Diaphragm Dysfunction Predicts Weaning Outcome after Bilateral Lung Transplant.

BACKGROUND: Diaphragm dysfunction and its effects on outcomes of ventilator weaning have been evaluated in mixed critical care populations using diaphragm thickening fraction (the ratio of the difference between ultrasound diaphragm thickness at end-inspiration and end-expiration to diaphragm thickness at end-expiration) or neuroventilatory efficiency (the ratio of tidal volume and peak electrical activity of the diaphragm). Such data are not available in bilateral-lung transplant recipients. The authors hypothesized that (1) diaphragm dysfunction, as defined by a diaphragm thickening fraction less than 29%, is more likely to occur in difficult weaning; (2) diaphragm thickening fraction and neuroventilatory efficiency predict weaning outcome; and (3) duration of mechanical ventilation before the first spontaneous breathing trial is associated with diaphragm dysfunction. METHODS: Adult bilateral-lung transplant patients admitted to the intensive care unit were screened at the time of the first spontaneous breathing trial (pressure-support of 5 cm H2O and 0 positive end-expiratory pressure). At the fifth minute, diaphragm thickening fraction and neuroventilatory efficiency were measured during three respiratory cycles. Weaning was classified as simple, difficult, or prolonged (successful extubation at the first spontaneous breathing trial, within three or after three spontaneous breathing trials, respectively). RESULTS: Forty-four subjects were enrolled. Diaphragm dysfunction occurred in 14 subjects (32%), all of whom had difficult weaning (78% of the subgroup of 18 patients experiencing difficult weaning). Both diaphragm thickening fraction (24 [20 to 29] vs. 39 [35 to 45]%) and neuroventilatory efficiency (34 [26 to 45] vs. 55 [43 to 62] ml/µV) were lower in difficult weaning (both P < 0.001). The areas under the receiver operator curve predicting difficult weaning were 0.88 (95% CI, 0.73 to 0.99) for diaphragm thickening fraction and 0.85 (95% CI, 0.71 to 0.95) for neuroventilatory efficiency. The duration of ventilation demonstrated a linear inverse correlation with both diaphragm thickening fraction and neuroventilatory efficiency. CONCLUSIONS: Diaphragm dysfunction is common after bilateral-lung transplantation and associated with difficult weaning. In such patients, average values for diaphragm thickening fraction and neuroventilatory efficiency were reduced compared to patients with simple weaning. Both parameters showed similar accuracy for predicting success of ventilator weaning, demonstrating an inverse relationship with duration of ventilation.

Gram-negative bacterial colonizations before bilateral lung transplant. The impact of 'targeted' versus 'standard' surgical prophylaxis.

BACKGROUND: Infections are one of the most common causes of death after lung transplant (LT). However, the benefit of 'targeted' prophylaxis in LT recipients pre-colonized by Gram-negative (GN) bacteria is still unclear. METHODS: All consecutive bilateral LT recipients admitted to the Intensive Care Unit of the University Hospital of Padua (February 2016-2023) were retrospectively screened. Only patients with pre-existing GN bacterial isolations were enrolled and analyzed according to the antimicrobial surgical prophylaxis ('standard' vs. 'targeted' on the preoperative bacterial isolation). RESULTS: One hundred eighty-one LT recipients were screened, 46 enrolled. Twenty-two (48%) recipients were exposed to 'targeted' prophylaxis, while 24 (52%) to 'standard' prophylaxis. Overall prevalence of postoperative multi-drug resistant (MDR) GN bacteria isolation was 65%, with no differences between the two surgical prophylaxis (p = 0.364). Eleven (79%) patients treated with 'standard' prophylaxis and twelve (75%) with 'targeted' therapy reconfirmed the preoperative GN pathogen (p = 0.999). The prevalence of postoperative infections due to MDR GN bacteria was 50%. Of these recipients, 4 belonged to the 'standard' and 11 to the 'targeted' prophylaxis (p = 0.027). CONCLUSIONS: The administration of a 'targeted' prophylaxis in LT pre-colonized recipients seemed not to prevent the occurrence of postoperative MDR GN infections.

Effects of non-invasive respiratory support in post-operative patients: a systematic review and network meta-analysis.

