Hypoxic, anemic and cardiac hypoxemia: When does tissue hypoxia begin? / Hypoxische, anämische und kardial bedingte Hypoxämie: Wann beginnt die Hypoxie im Gewebe?

In case of hypoxemia, the oxygen content is often still in the lower normal range, so that there is no hypoxia in the tissue. If the hypoxia-threshold is reached in the tissue in hypoxic, anemic and also cardiac-related hypoxemia, identical counterregulations occur in the cell metabolism, regardless of the cause of hypoxemia. In clinical practice, this pathophysiologic fact is sometimes ignored, although depending on the cause of hypoxemia, assessment and therapy vary widely. While restrictive and generally accepted rules are specified in the transfusion guidelines for anemic hypoxemia, in the case of hypoxic hypoxia, the indication for invasive ventilation is made very early. The clinical assessment and indication are limited to the parameters oxygen saturation, oxygen partial pressure and oxygenation index. During the corona pandemic, misinterpretations of pathophysiology have become evident and may have led to unnecessary intubations. However, there is no evidence for the treatment of hypoxic hypoxia with ventilation. This review addresses the pathophysiology of the different types of hypoxia focusing on the problems associated with intubation and ventilation in the intensive care unit.

Automated versus manual oxygen administration for patients admitted with acute cardiovascular disease - a study protocol of a randomised controlled trial.

INTRODUCTION: Oxygen treatment of hypoxaemia is considered an essential part of the treatment of patients who are acutely admitted with medical conditions affecting cardiovascular and/or pulmonary function. Despite the important role of oxygen administration for these patients, clinical evidence on how to control supplemental oxygen to avoid hypoxaemia and hyperoxia is limited. We aim to investigate whether an automatic closed-loop oxygen administration system (O2matic) may maintain normoxaemia better than usual care. METHODS: This study will be an investigator-initiated, prospective, randomised clinical trial. The patients are randomised during admission after informed consent is obtained, at a 1:1 ratio with conventional oxygen treatment or O2matic oxygen treatment for 24 hours. The primary outcome is time within the desired peripheral capillary oxygen saturation interval: 92-96%. CONCLUSION: This study will examine the clinical applicability of a novel automated feedback device termed O2matic and assess whether the device is superior to standard care in keeping the patients in the optimal saturation interval. We hypothesise that the O2matic will increase time within the desired saturation interval. FUNDING: Johannes Grand's salary during this project is supported by a research grant from the Danish Cardiovascular Academy funded by Novo Nordisk Foundation grant number NNF20SA0067242 and by The Danish Heart Foundation. CLINICALTRIALS: gov (ClinicalTrials.gov Identifier: NCT05452863). Registered on 11 July 2022.

Pathophysiology of Hypoxemia in COVID-19 Lung Disease.

As the pandemic has progressed, our understanding of hypoxemia in coronavirus disease 2019 (COVID-19) lung disease has become more nuanced, although much remains to be understood. In this article, we review ventilation-perfusion mismatching in COVID-19 and the evidence to support various biologic theories offered in explanation. In addition, the relationship between hypoxemia and other features of severe COVID-19 lung disease such as respiratory symptoms, radiographic abnormalities, and pulmonary mechanics is explored. Recognizing and understanding hypoxemia in COVID-19 lung disease remains essential for risk stratification, prognostication, and choice of appropriate treatments in severe COVID-19.

Non-invasive support for the hypoxaemic patient.

Optimisation of oxygenation strategies in patients with hypoxaemic respiratory failure is a top priority for acute care physicians, as hypoxaemic respiratory failure is one of the leading causes of admission. Various oxygenation methods range from non-invasive face masks to high flow nasal cannulae, which have advantages and disadvantages for this heterogeneous patient group. Focus has turned toward examining the benefits of non-invasive ventilation, as this was heavily researched in resource-limited settings during the COVID-19 pandemic. The oxygenation strategy should be determined on an individualised basis for patients, and with new evidence from the COVID-19 pandemic, providers may now consider placing further emphasis on non-invasive approaches. As non-invasive ventilation continues to be used in increasing frequency, new methods of monitoring patient response, including when to escalate ventilation strategy, will need to be validated.

Techniques for Oxygenation and Ventilation in Coronavirus Disease 2019.

