Severe pulmonary mucorales superinfection in three influenzapatients with and without influenza-associated aspergillosis

Mucormycosisis an opportunistic fungal disease which affects immunocompromised hosts including patients with haematologic malignancies and poorly controlled diabetes mellitus. Mucorales grow invasively and are associated with high mortality even if promptly diagnosed. Viral infection like influenza can cause severe pneumonia and is associated with pulmonary aspergillosis. Here we report three separate cases of Mucorales super infection in critically-ill patients with influenza infection, one of them histologically confirmed. Two patients also had influenza-associated pulmonary aspergillosis. Two patients had fatal clinical outcome despite intensive care. The simultaneous detection of these two rare mold infections in patients with severe influenza is highly remarkable and calls for increased awareness

Impact of the matching algorithm on the treatment effect estimate: A neutral comparison study

Propensity score matching is increasingly being used in the medical literature. Choice of matching algorithms, reporting quality, and estimands are oftentimes not discussed. We evaluated the impact of propensity score matching algorithms, based on a recent clinical dataset, with three commonly used outcomes. The resulting estimands for different strengths of treatment effects were compared in a neutral comparison study and based on a thoroughly designed simulation study. Different algorithms yielded different levels of balance after matching. Along with full matching and genetic matching with replacement, good balance was achieved with nearest neighbor matching with caliper but thereby more than one fifth of the treated units were discarded. Average marginal treatment effect estimates were least biased with genetic or nearest neighbor matching, both with replacement and full matching. Double adjustment yielded conditional treatment effects that were closer to the true values, throughout. The choice of the matching algorithm had an impact on covariate balance after matching as well as treatment effect estimates. In comparison, genetic matching with replacement yielded better covariate balance than all other matching algorithms. A literature review in the British Medical Journal including its subjournals revealed frequent use of propensity score matching; however, the use of different matching algorithms before treatment effect estimation was only reported in one out of 21 studies. Propensity score matching is a methodology for causal treatment effect estimation from observational data; however, the methodological difficulties and low reporting quality in applied medical research need to be addressed

Ventilation management and outcomes in out-of-hospital cardiac arrest: a protocol for a preplanned secondary analysis of the TTM2 trial

IntroductionMechanical ventilation is a fundamental component in the management of patients post cardiac arrest. However, the ventilator settings and the gas-exchange targets used after cardiac arrest may not be optimal to minimise post-anoxic secondary brain injury. Therefore, questions remain regarding the best ventilator management in such patients.Methods and analysisThis is a preplanned analysis of the international randomised controlled trial, targeted hypothermia versus targeted normothermia after out-of-hospital cardiac arrest (OHCA)–target temperature management 2 (TTM2). The primary objective is to describe ventilatory settings and gas exchange in patients who required invasive mechanical ventilation and included in the TTM2 trial. Secondary objectives include evaluating the association of ventilator settings and gas-exchange values with 6 months mortality and neurological outcome. Adult patients after an OHCA who were included in the TTM2 trial and who received invasive mechanical ventilation will be eligible for this analysis. Data collected in the TTM2 trial that will be analysed include patients’ prehospital characteristics, clinical examination, ventilator settings and arterial blood gases recorded at hospital and intensive care unit (ICU) admission and daily during ICU stay.Ethics and disseminationThe TTM2 study has been approved by the regional ethics committee at Lund University and by all relevant ethics boards in participating countries. No further ethical committee approval is required for this secondary analysis. Data will be disseminated to the scientific community by abstracts and by original articles submitted to peer-reviewed journals.Trial registration numberNCT02908308

Oxygen targets and 6-month outcome after out of hospital cardiac arrest: a pre-planned sub-analysis of the targeted hypothermia versus targeted normothermia after Out-of-Hospital Cardiac Arrest (TTM2) trial

Background: Optimal oxygen targets in patients resuscitated after cardiac arrest are uncertain. The primary aim of this study was to describe the values of partial pressure of oxygen values (PaO2) and the episodes of hypoxemia and hyperoxemia occurring within the first 72 h of mechanical ventilation in out of hospital cardiac arrest (OHCA) patients. The secondary aim was to evaluate the association of PaO2 with patients' outcome. Methods: Preplanned secondary analysis of the targeted hypothermia versus targeted normothermia after OHCA (TTM2) trial. Arterial blood gases values were collected from randomization every 4 h for the first 32 h, and then, every 8 h until day 3. Hypoxemia was defined as PaO2 300 mmHg. Mortality and poor neurological outcome (defined according to modified Rankin scale) were collected at 6 months. Results: 1418 patients were included in the analysis. The mean age was 64 ± 14 years, and 292 patients (20.6%) were female. 24.9% of patients had at least one episode of hypoxemia, and 7.6% of patients had at least one episode of severe hyperoxemia. Both hypoxemia and hyperoxemia were independently associated with 6-month mortality, but not with poor neurological outcome. The best cutoff point associated with 6-month mortality for hypoxemia was 69 mmHg (Risk Ratio, RR = 1.009, 95% CI 0.93-1.09), and for hyperoxemia was 195 mmHg (RR = 1.006, 95% CI 0.95-1.06). The time exposure, i.e., the area under the curve (PaO2-AUC), for hyperoxemia was significantly associated with mortality (p = 0.003). Conclusions: In OHCA patients, both hypoxemia and hyperoxemia are associated with 6-months mortality, with an effect mediated by the timing exposure to high values of oxygen. Precise titration of oxygen levels should be considered in this group of patients. Trial registration: clinicaltrials.gov NCT02908308 , Registered September 20, 2016. Keywords: Cardiac arrest; Hyperoxemia; Hypoxemia; Mortality; Neurological outcom

Non-invasive oxygenation support in acutely hypoxemic COVID-19 patients admitted to the ICU: a multicenter observational retrospective study

