A randomized controlled trial of oxygen therapy in acute myocardial infarction Air Verses Oxygen In myocarDial infarction study (AVOID Study)

doi:10.1016/j.ahj.2011.11.011

American Heart Journal

Volume 163, Issue 3, March 2012, Pages 339-345.e1

https://doi.org/10.1016/j.ahj.2011.11.011 Get rights and content

Background

The role of routine supplemental oxygen for patients with uncomplicated acute myocardial infarction (AMI) has recently been questioned. There is conflicting data on the possible effects of hyperoxia on ischemic myocardium. The few clinical trials examining the role of oxygen in AMI were performed prior to the modern approach of emergent reperfusion and advanced medical management.

Methods

Air Verses Oxygen In myocarDial infarction study (AVOID Study) is a prospective, multi-centre, randomized, controlled trial conducted by Ambulance Victoria and participating metropolitan Melbourne hospitals with primary percutaneous coronary intervention capabilities. The purpose of the study is to determine whether withholding routine supplemental oxygen therapy in patients with acute ST-elevation myocardial infarction but without hypoxia prior to reperfusion decreases myocardial infarct size. AVOID will enroll 490 patients, >18 years of age with acute ST-elevation myocardial infarction of less than 12 hours duration.

Conclusions

There is an urgent need for clinical trials examining the role of oxygen in AMI. AVOID will seek to clarify this important issue. Results from this study may have widespread implications on the treatment of AMI and the use of oxygen in both the pre-hospital and hospital settings.

Section snippets

Background

Coronary artery disease (CAD) is a leading cause of morbidity and mortality worldwide.¹ In particular, many patients with CAD present with ST-elevation myocardial infarction (STEMI) as a result of acute thrombotic coronary artery occlusion. The optimal treatment for patients presenting with STEMI is reperfusion therapy either with primary percutaneous coronary intervention (PCI) or administration of a thrombolytic drug.2, 3

Current guidelines recommend additional treatments for patients with

Study sites

This study will be conducted by Ambulance Victoria in partnership with 12 major metropolitan hospitals in Melbourne, Australia. The Mobile Intensive Care Ambulances (MICA) of Ambulance Victoria are equipped with 12 lead electrocardiogram (ECG) capability and pulse-oximetry monitors and have significant experience in successfully conducting pre-hospital clinical trials in critically ill patients.21, 22 Ambulance Victoria, also has a Melbourne wide field triage 12-lead ECG program to detect STEMI

Data collection

A study coordinator will extract all relevant study data to a secure stand alone study database.

Summary

Despite inhaled oxygen therapy being a routine component of pre-hospital and in-hospital care for AMI, there is concern that rendering patients hyperoxic may increase myocardial infarct size and possibly lead to worse outcomes. This has led to international guidelines cautioning against the use of routine oxygen in normoxic patients with uncomplicated AMI. The AVOID study will be one of the first clinical trials in the modern era of pre-hospital ECG field triage and PPCI to investigate the role

Disclosures

Conflicts of Interest: None to declare.

References (42)

