High Concentration Oxygen and Hypercapnia in Respiratory Disease

<p>Oxygen-induced elevations in arterial carbon dioxide tension have been demonstrated in patients with chronic obstructive pulmonary disease (COPD), asthma, pneumonia, obesity hypoventilation syndrome (OHS) and acute lung injury. A randomised controlled trial (RCT) in acute exacerbations of COPD (AECOPD) found an over two-fold increase in mortality in patients randomised to high concentration oxygen, compared to titrated oxygen. These findings support guideline recommendations for titration of oxygen therapy to a target oxygen saturation range, reducing the risks of hypoxaemia and hyperoxaemia. This thesis focuses on the potential implications of oxygen-induced elevations in carbon dioxide in the acute clinical setting. The reviews and studies in the following chapters are all aimed at addressing gaps in knowledge which may have practical implications for oxygen therapy and/or the identification of patients at risk of oxygen-induced hypercapnia in clinical practice. Numerous studies have demonstrated that high concentration oxygen continues to be administered to acutely unwell patients, despite guideline recommendations for titrated therapy. The first study in this thesis is a clinical audit evaluating the effects of a staff education program, which included face-to-face and written training for ambulance staff. The education program was associated with reduced the rates of high concentration oxygen administration to patients with AECOPD. This suggests active education may increase adherence to oxygen guidelines among clinical staff. The ability to avoid hypoxaemia and hyperoxaemia during titrated oxygen therapy relies on appropriate lower and upper target oxygen saturation limits, which may be impacted on by pulse oximeter accuracy. The second study in this thesis is a multicentre observational study in which 400 paired pulse oximeter (SpO₂) and arterial blood gas saturation (SaO₂) values were collected in the hospital setting. A SpO₂ <92% had 100% sensitivity for detecting SaO₂<90%. This indicates guideline recommended target oxygen saturations of 92-96% adequately avoid hypoxaemia. Two studies in OHS patients have investigated the effects of oxygen administration on carbon dioxide, however their designs, including recruitment of stable participants, have limited their generalisability to clinical practice. Therefore, a cross over RCT was conducted in 24 morbidly obese hospital inpatients, randomised to the order they received high concentration and titrated oxygen, each for 60 minutes. The mean change in the transcutaneous partial pressure of carbon dioxide (PtCO₂) from baseline was 3.2 mmHg higher during high concentration oxygen, compared with titrated oxygen (P=0.002). This supports guideline recommendations to titrate oxygen in patients with obesity, regardless of whether they have a diagnosis of OHS or not. The effects of oxygen in patients with bronchiectasis, neuromuscular disease or kyphoscoliosis are uncertain. Stable patients with these conditions were recruited to double-blind randomised cross over trials administering air and 50% oxygen, each for 30 minutes. A trial was also performed in stable COPD patients for comparison. There was no significant change in PtCO₂ with oxygen therapy in the neuromuscular disease/kyphoscoliosis patients. In the bronchiectasis and COPD patients, oxygen was associated with increased PtCO₂ from baseline compared to air, but the differences were not clinically significant (0.4 mmHg, P=0.012 and 1.3 mmHg, P<0.001, respectively). The lack of a clinically significant PtCO₂ increase in the COPD patients indicated the study findings were unlikely to be generalisable to the clinical setting, and highlights the potential limitations in applying data from stable participants to patients who require acute oxygen therapy. These studies support current guideline recommendations for titrated oxygen therapy, provide insight into the limits of studying the effects of oxygen in stable participants, and demonstrate the utility of an educational program to aid the translation of research findings into relevant changes in clinical practice.</p>