This paper discusses mechanisms of hypoxemia and interventions to oxygenate critically ill patients with COVID-19 which range from nasal cannula to noninvasive and mechanical ventilation. Noninvasive ventilation includes continuous positive airway pressure ventilation (CPAP) and high-flow nasal cannula (HFNC) with or without proning. The evidence for each of these modalities is discussed and thereafter, when to transition to mechanical ventilation (MV). Various techniques of MV, again with and without proning, and rescue strategies which would include extra corporeal membrane oxygenation (ECMO) when it is available and permissive hypoxemia where it is not, are discussed.

COVID-19 in patients with myasthenia gravis.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) has rapidly become a global pandemic, but little is known about its potential impact on patients with myasthenia gravis (MG). METHODS: We studied the clinical course of COVID-19 in five hospitalized patients with autoimmune MG (four with acetylcholine receptor antibodies, one with muscle-specific tyrosine kinase antibodies) between April 1, 2020-April 30-2020. RESULTS: Two patients required intubation for hypoxemic respiratory failure, whereas one required significant supplemental oxygen. One patient with previously stable MG had myasthenic exacerbation. One patient treated with tocilizumab for COVID-19 was successfully extubated. Two patients were treated for MG with intravenous immunoglobulin without thromboembolic complications. DISCUSSION: Our findings suggest that the clinical course and outcomes in patients with MG and COVID-19 are highly variable. Further large studies are needed to define best practices and determinants of outcomes in this unique population.

Use of almitrine in spontaneously breathing patients with COVID-19 treated with high-flow nasal cannula oxygen therapy and with persistent hypoxemia.

BACKGROUND: Almitrine, a selective pulmonary vasoconstrictor in hypoxic area, improves oxygenation in mechanically ventilated patients with COVID-19 but its effects in spontaneously breathing patients with COVID-19 remain to be determined. METHODS: We prospectively studied the effects of almitrine (16 µg/kg/min over 30 min followed by continuous administration in responders only) in 62 patients (66% of male, 63 [53-69] years old) with COVID-19 treated with high-flow nasal cannula oxygen therapy (HFNO) and with persistent hypoxemia, defined as a PaO2/FiO2 ratio < 100 with FiO2 > 80% after a single awake prone positioning session. Patients with an increase in PaO2/FiO2 ratio > 20% were considered as responders. RESULTS: Overall, almitrine increased the PaO2/FiO2 ratio by 50% (p < 0.01), decreased the partial arterial pressure of carbon dioxide by 7% (p = 0.01) whereas the respiratory rate remained unchanged and 46 (74%) patients were responders. No patient experienced right ventricular dysfunction or acute cor pulmonale. The proportion of responders was similar regardless of the CT-Scan radiological pattern: 71% for the pattern with predominant ground-glass opacities and 76% for the pattern with predominant consolidations (p = 0.65). Responders had lower intubation rate (33 vs. 88%, p < 0.01), higher ventilator-free days at 28-day (28 [20-28 ] vs. 19 [2-24] days, p < 0.01) and shorter ICU length of stay (5 [3-10] vs.12 [7-30] days, p < 0.01) than non-responders. CONCLUSIONS: Almitrine could be an interesting therapy in spontaneously breathing patients with COVID-19 treated with HFNO and with persistent hypoxemia, given its effects on oxygenation without serious adverse effects regardless of the CT-Scan pattern, and potentially on intubation rate. These preliminary results need to be confirmed by further randomized studies.

Response to the first awake prone positioning relates with intubation rate in SARS-CoV-2 patients suffering from acute respiratory failure with moderate to severe hypoxaemia: a retrospective study.