D. Freimark et al.
Timing of aspirin administration as a determinant of survival of patients with acute myocardial infarction treated with thrombolysis
Am J Cardiol
(2002)
R.F. Kelly et al.
Effect of 100% oxygen administration on infarct size and left ventricular function in a canine model of myocardial infarction and reperfusion
Am Heart J
(1995)
W.W. O'Neill et al.
Acute Myocardial Infarction With Hyperoxemic Therapy (AMIHOT): a prospective, randomized trial of intracoronary hyperoxemic reperfusion after percutaneous coronary intervention
J Am Coll Cardiol
(2007)
H. Farquhar et al.
Systematic review of studies of the effect of hyperoxia on coronary blood flow
Am Heart J
(2009)
R. Moradkhan et al.
Revisiting the role of oxygen therapy in cardiac patients
J Am Coll Cardiol
(2010)
S. Chia et al.
Utility of cardiac biomarkers in predicting infarct size, left ventricular function, and clinical outcome after primary percutaneous coronary intervention for ST-segment elevation myocardial infarction
J Am Coll Cardiol Intv
(2008)
J. Hallén et al.
Influence of ST-segment recovery on infarct size and ejection fraction in patients with ST-segment elevation myocardial infarction receiving primary percutaneous coronary intervention
Am J Cardiol
(2010)
R. Schroder et al.
Extent of early ST segment elevation resolution: a strong predictor of outcome in patients with acute myocardial infarction and a sensitive measure to compare thrombolytic regimens. A substudy of the International Joint Efficacy Comparison of Thrombolytics (INJECT) trial
J Am Coll Cardiol
(1995)
M.G. Friedrich et al.
The salvaged area at risk in reperfused acute myocardial infarction as visualized by cardiovascular magnetic resonance
J Am Coll Cardiol
(2008)
I. Eitel et al.
Prognostic significance and determinants of myocardial salvage assessed by cardiovascular magnetic resonance in acute reperfused myocardial infarction
J Am Coll Cardiol
(2010)

F. Roubille et al.

Routinely-feasible multiple biomarkers score to predict prognosis after revascularized STEMI

European journal of internal medicine

(2010)

K. Thygesen et al.

Universal definition of myocardial infarction

J Am Coll Cardiol

(2007)

AIHW

Australian Institute of Health and WelfareCardiovascular disease mortality: trends at different ages. Cardiovascular series no 31 Cat no47

(2010)

E.M. Antman et al.

ACC/AHA Guidelines for the Management of Patients With ST-Elevation Myocardial Infarction

Circulation

(2004)

Guidelines for the management of acute coronary syndromes 2006

Med J Aust

(2006)

R.E. O'Connor et al.

Part 10: Acute Coronary Syndromes: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care

Circulation

(2010)

J. Charvat et al.

Beneficial effect of intravenous nitroglycerin in patients with non-Q myocardial infarction

Cardiologia

(1990)

P.R. Maroko et al.

Reduction of infarct size by oxygen inhalation following acute coronary occlusion

Circulation

(1975)

A.C.F. Kenmure et al.

Circulatory and metabolic effects of oxygen in myocardial infarction

Br Med J

(1968)

J.M. Rawles et al.

Controlled trial of oxygen in uncomplicated myocardial infarction

Br Med J

(1976)

A.T. Wilson et al.

Hypoxaemia and supplemental oxygen therapy in the first 24 hours after myocardial infarction: the role of pulse oximetry

J R Coll Physicians Lond

(1997)

Cited by (53)

