Oxygen therapy: Liberal versus conservative in older patients with COVID disease

The management of acute respiratory failure is more complicated in elderly patients. The reasons behind this difficulty are mainly related to the frailty and the comorbidities. In particular, the frailty is characterised by a decline in physiological capacity across several organ systems, with a resultant increased susceptibility to stressors. In a few words, frailty means diminished organ reserve, including that of the lung. The first step in the management of acute respiratory failure remains to treat hypoxemia with oxygen therapy. The primary rationale of oxygen (O2) therapy is to prevent and correct arterial hypoxaemia (reduction of O2 in the blood) and any resulting hypoxia (the decrease of the O2 in the tissues) in patients with or at risk for impaired pulmonary gas exchange. The hypoxaemia is characterised by the partial pressure of O2 less than 60 mmHg in blood gas analysis or a SaO2 of <90% while breathing in room air [1]. Besides, over the last years, most acute treatment algorithms recommended the liberal use of a high fraction of inspired oxygen, even without first confirming the presence of a hypoxic insult. For example, for more than a century, supplemental oxygen has been used routinely in the treatment of patients with suspected acute myocardial infarction. The use of additional oxygen therapy in acute coronary syndromes (ACS) and cardiac emergencies has demonstrated to be controversial. In 2010, the American Heart Association (AHA) stated that oxygen should be delivered to patients with breathlessness, signs of heart failure, shock, or an arterial oxyhaemoglobin saturation <94% (Class I, LOE C) and not to all patients with ACS. Non-invasive monitoring of blood oxygen saturation can be useful to decide on the need for oxygen administration [2]. In 2015, some data questioned the consolidated clinical use of supplemental oxygen therapy. The Australian Air Versus Oxygen in Myocardial Infarction (AVOID) trial supported an adverse effect of oxygen. The trial reported larger infarct sizes in patients with ST-segment elevation myocardial infarction (STEMI) who received oxygen than in those who did not receive oxygen [3]. The history of oxygen supplementation in ACS is an example of the binary therapeutic option (liberal versus conservative use of oxygen). A Cochrane report from 2016 did not show any evidence supporting the routine use of oxygen in the treatment of patients with myocardial infarction [4]. In the same way for the treatment of stroke, the guidelines have affirmed that oxygen therapy may be harmful if used for non-hypoxemic patients with mild-moderate strokes [5]. Starting from these examples in this chapter, the authors analysed the evidence of oxygen therapy in the treatment of acute critical patients and acute respiratory distress syndrome (ARDS). The authors will investigate the use of oxygen therapy in light of the available physiopathological patterns of acute respiratory failure of COVID-19 disease. © Springer Nature Switzerland AG 2020.

Heterogeneous treatment effects of dexamethasone 12 mg versus 6 mg in patients with COVID-19 and severe hypoxaemia-Post hoc exploratory analyses of the COVID STEROID 2 trial.

BACKGROUND: Corticosteroids improve outcomes in patients with severe COVID-19. In the COVID STEROID 2 randomised clinical trial, we found high probabilities of benefit with dexamethasone 12 versus 6 mg daily. While no statistically significant heterogeneity in treatment effects (HTE) was found in the conventional, dichotomous subgroup analyses, these analyses have limitations, and HTE could still exist. METHODS: We assessed whether HTE was present for days alive without life support and mortality at Day 90 in the trial according to baseline age, weight, number of comorbidities, category of respiratory failure (type of respiratory support system and oxygen requirements) and predicted risk of mortality using an internal prediction model. We used flexible models for continuous variables and logistic regressions for categorical variables without dichotomisation of the baseline variables of interest. HTE was assessed both visually and with p and S values from likelihood ratio tests. RESULTS: There was no strong evidence for substantial HTE on either outcome according to any of the baseline variables assessed with all p values >.37 (and all S values <1.43) in the planned analyses and no convincingly strong visual indications of HTE. CONCLUSIONS: We found no strong evidence for HTE with 12 versus 6 mg dexamethasone daily on days alive without life support or mortality at Day 90 in patients with COVID-19 and severe hypoxaemia, although these results cannot rule out HTE either.

