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Objective We assessed the efficacy of a quality improvement programme to optimize the delivery of antimicrobial therapy in critically ill patients with hospital-acquired infections (HAI). Patients and methods Before–after trial in a university hospital in France. Consecutive adults receiving systemic antimicrobial therapy for HAI were included. Patients received standard care during the pre-intervention period (June 2017 to November 2017). The quality improvement programme was implemented in December 2017. During the intervention period (January 2018 to June 2019), clinicians were trained to dose adjustment based on therapeutic drug monitoring and continuous infusion of β-lactam antibiotics. The primary endpoint was the mortality rate at day 90. Results A total of 198 patients were included (58 pre-intervention, 140 intervention). The compliance with the therapeutic drug monitoring-dose adaptation increased from 20.3% to 59.3% after the intervention (P Conclusions Recommendations for therapeutic drug monitoring-dose adaptation and continuous infusion of β-lactam antibiotics were not associated with a reduction in the 90-day mortality rate in patients with HAI.

The objective was to determine the effects of continuous infusion of hypertonic saline solutions on outcomes of patients with brain injury.Preferred Reported Items for Systemic Reviews and Meta-Analysis guidelines were followed. We searched the MEDLINE and COCHRANE clinical trials register (through December 2021) and reference lists of articles. We included all clinical trials conducted in brain-injured patients hospitalized in intensive care units evaluating continuous infusion of hypertonic saline solution (osmolarity above 308 mOsm/L). Two reviewers extracted data that were checked by two others. The primary outcome was the in-hospital mortality rate. The main secondary outcomes were the rates of intracranial hypertension, an unfavorable neurological outcome at day 90, and adverse events.We identified 23 clinical trials reporting the use of continuous infusion of hypertonic saline solution in brain-injured patients. The primary outcome was available in 10 studies (n = 1883 patients). The odds ratio (OR) for in-hospital death with the intervention was 0.68 (95% confidence interval (CI), 0.54-0.85, IContinuous hypertonic saline solution infusion reduced in-hospital mortality without increasing the risk of unfavorable neurological outcome at day 90 in brain-injured patients hospitalized in intensive care units. Given the inclusion of observational and heterogeneous studies, further randomized studies are needed before developing recommendations for implementation at the bedside.PROSPERO CRD42021221367. Registered 13 May 2021.

Traumatic brain injury (TBI) induces instant activation of innate immunity in brain tissue, followed by a systematization of the inflammatory response. The subsequent response, evolved to limit an overwhelming systemic inflammatory response and to induce healing, involves the autonomic nervous system, hormonal systems, and the regulation of immune cells. This physiological response induces an immunosuppression and tolerance state that promotes to the occurrence of secondary infections. This review describes the immunological consequences of TBI and highlights potential novel therapeutic approaches using immune modulation to restore homeostasis between the nervous system and innate immunity.

ObjectivesTo investigate the potential impact of the syndromic multiplex FilmArray® Pneumonia plus Panel (FAPP) on the antimicrobial treatment guidance of patients with ventilated hospital-acquired pneumonia (VHAP).MethodsRespiratory fluids from 100 adult patients with VHAP, receiving invasive mechanical ventilation in three intensive care units from one French university hospital, were tested prospectively using FAPP. Conventional cultures were performed in parallel as routine practice. Clinicians were left blinded to the FAPP results. Antimicrobial therapies based on FAPP results were simulated by independent blinded experts according to a predefined algorithm and compared to 1) those prescribed in practice according to local guidelines (real-life), and 2) those that complied with the international ERS/ESICM/ESCMID/ALAT recommendations. The primary endpoint was the number of days of broad-spectrum antimicrobial therapy. Secondary endpoints were the rates of microbiological treatment failure and cost-effectiveness ratio.ResultsThe predicted median duration of broad-spectrum antibiotics was 0 [0-1.25] day in the FAPP-based simulation, versus 2 [0-6] days in real-life (pConclusionsOur results suggest that using FAPP in patients with VHAP has the potential to reduce the use of broad-spectrum antimicrobial therapy without increasing the risk of microbial treatment failure.

Resume Les complications infectieuses, acquises notamment en reanimation, representent les principales causes de morbi-mortalite secondaires des agressions cerebrales aigues. Elles sont majoritairement representees par les pneumonies acquises sous ventilation mecanique. Dans les suites d’une atteinte cerebrale aigue, le syndrome de reponse inflammatoire systemique (SRIS) est un phenomene physiologique qui entraine une reponse anti-inflammatoire compensatrice (CARS) afin de permettre un retour a l’homeostasie et d’eviter un syndrome de defaillance multiviscerale. Cette CARS met en jeu les systemes sympathique, parasympathique et hypothalamohypophysaire. Ces trois systemes entretiennent une reponse anti-inflammatoire en lien etroit avec les cellules de l’immunite innee via des mecanismes neurohormonaux. Au niveau cellulaire, cela se traduit par une paralysie de fonctions des cellules presentatrices de l’antigene (cellules dendritiques, monocytes), ainsi que des cellules lymphoides effectrices (lymphocytes T et NK). Lorsque cette reponse compensatrice est exacerbee et se prolonge dans le temps, elle induit un etat d’immunodepression favorisant la survenue d’infections secondaires. Plusieurs axes des traitements ont ete envisages afin de permettre le retour rapide a l’homeostasie immunitaire et d’eviter ces infections secondaires. Pour les patients souffrant de traumatismes crâniens graves, la corticotherapie a faible dose est une piste interessante, car elle agit non seulement en diminuant la CARS par un effet anti-inflammatoire, mais egalement en permettant la stimulation de la reponse immunitaire innee, en restaurant notamment les fonctions pro-inflammatoires des cellules effectrices, ainsi qu’en rendant leur role central de presentation de l’antigene aux cellules dendritiques.

