Human cytomegalovirus seropositivity is associated with reduced patient survival during sepsis.

BACKGROUND: Sepsis is one of the leading causes of death. Treatment attempts targeting the immune response regularly fail in clinical trials. As HCMV latency can modulate the immune response and changes the immune cell composition, we hypothesized that HCMV serostatus affects mortality in sepsis patients. METHODS: We determined the HCMV serostatus (i.e., latency) of 410 prospectively enrolled patients of the multicenter SepsisDataNet.NRW study. Patients were recruited according to the SEPSIS-3 criteria and clinical data were recorded in an observational approach. We quantified 13 cytokines at Days 1, 4, and 8 after enrollment. Proteomics data were analyzed from the plasma samples of 171 patients. RESULTS: The 30-day mortality was higher in HCMV-seropositive patients than in seronegative sepsis patients (38% vs. 25%, respectively; p = 0.008; HR, 1.656; 95% CI 1.135-2.417). This effect was observed independent of age (p = 0.010; HR, 1.673; 95% CI 1.131-2.477). The predictive value on the outcome of the increased concentrations of IL-6 was present only in the seropositive cohort (30-day mortality, 63% vs. 24%; HR 3.250; 95% CI 2.075-5.090; p < 0.001) with no significant differences in serum concentrations of IL-6 between the two groups. Procalcitonin and IL-10 exhibited the same behavior and were predictive of the outcome only in HCMV-seropositive patients. CONCLUSION: We suggest that the predictive value of inflammation-associated biomarkers should be re-evaluated with regard to the HCMV serostatus. Targeting HCMV latency might open a new approach to selecting suitable patients for individualized treatment in sepsis.

Current clinical use of intravenous fosfomycin in ICU patients in two European countries.

PURPOSE: In Europe, intravenous fosfomycin (IV) is used particularly in difficult-to-treat or complex infections, caused by both Gram-positive and Gram-negative pathogens including multidrug-resistant strains. Here, we investigated the efficacy and safety of intravenous fosfomycin under real-life conditions. METHODS: Prospective, multi-center, and non-interventional study in patients with bacterial infections from 20 intensive care units (ICU) in Germany and Austria (NCT01173575). RESULTS: Overall, 209 patients were included (77 females, 132 males, mean age: 59 ± 16 years), 194 of which were treated in intensive care (APACHE II score at the beginning of fosfomycin therapy: 23 ± 8). Main indications (± bacteremia or sepsis) were infections of the CNS (21.5%), community- (CAP) and hospital-acquired pneumonia (HAP)/ventilator-associated pneumonia (VAP, 15.3%), bone and joint infections (BJI, 11%), abdominal infections (11%), and bacteremia (10.5%). Most frequently identified pathogens were S. aureus (22.3%), S. epidermidis (14.2%), Enterococcus spp. (10.8%), E. coli (12.3%) and Klebsiella spp. (7.7%). At least one multidrug-resistant (MDR) pathogen was isolated from 51 patients (24.4%). Fosfomycin was administered with an average daily dose of 13.7 ± 3.5 g over 12.4 ± 8.6 days, almost exclusively (99%) in combination with other antibiotics. The overall clinical success was favorable in 81.3% (148/182) of cases, and in 84.8% (39/46) of patients with ≥ 1 MDR pathogen. Noteworthy, 16.3% (34/209) of patients developed at least one, in the majority of cases non-serious, adverse drug reaction during fosfomycin therapy. CONCLUSION: Our data suggest that IV fosfomycin is an effective and safe combination partner for the treatment of a broad spectrum of severe bacterial infections in critically ill patients.

Association between night-time surgery and occurrence of intraoperative adverse events and postoperative pulmonary complications.

