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BACKGROUND: Septic shock is a leading cause of acute kidney injury (AKI). Endotoxins and cytokine levels are associated with the occurrence and severity of AKI, and different blood purification devices are available to remove them from circulation. One such device, oXiris, is a hollow-fibre purification filter that clears both endotoxins and cytokines. Due to limited evidence, clinical use of this device is not currently advocated in guidelines. However, clinics do regularly use this device, and there is a critical need for guidance on the application of it in sepsis with and without AKI. METHOD: A modified Delphi-based method was used to collate -European experts' views on the indication(s), initiation and discontinuation criteria and success measures for oXiris. RESULTS: A panel of 14 participants was selected based on known clinical expertise in the areas of critical care and sepsis management, as well as their experience of using the oXiris blood purification device. The participants used different criteria to initiate treatment with oXiris in sepsis patients with and without AKI. Septic shock with AKI was the priority patient population, with oXiris used to rapidly improve haemodynamic parameters. Achieving haemodynamic stability within 72 h was a key factor for determining treatment success. CONCLUSION: In the absence of established guidelines, users of hollow-fibre purification devices such as oXiris may benefit from standardised approaches to selecting patients and initiating and terminating treatment, as well as measuring success. Further evidence in the form of randomised clinical trials is urgently required.

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AIMS: Sedation, as it is often required in critical care, is associated with immobilization, prolonged ventilation, and increased morbidity. Most sedation protocols are based on benzodiazepines. The presented study analyzes the benefit of benzodiazepine-free sedation. METHODS: In 2008, 134 patients were treated according to a protocol using benzodiazepine and propofol (Group 1). In 2009, we introduced a new sedation strategy based on sufentanil, nonsteroidal anti-inflammatory drugs, neuroleptics, and antidepressants, which was applied in 140 consecutive patients (Group 2). Depth of sedation, duration of mechanical ventilation, duration of Intensive Care Unit, and hospital stay were analyzed. RESULTS: Group 1 had both a longer duration of deep sedation (18.7 ± 2.5 days vs. 12.6 ± 1.85 days, P = 0.031) and a longer duration of controlled ventilation (311, 35 ± 32.69 vs. 143, 96 ± 20.76 h, P < 0.0001) than Group 2. Ventilator days were more frequent in Group 1 (653, 66 ± 98.37 h vs. 478, 89 ± 68.92 h, P = 0.128). CONCLUSIONS: The benzodiazepine-free sedation protocol has been shown to significantly reduce depth of sedation and controlled ventilation. Additional evidence is needed to ascertain reduction of ventilator days which would not only be of benefit for the patient but also for the hospital Management.

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BACKGROUND: Acute Aspergillus fumigatus infection in immunocompetent patients is rare. This is the first known case of a patient who survived Aspergillus sepsis after being treated early with veno-venous extracorporeal membrane (ECMO) and antifungal therapy. CASE PRESENTATION: An immunocompetent 54-year-old woman was exposed to plant mulch during gardening and subsequently developed pulmonary failure that progressed to sepsis with multiorgan failure. Owing to her severe clinical condition, she was treated for acute respiratory distress syndrome (ARDS) with veno-venous ECMO. Empiric antifungal therapy comprising voriconazole was also initiated owing to her history and a previous case report of aspergillosis after plant mulch exposure, though there was no microbiological proof at the time. A. fumigatus was later cultured and detected on antibody testing. The patient recovered, and ECMO was discontinued 1 week later. After 7 days of antifungal treatment, Aspergillus antibodies were undetectable. CONCLUSIONS: In cases of sepsis that occur after gardening, clinicians should consider Aspergillus inhalation as an aetiology, and early antimycotic therapy is recommended.

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BACKGROUND: The ability of an evoked motor response (EMR) with nerve stimulation to detect intraneural needle placement reliably at low current intensity has recently been challenged. In this study, we hypothesized that current intensity is higher in needle-nerve contact than in intraneural needle placement. METHODS: Brachial plexus nerves were exposed surgically in 6 anesthetized pigs. An insulated needle connected to a nerve stimulator was placed either with 1 mm distance to the nerve (control position), adjacent to nerve epineurium (needle-nerve contact position), or inside the nerve (intraneural position). Three pulse duration settings were applied in random fashion (0.1, 0.3, or 1.0 milliseconds) at each needle position. Starting at 0.0 mA, electrical current was increased until a minimal threshold current resulting in a specific EMR was observed. Fifty threshold current measurements were scheduled for each needle position-pulse duration setting. RESULTS: Four hundred-fifty threshold currents in 50 peripheral nerves were measured. Threshold current intensities (mA) to elicit EMR showed small differences between the needle-nerve contact position [median (25th-75th percentiles); 0.1 milliseconds: 0.12 (0.08-0.18) mA; 0.3 milliseconds: 0.10 (0.06-0.12) mA; 1.0 milliseconds: 0.06 (0.04-0.10) mA] and the intraneural position (0.1 milliseconds: 0.12 [0.10-0.16] mA; 0.3 milliseconds: 0.08 [0.06-0.10] mA; 1.0 milliseconds: 0.06 [0.06-0.08] mA) that are neither statistically significant nor clinically relevant. Regardless of the pulse duration that was applied, the 98.33% confidence interval revealed a difference of at most 0.02 mA. However, threshold current intensities to elicit EMR were lower for the needle-nerve contact position than for the control position (0.1 milliseconds: 0.28 [0.26-0.32] mA; 0.3 milliseconds: 0.20 [0.16-0.22] mA; 1.0 milliseconds: 0.12 [0.10-0.14] mA). CONCLUSIONS: The confidence interval for differences suggests minimal current intensity to elicit a motor response that cannot reliably discern between a needle-nerve contact from intraneural needle placement. In addition, an EMR at threshold currents <0.2 mA (irrespective of the applied pulse duration) indicates intraneural needle placement or needle-nerve contact.

