Air Versus Oxygen in ST-Segment–Elevation Myocardial Infarction PDF

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Literature review of Air Versus Oxygen in ST-Segment–Elevation Myocardial Infarction...

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Assessment Task 2 – Part 2 Richard Wessen (486441) Air Versus Oxygen in ST-Segment–Elevation Myocardial Infarction Introduction Treatment protocols directing the management of Acute Myocardial Infarction (AMI), most critically ST-Segment Elevated Myocardial Infarction (STEMI) include an array of initial and ongoing interventions. Oxygen (O 2) administration, both reactively and prophylactically remains a major pillar and integral intervention for patients identified with hypoxaemia, dyspnoea, shock or heart failure in pre-hospital and definitive care settings. (1) The body of evidence supporting liberal oxygen administration in patients differentially diagnosed with AMI remains inconclusive. Debate has continued to escalate in relation to the administration of oxygen in STEMI positive patients prompting implementation of multiple randomly controlled trials. Trials that systematically examined variations in multiple parameters documented in traditional treatment guidelines and the subsequent progression and outcomes observed in admitted patients included adjustment of oxygen administration flow-rates(2), the use of room air in place of supplemental oxygen(3-6) and titration of supplemental oxygen to maintain specified oxygen saturation (SpO 2) targets.(7, 8) The results of the above-mentioned trials have contributed to the controversy surrounding the topic of oxygen administration in STEMI patients. Additional studies that referenced data from tertiary care facilities and intensive care units, examined multiple end points in correlation to overall patient outcomes(7, 9) have further substantiated the requirement for clarity and formal evidence-based medical practice in this area. Traditional treatment guidelines directing the administration of oxygen in AMI patients are in need of review with recent peer-reviewed evidence as the foundation of optimsation. The aim of this review is to contribute to the optimisation process focused on guidelines influencing the management of AMI and STEMI patients in pre-hospital and tertiary care settings. The Evolution of O2 Therapy in Acute Myocardial Infarction Routine administration of oxygen to STEMI positive patients has been widely accepted for many decades with initial reported treatments dating back to 1900.(10) The treatment rationale assumed supplemental oxygen positively contributed to active management of dyspnoea, hypoxia and hypoxaemia and subsequent ischaemic injury in myocardial cells.(1012) Furthermore, expert opinion concluded that neurological injury was minimised with the prompt resolution of hypoxia.(8) Management of hypoxia and hypoxaemia is accepted as fundamental and of critical importance in all patients, especially those differentially or formally diagnosed as STEMI positive. Treatment protocols and long-standing advanced life support procedures, including current ANZCOR guidelines have long promoted the use of supplemental oxygen in breathless, hypoxaemic, shocked or potentially heart failure patients.(1) Interpretation of this guideline however did not exclude potentially normoxaemic patients and appears to defer to physician judgment. Sepehrvand et al further reinforced this situation having found occurrences of oxygen therapy due to ‘clinicians’ or physicians’ belief’ of its tissue oxygenation benefits without a substantial supporting body of evidence. (2) It is important to

