Hyperbaric oxygen as an adjuvant treatment for patients with COVID-19 severe hypoxaemia: a randomised controlled trial

BackgroundHyperbaric oxygen (HBO2) therapy has been proposed to treat hypoxaemia and reduce inflammation in COVID-19. Our objective was to analyse safety and efficacy of HBO2 in treatment of hypoxaemia in patients with COVID-19 and evaluate time to hypoxaemia correction.MethodsThis was a multicentre, open-label randomised controlled trial conducted in Buenos Aires, Argentina, between July and November 2020. Patients with COVID-19 and severe hypoxaemia (SpO2 ≤90% despite oxygen supplementation) were assigned to receive either HBO2 treatment or the standard treatment for respiratory symptoms for 7 days. HBO2 treatment was planned for ≥5 sessions (1 /day) for 90 min at 1.45 atmosphere absolute (ATA). Outcomes were time to normalise oxygen requirement to SpO2 ≥93%, need for mechanical respiratory assistance, development of acute respiratory distress syndrome and mortality within 30 days. A sample size of 80 patients was estimated, with a planned interim analysis after determining outcomes on 50% of patients.ResultsThe trial was stopped after the interim analysis. 40 patients were randomised, 20 in each group, age was 55.2±9.2 years. At admission, frequent symptoms were dyspnoea, fever and odynophagia; SpO2 was 85.1%±4.3% for the whole group. Patients in the treatment group received an average of 6.2±1.2 HBO2 sessions. Time to correct hypoxaemia was shorter in treatment group versus control group; median 3 days (IQR 1.0–4.5) versus median 9 days (IQR 5.5–12.5), respectively (p<0.010). OR for recovery from hypoxaemia in the HBO2 group at day 3 compared with the control group was 23.2 (95% CI 1.6 to 329.6; p=0.001) Treatment had no statistically significant effect on acute respiratory distress syndrome, mechanical ventilation or death within 30 days after admission.ConclusionOur findings support the safety and efficacy of HBO2 in the treatment of COVID-19 and severe hypoxaemia.Trial registration numberNCT04477954.

Hypoxaemia prevalence and management among children and adults presenting to primary care facilities in Uganda: a prospective cohort study.

Introduction Hypoxaemia (low blood oxygen) is common among hospitalised patients, increasing risk of death five-fold and requiring prompt detection and treatment. However, we know little about hypoxaemia prevalence in primary care and the role for pulse oximetry and oxygen therapy. This study assessed the prevalence and management of hypoxaemia at primary care facilities in Uganda. Methods Prospective cohort study in 30 primary care facilities in Uganda, Feb-Apr 2021. Clinical data collectors assessed blood oxygen level (SpO2) of all acutely unwell children, adolescents, and adults, and followed up children aged under 15 years with SpO2<93% to determine subsequent care and outcome. Primary outcome: proportion of children under 5 years of age with severe hypoxaemia (SpO2<90%). Secondary outcomes: severe/moderate hypoxaemia (SpO2 90-93%) by age/sex/complaint. Results Among children U5, the prevalence of severe hypoxaemia was 1.3% (95% CI 0.9 to 2.1); an additional 4.9% (3.9 to 6.1) had moderate hypoxaemia. Performing pulse oximetry according to World Health Organization guidelines exclusively on children with respiratory complaints would have missed 14% (3/21) of severe hypoxaemia and 11% (6/55) of moderate hypoxaemia. Hypoxaemia prevalence was low among children 5-14 years (0.3% severe, 1.1% moderate) and adolescents/adults 15+ years (0.1% severe, 0.5% moderate). A minority (12/27, 44%) of severely hypoxaemic patients were referred; 3 (12%) received oxygen. Conclusion Hypoxaemia is common among acutely unwell children under five years of age presenting to Ugandan primary care facilities. Routine pulse oximetry has potential to improve referral, management and clinical outcomes. Effectiveness, acceptability, and feasibility of pulse oximetry and oxygen therapy for primary care should be investigated in implementation trials.

