Evaluating the clinical and cost-effectiveness of a conservative approach to oxygen therapy for invasively ventilated adults in intensive care: Protocol for the UK-ROX trial.

Background: In the United Kingdom, around 184,000 adults are admitted to an intensive care unit (ICU) each year with over 30% receiving mechanical ventilation. Oxygen is the commonest therapeutic intervention provided to these patients but it is unclear how much oxygen should be administered for the best clinical outcomes. Methods: The UK-ROX trial will evaluate the clinical and cost-effectiveness of conservative oxygen therapy (the minimum oxygen concentration required to maintain an oxygen saturation of 90% ± 2%) versus usual oxygen therapy in critically ill adults receiving supplemental oxygen when invasively mechanically ventilated in ICUs in England, Wales and Northern Ireland. The trial will recruit 16,500 patients from approximately 100 UK adult ICUs. Using a deferred consent model, enrolled participants will be randomly allocated (1:1) to conservative or usual oxygen therapy until ICU discharge or 90 days after randomisation. Objectives: The primary clinical outcome is all cause mortality at 90 days following randomisation. Discussion: The UK-ROX trial has received ethical approval from the South Central - Oxford C Research Ethics Committee (Reference: 20/SC/0423) and the Confidentiality Advisory Group (Reference: 22/CAG/0154). The trial commenced in May 2021 and, at the time of publication, 95 sites had opened to recruitment.

Effect of a lower target oxygen saturation range on the risk of hypoxaemia and elevated NEWS2 scores at a university hospital: a retrospective study.

BACKGROUND: The optimal target oxygen saturation (SpO2) range for hospital inpatients not at risk of hypercapnia is unknown. The objective of this study was to assess the impact on oxygen usage and National Early Warning Score 2 (NEWS2) of changing the standard SpO2 target range from 94-98% to 92-96%. METHODS: In a metropolitan UK hospital, a database of electronic bedside SpO2 measurements, oxygen prescriptions and NEWS2 records was reviewed. Logistic regression was used to compare the proportion of hypoxaemic SpO2 values (<90%) and NEWS2 records ≥5 in 2019, when the target SpO2 range was 94-98%; with 2022, when the target range was 92-96%. RESULTS: In 2019, 218 of 224 936 (0.10%) observations on room air and 162 of 11 328 (1.43%) on oxygen recorded an SpO2 <90%, and in 2022, 251 of 225 970 (0.11%) and 233 of 12 845 (1.81%), respectively (risk difference 0.04%, 95% CI 0.02% to 0.07%). NEWS2 ≥5 was observed in 3009 of 236 264 (1.27%) observations in 2019 and 4061 of 238 815 (1.70%) in 2022 (risk difference 0.43%, 0.36% to 0.50%; p<0.001). The proportion of patients using supplemental oxygen with hyperoxaemia (SpO2 100%) was 5.4% in 2019 and 3.9% in 2022 (OR 0.71, 0.63 to 0.81; p<0.001). DISCUSSION: The proportion of observations with SpO2 <90% or NEWS2 ≥5 was greater with the 92-96% range; however, absolute differences were very small and of doubtful clinical relevance, in contrast to hyperoxaemia for which the proportion was markedly less in 2022. These findings support proposals that the British Thoracic Society oxygen guidelines could recommend a lower target SpO2 range.

Oxygen Use in Critical Illness.

Oxygen is the most commonly used drug in critical care. However, because it is a gas, most clinicians and most patients do not regard it as a drug. For this reason, the use of medical oxygen over the past century has been driven by custom, practice, and "precautionary principles" rather than by scientific principles. Oxygen is a life-saving drug for patients with severe hypoxemia, but, as with all other drugs, too much can be harmful. It has been known for many decades that the administration of supplemental oxygen is hazardous for some patients with COPD and other patients who are vulnerable to retention of carbon dioxide (ie, hypercapnia). It has been recognized more recently that excessive oxygen therapy is associated with significantly increased mortality in critically ill patients, even in the absence of risk factors for hypercapnia. This paper provides a critical overview of past and present oxygen use for critically ill patients and will provide guidance for safer oxygen use in the future.

Protocol for a feasibility randomised controlled trial of targeted oxygen therapy in mechanically ventilated critically ill patients.