Respiratory failure

Respiratory failure is a common problem, particularly in patients with pre-existing respiratory disease, but also in previously well patients in the perioperative setting. It carries a 90-day mortality of above 40%, representing a high-risk patient population. This article discusses the causes, presentation, assessment and management of respiratory failure, along with a brief overview of perioperative risk prediction and pathophysiology.

The effectiveness of high-flow nasal cannula and standard non-rebreathing mask for oxygen therapy in moderate category COVID-19 pneumonia: Randomised controlled trial.

Background: COVID-19 caused by the highly infectious severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection is a matter of concern and has led to severe health problems all over the world. Oxygen therapy is the mainstay for the management of patients suffering from various stages of the disease. Objectives: To compare the effectiveness of high-flow nasal cannula (HFNC) and standard non-rebreathing mask (NRBM) as oxygen delivery devices in moderate cases of COVID-19 pneumonia. Methods: A single-centre, open-label, randomised controlled trial was conducted between February 2021 and April 2021. All the enrolled patients (N=120) were randomly allocated into two groups according to the oxygen delivery device used. Group 1 (n=60) received HFNC and group 2 (n=60) received NRBM as the initial oxygen delivery device, to maintain a target saturation ≥96% in both groups. The progression-free survival without escalation of respiratory support, partial pressure of arterial oxygen (PaO2 ), a ratio of partial pressure of arterial oxygen to fractional inspiratory oxygen concentration (PaO2 /FiO2 ), respiratory rate, heart rate, blood pressure, number of patients requiring non-invasive ventilation or endotracheal intubation, time for de-escalation of oxygen therapy to lower FiO2 device, time to progression to severe disease, survival at day 28, and patient satisfaction level were compared between the two groups. Results: Demographic, clinical variables and treatment received were comparable in the two groups. In the HFNC group, 90% of patients had successful outcomes with the initial oxygen therapy device used as compared with 56.6% in the NRBM group (p<0.001; odds ratio (OR) 0.145; 95% confidence interval (CI) 0.054 - 0.389). Using HFNC also resulted in improved oxygenation (PaO2 /FiO2 ) (p<0.001), better patient satisfaction (p<0.001), and a shorter time for de-escalation of oxygen therapy to a lower FiO2 device (p<0.001). The 28-day survival was higher in the HFNC group, but the difference was statistically insignificant (p=0.468). Conclusion: HFNC is a reliable oxygen therapy modality for moderate category COVID-19 pneumonia and results in a higher success rate of oxygen therapy, better oxygenation, and a greater patient satisfaction level as compared with a NRBM.

Silent hypoxia is not an identifiable characteristic in patients with COVID-19 infection.

BACKGROUND: We aimed to assess whether asymptomatic ("happy") hypoxia was an identifiable physiological phenotype of COVID-19 acute respiratory distress syndrome (ARDS), and associated with need for ICU admission. METHODS: We performed an observational cohort study of all adult patients admitted with hypoxaemic respiratory failure to a large acute hospital Trust serving the East Midlands, UK. Patients with confirmed COVID-19 were compared to those without. Physiological response to hypoxaemia was modelled using a linear mixed effects model. RESULTS: Of 1,586 patients included, 75% tested positive for SARS-CoV-2. The ROX index was 2.08 min-1 lower (1.56-2.61, p < 0.001) in the COVID-19 cohort when adjusted for age and ethnicity, suggesting an enhanced respiratory response to hypoxia compared to the non-Covid-19 patients. There was substantial residual inter- and intra-patient variability in the respiratory response to hypoxaemia. 33% of the infected cohort required ICU, and of these 31% died within 60 days. ICU admission and mortality were both associated with an enhanced respiratory response for all degrees of hypoxaemia. CONCLUSIONS: Patients with COVID-19 display a more symptomatic phenotype in response to hypoxaemia than those with other causes of hypoxaemic respiratory failure, however individual patients exhibit a wide range of responses. As such although asymptomatic hypoxaemia may be a phenomenon in any individual patient with hypoxaemic respiratory failure, it is no more frequently observed in those with SARS-CoV-2 infection than without.

