Re-thinking the O2 in MONA:: Considerations for the RT treating MI patients Graham Werstiuk, RRT Instructor – Respiratory Therapy School of Health Sciences NAIT Respiratory Therapist Alberta Health Services "It ain’t so much the things we don't know that get us into trouble. It's the things we know that just ain't so.“ - Josh Billings Current Attitudes “…98.3% said they always or usually use oxygen... while only 1.3% reported that they thought 'it may even increase the risk of death.” Burls A, et al. EMJ 2010; 27(4):283-286 Cabello JB, et al. Emergencias 2009; 21: 422-428 Why do we give O2 for the MI patient? Dorland's Medical Dictionary for Health Consumers. © 2007 by Saunders, an imprint of Elsevier, Inc. All rights reserved Animal evidence. Maroko, et al. Circulation 1975; 52: 362 Potential Mechanisms by which O2 helps 1. 2. 3. 4. Augmentation of perfusion to ischemic myocardium by increasing total peripheral resistance Reduction of myocardial oxygen demand through slowing of heart rate or contractility Increases in oxygen tension Augmentation of myocardial blood flow to the ischemic myocardium Paraphrase from Lair GT, et al. Cardiovasc Res 1979, 13, p 160 Basis for O2 therapy in MI patients • Human studies ECG – changes in ST elevation Analgesia requirements Issues Does balloon occlusion in otherwise healthy animals reflect advanced CAD? Issues Human physiological studies often had poor methodology - lack of blinding - lacked randomization Mostly surrogate or secondary endpoints - Not patient/disease outcome Cardiovascular effects of Hyperoxemia ↓HR ↑PVR ↓SV ↑SVR ↓Cardiac Index ↑CVR ↓Myocardial Oxygen Consumption ↑BP “Patients who failed to increase their PaO2 to at least 200mmHg failed to change their peripheral resistance, cardiac index , and heart rate. From these observations, we have concluded that the major determinant of the hemodynamic response to inhalation of oxygen in patient with acute myocardial infarction is the rise in arterial PO2. “ Davidson RM, et al. Circulation 1973; 47:704-709 Thomas M, et al. Brit Heart J 1965; 27: 403 After oxygen there was a fall in myocardial blood flow in seven patients, a very small rise in one patient, and no change in two patients Fig 3. The mean value for all 10 patients showed a signficant fall (p<0.01) averaging 12.7%, although in some cases the reduction was as much as 33%. Kenmure A.C.F. et al. Cardiovasc Res. 1971, 5, 485 & 487 Farquhar et al. Am Heart J 2009;158:371-7 Farquhar et al. Am Heart J 2009;158:371-7 Farquhar et al. Am Heart J 2009;158:371-7 Right Coronary Angiogram . ©2005 by American Physiological Society McNulty PH, et al. AJP - Heart Circl. 2005; 288: H1057H1062 McNulty, J Appl Physiol. 2007. 102: 2040–2045 Cardiovascular effects of Hyperoxia “ The decrease in myocardial blood flow prevents any additional oxygen delivery to the heart despite a considerable increase in arterial oxygen content; indeed the decrease in blood flow may be so great as to reduce the total amount of oxygen available to the heart.” Rawles, J M., Kenmure, A C F. BMJ 1976; 1: 1123 Cardiovascular effects of Hyperoxia “Angina pectoris is accompanied by a rise of LVEDP to about 30 mmHg and might reflect cessation of blood flow to certain subendocardial areas of the myocardium. The increased amount of oxygen in the arterial blood during oxygen breathing might therefore not be transported to these ishaemic parts of the heart.” Lecerof H. Thorax. 1974. Vol 29, p675-676 Cardiovascular effects of Hyperoxia “…administration of 100% oxygen to patients with severe triple vessel disease may result in lactate production, suggesting that coronary blood flow was decreased sufficiently to increase myocardial ischemia. Comment on Bourassa MG. AM J Cardiol 1969; 24 172-7 In Farquhar et al. Am Heart J 2009;158:371-7 Our best evidence… Controlled clinical trials Rawles, 1976 • Participants – 157 patient, uncomplicated MI • Diagnosis – 2 of 3 ECG, Elevated Cardiac markers (AST), unstable angina • • • • Pre PCI era Double Blind – shrouded gas cylinders Sealed Envelope randomization 6LPM of either O2 or AIR Rawles JM, Kenmure ACF. BMJ 1976; 1: 1121-1123 Rawles, 1976 Outcomes: • Statistically significant increase in sinus tachycardia in O2 group • Statistically significant increase in infarct size as inferred by AST in O2 group • Double the rate of V-Tach in O2 (not statistically