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BACKGROUND: Influenza-associated acute necrotizing encephalitis (ANE) is a very rare, but severe complication from influenza infection. CASE DESCRIPTION: We present a 48 year old male who presented with fever, malaise, confusion and altered mental status (E4M5V2) and influenza A infection. He quickly develops convulsions after which he is intubated and admitted to the Intensive Care Unit following which he remains comatose (E1M1V1). The diagnosis of influenza associated acute necrotizing encephalitis is made based on his neurological symptoms, generalized slowing on electro-encephalogram, classic bilateral findings on MRI in the thalamus and basal ganglia and proven influenza infection in the cerebrospinal fluid. CONCLUSION: Acute necrotising encephalitis is a severe complication from a common infection. It is advised to consider early MRI imaging in patients with influenza and fitting neurological symptoms and to consider treatment with corticosteroids.

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Importance: It remains uncertain whether invasive ventilation should use low tidal volumes in critically ill patients without acute respiratory distress syndrome (ARDS). Objective: To determine whether a low tidal volume ventilation strategy is more effective than an intermediate tidal volume strategy. Design, Setting, and Participants: A randomized clinical trial, conducted from September 1, 2014, through August 20, 2017, including patients without ARDS expected to not be extubated within 24 hours after start of ventilation from 6 intensive care units in the Netherlands. Interventions: Invasive ventilation using low tidal volumes (n = 477) or intermediate tidal volumes (n = 484). Main Outcomes and Measures: The primary outcome was the number of ventilator-free days and alive at day 28. Secondary outcomes included length of ICU and hospital stay; ICU, hospital, and 28- and 90-day mortality; and development of ARDS, pneumonia, severe atelectasis, or pneumothorax. Results: In total, 961 patients (65% male), with a median age of 68 years (interquartile range [IQR], 59-76), were enrolled. At day 28, 475 patients in the low tidal volume group had a median of 21 ventilator-free days (IQR, 0-26), and 480 patients in the intermediate tidal volume group had a median of 21 ventilator-free days (IQR, 0-26) (mean difference, -0.27 [95% CI, -1.74 to 1.19]; P = .71). There was no significant difference in ICU (median, 6 vs 6 days; 0.39 [-1.09 to 1.89]; P = .58) and hospital (median, 14 vs 15 days; -0.60 [-3.52 to 2.31]; P = .68) length of stay or 28-day (34.9% vs 32.1%; hazard ratio [HR], 1.12 [0.90 to 1.40]; P = .30) and 90-day (39.1% vs 37.8%; HR, 1.07 [0.87 to 1.31]; P = .54) mortality. There was no significant difference in the percentage of patients developing the following adverse events: ARDS (3.8% vs 5.0%; risk ratio [RR], 0.86 [0.59 to 1.24]; P = .38), pneumonia (4.2% vs 3.7%; RR, 1.07 [0.78 to 1.47]; P = .67), severe atelectasis (11.4% vs 11.2%; RR, 1.00 [0.81 to 1.23]; P = .94), and pneumothorax (1.8% vs 1.3%; RR, 1.16 [0.73 to 1.84]; P = .55). Conclusions and Relevance: In patients in the ICU without ARDS who were expected not to be extubated within 24 hours of randomization, a low tidal volume strategy did not result in a greater number of ventilator-free days than an intermediate tidal volume strategy. Trial Registration: ClinicalTrials.gov Identifier: NCT02153294.

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OBJECTIVES: The presence of respiratory viruses and the association with outcomes were assessed in invasively ventilated ICU patients, stratified by admission diagnosis. DESIGN: Prospective observational study. SETTING: Five ICUs in the Netherlands. PATIENTS: Between September 1, 2013, and April 30, 2014, 1,407 acutely admitted and invasively ventilated patients were included. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Nasopharyngeal swabs and tracheobronchial aspirates were collected upon intubation and tested for 14 respiratory viruses. Out of 1,407 patients, 156 were admitted because of a severe acute respiratory infection and 1,251 for other reasons (non-severe acute respiratory infection). Respiratory viruses were detected in 28.8% of severe acute respiratory infection patients and 17.0% in non-severe acute respiratory infection (p < 0.001). In one third, viruses were exclusively detected in tracheobronchial aspirates. Rhinovirus and human metapneumovirus were more prevalent in severe acute respiratory infection patients (9.6% and 2.6% vs 4.5 and 0.2%; p = 0.006 and p < 0.001). In both groups, there were no associations between the presence of viruses and the number of ICU-free days at day 28, crude mortality, and mortality in multivariate regression analyses. CONCLUSIONS: Respiratory viruses are frequently detected in acutely admitted and invasively ventilated patients. Rhinovirus and human metapneumovirus are more frequently found in severe acute respiratory infection patients. Detection of respiratory viruses is not associated with worse clinically relevant outcomes in the studied cohort of patients.