BACKGROUND: The aim of this post hoc analysis of a large cohort study was to evaluate the association between night-time surgery and the occurrence of intraoperative adverse events (AEs) and postoperative pulmonary complications (PPCs). METHODS: LAS VEGAS (Local Assessment of Ventilatory Management During General Anesthesia for Surgery) was a prospective international 1-week study that enrolled adult patients undergoing surgical procedures with general anaesthesia and mechanical ventilation in 146 hospitals across 29 countries. Surgeries were defined as occurring during 'daytime' when induction of anaesthesia was between 8:00 AM and 7:59 PM, and as 'night-time' when induction was between 8:00 PM and 7:59 AM. RESULTS: Of 9861 included patients, 555 (5.6%) underwent surgery during night-time. The proportion of patients who developed intraoperative AEs was higher during night-time surgery in unmatched (43.6% vs 34.1%; P<0.001) and propensity-matched analyses (43.7% vs 36.8%; P=0.029). PPCs also occurred more often in patients who underwent night-time surgery (14% vs 10%; P=0.004) in an unmatched cohort analysis, although not in a propensity-matched analysis (13.8% vs 11.8%; P=0.39). In a multivariable regression model, including patient characteristics and types of surgery and anaesthesia, night-time surgery was independently associated with a higher incidence of intraoperative AEs (odds ratio: 1.44; 95% confidence interval: 1.09-1.90; P=0.01), but not with a higher incidence of PPCs (odds ratio: 1.32; 95% confidence interval: 0.89-1.90; P=0.15). CONCLUSIONS: Intraoperative adverse events and postoperative pulmonary complications occurred more often in patients undergoing night-time surgery. Imbalances in patients' clinical characteristics, types of surgery, and intraoperative management at night-time partially explained the higher incidence of postoperative pulmonary complications, but not the higher incidence of adverse events. CLINICAL TRIAL REGISTRATION: NCT01601223.

Effect of Intraoperative High Positive End-Expiratory Pressure (PEEP) With Recruitment Maneuvers vs Low PEEP on Postoperative Pulmonary Complications in Obese Patients: A Randomized Clinical Trial.

Importance: An intraoperative higher level of positive end-expiratory positive pressure (PEEP) with alveolar recruitment maneuvers improves respiratory function in obese patients undergoing surgery, but the effect on clinical outcomes is uncertain. Objective: To determine whether a higher level of PEEP with alveolar recruitment maneuvers decreases postoperative pulmonary complications in obese patients undergoing surgery compared with a lower level of PEEP. Design, Setting, and Participants: Randomized clinical trial of 2013 adults with body mass indices of 35 or greater and substantial risk for postoperative pulmonary complications who were undergoing noncardiac, nonneurological surgery under general anesthesia. The trial was conducted at 77 sites in 23 countries from July 2014-February 2018; final follow-up: May 2018. Interventions: Patients were randomized to the high level of PEEP group (n = 989), consisting of a PEEP level of 12 cm H2O with alveolar recruitment maneuvers (a stepwise increase of tidal volume and eventually PEEP) or to the low level of PEEP group (n = 987), consisting of a PEEP level of 4 cm H2O. All patients received volume-controlled ventilation with a tidal volume of 7 mL/kg of predicted body weight. Main Outcomes and Measures: The primary outcome was a composite of pulmonary complications within the first 5 postoperative days, including respiratory failure, acute respiratory distress syndrome, bronchospasm, new pulmonary infiltrates, pulmonary infection, aspiration pneumonitis, pleural effusion, atelectasis, cardiopulmonary edema, and pneumothorax. Among the 9 prespecified secondary outcomes, 3 were intraoperative complications, including hypoxemia (oxygen desaturation with Spo2 ≤92% for >1 minute). Results: Among 2013 adults who were randomized, 1976 (98.2%) completed the trial (mean age, 48.8 years; 1381 [69.9%] women; 1778 [90.1%] underwent abdominal operations). In the intention-to-treat analysis, the primary outcome occurred in 211 of 989 patients (21.3%) in the high level of PEEP group compared with 233 of 987 patients (23.6%) in the low level of PEEP group (difference, -2.3% [95% CI, -5.9% to 1.4%]; risk ratio, 0.93 [95% CI, 0.83 to 1.04]; P = .23). Among the 9 prespecified secondary outcomes, 6 were not significantly different between the high and low level of PEEP groups, and 3 were significantly different, including fewer patients with hypoxemia (5.0% in the high level of PEEP group vs 13.6% in the low level of PEEP group; difference, -8.6% [95% CI, -11.1% to 6.1%]; P < .001). Conclusions and Relevance: Among obese patients undergoing surgery under general anesthesia, an intraoperative mechanical ventilation strategy with a higher level of PEEP and alveolar recruitment maneuvers, compared with a strategy with a lower level of PEEP, did not reduce postoperative pulmonary complications. Trial Registration: ClinicalTrials.gov Identifier: NCT02148692.