Assessment Task 2 – Part 2 Richard Wessen (486441) note the evidence that existed until recently was described to be inconclusive and the product of ‘poor trials’, leaving clinicians to interpret and treat patients as they deemed appropriate(13) and incorporating the widely accepted concept that oxygen is harmless and may provide patients a sense of relief. (14) Randomly Controlled Trials of O2 Therapy in STEMI Challenges to routine use of oxygen in treatment of AMI and the associated evidence from the 1970s began gaining traction in the mid 2000s when the medical research community identified potentially harmful affects of reactive oxygen species (ROS), now thought to contribute to cell damage, increased ischaemic injury, induced cardiac arrhythmias, increased vascular resistance and decreased cardiac output in normoxaemic patients. (10, 14) The 2010 and 2016 Cochrane reviews (15) combined with controversy concerning oxygen therapy and recognition of potential patient harm served as a trigger spawning multiple randomly controlled trials. The objective was to establish stronger evidence-based protocols relating to oxygen treatment in acute coronary syndromes. Discussion of selected trials is included in the following paragraphs and summarised for reader convenience in . Nehme et al conducted the Air Versus Oxygen in Myocardial Infarction (AVOID) trial that examined the resultant infarct size (IS) 6 months post intervention in 441 patients randomly grouped.(3) Half the patients received continuous oxygen as per existing protocols from initial diagnosis until 12 hours post hospital intervention. The remaining patients received ambient air without supplemental oxygen unless the oxygen saturation fell below 94%. Nehme et al noted that normoxaemic patients administered continuous oxygen experienced a significantly larger infarct size; an estimated 17%-21% increase. The Supplemental Oxygen in Catherized Coronary Emergency Reperfusion (SOCCER) trial conducted at Lund University also questioned the relationship between oxygen therapy and benefits specifically reviewing myocardial salvage index (MSI) and infarction size.(5) Physical pain encountered by the test subjects as measured by the visual analog scale (VAS) was also recorded as a secondary end point. No significant improvements in any stated end point in the 111 normoxaemic patients broken into groups receiving 10 litres/minute continuous oxygen or room air throughout the process of percutaneous coronary intervention (PCI) were identified. (5) O’Neill et al were also unable to identify any significant improvement as measured by infarct size 14-21 days post PCI when trialling aqueous oxygen (AO) infusions in approximately 50% of their trial patients. Previous studies and the 2016 Cochrane report had noted the need for larger clinical trials(3, 4, 7, 9, 16) and consequently the Determination of the Role of Oxygen in Suspected Acute Myocardial Infarction (DETO2X-AMI) study was launched.(6) Hoffman et al enrolled over 6500 normoxaemic patients separating them into an oxygen group receiving 6 litres/minute oxygen over an average treatment period of 11.6 hours and the remainder receiving ambient air. The all-cause mortality rate of both groups within 1 year of the trial was analysed with no reduction in mortality identified in the oxygen group.(6) Published studies challenging the use of high flow oxygen administration in treatment of AMI and STEMI prompted research into whether the flow-rate represented a clinically significant relationship to the outcome of the patient. The High vs Low Oxygen Therapy in patients with Acute Heart Failure (HiLo-HF)(2) varied the flow-rate based on high and low oxygen saturation targets in 50 patients and examined changes in the N-terminal pro-braintype Natriuretic Peptite (NTproBNP). Consistent with previous trials, clinically significant

Assessment Task 2 – Part 2 Richard Wessen (486441) changes in pressure inside the heart as measured by NTproBNP were not found to correlate with oxygen flow-rate.(2) Girardis et al studied intensive care unit (ICU) mortality in 434 patients diagnosed as STEMI positive and currently admitted to ICU. Oxygen administration therapy protocols were established as conservative (SpO 2 between 94% - 98%) vs conventional (SpO2 between 97% - 100%).(7) The patient group administered conservative oxygen therapy was found to have lower mortality, though of important note is that the authors stressed the need for further research based on early termination of the trial.(7) Table 1: Summary of reviewed Randomly Controlled Trials examining the effects of O2 treatment in STEMI positive patients Trial Name

Groups 1.

AVOID(3, 4) 2.

SOCCER(5)

O2 – 8l/min or as per protocol Room Air

1. 2.

O2 – 10l/min Room Air

1. 2.

AO infusion No AO infusion

End Point

IS at 6 months

MSI IS VAS

Conclusion

Comments

Greater IS and patient harm in oxygen group identified.

Sample size: 41 Normoxaemic: SpO2 >= 94% Mean age: 63 Onset to treatment time < 12hrs

No identified improvement in MSI or IS in oxygen group. No evidence to support oxygen as an analgesic in AMI.

Sample size: 111 Normoxaemic: SpO2 >= 94% Mean age: 64 Onset to treatment time < 6hrs

IS at 14-21 days

No identified improvement in IS in oxygen group.

Sample size: 269 Mean age: 60 Onset to treatment time < 24hrs

NT-proBNP

No identified improvement in NT-proBNP in high-flow (SpO2 >=96%) group.

Sample size: 50 Mean age: 74 Onset to treatment time < 13hrs

DETO2X-AMI(6)

1. O2 – 6l/min 2. Room Air

Mortality in 1 year

No identified improvement in 1-year mortality in oxygen group.

Sample size6: 423 Normoxaemic: SpO2 >= 90% Mean age: 68 Onset to treatment time < 6hrs

Oxygen-ICU(7)

1. 2.

