Flurbiprofen in the subglottic space to prevent postoperative sore throat after cardiac surgery: A randomized double-blind study.

STUDY OBJECTIVE: Postoperative sore throat (POST) and hoarseness are common complications of tracheal intubation. This study aims to evaluate the efficacy of flurbiprofen administered through the subglottic port of tracheal tubes to prevent POST after cardiac surgery. DESIGN: Single-center, prospective, randomized, double-blind, placebo-controlled trial. SETTING: Tertiary Care Referral University Hospital (Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome). PATIENTS: Included 71 patients undergoing for elective cardiac surgery. Inclusion criteria were (a) age between 50 and 75 years, (b) NYHA class I or II, (c) surgery for myocardial revascularization or valve repair or replacement under cardiopulmonary bypass. INTERVENTION: Patients were double blind randomized to receive flurbiprofen or saline in the subglottic port of the endotracheal tube (groups F and P). The solution was injected ten minutes after tracheal tube placement, ten minutes after ICU admission and ten minutes before tracheal tube removal. MEASUREMENTS: The primary outcome was to assess the effect of topical flurbiprofen administered through the subglottic port of the tracheal tube to prevent post-operative sore throat (POST). The secondary outcomes were the presence of hoarseness safety and patient's subjective satisfaction with their recovery. We did not report any exploratory outcomes. MAIN RESULTS: We analyzed 68 patients, 34 patients in each group. In group F, two patients complained of POST and hoarseness (5.9%), while all controls did. The two groups significantly differed in the severity scores (VAS and TPS for sore throat and HOAR for hoarseness) at all time points. In group P, patients reported mild to moderate symptoms that significantly improved or disappeared 36 h after tracheal tube removal. According to the multivariable model, hoarseness affected women less than men, in the control group (p = 0.002). None of the patients in either group reported any adverse effects. CONCLUSIONS: Repeated administration of flurbiprofen through the subglottic port of tracheal tubes reduced the incidence of sore throat and hoarseness after cardiac surgery without evidence of complications.

Etiologies and Outcome of Patients with Solid Tumors Admitted to ICU with Acute Respiratory Failure: A Secondary Analysis of the EFRAIM Study.

BACKGROUND: Acute respiratory failure (ARF) remains the most frequent reason for ICU admission in patients who are immunocompromised. This study reports etiologies and outcomes of ARF in subjects with solid tumors. METHODS: This study was a post hoc analysis of the EFRAIM study, a prospective multinational cohort study that included 1611 subjects who were immunocompromised and with ARF admitted to the ICU. Subjects with solid tumors admitted to the ICU with ARF were included in the analysis. RESULTS: Among the subjects from the EFRAIM cohort, 529 subjects with solid tumors (32.8%) were included in the analysis. At ICU admission, the median (interquartile range) Sequential Organ Failure Assessment score was 5 (3-9). The types of solid tumor were mostly lung cancer (n = 111, 21%), breast cancer (n = 52, 9.8%), and digestive cancer (n = 47, 8.9%). A majority, 379 subjects (71.6%) were full code at ICU admission. The ARF was caused by bacterial or viral infection (n = 220, 41.6%), extrapulmonary sepsis (n = 62, 11.7%), or related to cancer or treatment toxicity (n = 83, 15.7%), or fungal infection (n = 23, 4.3%). For 63 subjects (11.9%), the ARF etiology remained unknown after an extensive diagnostic workup. The hospital mortality rate was 45.7% (n = 232/508). Hospital mortality was independently associated with chronic cardiac failure (odds ratio 1.78, 95% CI 1.09-2.92; P = .02), lung cancer (odds ratio 2.50, 95% CI 1.51-4.19; P < .001), day 1 Sequential Organ Failure Assessment score (odds ratio 1.97, 95% CI 1.32-2.96; P < .001). ARF etiologies other than infectious, related to cancer, or treatment toxicity were associated with better outcomes (odds ratio 0.32, 95% CI 0.16-0.61; P < .001). CONCLUSIONS: Infectious diseases remained the most frequent cause of ARF in subjects with solid tumors admitted to the ICU. Hospital mortality was related to severity at ICU admission, previous comorbidities, and ARF etiologies related to non-malignant causes or pulmonary embolism. Lung tumor was also independently associated with higher mortality.