Spinal cord injury (SCI) is a major cause of severe disability. This study aims to assess the effectiveness of a quality improvement program on neurological recovery after SCI. Before-after study during two phases was done in one intensive care unit in a university hospital. The quality improvement project comprised protective mechanical ventilation, early tracheostomy in anatomical injury above the sixth cervical vertebra, early enteral nutrition, early mobilization, and active perineal care in adult SCI patients. The primary endpoint was the difference between the American Spinal Injury Association (ASIA) motor score between discharge and intensive care unit (ICU) admission (Delta ASIA). Fifty-seven and 60 patients were included in the control and in the intervention period respectively. The ASIA motor score upon ICU admission was 16 (7-37) before and 11 (2-30) after the implementation (

Background To propose a combination of blood biomarkers for the prediction of hospital-acquired pneumonia (HAP) and for the selection of traumatic brain-injured (TBI) patients eligible for corticosteroid therapy for the prevention of HAP. Methods This was a sub-study of the CORTI-TC trial, a multicenter, randomized, double-blind, controlled trial evaluating the risk of HAP at day 28 in 336 TBI patients treated or not with corticosteroid therapy. Patients were between 15 and 65 years with severe traumatic brain injury (Glasgow coma scale score ≤ 8 and trauma-associated lesion on brain CT scan) and were enrolled within 24 h of trauma. The blood levels of CRP and cortisoltotal&free, as a surrogate marker of the pro/anti-inflammatory response balance, were measured in samples collected before the treatment initiation. Endpoint was HAP on day 28. Results Of the 179 patients with available samples, 89 (49.7%) developed an HAP. Cortisoltotal&free and CRP blood levels upon ICU admission were not significantly different between patients with or without HAP. The cortisoltotal/CRP ratio upon admission was 2.30 [1.25–3.91] in patients without HAP and 3.36 [1.74–5.09] in patients with HAP (p = 0.021). In multivariate analysis, a cortisoltotal/CRP ratio > 3, selected upon the best Youden index on the ROC curve, was independently associated with HAP (OR 2.50, CI95% [1.34–4.64] p = 0.004). The HR for HAP with corticosteroid treatment was 0.59 (CI95% [0.34–1.00], p = 0.005) in patients with a cortisoltotal/CRP ratio > 3, and 0.89 (CI95% [0.49–1.64], p = 0.85) in patients with a ratio Conclusion A cortisoltotal/CRP ratio > 3 upon admission may predict the development of HAP in severe TBI. Among these patients, corticosteroids reduce the occurrence HAP. We suggest that this ratio may select the patients who may benefit from corticosteroid therapy for the prevention of HAP.

Background. Stress cardiomyopathy is common after subarachnoid haemorrhage but has been scarcely described after traumatic brain injury. Methods. Mono-centric longitudinal study in moderate to severe traumatic brain injury (Glasgow coma score ≤ 12). Evaluation of global longitudinal strain and 2-dimension trans-thoracic echography at day-1, day-3 and day-7. The primary outcome was the incidence of stress cardiomyopathy assessed with global longitudinal strain. Secondary outcomes were the relationship between global longitudinal strain and mortality, plasma levels of metanephrine and normetanephrine in patients with traumatic brain injury and subarachnoid haemorrhage to explore the mechanisms of stress cardiomyopathy. Results. We included 100 patients from March 2014 to August 2017. Twenty (20%) patients died in the intensive care unit. At day 1, global longitudinal strain (-20.3(±3.6)%) and left ventricular ejection fraction (65.9 (±10.8)%) were preserved. Nine (9%) patients displayed impaired global longitudinal strain (-13.3[-14.5/-11.6]%) at baseline, with significant improvement at day-3 and day-7 (p

In the early phase following severe brain injury (BI), mechanical ventilation (MV) is often needed to prevent airway from aspiration, control PaCO2 and PaO2 and avoid secondary brain insults. Although patients with BI are frequently hospitalized in the intensive care unit (ICU) without respiratory problems, they display longer durations of MV and a challenging weaning process compared to other ICU populations. Historically, the MV settings of BI patients associated high tidal volume with low or no positive end-expiratory pressure (PEEP), for neurological reasons. The extensive data about the beneficial effects of protective ventilation in patients without acute respiratory distress syndrome, have questioned the consequences of such management in BI patients. Recent studies suggest that protective ventilation is safe and could even bear significant impact on morbidity in these patients. The MV weaning process is also challenging, since these patients display a high rate of extubation failure. Recently, new clinical scales of successful extubation have been highlighted combining airway and neurologic operators. A minimal level of arousal should be achieved before extubation, but the Glasgow Coma Score has been inconsistently associated with successful extubation, probably owing to the challenging quantification in intubated patients. Early tracheostomy seems to bear positive effects on morbidity in BI patients. Nonetheless the level of evidence remains poor and no strong recommendations can be made on this topic. Overall, the respiratory bundle of care in BI patients could be readapted with the new data available in the literature. Even if they bear positive impact on morbidity in ICU, their consequences on neurological recovery have yet to be adequately assessed.