AIMS OF THE STUDY: Awake prone positioning (aPP) in non-intubated patients with severe SARS-CoV-2-related pneumonia improves oxygenation and reduces the intubation rate, but no early predictors for success or failure of the strategy have been described. The main objective of this study was to assess whether response to the first aPP in terms of PaO2/FiO2, alveolar-arterial gradient (Aa-O2), respiratory rate and PaCO2 could predict the need for intubation. As secondary objective, we assessed the effects of aPP on the same parameters for all the sessions considered together. METHODS: Retrospective analysis of consecutive SARS-CoV-2 pneumonia patients suffering from acute respiratory failure with moderate to severe hypoxaemia for whom aPP was performed for at least 45 minutes based on the prescription of the clinician in charge according to predefined criteria. Respiratory rate, blood gases and oxygenation parameters (PaO2/FiO2 and Aa-O2), before and after the first aPP were compared between patients who were subsequently intubated or not. Effects of all the aPP sessions together were also analysed. RESULTS: One hundred and sixty-six patients were admitted for SARS-CoV-2 pneumonia during the study period. Among them, 50 received aPP lasting at least 45 minutes. Because 17 denied consent for data analysis and 2 were excluded because of a "do not intubate order", 31 patients (for a total of 116 aPP sessions without any severe adverse events reported) were included. Among them, 10 (32.3%) were intubated. Mean age ± standard deviation (SD) was 60 ± 12 years. At ICU admission, respiratory rate was 26 ± 7/minute, median PaO2/FiO2 94 (interquartile range [IQR] 74-116) mm Hg and median Aa-O2 412 (IQR 286-427) mm Hg (markedly increased). Baseline characteristics did not statistically differ between patients who subsequently needed intubation or not. During the first aPP, PaO2/FiO2 increased and Aa-O2 decreased. When comparing patients who later where intubated or not, we observed, in the non intubated group only, a clinically significant decrease in median Aa-O2, from 294 (280-414) to 204 (107-281) mm Hg, corresponding to a 40% (26-56%) reduction, and a PaO2/FiO2 increase, from 103 (84-116) to 162 (138-195), corresponding to an increase of 48% (11-93%). The p value is <0.005 for both. When all the aPP sessions (n = 80) were considered together, aPP was associated with a significant increase in PaO2/FiO2 from 112 (80-132) to 156 (86-183) mm Hg (p <0.001) and Aa-O2 decrease from 304 (244-418) to 224 (148-361) mm Hg (p = 0.001). CONCLUSIONS: Awake pronation in spontaneously breathing patients is feasible, and improves PaO2/FiO2 and Aa-O2. Response to the first session seems to be associated with lower intubation rate.

Providing respiratory and ventilation care in the face of shifting evidence: current opinion in critical care.

PURPOSE OF REVIEW: To review the clinical problem and noninvasive treatments of hypoxemia in critically-ill patients with coronavirus disease 2019 pneumonia and describe recent advances in evidence supporting bedside decision making. RECENT FINDINGS: High-flow nasal oxygen and noninvasive ventilation, along with awake prone positioning are potentially helpful therapies for acute hypoxemic respiratory failure. High-flow nasal oxygen therapy has been widely implemented as a form of oxygen support supported by prepandemic randomized controlled trials showing possible benefit over noninvasive ventilation. Given the sheer volume of patients, noninvasive ventilation was often required, and based on a well conducted randomized controlled trial there was a developing role for helmet-interface noninvasive. Coupled with noninvasive supports, the use of awake prone positioning demonstrated physiological benefits, but randomized controlled trial data did not demonstrate clear outcome superiority. SUMMARY: The use of noninvasive oxygen strategies and our understanding of the proposed mechanisms are evolving. Variability in patient severity and physiology may dictate a personalized approach to care. High-flow nasal oxygen may be paired with awake and spontaneously breathing prone-positioning to optimize oxygen and lung mechanics but requires further insight before widely applying to clinical practice.

Hyperbaric oxygen for COVID-19 patients with severe hypoxia prior to vaccine availability.

Introduction: Few treatments have demonstrated mortality benefits among hospitalized hypoxic COVID-19 patients. We evaluated the use of hyperbaric oxygen (HBO2) therapy as a therapeutic intervention among hospitalized patients with a high oxygen requirement prior to vaccine approval. Methods: We extracted data on patients with COVID-19 hypoxia who required oxygen supplementation ranging from a 6L nasal cannula up to a high-flow nasal cannula at 100% FiO2 at 60L/minute with a 100% non-rebreather mask at 15 L/minute and were eligible for off-label HBO2 therapy from October 2020 to February 2021. We followed the Monitored Emergency use of Unregistered and Investigational Interventions or (MEURI) in conjunction with the consistent re-evaluation of the protocol using the Plan-Do-Study-Act (PDSA) tool [1]. We compared patient characteristics and used Fisher's exact test and a survival analysis to assess the primary endpoint of inpatient death. Results: HBO2 therapy was offered to 36 patients, of which 24 received treatment and 12 did not receive treatment. Patients who did not receive treatment were significantly older (p ≺ 0.01) and had worse baseline hypoxia (p = 0.06). Three of the 24 (13%) patients who received treatment died compared to six of 12 (50%) patients who did not receive treatment (RR ratio: 0.25, p = 0.04, 95% CI: 0.08 to 0.83). In the survival analysis, there was a statistically significant reduction in inpatient mortality in the treatment group (HR: 0.19, p = 0.02, 95% CI: 0.05-0.74). However, after adjusting for age and baseline hypoxia, there was no difference in inpatient mortality (hazard ratio: 0.48, p = 0.42, 95% CI: 0.08-2.86). Conclusion: The survival benefit of HBO2 therapy observed in our unadjusted analysis suggests that there may be therapeutic benefits of HBO2 in treating COVID-19 hypoxia as an adjunct to standard care.