Mortality in ICU

Conservative SpO2 showed improvement in mortality rate.

Sample size: 434 Mean age: 64 Onset to treatment time unknown (Patients already admitted to ICU)

AMIHOT(9)

HiLo-HF(2)

1. SpO2: 90% – 92% 2. SpO2 >= 96%

SpO2: 97% – 100% SpO2: 94% – 98%

Assessment Task 2 – Part 2 Richard Wessen (486441) All trials researched in the course of this review revealed commonality and consensus in findings that conventional O2 therapy for STEMI positive patients found to be normoxaemic did not improve patient outcomes. Furthermore, risks of further myocardial infarction size and risk of reinfarction were noted in multiple studies.(3, 8) Other primary and secondary end points were also identified as unsupportive of suggestions that O 2 therapy in the absence of hypoxia contributed to positive patient outcomes. The definition of patients recognised as hypoxic was SpO2 >= 94% except in the DETO2X-AMI trial where hypoxia was defined as SpO2 >= 90%. The distinct lack of evidence supporting oxygen therapy for normoxaemic patients, coupled with the known risks of hyperoxaemic states suggests the focus should be on maintaining oxygen saturation within safe upper and lower targets as opposed to only lower limit.(8) ANZCOR guideline 14.2 recommends avoidance of initiation of O 2 therapy in patients with diagnosed or suspected AMI without clear identification of hypoxia by pulse oximetry.(1) This is re-iterated in guideline 11.6.1 for AMI patients where return to spontaneous circulation (ROSC) is achieved.(17) In-hospital protocols where oxygen is administered without carefully monitored oxygen saturation could be supplemented by the initial administration of ambient air unless hypoxaemia is or becomes clearly identified and not addressed through breathing and ventilation. Conclusion Current peer reviewed evidence established from multiple trials conducted since 2010 including AVOID, AMIHOT, SOCCER, Oxygen-ICU, HiLo-HF and DETO2X-AMI has consistently revealed no benefit from oxygen therapy in normoxaemic patients (as measured by SpO2 >= 94%) diagnosed with ST segment elevation myocardial infarction.(2-8) Furthermore, clinically significant evidence of greater myocardial injury and infarct size in normoxaemic patients post oxygen administration, negatively affecting longer term prognosis has been confirmed.(3, 7) Findings of this nature strongly support calls for optimisation in treatment guidelines concerning oxygen saturation thresholds and corresponding decisions to administer room air or supplemental oxygen to achieve safe saturation targets.(8) The author recommends further research to be conducted pre and post PCI of STEMI positive, normoxaemic patients with modified guidelines. It is proposed that initial trials concentrate on patient data review after follow-up, specifically examining the end-points used in previous trials including myocardial infarct size, myocardial salvage index, re-infarction rate and mortality rate. Additionally, given the identified variation in the threshold for hypoxaemia in the trials (90% < SpO2 < 94%) and consensus that oxygen saturation above 94% yields little to no benefit, further research into life threatening hyperoxia induced myocardial injury is warranted.(8) This review has established the existence of significant evidence contradicting conventional thinking and beliefs that liberal oxygen treatment does not cause harm. Conservative oxygen therapy should now be favoured in hypoxaemic patients and avoided in normoxaemic patients.(8) Independent review of available literature revealed a consensus that safe thresholds for oxygen saturation are between 94% and 96%(8), significantly lower than 98% to 100% as previously assumed. The primary conclusion of this review is for the Australian Resuscitation Council ANZCOR Guideline 14.2 to be reviewed with recommendation to modify section 1, paragraph 2 to reflect the evidence now available. Of particular importance is an inclusion articulating that oxygen saturation be managed carefully within a target range

Assessment Task 2 – Part 2 Richard Wessen (486441) of 94% to 96% using ambient air and conservative oxygen as appropriate, consequently balancing hypoxaemia and hyperoxaemia promoting improvement in patient outcomes.

