Article note: Part I is published at: doi: 10.1007/s00134-008-1338-7. Electronic supplementary material The online version of this article (doi: 10.1007/s00134-008-1339-6) contains supplementary material, which is available to authorized users.

Byline: Wen-Liang Yu (1), Zhu-Jin Lu (1), Ying Wang (2), Li-Ping Shi (3), Feng-Wu Kuang (4), Su-Yun Qian (5), Qi-Yi Zeng (6), Min-Hui Xie (7), Guo-Ying Zhang (8), De-Yi Zhuang (9), Xun-Mei Fan (5), Bo Sun (1) Keywords: Acute respiratory distress syndrome; Epidemiology; Intensive care; Mortality; Respiratory therapy Abstract: Objective To assess the incidence of, predisposing factors for, and the rates and relative risks of mortality from acute respiratory distress syndrome (ARDS) in pediatric patients. Design A prospective study in 12 consecutive months from 2004 to 2005 in 25 pediatric intensive care units (PICUs). Patients and setting ARDS was diagnosed according to the 1994 American--European Consensus Conference definitions, applied to all severely ill admissions between 1 month and 14 years of age. The PICUs were in major municipalities and provincial cities, and half were university affiliated. Measurements and results From a total of 12,018 admissions, 7,269 were severely ill. One hundred and five (1.44%) patients developed ARDS and 64 (61.0%) died, which accounts for 13.2%, of the total ICU death (n = 485, 6.7%) or a nine times relative risk of dying. The median age at onset of ARDS was 24 months and 40% were less than 12 month old. Median time from PICU admission to the onset of ARDS was 16 h, and in 63% Conclusions ARDS has a high mortality in these Chinese PICUs, especially in those with pneumonia and sepsis, and adequate management including lung protective ventilation strategy is required. Author Affiliation: (1) Children's Hospital of Fudan University, 183 Feng Lin Road, 200032, Shanghai, People's Republic of China (2) Shanghai Children's Medical Center of Shanghai Jiaotong University, Shanghai, People's Republic of China (3) Children's Hospital of Zhejiang University, Zhejiang, People's Republic of China (4) Children's Hospital of Chongqing Medical University, Chongqing, People's Republic of China (5) Beijing Children's Hospital of Capital University of Medical Sciences, Beijing, People's Republic of China (6) Guangzhou Children's Hospital, Guangdong, People's Republic of China (7) Children's Hospital of Suzhou University, Jiangsu, People's Republic of China (8) Chengdu Children's Hospital, Sichuan, People's Republic of China (9) Quanzhou Children's Hospital, Fujian, People's Republic of China Article History: Registration Date: 26/08/2008 Received Date: 20/07/2006 Accepted Date: 29/04/2008 Online Date: 30/09/2008 Article note: Electronic supplementary material The online version of this article (doi: 10.1007/s00134-008-1254-x) contains supplementary material, which is available to authorized users.

Byline: Mary R. Suchyta (1,2), Callie J. Beck (3), Colin W. Key (3), Al Jephson (1,2), Ramona O. Hopkins (1,2,3,4) Keywords: ICU; Critical care; Alcohol dependence; Drug dependence; Substance dependence; Psychiatric disorders Abstract: Objective Substance dependence disorders are common in hospitalized patients and are associated with poor recovery. We compared mortality and discharge disposition in critically ill patients with and without substance dependence and patients with and without psychiatric disorders. We also compared the prevalence of substance dependence and psychiatric disorders to population data. Methods All medical records of shock trauma intensive care unit (ICU) patients (mixed medical and surgical) at LDS Hospital were reviewed for pre-critical illness alcohol dependence, drug dependence, and psychiatric disorders. Results There were 742 critically ill patients of whom 54% were male, acute respiratory distress syndrome developed in 5.5% and hospital mortality was 21%. The mean acute physiology and chronic health evaluation II scores were 16.5 +- 7.9, sequential organ failure assessment scores were 6.7 +- 4.2, duration of mechanical ventilation was 5 +- 6.2 days, ICU length of stay (LOS) was 7.3 +- 10.1 days, hospital LOS was 12.3 +- 12.9 days. Multivariable regression analyses found psychiatric disorders predicted higher hospital mortality (Odds ratio = 1.50), but was not statistically significant (p = 0.08) substance dependence predicted shorter hospital LOS (R .sup.2 = 0.08, p = 0.01) after controlling for covariates. There was a higher prevalence of substance dependence compared to Utah (p < 0.001) and US population data (p < 0.001). The prevalence of psychiatric disorders was significantly lower in our patients compared to US population data (19 vs. 26%, p < 0.001). Conclusions Our data suggest that substance dependence increases hospital LOS and that patients with drug or alcohol dependence are at higher risk for ICU admission compared to the general population. Author Affiliation: (1) Department of Medicine, Pulmonary and Critical Care Division, LDS Hospital, Salt Lake City, UT, USA (2) Department of Pulmonary and Critical Care Medicine, Intermountain Medical Center, 5121 South Cotttonwood Street, Murray, UT, 84107, USA (3) Psychology Department, 1001 SWKT, Brigham Young University, Provo, UT, 84602, USA (4) Neuroscience Center, Brigham Young University, Provo, UT, USA Article History: Registration Date: 01/09/2008 Received Date: 25/01/2008 Accepted Date: 16/07/2008 Online Date: 18/09/2008 Article note: This article is discussed in the editorial available at: doi: 10.1007/s00134-008-1261-y.

Byline: Catharina F. M. Linssen (1), Jan A. Jacobs (1), Foekje F. Stelma (1), Walther N. K. A. Mook (2), Peter Terporten (1), Cornelis Vink (1), Marjolein Drent (3), Cathrien A. Bruggeman (1), Annick Smismans (1) Keywords: Viral pneumonia; Intensive care Abstract: Objective To evaluate the relationship between the HSV-1 and -2 loads in BAL fluid (BALF) and clinical outcome. Design Retrospective study. Setting The general intensive care unit of the University Hospital Maastricht. Patients Five hundred and twenty-one BALF samples from 462 patients were included. Patients were divided into three groups (1) patients admitted to the hospital 48 h before lavage (ICU) and (3) the remaining patients (non-ICU group). Interventions No additional interventions were conducted. Measurements and results HSV-1 and HSV-2 loads were determined by real-time polymerase chain reaction (PCR). HSV-1 DNA was detected in 4.3% (4/92) of samples in the community group, 15% (18/121) in the non-ICU group and in 32% (99/308) of the ICU group. In the age group 10.sup.5 genome equivalents (ge)/ml were associated with an increased 14-day in-hospital mortality compared to patients with a HSV-1 load a$?10.sup.5 ge/ml in BALF (41 vs. 20%, respectively, P = 0.001). HSV-1 pneumonia was histologically proven in two patients with a HSV-1 load exceeding 10.sup.5 ge/ml. Conclusions HSV-1 occurred more in critically ill patients and high loads in BALF were associated with an increased mortality. The higher mortality observed in patients with HSV-1 load >10.sup.5 ge/ml enforces its clinical relevance and necessitates to start randomized medical intervention studies. Author Affiliation: (1) Department of Medical Microbiology, University Hospital Maastricht, P.O. Box 5800, 6202 AZ, Maastricht, The Netherlands (2) Department of Intensive Care Medicine, University Hospital Maastricht, P.O. Box 5800, 6202 AZ, Maastricht, The Netherlands (3) Department of Respiratory Medicine, University Hospital Maastricht, P.O. Box 5800, 6202 AZ, Maastricht, The Netherlands Article History: Registration Date: 16/07/2008 Received Date: 11/10/2007 Accepted Date: 11/07/2008 Online Date: 05/08/2008 Article note: The abstract of this article was published in ESCV/SGM Conference, Birmingham, as an oral presentation.