Two innovative aortic bioprostheses evaluated in the real-world setting. First results from a two-center study.

BACKGROUND: The increasing use of biological substitutes for surgical aortic valve replacement (AVR), has led to the development of new bioprostheses with improved hemodynamics and expected durability. METHODS: In this observational retrospective two-center cohort study, two innovative bioprostheses, INSPIRIS Resilia and AVALUS were analyzed. We analyzed early and 2.4-year follow-up results in terms of safety, clinical outcome and hemodynamic performance. RESULTS: From November 2017 to February 2021, 148 patients underwent AVR with INSPIRIS Resilia (N.=74) or AVALUS (N.=74) bioprosthesis. The 30-day and mid-term mortality was comparable (1% vs. 3%, P=0.1 and 7% vs. 4%, P=0.4, respectively). Valve-related mortality was observed in one AVALUS patient. Three (4%) patients of the AVALUS group developed prosthetic endocarditis and two of them died after reoperation. No other cases of prosthetic endocarditis were observed. No cases of structural valve degeneration or significant paravalvular leak were detected at follow-up. Median follow-up peak pressure gradient was 21 vs. 23 mmHg (P=0.4) and the mean pressure gradient was 12 vs. 13 mmHg (P=0.9) for Inspiris and AVALUS, respectively. The effective orifice area (EOA) and indexed EOA were 1.5 cm2 vs. 1.4 cm2 (P=0.4) and 0.8 vs. 0.7 cm2/m2 (P=0.5), respectively. Indexed left ventricular mass regression was -33 vs. -52 g/m2 for the Inspiris and AVALUS groups, respectively, (R2-adjusted =0.14; P<0.01). CONCLUSIONS: INSPIRIS Resilia and AVALUS bioprostheses were reliable with comparable results in safety, clinical outcome and hemodynamic performance. After statistical adjustment, AVALUS was associated with better left ventricular mass reduction. Long-term follow-up would provide definitive comparative results.

When targeted therapy for cancer leads to ICU admission. RETRO-TARGETICU multicentric study.

PURPOSE: To study prevalence of targeted therapy (TT)-related adverse events requiring ICU admission in solid tumor patients. METHODS: Retrospective multicenter study from the Nine-i research group. Adult patients who received TT for solid tumor within 3 months prior to ICU admission were included. Patients admitted for TT-related adverse event were compared to those admitted for other reasons. RESULTS: In total, 140 patients, median age of 63 (52-69) years were included. Primary cancer site was mostly digestive (n=27, 19%), kidney (n=27, 19%), breast (n=24, 17%), and lung (n=20, 14%). Targeted therapy was anti-VEGF/VEGFR for 27% (n=38) patients, anti-EGFR for 22% (n=31) patients, anti-HER2 for 14% (n=20) patients and anti-BRAF for 9% (n=5) patients. ICU admission was related to TT adverse events for 30 (21%) patients. The most frequent complications were interstitial pneumonia (n=7), cardiac failure (n=5), anaphylaxis (n=4) and bleeding (n=4). At ICU admission, no significant difference was found between patients admitted for a TT-related adverse event and the other patients. One-month survival rate was higher in patients admitted for TT adverse event (OR=5.733 [2.031-16.182] P<0.001). CONCLUSIONS: Adverse events related to targeted therapy accounted for 20% of ICU admission in our population and carried a 16% one-month mortality. Outcome was associated with admission for TT related to adverse event, breast cancer and good performance status.