317 Aldosterone and interleukin-6: the synergic effect in COVID-19

Aims Several evidence have identified the role of Interleukin-6 (IL-6) in the cytokine storm induced by COVID-19. Interestingly, the correlation between the serum levels of IL-6 and the plasma aldosterone has already been demonstrated in patients affected by primary aldosteronism (PA). Thus, we suppose that hyperaldosteronism may increase IL-6 levels in COVID-19. Methods and results We report a case of 47-year-old female Covid-19 patient who had developed severe pneumonia complicated by Guillain–Barreé syndrome (GBS). Blood test revealed high levels of IL-6 (serum IL-6: 402 pg/ml) and of its soluble receptor (soluble IL-6 receptor &gt;1900 pg/ml) and she required mechanical ventilation for severe hypoxaemia. Furthermore, the evidence of right adrenal adenoma, resistant hypertension, severe hypokalaemia, and high serum levels of aldosterone with high aldosterone/renin ratio were also consistent with diagnosis of PA. Thus, Spironolactone was administered with rapid improvements in clinical condition. Finally, she was diagnosed with acute motor sensitive neuropathy and started the rehabilitation phase. Conclusions Elevated aldosterone levels in PA may stimulate IL-6 production, inducing more severe forms of COVID-19 with the development of serious complications such as GBS. Hyperaldosteronism may also contribute to the poorest prognosis of patients with secondary aldosteronism such as heart failure and COVID-19, in which elevated IL-6 levels could exert its detrimental effects, mostly on the progression of ventricular dysfunction. Further studies are necessary to evaluate therapy with mineralocorticoid receptors antagonists such as spironolactone in COVID-19.

COVID-19 pneumonia: pathophysiology and management

Coronavirus disease 2019 (COVID-19) pneumonia is an evolving disease. We will focus on the development of its pathophysiologic characteristics over time, and how these time-related changes determine modifications in treatment. In the emergency department: the peculiar characteristic is the coexistence, in a significant fraction of patients, of severe hypoxaemia, near-normal lung computed tomography imaging, lung gas volume and respiratory mechanics. Despite high respiratory drive, dyspnoea and respiratory rate are often normal. The underlying mechanism is primarily altered lung perfusion. The anatomical prerequisites for PEEP (positive end-expiratory pressure) to work (lung oedema, atelectasis, and therefore recruitability) are lacking. In the high-dependency unit: the disease starts to worsen either because of its natural evolution or additional patient self-inflicted lung injury (P-SILI). Oedema and atelectasis may develop, increasing recruitability. Noninvasive supports are indicated if they result in a reversal of hypoxaemia and a decreased inspiratory effort. Otherwise, mechanical ventilation should be considered to avert P-SILI. In the intensive care unit: the primary characteristic of the advance of unresolved COVID-19 disease is a progressive shift from oedema or atelectasis to less reversible structural lung alterations to lung fibrosis. These later characteristics are associated with notable impairment of respiratory mechanics, increased arterial carbon dioxide tension (PaCO2), decreased recruitability and lack of response to PEEP and prone positioning.

Oximetry neither to prescribe long-term oxygen therapy nor to screen for severe hypoxaemia

Background and ObjectiveTranscutaneous pulse oximetry saturation (SpO2) is widely used to diagnose severe hypoxaemia and to prescribe long-term oxygen therapy (LTOT) in chronic obstructive pulmonary disease (COPD). This practice is not based on evidence. The primary objective of this study was to determine the accuracy (false positive and false negative rates) of oximetry for prescribing LTOT or for screening for severe hypoxaemia in patients with COPD.MethodsIn a cross-sectional study, we correlated arterial oxygen saturation (SaO2) and SpO2 in patients with COPD and moderate hypoxaemia (n=240), and calculated the false positive and false negative rates of SaO2 at the threshold of ≤88% to identify severe hypoxaemia (PaO2 ≤55 mmHg or PaO2 <60 mmHg) in 452 patients with COPD with moderate or severe hypoxaemia.ResultsThe correlation between SaO2 and SpO2 was only moderate (intra-class coefficient of correlation: 0.43; 95% confidence interval: 0.32–0.53). LTOT would be denied in 40% of truly hypoxemic patients on the basis of a SaO2 ˃ 88% (i.e., false negative result). Conversely, LTOT would be prescribed on the basis of a SaO2≤88% in 2% of patients who would not qualify for LTOT (i.e., false positive result). Using a screening threshold of≤92%, 5% of severely hypoxemic patients would not be referred for further evaluation.ConclusionsSeveral patients who qualify for LTOT would be denied treatment using a prescription threshold of saturation ≤88% or a screening threshold of ≤92%. Prescription of LTOT should be based on PaO2 measurement.