Background: Non-invasive oxygenation strategies have a prominent role in the treatment of acute hypoxemic respiratory failure during the coronavirus disease 2019 (COVID-19). While the efficacy of these therapies has been studied in hospitalized patients with COVID-19, the clinical outcomes associated with oxygen masks, high-flow oxygen therapy by nasal cannula and non-invasive mechanical ventilation in critically ill intensive care unit (ICU) patients remain unclear. Methods: In this retrospective study, we used the best of nine covariate balancing algorithms on all baseline covariates in critically ill COVID-19 patients supported with > 10 L of supplemental oxygen at one of the 26 participating ICUs in Catalonia, Spain, between March 14 and April 15, 2020. Results: Of the 1093 non-invasively oxygenated patients at ICU admission treated with one of the three stand-alone non-invasive oxygenation strategies, 897 (82%) required endotracheal intubation and 310 (28%) died during the ICU stay. High-flow oxygen therapy by nasal cannula (n = 439) and non-invasive mechanical ventilation (n = 101) were associated with a lower rate of endotracheal intubation (70% and 88%, respectively) than oxygen masks (n = 553 and 91% intubated), p < 0.001. Compared to oxygen masks, high-flow oxygen therapy by nasal cannula was associated with lower ICU mortality (hazard ratio 0.75 [95% CI 0.58-0.98), and the hazard ratio for ICU mortality was 1.21 [95% CI 0.80-1.83] for non-invasive mechanical ventilation. Conclusion: In critically ill COVID-19 ICU patients and, in the absence of conclusive data, high-flow oxygen therapy by nasal cannula may be the approach of choice as the primary non-invasive oxygenation support strategy. Keywords: Acute hypoxemic respiratory failure; COVID-19; Intensive care; Non-invasive oxygenation

Increased Longevity of a Novel Gas Exchanger System for Low-Flow Veno-Venous Extracorporeal CO2 Removal in Acute Hypercapnic Respiratory Failure

Introduction: Low-flow veno-venous extracorporeal CO2 removal (ECCO2R) is an adjunctive therapy to support lung protective ventilation or maintain spontaneous breathing in hypercapnic respiratory failure. Low-flow ECCO2R is less invasive compared to higher flow systems, while potentially compromising efficiency and membrane lifetime. To counteract this shortcoming, a high-longevity system has recently been developed. Our hypotheses were that the novel membrane system provides runtimes up to 120 h, and CO2 removal remains constant throughout membrane system lifetime. Methods: Seventy patients with pH ≤ 7.25 and/or PaCO2 ≥9 kPa exceeding lung protective ventilation limits, or experiencing respiratory exhaustion during spontaneous breathing, were treated with the high-longevity ProLUNG system or in a control group using the original gas exchanger. Treatment parameters, gas exchanger runtime, and sweep-gas VCO2 were recorded across 9,806 treatment-hours and retrospectively analyzed. Results: 25/33 and 23/37 patients were mechanically ventilated as opposed to awake spontaneously breathing in both groups. The high-longevity system increased gas exchanger runtime from 29 ± 16 to 48 ± 36 h in ventilated and from 22 ± 14 to 31 ± 31 h in awake patients (p < 0.0001), with longer runtime in the former (p < 0.01). VCO2 remained constant at 86 ± 34 mL/min (p = 0.11). Overall, PaCO2 decreased from 9.1 ± 2.0 to 7.9 ± 1.9 kPa within 1 h (p < 0.001). Tidal volume could be maintained at 5.4 ± 1.8 versus 5.7 ± 2.2 mL/kg at 120 h (p = 0.60), and peak airway pressure could be reduced from 31.1 ± 5.1 to 27.5 ± 6.8 mbar (p < 0.01). Conclusion: Using a high-longevity gas exchanger system, membrane lifetime in low-flow ECCO2R could be extended in comparison to previous systems but remained below 120 h, especially in spontaneously breathing patients. Extracorporeal VCO2 remained constant throughout gas exchanger system runtime and was consistent with removal of approximately 50% of expected CO2 production, enabling lung protective ventilation despite hypercapnic respiratory failure

Eye-tracking to observe compliance with hand hygiene in the intensive care unit – a randomised feasibility study

Background: Healthcare-associated infections are associated with increased patient mortality. Hand hygiene is the most effective method to reduce these infections. Despite simplification of this easy intervention, compliance with hand disinfection remains low. Current assessment of hand hygiene is mainly based on observation by hygiene specialists. The aim of this study was to investigate additional benefits of eye-tracking during the analysis of hand hygiene compliance of healthcare professionals in the intensive care unit. Methods: In a simulated, randomised cross-over study conducted at the interdisciplinary intensive care unit of the University Hospital Zurich (Switzerland), doctors and nurses underwent eye-tracking and completed two everyday tasks (injection of 10 micrograms of norepinephrine via a central venous line, blood removal from the central line) in two scenarios where alcoholic dispenser locations differed ("in-sight" and "out-of-sight"). The primary outcomes were dwell time, revisits, first fixation duration and average fixation time on three areas of interest (central venous line, alcohol dispenser, protective glove box) for both scenarios. Compliance with hand hygiene guidelines was analysed. Findings: 49 participants (35 nurses, 14 doctors) were included. Eye-tracking provided additional useful information compared to conventional observations. Dwell time, revisits, first fixation duration and average fixation time did not differ between the two scenarios for all areas of interest. Overall compliance with recommended hand hygiene measures was low in both doctors (mean 20%) and nurses (mean 42.9%). Conclusion: Compared to conventional observations offered additional helpful insights and provided an in-depth analysis of gaze patterns during the recording of hand hygiene compliance in the intensive care unit. Keywords: compliance; eye-tracking; hand hygiene; intensive care unit