Remdesivir plus Dexamethasone in COVID-19: A cohort study of severe patients requiring high flow oxygen therapy or non-invasive ventilation.

INTRODUCTION: Remdesivir and Dexamethasone represent the cornerstone of therapy for critically ill patients with acute hypoxemic respiratory failure caused by Coronavirus Disease 2019 (COVID-19). However, clinical efficacy and safety of concomitant administration of Remdesivir and Dexamethasone (Rem-Dexa) in severe COVID-19 patients on high flow oxygen therapy (HFOT) or non-invasive ventilation (NIV) remains unknown. MATERIALS AND METHODS: Prospective cohort study that was performed in two medical Intensive Care Units (ICUs) of a tertiary university hospital. The clinical impact of Rem-Dexa administration in hypoxemic patients with COVID-19, who required NIV or HFOT and selected on the simplified acute physiology score II, the sequential organ failure assessment score and the Charlson Comorbidity Index score, was investigated. The primary outcome was 28-day intubation rate; secondary outcomes were end-of-treatment clinical improvement and PaO2/FiO2 ratio, laboratory abnormalities and clinical complications, ICU and hospital length of stay, 28-day and 90-day mortality. RESULTS: We included 132 patients and found that 28-day intubation rate was significantly lower among Rem-Dexa group (19.7% vs 48.5%, p<0.01). Although the end-of-treatment clinical improvement was larger among Rem-Dexa group (69.7% vs 51.5%, p = 0.05), the 28-day and 90-day mortalities were similar (4.5% and 10.6% vs. 15.2% and 16.7%; p = 0.08 and p = 0.45, respectively). The logistic regression and Cox-regression models showed that concomitant Rem-Dexa therapy was associated with a reduction of 28-day intubation rate (OR 0.22, CI95% 0.05-0.94, p = 0.04), in absence of laboratory abnormalities and clinical complications (p = ns). CONCLUSIONS: In COVID-19 critically ill patients receiving HFO or NIV, 28-day intubation rate was lower in patients who received Rem-Dexa and this finding corresponded to lower end-of-treatment clinical improvement. The individual contribution of either Remdesevir or Dexamethasone to the observed clinical effect should be further investigated.

Bleeding Complications in Patients With Perioperative COVID-19 Infection Undergoing Cardiac Surgery: A Single-Center Matched Case-Control Study.

OBJECTIVE: Previous studies reported a poor outcome in patients with coronavirus 2019 (COVID-19) undergoing cardiac surgery. Complications most frequently described were respiratory failure, renal failure, and thromboembolic events. In their recent experience, the authors observed a very high incidence of bleeding complications. The purpose of the study was to investigate a possible significant correlation between perioperative COVID-19 infection and hemorrhagic complications compared to non-COVID-19 patients. DESIGN: Single-center, observational, retrospective, matched case-control (1:2) study involving patients who underwent open-heart cardiac surgery from February 2020 and March 2021 with positive perioperative diagnosis of COVID-19 infection, matched with patients without COVID-19 infection. SETTING: Cardiac surgery unit and intensive care unit of a university tertiary center in a metropolitan area. PARTICIPANTS: In the study period, 773 patients underwent cardiac surgery on cardiopulmonary bypass (CPB). Among them, 23 consecutive patients had perioperative diagnosis of COVID-19 infection (study group). These patients were compared with 46 corresponding controls (control group) that matched for age, sex, body mass index, and Society of Thoracic Surgeons score. INTERVENTIONS: Open-heart cardiac surgery on CPB. MEASUREMENTS AND MAIN RESULTS: In the study group, 2 patients (9%) died in the intensive care unit from severe respiratory failure, shock, and multiple organ failure. In the study group, patients showed a significantly higher incidence of bleeding complications (48% v 2%, p = 0.0001) and cases of surgical reexploration for bleeding (35% v 2%, p = 0.0001), a higher incidence of severe postoperative thrombocytopenia (39% v 6%, p = 0.0007), and a higher need of blood components transfusions (74% v 30%, p = 0.0006). Chest tubes blood loss and surgical hemostasis time were markedly prolonged (p = 0.02 and p = 0.003, respectively). CONCLUSIONS: A worrisome increased risk of early and late bleeding complications in COVID-19 patients was observed, and it should be considered when assessing the operative risk. CPB-related inflammatory reaction could exacerbate the deleterious effect of COVID-19 on the coagulation system and likely deviate it toward a hemorrhagic pattern.

