Lung-protective ventilation increases cerebral metabolism and non-inflammatory brain injury in porcine experimental sepsis.

BACKGROUND: Protective ventilation with lower tidal volumes reduces systemic and organ-specific inflammation. In sepsis-induced encephalopathy or acute brain injury the use of protective ventilation has not been widely investigated (experimentally or clinically). We hypothesized that protective ventilation would attenuate cerebral inflammation in a porcine endotoxemic sepsis model. The aim of the study was to study the effect of tidal volume on cerebral inflammatory response, cerebral metabolism and brain injury. Nine animals received protective mechanical ventilation with a tidal volume of 6 mL × kg-1 and nine animals were ventilated with a tidal volume of 10 mL × kg-1. During a 6-h experiment, the pigs received an endotoxin intravenous infusion of 0.25 µg × kg-1 × h-1. Systemic, superior sagittal sinus and jugular vein blood samples were analysed for inflammatory cytokines and S100B. Intracranial pressure, brain tissue oxygenation and brain microdialysis were sampled every hour. RESULTS: No differences in systemic or sagittal sinus levels of TNF-α or IL-6 were seen between the groups. The low tidal volume group had increased cerebral blood flow (p < 0.001) and cerebral oxygen delivery (p < 0.001), lower cerebral vascular resistance (p < 0.05), higher cerebral metabolic rate (p < 0.05) along with higher cerebral glucose consumption (p < 0.05) and lactate production (p < 0.05). Moreover, low tidal volume ventilation increased the levels of glutamate (p < 0.01), glycerol (p < 0.05) and showed a trend towards higher lactate to pyruvate ratio (p = 0.08) in cerebral microdialysate as well as higher levels of S-100B (p < 0.05) in jugular venous plasma compared with medium-high tidal volume ventilation. CONCLUSIONS: Contrary to the hypothesis, protective ventilation did not affect inflammatory cytokines. The low tidal volume group had increased cerebral blood flow, cerebral oxygen delivery and cerebral metabolism together with increased levels of markers of brain injury compared with medium-high tidal volume ventilation.

Hidden sources of fluids, sodium and potassium in stabilised Swedish ICU patients: A multicentre retrospective observational study.

BACKGROUND: Fluid overload in ICU patients is associated with increased morbidity and mortality. Although studies report on optimisation of resuscitation fluids given to ICU patients, increasing evidence suggests that maintenance fluids and fluids used to administer drugs are important sources of fluid overload. OBJECTIVES: We aimed to evaluate the volume of maintenance fluids and electrolytes on overall fluid balance and their relation to mortality in stabilised ICU patients. DESIGN: Multicentre retrospective observational study. SETTING: Six mixed surgical and medical ICUs in Sweden. PATIENTS: A total of 241 adult patients who spent at least 7 days in the ICU during 2018. MAIN OUTCOME MEASURES: The primary endpoint was the volume of maintenance, resuscitation and drug diluent fluids administered on days 3 to 7 in the ICU. Secondary endpoints were to compare dispensed amounts of maintenance fluids and electrolytes with predicted requirements. We also investigated the effects of administered fluids and electrolytes on patient outcomes. RESULTS: During ICU days 3 to 7, 56.4% of the total fluids given were maintenance fluids, nutritional fluids or both, 25.4% were drug fluids and 18.1% were resuscitation fluids. Patients received fluids 1.29 (95% confidence interval 1.07 to 1.56) times their estimated fluid needs. Despite this, 93% of the cohort was treated with diuretics or renal replacement therapy. Patients were given 2.17 (1.57 to 2.96) times their theoretical sodium needs and 1.22 (0.75 to 1.77) times their potassium needs. The median [IQR] volume of fluid loss during the 5-day study period was 3742 [3156 to 4479] ml day-1, with urine output the main source of fluid loss. Death at 90 days was not associated with fluid or electrolyte balance in this cohort. CONCLUSION: Maintenance and drug fluids far exceeded resuscitative fluids in ICU patients beyond the resuscitative phase. This excess fluid intake, in conjunction with high urinary output and treatment for fluid offload in almost all patients, suggests that a large volume of the maintenance fluids given was unnecessary. TRIAL REGISTRATION: ClinicalTrials.org NCT03972475.

