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Whether the quality of the ethical climate in the intensive care unit (ICU) improves the identification of patients receiving excessive care and affects patient outcomes is unknown., SCOPUS: ar.j, info:eu-repo/semantics/published

Introduction Glucocorticosteroids (steroids) are widely used for sepsis patients. However, the potential benefits and harms of both high and low dose steroids remain unclear. A systematic review of randomised clinical trials with meta-analysis and trial sequential analysis (TSA) might shed light on this clinically important question. Methods A systematic review was conducted according to a published protocol and The Cochrane Handbook methodology including meta-analyses, TSA of randomised clinical trials, and external validity estimation (GRADE). Randomised clinical trials evaluating steroids were included for sepsis patients (systemic inflammatory response syndrome, sepsis, severe sepsis or septic shock) aged >18 years. Cochrane Central Register of Controlled Trials (CENTRAL), PubMed/Medline, Embase, Web of Science and Cinahl were searched until 18 February 2015. No language restrictions were applied. Primary outcomes were mortality at longest follow-up and serious adverse events. Results A total of 35 trials randomising 4682 patients were assessed and reviewed in full text. All trials but two had high risk of bias. No statistically significant effect was found for any dose of steroids versus placebo or no intervention on mortality at maximal follow-up [relative risk (RR) 0.89; TSA adjusted confidence interval (CI) 0.74–1.08]. Two trials with low risk of bias also showed no statistically significant difference (random-effects model RR 0.38, 95 % CI 0.06–2.42). Similar results were obtained in subgroups of trials stratified according to high (>500 mg) or low (≤500 mg) dose hydrocortisone (or equivalent) (RR 0.87; TSA-adjusted CI 0.38–1.99; and RR 0.90; TSA-adjusted CI 0.49–1.67, respectively). There were also no statistically significant effects on serious adverse events other than mortality (RR 1.02; TSA-adjusted CI 0.7–1.48). The effects did not vary according to the degree of sepsis. TSA showed that many more randomised patients are needed before definitive conclusions may be drawn. Conclusion Evidence to support or negate the use of steroids in any dose in sepsis patients is lacking. The results of ongoing and future well-designed, large randomised clinical trials are needed. Electronic supplementary material The online version of this article (doi:10.1007/s00134-015-3899-6) contains supplementary material, which is available to authorized users.

Critically ill patients show a variety of hormonal changes that appear to differ considerably in acute and prolonged critical illness. Whether these endocrine alterations serve as physiological adaptation or contribute to further deterioration remains an intriguing question. We review the recent literature and discuss whether measuring circulating hormone concentrations, performing stimulation tests, and intervening with hormone substitution could contribute to the recovery of critically ill patients.

Objective: To study the cefpirome pharmacokinetics of patients with sepsis and multiple organ failure treated with CVVH. Design: Measurements of serum and ultrafiltrate (UF) concentrations and in vitro sensitivity testing of isolated micro-organisms. Setting: University hospital-based, single ICU. Patients: Six critically ill CVVH- dependent patients with sepsis and multiple organ dysfunction syndrome in need of antimicrobial therapy. Age range: 60–75 years; APACHE II score for severity of illness on admission: 19–30. One patient survived. Interventions: Cefpirome i. v. was started at 2 g in 30 min, then continued 1 g i. v. b. i. d. Measurements: The UF rate was 27 ± 7 ml/min on day 1 and 34 ± 2 ml/min on day 2. Serum and ultrafiltrate samples were measured by a validated high performance liquid chromatography assay. Volume of distribution: 23 · 5(SD ± 4 · 6) l. Total cefpirome clearance was 32 ± 6 · 3 ml/min; cefpirome CVVH clearance (ClCVVH): 17 ± 4.2 ml/min; mean serum half-life (t1/2): 8.8 ± 2.3 h; mass transfer on day 1: 660 ± 123 mg/12 h (33 ± 6 % of administered dose)and day 2: 642 ± 66 mg/12 h (64 ± 7 %). Estimated sieving coefficient (ClCVVH/UF rate): 64 ± 11 %. In vitro sensitivity of isolated microbes was excellent except for two non-sensitive enterococci and Candida spp. Conclusions: The sieving coefficient (64 %) indicates that a substantial fraction of the drug is not filtered; clearance by pathways other than CVVH mounted to 50 % of the total clearance and increased on day 2, indicating that the dosing schedule used is appropriate for this setting. Cefpirome appeared to be safe in these patients and effective for most of the nosocomial microbial isolates. During more than 90 % of the time, serum levels were maintained above killing concentrations for susceptible micro-organisms.