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Up to the present day, pain management in the ICU (Intensive Care Units) is a unresolved clinical problem due to patient heterogeneity with complex variation in etiopathology and treatment of the underlying diseases. Therefore, therapeutic strategies in terms of standard operating procedure (SOP) are a necessary to improve the pain management for intensive care patients. Common guidelines for analgosedation are often inadequate to reflect the clinical situation. In particular, for an ICU setting without permanent presence of a physician a missing pain management SOP resulting in delayed pain therapy caused by a therapeutic uncertainty of the nurse staff. In addition to our pre-existing SOP for analgosedation we implemented a pain management SOP for our interdisciplinary, anaesthesiologic ICU. A exploratory survey among the nurse staff was conducted to assess the efficacy of the SOP. The results of the evaluation after a 6 month follow-up indicated a faster onset of pain management and good acceptance by the nursing staff.

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BACKGROUND: For nerve stimulator-guided regional anesthesia, one has to compromise between a presumed low success rate (using a high-current threshold) and a presumed increased risk of nerve damage (using a low-current threshold). We hypothesized that high-current thresholds in the range of 0.9 to 1.1 mA are not inferior with respect to the procedural and latency times compared with low threshold currents in the range of 0.3 to 0.5 mA for nerve stimulation in brachial plexus blocks. METHODS: Two hundred five patients scheduled for elective surgery were randomized to a low (0.3-0.5 mA, n = 103) or a high (0.9-1.1 mA, n = 102) stimulation current threshold for the axillary plexus block with 40 mL local anesthetic mixture (20 mL, each of prilocaine 1% and ropivacaine 0.75%). The primary end point was the time to complete sensory block. The secondary outcome measures were the time to readiness for surgery (defined as the time from the start of block procedure to complete sensory block) and the block performance time. The noninferiority margin was set at 5 minutes and was evaluated using the two-sided 95% bootstrap-confidence intervals ([CIs] 100,000 replications) for differences in means. RESULTS: The mean times to complete sensory block revealed a significant decrease with the low-current group (17.9 ± 12.1 (mean ± SD) versus 22.8 ± 12.4 minutes; 95% CI, 1.1 to 8.6; p = 0.012). The time to readiness for surgery was 30.3 ± 13.8 minutes in the low-current group and 31.7 ± 12.9 minutes in the high-current group (95% CI, -2.7 to 5.5; p = 0.49). The performance time was significantly shorter in the high-current threshold group (9.5 ± 4.7 versus 11.9 ± 5.7 minutes; 95% CI, -4 to 1.1; p = 0.001). CONCLUSION: Noninferiority for the high-current threshold technique could neither be confirmed for the primary end point nor for secondary end points. However, we consider a difference in mean times of approximately 8.5 minutes to achieve readiness for surgery acceptable for clinical practice.

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BACKGROUND/AIMS: Atrial fibrillation is the most common arrhythmia in the elderly, and potassium channels with atrium-specific expression have been discussed as targets to treat atrial fibrillation. Our aim was to characterize TASK-1 channels in human heart and to functionally describe the role of the atrial whole cell current I(TASK-1). METHODS AND RESULTS: Using quantitative PCR, we show that TASK-1 is predominantly expressed in the atria, auricles and atrio-ventricular node of the human heart. Single channel recordings show the functional expression of TASK-1 in right human auricles. In addition, we describe for the first time the whole cell current carried by TASK-1 channels (I(TASK-1)) in human atrial tissue. We show that I(TASK-1) contributes to the sustained outward current I(Ksus) and that I(TASK-1) is a major component of the background conductance in human atrial cardiomyocytes. Using patch clamp recordings and mathematical modeling of action potentials, we demonstrate that modulation of I(TASK-1) can alter human atrial action potential duration. CONCLUSION: Due to the lack of ventricular expression and the ability to alter human atrial action potential duration, TASK-1 might be a drug target for the treatment of atrial fibrillation.

