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.

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.

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.

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.

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.

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.

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.

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.

Resilient performance in healthcare during the COVID-19 pandemic (ResCOV): study protocol for a multilevel grounded theory study on adaptations, working conditions, ethics and patient safety.

INTRODUCTION: Since early 2020, the COVID-19 pandemic has challenged societies and revealed the built-in fragility and dependencies in complex adaptive systems, such as healthcare. The pandemic has placed healthcare providers and systems under unprecedented amounts of strain with potential consequences that have not yet been fully elucidated. This multilevel project aims to explore resilient performance with the purpose of improving the understanding of how healthcare has adapted during the pandemic's rampage, the processes involved and the consequences on working conditions, ethics and patient safety. METHODS: An emerging explorative multilevel design based on grounded theory methodology is applied. Open and theoretical sampling is performed. Empirical data are gathered over time from written narratives and qualitative interviews with staff with different positions in healthcare organisations in two Swedish regions. The participants' first-person stories are complemented with data from the healthcare organisations' internal documents and national and international official documents. ANALYSIS: Experiences and expressions of resilient performance at different system levels and times, existing influencing risk and success factors at the microlevels, mesolevels and macrolevels and inter-relationships and consequences in different healthcare contexts, are explored using constant comparative analysis. Finally, the data are complemented with the current literature to develop a substantive theory of resilient performance during the pandemic. ETHICS AND DISSEMINATION: This project is ethically approved and recognises the ongoing strain on the healthcare system when gathering data. The ongoing pandemic provides unique possibilities to study system-wide adaptive capacity across different system levels and times, which can create an important basis for designing interventions focusing on preparedness to manage current and future challenges in healthcare. Feedback is provided to the settings to enable pressing improvements. The findings will also be disseminated through scientific journals and conferences.

Unmet need of essential treatments for critical illness in Malawi.

BACKGROUND: Critical illness is common throughout the world and has been the focus of a dramatic increase in attention during the COVID-19 pandemic. Severely deranged vital signs such as hypoxia, hypotension and low conscious level can identify critical illness. These vital signs are simple to check and treatments that aim to correct derangements are established, basic and low-cost. The aim of the study was to estimate the unmet need of such essential treatments for severely deranged vital signs in all adults admitted to hospitals in Malawi. METHODS: We conducted a point prevalence cross-sectional study of adult hospitalized patients in Malawi. All in-patients aged ≥18 on single days Queen Elizabeth Central Hospital (QECH) and Chiradzulu District Hospital (CDH) were screened. Patients with hypoxia (oxygen saturation <90%), hypotension (systolic blood pressure <90mmHg) and reduced conscious level (Glasgow Coma Scale <9) were included in the study. The a-priori defined essential treatments were oxygen therapy for hypoxia, intravenous fluid for hypotension and an action to protect the airway for reduced consciousness (placing the patient in the lateral position, insertion of an oro-pharyngeal airway or endo-tracheal tube or manual airway protection). RESULTS: Of the 1135 hospital in-patients screened, 45 (4.0%) had hypoxia, 103 (9.1%) had hypotension, and 17 (1.5%) had a reduced conscious level. Of those with hypoxia, 40 were not receiving oxygen (88.9%). Of those with hypotension, 94 were not receiving intravenous fluids (91.3%). Of those with a reduced conscious level, nine were not receiving an action to protect the airway (53.0%). CONCLUSION: There was a large unmet need of essential treatments for critical illness in two hospitals in Malawi.

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.

Pre-exposure to mechanical ventilation and endotoxemia increases Pseudomonas aeruginosa growth in lung tissue during experimental porcine pneumonia.

BACKGROUND: Immune system suppression during critical care contributes to the risk of acquired bacterial infections with Pseudomonas (P.) aeruginosa. Repeated exposure to endotoxin can attenuate systemic inflammatory cytokine responses. Mechanical ventilation affects the systemic inflammatory response to various stimuli. AIM: To study the effect of pre-exposure to mechanical ventilation with and without endotoxin-induced systemic inflammation on P. aeruginosa growth and wet-to-dry weight measurements on lung tissue and plasma and bronchoalveolar lavage levels of tumor necrosis factor alpha, interleukins 6 and 10. METHODS: Two groups of pigs were exposed to mechanical ventilation for 24 hours before bacterial inoculation and six h of experimental pneumonia (total experimental time 30 h): A30h+Etx (n = 6, endotoxin 0.063 µg x kg-1 x h-1) and B30h (n = 6, saline). A third group, C6h (n = 8), started the experiment at the bacterial inoculation unexposed to endotoxin or mechanical ventilation (total experimental time 6 h). Bacterial inoculation was performed by tracheal instillation of 1x1011 colony-forming units of P. aeruginosa. Bacterial cultures and wet-to-dry weight ratio analyses were done on lung tissue samples postmortem. Separate group comparisons were done between A30h+Etx vs.B30h (Inflammation) and B30h vs. C6h (Ventilation Time) during the bacterial phase of 6 h. RESULTS: P. aeruginosa growth was highest in A30h+Etx, and lowest in C6h (Inflammation and Ventilation Time both p<0.05). Lung wet-to-dry weight ratios were highest in A30h+Etx and lowest in B30h (Inflammation p<0.01, Ventilation Time p<0.05). C6h had the highest TNF-α levels in plasma (Ventilation Time p<0.01). No differences in bronchoalveolar lavage variables between the groups were observed. CONCLUSIONS: Mechanical ventilation and systemic inflammation before the onset of pneumonia increase the growth of P. aeruginosa in lung tissue. The attenuated growth of P. aeruginosa in the non-pre-exposed animals (C6h) was associated with a higher systemic TNF-α production elicited from the bacterial challenge.