BACKGROUND: Re-intubation secondary to post-extubation respiratory failure in post-operative patients is associated with increased patient morbidity and mortality. Non-invasive respiratory support (NRS) alternative to conventional oxygen therapy (COT), i.e., high-flow nasal oxygen, continuous positive airway pressure, and non-invasive ventilation (NIV), has been proposed to prevent or treat post-extubation respiratory failure. Aim of the present study is assessing the effects of NRS application, compared to COT, on the re-intubation rate (primary outcome), and time to re-intubation, incidence of nosocomial pneumonia, patient discomfort, intensive care unit (ICU) and hospital length of stay, and mortality (secondary outcomes) in adult patients extubated after surgery. METHODS: A systematic review and network meta-analysis of randomized and non-randomized controlled trials. A search from Medline, Embase, Scopus, Cochrane Central Register of Controlled Trials, and Web of Science from inception until February 2, 2024 was performed. RESULTS: Thirty-three studies (11,292 patients) were included. Among all NRS modalities, only NIV reduced the re-intubation rate, compared to COT (odds ratio 0.49, 95% confidence interval 0.28; 0.87, p = 0.015, I2 = 60.5%, low certainty of evidence). In particular, this effect was observed in patients receiving NIV for treatment, while not for prevention, of post-extubation respiratory failure, and in patients at high, while not low, risk of post-extubation respiratory failure. NIV reduced the rate of nosocomial pneumonia, ICU length of stay, and ICU, hospital, and long-term mortality, while not worsening patient discomfort. CONCLUSIONS: In post-operative patients receiving NRS after extubation, NIV reduced the rate of re-intubation, compared to COT, when used for treatment of post-extubation respiratory failure and in patients at high risk of post-extubation respiratory failure.

Asymmetrical high-flow nasal cannula performs similarly to standard interface in patients with acute hypoxemic post-extubation respiratory failure: a pilot study.

BACKGROUND: Standard high-flow nasal cannula (HFNC) is a respiratory support device widely used to manage post-extubation hypoxemic acute respiratory failure (hARF) due to greater comfort, oxygenation, alveolar recruitment, humidification, and reduction of dead space, as compared to conventional oxygen therapy. On the contrary, the effects of the new asymmetrical HFNC interface (Optiflow® Duet system (Fisher & Paykel, Healthcare, Auckland, New Zealand) is still under discussion. Our aim is investigating whether the use of asymmetrical HFNC interface presents any relevant difference, compared with the standard configuration, on lung aeration (as assessed by end-expiratory lung impedance (EELI) measured by electrical impedance tomography (EIT)), diaphragm ultrasound thickening fraction (TFdi) and excursion (DE), ventilatory efficiency (estimated by corrected minute ventilation (MV)), gas exchange, dyspnea, and comfort. METHODS: Pilot physiological crossover randomized controlled study enrolling 20 adults admitted to the Intensive Care unit, invasively ventilated for at least 24 h, and developing post-extubation hARF, i.e., PaO2/set FiO2 < 300 mmHg during Venturi mask (VM) within 120 min after extubation. Each HFNC configuration was applied in a randomized 60 min sequence at a flow rate of 60 L/min. RESULTS: Global EELI, TFdi, DE, ventilatory efficiency, gas exchange and dyspnea were not significantly different, while comfort was greater during asymmetrical HFNC support, as compared to standard interface (10 [7-10] and 8 [7-9], p-value 0.044). CONCLUSIONS: In post-extubation hARF, the use of the asymmetrical HFNC, as compared to standard HFNC interface, slightly improved patient comfort without affecting lung aeration, diaphragm activity, ventilatory efficiency, dyspnea and gas exchange. CLINICAL TRIAL NUMBER: ClinicalTrial.gov. REGISTRATION NUMBER: NCT05838326 (01/05/2023). NEW & NOTEWORTHY: The asymmetrical high-flow nasal cannula oxygen therapy (Optiflow® Duet system (Fisher & Paykel, Healthcare, Auckland, New Zealand) provides greater comfort as compared to standard interface; while their performance in term of lung aeration, diaphragm activity, ventilatory efficiency, dyspnea, and gas exchange is similar.

Comprehensive bronchoalveolar lavage characterization in COVID-19 associated acute respiratory distress syndrome patients: a prospective cohort study.

COVID-19-related acute respiratory distress syndrome (CARDS) is associated with high mortality rates. We still have limited knowledge of the complex alterations developing in the lung microenvironment. The goal of the present study was to comprehensively analyze the cellular components, inflammatory signature, and respiratory pathogens in bronchoalveolar lavage (BAL) of CARDS patients (16) in comparison to those of other invasively mechanically ventilated patients (24). In CARDS patients, BAL analysis revealed: SARS-CoV-2 infection frequently associated with other respiratory pathogens, significantly higher neutrophil granulocyte percentage, remarkably low interferon-gamma expression, and high levels of interleukins (IL)-1ß and IL-9. The most important predictive variables for worse outcomes were age, IL-18 expression, and BAL neutrophilia. To the best of our knowledge, this is the first study that was able to identify, through a comprehensive analysis of BAL, several aspects relevant to the complex pathophysiology of CARDS.

High-Flow Nasal Oxygen for Severe Hypoxemia: Oxygenation Response and Outcome in Patients with COVID-19.