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The "Acute Respiratory Distress Syndrome" (ARDS) is a life threatening disease and is associated with a high mortality, mainly due to multi-organ failure. Invasive mechanical ventilation can worsen multi-organ failure which must be avoided. A tidal volume of 6 ml/kg bodyweight should be the aim. Extracorporeal lung assist devices like ECMO or iLA can contribute to lung-protective mechanical ventilation.

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Cervical plexus blocks have been established as safe and feasible procedures for carotid endarterectomy. Comparable perioperative complication rates have been reported for plexus techniques and general anaesthesia. The results of the GALA trial support the theory that the indication for insertion of intraluminal shunts was significantly reduced by regional procedures (14 % vs. 43 %) in consequence of the more reliable diagnosis of neurological complications. However, it has not been identified yet which technique (superficial, deep or a combination) offers the highest effectiveness.

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BACKGROUND: The authors tested the effects of LL-37 prophylaxis or therapy on the outcome after intraabdominal sepsis and examined whether hyperthermic preconditioning plus LL-37 therapy augments host immune response and improves survival. METHODS: A rat model of peritoneal contamination and infection (PCI) with human stool was used to simulate clinical conditions. In trial 1, the authors compared (1) PCI, (2) LL-37 prophylaxis (0.5 mg/kg, 12 h before PCI), and (3) LL-37 therapy (0.5 mg/kg, 1 h after PCI). In trial 2, the authors compared (1) PCI, (2) LL-37 therapy, (3) hyperthermic preconditioning (41 degrees C for 1 h, 24 h before PCI), and (4) LL-37 therapy and hyperthermic preconditioning. The primary endpoint was mortality at 120 h. In trial 2, secondary endpoints were systemic levels of tumor necrosis factor alpha, interleukin 6, macrophage inflammatory protein 2, and heat shock protein 70; leukocyte counts; and neutrophil granulocyte phagocytosis. RESULTS: In trial 1, 30% of the control group compared with 70% of the LL-37 therapy group survived, but 55% after LL-37 prophylaxis survived (P = 0.038). In trial 2, 38% of the controls, 67% of the LL-37 therapy, 59% of the hyperthermic preconditioned, and 90% of the hyperthermic preconditioned plus LL-37 therapy group survived (P = 0.01). LL-37 therapy plus hyperthermic preconditioning reduced proinflammatory cytokine concentrations after sepsis; specifically compared with controls, macrophage inflammatory protein-2 and interleukin-6 levels were 1.5 +/- 1.5 versus 11 +/- 6 pg/ml (P = 0.028) and 13 +/- 8 versus 86 +/- 31 pg/ml, (P = 0.015), respectively. CONCLUSIONS: In this model of intraabdominal sepsis, LL-37 therapy improved outcome. Hyperthermic preconditioning per se was not successful, but in combination with LL-37 therapy, the survival rate after sepsis was increased and the proinflammatory cytokine response was downgraded.

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The aim of this study was to compare the effect of a physical therapy regimen including active exercises with the current standard treatment on reduction of pain 6 weeks and 6 months after whiplash injury caused by motor vehicle collision. Two hundred patients were enrolled in a prospective randomized controlled trial. In the standard group, treatment consisted of immobilization with a soft collar over 7 days. In the physical therapy group, patients were scheduled for 10 physical therapy appointments including active exercises within 14 days after enrollment. Pain intensity was rated by all patients daily during the first week, the sixth week, and 6 months after recruitment, using a numeric rating scale (0-10). Data analyses were performed by comparing the mean (over 1 week) pain scores between the two different treatment groups. Ninety-seven patients were randomly assigned to the standard treatment group and 103 to the physical therapy group. During the first week, there was no significant difference in mean pain intensity between the standard treatment group (4.76+/-2.15) and the physical therapy group (4.36+/-2.14). However, after 6 weeks, mean pain intensity was significantly (p=0.002) lower in the physical therapy group (1.49+/-2.26 versus 2.7+/-2.78). Similarly, after 6 months, significantly (p<0.001) less pain was reported in the physical therapy group (1.17+/-2.13) than the standard treatment group (2.33+/-2.56). We conclude that a physical therapy regimen which includes active exercises is superior in reducing pain 6 weeks and 6 months after whiplash injury compared to the current standard treatment with a soft collar.

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Remifentanil, mivacurium and ropivacaine are the latest innovations in clinical anaesthesia and have gained increasing importance in daily practise due to their unique pharmacodynamic and pharmacokinetic properties. However, drug acquisition costs for these agents are considerably higher in most countries than for comparable substances. This review provides a systematic, critical appraisal of pharmacoeconomic studies with remifentanil, mivacurium and ropivacaine, primarily based on prospective, randomised trials. Results from analyses using cost-minimising techniques stress the issue of the higher drug acquisition costs. However, studies using a more sophisticated method (e.g., cost-effectiveness analysis) indicate comparable costs or even financial advantage in favour of the newer investigative drugs remifentanil, mivacurium and ropivacaine.

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