Assessment Task 2 – Part 2 Richard Wessen (486441) References 1. Council AR. ANZCOR Guideline 14.2 – Acute Coronary Syndromes: Initial Medical Therapy [Internet]. Australia: Australian Resuscitation Council; 2016 [updated 2016 January. Available from: https://secureservercdn.net/184.168.47.225/777.066.myftpupload.com/download/section_14/ anzcor-guideline-14-2-jan16.pdf. 2. Sepehrvand N, Alemayehu W, Rowe BH, McAlister FA, van Diepen S, Stickland M, et al. High vs. low oxygen therapy in patients with acute heart failure: HiLo-HF pilot trial. ESC Heart Fail. 2019;6(4):667-77. 3. Nehme Z, Stub D, Bernard S, Stephenson M, Bray JE, Cameron P, et al. Effect of supplemental oxygen exposure on myocardial injury in ST-elevation myocardial infarction. Heart. 2016;102(6):444-51. 4. Stub D, Smith K, Bernard S, Nehme Z, Stephenson M, Bray JE, et al. Air Versus Oxygen in ST-Segment-Elevation Myocardial Infarction. Circulation. 2015;131(24):2143-50. 5. Khoshnood A, Akbarzadeh M, Carlsson M, Sparv D, Bhiladvala P, Mokhtari A, et al. Effect of oxygen therapy on chest pain in patients with ST elevation myocardial infarction: results from the randomized SOCCER trial. Scand Cardiovasc J. 2018;52(2):69-73. 6. Hofmann R, James SK, Jernberg T, Lindahl B, Erlinge D, Witt N, et al. Oxygen Therapy in Suspected Acute Myocardial Infarction. N Engl J Med. 2017;377(13):1240-9. 7. Girardis M, Busani S, Damiani E, Donati A, Rinaldi L, Marudi A, et al. Effect of Conservative vs Conventional Oxygen Therapy on Mortality Among Patients in an Intensive Care Unit: The Oxygen-ICU Randomized Clinical Trial. JAMA. 2016;316(15):1583-9. 8. Chu DK, Kim LHY, Young PJ, Zamiri N, Almenawer SA, Jaeschke R, et al. Mortality and morbidity in acutely ill adults treated with liberal versus conservative oxygen therapy (IOTA): a systematic review and meta-analysis. The Lancet. 2018;391(10131):1693-705. 9. O'Neill WW, Martin JL, Dixon SR, Bartorelli AL, Trabattoni D, Oemrawsingh PV, 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;50(5):397-405. 10. Cameron P, Jelinek G, Kelly A-M, Brown A, Little M. Textbook of Adult Emergency Medicine. 4th ed: Churchill Livingstone Elsevier; 2015. 1077 p. 11. Craft JA, Gordon CJ, Huether SE, McCance KL, Brashers VL, Rote NS. Understanding Pathophysiology. 2 ed. Chatswood: Elsevier Australia; 2015. 1328 p. 12. Moradkhan R, Sinoway LI. Revisiting the Role of Oxygen Therapy in Cardiac Patients. Journal of the American College of Cardiology. 2010;56(13):1013-6. 13. Khoshnood A. High time to omit oxygen therapy in ST elevation myocardial infarction. BMC Emerg Med. 2018;18(1):35. 14. Shuvy M, Lotan C. Oxygen Therapy in Myocardial Infarction? Still Waiting for an Answer. Cardiology. 2015;132(1):68-70. 15. Cabello JB, Burls A, Emparanza JI, Bayliss SE, Quinn T. Oxygen therapy for acute myocardial infarction. Cochrane Database Syst Rev. 2016;12:CD007160. 16. Khoshnood A, Carlsson M, Akbarzadeh M, Bhiladvala P, Roijer A, Bodetoft S, et al. The Effects of Oxygen Therapy on Myocardial Salvage in ST Elevation Myocardial Infarction Treated with Acute Percutaneous Coronary Intervention: The Supplemental Oxygen in Catheterized Coronary Emergency Reperfusion (SOCCER) Study. Cardiology. 2015;132(1):16-21. 17. Council AR. ANZCOR Guideline 11.6.1 – Targeted Oxygen Therapy in Adult Advanced Life Support [Internet]. Australia: Australian Resuscitation Council; 2016 [updated 2016 January. Available from:

Assessment Task 2 – Part 2 Richard Wessen (486441) https://secureservercdn.net/184.168.47.225/777.066.myftpupload.com/download/section_11/a nzcor-guideline-11-6-1-targeted-oxygen-therapy-jan16.pdf....