Rationale: The "Berlin definition" of acute respiratory distress syndrome (ARDS) does not allow inclusion of patients receiving high-flow nasal oxygen (HFNO). However, several articles have proposed that criteria for defining ARDS should be broadened to allow inclusion of patients receiving HFNO. Objectives: To compare the proportion of patients fulfilling ARDS criteria during HFNO and soon after intubation, and 28-day mortality between patients treated exclusively with HFNO and patients transitioned from HFNO to invasive mechanical ventilation (IMV). Methods: From previously published studies, we analyzed patients with coronavirus disease (COVID-19) who had PaO2/FiO2 of ⩽300 while treated with ⩾40 L/min HFNO, or noninvasive ventilation (NIV) with positive end-expiratory pressure of ⩾5 cm H2O (comparator). In patients transitioned from HFNO/NIV to invasive mechanical ventilation (IMV), we compared ARDS severity during HFNO/NIV and soon after IMV. We compared 28-day mortality in patients treated exclusively with HFNO/NIV versus patients transitioned to IMV. Measurements and Main Results: We analyzed 184 and 131 patients receiving HFNO or NIV, respectively. A total of 112 HFNO and 69 NIV patients transitioned to IMV. Of those, 104 (92.9%) patients on HFNO and 66 (95.7%) on NIV continued to have PaO2/FiO2 ⩽300 under IMV. Twenty-eight-day mortality in patients who remained on HFNO was 4.2% (3/72), whereas in patients transitioned from HFNO to IMV, it was 28.6% (32/112) (P < 0.001). Twenty-eight-day mortality in patients who remained on NIV was 1.6% (1/62), whereas in patients who transitioned from NIV to IMV, it was 44.9% (31/69) (P < 0.001). Overall mortality was 19.0% (35/184) and 24.4% (32/131) for HFNO and NIV, respectively (P = 0.2479). Conclusions: Broadening the ARDS definition to include patients on HFNO with PaO2/FiO2 ⩽300 may identify patients at earlier stages of disease but with lower mortality.

General anesthesia or conscious sedation for thrombectomy in stroke patients: an updated systematic review and meta-analysis.

PURPOSE: Endovascular treatment for stroke patients usually requires anesthesia care, with no current consensus on the best anesthetic management strategy. Several randomized controlled trials and meta-analyses have attempted to address this. In 2022, additional evidence from three new trials was published: the GASS trial, the CANVAS II trial, and preliminary results from the AMETIS trial, prompting the execution of this updated systematic review and meta-analysis. The primary objective of this study was to evaluate the effects of general anesthesia and conscious sedation on functional outcomes measured with the modified Rankin scale (mRS) at three months. METHODS: We performed a systematic review and meta-analysis of randomized controlled trials investigating conscious sedation and general anesthesia in endovascular treatment. The following databases were examined: PubMed, Scopus, Embase, and the Cochrane Database of Randomized Controlled Trials and Systematic Reviews. The Risk of Bias 2 tool was used to assess bias. In addition, trial sequence analysis was performed on the primary outcome to estimate if the cumulative effect is significant enough to be unaffected by further studies. RESULTS: Nine randomized controlled trials were identified, including 1,342 patients undergoing endovascular treatment for stroke. No significant differences were detected between general anesthesia and conscious sedation with regards to mRS, functional independence (mRS, 0-2), procedure duration, onset to reperfusion, mortality, hospital length of stay, and intensive care unit length of stay. Patients treated under general anesthesia may have more frequent successful reperfusion, though the time from groin to reperfusion was slightly longer. Trial sequential analysis showed that additional trials are unlikely to show marked differences in mean mRS at three months. CONCLUSIONS: In this updated systematic review and meta-analysis, the choice of anesthetic strategy for endovascular treatment of stroke patients did not significantly impact functional outcome as measured with the mRS at three months. Patients managed with general anesthesia may have more frequent successful reperfusion. TRIAL REGISTRATION: PROSPERO (CRD42022319368); registered 19 April 2022.

