Evaluation of hyperoxia-induced hypercapnia in obese patients after cardiac surgery: a randomized crossover comparison of conservative and liberal oxygen administration.

PURPOSE: Recent studies on patients with stable obesity-hypoventilation syndrome have raised concerns about hyperoxia-induced hypercapnia in this population. This study aimed to evaluate whether a higher oxygen saturation target would increase arterial partial pressure of carbon dioxide (PaCO2) in obese patients after coronary artery bypass grafting surgery (CABG). METHODS: Obese patients having CABG were recruited. With a randomized crossover design, we compared two oxygenation strategies for 30 min each, immediately after extubation: a peripheral oxygen saturation (SpO2) target of ≥ 95% achieved with manual oxygen titration (liberal) and a SpO2 target of 90% achieved with FreeO2, an automated oxygen titration device (conservative). The main outcome was end-of-period arterial PaCO2. RESULTS: Thirty patients were included. Mean (standard deviation [SD]) body mass index (BMI) was 34 (3) kg·m-2 and mean (SD) baseline partial pressure of carbon dioxide (PCO2) was 40.7 (3.1) mmHg. Mean (SD) end-of-period PaCO2 was 42.0 (5.4) mmHg in the conservative period, compared with 42.6 (4.6) mmHg in the liberal period [mean difference - 0.6 (95% confidence interval - 2.2 to 0.9) mmHg; P = 0.4]. Adjusted analysis for age, BMI, narcotics, and preoperative PaCO2 did not substantively change the results. Fourteen patients were retainers, showing an elevation in mean (SD) PaCO2 in the liberal period of 3.3 (4.1) mmHg. Eleven patients had the opposite response, with a mean (SD) end-of-period PaCO2 decrease of 1.8 (2.2) mmHg in the liberal period. Five patients had a neutral response. CONCLUSION: This study did not show a clinically important increase in PaCO2 associated with higher SpO2 values in this specific population of obese patients after CABG. Partial pressure of carbon dioxide increased with liberal oxygen administration in almost half of the patients, but no predictive factor was identified. TRIAL REGISTRATION: www.clinicaltrials.gov (NCT02917668); registered 25 September, 2016.

Automatic versus Manual Oxygen Titration in Patients Requiring Supplemental Oxygen in the Hospital: A Systematic Review and Meta-Analysis.

BACKGROUND: Closed-loop oxygen titration devices have been developed to avoid periods of hypoxemia and hyperoxemia, both detrimental to patients hospitalized for respiratory failure and requiring supplemental oxygen. However, their clinical impact remains unknown. OBJECTIVE: To compare the effect of automatic versus manual oxygen titration on clinical outcomes in pediatric and adult patients requiring supplemental oxygen in the hospital. METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials. We searched MEDLINE, EMBASE, and CENTRAL electronic databases (from inception to August 2018), and conference proceedings of major societies in respiratory medicine (2015-2018). Randomized controlled trials were included if they compared automatic to manual oxygen titration in hypoxemic inpatients and if they assessed at least one of the following: length of hospital stay (primary outcome), length of oxygen therapy, need and duration of mechanical ventilation, mortality, percentage of time within, above, and below the oxygen saturation target range, as well as the percentage of time spent in hypoxemia and hyperoxemia. RESULTS: We included 9 trials (354 patients, adults and preterm infants, with or without ventilatory assistance). Eight of these trials were at high risk of bias due to lack of blinding and selective reporting. Automatic titration was associated with a significant decrease in the length of hospital stay (mean difference: -2.2 days; 95% CI: -3.8 to -0.6; p = 0.009; I2 = 0%; n = 237, 2 trials), and a decrease in the length of oxygen therapy (mean difference: -1.6 days; 95% CI: -3.1 to 0.0; p = 0.05; I2 = 0%; n = 237; 2 trials). We did not observe a reduction in the need for ventilatory assistance or in mortality in the automatic titration period. An increase in the percentage of time spent within target (mean difference: 18.23%; 95% CI: 10.93-25.52; I2 = 81%; n = 351, 7 trials) and a significant reduction in the percentage of time spent in both hypoxemia and hyperoxemia with automatic compared to manual oxygen titration were, however, observed. CONCLUSIONS: In patients requiring supplemental oxygen in the hospital, automatic oxygen titration was associated with a reduction in length of both hospital stay and oxygen therapy, as well as a greater percentage of time spent within the saturation target range. However, it was not associated with a significant difference in the need for mechanical ventilation or in mortality. Results should be interpreted with caution due to the small number of included trials and their high risk of bias.