Hyperoxia-induced deterioration of diastolic function in anaesthetised patients with coronary artery disease – Randomised crossover trial
2023, BJA Open
There are no current recommendations for oxygen titration in patients with stable coronary artery disease. This study investigates the effect of iatrogenic hyperoxia on cardiac function in patients with coronary artery disease undergoing general anaesthesia.
Patients scheduled for elective coronary artery bypass graft surgery were prospectively recruited into this randomised crossover clinical trial. All patients were exposed to inspired oxygen fractions of 0.3 (normoxaemia) and 0.8 (hyperoxia) in randomised order. A transoesophageal echocardiographic imaging protocol was performed during each exposure. Primary analysis investigated changes in 3D peak strain, whereas secondary analyses investigated other systolic and diastolic responses.
There was no statistical difference in systolic function between normoxaemia and hyperoxia. However, the response in systolic function to hyperoxia was dependent on ventricular function at normoxaemia. Patients with a normoxaemic left ventricular (LV) global longitudinal strain (GLS) poorer than the derived cut-off (>–15.4%) improved with hyperoxia (P<0.01), whereas in patients with normoxaemic LV-GLS <–15.4%, LV-GLS worsened with transition to hyperoxia (P<0.01). The same was seen for right ventricular GLS with a cut-off at –24.1%. Diastolic function worsened during hyperoxia indicated by a significant increase of averaged E/e′ (8.6 [2.6]. vs 8.2 [2.4], P=0.01) and E/A ratio (1.4 (0.4) vs 1.3 (0.4), P=0.01).
Although the response of biventricular systolic variables is dependent on systolic function at normoxaemia, diastolic function consistently worsens under hyperoxia. In coronary artery disease, intraoperative strain analysis may offer guidance for oxygen titration.
NCT04424433.
Hyperoxia and mortality in conventional versus extracorporeal cardiopulmonary resuscitation
2022, Journal of Critical Care
Hyperoxia has been associated with adverse outcomes in post cardiac arrest (CA) patients. Study-objective was to examine the association between hyperoxia and 30-day mortality in a mixed cohort of two different modes of Cardiopulmonary Resuscitation (CPR): Extracorporeal (ECPR) vs. Conventional (CCPR).
In this retrospective cohort study of CA patients admitted to a tertiary level CA centre in Australia (over a 6.5-year time period) mean arterial oxygen levels (PaO₂) and episodes of extreme hyperoxia (maximum of mean PaO₂ ≥ 300 mmHg) were analysed over the first 8 days post CA.
One hundred and sixty-nine post CA patients were assessed (ECPR n = 79 / CCPR n = 90). Mean PaO₂-levels were higher in the ECPR vs CCPR group (211 mmHg ± 58.4 vs 119 mmHg ± 18.1; p < 0.0001) as was the proportion with at least one episode of extreme hyperoxia (74.7% vs 16.7%; p < 0.001). After adjusting for confounders and the mode of CPR any episode of extreme hyperoxia was independently associated with a 2.52-fold increased risk of 30-day mortality (OR: 2.52, 95% CI: 1.06–5.98; p = 0.036).
We found extreme hyperoxia was more common in ECPR patients in the first 8 days post CA and independently associated with higher 30-day mortality, irrespective of the CPR-mode.
Association between pre-hospital chest pain severity and myocardial injury in ST elevation myocardial infarction: A post-hoc analysis of the AVOID study
2021, IJC Heart and Vasculature
Citation Excerpt :
This study is an exploratory, secondary observational analysis of the Air Versus Oxygen in Myocardial Infarction (AVOID) trial. A detailed description of the AVOID study design and results has been previously published (NCT 01272713) [6,7]. Briefly, this was a prospective, multicenter, randomized controlled trial enrolling 638 patients with suspected STEMI between October 2011 and July 2014 transferred to 9 Percutaneous Coronary Intervention (PCI) capable hospitals in Melbourne, Australia.
We sought to determine if an association exists between prehospital chest pain severity and markers of myocardial injury.
Patients with confirmed ST elevation myocardial infarction (STEMI) treated by emergency medical services were included in this retrospective cohort analysis of the AVOID study. The primary endpoint was the association of pre-hospital initial chest pain severity, cardiac biomarkers and infarct size based on cardiac magnetic resonance imaging. Groups were categorized based on moderate to severe chest pain (numerical rating scale pain ≥ 5/10) or less than moderate severity to compare procedural and clinical outcomes. 414 patients were included in the analysis. There was a weak correlation between initial pre-hospital chest pain severity and peak creatine kinase (r = 0.16, p = 0.001) and peak cardiac troponin I (r = 0.14, p = 0.005). Both were no longer significant after adjusting for known confounders. There was no association between moderate to severe chest pain on arrival and major adverse cardiac events at 6 months (20% vs. 14%, p=0.12). There was a weak correlation between history of ischemic heart disease (r = 0.16, p = 0.001), percutaneous coronary intervention (r = 0.16, p = 0.001), left anterior descending artery (r = 0.12, p = 0.012) as the culprit vessel and a weak negative correlation between age (r = -0.14, p = 0.039) and chest pain.
Only a weak association between pre-hospital chest pain severity and markers of myocardial injury was identified, supporting more judicious use of opioid analgesia with a focus on patient comfort.
Conservative versus liberal oxygen therapy for acutely ill medical patients: A systematic review and meta-analysis
2021, International Journal of Nursing Studies
Citation Excerpt :