RéSUMé: OBJECTIF: Le traitement endovasculaire pour les patient·es victimes d'un accident vasculaire cérébral (AVC) nécessite généralement des soins d'anesthésie, mais il n'existe actuellement aucun consensus sur la meilleure stratégie de prise en charge anesthésique. Plusieurs études randomisées contrôlées et méta-analyses ont tenté d'aborder cette question. En 2022, des données probantes supplémentaires provenant de trois nouvelles études ont été publiées : l'étude GASS, l'étude CANVAS II et les résultats préliminaires de l'étude AMETIS, ce qui a motivé la réalisation de cette revue systématique et méta-analyse mises à jour. L'objectif principal de cette étude était d'évaluer les effets de l'anesthésie générale et de la sédation consciente sur les devenirs fonctionnels mesurés avec l'échelle de Rankin modifiée (mRS) à trois mois. MéTHODE: Nous avons réalisé une revue systématique avec méta-analyse d'études randomisées contrôlées portant sur la sédation consciente et l'anesthésie générale dans le traitement endovasculaire. Les bases de données suivantes ont été examinées : PubMed, Scopus, Embase et la base de données Cochrane des études randomisées contrôlées et des revues systématiques. L'outil Risque de biais 2 a été utilisé pour évaluer le biais. De plus, une analyse séquentielle des études a été effectuée sur le critère d'évaluation principal afin d'estimer si l'effet cumulatif était suffisamment significatif pour ne pas être affecté par d'autres études. RéSULTATS: Neuf études randomisées contrôlées ont été identifiées, incluant 1342 patient·es bénéficiant d'un traitement endovasculaire pour un AVC. Aucune différence significative n'a été détectée entre l'anesthésie générale et la sédation consciente en ce qui concerne la mRS, l'indépendance fonctionnelle (mRS, 0-2), la durée de l'intervention, le moment d'apparition de la reperfusion, la mortalité, la durée de séjour à l'hôpital et la durée de séjour en unité de soins intensifs. Les patient·es traité·es sous anesthésie générale pourraient avoir une reperfusion réussie plus fréquente, bien que le temps entre l'aine et la reperfusion était légèrement plus long. L'analyse séquentielle des études a montré qu'il est peu probable que d'autres études montrent des différences marquées dans la mRS moyenne à trois mois. CONCLUSION: Dans cette revue systématique et méta-analyse mises à jour, le choix de la stratégie anesthésique pour le traitement endovasculaire des personnes victimes d'un AVC n'a pas eu d'impact significatif sur les devenirs fonctionnels mesurés avec la mRS à trois mois. La réussite de la reperfusion pourrait être plus fréquente chez les patient·es pris·es en charge par anesthésie générale. ENREGISTREMENT DE L'éTUDE: PROSPERO (CRD42022319368); enregistrée le 19 avril 2022.

Radiomics of spinal muscles: toward a radiological biomarker for allograft rejection in lung transplant.

PURPOSE: To assess the role of muscle composition and radiomics in predicting allograft rejection in lung transplant. MATERIAL AND METHODS: The last available HRCT before surgery of lung transplant candidates referring to our tertiary center from January 2010 to February 2020 was retrospectively examined. Only scans with B30 kernel reconstructions and 1 mm slice thickness were included. One radiologist segmented the spinal muscles of each patient at the level of the 11th dorsal vertebra by an open-source software. The same software was used to extract Hu values and 72 radiomic features of first and second order. Factor analysis was applied to select highly correlating features and then their prognostic value for allograft rejection was investigated by logistic regression analysis (level of significance p < 0.05). In case of significant results, the diagnostic value of the model was computed by ROC curves. RESULTS: Overall 200 patients had a HRCT prior to the transplant but only 97 matched the inclusion criteria (29 women; mean age 50.4 ± 13 years old). Twenty-one patients showed allograft rejection. The following features were selected by the factor analysis: cluster prominence, Imc2, gray level non-uniformity normalized, median, kurtosis, gray level non-uniformity, and inverse variance. The radiomic-based model including also Hu demonstrated that only the feature Imc2 acts as a predictor of allograft rejection (p = 0.021). The model showed 76.6% accuracy and the Imc2 value of 0.19 demonstrated 81% sensitivity and 64.5% specificity in predicting lung transplant rejection. CONCLUSION: The radiomic feature Imc2 demonstrated to be a predictor of allograft rejection in lung transplant.

Multidrug-resistant organisms in lung transplant: a narrative review.

PURPOSE OF REVIEW: The purpose of this narrative review is presenting the current knowledge of multidrug-resistant (MDR) pathogens in lung transplant recipients, considering both Gram-positive and Gram-negative bacteria. RECENT FINDINGS: Overall prevalence of Gram-negative pathogens has increased remarkably (4.33/1000 recipient-days) in solid organ transplant recipients, while the prevalence of Gram-positive bacteria seems to be decreasing (0.20 cases/100 transplant-years). In lung transplant, the prevalence of postoperative infections due to MDR-GN bacteria has been assessed between 31 and 57%, and the incidence of carbapenem-resistant Enterobacterales is between 0.4 and 20%, with a related mortality up to 70%. MDR Pseudomonas aeruginosa is common in lung transplant recipients with cystic fibrosis and may contribute to bronchiolitis obliterans syndrome. The prevalence of MDR Gram-positive bacteria is around 30% (predominantly Methicillin-resistant Staphylococcus aureus and Coagulase-negative staphylococcus). SUMMARY: Survival after lung transplant, although lower than in other SOT, is increasing and currently at 60% at 5 years. This review highlights the potential clinical and social burden of postoperative infections in lung transplant recipients, and confirmed that a PI due to MDR bacteria negatively affects survival. A prompt diagnosis, prevention and management of these MDR pathogens should remain the cornerstone for higher goals of care.

Early Physiologic Effects of Prone Positioning in COVID-19 Acute Respiratory Distress Syndrome.

