Effect on post-operative pulmonary complications frequency of high flow nasal oxygen versus standard oxygen therapy in patients undergoing esophagectomy for cancer: study protocol for a randomized controlled trial-OSSIGENA study.

Background: Postoperative pulmonary complications (PPCs) remain a challenge after esophagectomy. Despite improvement in surgical and anesthesiological management, PPCs are reported in as many as 40% of patients. The main aim of this study is to investigate whether early application of high-flow nasal cannula (HFNC) after extubation will provide benefit in terms of reduced PPC frequency compared to standard oxygen therapy. Methods: Patients aged 18-85 years undergoing esophagectomy for cancer treatment with radical intent, excluding those with American Society of Anesthesiologists (ASA) score >3 and severe systemic comorbidity (cardiac, pulmonary, renal or hepatic disease) will be randomized at the end of surgery to receive HFNC or standard oxygen therapy (Venturi mask or nasal goggles) after early extubation (within 12 hours after the end of surgery) for 48 hours. The main postoperative goals are to obtain SpO2 ≥94% and adequate pain control. Oxygen therapy after 48 hours will be stopped unless the physician deems it necessary. In case of respiratory clinical worsening, patients will be supported with the most appropriate tool (noninvasive ventilation or invasive mechanical ventilation). Pulmonary [pneumonia, pleural effusion, pneumothorax, atelectasis, acute respiratory distress syndrome (ARDS), tracheo-bronchial injury, air leak, reintubation, and/or respiratory failure] complications will be recorded as main outcome. Secondary outcomes, including cardiovascular, surgical, renal and infective complications will also be recorded. The primary analysis will be carried out on 320 patients (160 per group) and performed on an intention-to-treat (ITT) basis, including all participants randomized into the treatment groups, regardless of protocol adherence. The primary outcome, the PPC rate, will be compared between the two treatment groups using a chi-square test for categorical data, or Fisher's exact test will be used if the assumptions for the chi-square test are not met. Discussion: Recent evidence demonstrated that early application of HFNC improved the respiratory rate oxygenation index (ROX index) after esophagectomy but did not reduce PPCs. This randomized controlled multicenter trial aims to assess the potential effect of the application of HFNC versus standard oxygen over PPCs in patients undergoing esophagectomy. Trial Registration: This study is registered at clinicaltrial.gov NCT05718284, dated 30 January 2023.

Retrospective ANalysis of multi-drug resistant Gram-nEgative bacteRia on veno-venous extracorporeal membrane oxygenation. The multicenter RANGER STUDY.

BACKGROUND: Veno-venous extracorporeal membrane oxygenation (V-V ECMO) is a rapidly expanding life-support technique worldwide. The most common indications are severe hypoxemia and/or hypercapnia, unresponsive to conventional treatments, primarily in cases of acute respiratory distress syndrome. Concerning potential contraindications, there is no mention of microbiological history, especially related to multi-drug resistant (MDR) bacteria isolated before V-V ECMO placement. Our study aims to investigate: (i) the prevalence and incidence of MDR Gram-negative (GN) bacteria in a cohort of V-V ECMOs; (ii) the risk of 1-year mortality, especially in the case of predetected MDR GN bacteria; and (iii) the impact of annual hospital V-V ECMO volume on the probability of acquiring MDR GN bacteria. METHODS: All consecutive adults admitted to the Intensive Care Units of 5 Italian university-affiliated hospitals and requiring V-V ECMO were screened. Exclusion criteria were age < 18 years, pregnancy, veno-arterial or mixed ECMO-configuration, incomplete records, survival < 24 h after V-V ECMO. A standard protocol of microbiological surveillance was applied and MDR profiles were identified using in vitro susceptibility tests. Cox-proportional hazards models were applied for investigating mortality. RESULTS: Two hundred and seventy-nine V-V ECMO patients (72% male) were enrolled. The overall MDR GN bacteria percentage was 50%: 21% (n.59) detected before and 29% (n.80) after V-V ECMO placement. The overall 1-year mortality was 42%, with a higher risk observed in predetected patients (aHR 2.14 [1.33-3.47], p value 0.002), while not in 'V-V ECMO-acquired MDR GN bacteria' group (aHR 1.51 [0.94-2.42], p value 0.090), as compared to 'non-MDR GN bacteria' group (reference). Same findings were found considering only infections. A larger annual hospital V-V ECMO volume was associated with a lower probability of acquiring MDR GN bacteria during V-V ECMO course (aOR 0.91 [0.86-0.97], p value 0.002). CONCLUSIONS: 21% of MDR GN bacteria were detected before; while 29% after V-V ECMO connection. A history of MDR GN bacteria, isolated before V-V ECMO, was an independent risk factor for mortality. The annual hospital V-V ECMO volume affected the probability of acquiring MDR GN bacteria. Trial Registration ClinicalTrial.gov Registration Number NCTNCT06199141, date 12.26.2023.

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.

Fungal Infections and Colonization after Bilateral Lung Transplant: A Six-Year Single-Center Experience.