Objective: Kinetics of piperacillin (pip), in combination with the beta-lactamase inhibitor tazobactam (taz) have been studied in volunteers and patients in relatively stable conditions. The fixed drug preparation appeared to have ideal pharmacokinetic properties if renal function was normal or slightly impaired, but no data are available for critically ill patients in anuric renal failure. This study should provide such data. Patients, design: We studied the pharmacokinetics in nine patients with multiple organ failure, including anuric renal failure, treated with continuous veno-venous hemofiltration (CVVH). Patients received a standard schedule of 4 g pip and 0.5 g taz administered over 0.5 h intravenously, 8 hourly. During 2 consecutive days, the serum levels of both compounds were determined, and total clearance (CIT) was calculated from serum concentrations. Results: All nine patients completed day 1, and 8 completed day 2 of the protocol. On day 1, single-dose kinetics showed considerable spread, but pip/taz serum levels followed the pattern as expected, with a pip/taz concentration ratio of 20 : 1. On day 2, however, taz serum concentrations showed a relative increase as compared to pip, resulting in a change in the serum pip/taz concentration ratio to 10 : 1 on day 2. The CIT of pip was 2.52 +/- 1.38 l/h (t 1/2 : 5.9 +/- 2.9 h), and CIT of taz 4.44 +/- 2.28 l/h (t 1/2 : 8.1 +/- 3.7 h). The CIT and t 1/2 of pip and taz correlated highly significantly with clearance by CVVH. Despite a higher CI, taz has a longer half-life, because of a higher volume of distribution. Conclusion: In CVVH dependent patients, pip/taz fixed drug preparations can be used initially, but the pip dosage should be increased relative to that of taz (or interval-adjusted) to prevent cumulation of taz, as compared to the active antimicrobial agent pip.

Dear Editor, Critically ill patients are transferred more safely with a mobile intensive care unit (MICU) and specialised retrieval team [1, 2], although incidents still occur [3]. However, transports are becoming more challenging [4]. During MICU transports, we repeatedly observed arterial blood pressure variations, concurrent with ambulance accelerations and decelerations. We aimed to evaluate whether the observed influence of acceleration on blood pressure is a real blood pressure change or a physical measurement artefact. Usually, the pressure transducer is positioned at the rear end of the trolley and the distance to the arterial cannula varies between 100 and 150 cm. In an experimental setting, pressure lines (Edwards Lifesciences, Irvine, USA) were positioned on the trolley. At the site of normal catheter insertion, the line was connected to a pressurised bag to simulate a static mean arterial pressure (MAP). The length of the pressure line and the baseline pressure were varied (0, 50, 100, 150 cm and 50, 75, 100 mmHg). To simulate acceleration and deceleration the trolley was moved forward and backward in several test runs. Pressures and accelerations (accelerometer, University of Twente, Enschede, the Netherlands) were measured for the different pressures and different pressure line lengths. Pressure data were plotted against acceleration data (Fig. 1). The Pearson’s correlation coefficients r, p values, R and the slopes of the linear regression lines (b) and their 95 % confidence intervals are listed in Table 1. In this experimental setting both an increase in the baseline pressure and in pressure line length were associated with significant increases in pressure variations during accelerations. To confirm the findings that pressure variations may be a physical phenomenon, MAP and acceleration data were collected during six transports. The medical ethics committee approved this study and the need for consent was waived. The pressure transducer was initially positioned at the rear end of the trolley and halfway changed to directly on top of the arterial cannula so that patients served as their own control. The effect of acceleration on MAP was analysed for both positions of the transducer. In patient transfers, a weak correlation was observed between acceleration and blood pressure with the transducer positioned on top of the arterial cannula. The mean Pearson’s r significantly increased from 0.09 to 0.50 when the transducer changed position to the rear end of the trolley. The inertial mass effect of the fluid column in the tubing explains most of the blood pressure variation. The