BACKGROUND: The mechanisms underlying oxygenation improvement after prone positioning in COVID-19 acute respiratory distress syndrome have not been fully elucidated yet. The authors hypothesized that the oxygenation increase with prone positioning is secondary to the improvement of ventilation-perfusion matching. METHODS: In a series of consecutive intubated COVID-19 acute respiratory distress syndrome patients receiving volume-controlled ventilation, the authors prospectively assessed the percent variation of ventilation-perfusion matching by electrical impedance tomography before and 90 min after the first cycle of prone positioning (primary endpoint). The authors also assessed changes in the distribution and homogeneity of lung ventilation and perfusion, lung overdistention and collapse, respiratory system compliance, driving pressure, optimal positive end-expiratory pressure, as assessed by electrical impedance tomography, and the ratio of partial pressure to fraction of inspired oxygen (Pao2/Fio2; secondary endpoints). Data are reported as medians [25th to 75th] or percentages. RESULTS: The authors enrolled 30 consecutive patients, all analyzed without missing data. Compared to the supine position, prone positioning overall improved ventilation-perfusion matching from 58% [43 to 69%] to 68% [56 to 75%] (P = 0.042), with a median difference of 8.0% (95% CI, 0.1 to 16.0%). Dorsal ventilation increased from 39% [31 to 43%] to 52% [44 to 62%] (P < 0.001), while dorsal perfusion did not significantly vary. Prone positioning also reduced lung overdistension from 9% [4 to 11%] to 4% [2 to 6%] (P = 0.025), while it did not significantly affect ventilation and perfusion homogeneity, lung collapse, static respiratory system compliance, driving pressure, and optimal positive end-expiratory pressure. Pao2/Fio2 overall improved from 141 [104 to 182] mmHg to 235 [164 to 267] mmHg (P = 0.019). However, 9 (30%) patients were nonresponders, experiencing an increase in Pao2/Fio2 less than 20% with respect to baseline. CONCLUSIONS: In COVID-19 acute respiratory distress syndrome patients, prone positioning overall produced an early increase in ventilation-perfusion matching and dorsal ventilation. These effects were, however, heterogeneous among patients.

Inappropriate Citation of Retracted Articles in Anesthesiology and Intensive Care Medicine Publications.

BACKGROUND: Retracted articles represent research withdrawn from the existing body of literature after publication. Research articles may be retracted for several reasons ranging from honest errors to intentional misconduct. They should not be used as reliable sources, and it is unclear why they are cited occasionally by other articles. This study hypothesized that several mechanisms may contribute to citing retracted literature and aimed to analyze the characteristics of articles citing retracted literature in anesthesiology and critical care. METHODS: Using the Retraction Watch database, we retrieved retracted articles on anesthesiology and intensive care medicine up to August 16, 2021, and identified the papers citing these retracted articles. A survey designed to investigate the reasons for citing these articles was sent to the corresponding authors of the citing papers. RESULTS: We identified 478 retracted articles, 220 (46%) of which were cited at least once. We contacted 1297 corresponding authors of the papers that cited these articles, 417 (30%) of whom responded to our survey and were included in the final analysis. The median number of authors in the analyzed articles was five, and the median elapsed time from retraction to citation was 3 yr. Most of the corresponding authors (372, 89%) were unaware of the retracted status of the cited article, mainly because of inadequate notification of the retraction status in journals and/or databases and the use of stored copies. CONCLUSIONS: The corresponding authors were generally unaware of the retraction of the cited article, usually because of inadequate identification of the retracted status in journals and/or web databases and the use of stored copies. Awareness of this phenomenon and rigorous control of the cited references before submitting a paper are of fundamental importance in research.

Machine learning-based analysis of alveolar and vascular injury in SARS-CoV-2 acute respiratory failure.

Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) pneumopathy is characterized by a complex clinical picture and heterogeneous pathological lesions, both involving alveolar and vascular components. The severity and distribution of morphological lesions associated with SARS-CoV-2 and how they relate to clinical, laboratory, and radiological data have not yet been studied systematically. The main goals of the present study were to objectively identify pathological phenotypes and factors that, in addition to SARS-CoV-2, may influence their occurrence. Lungs from 26 patients who died from SARS-CoV-2 acute respiratory failure were comprehensively analysed. Robust machine learning techniques were implemented to obtain a global pathological score to distinguish phenotypes with prevalent vascular or alveolar injury. The score was then analysed to assess its possible correlation with clinical, laboratory, radiological, and tissue viral data. Furthermore, an exploratory random forest algorithm was developed to identify the most discriminative clinical characteristics at hospital admission that might predict pathological phenotypes of SARS-CoV-2. Vascular injury phenotype was observed in most cases being consistently present as pure form or in combination with alveolar injury. Phenotypes with more severe alveolar injury showed significantly more frequent tracheal intubation; longer invasive mechanical ventilation, illness duration, intensive care unit or hospital ward stay; and lower tissue viral quantity (p < 0.001). Furthermore, in this phenotype, superimposed infections, tumours, and aspiration pneumonia were also more frequent (p < 0.001). Random forest algorithm identified some clinical features at admission (body mass index, white blood cells, D-dimer, lymphocyte and platelet counts, fever, respiratory rate, and PaCO2 ) to stratify patients into different clinical clusters and potential pathological phenotypes (a web-app for score assessment has also been developed; https://r-ubesp.dctv.unipd.it/shiny/AVI-Score/). In SARS-CoV-2 positive patients, alveolar injury is often associated with other factors in addition to viral infection. Identifying phenotypical patterns at admission may enable a better stratification of patients, ultimately favouring the most appropriate management. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Extensively drug-resistant and multidrug-resistant gram-negative pathogens in the neurocritical intensive care unit.