Beyond PACIFIC: Real-World Outcomes of Adjuvant Durvalumab According to Treatment Received and PD-L1 Expression.

Adjuvant durvalumab after chemoradiotherapy (CRT) is the standard of care for unresectable stage III non-small cell lung cancer (NSCLC). A post hoc exploratory analysis of PACIFIC revealed no OS benefit in the PD-L1 < 1% subgroup. This retrospective analysis assesses the real-world impact of durvalumab on OS according to PD-L1 tumor proportion score (TPS). Patients with stage III, unresectable NSCLC treated by CRT, with available PD-L1 TPS, from 1 March 2018 to 31 December 2020, at BC Cancer, British Columbia, Canada were included. Patients were divided into two groups, CRT + durvalumab and CRT alone. OS and PFS were analyzed in the PD-L1 ≥ 1% and <1% subgroups. A total of 134 patients were included in the CRT + durvalumab group and 117, in the CRT alone group. Median OS was 35.9 months in the CRT + durvalumab group and 27.4 months in the CRT alone group [HR 0.59 (95% CI 0.42-0.83), p = 0.003]. Durvalumab improved OS in the PD-L1 ≥ 1% [HR 0.53 (95% CI 0.34-0.81), p = 0.003, n = 175], but not in the <1% subgroup [HR 0.79 (95% CI 0.44-1.42), p = 0.4, n = 76]. This retrospective study demonstrates a statistically significant improvement in OS associated with durvalumab after CRT in PD-L1 ≥ 1%, but not PD-L1 < 1% NSCLC. Variables not accounted for may have biased the survival analysis. A prospective study would bring more insight.

Automated O2 Titration Alone or With High-Flow Nasal Cannula During Walking Exercise in Chronic Lung Diseases.

BACKGROUND: Exercise-induced O2 desaturation contributes to dyspnea and exercise intolerance in various respiratory diseases. This study assessed whether automated O2 titration was superior to fixed-flow O2 to improve exertional dyspnea and walking exercise endurance. We also aimed at evaluating possible additive effects of high-flow nasal cannula coupled with automated O2 titration on these outcomes. METHODS: Subjects with chronic respiratory diseases and exercise-induced desaturation performed a 3-min constant-speed shuttle test (CSST) and an endurance shuttle walking test (ESWT) with either (1) fixed-flow O2, (2) automated O2 titration targeting an SpO2 of 94% (± 2%), and (3) automated O2 titration + high-flow nasal cannula according to a randomized sequence. The main outcome was Borg dyspnea score at the end of the 3-min CSST. Secondary outcomes included endurance time and dyspnea during ESWT and oxygenation status during exercise. RESULTS: Ten subjects with COPD, 10 with interstitial lung disease, 5 with pulmonary hypertension, and 3 with cystic fibrosis completed the study. Compared to fixed-flow O2, automated O2 titration did not reduce dyspnea at the end of the 3-min CSST. Endurance time during the ESWT was prolonged with automated O2 titration (mean difference 298 [95% CI 205-391] s, P < .001), and dyspnea at isotime was reduced. No further improvement was noted when high-flow nasal cannula was added to automated O2 titration. Compared to fixed-flow O2, O2 flows were higher with automated O2 titration, resulting in better oxygenation. CONCLUSIONS: Automated O2 titration was superior to fixed-flow O2 to alleviate dyspnea and improve exercise endurance during the ESWT in subjects with a variety of chronic respiratory diseases. Adding high-flow nasal cannula to automated O2 titration provided no further benefits.