Trainee Performance After Laparoscopic Simulator Training Using a Blackbox versus LapMentor.

BACKGROUND: Training using laparoscopic high-fidelity simulators (LHFSs) to proficiency levels improves laparoscopic cholecystectomy skills. However, high-cost simulators and their limited availability could negatively impact residents' laparoscopic training opportunities. We aimed to assess whether motivation and surgical skill performance differ after basic skills training (BST) using a low-cost (Blackbox) versus LHFS (LapMentor) among medical students. MATERIALS AND METHODS: Sixty-three medical students from Karolinska Institutet volunteered, completing written informed consent, questionnaire regarding expectations of the simulation training, and a visuospatial ability test. They were randomized into two groups that received BST using Blackbox (n = 32) or LapMentor (n = 31). However, seven students absence resulted in 56 participants, followed by another 9 dropouts. Subsequently, after training, 47 students took up three consecutive tests using the minimally invasive surgical trainer-virtual reality (MIST-VR) simulator, finalizing a questionnaire. RESULTS: More Blackbox group participants completed all MIST-VR tests (29/31 versus 18/25). Students anticipated mastering LapMentor would be more difficult than Blackbox (P = 0.04). In those completing the simulation training, a trend toward an increase was noted in how well participants in the Blackbox group liked the simulator training (P = 0.07). Subgroup analysis of motivation and difficulty in liking the training regardless of simulator was found only in women (Blackbox [P = 0.02]; LapMentor [P = 0.06]). In the Blackbox group, the perceived difficulty of training, facilitation, and liking the Blackbox training (significant only in women) were significantly correlated with the students' performance in the MIST-simulator. No such correlations were found in the LapMentor group. CONCLUSIONS: Results indicate an important role for low-tech/low-cost Blackbox laparoscopic BST of students in an otherwise high-tech surrounding. Furthermore, experience of Blackbox BST procedures correlate with students' performance in the MIST-VR simulator, with some gender-specific differences.

Lung-protective ventilation suppresses systemic and hepatic vein levels of cell-free DNA in porcine experimental post-operative sepsis.

BACKGROUND: Plasma levels of cell-free DNA (cf-DNA) are known to be elevated in sepsis and high levels are associated with a poor prognosis. Mechanical ventilation affects systemic inflammation in which lung-protective ventilation attenuates the inflammatory response. The aim was to study the effect of a lung protective ventilator regime on arterial and organ-specific venous blood as well as on trans-organ differences in cf-DNA levels in a porcine post-operative sepsis model. METHOD: One group of anaesthetised, domestic-breed, 9-12 weeks old, pigs were ventilated with protective ventilation (VT 6 mL x kg- 1, PEEP 10 cmH2O) n = 20. Another group, ventilated with a medium high tidal volume and lower PEEP, served as a control group (VT 10 mL x kg- 1, PEEP 5 cm H2O) n = 10. Blood samples were taken from four sources: artery, hepatic vein, portal vein and, jugular bulb. A continuous endotoxin infusion at 0.25 µg x kg- 1 x h- 1 for 5 h was started following 2 h of laparotomy, which simulated a surgical procedure. Inflammatory cytokines and cf-DNA in plasma were analysed and trans-organ differences calculated. RESULTS: The protective ventilation group had lower levels of cf-DNA in arterial (p = 0.02) and hepatic venous blood (p = 0.03) compared with the controls. Transhepatic differences in cf-DNA were lower in the protective group, compared with the controls (p = 0.03). No differences between the groups were noted as regards the transcerebral, transsplanchnic or the transpulmonary cf-DNA differences. CONCLUSIONS: Protective ventilation suppresses arterial levels of cf-DNA. The liver seems to be a net contributor to the systemic cf-DNA levels, but this effect is attenuated by protective ventilation.

