Can oxygen hurt?
Drug we use most often can cause harm if we give it without good reason
By Mike McEvoy
EMS providers began giving oxygen not because it had medically or scientifically demonstrated benefits for patients, but because they could. Yet, inarguably, hypoxia is bad.
John Scott Haldane, who formulated much of our understanding of gas physiology, said in 1917, “Hypoxia not only stops the motor, it wrecks the engine.”
Patients begin to suffer impaired mental function at oxygen saturations below 64 percent. People typically lose consciousness at saturations less than 56 percent, giving airplane passengers no more than 60 seconds to breathe supplemental oxygen when an airplane flying at 30,000 feet suddenly depressurizes1-3.
More recent studies suggest that hyperoxia, or too much oxygen, can be equally dangerous. Hence the drug EMS providers administer most often may not be as safe as originally thought.
Studies on benefits and dangers of oxygen therapy are not new; intensive care practitioners have long recognized the adverse effects of using high concentration oxygen4.
The Guidelines for Emergency Cardiac Care (ECC) in 2000 and 2005 recommended against supplemental oxygen for patients with saturations above 90 percent. The current 2010 ECC Guidelines call for supplemental oxygen only when saturations are less than 94 percent, perhaps in an effort to soften the impact of change5.
What is new are prehospital research studies comparing outcomes of patients treated without oxygen or with oxygen titrated to saturations versus patients routinely given high flow oxygen. These data are frightening; they invariably show impressive patient harm from even short periods of hyperoxia.
We’ve known since 1999 that oxygen worsened survival in patients with minor to moderate strokes and made no difference for patients with severe stroke6. In fact, the American Heart Association recommended in 1994 against supplemental oxygen for non-hypoxemic stroke patients.
The dangers from giving oxygen to neonates have also been long appreciated7. The most compelling outcome studies of neonates published in 2004 and repeated in 2007 showed a significant increase in mortality of depressed newborns resuscitated with oxygen (13 percent) versus room air (8 percent)9. This led to the current neonatal resuscitation recommendations for use of room air positive pressure ventilation.
In 2002, a study of 5,549 trauma patients in Texas showed prehospital supplemental oxygen administration nearly doubled mortality9. A Tasmanian study of prehospital difficulty breathing patients published in 2010 compared patients treated with oxygen titrated to saturations of 88 to 92 percent to patients treated with non-rebreather oxygen masks.
It showed a reduction in deaths during subsequent hospitalization of 78 percent in COPD patients and 58 percent in all patients10. New studies are showing a troubling pattern of worse outcomes associated with hyperoxia post cardiac arrest11.
Why would oxygen worsen patient outcomes? One mechanism may be absorption atelectasis. Gas laws mandate that increases in the concentration of one gas will displace or lower the concentration of others. Room air normally contains 21 percent oxygen, 78 percent nitrogen, and less than 1 percent carbon dioxide and other gases.
Nitrogen, the most abundant room air gas, is responsible for secretion of surfactant, the chemical that prevents collapse of the alveoli at end expiration. Premature infants often are not developed sufficiently to produce surfactant and require endotracheal administration of animal surfactant.
“Washout” of nitrogen in adult lungs occurs when high concentration oxygen is administered. Lower concentrations of nitrogen can lead to decreased surfactant production with subsequent atelectasis and collapse of alveoli, significantly impeding oxygen exchange.
Oxygen is also a free radical, meaning that it is a highly reactive species owing to its two unpaired electrons. From a physics perspective, free radicals have potential to do harm in the body.
The sun, chemicals in the atmosphere, radiation, drugs, viruses and bacteria, dietary fats, and stress all produce free radicals. Cells in the body endure thousands of hits from free radicals daily.
Normally, the body fends off free radical attacks using antioxidants. With aging and in cases of trauma, stroke, heart attack or other tissue injury, the balance of free radicals to antioxidants shifts.
Cell damage occurs when free radicals outnumber antioxidants, a condition called oxidative stress. Many disease processes including arthritis, cancer, diabetes, Alzheimer’s and Parkinson’s result from oxidative stress.
The concept of free radical damage suggests the old EMS notion that, “high flow oxygen won’t hurt anyone in the initial period of resuscitation” may be dead wrong.
Tissue damage is directly proportionate to the quantity of free radicals present at the site of injury. Supplemental oxygen administration during the initial moments of a stroke, myocardial infarct (MI) or major trauma may well increase tissue injury by flooding the injury site with free radicals.
Finally, consider this: five minutes of supplemental oxygen by non-rebreather decreases coronary blood flow by 30 percent, increases coronary resistance by 40 percent due to coronary artery constriction, and blunts the effect of vasodilator medications like nitroglycerine12. These effects were demonstrated dramatically in cath lab studies13 published in 2005.