Fungal infections (FIs) are one of the leading causes of morbidity and mortality within the first year of lung transplant (LT) in LT recipients (LTRs). Their prompt identification and treatment are crucial for a favorable LTR outcome. The objectives of our study were to assess (i) the FI incidence and colonization during the first year after a bilateral LT, (ii) the risk factors associated with FI and colonization, and (iii) the differences in fungal incidence according to the different prophylactic strategies. All bilateral LTRs admitted to the intensive care unit of Padua University Hospital were retrospectively screened, excluding patients <18 years of age, those who had been re-transplanted, and those who had received ventilation and/or extracorporeal membrane oxygenation before LT. Overall, 157 patients were included. A total of 13 (8%) patients developed FI, and 36 (23%) developed colonization, which was mostly due to Aspergillus spp. We did not identify independent risk factors for FI. Groups of patients receiving different prophylactic strategies reported a similar incidence of both FI and colonization. The incidence of FI and fungal colonization was 8% and 23%, respectively, with no differences between different antifungal prophylaxes or identified predisposing factors. Further studies with larger numbers are needed to confirm our results.

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.

The Impact of New Treatments on Short- and MID-Term Outcomes in Bilateral Lung Transplant: A Propensity Score Study.

BACKGROUND: Despite many efforts to improve organ preservation and recipient survival, overall lung transplant (LT) mortality is still high. We aimed to investigate the impact of 'prophylactic' veno-arterial extracorporeal membrane oxygenation (VA ECMO) and tacrolimus on 72-h primary graft dysfunction (PGD) and 30-day acute cellular rejection, respectively. METHODS: All consecutive LT patients admitted to the Intensive Care Unit of the Padua University Hospital (February, 2016-2022) were screened. Only adult patients undergoing first bilateral LT and not requiring cardio-pulmonary bypass, invasive mechanical ventilation, and/or ECMO before LT, were included. A propensity score weighting analysis was employed to account for the non-random allocation of the subjects to different treatments. RESULTS: A total of 128 LT recipients were enrolled. Compared to the 'off-pump'-group (n.47, 37%), 'prophylactic' VA ECMO (n.51,40%) recorded similar 72-h PGD values, perioperative blood products and lower acute kidney dysfunction. Compared with cyclosporine (n.86, 67%), tacrolimus (n.42, 33%) recorded a lower risk of 30-day cellular rejection, kidney dysfunction, and bacteria isolation. CONCLUSIONS: 'Prophylactic' VA ECMO recorded 72-h PGD values comparable to the 'off-pump'-group; while tacrolimus showed a lower incidence of 30-day acute cellular rejection.

Outcomes of COVID-19 Patients with Severe Hypoxemic Acute Respiratory Failure: Non-Invasive Ventilation vs. Straight Intubation-A Propensity Score-Matched Multicenter Cohort Study.

The best timing for endotracheal intubation in patients with coronavirus disease 2019 (COVID-19) hypoxemic acute respiratory failure (hARF) remains debated. Aim of this study is to compare the outcomes of COVID-19 patients with hARF receiving either a trial of non-invasive ventilation (NIV) or intubated with no prior attempt of NIV ("straight intubation"). All consecutive patients admitted to the 25 participating ICUs were included and divided in two groups: the "straight intubation" group and the "NIV" group. A propensity score matching was performed to correct for biases associated with the choice of the respiratory support. Primary outcome was in-hospital mortality. Secondary outcomes were length of mechanical ventilation, hospital stay and reintubation rate. A total of 704 COVID-19 patients were admitted to ICUs during the study period. After matching, 141 patients were included in each group. No clinically relevant difference at ICU admission was found between groups. In-hospital mortality was significantly lower in the NIV group (22.0% vs. 36.2%), with no significant difference in secondary endpoints. There was no significant mortality difference between patients who received straight intubation and those intubated after NIV failure. In COVID-19 patients with hARF it is worth and safe attempting a trial of NIV prior to intubation.

How to recognize patients at risk of self-inflicted lung injury.

INTRODUCTION: Patient self-inflicted lung injury (P-SILI) has been proposed as a form of lung injury caused by strong inspiratory efforts consequent to a high respiratory drive in patients with hypoxemic acute respiratory failure (hARF). Increased respiratory drive and effort may lead to variable combinations of deleterious phenomena, such as excessive transpulmonary pressure, pendelluft, intra-tidal recruitment, local lung volutrauma, and pulmonary edema. Gas exchange and respiratory mechanics derangements further increase respiratory drive and effort, thus inducing a vicious circle. Forms of partial ventilatory support may further add to the detrimental effects of P-SILI. Since P-SILI may worsen patient outcome, strategies aimed at identifying and preventing P-SILI would be of great importance. AREAS COVERED: We systematically searched Pubmed since inception until 15 April 2022 to review the patho-physiological mechanisms of P-SILI and the strategies to identify those patients at risk of P-SILI. EXPERT OPINION: Although the concept of P-SILI has been increasingly supported by experimental and clinical data, no study has insofar demonstrated the efficacy of any strategy to identify it in the clinical setting. Further research is thus needed to ascertain the detrimental effects of spontaneous breathing and identify patients with hARF at high risk of developing P-SILI.