Validation of a Novel Needle Holder to Train Advanced Laparoscopy Skills to Novices in a Simulator Environment.

Background. Our aim was to determine if a newly designed Najar needle holder (NNH) shortens the time for novices to improve advanced laparoscopy (AL) techniques (suturing/knot tying), compared with a conventional macro needle holder (MNH) in a simulator. Furthermore, we aimed to validate a new video scoring system determining AL skills. Methods. Forty-six medical students performed identical surgical tasks in a prospective, crossover study evaluating AL skills (NNH vs MNH). All subjects performed a double-throw knot, 2 single-throw knots following 3 running sutures in the Simball Box (SB) simulator. After resting, subjects switched needle holders. All tasks were videotaped and analyzed using SB software and by 2 independent reviewers using the Objective Video Evaluation Scoring Table (OVEST). Trial performance expressed as SB Overall Score (SBOS) and OVEST. Results. In the group starting with NNH (followed by MNH) OVEST was consistently high during both trials (median = 12.5, range = 6.5-18.0, and median = 13.5, range = 6.5-21.0; P = .2360). However, in the group starting with MNH, OVEST improved significantly when the participants changed to NNH (median = 10.0, range = 2.5-19.5, vs median = 14.5, range = 4.5-18.0; P = .0003); an improvement was also found with SBOS (median = 37%, range = 27% to 92%, vs median = 48%, range = 34% to 70%; P = .0289). In both trials, both independent reviewers' OVEST measures correlated well: Trial 1: ß = 0.97, P < .0001; and Trial 2: ß = 0.95, P < .0001. A correlation also existed between SBOS and OVEST in both trials (ß = 2.1, P < .0001; and ß = 1.9, P = .0002). Conclusions. This study indicates a significantly higher improvement in laparoscopic suturing skills in novices training AL skills using NNH compared with MNH. Starting early, AL training in novices using NNH is a feasible option. Furthermore, OVEST used in experimental settings as an evaluation tool is comparable with the validated SBOS.

Dynamics of Endotoxin, Inflammatory Variables, and Organ Dysfunction After Treatment With Antibiotics in an Escherichia coli Porcine Intensive Care Sepsis Model.

OBJECTIVES: To investigate the dynamics of antibiotic-induced endotoxin liberation and inflammatory response in vivo in a clinically relevant large animal intensive care sepsis model and whether the addition of an aminoglycoside to a ß-lactam antibiotic affects these responses. DESIGN: Prospective, placebo-controlled interventional experimental study. SETTING: University research unit. SUBJECTS: Thirty-six healthy pigs administered Escherichia coli as a 3-hour infusion. INTERVENTIONS: After 2 hours, during E. coli infusion, the animals were exposed to cefuroxime alone, the combination of cefuroxime and tobramycin, or saline. MEASUREMENTS AND MAIN RESULTS: Plasma endotoxin, interleukin-6, tumor necrosis factor-α, leucocytes, and organ dysfunction were recorded for 4 hours after antibiotic treatment, and differences to the values before treatment were calculated. In vitro experiments were performed to ascertain whether endotoxin is released during antibiotic-induced bacterial killing of this E. coli strain. Despite differences between the treatment arms in vitro, no differences in plasma endotoxin were observed in vivo. Antibiotic-treated animals demonstrated a higher interleukin-6 response (p < 0.001), greater leucocyte activation (p < 0.001), and more pronounced deterioration in pulmonary static compliance (p < 0.01) over time than controls. Animals treated with the combination showed a trend toward less inflammation. CONCLUSIONS: Treatment with antibiotics may elicit an increased inflammatory interleukin-6 response that is associated with leucocyte activation and pulmonary organ dysfunction. No observable differences were detected in plasma endotoxin concentrations. The reduction in cefuroxime-induced endotoxin release after the addition of an aminoglycoside in vitro could not be reproduced in this model.

The global need for essential emergency and critical care.