Inhaled nitric oxide improves the hepatopulmonary syndrome: a physiologic analysis

The hepatopulmonary syndrome (HPS) is defined by liver dysfunction, intrapulmonary vasodilatation and abnormal oxygenation. Hypoxaemia is progressive and liver transplant is the only effective treatment. Severe hypoxaemia is a life-threatening HPS complication, particularly after transplant. We evaluated gas-exchange and haemodynamic effects of invasive therapies in a consecutive sample of 26 pre-transplant patients. Inhaled nitric oxide significantly improved partial pressure of oxygen (12.4 mm Hg; p=0.001) without deleterious effects on cardiac output. Trendelenburg positioning resulted in a small improvement, and methylene blue did not, though individual responses were variable. Future studies should prospectively evaluate these strategies in severe post-transplant hypoxaemia.

Súlyos hypoxaemia légszomj nélkül COVID–19-pneumoniában

Összefoglaló. Számos közlemény született arról, hogy a COVID–19-pneumoniás betegek jelentős hányadában az artériás parciális oxigéntenzió kifejezetten alacsony, mégsem jellemző a dyspnoe, és a pulzusoximetria sem mutat – a csökkent oxigéntenzióval arányos – súlyos hypoxaemiát. A jelenséget „happy hypoxaemia” néven említik. Ugyanakkor a légszomjról nem panaszkodó, de súlyos alveolocapillaris O2-felvételi zavarban szenvedő COVID–19-pneumoniás betegek a legkisebb fizikai megterhelést sem tűrik, és állapotuk gyorsan kritikussá válhat, tehát a hypoxaemia mértékének időben való felismerése kulcskérdés. A jelen közleményben egy ilyen eset rövid ismertetése után összefoglaljuk a súlyos, de tünetmentes hypoxaemia hátterében meghúzódó élettani okokat. Ezek között szerepel a hypocapnia (respiratoricus alkalosis) is, mely alacsony oxigéntenzió mellett is a hemoglobin viszonylag megtartott oxigénszaturációját eredményezi. Ezért a mindennapi COVID–19-ellátásban a megismételt artériásvérgáz-meghatározások jelentősége nem hangsúlyozható eléggé. Orv Hetil. 2021; 162(10): 362–365. Summary. Many COVID-19 patients have very low arterial partial oxigen tension while severe dyspnoe does not develop. Pulse oxymetry indicates only moderate reduction of arterial O2 saturation in these patients. The phenomenon is named “happy hypoxaemia”. Lack of (severe) dyspnoe and only moderately decreased O2 saturation in severely impaired alveolo-capillary O2 uptake may partially be explained by an increased oxygen affinity of hemoglobin in the presence of low arterial partial pressure of CO2. The latter results from increased alveolar ventilation, while low partial pressure of O2 in COVID-19 patients reflects right-to-left shunting of pulmonary blood flow and ventilation-perfusion mismatch of the diseased lungs. While such patients may have mild complaints as related to the real impairment of alveolo-capillary oxygen exchange, severe hypoxaemia is a negative prognostic factor of outcome in this state where severe clinical deterioration may rapidly appear. The latter circumstance together with the unusual relationship of O2 partial pressure and O2 saturation of hemoglobin in COVID-19 emphasize the importance of repeated complete arterial blood gas analyses in these patients. Orv Hetil. 2021; 162(10): 362–365.