Intraoperative ventilation settings and their associations with postoperative pulmonary complications in obese patients.

BACKGROUND: There is limited information concerning the current practice of intraoperative mechanical ventilation in obese patients, and the optimal ventilator settings for these patients are debated. We investigated intraoperative ventilation parameters and their associations with the development of postoperative pulmonary complications (PPCs) in obese patients. METHODS: We performed a secondary analysis of the international multicentre Local ASsessment of VEntilatory management during General Anesthesia for Surgery' (LAS VEGAS) study, restricted to obese patients, with a predefined composite outcome of PPCs as primary end-point. RESULTS: We analysed 2012 obese patients from 135 hospitals across 29 countries in Europe, North America, North Africa, and the Middle East. Tidal volume was 8.8 [25th-75th percentiles: 7.8-9.9] ml kg-1 predicted body weight, PEEP was 4 [1-5] cm H2O, and recruitment manoeuvres were performed in 7.7% of patients. PPCs occurred in 11.7% of patients and were independently associated with age (P<0.001), body mass index ≥40 kg m-2 (P=0.033), obstructive sleep apnoea (P=0.002), duration of anaesthesia (P<0.001), peak airway pressure (P<0.001), use of rescue recruitment manoeuvres (P<0.05) and routine recruitment manoeuvres performed by bag squeezing (P=0.021). PPCs were associated with an increased length of hospital stay (P<0.001). CONCLUSIONS: Obese patients are frequently ventilated with high tidal volume and low PEEP, and seldom receive recruitment manoeuvres. PPCs increase hospital stay, and are associated with preoperative conditions, duration of anaesthesia and intraoperative ventilation settings. Randomised trials are warranted to clarify the role of different ventilatory parameters in obese patients. CLINICAL TRIAL REGISTRATION: NCT01601223.

Is internal jugular vein extensibility associated with indices of fluid responsiveness in ventilated patients?

BACKGROUND: Ultrasound of the inferior vena cava provides rapid and non-invasive assessment of fluid responsiveness. We hypothesized that the extensibility of the internal jugular vein (IJV) as well reflects intravascular volume state. We assessed IJV dimensions together with pulse pressure variation (PPV) as dynamic index for fluid responsiveness in mechanically ventilated patients. METHODS: Of 50 patients after cardiac surgery were assessed. Ultrasound of IJV dimensions as well as collection of hemodynamic data were performed in 30° and horizontal (0°) position, and the ventilator- and position-induced IJV extensibilities (E-IJV) were calculated. RESULTS: Mean ventilator-induced E-IJV in 30° position was 56%, and mean PPV in 30° position was 13.7%. Changing the patient's position from 30° to 0° significantly reduced ventilator-induced E-IJV as well as PPV. Pearson's correlation test revealed significant association between ventilator-induced E-IJV and fluid responsiveness deduced from PPV in 0° position (r = 0.43, P < 0.005). An E-IJV threshold >5% identified patients with significantly elevated PPV values. CONCLUSION: Ultrasound of the IJV and PPV as a dynamic index for fluid responsiveness can be associated under certain defined conditions. Whether or not ultrasound of the IJV can be useful to predict patient intravascular volume state should be further studied using invasive cardiac output monitoring.

Predictors of hippocampal atrophy in critically ill patients.

