Re-thinking the O in MONA:: 2 Graham Werstiuk, RRT

Re-thinking the O2 in MONA::
Considerations for the RT treating MI patients
Graham Werstiuk, RRT
Instructor – Respiratory Therapy
School of Health Sciences
Respiratory Therapist
Alberta Health Services
"It ain’t so much the things we
don't know that get us into
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
Augmentation of perfusion to ischemic
myocardium by increasing total peripheral
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
Does balloon occlusion in otherwise healthy
animals reflect advanced CAD?
Human physiological studies often had poor
- lack of blinding
- lacked randomization
Mostly surrogate or secondary endpoints
- Not patient/disease outcome
Cardiovascular effects of Hyperoxemia
↓Cardiac Index
↓Myocardial Oxygen Consumption
“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
• Statistically significant increase in sinus tachycardia in O2
• 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
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
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
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
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
– Potential for significant overlap between two
groups .
– Blinding during analysis?
– Poor compliance with later parts of trial MRI,
– 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
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
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
Keep SpO2 low normal ~94% this may mean you don’t need
any oxygen for many patients
Caution - with known exterme athereosclerosis, triple vessel
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