The papers were published between 1976 and 2020, and all studies were conducted in developed countries. Eight (NCT 00414726) (Ali et al., 2014; Mazdeh et al., 2015; Padma et al., 2010; Roffe et al., 2017; Ronning and Guldvog, 1999; Shi et al., 2017; Singhal et al., 2005) of the included trials were in stroke, seven (NCT02378545) (Asfar et al., 2017; Barrot et al., 2020; Girardis et al., 2016; He et al., 2019; Mackle et al., 2020; Panwar et al., 2016) in critical care or sepsis, three (Baekgaard et al., 2019; Lång et al., 2018; Taher et al., 2016) in trauma, seven (Heidari et al., 2017; Hofmann et al., 2017; Khoshnood et al., 2015; Ranchord et al., 2012; Rawles and Kenmure, 1976; Stub et al., 2012; Ukholkina et al., 2005) in myocardial infarction, four (Jakkula et al., 2018; Kuisma et al., 2006; Thomas et al., 2019; Young et al., 2014) in cardiac arrest, and four (NCT 02687217) (Bickel et al., 2011; Butler et al., 1987; Schietroma et al., 2016) in emergency surgery. The risk of bias is shown in Fig. 4, and the justifications for risk assessments are presented in supplement eTable 4.
The role of conservative versus liberal oxygen therapy for acutely ill patients remains controversial.
To systematically review the available evidence regarding the efficacy and safety of conservative oxygen therapy compared with liberal oxygen therapy for acutely ill patients.
A systematic search of Medline, Embase, and the Cochrane Central Register was conducted from their inception until April 5, 2020. Randomized clinical trials evaluating a high-target (liberal) or a low-target (conservative) oxygenation strategy in adults with an acutely ill condition were eligible for inclusion. A meta-analysis using random-effects models was conducted to calculate the risk ratio with corresponding 95% confidence intervals. Heterogeneity and publication bias were evaluated.
The analyses included 33 randomized clinical trials with a total of 17,780 participants. Compared with conservative oxygen therapy, liberal oxygen therapy was not associated with increased mortality at 30 days (risk ratio 1.09, 95% confidence intervals 0.98–1.22; I²=0%), at 90 days (risk ratio 1.00, 95% confidence intervals 0.88–1.13, I²=37%), or at the longest follow-up (risk ratio 1.04, 95% confidence intervals 0.96–1.12, I²=0%). Good functional outcome was similar between groups. Findings were robust to trial sequential, subgroup, and sensitivity analyses.
Compared with liberal oxygen therapy, conservative oxygen therapy was not associated with decreased mortality.
Tweetable abstract: Compared with liberal oxygen therapy, conservative oxygen therapy was not associated with decreased mortality.
Effect of early hyperoxemia on the outcome in servere blunt chest trauma: A propensity score-based analysis of a single-center retrospective cohort
2021, Journal of Critical Care
Our study aimed to explore the association between early hyperoxemia of the first 24 h on outcomes in patients with severe blunt chest trauma.
In a level I trauma center, we conducted a retrospective study of 426 consecutive patients. Hyperoxemic groups were classified in severe (average PaO₂ ≥ 200 mmHg), moderate (≥150 and < 200 mmHg) or mild (≥ 100 and < 200 mmHg) and compared to control group (≥60 and < 100 mmHg) using a propensity score based analysis. The first endpoint was the incidence of a composite outcome including death and hospital-acquired pneumonia occurring from admission to day 28. The secondary endpoints were the incidence of death, the number of hospital-acquired pneumonia, mechanical ventilation-free days and intensive care unit-free day at day 28.
The incidence of the composite endpoint was lower in the severe hyperoxemia group(OR, 0.25; 95%CI, 0.09–0.73; P < 0.001) compared with control. The 28-day mortality incidence was lower in severe (OR, 0.23; 95%CI, 0.08–0.68; P < 0.001) hyperoxemia group (OR, 0.41; 95%CI, 0.17–0.97; P = 0.04). Significant association was found between hyperoxemia and secondary outcomes.
In our cohort early hyperoxemia during the first 24 h of admission after severe blunt chest trauma was not associated with worse outcome.
Effects of intraoperative high versus low inspiratory oxygen fraction (FiO<inf>2</inf>) on patient's outcome: A systematic review of evidence from the last 20 years
2020, Anaesthesia Critical Care and Pain Medicine
Despite numerous studies, controversies about the best intraoperative FiO₂ remain. In 2016, the World Health Organization (WHO) recommended that adult patients undergoing general anaesthesia should be ventilated intraoperatively with an 80% FiO₂ to reduce surgical site infection (SSI). However, several data suggest that hyperoxia could have adverse effects. In order to determine the potential effect of FiO₂ on SSI, we included in this systematic review 23 studies (among which 21 randomised controlled trials [RCT]) published between 1999 and 2020, comparing intraoperative high versus low FiO₂. Results were heterogeneous but most recent studies on one hand, and the largest RCTs on the other hand, reported no difference on the incidence of SSI regarding intraoperative FiO₂ during general anaesthesia. There was also no difference in the incidence of SSI depending of intraoperative FiO₂ in patients receiving regional anaesthesia. The review on secondary endpoints (respiratory and cardiovascular adverse events, postoperative nausea and vomiting, postoperative length-of-stay and mortality) also failed to support the use of high FiO₂. On the opposite, some data from follow-up analyses and registry studies suggested a possible negative effect of high intraoperative FiO₂ on long-term outcomes. In conclusion, the systematic administration of a high intraoperative FiO₂ in order to decrease SSI or improve other perioperative outcomes seems unjustified in the light of the evidence currently available in the literature.