Byline: Evangelos Papadomichelakis (1), Flora Kontopidou (2), Anastasia Antoniadou (2), Garifalia Poulakou (2), Evangelos Koratzanis (2), Petros Kopterides (1), Irini Mavrou (1), Apostolos Armaganidis (1), Helen Giamarellou (2) Keywords: Multidrug-resistant bacteria; Gram-negative bacteria; Colonization; Surveillance; Ventilator-associated pneumonia; Bacteremia Abstract: Objective To define the potential of resistant gram-negative colonization surveillance to predict etiology of subsequent infection and improve adequacy of empiric antimicrobial treatment. Design Retrospective cohort study. Setting A mixed medical--surgical six-bed intensive care unit (ICU), from November 2003 to December 2006. Patients All patients having at least one episode of ventilator-associated pneumonia (VAP) or bloodstream infection (BSI) caused by a resistant gram-negative pathogen during the study period. Interventions Colonization surveillance of the respiratory tract and gastrointestinal tract was systematically performed in all ICU patients. Tracheal aspirates were obtained twice weekly and rectal swabs once weekly. Both tracheal and rectal samples were cultured in antibiotic-enriched media (containing ceftazidime, ciprofloxacin, imipenem or piperacillin/tazobactam), to focus on resistant gram-negative pathogen isolation. Measurements and results Colonization concordance between resistant, gram-negative pathogens of infectious episodes and previous, recent (a$?7 days) colonization of the respiratory and gastrointestinal tract was determined, based on species identity and antimicrobial susceptibility. Concordance was 82% in VAP and 86% in BSI cases and was further confirmed by molecular testing of 15 randomly selected cases by REP-PCR. Previous colonization had high sensitivity and specificity in VAP, but was less specific in BSI cases. Knowledge of previous colonization improved the rate of adequate empiric antimicrobial treatment (91 vs. 40% in VAP and 86 vs. 50% in BSI cases, P < 0.05). Conclusions Colonization surveillance for resistant gram-negative microorganisms is predictive of subsequent infection etiology and can improve empiric antimicrobial treatment adequacy in a critical care setting. Author Affiliation: (1) 2nd Critical Care Department, Athens University Medical School, University General Hospital 'ATTIKON', Rimini 1, Athens, 12462, Greece (2) 4th Department of Internal Medicine, Athens University Medical School, University General Hospital 'ATTIKON', Athens, Greece Article History: Registration Date: 18/07/2008 Received Date: 30/09/2007 Accepted Date: 05/06/2008 Online Date: 19/08/2008 Article note: This article is discussed in the editorial available at: doi: 10.1007/s00134-008-1249-7.

Byline: John A. Myburgh (1), Alisa Higgins (2), Alina Jovanovska (1), Jeffrey Lipman (3), Naresh Ramakrishnan (4), John Santamaria (5) Keywords: Epinephrine; Norepinephrine; Adrenaline; Noradrenaline; Shock; Sepsis Abstract: Objective To determine whether there was a difference between epinephrine and norepinephrine in achieving a mean arterial pressure (MAP) goal in intensive care (ICU) patients. Design Prospective, double-blind, randomised-controlled trial. Setting Four Australian university-affiliated multidisciplinary ICUs. Patients and participants Patients who required vasopressors for any cause at randomisation. Patients with septic shock and acute circulatory failure were analysed separately. Interventions Blinded infusions of epinephrine or norepinephrine to achieve a MAP aY=70 mmHg for the duration of ICU admission. Measurements Primary outcome was achievement of MAP goal >24 h without vasopressors. Secondary outcomes were 28 and 90-day mortality. Two hundred and eighty patients were randomised to receive either epinephrine or norepinephrine. Median time to achieve the MAP goal was 35.1 h (interquartile range (IQR) 13.8--70.4 h) with epinephrine compared to 40.0 h (IQR 14.5--120 h) with norepinephrine (relative risk (RR) 0.88 95% confidence interval (CI) 0.69--1.12 P = 0.26). There was no difference in the time to achieve MAP goals in the subgroups of patients with severe sepsis (n = 158 RR 0.81 95% CI 0.59--1.12 P = 0.18) or those with acute circulatory failure (n = 192 RR 0.89 95% CI 0.62--1.27 P = 0.49) between epinephrine and norepinephrine. Epinephrine was associated with the development of significant but transient metabolic effects that prompted the withdrawal of 18/139 (12.9%) patients from the study by attending clinicians. There was no difference in 28 and 90-day mortality. Conclusions Despite the development of potential drug-related effects with epinephrine, there was no difference in the achievement of a MAP goal between epinephrine and norepinephrine in a heterogenous population of ICU patients. Author Affiliation: (1) Department of Intensive Care Medicine, The St George Hospital, Gray Street, Kogarah, Sydney, 2217, Australia (2) Australian and New Zealand Intensive Care Research Centre, Monash University, Melbourne, Australia (3) Department of Intensive Care Medicine, Royal Brisbane Hospital and University of Queensland, Brisbane, Australia (4) Intensive Therapy Unit, Royal North Shore Hospital, Sydney, Australia (5) Department of Intensive Care Medicine, St Vincent's Hospital, Melbourne, Australia Article History: Registration Date: 09/07/2008 Received Date: 01/01/2008 Accepted Date: 19/06/2008 Online Date: 25/07/2008 Article note: This study was presented at the Annual Congress of the European Society of Intensive Care Medicine in Berlin on October 10 2007. The presentation received the International Sepsis Forum prize for best abstract and paper. This study has been published in abstract form: Myburgh J.A., Higgins A., Jovanovska A., Lipman J., Ramakrishnan N., Santamaria J and the CAT Study Investigators. (2007). A comparison of epinephrine and norepinephrine on reversal of shock. Intensive Care Medicine 33 (Supplement 2): S197. Trial registration: The study was registered with Current Controlled Studies: ISRCTN number 92846592.

Byline: Chin-Chung Shu (1), Chih-Hsin Lee (2), Jann-Yuan Wang (3), Jih-Shuin Jerng (4), Chong-Jen Yu (4), Po-Ren Hsueh (5), Li-Na Lee (5), Pan-Chyr Yang (4) Keywords: Nontuberculous mycobacteria; Pulmonary infection; Intensive care unit Abstract: Background The clinical significance of nontuberculous mycobacteria (NTM) pulmonary infection in medical intensive care unit (ICU) is still unclear. Materials and methods We conducted a retrospective study in the medical ICUs of a medical center in Taiwan from January 1999 to June 2007. Patients with NTM isolated from respiratory specimens within 1 month before or during the ICU course were identified. Those who fulfilled the diagnostic criteria of NTM pulmonary infection were identified and compared with patients with NTM colonization and control subjects who were culture-negative for mycobacteria. Results Among the 5,378 patients admitted to medical ICUs, 2,866 (53.3%) had received mycobacterial culture for respiratory specimens. NTM were isolated from 169 (5.8%) patients. Of them, 47 (27.8%) were considered NTM pulmonary infection. M. avium complex and M. abscessus were the most common pathogens. Within 100 days after ICU admission, significantly more patients with NTM infection died than those with NTM colonization and control subjects (47 vs. 8 vs. 14%, P < 0.001). Twenty-one (49%) patients with NTM pulmonary infection received anti-NTM treatment, with four experiencing adverse effects. Although statistically insignificant, anti-NTM treatment was associated with prolonged survival for those who died in the ICU and shorter ICU stay for those who survived the ICU course. Conclusion Our findings suggest that NTM pulmonary infection seems to associate with higher mortality in medical ICUs. Anti-NTM treatment is probably associated with a better outcome. Therefore, keeping a high suspicion when NTM is isolated and using careful consideration when starting anti-NTM treatment should be emphasized. Author Affiliation: (1) Department of Internal Medicine, National Taiwan University Hospital, Yun-Lin Branch, Yun Lin, Taiwan (2) Department of Internal Medicine, Buddhist Tzu Chi General Hospital, Taipei Branch, Taipei, Taiwan (3) Department of Internal Medicine, National Taiwan University Hospital, 7, Chung-Shan South Road, Taipei, 100, Taiwan (4) Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan (5) Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan Article History: Registration Date: 09/07/2008 Received Date: 31/03/2008 Accepted Date: 07/07/2008 Online Date: 22/07/2008 Article note: Taiwan Anti-Mycobacteria Investigation (TAMI) group: J.-Y. Wang, L.-N. Lee, C.-J. Yu, P.-C. Yang, W.-J. Su, C.-C. Shu, H.-C. Lai, C.-H. Lee and M.-C. Yu.