INTRODUCTION: Oxygen is the most commonly administered drug to mechanically ventilated critically ill adults, yet little is known about the optimum oxygen saturation (SpO2) target for these patients; the current standard of care is an SpO2 of 96% or above. Small pilot studies have demonstrated that permissive hypoxaemia (aiming for a lower SpO2 than normal by using a lower fractional inspired oxygen concentration (FIO2)) can be achieved in the critically ill and appears to be safe. This approach has not been evaluated in a National Health Service setting. It is possible that permissive hypoxaemia may be beneficial to critically ill patients thus it requires robust evaluation. METHODS AND ANALYSIS: Targeted OXygen therapY in Critical illness (TOXYC) is a feasibility randomised controlled trial (RCT) to evaluate whether recruiting patients to a study of permissive hypoxaemia is possible in the UK. It will also investigate biological mechanisms that may underlie the links between oxygenation and patient outcomes. Mechanically ventilated patients with respiratory failure will be recruited from critical care units at two sites and randomised (1:1 ratio) to an SpO2 target of either 88%-92% or ≥96% while intubated with an endotracheal tube. Clinical teams can adjust FIO2 and ventilator settings as they wish to achieve these targets. Clinical information will be collected before, during and after the intervention and blood samples taken to measure markers of systemic oxidative stress. The primary outcome of this study is feasibility, which will be assessed by recruitment rate, protocol adherence and withdrawal rates. Secondary outcomes will include a comparison of standard critical care outcome measures between the two intervention groups, and the measurement of biomarkers of systemic oxidative stress. The results will be used to calculate a sample size, likely number of sites and overall length of time required for a subsequent large multicentre RCT. ETHICS AND DISSEMINATION: This study was approved by the London - Harrow Research Ethics Committee on 2 November 2017 (REC Reference 17/LO/1334) and received HRA approval on 13 November 2017. Results from this study will be disseminated in peer-reviewed journals, at medical and scientific meetings, in the NIHR Journals Library and patient information websites. TRIAL REGISTRATION NUMBER: NCT03287466; Pre-results.

Reversible pulmonary artery perfusion abnormalities in the postpartum period as a precursor to the development of pulmonary arterial hypertension.

Deterioration, or a new presentation, of pulmonary arterial hypertension (PAH), are recognized complications of pregnancy. In this report, we describe a patient with a family history of PAH who developed peripartum breathlessness and hypoxemia with ventilation-perfusion mismatch but no evidence of thromboembolism or PAH. Significantly reduced perfusion at both lung bases was noted on perfusion scintigraphy and three-dimensional magnetic resonance (3D-MR) perfusion maps in the immediate postpartum period. These abnormalities spontaneously resolved by 16 weeks postpartum, consistent with reversible pulmonary abnormalities of pulmonary perfusion. However, she developed new breathlessness four years later and was found to have developed PAH. This case provides a mechanism which may contribute to the high mortality seen in pregnant patients with PAH in the peripartum period.

A study of attitudes, beliefs and organisational barriers related to safe emergency oxygen therapy for patients with COPD (chronic obstructive pulmonary disease) in clinical practice and research.

BACKGROUND: Patients can be harmed by receiving too little or too much oxygen. There is ongoing disagreement about the use of oxygen in medical emergencies. METHODS: This was a mixed methods study (survey, telephone interviews and focus groups) involving patients, the public and healthcare professionals (HCPs). RESULTS: 62 patients with chronic obstructive pulmonary disease (COPD), 65 members of the public, 68 ambulance crew members, 22 doctors, 22 nurses and 10 hospital managers took part. For five factual questions about oxygen therapy, the average score for correct answers was 28% for patients with COPD, 33% for the general public and 75% for HCPs. The HCPs had an average score of 66% for five technical questions. Patients (79%) and members of the public (68%) were more likely than HCPs (36%) to believe that oxygen was beneficial in most medical emergencies and less likely to have concerns that it might harm some people (35%, 25% and 68%). All groups had complex attitudes about research into oxygen use in medical emergencies. Many participants would not wish for themselves or their loved ones to have their oxygen therapy determined by a randomised protocol, especially if informed consent was not possible in an emergency situation. CONCLUSIONS: We have found low levels of factual knowledge about oxygen use among patients with COPD and the general public and many false beliefs about the potential benefits and harms of using oxygen. HCPs had a higher level of factual knowledge. All groups had complex attitudes towards research into emergency oxygen use.

A crossover study of short burst oxygen therapy (SBOT) for the relief of exercise-induced breathlessness in severe COPD.

BACKGROUND: Previous small studies suggested SBOT may be ineffective in relieving breathlessness after exercise in COPD. METHODS: 34 COPD patients with FEV1 <40% predicted and resting oxygen saturation ≥93% undertook an exercise step test 4 times. After exercise, patients were given 4 l/min of oxygen from a simple face mask, 4 l/min air from a face mask (single blind), air from a fan or no intervention. RESULTS: Average oxygen saturation fell from 95.0% to 91.3% after exercise. The mean time to subjective recovery was 3.3 minutes with no difference between treatments. The mean Borg breathlessness score was 1.5/10 at rest, rising to 5.1/10 at the end of exercise (No breathlessness = 0, worst possible breathlessness = 10). Oxygen therapy had no discernable effect on Borg scores even for 14 patients who desaturated below 90%. 15 patients had no preferred treatment, 7 preferred oxygen, 6 preferred the fan, 3 preferred air via a mask and 3 preferred room air. CONCLUSIONS: This study provides no support for the idea that COPD patients who are not hypoxaemic at rest derive noticeable benefit from oxygen therapy after exercise. Use of air from a mask or from a fan had no apparent physiological or placebo effect.

Breathless on bortezomib.

The authors describe a case of episodic acute pneumonitis occurring after repeated doses of bortezomib, a drug being used increasingly to treat multiple myeloma. The delay in presentation each time with fever, dyspnoea, hypoxia and interstitial radiological changes contributed to under-recognition of this complication, which has so far been described in only a handful of patients, but the pattern seen may offer clues to pathogenesis and potential treatments. This case highlights the need for both physicians and patients consenting to bortezomib treatment to be more aware of this potentially fatal adverse effect.