The Patient's Gender Influencing the Accuracy of Diagnosis and Proposed Sepsis Treatment in Constructed Cases.

BACKGROUND: Male sex is an independent risk factor for sepsis development. In addition to immunological gender differences, women less often receive sepsis treatment once diagnosed. Gender differences have also been described in other medical conditions, such as acute coronary syndrome. AIM: To study whether the gender of patients influenced physicians' tendency to suspect sepsis and propose correct initial sepsis treatment in constructed cases. METHOD: Four cases were constructed to fulfil the sepsis-3 criteria as well as raise clinical suspicions of other common medical differential diagnoses. Two of the cases were drafted in two versions, only differing in the gender of the patient. The two versions were randomly distributed to all clinical physicians in a medical region in Sweden. The responding physicians were asked to state the three most important diagnoses and the three most important initial treatments for each case. If sepsis were among the stated diagnoses together with fluids and antibiotics, the case was considered as correctly identified and initially treated sepsis. RESULTS: 120 hospital physicians answered the cases. In the case the patient was a female, the respondents correctly identified and treated sepsis significantly more often than if the patient was of the male sex (Case 1: 12/58 vs 2/62, p < 0.01 and Case 2: 25/62 vs 13/58, p < 0.05). CONCLUSION: A low proportion of Swedish physicians identified and proposed treatment for sepsis in four constructed cases. In the case the patient strongly mimicked other diagnoses common in the male sex, the male cases were less often correctly identified and treated for sepsis.

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.

Vital Signs Directed Therapy for the Critically Ill: Improved Adherence to the Treatment Protocol Two Years after Implementation in an Intensive Care Unit in Tanzania.

Treating deranged vital signs is a mainstay of critical care throughout the world. In an ICU in a university hospital in Tanzania, the implementation of the Vital Signs Directed Therapy Protocol in 2014 led to an increase in acute treatments for deranged vital signs. The mortality rate for hypotensive patients decreased from 92% to 69%. In this study, the aim was to investigate the sustainability of the implementation two years later. An observational, patient-record-based study was conducted in the ICU in August 2016. Data on deranged vital signs and acute treatments were extracted from the patients' charts. Adherence to the protocol, defined as an acute treatment in the same or subsequent hour following a deranged vital sign, was calculated and compared with before and immediately after implementation. Two-hundred and eighty-nine deranged vital signs were included. Adherence was 29.8% two years after implementation, compared with 16.6% (p < 0.001) immediately after implementation and 2.9% (p < 0.001) before implementation. Consequently, the implementation of the Vital Signs Directed Therapy Protocol appears to have led to a sustainable increase in the treatment of deranged vital signs. The protocol may have potential to improve patient safety in other settings where critically ill patients are managed.

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.

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.

The Prevalence and Outcomes of Sepsis in Adult Patients in Two Hospitals in Malawi.

There are an estimated 19.4 million sepsis cases every year, many of them in low-income countries. The newly adopted definition of sepsis uses Sequential Organ Failure Assessment Score (SOFA), a score which is not feasible in many low-resource settings. A simpler quick-SOFA (qSOFA) based solely on vital signs score has been devised for identification of suspected sepsis. This study aimed to determine in-hospital prevalence and outcomes of sepsis, as defined as suspected infection and a qSOFA score of 2 or more, in two hospitals in Malawi. The secondary aim was to evaluate qSOFA as a predictor of mortality. A cross-sectional study of adult in-patients in two hospitals in Malawi was conducted using prospectively collected single-day point-prevalence data and in-hospital follow-up. Of 1,135 participants, 81 (7.1%) had sepsis. Septic patients had a higher hospital mortality rate (17.5%) than non-septic infected patients (9.0%, p = 0.027, odds ratio 2.1 [1.1-4.3]), although the difference was not statistically significant after adjustment for baseline characteristics. For in-hospital mortality among patients with suspected infection, qSOFA ≥ 2 had a sensitivity of 31.8%, specificity of 82.1%, a positive predictive value of 17.5%, and a negative predictive value of 91.0%. In conclusion, sepsis is common and is associated with a high risk of death in admitted patients in hospitals in Malawi. In low-resource settings, qSOFA score that uses commonly available vital signs data may be a tool that could be used for identifying patients at risk-both for those with and without a suspected infection.