BACKGROUND: Abrupt increase of multidrug-resistant, extensively drug-resistant, and pandrug-resistant bacteria may complicate the course, management, and costs of neurocritical patients and is associated with high morbidity and mortality rates. No data exists regarding risk factors for colonization by gram-negative pathogens in neurocritical patients. The aim of the study was to identify risk factors associated with colonization by multidrug-resistant, extensively drug-resistant, and pandrug-resistant gram-negative bacteria in neurocritical patients. METHODS: We conducted a retrospective cohort study in a neurointensive care unit over a period of 3 years. We included adult neurocritical patients admitted for more than 48 h. We analyzed several factors including both anamnestic factors and admission diagnosis. RESULTS: Four hundred twenty neurocritical patients were retrospectively enrolled. Seventy-three patients developed colonization by multidrug-resistant and 53 by extensively drug-resistant gram negative pathogens. Logistic regression identified intensive care unit length of stay (LOS) as the strongest predictor for both multidrug-resistant (AUC 0.877; 95% CI 0.841-0.913) and extensively drug-resistant (AUC 0.839 0.787-0.892) gram negative pathogens. In addition, external ventricular drainage and intracerebral pressure monitoring catheter were risk factors for XDR. Survival analysis revealed that MDR bacteria colonization happens earlier (log-rank test p = 0.017). CONCLUSIONS: Optimization of healthcare strategies is required in order to reduce patients' length of stay to prevent multi- and extensively-drug gram-negative colonizations. Indeed, an early external ventricular drainage and intracerebral pressure monitoring catheter removal is deemed necessary as soon as clinically appropriate.

A Comparison Between Enteral and Intravenous Nimodipine in Subarachnoid Hemorrhage: A Systematic Review and Network Meta-Analysis.

Our objective was to compare the effectiveness of intravenous and enteral nimodipine in preventing poor outcome from delayed cerebral ischemia in patients with subarachnoid hemorrhage. We performed a systematic search and a network meta-analysis using the following databases: PubMed, Scopus, the Cochrane Central Register of Controlled Trials, and Google Scholar. Risk of Bias 2 tool was used to assess risk of bias of included studies. A ranking among methods was performed on the basis of the frequentist analog of the surface under the cumulative ranking curve. Published studies that met the following population, intervention, comparison, outcomes and study (PICOS) criteria were included: patients with subarachnoid hemorrhage aged 15 years or older (P); nimodipine, intravenous and oral formulation (I); placebo or no intervention (C); poor outcome measured at 3 months (defined as death, vegetative state, or severe disability), case fatality at 3 months, delayed cerebral ischemia, delayed ischaemic neurologic deficit, and vasospasm measured with transcranial Doppler or digital subtraction angiography (O); and randomized controlled trials (S). No language or publication date restrictions were applied. Ten studies were finally included, with a total of 1527 randomly assigned patients. Oral and intravenous nimodipine were both effective in preventing poor outcome, delayed cerebral ischemia, and delayed ischaemic neurological deficit. Neither treatment was effective in improving case fatality. Evolving clinical protocols over a 30-year period and the risk of bias of the included studies may limit the strength of our results. Enteral and intravenous nimodipine may have a similar effectiveness in terms of preventing poor outcome, delayed cerebral ischemia, and delayed ischaemic neurological deficit. More research may be needed to fully establish the role of intravenous nimodipine in current clinical practice.

Single-injection regional analgesia techniques for mastectomy surgery: A network meta-analysis.