Byline: Jose Garnacho-Montero (1), Teresa Aldabo-Pallas (1), Mercedes Palomar-Martinez (2), Jordi Valles (3), Benito Almirante (4), Rafael Garces (5), Fabrio Grill (6), Miquel Pujol (7), Cristina Arenas-Gimenez (8), Eduard Mesalles (9), Ana Escoresca-Ortega (1), Marina Cueto (10), Carlos Ortiz-Leyba (1) Keywords: Bacteremia; Catheter; Peripherically inserted central venous catheters; Catheter-related bloodstream infection; Risk factor; Prognosis Abstract: Objective To assess the risk factors associated with CR-BSI development in critically ill patients with non-tunneled, non-cuffed central venous catheters (CVC) and the prognosis of the episodes of CR-BSI. Design and setting prospective, observational, multicenter study in nine Spanish Hospitals. Patients All subjects admitted to the participating ICUs from October 2004 to June 2005 with a CVC. Interventions None. Measurement and results Overall, 1,366 patients were enrolled and 2,101 catheters were analyzed. Sixty-six episodes of CR-BSI were diagnosed. The incidence of CR-BSI was significantly higher in CVC compared with peripherically inserted central venous catheters (PICVC) without significant differences among the three locations of CVC. In the multivariate analysis, duration of catheterization and change over a guidewire were the independent variables associated with the development of CR-BSI whereas the use of a PICVC was a protective factor. Excluding PICVC, 1,598 conventional CVC were analyzed. In this subset, duration of catheterization, tracheostomy and change over a guidewire were independent risk factors for CR-BSI. A multivariate analysis of predictors for mortality among 66 patients with CRSI showed that early removal of the catheter was a protective factor and APACHE II score at the admission was a strong determinant of in-hospital mortality. Conclusions Peripherically inserted central venous catheters is associated with a lower incidence of CR-BSI in critically ill patients. Exchange over a guidewire of CVC and duration of catheterization are strong contributors to CR-BSI. Our results reinforce the importance of early catheter removal in critically ill patients with CR-BSI. Author Affiliation: (1) Intensive Care Unit, Hospital Virgen del Rocio, Sevilla, Spain (2) Intensive Care Unit, Hospital de la Vall d'Hebron, Barcelona, Spain (3) Intensive Care Unit, Hospital Hospital Parc Tauli, Sabadell (Barcelona), Spain (4) Infectious Diseases Service, Hospital de la Vall d'Hebron, Barcelona, Spain (5) Intensive Care Unit, Hospital de la Ribera, Alcira (Valencia), Spain (6) Microbiology Service, Hospital Ramon y Cajal, Madrid, Spain (7) Infectious Diseases Service, Hospital de Bellvitge, Barcelona, Spain (8) Microbiology Service, Hospital Gregorio Maranon, Madrid, Spain (9) Intensive Care Unit, Hospital Germans Trias y Pujol, Badalona (Barcelona), Spain (10) Microbiology Service, Hospital Virgen Macarena, Sevilla, Spain Article History: Registration Date: 24/06/2008 Received Date: 19/02/2008 Accepted Date: 03/06/2008 Online Date: 12/07/2008 Article note: Supported by Ministerio de Sanidad y Consumo, Instituto de Salud Carlos III, Spanish Network for the Research in Infectious Diseases (REIPI C03/14) and Spanish Network for the Research in Infectious Diseases (REIPI RD06/0008).

Byline: Paul E. Marik (1), Gary P. Zaloga (2) Keywords: Immunonutrition; Critical illness; ICU; Sepsis; ARDS; Burns; Trauma; Arginine; Omega 3 fatty acids; Glutamine; Enteral nutrition Abstract: Background The role of immuno-modulating diets (IMDs) in critically ill patients is controversial. Objective The goal of this meta-analysis was to determine the impact of IMD's on hospital mortality, nosocomial infections and length of stay (LOS) in critically ill patients. Outcome was stratified according to type of IMD and patient setting. Data sources MEDLINE, Embase, Cochrane Register of Controlled Trials. Study selection RCT's that compared the outcome of critically ill patients randomized to an IMD or a control diet. Data synthesis Twenty-four studies (with a total of 3013 patients) were included in the meta-analysis 12 studies included ICU patients, 5 burn patients and 7 trauma patients. Four of the studies used formulas supplemented with arginine, two with arginine and glutamine, nine with arginine and fish oil (FO), two with arginine, glutamine and FO, six with glutamine alone and three studies used a formula supplemented with FO alone. Overall IMD's had no effect on mortality or LOS, but reduced the number of infections (OR 0.63 95% CI 0.47--0.86, P = 0.004, I .sup.2 = 49%). Mortality, infections and LOS were significantly lower only in the ICU patients receiving the FO IMD (OR 0.42, 95% CI 0.26--0.68 OR 0.45, 95% CI 0.25--0.79 and WMD -6.28 days, 95% CI -9.92 to -2.64, respectively). Conclusions An IMD supplemented with FO improved the outcome of medical ICU patients (with SIRS/sepsis/ARDS). IMDs supplemented with arginine with/without additional glutamine or FO do not appear to offer an advantage over standard enteral formulas in ICU, trauma and burn patients. Author Affiliation: (1) Division of Pulmonary and Critical Care Medicine, Thomas Jefferson University, 834 Walnut Street, Suite 650, Philadelphia, PA, 19107, USA (2) Baxter Healthcare, Deerfield, IL, USA Article History: Registration Date: 03/07/2008 Received Date: 24/01/2008 Accepted Date: 22/06/2008 Online Date: 15/07/2008

Byline: Jaime M. Beecroft (1), Michael Ward (2), Magdy Younes (2), Shelley Crombach (2), Orla Smith (2), Patrick J. Hanly (1,3) Keywords: Intensive care unit; Sleep; Actigraphy; Polysomnography; Nurse assessment; Behavioural assessment; Critical illness Abstract: Objective Sleep loss and sleep disruption are common in critically ill patients and may adversely affect clinical outcomes. Although polysomnography remains the most accurate and reliable way to measure sleep, it is costly and impractical for regular use in the intensive care unit. This study evaluates the accuracy of two other methods currently used for measuring sleep, actigraphy (monitoring of gross motor activity) and behavioural assessment by the bedside nurse, by comparing them to overnight polysomnography in critically ill patients. Design Observational study with simultaneous polysomnography, actigraphy and behavioural assessment of sleep. Setting Medical-surgical intensive care unit. Patients and participants Twelve stable, critically ill, mechanically ventilated patients [68 (13) years, Glasgow coma scale 11 (0)]. Interventions None. Measurements and results Sleep was severely disrupted, reflected by decreased total sleep time and sleep efficiency, high frequency of arousals and awakenings and abnormal sleep architecture. Actigraphy overestimated total sleep time and sleep efficiency. The overall agreement between actigraphy and polysomnography was Conclusions Actigraphy and behavioural assessment by the bedside nurse are inaccurate and unreliable methods to monitor sleep in critically ill patients. Author Affiliation: (1) Department of Medicine, University of Calgary, Calgary, AB, Canada (2) Department of Medicine, University of Toronto, Toronto, ON, Canada (3) 1421 Health Sciences Center, 3330 Hospital Drive NW, Calgary, AB, Canada, T2N 4N1 Article History: Registration Date: 27/05/2008 Received Date: 12/10/2007 Accepted Date: 22/05/2008 Online Date: 03/06/2008

Byline: Paolo Calzavacca (1), Elisa Licari (1), Augustine Tee (1), Moritoki Egi (1), Michael Haase (1), Anja Haase-Fielitz (1), Rinaldo Bellomo (1) Keywords: Medical Emergency Team; Rapid response system; Critical illness; Vital signs; Mortality Abstract: Objective To identify factors that predict outcome in patients receiving a Medical Emergency Team review. Design Prospective observational study. Setting Tertiary hospital. Patients Cohort of 228 patients receiving one or more Medical Emergency Team reviews during daytime hours over a 1-year-period. Control cohort of all patients (n = 900) receiving a Medical Emergency Team review in the same period. Measurements and results We prospectively collected information from patients receiving a Medical Emergency Team review during daytime hours from Monday to Friday (audit group) including the clinical cause of deterioration and timing of call in relation to the first documented Medical Emergency Team call criterion (activation delay). We also collected information from the hospital Medical Emergency Team database regarding all patients visited by the Medical Emergency Team during the same period (complete cohort). Audit group patients had several similar characteristics to complete cohort patients but were less likely to be not-for-resuscitation before Medical Emergency Team review and more likely to receive a Medical Emergency Team review because of hypotension, change in neurological status and oliguria. Delayed Medical Emergency Team activation and not-for resuscitation orders were the only factors to show an independent statistical association with mortality (OR 2.53, 95% CI: 1.2--5.31, P = 0.01 and OR 5.63, 95% CI: 2.81--11.28, P < 0.01, respectively). Conclusion Delayed Medical Emergency Team activation and NFR orders are the strongest independent predictors of mortality in patients receiving a Medical Emergency Team review. Avoidance of delayed Medical Emergency Team activation should be a priority for hospitals operating rapid response systems. Author Affiliation: (1) Department of Intensive Care and Department of Medicine, Austin Hospital, Studley Rd, Heidelberg, Melbourne, VIC, 3084, Australia Article History: Registration Date: 16/07/2008 Received Date: 26/02/2008 Accepted Date: 12/07/2008 Online Date: 24/07/2008