High Concentration Oxygen and Hypercapnia in Respiratory Disease

<p>Oxygen-induced elevations in arterial carbon dioxide tension have been demonstrated in patients with chronic obstructive pulmonary disease (COPD), asthma, pneumonia, obesity hypoventilation syndrome (OHS) and acute lung injury. A randomised controlled trial (RCT) in acute exacerbations of COPD (AECOPD) found an over two-fold increase in mortality in patients randomised to high concentration oxygen, compared to titrated oxygen. These findings support guideline recommendations for titration of oxygen therapy to a target oxygen saturation range, reducing the risks of hypoxaemia and hyperoxaemia. This thesis focuses on the potential implications of oxygen-induced elevations in carbon dioxide in the acute clinical setting. The reviews and studies in the following chapters are all aimed at addressing gaps in knowledge which may have practical implications for oxygen therapy and/or the identification of patients at risk of oxygen-induced hypercapnia in clinical practice. Numerous studies have demonstrated that high concentration oxygen continues to be administered to acutely unwell patients, despite guideline recommendations for titrated therapy. The first study in this thesis is a clinical audit evaluating the effects of a staff education program, which included face-to-face and written training for ambulance staff. The education program was associated with reduced the rates of high concentration oxygen administration to patients with AECOPD. This suggests active education may increase adherence to oxygen guidelines among clinical staff. The ability to avoid hypoxaemia and hyperoxaemia during titrated oxygen therapy relies on appropriate lower and upper target oxygen saturation limits, which may be impacted on by pulse oximeter accuracy. The second study in this thesis is a multicentre observational study in which 400 paired pulse oximeter (SpO₂) and arterial blood gas saturation (SaO₂) values were collected in the hospital setting. A SpO₂ <92% had 100% sensitivity for detecting SaO₂<90%. This indicates guideline recommended target oxygen saturations of 92-96% adequately avoid hypoxaemia. Two studies in OHS patients have investigated the effects of oxygen administration on carbon dioxide, however their designs, including recruitment of stable participants, have limited their generalisability to clinical practice. Therefore, a cross over RCT was conducted in 24 morbidly obese hospital inpatients, randomised to the order they received high concentration and titrated oxygen, each for 60 minutes. The mean change in the transcutaneous partial pressure of carbon dioxide (PtCO₂) from baseline was 3.2 mmHg higher during high concentration oxygen, compared with titrated oxygen (P=0.002). This supports guideline recommendations to titrate oxygen in patients with obesity, regardless of whether they have a diagnosis of OHS or not. The effects of oxygen in patients with bronchiectasis, neuromuscular disease or kyphoscoliosis are uncertain. Stable patients with these conditions were recruited to double-blind randomised cross over trials administering air and 50% oxygen, each for 30 minutes. A trial was also performed in stable COPD patients for comparison. There was no significant change in PtCO₂ with oxygen therapy in the neuromuscular disease/kyphoscoliosis patients. In the bronchiectasis and COPD patients, oxygen was associated with increased PtCO₂ from baseline compared to air, but the differences were not clinically significant (0.4 mmHg, P=0.012 and 1.3 mmHg, P<0.001, respectively). The lack of a clinically significant PtCO₂ increase in the COPD patients indicated the study findings were unlikely to be generalisable to the clinical setting, and highlights the potential limitations in applying data from stable participants to patients who require acute oxygen therapy. These studies support current guideline recommendations for titrated oxygen therapy, provide insight into the limits of studying the effects of oxygen in stable participants, and demonstrate the utility of an educational program to aid the translation of research findings into relevant changes in clinical practice.</p>

Transhiatal Chest Drainage Reduces The Frequency of Postoperative Thoracentesis In Transmediastinal Esophagectomy For Esophageal Cancer: A Retrospective Study

Background: Transmediastinal esophagectomy for esophageal cancer occasionally results in the postoperative accumulation of pleural effusion despite the preservation of the mediastinal pleura. Transhiatal chest drainage has reported utility in thoracic esophagectomy; however, its use in transmediastinal esophagectomy remains unelucidated. This study aimed to evaluate the effectiveness and safety of transhiatal chest drainage in transmediastinal esophagectomy.Methods: This retrospective study included patients who underwent transmediastinal esophagectomy for esophageal cancer from 2018 to 2020. The transhiatal chest drainage involved the insertion of a 19-Fr Blake® drain from the inferior hepatic space to the left thoracic cavity through the hiatus. The drainage group comprising 13 patients was compared with the non-drainage group comprising 13 patients in whom a transhiatal chest drainage tube was not placed during transmediastinal esophagectomy.Results: The frequency of thoracentesis in the drainage group was significantly lower than that in the non-drainage group (p = 0.03). There were no significant differences between the two groups in terms of the occurrence of other postoperative complications, duration of oxygen administration, and postoperative hospital stay.Conclusions: Transhiatal chest drainage could evacuate pleural effusion effectively and safely after transmediastinal esophagectomy. Therefore, this procedure is clinically useful in transmediastinal esophagectomy for esophageal cancer.