Extracorporeal membrane oxygenation for paediatric refractory hypoxic respiratory failure caused by adenovirus in Shanghai: a case series.

BACKGROUND: To assess the outcome of extracorporeal membrane oxygenation (ECMO) for severe adenovirus (Adv) pneumonia with refractory hypoxic respiratory failure (RHRF) in paediatric patients. METHODS: A retrospective observational study was performed in a tertiary paediatric intensive care unit (PICU) in China. Patients with RHRF caused by Adv pneumonia who received ECMO support after mechanical ventilation failed to achieve adequate oxygenation between 2017 and 2020 were included. The outcome variables were the in-hospital survival rate and the effects of ECMO on the survival rate. RESULTS: In total, 18 children with RHRF received ECMO. The median age was 19 (9.5, 39.8) months, and the median ECMO duration was 196 (152, 309) h. The in-hospital survival rate was 72.2% (13/18). Thirteen patients (72.2%) required continuous renal replacement therapy (CRRT) due to fluid imbalance or acute kidney injury (AKI). At ECMO initiation, compared with survivors, nonsurvivors had a lower PaO2/FiO2 ratio [49 (34.5, 62) vs. 63 (56, 71); p = 0.04], higher oxygen index (OI) [41 (34.5, 62) vs. 30 (26.5, 35); p = 0.03], higher vasoactive inotropic score (VIS) [30 (16.3, 80) vs. 100 (60, 142.5); p = 0.04], longer duration from mechanical ventilation to ECMO support [8 (4, 14) vs. 4 (3, 5.5) h, p=0.02], and longer time from confirmed RHRF to ECMO initiation [9 (4.8, 13) vs. 5 (1.3, 5.5) h; p = 0.004]. Patients with PaO2/FiO2 <61 mmHg or an OI >43 and hypoxic respiratory failure for more than 9 days before the initiation of ECMO had worse outcomes. CONCLUSIONS: ECMO seemed to be effective, as severe paediatric Adv pneumonia patients with RHRF had a cumulative survival rate of 72.2% in our study. Our study provides insight into ECMO rescue in children with severe Adv pneumonia.

Demographic and clinical profile of patients suffering prolonged severe hypoxia in COVID-19.

BACKGROUND: Coronavirus disease 2019 (COVID-19) may result in rapid onset of hypoxemic respiratory failure. This study aimed to characterize the factors and outcomes associated with prolonged hypoxia in patients with COVID-19. Prolonged severe hypoxia (PSH) was defined as hypoxia requiring ≥6 L/min of oxygen by nasal cannula or equivalent for more than 10 days. RESEARCH DESIGN AND METHODS: This study was designed as a single-center retrospective analysis. Multivariable logistic regression was utilized to assess factors associated with PSH. RESULTS: The sample included 554 patients with 117 (21%) having PSH. Median length of stay of patients with PSH was significantly longer (median IQR: 18 days vs 6 days, p < 0.0001). Patients with PSH had significantly higher rates of venous thromboembolism (p < 0.0001) and major bleeding (p < 0.004). The presence of cirrhosis (OR 3.32, 95% CI [1.02 to 10.83]) and hypertension (OR 1.99, 95% CI [1.12 to 3.53]) were independently associated with PSH, while outpatient use of anti-platelet agents had an inverse association (OR 0.57, 95% CI [0.36 to 0.91]). CONCLUSION: PSH is associated with increased length of stay, morbidity, and mortality. Hypertension and liver cirrhosis were significantly associated with higher odds of PSH, while use of anti-platelet therapy had a protective effect.

In COVID-19 acute hypoxemia, awake prone positioning vs. usual care did not reduce intubation at 30 d.