Byline: Yasser Sakr (1), Christian Madl (2), Daniela Filipescu (3), Rui Moreno (4), Johan Groeneveld (5), Antonio Artigas (6), Konrad Reinhart (1), Jean-Louis Vincent (7) Keywords: Body mass index; Multicentre; Outcome; Intensive care; Nosocomial infection Abstract: Objective To investigate the possible impact of obesity on morbidity and mortality in intensive care unit (ICU) patients included in the European observational sepsis occurrence in acutely ill patients (SOAP) study. Design Planned substudy from the SOAP database. Setting One hundred and ninety-eight ICUs in 24 European countries. Patients All patients admitted to one of the participating ICUs. Patients were classified, according to their body mass index (BMI), as underweight ( Measurements and results The BMI was available in 2,878 (91%) of the 3,147 patients included in the SOAP study 120 patients (4.2%) were underweight, 1,206 (41.9%) had a normal BMI, 1,047 (36.4%) were overweight, 424 (14.7%) were obese, and 81 (2.8%) were very obese. Obese and very obese patients more frequently developed ICU-acquired infections than patients in lower BMI categories. Very obese patients showed a trend towards longer ICU [median (IQ): 4.1 (1.8--12.1) vs. 3.1 (1.7--7.2) days, P = 0.056) and hospital lengths of stay [14.3 (8.4--27.4) vs. 12.3 (5.1--24.4), days P = 0.077] compared to those with a normal BMI. However, there were no significant differences among the groups in ICU or hospital mortality rates. In a multivariate Cox regression analysis, none of the BMI categories was associated with an increased risk of 60-day in-hospital death. Conclusion BMI did not have a significant impact on mortality in this mixed population of ICU patients. Author Affiliation: (1) Department of Anaesthesiology and Intensive Care, Friedrich-Schiller-University Jena, Jena, Germany (2) Intensive Care Unit 13H1, Department of Internal Medicine IV, Medical University of Vienna, Vienna, Austria (3) Department of Anesthesiology and Cardiac Intensive Care, Institute of Cardiovascular Diseases, Bucharest, Romania (4) Department of Intensive Care, Hospital de St Antonio dos Capuchos, Lisbon, Portugal (5) Department of Intensive Care, VU University Medical Center, Amsterdam, The Netherlands (6) Department of Intensive Care, Sabadell Hospital, Sabadell, Spain (7) Department of Intensive Care, Hopital Erasme, Universite libre de Bruxelles, Route de Lennik, 808, 1070, Brussels, Belgium Article History: Registration Date: 18/07/2008 Received Date: 09/11/2007 Accepted Date: 01/06/2008 Online Date: 01/08/2008 Article note: This article is discussed in the editorial available at doi: 10.1007/s00134-008-1244-z

Byline: Thomas Geeraerts (1), Sybille Merceron (1), Dan Benhamou (1), Bernard Vigue (1), Jacques Duranteau (1) Keywords: Ocular ultrasound; Traumatic brain injury; Subarachnoid hemorrhage; Elevated intracranial pressure; Optic nerve sheath Abstract: Objective To assess the relationship between optic nerve sheath diameter (ONSD) and intracranial pressure (ICP) in neurocritical care patients. Design Prospective, observational study. Setting Surgical critical care unit, level 1 trauma center. Patients A total number of 37 adult patients requiring sedation and ICP monitoring after severe traumatic brain injury, subarachnoid hemorrhage, intracranial hematoma, or stroke. Measurements and main results Optic nerve sheath diameter was measured with a 7.5 MHz linear ultrasound probe. ICP was measured invasively via a parenchymal device. Simultaneous measurements were performed atleast once a day during the first 2 days after ICP insertion and in cases of acute changes. There was a significant relationship between ONSD and ICP (78 simultaneous measures, r = 0.71, P < 0.0001). Changes in ICP were strongly correlated with changes in ONSD (39 measures, r = 0.73, P < 0.0001). Enlarged ONSD was a suitable predictor of elevated ICP (>20 mmHg) (area under ROC curve = 0.91). When ONSD was less than 5.86 mm, the negative likehood ratio for raised ICP was 0.06. Conclusion In sedated neurocritical care patients, non-invasive sonographic measurements of ONSD are correlated with invasive ICP, and the probability to have raised ICP if ONSD is less than 5.86 mm is very low. This method could be used as a screening test when raised ICP is suspected. Author Affiliation: (1) AP-HP, Departement d'Anesthesie-Reanimation Chirurgicale, Univ Paris-Sud, Centre Hospitalier Universitaire Bicetre, 94275, Le Kremlin Bicetre, France Article History: Registration Date: 06/05/2008 Received Date: 08/03/2008 Accepted Date: 02/05/2008 Online Date: 29/05/2008 Article note: The authors received no financial support for this work.

Byline: Nektaria Xirouchaki (1), Eumorfia Kondili (1), Katerina Vaporidi (1), George Xirouchakis (1), Maria Klimathianaki (1), George Gavriilidis (1), Evi Alexandopoulou (1), Maria Plataki (1), Christina Alexopoulou (1), Dimitris Georgopoulos (1) Keywords: Controlled modes; Assisted modes; Patient--ventilator interaction Abstract: Objectives It is not known if proportional assist ventilation with load-adjustable gain factors (PAV+) may be used as a mode of support in critically ill patients. The aim of this study was to examine the effectiveness of sustained use of PAV+ in critically ill patients and compare it with pressure support ventilation (PS). Design and setting Randomized study in the intensive care unit of a university hospital. Methods A total of 208 critically ill patients mechanically ventilated on controlled modes for at least 36 h and meeting certain criteria were randomized to receive either PS (n = 100) or PAV+ (n = 108). Specific written algorithms were used to adjust the ventilator settings in each mode. PAV+ or PS was continued for 48 h unless the patients met pre-defined criteria either for switching to controlled modes (failure criteria) or for breathing without ventilator assistance. Results Failure rate was significantly lower in PAV+ than that in PS (11.1 vs. 22.0%, P = 0.040, OR 0.443, 95% CI 0.206--0.952). The proportion of patients exhibiting major patient--ventilator dyssynchronies at least during one occasion and after adjusting the initial ventilator settings, was significantly lower in PAV+ than in PS (5.6 vs. 29.0%, P < 0.001, OR 0.1, 95% CI 0.06--0.4). The proportion of patients meeting criteria for unassisted breathing did not differ between modes. Conclusions PAV+ may be used as a useful mode of support in critically ill patients. Compared to PS, PAV+ increases the probability of remaining on spontaneous breathing, while it considerably reduces the incidence of patient--ventilator asynchronies. Author Affiliation: (1) Intensive Care Medicine Department, University Hospital of Heraklion, Medical School, University of Crete, Heraklion, Crete, Greece Article History: Registration Date: 25/06/2008 Received Date: 08/04/2008 Accepted Date: 16/06/2008 Online Date: 08/07/2008 Article note: Supported by the Society of Critical Care of Crete. Electronic supplementary material The online version of this article (doi: 10.1007/s00134-008-1209-2) contains supplementary material, which is available to authorized users.

Byline: Adelaida Lamas (1), Jesus Lopez-Herce (1), Luis Sancho (1), Santiago Mencia (1), Angel Carrillo (1), Maria Jose Santiago (1), Vicente Martinez (2) Keywords: Bispectral index; Auditory-evoked potentials; COMFORT scale; Ramsay scale; Sedation; Critically ill children Abstract: Objective To evaluate the correlation and agreement between the bispectral index (BIS), middle latency auditory-evoked potential index (AEP index), Ramsay scale (RS) and COMFORT scale (CS) for evaluation of the level of sedation in critically ill children. Design Prospective observational study. Setting Pediatric critical care unit. Patients Seventy-seven critically ill children receiving sedation and mechanical ventilation. Measurements and results Simultaneous recording of BIS, AEP index, RS and CS were performed once a day, for a maximum of 5 days. Two levels of sedation were categorized: light--moderate versus deep--very deep. Correlations between methods were determined using Spearman rank correlation test and the agreement using Cohen's Kappa test. The correlation and agreement between the four methods was moderate-to-good. Correlation was not found in paralyzed children. There was no correlation between the four methods and the heart rate or blood pressure, or with the type or dose of sedative medication. Receiver-operating characteristic (ROC) analysis revealed best discrimination between light--moderate and deep--very deep sedation at BIS and AEP index values of 63.5 and 33.5 when the level of sedation was classified by the RS, and at BIS and AEP index values of 67 and 37.5, respectively, when the level of sedation was classified by the CS. Conclusion There is a moderate-to-good correlation and agreement of BIS and AEP index with the clinical scales in critically ill children without neuromuscular blockade. BIS and AEP index could be useful to evaluate the level of sedation in critically ill children with and without neuromuscular blockade. Author Affiliation: (1) Pediatric Intensive Care Unit, Hospital General Universitario Gregorio Maranon, Dr Castelo 47, 28009, Madrid, Spain (2) Center for Health and Social Studies (CESS), Universidad de Castilla-La Mancha, Cuenca, Spain Article History: Registration Date: 24/06/2008 Received Date: 22/10/2007 Accepted Date: 06/06/2008 Online Date: 04/07/2008