BACKGROUND AND PURPOSE: Hippocampal atrophy is presumably one morphological sign of critical illness encephalopathy; however, predictors have not yet been determined. METHODS: The data for this report derived from patients treated at the intensive care units (ICUs) of the University Hospital in Bonn in the years 2004-2006. These patients underwent structural magnetic resonance imaging 6-24 months after discharge. Volumes (intracranial, whole brain, white matter, grey matter, cerebral spinal fluid, bilateral hippocampus) were compared with healthy controls. Pro-inflammatory parameters and ICU scoring systems were explored in conjunction with brain volumes. Cut-scores were defined to differentiate patients with high from those with low inflammatory response. RESULTS: Hippocampal and white matter volume were reduced in critically ill patients compared with healthy controls. Procalcitonin showed a very strong correlation (r = -0.903, P = 0.01) and interleukin-6 a moderate correlation (r = -0.538, P = 0.031) with hippocampal volume, but not with other brain volumes. C-reactive protein was linked to grey matter volume. There was no correlation with systemic inflammatory response syndrome criteria (body temperature, heart rate, respiratory rate, white blood cell count) or for hippocampal or whole brain volume. Furthermore, parameters representing severity of disease (APACHE II score, SOFA score, duration of stay and duration of mechanical ventilation) were not associated with hippocampal or other brain volumes. CONCLUSIONS: This analysis suggests that high levels of procalcitonin and interleukin-6 in the blood serum of critically ill patients are associated with a high likelihood of hippocampal atrophy irrespective of the severity of disease measured by ICU scoring systems and other inflammatory parameters.

COPD patients with ventilator-associated pneumonia: implications for management.

Data on the occurrence and outcome of patients with chronic obstructive pulmonary disease (COPD) and ventilator-associated pneumonia (VAP) are quite limited. The aim of this study was to determine if COPD intensive care unit (ICU) patients have a higher rate of VAP development, different microbiological aetiology or have worse outcomes than other patients without VAP. A secondary analysis of a large prospective, observational study conducted in 27 European ICUs was carried out. Trauma patients were excluded. Of 2082 intubated patients included in the study, 397 (19.1%) had COPD; 79 (19.9%) patients with COPD and 332 (19.7%) patients without COPD developed VAP. ICU mortality increased by 17% (p < 0.05) when COPD patients developed VAP, remaining an independent predictor of mortality [odds ratio (OR) 2.28; 95% confidence interval (CI) 1.35-3.87]. The development of VAP in COPD patients was associated with a median increase of 12 days in the duration of mechanical ventilation and >13 days in ICU stay (p < 0.05). Pseudomonas aeruginosa was more common in VAP when COPD was present (29.1% vs. 18.7%, p = 0.04) and was the most frequent isolate in COPD patients with early-onset VAP, with a frequency 2.5 times higher than in patients without early-onset VAP (33.3% vs. 13.3%, p = 0.03). COPD patients are not more predisposed to VAP than other ICU patients, but if COPD patients develop VAP, they have a worse outcome. Antibiotic coverage for non-fermenters needs to be included in the empiric therapy of all COPD patients, even in early-onset VAP.

[Noninvasive Mechanical Ventilation in Acute Respiratory Failure]. / Nicht-invasive Beatmung als Therapie der akuten respiratorischen Insuffizienz.

The non-invasive ventilation (NIV) is widespread in the clinical medicine and has attained meanwhile a high value in the clinical daily routine. The application of NIV reduces the length of ICU stay and hospitalization as well as mortality of patients with hypercapnic acute respiratory failure. Patients with acute respiratory failure in context of a cardiopulmonary edema should be treated in addition to necessary cardiological interventions with continuous positive airway pressure (CPAP) or NIV. In case of other forms of acute hypoxaemic respiratory failure it is recommended the application of NIV to be limited to mild forms of ARDS as the application of NIV in severe forms of ARDS is associated with higher rates of treatment failure and mortality. In weaning process from invasive ventilation the NIV reduces the risk of reintubation essentially in hypercapnic patients. A delayed intubation of patients with NIV failure leads to an increase of mortality and should therefore be avoided. With appropriate monitoring in intensive care NIV can also be successfully applied in pediatric patients with acute respiratory insufficiency. Furthermore NIV can be useful within palliative care for reduction of dyspnea and improving quality of life. The aim of the guideline update is, taking into account the growing scientific evidence, to outline the advantages as well as the limitations of NIV in the treatment of acute respiratory failure in daily clinical practice and in different indications.

Pumpless extracorporeal CO(2) removal restores normocapnia and is associated with less regional perfusion in experimental acute lung injury.