Critical illness results in millions of deaths each year. Care for those with critical illness is often neglected due to a lack of prioritisation, co-ordination, and coverage of timely identification and basic life-saving treatments. To improve care, we propose a new focus on essential emergency and critical care (EECC)-care that all critically ill patients should receive in all hospitals in the world. Essential emergency and critical care should be part of universal health coverage, is appropriate for all countries in the world, and is intended for patients irrespective of age, gender, underlying diagnosis, medical specialty, or location in the hospital. Essential emergency and critical care is pragmatic and low-cost and has the potential to improve care and substantially reduce preventable mortality.

Effects of surgery and propofol-remifentanil total intravenous anesthesia on cerebrospinal fluid biomarkers of inflammation, Alzheimer's disease, and neuronal injury in humans: a cohort study.

BACKGROUND: Surgery and anesthesia have been linked to postoperative cognitive disturbance and increased risk of Alzheimer's disease. It is not clear by which mechanisms this increased risk for cognitive disease is mediated. Further, amyloid ß production has been suggested to depend on the sleep-wake cycle and neuronal activity. The aim of the present study was to examine if cerebrospinal fluid (CSF) concentrations of a number of biomarkers for Alzheimer's disease-related processes, including amyloid ß, neuronal injury, and inflammation, changed over time during intravenous anesthesia in surgical patients. METHODS: We included patients scheduled for hysterectomy via laparotomy during general anesthesia with intravenous propofol and remifentanil. CSF samples were obtained before, during, and after surgery (5 h after induction) and tested for 27 biomarkers. Changes over time were tested with linear mixed effects models. RESULTS: A total of 22 patients, all females, were included. The mean age was 50 years (± 9 SD). The mean duration of the anesthesia was 145 min (± 40 SD). Interleukin (IL)-6, IL-8, monocyte chemoattractant protein 1, and vascular endothelial growth factor A increased over time. IL-15 and IL-7 decreased slightly over time. Macrophage inflammatory protein 1ß and placental growth factor also changed significantly. There were no significant effects on amyloid ß (Aß) or tau biomarkers. CONCLUSIONS: Surgery and general anesthesia with intravenous propofol and remifentanil induce, during and in the short term after the procedure, a neuroinflammatory response which is dominated by monocyte attractants, without biomarker signs of the effects on Alzheimer's disease pathology or neuronal injury.

Single Deranged Physiologic Parameters Are Associated With Mortality in a Low-Income Country.

OBJECTIVE: To investigate whether deranged physiologic parameters at admission to an ICU in Tanzania are associated with in-hospital mortality and compare single deranged physiologic parameters to a more complex scoring system. DESIGN: Prospective, observational cohort study of patient notes and admission records. Data were collected on vital signs at admission to the ICU, patient characteristics, and outcomes. Cutoffs for deranged physiologic parameters were defined a priori and their association with in-hospital mortality was analyzed using multivariable logistic regression. SETTING: ICU at Muhimbili National Hospital, Dar es Salaam, Tanzania. PATIENTS: All adults admitted to the ICU in a 15-month period. MEASUREMENTS AND MAIN RESULTS: Two hundred sixty-nine patients were included: 54% female, median age 35 years. In-hospital mortality was 50%. At admission, 69% of patients had one or more deranged physiologic parameter. Sixty-four percent of the patients with a deranged physiologic parameter died in hospital compared with 18% without (p < 0.001). The presence of a deranged physiologic parameter was associated with mortality (adjusted odds ratio, 4.64; 95% CI, 1.95-11.09). Mortality increased with increasing number of deranged physiologic parameters (odds ratio per deranged physiologic parameter, 2.24 [1.53-3.26]). Every individual deranged physiologic parameter was associated with mortality with unadjusted odds ratios between 1.92 and 16.16. A National Early Warning Score of greater than or equal to 7 had an association with mortality (odds ratio, 2.51 [1.23-5.14]). CONCLUSION: Single deranged physiologic parameters at admission are associated with mortality in a critically ill population in a low-income country. As a measure of illness severity, single deranged physiologic parameters are as useful as a compound scoring system in this setting and could be termed "danger signs." Danger signs may be suitable for the basis of routines to identify and treat critically ill patients.