Effect of extracorporeal carbon dioxide removal on respiratory quotient measured by indirect calorimetry: Unravelling the mystery.

NEW FINDINGS: What is the main observation in this case? Several studies have reported progressive hypoxaemia once extracorporeal carbon dioxide removal is started in patients with hypercapnic respiratory failure, possibly attributable to an altered respiratory quotient. What insights does it reveal? In this quality control report, we show that the respiratory quotient exhibits only minimal alteration when extracorporeal carbon dioxide removal is started and assume that the progressive hypoxaemia is attributable to an increase in intrapulmonary shunt. ABSTRACT: The use of extracorporeal carbon dioxide removal (ECCO2 R) has been proposed in patients with acute respiratory distress syndrome to achieve lung-protective ventilation and in patients with selective hypercapnic respiratory failure. However, several studies have reported progressive hypoxaemia, as expressed by a need to increase the inspired oxygen fraction (Fi O2 ) to maintain adequate oxygenation or by a decrease in the ratio of arterial oxygen tension (Pa O2 ) to Fi O2 once ECCO2 R is started. We present the case of a patient who was admitted to the intensive care unit for a coronavirus disease 2019 pneumonia and who was intubated because of hypercapnic respiratory insufficiency. Extracorporeal carbon dioxide removal was started, and the patient subsequently developed progressive hypoxaemia. To test whether the hypoxaemia was attributable to the ECCO2 R, blood samples were taken in different settings: (1) 'no ECCO2 R', blood flow 150 ml/min with a ECCO2 R gas flow of 0 L/min; and (2) 'with ECCO2 R', blood flow 400 ml/min with gas flow 12 L/min. We measured Pa O2 , alveolar oxygen tension, Pa O2 /Fi O2 , alveolar-arterial oxygen tension difference, arterial carbon dioxide tension and the respiratory quotient (RQ) by indirect calorimetry in each setting. The RQ was 0.60 without ECCO2 R and 0.57 with ECCO2 R. The alveolar oxygen tension was 220.4 mmHg without ECCO2 R and increased to 240.3 mmHg with ECCO2 R, whereas Pa O2 /Fi O2 decreased from 177 to 171. Our study showed only a minimal change in RQ when ECCO2 R was started. We were the first to measure the RQ directly, before and after the initiation of ECCO2 R, in a patient with hypercapnic respiratory failure.

Dexamethasone 12 mg versus 6 mg for patients with COVID-19 and severe hypoxaemia: a pre-planned, secondary Bayesian analysis of the COVID STEROID 2 trial.

PURPOSE: We compared dexamethasone 12 versus 6 mg daily for up to 10 days in patients with coronavirus disease 2019 (COVID-19) and severe hypoxaemia in the international, randomised, blinded COVID STEROID 2 trial. In the primary, conventional analyses, the predefined statistical significance thresholds were not reached. We conducted a pre-planned Bayesian analysis to facilitate probabilistic interpretation. METHODS: We analysed outcome data within 90 days in the intention-to-treat population (data available in 967 to 982 patients) using Bayesian models with various sensitivity analyses. Results are presented as median posterior probabilities with 95% credible intervals (CrIs) and probabilities of different effect sizes with 12 mg dexamethasone. RESULTS: The adjusted mean difference on days alive without life support at day 28 (primary outcome) was 1.3 days (95% CrI -0.3 to 2.9; 94.2% probability of benefit). Adjusted relative risks and probabilities of benefit on serious adverse reactions was 0.85 (0.63 to 1.16; 84.1%) and on mortality 0.87 (0.73 to 1.03; 94.8%) at day 28 and 0.88 (0.75 to 1.02; 95.1%) at day 90. Probabilities of benefit on days alive without life support and days alive out of hospital at day 90 were 85 and 95.7%, respectively. Results were largely consistent across sensitivity analyses, with relatively low probabilities of clinically important harm with 12 mg on all outcomes in all analyses. CONCLUSION: We found high probabilities of benefit and low probabilities of clinically important harm with dexamethasone 12 mg versus 6 mg daily in patients with COVID-19 and severe hypoxaemia on all outcomes up to 90 days.