BACKGROUND: Lung protective ventilation may lead to hypoventilation with subsequent hypercapnic acidosis (HA). If HA cannot be tolerated or occurs despite increasing respiratory rate or buffering, extracorporeal CO2-removal using a percutaneous extracorporeal lung assist (pECLA) is an option. We hypothesised that compensation of HA using pECLA impairs regional perfusion. To test this hypothesis we determined organ blood flows in a lung-injury model with combined hypercapnic and metabolic acidosis. METHODS: After induction of lung injury using hydrochloric acid (HCl) aspiration and metabolic acidosis by intravenous HCl infusion in nine pigs, an arterial-venous pECLA device was inserted. In randomised order, four treatments were tested: pECLA shunt (1) with and (2) without HA, and clamped pECLA shunt (3) with and (4) without HA. Regional blood flows were measured with the coloured microsphere technique. RESULTS: HA resulted in higher perfusion in adrenal glands, spleen and parts of splanchnic area (P < 0.05) compared with normocapnia. During CO2-removal with pECLA, regional perfusion decreased to levels comparable with those without pECLA and normocapnia. Cardiac output (CO) increased during HA without a pECLA shunt and was highest during HA with a pECLA shunt compared with normocapnia. During CO2-removal with pECLA, this variable decreased but stayed higher than during normocapnia with clamped pECLA shunt (P < 0.05). CONCLUSION: In our lung-injury model, HA was associated with increased systemic and regional blood flow in several organs. pECLA provides effective CO2 removal, requiring a higher CO for perfusion of the pECLA device without improvement of regional organ perfusion.

[Traumatic tricuspid valve insufficiency with right-to-left shunt: bridging using extracorporeal venovenous membrane oxygenation]. / Traumatische Trikuspidalklappeninsuffizienz mit Rechts-links-Shunt: "Bridging" mithilfe der extrakorporalen venovenösen Membranoxygenierung.

The case of a young male motor vehicle driver is reported who suffered multiple trauma in a car accident with pulmonary and cardiac contusions. In the course of severe pneumonia and traumatic tricuspid valve insufficiency a right-to-left shunt with refractory hypoxemia developed across a pre-existing atrial septal defect (ASD). The patient could be successfully treated by the combination of extracorporeal membrane oxygenation for bridging, interventional ASD occlusion and in the long-term by operative reconstruction of the tricuspid valve.

Determinants of prescription and choice of empirical therapy for hospital-acquired and ventilator-associated pneumonia.

The objectives of this study were to assess the determinants of empirical antibiotic choice, prescription patterns and outcomes in patients with hospital-acquired pneumonia (HAP)/ventilator-associated pneumonia (VAP) in Europe. We performed a prospective, observational cohort study in 27 intensive care units (ICUs) from nine European countries. 100 consecutive patients on mechanical ventilation for HAP, on mechanical ventilation>48 h or with VAP were enrolled per ICU. Admission category, sickness severity and Acinetobacter spp. prevalence>10% in pneumonia episodes determined antibiotic empirical choice. Trauma patients were more often prescribed non-anti-Pseudomonas cephalosporins (OR 2.68, 95% CI 1.50-4.78). Surgical patients received less aminoglycosides (OR 0.26, 95% CI 0.14-0.49). A significant correlation (p<0.01) was found between Simplified Acute Physiology Score II score and carbapenem prescription. Basal Acinetobacter spp. prevalence>10% dramatically increased the prescription of carbapenems (OR 3.5, 95% CI 2.0-6.1) and colistin (OR 115.7, 95% CI 6.9-1,930.9). Appropriate empirical antibiotics decreased ICU length of stay by 6 days (26.3±19.8 days versus 32.8±29.4 days; p=0.04). The antibiotics that were prescribed most were carbapenems, piperacillin/tazobactam and quinolones. Median (interquartile range) duration of antibiotic therapy was 9 (6-12) days. Anti-methicillin-resistant Staphylococcus aureus agents were prescribed in 38.4% of VAP episodes. Admission category, sickness severity and basal Acinetobacter prevalence>10% in pneumonia episodes were the major determinants of antibiotic choice at the bedside. Across Europe, carbapenems were the antibiotic most prescribed for HAP/VAP.