Evaluating the effects of protective ventilation on organ-specific cytokine production in porcine experimental postoperative sepsis.

BACKGROUND: Protective ventilation with lower tidal volume (VT) and higher positive end-expiratory pressure (PEEP) reduces the negative additive effects of mechanical ventilation during systemic inflammatory response syndrome. We hypothesised that protective ventilation during surgery would affect the organ-specific immune response in an experimental animal model of endotoxin-induced sepsis-like syndrome. METHODS: 30 pigs were laparotomised for 2 hours (h), after which a continuous endotoxin infusion was started at 0.25 micrograms × kg(-1) × h(-1) for 5 h. Catheters were placed in the carotid artery, hepatic vein, portal vein and jugular bulb. Animals were randomised to two protective ventilation groups (n = 10 each): one group was ventilated with VT 6 mL × kg(-1) during the whole experiment while the other group was ventilated during the surgical phase with VT of 10 mL × kg(-1). In both groups PEEP was 5 cmH2O during surgery and increased to 10 cmH2O at the start of endotoxin infusion. A control group (n = 10) was ventilated with VT of 10 mL × kg(-1) and PEEP 5 cm H20 throughout the experiment. In four sample locations we a) simultaneously compared cytokine levels, b) studied the effect of protective ventilation initiated before and during endotoxemia and c) evaluated protective ventilation on organ-specific cytokine levels. RESULTS: TNF-alpha levels were highest in the hepatic vein, IL-6 levels highest in the artery and jugular bulb and IL-10 levels lowest in the artery. Protective ventilation initiated before and during endotoxemia did not differ in organ-specific cytokine levels. Protective ventilation led to lower levels of TNF-alpha in the hepatic vein compared with the control group, whereas no significant differences were seen in the artery, portal vein or jugular bulb. CONCLUSIONS: Variation between organs in cytokine output was observed during experimental sepsis. We see no implication from cytokine levels for initiating protective ventilation before endotoxemia. However, during endotoxemia protective ventilation attenuates hepatic inflammatory cytokine output contributing to a reduced total inflammatory burden.

Influenza-associated invasive aspergillosis in patients admitted to the intensive care unit in Sweden: a prospective multicentre cohort study.

BACKGROUND: The purpose of this study was to prospectively investigate the incidence of influenza-associated pulmonary aspergillosis (IAPA) in influenza patients admitted to intensive care units in Sweden. METHODS: The study included consecutive adult patients with PCR-verified influenza A or B in 12 Swedish intensive care units (ICUs) over four influenza seasons (2019-2023). Patients were screened using serum galactomannan and ß-d-glucan tests and fungal culture of a respiratory sample at inclusion and weekly during the ICU stay. Bronchoalveolar lavage was performed if clinically feasible. IAPA was classified according to recently proposed case definitions. RESULTS: The cohort included 55 patients; 42% were female, and the median age was 59 (IQR 48-71) years. All patients had at least one galactomannan test, ß-d-glucan test and respiratory culture performed. Bronchoalveolar lavage was performed in 24 (44%) of the patients. Five (9%, 95% CI 3.8% - 20.4%) patients were classified as probable IAPA, of which four lacked classical risk factors. The overall ICU mortality was significantly higher among IAPA patients than non-IAPA patients (60% vs 8%, p = 0.01). CONCLUSIONS: The study represents the first prospective investigation of IAPA incidence. The 9% incidence of IAPA confirms the increased risk of invasive pulmonary aspergillosis among influenza patients admitted to the ICU. Therefore, it appears reasonable to implement a screening protocol for the early diagnosis and treatment of IAPA in influenza patients receiving intensive care. TRIAL REGISTRATION: ClinicalTrials.gov NCT04172610, registered November 21, 2019.

An experimental porcine model of invasive candidiasis.