Byline: Kwok M. Ho (1), Joseph Y. Ng (1) Keywords: Length of stay; Mortality; Sedative agents; Sedative drugs Abstract: Objective To investigate the effects of using propofol for medium and long-term sedation on mortality and length of intensive care unit (ICU) stay of critically ill adult patients. Design Randomised controlled studies comparing propofol with an alternative sedative agent in critically ill adult patients were included without language restriction from the Cochrane Controlled Trial Register (2007 issue 3), EMBASE, and MEDLINE databases (1966 to 1 December 2007). Two reviewers reviewed the quality of the studies and performed data extraction independently. Measurements and results Sixteen randomised controlled studies with a total of 1,386 critically ill adult patients were considered. Nine of the pooled studies (56%) limited the doses of propofol infusion to Conclusions Using propofol for prolonged sedation in critically ill patients appears to be safe and may reduce duration of mechanical ventilation. It reduces the length of ICU stay when compared to long acting benzodiazepines, but not when compared to midazolam. Author Affiliation: (1) Intensive Care Unit, Royal Perth Hospital, Perth, WA, 6000, Australia Article History: Registration Date: 10/06/2008 Received Date: 11/01/2008 Accepted Date: 04/06/2008 Online Date: 25/06/2008

Byline: A. Morandi (1,2,3), P. Pandharipande (4), M. Trabucchi (3), R. Rozzini (2,3), G. Mistraletti (5), A. C. Trompeo (6), C. Gregoretti (7), L. Gattinoni (8), M. V. Ranieri (6), L. Brochard (9), D. Annane (10), C. Putensen (11), U. Guenther (11), P. Fuentes (12), E. Tobar (13), A. R. Anzueto (14), A. Esteban (15), Y. Skrobik (16), J. I. F. Salluh (17), M. Soares (17), C. Granja (18), A. Stubhaug (19), S. E. Rooij (20), E. Wesley Ely (1,21,22) Keywords: Delirium; Delirio; Delire; Delier; Delir; Delire; Confusion; Confusione; Coma; Acute brain dysfunction; Psychosis; Delirium tremens; Durchgangs-Syndrom; Acute verwardheid Abstract: Background Delirium (acute brain dysfunction) is a potentially life threatening disturbance in brain function that frequently occurs in critically ill patients. While this area of brain dysfunction in critical care is rapidly advancing, striking limitations in use of terminology related to delirium internationally are hindering cross-talk and collaborative research. In the English literature, synonyms of delirium such as the Intensive Care Unit syndrome, acute brain dysfunction, acute brain failure, psychosis, confusion, and encephalopathy are widely used. This often leads to scientific 'confusion' regarding published data and methodology within studies, which is further exacerbated by organizational, cultural and language barriers. Objective We undertook this multinational effort to identify conflicts in terminology and phenomenology of delirium to facilitate communication across medical disciplines and languages. Methods The evaluation of the terminology used for acute brain dysfunction was determined conducting communications with 24 authors from academic communities throughout countries/regions that speak the 13 variants of the Romanic languages included into this manuscript. Results In the 13 languages utilizing Romanic characters, included in this report, we identified the following terms used to define major types of acute brain dysfunction: coma, delirium, delirio, delirium tremens, delire, confusion mentale, delir, delier, Durchgangs-Syndrom, acute verwardheid, intensiv-psykose, IVA-psykos, IVA-syndrom, akutt konfusion/forvirring. Interestingly two terms are very consistent: 100 % of the selected languages use the term coma or koma to describe patients unresponsive to verbal and/or physical stimuli, and 100% use delirium tremens to define delirium due to alcohol withdrawal. Conversely, only 54% use the term delirium to indicate the disorder as defined by the DSM-IV as an acute change in mental status, inattention, disorganized thinking and altered level of consciousness. Conclusions Attempts towards standardization in terminology, or at least awareness of differences across languages and specialties, will help cross-talk among clinicians and researchers. Author Affiliation: (1) Center for Health Services Research, 6100 Medical Center East, Nashville, TN, 37232-8300, USA (2) Department of Internal Medicine and Geriatrics, Poliambulanza Hospital, Brescia, Italy (3) Geriatric Research Group, Brescia, Italy (4) Division of Critical Care Medicine, Department of Anesthesiology, Vanderbilt Medical Center, Nashville, USA (5) Istituto di Anestesiologia e Rianimazione, Universita degli Studi di Milano, U.O. di Anestesia e Rianimazione, Azienda Ospedaliera San Paolo, Polo Universitario, Milan, Italy (6) Intensive Care Unit, Molinette Hospital, Universita' di Torino, Torino, Italy (7) Intensive Care Unit, Azienda Ospedaliera CTO-CRF-ICORMA, Torino, Italy (8) Istituto di Anestesiologia e Rianimazione, Universita degli Studi di Milano, U.O. di Anestesia e Rianimazione, Dipartimento di Anestesia, Rianimazione (Intensiva e Subintensiva) e Terapia del Dolore, Fondazione IRCCS, Ospedale Maggiore Policlinico, Mangiagalli, Regina Elena di Milano, Milan, Italy (9) Reanimation Medicale, AP-HP, centre hospitalier Albert Chenevier, Henri Mondor, Universite Paris 12, Creteil, France (10) Service de reanimation, hopital Raymond Poincare (AP-HP), Universite de Versailles, Garches, France (11) Department of Anesthesiology and Intensive Care Medicine, University Hospital Sigmund Freud, Bonn, Germany (12) Geriatrics Section, Medicine Department, Clinical Hospital University of Chile, Santiago, Chile (13) Medicina Intensiva, Hospital Clinico Universidad de Chile, Santiago, Chile (14) South Texas Veterans Health Care System, Audie L. Murphy Division, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA (15) Intensive Care Unit, Hospital Universitario de Getafe, CIBER de Enfermedades Respiratorias, Madrid, Spain (16) Intensive Care Unit, Universite de Montreal, Hospital Maisonnevue-Rosemont, Montreal, QC, Canada (17) Intensive Care Unit, Centro de Tratamento Intensivo, Instituto Nacional de Cancer, INCA, Rio de Janeiro, Brazil (18) Medical Intensive Care Unit, Hospital Pedro Hispano, Matosinhos, Portugal (19) Department of Anesthesiology and Intensive Care, Rikshopitalet University Hospital, Oslo, Norway (20) Department of Geriatrics, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands (21) VA Tennessee Valley Geriatric Research, Education and Clinical Center (GRECC), Nashville, TN, USA (22) Division of Allergy/Pulmonary/Critical Care Medicine, Vanderbilt Medical Center, Nashville, TN, USA Article History: Registration Date: 26/05/2008 Received Date: 10/04/2008 Accepted Date: 21/05/2008 Online Date: 18/06/2008