Video vs. direct laryngoscopy for adult surgical and intensive care unit patients requiring tracheal intubation: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: This systematic review and meta-analysis aimed to determine whether a specific videolaryngoscopy technique is superior to standard direct laryngoscopy using a Macintosh blade to reduce the risk of difficult intubation in surgical and intensive care unit patients. MATERIALS AND METHODS: We identified all randomized controlled trials comparing videolaryngoscopes (VLSs) to direct laryngoscopy in the Cochrane Central Register of Controlled Trials, MEDLINE, and EMBASE (from inception to April 2020). The primary outcome was difficult intubation in adult surgical and intensive care unit patients. Secondary outcomes were successful intubation at the first attempt, airway trauma, sore throat, hoarseness, hypoxia, and mortality. RESULTS: We included 97 randomized controlled trials to evaluate 12775 patients. A high risk of bias was found in at least 50% of the included studies for each outcome. VLSs reduced the risk of difficult intubation compared to direct Macintosh laryngoscopy (RR 0.48, 95% CI from 0.35 to 0.65). VLSs increased the rate of successful intubation at the first attempt when compared to direct Macintosh laryngoscopy (RR 1.03, 95% CI from 1.00 to 1.07). Lower risks of airway trauma were found with VLSs (RR 0.69, 95% CI from 0.55 to 0.86). A decreased risk of hoarseness was associated with the use of VLSs (RR 0.67, 95% CI from 0.54 to 0.83). In addition, VLSs did not significantly reduce the risk of hypoxia compared with direct laryngoscopy (RR 0.83, 95% CI from 0.60 to 1.16). CONCLUSIONS: In this systematic review and meta-analysis, we found that the use of VLSs reduced the risk of difficult intubation and slightly increased the ratio of successful intubation at the first attempt among adult patients.

Repinotan, a selective 5-HT1A-R-agonist, antagonizes morphine-induced ventilatory depression in anesthetized rats.

BACKGROUND: Spontaneous breathing during mechanical ventilation improves arterial oxygenation and cardiovascular function, but is depressed by opioids during critical care. Opioid-induced ventilatory depression was shown to be counteracted in anesthetized rats by serotonin(1A)-receptor (5-HT(1A)-R)-agonist 8-OH-DPAT, which cannot be applied to humans. Repinotan hydrochloride is a selective 5-HT(1A)-R-agonist already investigated in humans, but the effects on ventilation and nociception are unknown. In this study, we sought to establish (a) the effects of repinotan on spontaneous breathing and nociception, and (b) the interaction with the standard opiate morphine. METHODS: The dose-dependent effects of repinotan, given alone or in combination with morphine, on spontaneous minute ventilation (MV) and nociceptive tail-flick reflex latencies (TFLs) were measured simultaneously in spontaneously breathing anesthetized rats. An additional series with NaCl 0.9% and the 5-HT(1A)-R-antagonist WAY 100 135 served as controls. RESULTS: (a) Repinotan dose-dependently activated spontaneous breathing (MV, mean [95% confidence interval]; 53% [29%-77%]) of pretreatment level) and suppressed nociception (TLF, 91% maximum possible effect [68%-114%]) with higher doses of repinotan (2-200 µg/kg). On the contrary, nociception was enhanced with a small dose of repinotan (0.2 µg/kg; TFL, -47% maximum possible effect [-95% to 2%]). Effects were prevented by 5-HT(1A)-antagonist WAY 100 135. (B) Morphine-induced depression of ventilation (MV, -72% [-100% to -44%]) was reversed by repinotan (20 µg/kg), which returned spontaneous ventilation to pretreatment levels (MV, 18% [-40% to 77%]). The morphine-induced complete depression of nociception was sustained throughout repinotan and NaCl 0.9% administration. Despite a mild decrease in mean arterial blood pressure, there were no serious cardiovascular side effects from repinotan. CONCLUSIONS: The 5-HT(1A)-R-agonist repinotan activates spontaneous breathing in anesthetized rats even in morphine-induced ventilatory depression. The potency of 5-HT(1A)-R-agonists to stimulate spontaneous breathing and their antinociceptive effects should be researched further.