BACKGROUND: Invasive candidiasis (IC) is a severe and often fatal fungal infection that affects critically ill patients. The development of animal models that mimic human disease is essential for advancing our understanding of IC pathophysiology and testing experimental or novel treatments. We aimed to develop a large animal model of IC that could provide a much-needed addition to the widely used murine models. RESULTS: A total of 25 pigs (including one control), aged between 9 and 12 weeks, with a median weight of 25.1 kg (IQR 24.1-26.2), were used to develop the porcine IC model. We present the setup, the results of the experiments, and the justification for the changes made to the model. The experiments were conducted in an intensive care setting, using clinically relevant anaesthesia, monitoring and interventions. The final model used corticosteroids, repeated Candida inoculation, and continuous endotoxin. The model consistently demonstrated quantifiable growth of Candida in blood and organs. The registered physiological data supported the development of the sepsis-induced circulatory distress observed in IC patients in the ICU. CONCLUSIONS: Our proposed porcine model of IC offers a potential new tool in the research of IC.

From Threatening Chaos to Temporary Order through a Complex Process of Adaptation: A Grounded Theory Study of the Escalation of Intensive Care during the COVID-19 Pandemic.

To ensure high-quality care, operationalize resilience and fill the knowledge gap regarding how to improve the prerequisites for resilient performance, it is necessary to understand how adaptive capacity unfolds in practice. The main aim of this research was to explain the escalation process of intensive care during the first wave of the pandemic from a microlevel perspective, including expressions of resilient performance, intervening conditions at the micro-meso-macrolevels and short- and long-term consequences. A secondary aim was to provide recommendations regarding how to optimize the prerequisites for resilient performance in intensive care. A grounded theory methodology was used. First-person stories from different healthcare professionals (n70) in two Swedish regions were analyzed using the constant comparative method. This resulted in a novel conceptual model (including 6 main categories and 24 subcategories), and 41 recommendations. The conclusion of these findings is that the escalation of intensive care can be conceptualized as a transition from threatening chaos to temporary order through a complex process of adaptation. To prepare for the future, the components of space, stuff, staff, system and science, with associated continuity plans, must be implemented, anchored and communicated to actors at all levels of the system.

The burden of critical illness among adults in a Swedish region-a population-based point-prevalence study.

BACKGROUND: Patients with critical illness have a high risk of mortality. Key decision-making in the health system affecting the outcomes of critically ill patients requires epidemiological evidence, but the burden of critical illness is largely unknown. This study aimed to estimate the prevalence of critical illness in a Swedish region. Secondary objectives were to estimate the proportion of hospital inpatients who are critically ill and to describe the in-hospital location of critically ill patients. METHODS: A prospective, multi-center, population-based, point-prevalence study on specific days in 2017-2018. All adult (> 18 years) in-patients, regardless of admitting specially, in all acute hospitals in Sörmland, and the patients from Sörmland who had been referred to university hospitals, were included. Patients in the operating theatres, with a psychiatric cause of admission, women in active labor and moribund patients, were excluded. All participants were examined by trained data collectors. Critical illness was defined as "a state of ill health with vital organ dysfunction, a high risk of imminent death if care is not provided and a potential for reversibility". The presence of one or more severely deranged vital signs was used to classify critical illness. The prevalence of critical illness was calculated as the number of critically ill patients divided by the number of adults in the region. RESULTS: A total of 1269 patients were included in the study. Median age was 74 years and 50% of patients were female. Critical illness was present in 133 patients, resulting in an adult population prevalence of critical illness per 100,000 people of 19.4 (95% CI 16.4-23.0). The proportion of patients in hospital who were critically ill was 10.5% (95% CI 8.8-12.3%). Among the critically ill, 125 [95% CI 94.0% (88.4-97.0%)] were cared for in general wards. CONCLUSIONS: The prevalence of critical illness was higher than previous, indirect estimates. One in ten hospitalized patients were critically ill, the large majority of which were cared for in general wards. This suggests a hidden burden of critical illness of potential public health, health system and hospital management significance.