Wait Times and Survival in Lung Cancer Patients across the Province of Quebec, Canada.

Lung cancer is the leading cause of cancer death worldwide, with a five-year survival of 22% in Canada. Guidelines recommend rapid evaluation of patients with suspected lung cancer, but the impact on survival remains unclear. We reviewed medical records of all patients with newly diagnosed lung cancer in four hospital networks across the province of Quebec, Canada, between 1 February and 30 April 2017. Patients were followed for 3 years. Wait times for diagnosis and treatment were collected, and survival analysis using a Cox regression model was conducted. We included 1309 patients, of whom 39% had stage IV non-small cell lung cancer (NSCLC). Median wait times were, in general, significantly shorter in patients with stage III-IV NSCLC or SCLC. Surgery was associated with delays compared to other types of treatments. Median survival was 12.9 (11.1-15.7) months. The multivariate survival model included age, female sex, performance status, histology and stage, treatment, and the time interval between diagnosis and treatment. Longer wait times had a slightly protective to neutral effect on survival, but this was not significant in the stage I-II NSCLC subgroup. Wait times for the diagnosis and treatment of lung cancer were generally within targets. The shorter wait times observed for advanced NSCLC and SCLC might indicate a tendency for clinicians to act quicker on sicker patients. This study did not demonstrate the detrimental effect of longer wait times on survival.

Comparison of 2-Weekly Versus 4-Weekly Durvalumab Consolidation for Locally Advanced NSCLC Treated With Chemoradiotherapy: A Brief Report.

Introduction: Durvalumab 10 mg/kg every 2 weeks for 1 year after chemoradiation has improved overall survival (OS) in unresectable stage III NSCLC. Subsequently, a 20 mg/kg 4-weekly regimen was approved. The study goal was to compare the efficacy and toxicity of the two regimens. Methods: All patients with NSCLC treated with curative-intent chemoradiation followed by durvalumab from March 1, 2018 to December 31, 2020 at BC Cancer, British Columbia, Canada were included in this retrospective review. Durvalumab dosing schedule, toxicity, progression, and OS were collected. Comparisons between treatment groups were made using chi-square and independent t tests. Kaplan-Meier curves and log-rank test were used to analyze OS. Results: A total of 152 patients were included in the 2-weekly group and 53 patients in the 4-weekly group. The median follow-up was 19.7 months and 12.0 months, respectively. The median OS was not reached, but 12-month survival rates were 88.4% versus 85.2% (p = 0.55). Toxicity profiles were similar in terms of sites and severity. Conclusions: There was no significant difference in efficacy or toxicity between the 2-weekly and 4-weekly durvalumab in this cohort of patients with advanced NSCLC previously treated with curative-intent chemoradiation.

Immunotherapy in the First-Line Setting in Wild-Type NSCLC.

Treatment algorithms in the treatment of advanced non-small cell lung cancer (NSCLC) continue to evolve as new therapeutics show positive efficacy improvements. This review article summarizes the data for the use of immunotherapy for treatment in first-line stage IV NSCLC, organized by the following four sections: single-agent immunotherapy, immunotherapy and chemotherapy, dual immunotherapy, and dual immunotherapy and chemotherapy. The results are summarized and tabulated. Finally, application of the trial data is illustrated in four clinical scenarios depending on the programmed death-ligand 1 (PD-L1) expression levels. Single checkpoint inhibitors have become an easy and excellent treatment in patients whose tumors have high PD-L1 expression. Adding chemotherapy to immunotherapy benefits our patients. Immunotherapy, with or without chemotherapy, is now the standard of care in the first-line setting in patients without EGFR, ALK, or ROS driver mutations.