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BACKGROUND: It is uncertain whether lung-protective mechanical ventilation using low tidal volumes should be used in all critically ill patients, irrespective of the presence of the acute respiratory distress syndrome (ARDS). A low tidal volume strategy includes use of higher respiratory rates, which could be associated with increased sedation needs, a higher incidence of delirium, and an increased risk of patient-ventilator asynchrony and ICU-acquired weakness. Another alleged side-effect of low tidal volume ventilation is the risk of atelectasis. All of these could offset the beneficial effects of low tidal volume ventilation as found in patients with ARDS. METHODS/DESIGN: PReVENT is a national multicenter randomized controlled trial in invasively ventilated ICU patients without ARDS with an anticipated duration of ventilation of longer than 24 hours in 5 ICUs in The Netherlands. Consecutive patients are randomly assigned to a low tidal volume strategy using tidal volumes from 4 to 6 ml/kg predicted body weight (PBW) or a high tidal volume ventilation strategy using tidal volumes from 8 to 10 ml/kg PBW. The primary endpoint is the number of ventilator-free days and alive at day 28. Secondary endpoints include ICU and hospital length of stay (LOS), ICU and hospital mortality, the incidence of pulmonary complications, including ARDS, pneumonia, atelectasis, and pneumothorax, the cumulative use and duration of sedatives and neuromuscular blocking agents, incidence of ICU delirium, and the need for decreasing of instrumental dead space. DISCUSSION: PReVENT is the first randomized controlled trial comparing a low tidal volume strategy with a high tidal volume strategy, in patients without ARDS at onset of ventilation, that recruits a sufficient number of patients to test the hypothesis that a low tidal volume strategy benefits patients without ARDS with regard to a clinically relevant endpoint. TRIAL REGISTRATION: The trial is registered at www.clinicaltrials.gov under reference number NCT02153294 on 23 May 2014.

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Many ICU survivors experience physical, cognitive and mental complications of critical care. This phenomenon has recently been defined as post-intensive care syndrome (PICS). We present 2 patients who survived treatment in an ICU. One of these patients, a 71-year-old male, had pneumosepsis and multiple organ failure. He was treated for 10 days in the ICU. He made a full recovery after 3 months of rehabilitation. The second patient, a 61-year-old male, developed multiple organ failure as complication of acute necrotizing pancreatitis. He was treated for 55 days in the ICU. He ultimately survived, but later developed a post-intensive care syndrome that had a long-lasting impact on his quality of life. Early rehabilitation and the limited use of sedatives might mitigate the severity of this syndrome.

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OBJECTIVE: The purpose of our study was to determine if central venous oxygen saturation and femoral venous oxygen saturation can be used interchangeably during surgery and in critically ill patients. DESIGN: Prospective observational controlled study. SETTING: Nonacademic university-affiliated teaching hospital in The Netherlands. PATIENTS: One hundred cardiac outpatients, 30 high-risk surgical patients, and 30 critically ill patients. INTERVENTIONS: None. METHODS AND MAIN RESULTS: We concurrently determined femoral venous oxygen saturation and central venous oxygen saturation in a group of 100 stable cardiac patients, which served as control group. Furthermore, we determined simultaneously femoral venous oxygen saturation and central venous oxygen saturation in 30 surgical patients and in 30 critically ill patients and evaluated changes over time. Correlation and agreement of femoral venous oxygen saturation and central venous oxygen saturation were assessed, including the difference between femoral venous oxygen saturation and central venous oxygen saturation.Despite significant correlation between obtained values of femoral venous oxygen saturation and central venous oxygen saturation (rs = 0.55; p < .001), the limits of agreement were wide in the control group (mean bias 2.7% ± 7.9%; 95% limits of agreement -12.9% to 18.2%). In both the surgical and critically ill patients, limits of agreement (mean bias of -1.9% ± 9.3%; 95% limits of agreement -20.0% to 16.3%, and mean bias of 4.6% ± 14.3%; 95% limits of agreement -23.5% to 32.6%, respectively) were wide. Results for changes of femoral venous oxygen saturation and central venous oxygen saturation were similar. During initial treatment of critically ill patients, the difference between femoral venous oxygen saturation and central venous oxygen saturation including its range of variation diminished. CONCLUSION: There is lack of agreement between femoral venous oxygen saturation and central venous oxygen saturation in both stable and unstable medical conditions. Thus, femoral venous oxygen saturation should not be used as surrogate for central venous oxygen saturation.