[Prevention and follow-up care of sepsis. 1st revision of S2k guidelines of the German Sepsis Society (Deutsche Sepsis-Gesellschaft e.V., DSG) and the German Interdisciplinary Association of Intensive Care and Emergency Medicine (Deutsche Interdisziplinäre Vereinigung für Intensiv- und Notfallmedizin, DIVI)]. / Prävention und Nachsorge der Sepsis. 1. Revision der S2k-Leitlinien der Deutschen Sepsis-Gesellschaft e.V. (DSG) und der Deutschen Interdisziplinären Vereinigung für Intensiv- und Notfallmedizin (DIVI).

The 1st revision of the S2k guideline on the prevention and follow-up care of sepsis, provided by the German Sepsis Society in collaboration with 17 German medical scientific societies and one self-help group provides state-of-the-art information on the effective and appropriate medical care of critically ill patients with severe sepsis or septic shock. The guideline recommendations may not be applied under all circumstances. It rests with the clinician to decide whether a certain recommendation should be adopted or not, taking into consideration the unique set of clinical facts presented in connection with each individual patient as well as the available resources.

Maternal haemodynamics and lung water content during percutaneous fetoscopic interventions under general anaesthesia.

BACKGROUND: The purpose of our study was to evaluate the maternal cardiopulmonary function and lung water content during percutaneous fetoscopic interventions under general maternal-fetal anaesthesia and continuous tocolytic medication. METHODS: We prospectively studied 13 women between 19 and 30 weeks of gestation undergoing percutaneous fetoscopic procedures that were performed under general maternal-fetal anaesthesia and tocolysis using indomethacin. Invasive haemodynamic monitoring using pulmonary artery catheters and the transpulmonary indicator dilution technique was applied to determine intrathoracic blood volume (ITBV), cardiac output, and extravascular lung water (EVLW). Pulmonary vascular permeability was estimated as the ratio of EVLW/ITBV. Measurements were performed during and for 24 h after the interventions. RESULTS: Respective mean (SD) maternal ITBV and cardiac output were 894 (191) ml min(-1) m(-2) and 3.29 (0.51) litre(-1) min(-1) m(-2) intraoperatively, and 843 (169) ml min(-1) m(-2) and 4.47 (0.55) litre min(-1) m(-2) during the first postoperative day. EVLW was 7.9 (2.7) ml kg(-1) during the interventions and 7.7 (1.8) ml kg(-1) during the first postoperative day. The pulmonary vascular permeability index was calculated as 0.35 (0.06) during the interventions and 0.38 (0.14) for the first postoperative day. Clinically overt pulmonary oedema was not detected in any woman while pulmonary gas exchange remained normal. CONCLUSIONS: In mid-gestational women undergoing percutaneous fetoscopic interventions under general maternal-fetal anaesthesia, cardiopulmonary function remained stable. However, a moderate increase in EVLW and pulmonary vascular permeability indicates an increased risk for maternal pulmonary oedema.

Understanding international differences in terminology for delirium and other types of acute brain dysfunction in critically ill patients.

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, délire, 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.

Protective intraoperative ventilation with higher versus lower levels of positive end-expiratory pressure in obese patients (PROBESE): study protocol for a randomized controlled trial.

BACKGROUND: Postoperative pulmonary complications (PPCs) increase the morbidity and mortality of surgery in obese patients. High levels of positive end-expiratory pressure (PEEP) with lung recruitment maneuvers may improve intraoperative respiratory function, but they can also compromise hemodynamics, and the effects on PPCs are uncertain. We hypothesized that intraoperative mechanical ventilation using high PEEP with periodic recruitment maneuvers, as compared with low PEEP without recruitment maneuvers, prevents PPCs in obese patients. METHODS/DESIGN: The PRotective Ventilation with Higher versus Lower PEEP during General Anesthesia for Surgery in OBESE Patients (PROBESE) study is a multicenter, two-arm, international randomized controlled trial. In total, 2013 obese patients with body mass index ≥35 kg/m2 scheduled for at least 2 h of surgery under general anesthesia and at intermediate to high risk for PPCs will be included. Patients are ventilated intraoperatively with a low tidal volume of 7 ml/kg (predicted body weight) and randomly assigned to PEEP of 12 cmH2O with lung recruitment maneuvers (high PEEP) or PEEP of 4 cmH2O without recruitment maneuvers (low PEEP). The occurrence of PPCs will be recorded as collapsed composite of single adverse pulmonary events and represents the primary endpoint. DISCUSSION: To our knowledge, the PROBESE trial is the first multicenter, international randomized controlled trial to compare the effects of two different levels of intraoperative PEEP during protective low tidal volume ventilation on PPCs in obese patients. The results of the PROBESE trial will support anesthesiologists in their decision to choose a certain PEEP level during general anesthesia for surgery in obese patients in an attempt to prevent PPCs. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02148692. Registered on 23 May 2014; last updated 7 June 2016.