Early nasal high-flow versus Venturi mask oxygen therapy after lung resection: a randomized trial.

BACKGROUND: Data on high-flow nasal oxygen after thoracic surgery are limited and confined to the comparison with low-flow oxygen. Different from low-flow oxygen, Venturi masks provide higher gas flow at a predetermined fraction of inspired oxygen (FiO2). We conducted a randomized trial to determine whether preemptive high-flow nasal oxygen reduces the incidence of postoperative hypoxemia after lung resection, as compared to Venturi mask oxygen therapy. METHODS: In this single-center, randomized trial conducted in a teaching hospital in Italy, consecutive adult patients undergoing thoracotomic lung resection, who were not on long-term oxygen therapy, were randomly assigned to receive high-flow nasal or Venturi mask oxygen after extubation continuously for two postoperative days. The primary outcome was the incidence of postoperative hypoxemia (i.e., ratio of the partial pressure of arterial oxygen to FiO2 (PaO2/FiO2) lower than 300 mmHg) within four postoperative days. RESULTS: Between September 2015 and April 2018, 96 patients were enrolled; 95 patients were analyzed (47 in high-flow group and 48 in Venturi mask group). In both groups, 38 patients (81% in the high-flow group and 79% in the Venturi mask group) developed postoperative hypoxemia, with an unadjusted odds ratio (OR) for the high-flow group of 1.11 [95% confidence interval (CI) 0.41-3] (p = 0.84). No inter-group differences were found in the degree of dyspnea nor in the proportion of patients needing oxygen therapy after treatment discontinuation (OR 1.34 [95% CI 0.60-3]), experiencing pulmonary complications (OR 1.29 [95% CI 0.51-3.25]) or requiring ventilatory support (OR 0.67 [95% CI 0.11-4.18]). Post hoc analyses revealed that PaO2/FiO2 during the study was not different between groups (p = 0.92), but patients receiving high-flow nasal oxygen had lower arterial pressure of carbon dioxide, with a mean inter-group difference of 2 mmHg [95% CI 0.5-3.4] (p = 0.009), and were burdened by a lower risk of postoperative hypercapnia (adjusted OR 0.18 [95% CI 0.06-0.54], p = 0.002). CONCLUSIONS: When compared to Venturi mask after thoracotomic lung resection, preemptive high-flow nasal oxygen did not reduce the incidence of postoperative hypoxemia nor improved other analyzed outcomes. Further adequately powered investigations in this setting are warranted to establish whether high-flow nasal oxygen may yield clinical benefit on carbon dioxide clearance. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02544477 . Registered 9 September 2015.

Acute hypoxemic respiratory failure in immunocompromised patients: the Efraim multinational prospective cohort study.