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BACKGROUND AND OBJECTIVES: To study the characteristics of patients dying in the ICU, dying after ICU treatment during the same hospitalization period in general wards and post-ICU hospital survivors. In addition, causes of death and post-ICU mortality (PICUM) predictors were addressed. METHODS: The present study is a retrospective single centre cohort study in a mixed medical-surgical 12-bed ICU. Patients were divided into three groups: ICU deaths, post-ICU deaths and hospital survivors. Causes of death were determined by an independent review panel of three intensive care physicians. Daly's mortality prediction model was applied in retrospect to evaluate risk of PICUM. Other predictors were also tested for predictive value. RESULTS: In total, 405 patients were included: 146 ICU deaths, 92 post-ICU deaths and 167 survivors (random computerized sample from 680 survivors). ICU mortality was 16.3% and PICUM 10.3%. Sepsis was the most common cause of death in both ICU deaths (48.3%) and post-ICU deaths (30.1%). Multivariate analysis identified age, comorbidities, length of stay in ICU, Acute Physiology and Chronic Health Evaluation II score and a do-not-resuscitate code as independent predictors of PICUM. Based on Daly's mortality prediction model, 63% of patients were discharged with a high risk of PICUM. Of these, 51% actually died. Specificity was low. CONCLUSION: Causes of deaths were equally distributed among study groups, except for sepsis. Sepsis was more frequently encountered among ICU deaths. Five PICUM predictors were found: age, Acute Physiology and Chronic Health Evaluation II score, length of ICU stay, do-not-resuscitate code and comorbidities. A do-not-resuscitate code during the first 24 h after admission was the most important predictor of PICUM. Prospective research is warranted to evaluate the applicability of PICUM prediction models in individual ICU patients.

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BACKGROUND AND OBJECTIVE: Mild therapeutic hypothermia (MTH) is used after out-of-hospital cardiac arrest (OHCA) to minimize cerebral damage. Induced hypothermia may further interfere with cardiac function and influence haemodynamics after OHCA. METHODS: This was a prospective study of haemodynamic variables in 50 consecutive patients with OHCA treated with MTH. Patients were cooled to a core body temperature of 32.5 degrees C for 24 h. Induction and maintenance of cooling was accomplished via infusion of 2 l of cold isotonic saline (4 degrees C) and a cooling blanket. Rewarming was performed to 36 degrees C at a rate of 0.3 degrees C per hour. Haemodynamic data were analysed and compared in individual patients during different temperature phases. RESULTS: Heart rate dropped from a mean of 85 to 60 beats per min (P=0.001) during hypothermia. Mean arterial pressure dropped from 79 to 72 mmHg, despite a rise in vasopressors and inotropes. Lactate levels were elevated throughout the induction (mean+/-SD) and maintenance phase (mean+/-SD); however, this did not correlate with a decrease in SVO2. Pulmonary artery pressures decreased during induction of hypothermia despite rapid infusion. CONCLUSION: MTH after OHCA lowered the heart rate. Despite induction of hypothermia with cold fluids, filling pressures decreased. Lower mean arterial pressure and cardiac output were observed during MTH, without deleterious effect on ScVO2. Lactate levels were elevated during MTH; however, levels did not correlate with outcome. Although the need for vasopressors and inotropes increases, this hypothermia-induced metabolic beta-blocker-like effect seems to have no negative effect on oxygen consumption and only temporarily affects anaerobic metabolism. No association of haemodynamic changes during MTH with outcome was found.

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Strategies that increase the ability of human hematopoietic stem and progenitor cells to repair alkylator-induced DNA damage may prevent the severe hematopoietic toxicity in patients with cancer undergoing high-dose alkylator therapy. In the context of genetic diseases, this approach may allow for selection of small numbers of cells that would not otherwise have a favorable growth advantage. No studies have tested this approach in vivo using human hematopoietic stem and progenitor cells. Human CD34(+) cells were transduced with a bicistronic oncoretrovirus vector that coexpresses a mutant form of O(6)-methylguanine DNA methyltransferase (MGMT(P140K)) and the enhanced green fluorescent protein (EGFP) and transplanted into nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice. Mice were either not treated or treated with O(6)-benzylguanine (6BG) and 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). At 8-weeks postinjection, a 2- to 8-fold increase in the percentage of human CD45(+)EGFP(+) cells in 6BG/BCNU-treated versus nontreated mice was observed in the bone marrow and was associated with increased MGMT(P140K)-repair activity. Functionally, 6BG/BCNU-treated mice demonstrated multilineage differentiation in vivo, although some skewing in the maturation of myeloid and B cells was observed in mice transplanted with granulocyte-colony stimulating factor (G-CSF)-mobilized peripheral blood compared to umbilical cord blood. Expansion of human cells in 6BG/BCNU-treated mice was observed in the majority of mice previously transplanted with transduced umbilical cord blood cells. In addition, a significant increase in the number of EGFP(+) progenitor colonies in treated versus nontreated mice were observed in highly engrafted mice indicating that selection and maintenance of human progenitor cells can be accomplished by expression of MGMT(P140K) and treatment with 6BG/BCNU.

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