Mesenchymal stromal cells as treatment for acute respiratory distress syndrome. Case Reports following hematopoietic cell transplantation and a review.

Acute respiratory distress syndrome (ARDS) is a life-threatening lung disease. It may occur during the pancytopenia phase following allogeneic hematopoietic cell transplantation (HCT). ARDS is rare following HCT. Mesenchymal stromal cells (MSCs) have strong anti-inflammatory effect and first home to the lung following intravenous infusion. MSCs are safe to infuse and have almost no side effects. During the Covid-19 pandemic many patients died from ARDS. Subsequently MSCs were evaluated as a therapy for Covid-19 induced ARDS. We report three patients, who were treated with MSCs for ARDS following HCT. Two were treated with MSCs derived from the bone marrow (BM). The third patient was treated with MSCs obtained from the placenta, so-called decidua stromal cells (DSCs). In the first patient, the pulmonary infiltrates cleared after infusion of BM-MSCs, but he died from multiorgan failure. The second patient treated with BM-MSCs died of aspergillus infection. The patient treated with DSCs had a dramatic response and survived. He is alive after 7 years with a Karnofsky score of 100%. We also reviewed experimental and clinical studies using MSCs or DSCs for ARDS. Several positive reports are using MSCs for sepsis and ARDS in experimental animals. In man, two prospective randomized placebo-controlled studies used adipose and BM-MSCs, respectively. No difference in outcome was seen compared to placebo. Some pilot studies used MSCs for Covid-19 ARDS. Positive results were achieved using umbilical cord and DSCs however, optimal source of MSCs remains to be elucidated using randomized trials.

Oxygen provision to severely ill COVID-19 patients at the peak of the 2020 pandemic in a Swedish district hospital.

Oxygen is a low-cost and life-saving therapy for patients with COVID-19. Yet, it is a limited resource in many hospitals in low income countries and in the 2020 pandemic even hospitals in richer countries reported oxygen shortages. An accurate understanding of oxygen requirements is needed for capacity planning. The World Health Organization estimates the average flow-rate of oxygen to severe COVID-19-patients to be 10 l/min. However, there is a lack of empirical data about the oxygen provision to patients. This study aimed to estimate the oxygen provision to COVID-19 patients with severe disease in a Swedish district hospital. A retrospective, medical records-based cohort study was conducted in March to May 2020 in a Swedish district hospital. All adult patients with severe COVID-19 -those who received oxygen in the ward and had no ICU-admission during their hospital stay-were included. Data were collected on the oxygen flow-rates provided to the patients throughout their hospital stay, and summary measures of oxygen provision calculated. One-hundred and twenty-six patients were included, median age was 70 years and 43% were female. On admission, 27% had a peripheral oxygen saturation of ≤91% and 54% had a respiratory rate of ≥25/min. The mean oxygen flow-rate to patients while receiving oxygen therapy was 3.0 l/min (SD 2.9) and the mean total volume of oxygen provided per patient admission was 16,000 l (SD 23,000). In conclusion, the provision of oxygen to severely ill COVID-19-patients was lower than previously estimated. Further research is required before global estimates are adjusted.

Combining T2Bacteria and T2Candida Panels for Diagnosing Intra-Abdominal Infections: A Prospective Multicenter Study.

The T2Bacteria panel is a direct-from-blood assay that delivers rapid results, targeting E. coli, S. aureus, K. pneumoniae, A. baumanii, P. aeruginosa, and E. faecium (ESKAPE pathogens). In this study, T2Bacteria and T2Candida (targeting C. albicans/C. tropicalis, C. glabrata/C. krusei, and C. parapsilosis) were evaluated in parallel with blood cultures in 101 consecutive surgical patients with suspected intra-abdominal infection admitted to the intensive care unit or high dependency unit. Fifteen patients had bacteremia, with T2Bacteria correctly identifying all on-panel (n = 8) pathogens. T2Bacteria was positive in 19 additional patients, 11 of whom had supportive cultures from other normally sterile sites (newly inserted drains, perioperative cultures or blood cultures) within seven days. Six of these eleven patients (55%) received broad-spectrum antibiotics at the sampling time. T2Candida identified the two cases of blood-culture-positive candidemia and was positive in seven additional patients, three of whom were confirmed to have intra-abdominal candidiasis. Of four patients with concurrent T2Bacteria and T2Candida positivity, only one patient had positive blood cultures (candidemia), while three out of four patients had supporting microbiological evidence of a mixed infection. T2Bacteria and T2Candida were fast and accurate in diagnosing on-panel bloodstream infections, and T2Bacteria was able to detect culture-negative intra-abdominal infections.