Transient adverse events after REGN-CoV2 administration for mild COVID-19 patients and their potential predictive factors: a single center analysis

Background The efficacy of REGN-COV2 in preventing severe COVID-19 has been proven, and its use in outpatient and home settings is expanding. Adverse events such as fever and decreased oxygen saturation, which are often seen after REGN-COV2 administration, are generally transient, but predicting these events is useful in developing a monitoring plan for patients. Methods We performed a retrospective analysis of 76 patients who received REGN-CoV2 between August and September 2021. The clinical course of the patients' fever and oxygen administration was collected from their medical records, and the patients were divided into two groups based on the presence or absence of these adverse events, and the underlying pathology and blood sampling data were compared. Parameters that showed significant differences were further examined by Fisher's exact probability test to see if the use of appropriate thresholds would significantly correlate with the occurrence of adverse events. Findings Of the 76 patients, 47 had fever of 38.5°C or higher within 24 hours after administration, and 27 of these patients had a body temperature of 37.5°C or lower before administration. Oxygen was required in 14 cases, 5 of which required oxygen more than 24 hours after administration of REGN-COV2, and additional treatment such as dexamethasone was given as a transition to moderate disease. Among the parameters analyzed, except for fever before administration, lymphocyte count and IFNλ3 showed significant differences between the fever and non-fever groups. There was also a significant difference in ferritin and CRP between the oxygen required and non-required groups. This was also the case in the comparison excluding patients who had fever before administration. In addition to IFNλ3, ferritin, and CRP, there was a significant difference in LDH between the group that required additional treatment and the group that did not. Fisher's exact test was used to examine the prediction threshold for fever and non-fever groups. The sensitivity and specificity were 55% and 79%, respectively with odds ratio 4.746 (95% CI: 1.666 to 14.12) when lymphocytes counts <950/μL was used (p=0.004). Similarly, when IFNλ3>5.0 was used as the cutoff, sensitivity 72%, specificity 76%, odds ratio 8.220 (2.857 to 22.22; p<0.0001). Interpretations Fever and decreased oxygen saturation after administration of REGN-Cov2 were found to correlate with the severity factors of COVID-19 itself. Evaluation of these items at the time of administration is useful not only for predicting the severity of illness but also for the development of adverse events in patients.

Attaining Sustainable Development Goal for Newborn Survival: Reinforcing Postnatal Interventions

Under the sustainable development goals (SDG), the target for neonatal mortality rate (NMR) was proposed to be less than 12 per 1000 live births by 2030 and may not meet the SDG 2030 NMR target. It may be prudent to focus on moderately low birth weight babies, 1500-2499 g, to reach the goal. This category of babies constitutes 37% of newborn deaths. They need supervised care for a short period that consists of the provision of warmth and breastfeeding with or without antibiotic therapy, and with or without oxygen administration. Despite knowing that these interventions can reduce neonatal deaths, deficiencies in how to implement these measures may be making all the difference to the expected outcome. This paper suggests possible ways to enhance the effectiveness of some of the better-known interventions such as the provision of warmth, feeding, resuscitation, oxygen administration, delivery of continuous positive airway support, and antibiotic therapy.

Revisited Hyperoxia Pathophysiology in the Perioperative Setting: A Narrative Review

The widespread use of high-dose oxygen, to avoid perioperative hypoxemia along with WHO-recommended intraoperative hyperoxia to reduce surgical site infections, is an established clinical practice. However, growing pathophysiological evidence has demonstrated that hyperoxia exerts deleterious effects on many organs, mainly mediated by reactive oxygen species. The purpose of this narrative review was to present the pathophysiology of perioperative hyperoxia on surgical wound healing, on systemic macro and microcirculation, on the lungs, heart, brain, kidneys, gut, coagulation, and infections. We reported here that a high systemic oxygen supply could induce oxidative stress with inflammation, vasoconstriction, impaired microcirculation, activation of hemostasis, acute and chronic lung injury, coronary blood flow disturbances, cerebral ischemia, surgical anastomosis impairment, gut dysbiosis, and altered antibiotics susceptibility. Clinical studies have provided rather conflicting results on the definitions and outcomes of hyperoxic patients, often not speculating on the biological basis of their results, while this review highlighted what happens when supranormal PaO2 values are reached in the surgical setting. Based on the assumptions analyzed in this study, we may suggest that the maintenance of PaO2 within physiological ranges, avoiding unnecessary oxygen administration, may be the basis for good clinical practice.