significant ) • 9 deaths in O2 group vs 3 in AIR group (not statistically significant) Rawles JM, Kenmure ACF. BMJ 1976,1,1121-1123 “Thus oxygen treatment far from achieving the desired effect of limiting the ischemic area might actually result in an extension of the area of infarction… …the administration of oxygen does not appear to be of any benefit to patients with uncomplicated myocardial infarction. “ Rawles, J M., Kenmure, A C F. BMJ 1976; Volume 1, p. 1123 Issues with Rawles 1976 Pre- PCI era Blinding could be easily circumvented MI was not confirmed in 43 patients Ukholkina, 2005 Participants – 137, Uncomplicated MI Diagnosis – ECG, Cardiac Biomarkers (CPK-MB), Clinical Hx PCI era Randomized but not blinded 3-6 LPM 02 for 3 hours post PCI or RA for 3 hours post PCI Ukoholkina GB, et al. Int J Interventional Cardioangiology, 2005. No. 9, 45-50 Ukholkina, 2005 Outcomes: 1 death in the O2 arm, None in Air arm Less necrotic myocardium day 10 (p<0.0001) Less complications of MI in O2 arm Arrhythmia, Circulatory failure, Pericarditis (p <0.025) Ukoholkina GB, et al. Int J Interventional Cardioangiology, 2005. No. 9, 45-50 Ukholkina, 2005 ISSUES: No description of randomization No blinding Some patient data missing O2 patients had tended to have worse class of MI than Air patients at admission (Killip Class II) As identified in Burls A, et al. Emerg Med J 2011; 28: 917-923 Ukholkina, 2005 Author’s conclusions “The results substantiate the use of oxygen therapy in combination with endovasclar reperfusion of myocardium and its safety.” Ukoholkina GB, et al. Int J Interventional Cardioangiology, 2005. No. 9, 45-50 Optomize Pilot, 2012 Participants – 136 patients, Uncomplicated, first time MI Diagnosis - ECG PCI era Randomized, Not blinded 6 hours of High Concentration (6 LPM) or Titrated (to keep SpO2 between 93-96%) Ranchord AM, et al. Amer Heart J. 2012. Vol 163. No 2. 168-175 OPTIMISE Pilot, 2012 Outcomes: 1 death in “High” concentration arm vs. 2 in Titrated O2 arm No statistical difference in infarct size Ranchord AM, et al. Amer Heart J. 2012. 163. 168-175. OPTIMSE pilot, 2012 Issues – Potential for significant overlap between two groups . – Blinding during analysis? – Poor compliance with later parts of trial MRI, Ultrasound. – Pre-hospital oxygen administration The evidence as a whole Ranchord AM, et al. Am Heart J 2012;163:168-75 The evidence as a whole Burls A, et al. CDSR 2010, Issue 6. CD007160 “Current evidence neither supports nor refutes the routine use of oxygen in patients with uncomplicated MI.” Burls et al. Emerg Med J 2011;28:917-923 “...these findings provide no support for the view that oxygen therapy was either beneficial or safe in terms of either the size of the myocardial infarction or mortality rate, which would have been necessary to justify the use of a therapeutic intervention (i.e. first do no harm)...” Beasly et al.. JRSM. Vol 100. March 2007. p130-133 Resuscitation: another angle Kilgannon JH, et al. JAMA 2010; 303 (21): 2169 Bellomo R, et al. Critical Care 2011; 15: R90 So now what do I do? “…oxygen is itself a vasoactive substance most appropriately dispensed in precise doses titrated against the measured arterial PO2. “ McNulty PH, et al. AJP- Heart 2005; 288: H1062 Nobody needs to be Hypoxic or Hyperoxic Common practice has been for basic EMT's to administer oxygen during the initial assessment of patients with suspected ACS. However, there is insufficient evidence to ‘support or refute oxygen use in uncomplicated ACS. If the patient is dyspneic, hypoxemic, has obvious signs of heart failure, or an oxyhemoglobin saturation <94%, providers should administer oxygen and titrate therapy to provide the lowest administered oxygen concentration that will maintain the oxyhemoglobin saturation ≥94% (Class I, LOE C). (Robert, S694-695) 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science Nobody needs to be Hypoxic or Hyperoxic Keep SpO2 low normal ~94% this may mean you don’t need any oxygen for many patients Caution - with known exterme athereosclerosis, triple vessel disease. The take home… •Oxygen is in fact a vasoactive substance! • In patients with advance CAD it is theoretically possible to make the infarction worse. •Data for oxygen’s use is limited – No proven harm or benefit • Practice Goldilocks medicine - Avoid both hypoxia and hyperoxia aiming for ~94% SpO2