BACKGROUND: Patients undergoing mastectomy surgery experience severe postoperative pain. Several regional techniques have been developed to reduce pain intensity but it is unclear, which of these techniques is most effective. OBJECTIVES: To synthesise direct and indirect comparisons for the relative efficacy of different regional and local analgesia techniques in the setting of unilateral mastectomy. Postoperative opioid consumption at 24 h, postoperative pain at extubation, 1, 12 and 24 h, postoperative nausea and vomiting were collected. DESIGN: Systematic review with network meta-analysis (PROSPERO:CRD42021250651). DATA SOURCE: PubMed, Scopus, the Cochrane Central Register of Controlled Trials (from inception until 7 July 2021). ELIGIBILITY CRITERIA: All randomised controlled trials investigating single-injection regional and local analgesia techniques in adult patients undergoing unilateral mastectomy were included in our study without any language or publication date restriction. RESULTS: Sixty-two included studies randomising 4074 patients and investigating nine techniques entered the analysis. All techniques were associated with less opioid consumption compared with controls The greatest mean difference [95% confidence interval (CI)] was associated with deep serratus anterior plane block: mean difference -16.1 mg (95% CI, -20.7 to -11.6). The greatest reduction in pain score was associated with the interpectoral-pecto-serratus plane block (mean difference -1.3, 95% CI, -1.6 to - 1) at 12 h postoperatively, and with superficial serratus anterior plane block (mean difference -1.4, 95% CI, -2.4 to -0.5) at 24 h. Interpectoral-pectoserratus plane block resulted in the greatest statistically significant reduction in postoperative nausea/vomiting when compared with placebo/no intervention with an OR of 0.23 (95% CI, 0.13 to 0.40). CONCLUSION: All techniques were associated with superior analgesia and less opioid consumption compared with controls. No single technique was identified as superior to others. In comparison, local anaesthetic infiltration does not offer advantages over multimodal analgesia alone. TRIAL REGISTRATION: PROSPERO (CRD4202125065).

A practical guide to patient position and complication management in neurosurgery: a systematic qualitative review.

PURPOSE: Adequate patient positioning is of paramount importance in neurosurgery. Complications related to the position are common and make up for more than 16% of the claims towards anaesthesiologists and neurosurgeons. This paper aims to provide the anaesthesiologist with a practical guide to avoid common pitfalls related to the patient positioning process. METHOD: We performed a systematic review of the medical literature for the identification, screening, and inclusion of articles. The bibliographic search was conducted on June 1st, 2021 by two of the authors. In this review, we included articles indexed by MEDLINE, Cochrane Library, or Google Scholar. RESULTS: We retrieved a total of 5706 unique papers from our initial search. However, after the initial screening, 5363 papers were removed is not related to our research leaving a total of 343 papers. We examined the full text of all the 343 articles including 68 of them in the final qualitative analysis. DISCUSSION: In this review we examine the most common neurosurgical positions: supine, sitting, lateral, park-bench, prone, jack-knife, and knee-chest. For each of them, the proper positioning and related complications are described. Particular attention is given to the prevention and management of these complications, providing a practical guide for clinicians.

Thrombin generation in patients with COVID-19 with and without thromboprophylaxis.

OBJECTIVES: Thrombin generation (TG) with and without thrombomodulin (TM) was evaluated in COVID-19 patients with different disease severity and thromboprophylaxis regimen, in order to understand the prothrombotic profile. METHODS: We enrolled consecutive patients with confirmed diagnosis of COVID-19 admitted to Medical Departments (MD) or Intensive Care Units (ICU), and 54 healthy controls. RESULTS: Eighty-nine patients were included (mean age 60.4±16.1 years, 68.5% male); 33.7% admitted to ICU. Twenty-four patients (26.9%) were enrolled before thromboprophylaxis administration; 45 patients (50.6%) received standard and 20 (22.5%) intermediate sub-therapeutic dose thromboprophylaxis. Overall, patients with COVID-19 showed a TG profile comparable to that of healthy subjects (i.e. comparable peak height, endogenous thrombin potential [ETP] with and without TM). The only exception was lag time and time to peak, prolonged in COVID-19 patients vs. controls. MD patients showed a similar TG profile to healthy controls, and ICU patients showed significantly decrease ETP (p=0.030) compared to MD. As for thromboprophylaxis, TG profile was significantly increased in COVID-19 patients without thromboprophylaxis vs. controls and vs. those with thromboprophylaxis. In this latter group, ETP inhibition was significantly decreased (p=0.0003) and positively correlated with anti-Xa activity (r=0.49, p=0.0017). However, patients with thromboprophylaxis had similar TG profile vs. controls. Intermediate dose thromboprophylaxis more effectively inhibited TG in severe COVID-19 patients by increasing ETP inhibition via ETP with TM reduction vs. standard dose. CONCLUSIONS: COVID-19 patients showed increased TG at diagnosis. Standard thromboprophylaxis reduced TG to levels of healthy controls. Intermediate sub-therapeutic thromboprophylaxis more effectively inhibited TG by decreasing ETP with TM.

Higher versus lower positive end-expiratory pressure in patients without acute respiratory distress syndrome: a meta-analysis of randomized controlled trials.