BACKGROUND: In immunocompromised patients with acute hypoxemic respiratory failure (ARF), initial management aims primarily to avoid invasive mechanical ventilation (IMV). METHODS: To assess the impact of initial management on IMV and mortality rates, we performed a multinational observational prospective cohort study in 16 countries (68 centers). RESULTS: A total of 1611 patients were enrolled (hematological malignancies 51.9%, solid tumors 35.2%, systemic diseases 17.3%, and solid organ transplantation 8.8%). The main ARF etiologies were bacterial (29.5%), viral (15.4%), and fungal infections (14.7%), or undetermined (13.2%). On admission, 915 (56.8%) patients were not intubated. They received standard oxygen (N = 496, 53.9%), high-flow oxygen (HFNC, N = 187, 20.3%), noninvasive ventilation (NIV, N = 153, 17.2%), and NIV + HFNC (N = 79, 8.6%). Factors associated with IMV included age (hazard ratio = 0.92/year, 95% CI 0.86-0.99), day-1 SOFA (1.09/point, 1.06-1.13), day-1 PaO2/FiO2 (1.47, 1.05-2.07), ARF etiology (Pneumocystis jirovecii pneumonia (2.11, 1.42-3.14), invasive pulmonary aspergillosis (1.85, 1.21-2.85), and undetermined cause (1.46, 1.09-1.98). After propensity score matching, HFNC, but not NIV, had an effect on IMV rate (HR = 0.77, 95% CI 0.59-1.00, p = 0.05). ICU, hospital, and day-90 mortality rates were 32.4, 44.1, and 56.4%, respectively. Factors independently associated with hospital mortality included age (odds ratio = 1.18/year, 1.09-1.27), direct admission to the ICU (0.69, 0.54-0.87), day-1 SOFA excluding respiratory score (1.12/point, 1.08-1.16), PaO2/FiO2 < 100 (1.60, 1.03-2.48), and undetermined ARF etiology (1.43, 1.04-1.97). Initial oxygenation strategy did not affect mortality; however, IMV was associated with mortality, the odds ratio depending on IMV conditions: NIV + HFNC failure (2.31, 1.09-4.91), first-line IMV (2.55, 1.94-3.29), NIV failure (3.65, 2.05-6.53), standard oxygen failure (4.16, 2.91-5.93), and HFNC failure (5.54, 3.27-9.38). CONCLUSION: HFNC has an effect on intubation but not on mortality rates. Failure to identify ARF etiology is associated with higher rates of both intubation and mortality. This suggests that in addition to selecting the appropriate oxygenation device, clinicians should strive to identify the etiology of ARF.

Clinical impact of pulmonary sampling site in the diagnosis of ventilator-associated pneumonia: A prospective study using bronchoscopic bronchoalveolar lavage.

PURPOSE: It is unclear whether ventilator-associated pneumonia (VAP) is actually a bilateral and multifocal process. In addition, the diagnostic role of chest x-ray is under debate. Assuming a low microbiologic concordance between the left and right lungs, the reliability of a single pulmonary sampling becomes questionable. The purpose of this study was to determine whether the choice of the pulmonary sampling area is clinically relevant in the management of VAP. METHODS: In 79 patients admitted to a university general intensive care unit with clinically suspected VAP, right- and left-lung bronchoalveolar lavage (BAL) samples were taken with separate bronchoscopes and quantitatively cultured. Primary end-point variable was microbiologic concordance rate between right- and left-lung BAL cultures. Secondary outcomes included predictors of microbiologic concordance, rates of appropriate antibiotic treatment, and diagnostic accuracy of chest x-ray. RESULTS: BAL cultures were bilaterally negative in 21 (27%) of 79 patients, bilaterally positive in 36 (46%), and unilaterally positive (right in 12, left in 10) in 22 (28%). Intra-patient concordance was observed in 47 (59.5%) of 79 cases and independently associated with purulent secretions and bilateral infiltrates on chest x-ray. In simulated prescribing experiments, treatments chosen based on right or left cultures alone were as appropriate as those based on bilateral data in >90% of cases. The presence of a radiographic infiltrate in the sampling area predicted BAL culture positivity with a positive predictive value of only 61%. CONCLUSIONS: In patients with clinically suspected VAP (especially those without purulent secretions or without radiographically documented bilateral infiltrates), quantitative culture of a single BAL sample may provide an incomplete assessment of lung microbiology, without having a relevant impact on the appropriateness of antimicrobial treatment. These findings suggest that single sampling of respiratory secretions, regardless radiographic opacity, seems to be a reliable diagnostic method in the management of VAP.