Byline: Francois Blot (1), Thomas Similowski (2), Jean-Louis Trouillet (3), Patrick Chardon (4), Jean-Michel Korach (5), Marie-Alyette Costa (6), Didier Journois (7), Guillaume Thiery (8), Muriel Fartoukh (9), Isabelle Pipien (10), Nicolas Bruder (11), David Orlikowski (12), Frederic Tankere (13), Isabelle Durand-Zaleski (14), Christian Auboyer (15), Gerard Nitenberg (1), Laurent Holzapfel (16), Alain Tenaillon (17), Jean Chastre (3), Agnes Laplanche (18) Keywords: Tracheotomy; Tracheostomy; Mechanical ventilation; Intensive care unit; Critical care; ICU-acquired pneumonia; Hospital mortality; Randomised controlled trial Abstract: Objective Although several advantages are attributed to tracheotomy in ICU patients requiring mechanical ventilation (MV), true benefits and the optimal timing of tracheotomy remain controversial. In this study, we compared early tracheotomy (ET) with prolonged intubation (PI) in severely ill patients requiring prolonged MV. Design Prospective, randomized study. Setting Twenty-five medical and surgical ICUs in France. Patients Patients expected to require MV > 7 days. Measurements and results Patients were randomised to either (open or percutaneous) ET within 4 days or PI. The primary end-point was 28-day mortality. Secondary end-points were: the incidence of ICU-acquired pneumonia, number of d1-d28 ventilator-free days, time spent in the ICU, 60-day mortality, number of septic episodes, amount of sedation, comfort and laryngeal and tracheal complications. A sample size of 470 patients was considered necessary to obtain a reduction from 45 to 32% in 28-day mortality. After 30 months, 123 patients had been included (ET = 61, PI = 62) in 25 centres and the study was prematurely closed. All group characteristics were similar upon admission to ICU. No difference was found between the two groups for any of the primary or secondary end-points. Greater comfort was the sole benefit afforded by tracheotomy after subjective self-assessment by patients. Conclusions The trial did not demonstrate any major benefit of tracheotomy in a general population of ICU patients, as suggested in a previous meta-analysis, but was underpowered to draw any firm conclusions. The potential advantage of ET may be restricted to selected groups of patients. Author Affiliation: (1) Intensive Care Unit, Institut Gustave Roussy, 39 rue Camille Desmoulins, 94805, Villejuif Cedex, France (2) Department of Respiratory Medicine and Intensive Care, Groupe Hospitalier Pitie-Salpetriere, AP-HP, Paris, France (3) Intensive Care Unit, Groupe Hospitalier Pitie-Salpetriere, AP-HP, Paris, France (4) Medical-surgical ICU, Hopital Lapeyronie, Montpellier, France (5) Medical-surgical ICU, Centre Hospitalier, Chalons-en-Champagne, France (6) Nephrology ICU, Hopital Tenon, AP-HP, Paris, France (7) Universite Descartes, Intensive Care Unit, Hopital Europeen Georges Pompidou, AP-HP, Paris, France (8) Medical ICU, Hopital Saint Louis, AP-HP, Paris, France (9) Pneumology ICU, Hopital Tenon, AP-HP, Paris, France (10) Medical-surgical ICU, Centre Hospitalier des Quatre Villes, Saint-Cloud, France (11) Medical-surgical ICU, Hopital Timone, Marseille, France (12) Medical ICU, Hopital Raymond Poincare, AP-HP, Garches, France (13) Department of Otorhinolaryngology, Groupe Hospitalier Pitie-Salpetriere, AP-HP, Paris, France (14) Department of Public Health, Hopital Henri Mondor, AP-HP, Creteil, France (15) Medical-surgical ICU, Hopital Nord, Saint-Etienne, France (16) Medical-surgical ICU, Centre Hospitalier, Bourg en Bresse, France (17) Medical-surgical ICU, Centre Hospitalier Sud Francilien, Evry, France (18) Biostatistics Unit, Institut Gustave Roussy, Villejuif, France Article History: Registration Date: 12/06/2008 Received Date: 05/12/2007 Accepted Date: 31/05/2008 Online Date: 01/07/2008 Article note: This article is discussed in the editorial available at: doi: 10.1007/s00134-008-1194-5 Electronic supplementary material The online version of this article (doi: 10.1007/s00134-008-1195-4) contains supplementary material, which is available to authorized users.

Byline: Donald E. G. Griesdale (1,2,3), T. Laine Bosma (1), Tobias Kurth (4), George Isac (1,2,3), Dean R. Chittock (3) Keywords: Intubation, intratracheal; Complications; Critical care; Propensity score Abstract: Objective Assess the risk of complications during endotracheal intubation (ETI) and their association with the skill level of the intubating physician. Design Prospective cohort study of 136 patients intubated by the intensive care team during a 5-month period. Standardized data forms were used to collect detailed information on the intubating physicians, supervisors, techniques, medications and complications. Setting Canadian academic intensive care unit. Measurements and results All intubations were successful and there were no deaths during intubation. Non-experts were supervised in 92% of procedures. Expert operators were successful within two attempts in 94%, compared to only 82% of non-experts (P = 0.03), with 13.2% of all intubations requiring aY=3 attempts. Furthermore, 10.3% of intubations required 10 or more minutes. Difficult intubation (3 or more attempts by an expert) occurred in 6.6%. Overall risk of complications was 39%, including: severe hypoxemia (19.1%), severe hypotension (9.6%), esophageal intubation (7.4%) and frank aspiration (5.9%). ICU and hospital mortality were 15.4 and 29.4%, respectively. Compared with non-expert intubating physicians, propensity score-adjusted odds ratios (95% confidence interval) for expert physicians were 0.92 (95% CI: 0.28, 3.05, P = 0.89) for any complication, 0.45 (95% CI: 0.09, 2.20, P = 0.32) for ICU mortality and 0.47 (95% CI: 0.13, 1.70, P = 0.25) for hospital mortality. Two or more attempts at ETI was independently associated with an increased risk of severe complications (OR 3.31, 95% CI: 1.30, 8.40, P = 0.01). Conclusions These prospective data show a high risk of serious complications, and difficult intubations, that are associated with ETI of the critically ill. Descriptor Artificial airways and complications. Author Affiliation: (1) Department of Anesthesiology, Pharmacology and Therapeutics, University of British Columbia, Vancouver, BC, Canada (2) Department of Anesthesia, Critical Care Medicine, Vancouver General Hospital, Room 2438, Jim Pattison Pavilion, 2nd Floor, 855 West 12th Avenue, Vancouver, V5Z 1M9, BC, Canada (3) Department of Medicine, Division of Critical Care Medicine, University of British Columbia and Program of Critical Care Medicine, Vancouver General Hospital, Vancouver, BC, Canada (4) Department of Epidemiology, Harvard School of Public Health and Divisions of Preventive Medicine and Aging, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA Article History: Registration Date: 24/06/2008 Received Date: 25/02/2008 Accepted Date: 10/06/2008 Online Date: 05/07/2008

Byline: Didier Ledoux (1), Jean-Luc Canivet (1), Jean-Charles Preiser (1), JoA< Keywords: Severity of illness index; SAPS 3; APACHE; Outcome assessment; Critical care Abstract: Objectives To validate the SAPS 3 admission score in an independent general intensive care case mix and to compare its performances with the APACHE II and the SAPS II scores. Design Cohort observational study. Setting A 26-bed general ICU from a Tertiary University Hospital. Patients and participants Eight hundred and fifty-one consecutive patients admitted to the ICU over an 8-month period. Of these patients, 49 were readmissions, leaving 802 patients for further analysis. Intervention None. Measurements and results APACHE II, SAPS II and SAPS 3 variables were prospectively collected scores and their derived probability of death were calculated according to their original manuscript description. The discriminative power was assessed using the area under the ROC curve (AUROC) and calibration was verified with the Hosmer--Lemeshow goodness-of-fit test. The AUROC of the APACHE II model (AUROC = 0.823) was significantly lower than those of the SAPS II (AUROC = 0.850) and SAPS 3 models (AUROC = 0.854) (P = 0.038). The calibration of the APACHE II model (P = 0.037) and of the SAPS 3 global model (P = 0.035) appeared unsatisfactory. On the contrary, both SAPS II model and SAPS 3 model customised for Central and Western Europe had a good calibration. However, in our study case mix, SAPS II model tended to overestimate the probability of death. Conclusion In this study, the SAPS 3 admission score and its prediction model customised for Central and Western Europe was more discriminative and better calibrated than APACHE II, but it was not significantly better than the SAPS II. Author Affiliation: (1) Soins Intensifs Generaux, Centre Hospitalier Universitaire de Liege, Domaine Universitaire de Sart Tilman Bat B35, 4000, Liege, Belgium Article History: Registration Date: 11/06/2008 Received Date: 18/12/2007 Accepted Date: 28/05/2008 Online Date: 01/07/2008 Article note: Electronic supplementary material The online version of this article (doi: 10.1007/s00134-008-1187-4) contains supplementary material, which is available to authorized users.

Byline: Rafael Fernandez (1), Nestor Bacelar (1), Gonzalo Hernandez (2), Isabel Tubau (1), Francisco Baigorri (1), Gisela Gili (1), Antonio Artigas (1) Keywords: Mechanical ventilation; Tracheostomy; Hospital survival; Outcome research; Scoring system Abstract: Objective To determine the effect of discharge from the ICU with a tracheostomy tube on ward mortality and its relation to patient vulnerability. Design and setting Retrospective single-center cohort study. Methods Database (2003--2006) review of patients undergoing mechanical ventilation (MV) > 24 h and discharged from the ICU with or without tracheostomy tube in place and followed up to hospital discharge or death. We recorded clinical characteristics, complications, major ICU procedures, subjective prognosis at ICU discharge (Sabadell score), and hospital outcome. Factors associated with ward mortality were analyzed by multiple logistic regression. Results From 3,065 patients admitted to the ICU, 1,502 needed MV > 24 h. Only 936 patients (62%) survived the ICU and were transferred to the ward of these, 130 (13.9%) had a tracheostomy tube in place. Ward mortality was higher in patients with a tracheostomy tube in place than in those without (26 vs. 7%, P < 0.001). Increased ward mortality among cannulated patients was seen only in those with intermediate Sabadell score (24 vs. 9% in score 1, P = 0.02, and 38 vs. 24% in score 2, P = 0.06), but not in the 'good prognosis' (2 vs. 2%, score 0) and 'expected to die in hospital' (80 vs. 75%, score 3) groups. Multivariate analysis found three factors associated with ward mortality: age, tracheostomy tube in place, and Sabadell score. Conclusion Lack of tracheostomy decannulation in the ICU appears to be associated with ward mortality, but only in the group with a Sabadell score of 1. Author Affiliation: (1) Critical Care Center, Hospital de Sabadell, CIBERES, Parc Tauli s/n., 08208, Sabadell, Spain (2) Critical Care Center, Hospital de Toledo, Toledo, Spain Article History: Registration Date: 16/05/2008 Received Date: 21/12/2007 Accepted Date: 14/05/2008 Online Date: 03/06/2008 Article note: Electronic supplementary material The online version of this article (doi: 10.1007/s00134-008-1169-6) contains supplementary material, which is available to authorized users.