Tie2 is predominantly expressed by endothelial cells and is involved in vascular integrity control during sepsis. Changes in Tie2 expression during sepsis development may contribute to microvascular dysfunction. Understanding the kinetics and molecular basis of these changes may assist in the development of therapeutic intervention to counteract microvascular dysfunction.To investigate the molecular mechanisms underlying the changes in Tie2 expression upon lipopolysaccharide (LPS) challenge.Studies were performed in LPS and pro-inflammatory cytokine challenged mice as well as in mice subjected to hemorrhagic shock, primary endothelial cells were used for in vitro experiments in static and flow conditions. Eight hours after LPS challenge, Tie2 mRNA loss was observed in all major organs, while loss of Tie2 protein was predominantly observed in lungs and kidneys, in the capillaries. A similar loss could be induced by secondary cytokines TNF-alpha and IL-1 beta. Ang2 protein administration did not affect Tie2 protein expression nor was Tie2 protein rescued in LPS-challenged Ang2-deficient mice, excluding a major role for Ang2 in Tie2 down regulation. In vitro, endothelial loss of Tie2 was observed upon lowering of shear stress, not upon LPS and TNF-alpha stimulation, suggesting that inflammation related haemodynamic changes play a major role in loss of Tie2 in vivo, as also hemorrhagic shock induced Tie2 mRNA loss. In vitro, this loss was partially counteracted by pre-incubation with a pharmacologically NF-(DB)-B-0 inhibitor (BAY11-7082), an effect further substantiated in vivo by pre-treatment of mice with the NF-(DB)-B-0 inhibitor prior to the inflammatory challenge.Microvascular bed specific loss of Tie2 mRNA and protein in vivo upon LPS, TNF alpha, IL-1 beta challenge, as well as in response to hemorrhagic shock, is likely an indirect effect caused by a change in endothelial shear stress. This loss of Tie2 mRNA, but not Tie2 protein, induced by TNF alpha exposure was shown to be controlled by NF-(DB)-B-0 signaling. Drugs aiming at restoring vascular integrity in sepsis could focus on preventing the Tie2 loss.

A 65-year-old polytrauma patient was admitted post-operatively to the intensive care unit. His situation deteriorated with hemodynamic instability and continuous high fever. An infectious focus could not be found and repeated cultures remained negative. Empirical administration of antibiotics and changing of lines did not have any effect on the clinical picture. It was impossible to lower the dose of catecholamines because of repeated occurrence of hypotension, despite optimal hydration state and filling pressures. On the 15th day of admission intravenous hydrocortisone was started on suspicion of relative adrenal insufficiency. This action resulted in rapid hemodynamic recovery, disappearance of fever and enabled rapid tapering of the dose of noradrenaline. Incidence of relative adrenal insufficiency and diagnostic strategies are discussed in the population of critically intensive care patients.

We describe the cases of two patients discharged home directly from the ICU. Both patients had the strong wish to die at home after being told that there were no therapeutic options. Sometimes discharge is feasible and can mean very much for patients and their family. Taking measures to ensure a "good deathbed" is an obligation for doctors and nursing staff. However, due to the focus on cure this palliative goal is not always pursued.

Objective:The Brugada syndrome is a clinical and electrocardiographic familial entity, which may lead to sudden cardiac death. A Brugada pattern ECG may occasionally be caused by conditions such as an overdose of tricyclic antidepressants (TCA). Toxicity of TCA frequently results in the need for critical care support. We retrospectively studied characteristics and electrocardiographic indicators of toxicity of all TCA poisoned patients. Setting:All patients admitted from 1/1/2000 to 1/11/2004 to our ICU after an act of deliberate self-poisoning were included. The ECG's were analysed retrospectively by a cardiologist. Patients with an overdose of TCA were divided in three groups; I. without ECG abnormalities, II. Presence of ECG abnormalities but without Brugada signs, III patients with a Brugada pattern ECG. Results:134 patients were admitted. In 35 patients a TCA was the main toxic substance. In 12 (34%) TCA patients no ECG abnormalities were found. An increase in QRS duration (> 100 ms) was seen in 13 (37%) cases. Six (17%) of them demonstrated a Brugada like pattern. The ECG abnormalities resolved quickly after administration of sodium bicarbonate. Length of stay did not differ between groups. APACHE II and the amount of sodium bicarbonate administered were the highest in the Brugada pattern group. Two patients died. Conclusions:in TCA poisoning the Brugada pattern ECG is a particular manifestation of the frequently occurring intraventricular conduction disturbances. In intoxicated patients in whom the substance is unknown early recognition of the conduction disturbances is important for suspecting a poisoning with TCA.

Occasionally, a dog-bite is complicated by a systemic overwhelming infection. We report four consecutive patients who were admitted to our intensive care unit because of sepsis syndrome following dog-bites. The history of these patients did not reveal any immunocompromising conditions. Capnocytophaga canimorsus (C. canimorsus) was cultured from the blood culture of 2 patients. Our data illustrate that in patients with lack of immune-deficiency severe sepsis may develop.