The Roth score as a triage tool for detecting hypoxaemia in general practice: a diagnostic validation study in patients with possible COVID-19.

AIM: To validate the Roth score as a triage tool for detecting hypoxaemia. BACKGROUNDS: The virtual assessment of patients has become increasingly important during the corona virus disease (COVID-19) pandemic, but has limitations as to the evaluation of deteriorating respiratory function. This study presents data on the validity of the Roth score as a triage tool for detecting hypoxaemia remotely in potential COVID-19 patients in general practice. METHODS: This cross-sectional validation study was conducted in Dutch general practice. Patients aged ≥18 with suspected or confirmed COVID-19 were asked to rapidly count from 1 to 30 in a single breath. The Roth score involves the highest number counted during exhalation (counting number) and the time taken to reach the maximal count (counting time).Outcome measures were (1) the correlation between both Roth score measurements and simultaneous pulse oximetry (SpO2) on room air and (2) discrimination (c-statistic), sensitivity, specificity and predictive values of the Roth score for detecting hypoxaemia (SpO2 < 95%). FINDINGS: A total of 33 physicians enrolled 105 patients (52.4% female, mean age of 52.6 ± 20.4 years). A positive correlation was found between counting number and SpO2 (rs = 0.44, P < 0.001), whereas only a weak correlation was found between counting time and SpO2 (rs = 0.15, P = 0.14). Discrimination for hypoxaemia was higher for counting number [c-statistic 0.91 (95% CI: 0.85-0.96)] than for counting time [c-statistic 0.77 (95% CI: 0.62-0.93)]. Optimal diagnostic performance was found at a counting number of 20, with a sensitivity of 93.3% (95% CI: 68.1-99.8) and a specificity of 77.8% (95% CI: 67.8-85.9). A counting time of 7 s showed the best sensitivity of 85.7% (95% CI: 57.2-98.2) and specificity of 81.1% (95% CI: 71.5-88.6). CONCLUSIONS: A Roth score, with an optimal counting number cut-off value of 20, maybe of added value for signalling hypoxaemia in general practice. Further external validation is warranted before recommending integration in telephone triage.

High risk of patient self-inflicted lung injury in COVID-19 with frequently encountered spontaneous breathing patterns: a computational modelling study.

BACKGROUND: There is on-going controversy regarding the potential for increased respiratory effort to generate patient self-inflicted lung injury (P-SILI) in spontaneously breathing patients with COVID-19 acute hypoxaemic respiratory failure. However, direct clinical evidence linking increased inspiratory effort to lung injury is scarce. We adapted a computational simulator of cardiopulmonary pathophysiology to quantify the mechanical forces that could lead to P-SILI at different levels of respiratory effort. In accordance with recent data, the simulator parameters were manually adjusted to generate a population of 10 patients that recapitulate clinical features exhibited by certain COVID-19 patients, i.e., severe hypoxaemia combined with relatively well-preserved lung mechanics, being treated with supplemental oxygen. RESULTS: Simulations were conducted at tidal volumes (VT) and respiratory rates (RR) of 7 ml/kg and 14 breaths/min (representing normal respiratory effort) and at VT/RR of 7/20, 7/30, 10/14, 10/20 and 10/30 ml/kg / breaths/min. While oxygenation improved with higher respiratory efforts, significant increases in multiple indicators of the potential for lung injury were observed at all higher VT/RR combinations tested. Pleural pressure swing increased from 12.0 ± 0.3 cmH2O at baseline to 33.8 ± 0.4 cmH2O at VT/RR of 7 ml/kg/30 breaths/min and to 46.2 ± 0.5 cmH2O at 10 ml/kg/30 breaths/min. Transpulmonary pressure swing increased from 4.7 ± 0.1 cmH2O at baseline to 17.9 ± 0.3 cmH2O at VT/RR of 7 ml/kg/30 breaths/min and to 24.2 ± 0.3 cmH2O at 10 ml/kg/30 breaths/min. Total lung strain increased from 0.29 ± 0.006 at baseline to 0.65 ± 0.016 at 10 ml/kg/30 breaths/min. Mechanical power increased from 1.6 ± 0.1 J/min at baseline to 12.9 ± 0.2 J/min at VT/RR of 7 ml/kg/30 breaths/min, and to 24.9 ± 0.3 J/min at 10 ml/kg/30 breaths/min. Driving pressure increased from 7.7 ± 0.2 cmH2O at baseline to 19.6 ± 0.2 cmH2O at VT/RR of 7 ml/kg/30 breaths/min, and to 26.9 ± 0.3 cmH2O at 10 ml/kg/30 breaths/min. CONCLUSIONS: Our results suggest that the forces generated by increased inspiratory effort commonly seen in COVID-19 acute hypoxaemic respiratory failure are comparable with those that have been associated with ventilator-induced lung injury during mechanical ventilation. Respiratory efforts in these patients should be carefully monitored and controlled to minimise the risk of lung injury.