Byline: Karen E. A. Burns (1,2), Francois Lellouche (3), Martin R. Lessard (4) Abstract: Background Limiting the duration of invasive ventilation is an important goal in caring for critically ill patients. Several clinical trials have shown that compared to traditional care, protocols can reduce the total duration of mechanical ventilation. Computerized or automated weaning has the potential to improve weaning, while decreasing associated workload, and to transfer best evidence into clinical practice by integrating closed-loop technology into protocols that can be operationalized continuously. Discussion In this article, we review the principles of automated systems, discuss automated systems that can be used during weaning, and examine the best-current evidence from randomized trials and observational studies supporting their use. We highlight three commercially available systems (Mandatory Minute Ventilation, Adaptive Support Ventilation and SmartCare[TM]) that can be used to automate the weaning process. We note advantages and disadvantages associated with individual weaning systems and differences among them. Conclusions We discuss the potential role for automation in complimenting clinical acumen, reducing practice pattern variation and facilitating knowledge translation into clinical practice, and underscore the need for additional high quality investigations to evaluate automated weaning systems in different practice settings and diverse patient populations. Author Affiliation: (1) Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, ON, Canada (2) Keenan Research Centre, Li Ka Shing Knowledge Institute, R. Samuel McLaughlin Foundation, St Michael's Hospital, the University of Toronto, 30 Bond Street, Room 4-045 Queen Wing, Toronto, ON, M5B 1W8, Canada (3) Department of Critical Care, Centre de recherche de l'Hopital Laval, Institut Universitaire de Cardiologie et de Pneumologie, Universite LAVAL, Quebec City, QC, Canada (4) Departments of Anesthesia and Critical Care, Hopital de l'Enfant-Jesus, Universite Laval, Quebec City, QC, Canada Article History: Registration Date: 08/05/2008 Received Date: 04/02/2008 Accepted Date: 04/05/2008 Online Date: 03/06/2008 Article note: Dr. Burns holds a Clinician Scientist award from the Canadian Institutes of Health Research. Dr. Burns and Dr. Lellouche hold a travel bursary from Draeger Medical Inc.

Byline: Jennifer L. McAdam (1), Shoshana Arai (1), Kathleen A. Puntillo (1) Keywords: Intensive care units; Family; Critical care; Family experiences; Family roles; End-of-life care Abstract: Objective To describe the contributions to care that family members perform while their loved one is at high risk of dying in the intensive care unit. Design Exploratory, descriptive analysis. Setting Two intensive care units at a tertiary medical center in the western United States. Participants Through purposive sampling, 25 family members of 24 ICU patients at high risk of dying participated in the study. Interventions None. Measurements and results A qualitative, descriptive technique was used for data analysis. Three independent raters coded transcripts of audiotaped interviews with family members about their experiences in the ICU. Recurring themes were categorized into roles that family members take on while their loved one is in the ICU. These work roles consisted of active presence, patient protector, facilitator, historian, coach, and voluntary caregiver. Conclusions Family members are important to patient care in the ICU. They perform multiple roles that are often not valued or go unrecognized by ICU health care providers. More support and appreciation of family members' contributions to care may provide families opportunities for intimacy and promote a sense of belonging in the highly technical environment of an ICU. Author Affiliation: (1) Department of Physiological Nursing, University of California, San Francisco School of Nursing, 94143-0610, San Francisco, CA, USA Article History: Registration Date: 28/02/2008 Received Date: 22/11/2007 Accepted Date: 07/02/2008 Online Date: 28/03/2008 Article note: Electronic supplementary material The online version of this article (doi: 10.1007/s00134-008-1066-z) contains supplementary material, which is available to authorized users. Partial funding from Soros Project on Death in America to Dr. Puntillo, Soros Faculty Scholar.

Byline: Arnaud Desachy (1), Marc Clavel (2,3), Albert Vuagnat (1), Sandrine Normand (2), Valerie Gissot (1), Bruno Francois (2,3) Keywords: Early enteral nutrition; Calorie requirements; Residual gastric volume; Mechanical ventilation; Intensive care unit Abstract: Objective To compare the initial (D7) calorie intake and tolerability of two early enteral nutrition protocols in which the optimal flow rate was introduced either immediately or gradually. Design Open, prospective, randomized study. Setting Two medical-surgical intensive care units. Patients One hundred consecutive intubated and mechanically ventilated patients. Interventions Early enteral nutrition was started within 24a-h following intubation, and the optimal flow rate (25a-Kcal/kga-day.sup.-1) was either introduced immediately or reached in increments. Flow rate of the nutritional solution was adapted to the residual gastric volume, measured every 8a-h, and the use of prokinetic agents was encouraged. Vomiting, regurgitation, colectasia, and suspected aspiration were defined as serious adverse events requiring withdrawal of enteral nutrition. Measurements and results When introduced immediately at optimal flow rate, early enteral nutrition led to a significant improvement in actual calorie supply (pa-a-300a-ml) was more frequent when optimal flow rate was introduced immediately (a-pa-=a-0.04), frequency of serious adverse events necessitating withdrawal of enteral nutrition was similar in the two groups (pa-=a-0.64). Conclusions When residual gastric volume is measured regularly and prokinetic agents are used, enteral nutrition can be started early and be introduced at optimal dose regimen, thereby providing better calorie intake. Serious adverse events required early enteral nutrition withdrawal in only 15a-patients, with no difference in frequency between the groups. Author Affiliation: (1) Service de Reanimation Polyvalente, Centre Hospitalier d'Angouleme, 16470, Saint Michel, France (2) Medical-Surgical Intensive Care unit, Hopital Universitaire Dupuytren, Limoges, France (3) Clinical Research Center, Hopital Universitaire Dupuytren, Limoges, France Article History: Registration Date: 12/12/2007 Received Date: 22/08/2007 Accepted Date: 29/11/2007 Online Date: 22/01/2008

Byline: Jamie L. Nelsen, PharmD (Department of Emergency Medicine, State University of New York, Upstate Medical University, Syracuse, nelsenj@upstate.edu); Curtis E. Haas, PharmD, FCCP (Department of Pharmacy, University of Rochester [...]

Byline: Lidia Dalfino (1), Livio Tullo (2), Ilaria Donadio (1), Vincenzo Malcangi (1), Nicola Brienza (1) Keywords: Intra-abdominal hypertension; Intra-abdominal pressure; Abdominal compartmentsyndrome; Acute renal failure; Critically ill patients Abstract: Objective To investigate the relationship between intra-abdominal hypertension (IAH) and acute renal failure (ARF) in critically ill patients. Design and setting Prospective, observational study in a general intensive care unit. Patients Patients consecutively admitted fora->a-24a-h during a 6-month period. Interventions None. Measurements and results Intra-abdominal pressure (IAP) was measured through the urinary bladder pressure measurement method. The IAH was defined as a IAP aY=12a-mmHg in at least two consecutive measurements performed at 24-h intervals. The ARF was defined as the failure class of the RIFLE classification. Of 123 patients, 37 (30.1%) developed IAH. Twenty-three patients developed ARF (with an overall incidence of 19%), 16 (43.2%) in IAH and 7 (8.1%) in non-IAH group (pa- Conclusions In critically ill patients IAH is an independent predictive factor of ARF at IAP levels as low as 12a-mmHg, although the contribution of impaired systemic haemodynamics should also be considered. Author Affiliation: (1) Department of Emergency and Organ Transplantation, Anesthesia and Intensive Care Unit, University of Bari, Piazza G. Cesare 11, 70124, Bari, Italy (2) Department of Surgical Sciences, Anesthesia and Intensive Care Unit, University of Foggia, Viale L. Pinto, 71100, Foggia, Italy Article History: Registration Date: 27/11/2007 Received Date: 14/02/2007 Accepted Date: 21/11/2007 Online Date: 19/12/2007