Wonder why the 2010 ECC Guidelines recommended against supplemental oxygen for chest pain patients without hypoxia? Now you know: supplemental oxygen reduces coronary blood flow and renders the vasodilators ALS providers use to treat chest pain ineffective.
Where do we go from here? Knowing that both hypoxia and hyperoxia are bad, EMS providers must stop giving oxygen routinely. Oxygen saturations should be measured on every patient.
Protocols need to be aligned to reflect the 2010 ECC guidelines: administer oxygen to keep saturations between 94 and 96 percent. No patient needs oxygen saturations above 97 percent and in truth, there is little to no evidence suggesting any clinical benefit of oxygen saturations above 90 percent in any patient.
Modifications in prehospital equipment will be inherent in controlling oxygen doses administered to patients. In all likelihood, the venturi mask will make a comeback, allowing EMS providers to deliver varied concentrations of oxygen as needed to keep oxygen saturations between 94 and 96 percent.
Few patients will require non-rebreather masks which are prone to deliver too much oxygen (hyperoxia). CPAP (Continuous Positive Airway Pressure) devices will also need redesign as most conventional EMS CPAP delivers 100 percent oxygen. A study conducted by Bledsoe, et al in Las Vegas found that prehospital CPAP using low oxygen levels (28 to 30 percent) was highly effective and safe14.
Bottom line: the drug we use most often can cause harm if we give it without good reason. In the absence of low saturations, oxygen will not help patients with shortness of breath and it may actually hurt them. The same holds true for neonates and virtually any patient with ongoing tissue injury from stroke, MI or trauma. Indeed, oxygen can be bad.
Akero A, Christensen CC, Edvardsen A, et al. Hypoxaemia in chronic obstructive pulmonary disease patients during a commercial flight. Eur Respir J 2005;25:725–30.
Cottrell JJ, Lebovitz BL, Fennell RG, et al. Inflight arterial saturation: continuous monitoring by pulse oximetry. Aviat Space Environ Med 1995;66:126–30.
Hoffman CE, Clark RT, Brown EB. Blood oxygen saturations and duration of consciousness in anoxia at high altitudes. Am J Physiol 1946;145:685–92.
Alteiemer WA, Sinclair SE. Hyperoxia in the intensive care unit: why more is not always better. Curr Opin Crit Care 2007;13:73-78.
O'Connor RE, Brady W, Brooks SC, Diercks D, Egan J, Ghaemmaghami C, Menon V, O'Neil BJ, Travers AH and Yannopoulos D. 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science Part 10: Acute Coronary Syndromes. Circulation 2010; 122: S787-S817.
Ronning OM, Guldvog B. Should Stroke Victims Routinely Receive Supplemental Oxygen? A Quasi-Randomized Controlled Trial. Stroke 1999;30:2033-2037.
Rabi Y, Rabi D, Yee W: Room air resuscitation of the depressed newborn: a systematic review and meta-analysis. Resuscitation 2007;72:353-363.
Davis PG, Tan A, O’Donnell CP, et al: Resuscitation of newborn infants with 100% oxygen or air: a systematic review and meta-analysis. Lancet 2004;364:1329-1333.
Stockinger ZT, McSwain NE. Prehospital Supplemental Oxygen in Trauma Patients: Its Efficacy and Implications for Military Medical Care. Mil Med. 2004;169:609-612.
Austin MA, Wills KE, Blizzard L, Walters EH, Wood-Baker R. Effect of high flow oxygen on mortality in chronic obstructive pulmonary disease patients in prehospital setting: randomised controlled trial. BMJ 2010;341:c5462.
Kilgannon JH, Jones AE, Parillo JE, at al. Emergency Medicine Shock Research Network (EMShockNet) Investigators. Relationship between supranormal oxygen tension and outcome after resuscitation from cardiac arrest. Circulation 2011;14:2717-2722.
Harten JM, Anderson KJ, Kinsella J, et al. Normobaric hyperoxia reduces cardiac index in patients after coronary artery bypass surgery. J Cardiothorac Vasc Anesth 2005;19:173–5.
McNulty PH, et al. Effects of supplemental oxygen administration on coronary blood flow in patients undergoing cardiac catheterization. Am J Physiol Heart Circ Physiol 2005; 288: H1057-H1062.
Bledsoe BE, Anderson E, Hodnick R, Johnson S, Dievendorf E. Low-Fractional Oxygen Concentration Continuous Positive Airway Pressure Is Effective In The Prehospital Setting. Prehosp Emerg Care 2012;16:217-221.