View all citing articles on Scopus

: Clinical Trial Registration: The AVOID study has been registered with clinicaltrials.gov (NCT01272713).

^f: Dr Stub and Dr Smith contributed equally to this manuscript.

^g: On behalf of AVOID Investigators. See online Appendix for complete listing.

View full text

Trial DesignA randomized controlled trial of oxygen therapy in acute myocardial infarction Air Verses Oxygen In myocarDial infarction study (AVOID Study)

Background

Methods

Conclusions

Section snippets

Background

Study sites

Data collection

Summary

Disclosures

Am J Cardiol

Am Heart J

J Am Coll Cardiol

Am Heart J

J Am Coll Cardiol

J Am Coll Cardiol Intv

Am J Cardiol

J Am Coll Cardiol

J Am Coll Cardiol

J Am Coll Cardiol

European journal of internal medicine

J Am Coll Cardiol

Australian Institute of Health and WelfareCardiovascular disease mortality: trends at different ages. Cardiovascular series no 31 Cat no47

ACC/AHA Guidelines for the Management of Patients With ST-Elevation Myocardial Infarction

Circulation

Guidelines for the management of acute coronary syndromes 2006

Med J Aust

Part 10: Acute Coronary Syndromes: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care

Circulation

Beneficial effect of intravenous nitroglycerin in patients with non-Q myocardial infarction

Cardiologia

Reduction of infarct size by oxygen inhalation following acute coronary occlusion

Circulation

Circulatory and metabolic effects of oxygen in myocardial infarction

Br Med J

Controlled trial of oxygen in uncomplicated myocardial infarction

Br Med J

Hypoxaemia and supplemental oxygen therapy in the first 24 hours after myocardial infarction: the role of pulse oximetry

J R Coll Physicians Lond

Trial Design
A randomized controlled trial of oxygen therapy in acute myocardial infarction Air Verses Oxygen In myocarDial infarction study (AVOID Study)