Byline: Atle Ulvik (1,2), Reidar Kvale (1), Tore Wentzel-Larsen (3), Hans Flaatten (1,2) Keywords: Trauma patients; Intensive care; Sexual function; Erectile dysfunction; Long-term outcome Abstract: Objective To study sexual function in trauma patients 3--8 years after discharge from an ICU and to assess determinants of poor sex life. Design and setting A postal questionnaire survey was conducted in 2006 on a cohort of 325 consecutive adult ICU trauma patients admitted to a university hospital during 1998--2003. Patients Of 210 eligible patients 156 (74%) answered the questionnaires. Mean age was 46 years, and 124 were males. Measurements and results Sexual function was assessed by a self-report measure, and patients were asked to describe sexual life both currently and prior to trauma. The International Index of Erectile Function evaluated erectile function in males. At follow-up 50% reported sexual function to be unchanged, 41% impaired, and 9% to be better than preinjury status 34% reported that the trauma impaired current sex life. Erectile dysfunction was found in 27% of men younger than 40 years and 51% of men 40 years or older. Age, being single, Injury Severity Score, and depression were associated with poor sexual function. Of 17 patients experiencing breakdown of a regular relationship 71% reported the trauma to be a significant contributor. Conclusions At follow-up more than 3 years after injury one-third of our ICU trauma patients reported that the trauma impaired sexual function. Erectile dysfunction was significantly more frequent among men younger than 40 years than found in studies of the normal population. Evaluation of sexual function should be part of long-term outcome assessment after major trauma. Author Affiliation: (1) Department of Anaesthesia and Intensive Care, Haukeland University Hospital, 5021, Bergen, Norway (2) Section for Anaesthesiology and Intensive Care, Department of Surgical Sciences, University of Bergen, Bergen, Norway (3) Centre for Clinical Research, Haukeland University Hospital, Bergen, Norway Article History: Registration Date: 02/11/2007 Received Date: 03/09/2007 Accepted Date: 26/10/2007 Online Date: 28/11/2007 Article note: Electronic supplementary material The online version of this article (doi: 10.1007/s00134-007-0936-0) contains supplementary material, which is available to authorized users.

Byline: Stephane Legriel (1), Bruno Mourvillier (2), Nicolas Bele (1), Jose Amaro (2), Pierre Fouet (2), Philippe Manet (2), Francois Hilpert (2) Keywords: Cerebral insult; Electroencephalogram; Anticonvulsant therapy; Status epilepticus; ICU Abstract: Objective Despite recent management guidelines, no recent study has evaluated outcomes in ICU patients with status epilepticus (SE). Design and setting An 8-year retrospective study. Subjects and intervention Observational study in 140 ICU patients with SE, including 81 (58%) with continuous SE and 59 (42%) with intermittent SE (repeated seizures without interictal recovery). Measurements and results The 95 men and 45 women had a median age of 49a-years (IQR 24--71). Median seizure time was 60a-min (IQR 20--180), and 58 patients had seizures longer than 30a-min. The SE was nonconvulsive in 16 (11%) patients and convulsive in 124 (89%), including 89 (64%) with tonic-clonic generalized seizures, 27 (19%) with partial seizures, 7 (5%) with myoclonic seizures, and 1 with tonic seizures. The most common causes of SE were cerebral insult in 53% and anticonvulsant drug withdrawal in 20% of patients. No cause was identified in 35% of patients. Median time from SE to treatment was 5a-min (IQR 0--71). The SE was refractory in 35 (25%) patients. Mechanical ventilation was needed in 106a-patients. Hospital mortality was 21%. By multivariate analysis, independent predictors of 30-day mortality were age (OR 1.03/year 95% CI 1.00--1.06), GCS at scene (OR 0.84/point 95% CI 0.72--0.98), continuous SE (OR 3.17 95% CI 1.15--8.77), symptomatic SE (OR 4.08 95% CI 1.49--11.10), and refractory SE (OR 2.83 95% CI 1.06--7.54). Conclusion Mortality in SE patients remains high and chiefly determined by seizure severity. Further studies are needed to evaluate the possible impact of early maximal anticonvulsant treatment on outcomes. Author Affiliation: (1) Service de Reanimation Medicale, Hopital Saint-Louis, 1 Avenue Claude Vellefaux, 75010, Paris, France (2) Service de reanimation polyvalente, Hopital Robert Ballanger, Boulevard Robert Ballanger, 93602, Aulnay-sous-bois cedex, France Article History: Registration Date: 04/10/2007 Received Date: 06/06/2007 Accepted Date: 30/09/2007 Online Date: 27/10/2007 Article note: An erratum to this article can be found at http://dx.doi.org/10.1007/s00134-007-0944-0

Byline: Thomas Pohl (1), Jan Kozieras (1), Samir G. Sakka (2) Keywords: Extravascular lungwater; Thermo-dye dilution technique; Cardiac index; Intrathoracic blood volume index; Extravascular lung water index Abstract: Objective The transpulmonary thermo-dye dilution technique enables assessment of cardiac index (CI) intrathoracic blood volume index (ITBVI) and extravascular lung water index (EVLWI). Since the extent of lung edema may influence the reliability of CI measurement by transpulmonary thermodilution due to loss of indicator, we analyzed the impact of EVLWI on transpulmonary thermodilution-derived CI in critically ill patients. Design Retrospective, clinical study. Setting Surgical intensive care unit in a university hospital Patients and methods With ethics approval we analyzed data from 57 patients (38 men, 19 women age range 18--79 years) who, for clinical indication, underwent hemodynamic monitoring by transpulmonary thermo-dye dilution and pulmonary artery thermodilution (572 measurements). All patients were mechanically ventilated and had received a femoral artery thermo-fiberoptic and pulmonary artery catheter which were connected to a computer system (Cold-Z021, Pulsion Medical Systems, Munich, Germany). For each measurement, 15--17a-ml indocyanine green(4--6a-degC) was injected central venously. Injections were made manually and independently from the respiratory cycle. Linear regression was used for statistical analysis. Interventions and main results The difference between transpulmonary and pulmonary artery thermodilution CI was not correlated with EVLWIfor all measurements (na-=a-572, ra-=a-0.01, pa-=a-0.76) and when using only the first simultaneous measurement (na-=a-57, ra-=a-0.08, pa-=a-0.56). Furthermore, EVLWI was not correlated with transpulmonary thermodilution CI (na-=a-572, ra-=a-0.07, pa-=a-0.08). Coefficient of variation for transpulmonary thermodilution CI was 7.7a-+-a-4.3%. Conclusion Measurement of cardiac output by transpulmonary thermodilution is not influenced by EVLWI in critically ill patients and loss of indicator as the underlying reason is probably overestimated. Author Affiliation: (1) Friedrich Schiller University of Jena, Jena, Germany (2) Department of Anesthesiology and Intensive Care Medicine, University Witten/Herdecke, Medical Center Cologne-Merheim, Ostmerheimerstrasse 200, 51109, Cologne, Germany Article History: Registration Date: 05/10/2007 Received Date: 06/06/2007 Accepted Date: 02/10/2007 Online Date: 03/11/2007

Thyroid hormone is a critical determinant of cellular metabolism and differentiation. Precise tissue-specific regulation of the active ligand 3,5,3&apos;-triiodothyronine (T3) is achieved by the sequential removal of iodine groups from the thyroid hormone molecule, with type 3 deiodinase (D3) comprising the major inactivating pathway that terminates the action of T3 and prevents activation of the prohormone thyroxine. Using cells endogenously expressing D3, we found that hypoxia induced expression of the D3 gene DIO3 by a hypoxia-inducible factor--dependent (HIF-dependent) pathway. D3 activity and mRNA were increased both by hypoxia and by hypoxia mimetics that increase HIF-1. Using ChIP, we found that HIF-1[alpha] interacted specifically with the DIO3 promoter, indicating that DIO3 may be a direct transcriptional target of HIF-1. Endogenous D3 activity decreased T3-dependent oxygen consumption in both neuronal and hepatocyte cell lines, suggesting that hypoxia-induced D3 may reduce metabolic rate in hypoxic tissues. Using a rat model of cardiac failure due to RV hypertrophy, we found that HIF-1[alpha] and D3 proteins were induced specifically in the hypertrophic myocardium of the RV, creating an anatomically specific reduction in local T3 content and action. These results suggest a mechanism of metabolic regulation during hypoxic-ischemic injury in which HIF-1 reduces local thyroid hormone signaling through induction of D3., Introduction During illness, humans experience a fall in serum thyroid hormones termed the nonthyroidal illness syndrome (1). An inverse relationship between serum thyroxine (T4) and mortality in critically ill patients [...]