T2Candida Assay in the Diagnosis of Intraabdominal Candidiasis: A Prospective Multicenter Study.

The T2Candida magnetic resonance assay is a direct-from-blood pathogen detection assay that delivers a result within 3-5 h, targeting the most clinically relevant Candida species. Between February 2019 and March 2021, the study included consecutive patients aged >18 years admitted to an intensive care unit or surgical high-dependency unit due to gastrointestinal surgery or necrotizing pancreatitis and from whom diagnostic blood cultures were obtained. Blood samples were tested in parallel with T2Candida and 1,3-ß-D-glucan. Of 134 evaluable patients, 13 (10%) were classified as having proven intraabdominal candidiasis (IAC) according to the EORTC/MSG criteria. Two of the thirteen patients (15%) had concurrent candidemia. The sensitivity, specificity, positive predictive value, and negative predictive value, respectively, were 46%, 97%, 61%, and 94% for T2Candida and 85%, 83%, 36%, and 98% for 1,3-ß-D-glucan. All positive T2Candida results were consistent with the culture results at the species level, except for one case of dual infection. The performance of T2Candida was comparable with that of 1,3-ß-D-glucan for candidemic IAC but had a lower sensitivity for non-candidemic IAC (36% vs. 82%). In conclusion, T2Candida may be a valuable complement to 1,3-ß-D-glucan in the clinical management of high-risk surgical patients because of its rapid results and ease of use.

The Contribution of Plasma Urea to Total Osmolality During Iatrogenic Fluid Reduction in Critically Ill Patients.

Hyperosmolality is common in critically ill patients during body fluid volume reduction. It is unknown whether this is only a result of decreased total body water or an active osmole-producing mechanism similar to that found in aestivating animals, where muscle degradation increases urea levels to preserve water. We hypothesized that fluid volume reduction in critically ill patients contributes to a shift from ionic to organic osmolytes similar to mechanisms of aestivation. We performed a post-hoc analysis on data from a multicenter observational study in adult intensive care unit (ICU) patients in the postresuscitative phase. Fluid, electrolyte, energy and nitrogen intake, fluid loss, estimated glomerular filtration rate (eGFR), and estimated plasma osmolality (eOSM) were registered. Contributions of osmolytes Na+, K+, urea, and glucose to eOSM expressed as proportions of eOSM were calculated. A total of 241 patients were included. eOSM increased (median change 7.4 mOsm/kg [IQR-1.9-18]) during the study. Sodium's and potassium's proportions of eOSM decreased (P < .05 and P < .01, respectively), whereas urea's proportion increased (P < .001). The urea's proportion of eOSM was higher in patients with negative vs. positive fluid balance. Urea's proportion of eOSM increased with eOSM (r = 0.63; adjusted for eGFR r = 0.80), but not nitrogen intake. In patients without furosemide and/or renal replacement therapy (n = 17), urea's proportion of eOSM and eOSM correlated strongly (r = 0.92). Urea's proportion of eOSM was higher in patients not surviving up to 90 d. In stabilized ICU patients, the contribution of urea to plasma osmolality increased during body water volume reduction, statistically independently of nitrogen administration and eGFR. The shift from ionic osmolytes to urea during body fluid volume reduction is similar to that seen in aestivating animals. ClinicalTrials.org Identifier: NCT03972475.