Analysis of an Ambulatory Care Pathway for Patients With COVID-19 Utilising Remote Pulse Oximetry at a London District General Hospital.

The identification of coronavirus disease 2019 (COVID-19) patients with oxygen saturations between 90-94% who can be safely discharged from the emergency department (ED) is challenging due to the difficulty of community monitoring. A pathway consisting of home pulse oximetry with telephone follow-up was devised and implemented at a London District General Hospital to facilitate the safe discharge of these patients from the ED. Twenty patients with confirmed or suspected COVID-19 with oxygen saturations between 90%-94% were discharged on this novel ambulatory care pathway. Eighty-five percent of patients successfully avoided hospitalisation, whilst 15% were re-assessed and subsequently admitted to hospital. Home pulse oximetry monitoring was utilised to aid discharge from the ED and therefore prevent hospital admission. Telephone follow-up identified patients requiring further assessment. This study demonstrates the potential for safe ambulation of a subgroup of patients with COVID-19.

Silent hypoxaemia in COVID-19 patients.

The clinical presentation of COVID-19 due to infection with SARS-CoV-2 is highly variable with the majority of patients having mild symptoms while others develop severe respiratory failure. The reason for this variability is unclear but is in critical need of investigation. Some COVID-19 patients have been labelled with 'happy hypoxia', in which patient complaints of dyspnoea and observable signs of respiratory distress are reported to be absent. Based on ongoing debate, we highlight key respiratory and neurological components that could underlie variation in the presentation of silent hypoxaemia and define priorities for subsequent investigation.

Considerations for scuba and breath-hold divers during the COVID-19 pandemic: A call for awareness.

In late 2019, a highly pathogenic novel coronavirus (CoV), severe acute respiratory syndrome (SARS)-CoV-2 emerged from Wuhan, China and led to a global pandemic. SARS-CoV-2 has a predilection for the pulmonary system and can result in serious pneumonia necessitating hospitalisation. Computed tomography (CT) chest scans of patients with severe symptoms, show signs of multifocal bilateral ground or ground-glass opacities (GGO) associated with consolidation areas with patchy distribution. However, it is less well known that both asymptomatic and mild symptomatic patients may exhibit similar lung changes. Presumably, the various pathological changes in the lungs may increase the risk of adverse events during diving (e.g., lung barotrauma, pulmonary oedema, etc.), thus these lung manifestations need to be considered prior to allowing resumption of diving. Presently, it is not known how the structural changes in the lungs develop and to what extent they resolve, in particular in asymptomatic carriers and patients with mild disease. However, current evidence indicates that a month of recovery may be too short an interval to guarantee complete pulmonary restitution even after COVID-19 infections not demanding hospital care.

Beneficial effect of awake prone position in hypoxaemic patients with COVID-19: case reports and literature review.

We hereby present two case reports of moderate coronavirus disease patients, suffering from profound hypoxaemia, further deteriorating later on. A schedule pre-planned awake prone position manoeuvres were executed during their hospital stay. Following this, the patients' saturation improved, later to be weaned from oxygen support. Paucity of evidence and data regarding this topic led us to review the concept of awake prone position.