[Nursing workload indices TISS-10, TISS-28, and NEMS : Higher workload with agitation and delirium is not reflected]. / Pflegeaufwandsindizes TISS-10, TISS-28 und NEMS : Erhöhter Arbeitsaufwand bei Agitation und Delir wird nicht erfasst.

BACKGROUND: Financial resources for the treatment of ICU patients requiring high nursing workload are allocated within the German diagnostic-related groups (DRG) system in part through the Therapeutic Intervention Scoring System-10 (TISS-10). TISS-10, however, has never been validated. This study evaluated whether delirium and agitation in ICU were reflected by TISS-10, and also by the established workload indices TISS-28 and Nine Equivalents of Nursing Manpower (NEMS). Secondary aims were if indices correlated, and what effects delirium and agitation had on financial balances. MATERIALS AND METHODS: Analyses were performed retrospectively in 521 datasets from 152 patients. Nursing workload was assessed with TISS-28, TISS-10, and NEMS, delirium with the Confusion Assessment Method for Intensive Care Units (CAM-ICU), and vigilance with the Richmond Agitation-Sedation Scale (RASS). Revenues were retrieved from the institution's patient data management system, and costs calculated with the Budget Calculation Tool 2007 provided by the German Society of Anaesthesiologists. RESULTS: Delirium was found in 36.2 % of patients (n = 55). TISS-28, TISS-10, and NEMS were not higher in patients with delirium, if corrected for mechanical ventilation. TISS-28, TISS-10, and NEMS were significantly higher in deeply sedated and comatose patients (RASS ≤ - 3, p < 0.001), but not in agitated (RASS ≥ 1) and lightly sedated patients (RASS - 1/- 2). TISS-10 and TISS-28 had a linear correlation (r (2) = 0.864). Median financial balances were negative, but much more pronounced in patients with delirium that without (- 3174 € with delirium vs. - 1721 € without delirium, p = 0.0147). CONCLUSION: The standard workload-scores (TISS-10, TISS-28, NEMS) do not reflect higher daily workload associated with patients with delirium and agitation.

Schmidt syndrome presenting as acute liver failure.

The Schmidt Syndrome (Type II Autoimmune-Syndrome) is characterised by an autoimmune adrenalitis in combination with a chronic lymphocellular thyreoiditis resulting in insufficiency of these organs in adulthood. Combination with diabetes is possible. The diagnosis is usually established by clinical examination and analysis of serum hormone levels (adrenocorticotropin hormone [ACTH], cortisol, thyroid stimulating hormone [TSH], triiodothyronine [fT3], thyroxine [fT4]). In the present case, initial diagnosis was rapid progressive liver failure of unknown origin with consecutive multiple organ dysfunction syndrome including dysfunction of heart, lungs, and kidneys. Frequent and less frequent causes of liver failure were ruled out, e.g. viral or autoimmune hepatitis, Budd-Chiari-syndrome, toxic, or drug induced liver failure. In retrospect, the multiple organ dysfunction syndrome was caused by hypoperfusion due to severe hypovolemia and hypoperfusion was induced by adrenocortical insufficiency proven by endocrinological testing. The clinical course of this case stresses the importance of the hormone balance in the critical ill patient. The guideline for treatment of patients with assumed hormonal dysregulation should include a full hormone status prior to substitution. The present case report also illustrates the importance of clinical signs and careful consideration of the medical history in detecting an autoimmune endocrine disease.