BACKGROUND: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to assess the association of higher positive end-expiratory pressure (PEEP), as opposed to lower PEEP, with hospital mortality in adult intensive care unit (ICU) patients undergoing invasive mechanical ventilation for reasons other than acute respiratory distress syndrome (ARDS). METHODS: We performed an electronic search of MEDLINE, EMBASE, Scopus, Cochrane Central Register of Controlled Trials, CINAHL, and Web of Science from inception until June 16, 2021 with no language restrictions. In addition, a research-in-progress database and grey literature were searched. RESULTS: We identified 22 RCTs (2225 patients) comparing higher PEEP (1007 patients) with lower PEEP (991 patients). No statistically significant association between higher PEEP and hospital mortality was observed (risk ratio 1.02, 95% confidence interval 0.89-1.16; I2 = 0%, p = 0.62; low certainty of evidence). Among secondary outcomes, higher PEEP was associated with better oxygenation, higher respiratory system compliance, and lower risk of hypoxemia and ARDS occurrence. Furthermore, barotrauma, hypotension, duration of ventilation, lengths of stay, and ICU mortality were similar between the two groups. CONCLUSIONS: In our meta-analysis of RCTs, higher PEEP, compared with lower PEEP, was not associated with mortality in patients without ARDS receiving invasive mechanical ventilation. Further large high-quality RCTs are required to confirm these findings.

Static compliance and driving pressure are associated with ICU mortality in intubated COVID-19 ARDS.

BACKGROUND: Pathophysiological features of coronavirus disease 2019-associated acute respiratory distress syndrome (COVID-19 ARDS) were indicated to be somewhat different from those described in nonCOVID-19 ARDS, because of relatively preserved compliance of the respiratory system despite marked hypoxemia. We aim ascertaining whether respiratory system static compliance (Crs), driving pressure (DP), and tidal volume normalized for ideal body weight (VT/kg IBW) at the 1st day of controlled mechanical ventilation are associated with intensive care unit (ICU) mortality in COVID-19 ARDS. METHODS: Observational multicenter cohort study. All consecutive COVID-19 adult patients admitted to 25 ICUs belonging to the COVID-19 VENETO ICU network (February 28th-April 28th, 2020), who received controlled mechanical ventilation, were screened. Only patients fulfilling ARDS criteria and with complete records of Crs, DP and VT/kg IBW within the 1st day of controlled mechanical ventilation were included. Crs, DP and VT/kg IBW were collected in sedated, paralyzed and supine patients. RESULTS: A total of 704 COVID-19 patients were screened and 241 enrolled. Seventy-one patients (29%) died in ICU. The logistic regression analysis showed that: (1) Crs was not linearly associated with ICU mortality (p value for nonlinearity = 0.01), with a greater risk of death for values < 48 ml/cmH2O; (2) the association between DP and ICU mortality was linear (p value for nonlinearity = 0.68), and increasing DP from 10 to 14 cmH2O caused significant higher odds of in-ICU death (OR 1.45, 95% CI 1.06-1.99); (3) VT/kg IBW was not associated with a significant increase of the risk of death (OR 0.92, 95% CI 0.55-1.52). Multivariable analysis confirmed these findings. CONCLUSIONS: Crs < 48 ml/cmH2O was associated with ICU mortality, while DP was linearly associated with mortality. DP should be kept as low as possible, even in the case of relatively preserved Crs, irrespective of VT/kg IBW, to reduce the risk of death.

Cardiopulmonary bypass-induced coagulopathy in pediatric patients: The role of platelets in postoperative bleeding. A preliminary study.

Pediatric patients are particularly prone to cardiopulmonary bypass (CPB)-induced coagulopathy mainly due to hemodilution, consumption of coagulation factors and hypothermia. The aim of the present study was to examine the possible role of platelet count and function as it relates to the bleeding risk after CPB in the pediatric population. All consecutive patients (age <13 years) scheduled for elective cardiac surgery between January 2019 and November 2019 were retrospectively considered for the study. We gathered demographic characteristics, perioperative laboratory data (mainly platelet count and function), transfusion requirements, and blood loss for each patient. Patients with a chest tube output during the first 24 hours after surgery >75th percentile were bleeders (cases). Controls were nonbleeders. A total of 31 patients were enrolled [median age 17 (4-57) months]. A significant postoperative reduction in platelet count (P < .001) and function either in ADP-test (P < .001), TRAP-test (P < .001) and ASPI-test (P < .001) was found, with positive correlations between chest tube output within the first 24 hours after surgery and postoperative impairment of platelet count (R = 0.553, P = .001), ADP-test (R = 0.543, P = .001), TRAP-test (R = 0.627, P < .001) and ASPI-test (R = 0.436, P = .014). Eight children (26%) experienced major postoperative bleeding. Bleeders were significantly younger (P = .015) and underwent longer CPB duration (P = .015). Despite no significant differences in postoperative platelet count and function between cases and controls, the postoperative reduction (Δ) in platelet count (P = .002) and function in ADP-test (P = .007), TRAP-test (P = .020) and ASPI-test (P = .042) was significantly greater in bleeders vs. nonbleeders. A ΔPLT >262 500 ×109 /L, a ΔADP-test >29 U, a ΔTRAP-test >44 U and a ΔASPI-test >26 U showed to be predictive of major postoperative bleeding. Postoperative bleeding in children undergoing cardiac surgery with CPB was linked to younger age, longer CPB duration, and significant postoperative reduction in platelet count and function. Larger studies are needed to confirm our results and define strategies to reduce postoperative bleeding in these patients.