SOURCE CITATION: Alhazzani W, Parhar KK, Weatherald J, et al. Effect of awake prone positioning on endotracheal intubation in patients with COVID-19 and acute respiratory failure: a randomized clinical trial. JAMA. 2022;327:2104-13. 35569448.

Cost-effectiveness and sustainability of improved hospital oxygen systems in Nigeria.

INTRODUCTION: Improving hospital oxygen systems can improve quality of care and reduce mortality for children, but we lack data on cost-effectiveness or sustainability. This study evaluated medium-term sustainability and cost-effectiveness of the Nigeria Oxygen Implementation programme. METHODS: Prospective follow-up of a stepped-wedge trial involving 12 secondary-level hospitals. Cross-sectional facility assessment, clinical audit (January-March 2021), summary admission data (January 2018-December 2020), programme cost data. INTERVENTION: pulse oximetry introduction followed by solar-powered oxygen system installation with clinical and technical training and support. PRIMARY OUTCOMES: (i) proportion of children screened with pulse oximetry; (ii) proportion of hypoxaemic (SpO2 <90%) children who received oxygen. Comparison across three time periods: preintervention (2014-2015), intervention (2016-2017) and follow-up (2018-2020) using mixed-effects logistic regression. Calculated cost-effectiveness of the intervention on child pneumonia mortality using programme costs, recorded deaths and estimated counterfactual deaths using effectiveness estimates from our effectiveness study. Reported cost-effectiveness over the original 2-year intervention period (2016-2017) and extrapolated over 5 years (2016-2020). RESULTS: Pulse oximetry coverage for neonates and children remained high during follow-up (83% and 81%) compared with full oxygen system period (94% and 92%) and preintervention (3.9% and 2.9%). Oxygen coverage for hypoxaemic neonates/children was similarly high (94%/88%) compared with full oxygen system period (90%/82%). Functional oxygen sources were present in 11/12 (92%) paediatric areas and all (8/8) neonatal areas; three-quarters (15/20) of wards had a functional oximeter. Of 32 concentrators deployed, 23/32 (72%) passed technical testing and usage was high (median 10 797 hours). Estimated 5-year cost-effectiveness US$86 per patient treated, $2694-4382 per life saved and $82-125 per disability-adjusted life year-averted. We identified practical issues for hospitals and Ministries of Health wishing to adapt and scale up pulse oximetry and oxygen. CONCLUSION: Hospital-level improvements to oxygen and pulse oximetry systems in Nigerian hospitals have been sustained over the medium-term and are a highly cost-effective child pneumonia intervention.

Prospective cohort study of referred Malawian children and their survival by hypoxaemia and hypoglycaemia status.

Objective: To investigate survival in children referred from primary care in Malawi, with a focus on hypoglycaemia and hypoxaemia progression. Methods: The study involved a prospective cohort of children aged 12 years or under referred from primary health-care facilities in Mchinji district, Malawi in 2019 and 2020. Peripheral blood oxygen saturation (SpO2) and blood glucose were measured at recruitment and on arrival at a subsequent health-care facility (i.e. four hospitals and 14 primary health-care facilities). Children were followed up 2 weeks after discharge or their last clinical visit. The primary study outcome was the case fatality ratio at 2 weeks. Associations between SpO2 and blood glucose levels and death were evaluated using Cox proportional hazards models and the treatment effect of hospitalization was assessed using propensity score matching. Findings: Of 826 children recruited, 784 (94.9%) completed follow-up. At presentation, hypoxaemia was moderate (SpO2: 90-93%) in 13.1% (108/826) and severe (SpO2: < 90%) in 8.6% (71/826) and hypoglycaemia was moderate (blood glucose: 2.5-4.0 mmol/L) in 9.0% (74/826) and severe (blood glucose: < 2.5 mmol/L) in 2.3% (19/826). The case fatality ratio was 3.7% (29/784) overall but 26.3% (5/19) in severely hypoglycaemic children and 12.7% (9/71) in severely hypoxaemic children. Neither moderate hypoglycaemia nor moderate hypoxaemia was associated with mortality. Conclusion: Presumptive pre-referral glucose treatment and better management of hypoglycaemia could reduce the high case fatality ratio observed in children with severe hypoglycaemia. The morbidity and mortality burden of severe hypoxaemia was high; ways of improving hypoxaemia identification and management are needed.