Nadir Kharma

Background/Objectives: Reported infection rates during extracorporeal membrane oxygenation (ECMO) vary widely, partly because case definitions are applied inconsistently. We synthesized the prevalence and prognostic association of nosocomial and bloodstream infection (BSI) acquired during adult ECMO. Methods: PubMed/MEDLINE, Embase, Scopus and CENTRAL were searched through December 2025 for observational studies of at least 10 adults on ECMO with an explicit infection definition. We classified case definitions by the criteria actually applied. We pooled crude mortality odds ratios (ORs) and patient-level BSI prevalence in studies applying laboratory-confirmed criteria, assessed risk of bias with ROBINS-I and the JBI checklist, and rated certainty with GRADE. Results: Forty-seven reports (46 cohorts; 11,573 patients) were included. Pooled BSI prevalence was 25.8% (95% CI 17.3–36.5%; 7 studies, 1193 patients), 18.2% in pre-pandemic and 39.2% in COVID-19 cohorts (post hoc). Infection was associated with higher crude odds of death (OR 1.65, 1.33–2.04; prediction interval 0.95–2.85; 24 studies), but analyses modeling infection as time-varying were inconsistent, including no association in a multistate model (adjusted hazard ratio 1.00, 0.79–1.26), and small-study effects were suggested. Certainty was very low for both outcomes. Conclusions: Roughly one in four adults on ECMO developed laboratory-confirmed BSI, more often in COVID-19 cohorts. Whether infection acquired on ECMO increases mortality remains uncertain.

Objectives: To assess the effect of anticoagulation with bivalirudin administered intravenously on gas-exchange in patients with COVID-19 and respiratory failure using invasive mechanical ventilation. Trial design: This is a single centre parallel group, superiority, randomized (1:1 allocation ratio) controlled trial. Participants: All patients admitted to the Hamad Medical Corporation -ICU in Qatar for COVID-19 associated respiratory distress and in need of mechanical ventilation are screened for eligibility. Inclusion criteria: all adult patients admitted to the ICU who test positive for COVID-19 by PCR-test and in need for mechanical ventilation are eligible for inclusion. Upon crossing the limit of D-dimers (1.2 mg/L) these patients are routinely treated with an increased dose of anticoagulant according to our local protocol. This will be the start of randomization. Exclusion criteria: pregnancy, allergic to the drug, inherited coagulation abnormalities, no informed consent. Intervention and comparator: The intervention group will receive the anticoagulant bivalirudin intravenously with a target aPTT of 45-70 sec for three days while the control group will stay on the standard treatment with low-molecular-weight heparins /unfractionated heparin subcutaneously (see scheme in Additional file 1). All other treatment will be unchanged and left to the attending physicians. Main outcomes: As a surrogate parameter for clinical improvement and primary outcome we will use the PaO2/FiO2 (P/F) ratio. Randomisation: After inclusion, the patients will be randomized using a closed envelope method into the conventional treatment group, which uses the standard strategy and the experimental group which receives anticoagulation treatment with bivalirudin using an allocation ratio of 1:1. Blinding (masking): Due to logistical and safety reasons (assessment of aPTT to titrate the study drug) only the data-analyst will be blinded to the groups. Numbers to be randomised (sample size): We performed a sample size calculation and assumed the data for P/F ratio (according to literature) is normally distributed and used the mean which would be: 160 and SD is 80. We expect the treatment will improve this by 30%. In order to reach a power of 80% we would need 44 patients per group (in total 88 patients). Taking approximately 10% of dropout into account we will include 100 patients (50 in each group). Trial Status: The local registration number is MRC-05-082 with the protocol version number 2. The date of approval is 18th June 2020. Recruitment started on 28^th June and is expected to end in November 2020. Trial registration: The protocol is registered before starting subject recruitment under the title: “Anticoagulation in patients suffering from COVID-19 disease. The ANTI-CO Trial” in ClinicalTrials.org with the registration number: NCT04445935. Registered on 24 June 2020. Full protocol: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 2). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Weaning is the process of successfully liberating the patient from mechanical ventilation. The majority of patients will separate from the ventilator after a successful spontaneous breathing trial (SBT). In a minority of patients, weaning can be challenging and prolonged. Finding the cause of weaning difficulty is crucial to minimize the rates of extubation failure and prolonged ventilation. Diaphragm dysfunction (DD) has been described as a separate entity responsible for weaning failure with an incidence of 23–80%. It has also been associated with difficult weaning, prolonged intensive care unit (ICU) stay and mechanical ventilation, and increased ICU and hospital mortality. Sepsis, shock, and ventilator induced diaphragm dysfunction are important risk factors of DD. Diaphragm dysfunction has several mechanisms. Disuse atrophy and microstructural changes of the diaphragm have been described as the two cardinal pathophysiologic features. Establishing the diagnosis of DD can be complex in critically ill patients. Bilateral anterior magnetic phrenic stimulation is widely considered as the gold standard but is only available in large research centers with limited availability. Ultrasonography of the diaphragm is a promising tool given its wide availability, affordability, and non-invasive nature. Ultrasound is operator dependent, however and it does not provide continuous monitoring capabilities. The diaphragm thickening fraction (DTF) can be calculated from measuring the end-expiratory and end-inspiratory diaphragm thickness at the bedside. It correlates well with transdiaphragmatic pressure. Electromyography of the diaphragm may overcome the limitation of ultrasound by offering a continuous assessment of the diaphragmatic electrical activity, but it requires the placement of a specialized nasogastric tube. Management of DD is better approached by implementing a preventive and a curative strategy. From animal studies, allowing for spontaneous breathing on mechanical ventilation may prevent the problem. The degree of the recommended patient effort and ventilator assistance to achieve optimal balance between diaphragmatic loading and unloading are yet to be defined. Monitoring DTF while finding the optimal ventilator support level can be useful in this context. Another modality to prevent DD is diaphragm pacing applied through a transvenous phrenic nerve pacing system. Animal studies in pigs showed that this modality resulted in less diaphragm atrophy when pacing was synchronized with ventilation. There is an ongoing study to assess the role of diaphragm pacing to recondition and strengthen the diaphragm in difficult to wean mechanically ventilated patients (Clinicaltrials.gov NCT03107949). Once diaphragm dysfunction is established, no specific treatments exist at this time. Other causes of weaning failure like cardiac dysfunction have to be excluded and treated. Improving respiratory load and respiratory muscle weakness imbalance is also crucial. While it appears to improve inspiratory muscle strength parameters, inspiratory muscle training has not consistently shown improvements in weaning success. Levosemindan showed some benefit in improving diaphragm contractility and efficiency in healthy volunteers but was later found to increase likelihood of weaning failure in septic patients. Anabolic steroids were not found to be effective in treating diaphragm dysfunction in several studies. More evidence is needed before recommending non-invasive ventilation post-extubation in all DD patients.