Association of Hyperoxygenation with Cardiac Arrest

Sudden cardiac arrest is the most common lethal consequence of cardiac disease. In-hospital cardiac arrest is a major adverse event with an occurrence every 1-6 admissions out of 1000 (Schluep, M.,et al. 2018). Several research studies have recently reproached the important concern that administration of excess oxygen during and early after resuscitation from cardiac arrest (CA) may have deleterious effects on a patients clinical outcome. Depending on the hospital, the survival rates after in-hospital cardiac arrest vary substantially with a mean survival rate of only 23.8% (Chan, P. Et al. 2016). The purpose of this paper is to improve nursing practice by reviewing research studies regarding hyperoxygenation during and after cardiac resuscitation. This paper will discuss studies with different approaches to this topic such as the harmful effects of hyperoxaemia after resuscitation at a cellular level, the in-hospital mortality rate related to arterial blood gasses (ABGs), and the importance of the nurses role.

The beneficial effects of oxygen are widely known, but the potentially harmful effects of high oxygenation concentrations in blood and tissues have been less widely discussed. Providing supplemental oxygen can increase oxygen delivery in hypoxaemic patients, thus supporting cell function and metabolism and limiting organ dysfunction, but, in patients who are not hypoxaemic, it is believed that supplemental oxygen will increase oxygen concentrations into detrimental hyperoxaemic ranges and may be associated with harmful effects (Vincent et al. 2017). In a study by Angelos et al. 2011, they measured mitochondria isolated from hearts of rats and dogs exposed to 60 minutes of hyperoxia with 100%fiO2 or normoxic with 40% fiO2 following return of spontaneous circulation (ROSC) after cardiac arrest. The study was based upon the physiology of what occurs to the organ systems of the brain and heart during and after cardiac arrest. Within a few seconds of going into cardiac arrest the heart is incapable of maintaining effective contraction which in return disables the ability of the body to perfuse the brain and vital organs.

Even within a short amount of time after cardiac arrest, the brain and heart are easily vulnerable to ischemic injury due to their high oxygen demand and inability to store oxygen. The high rate of mortality associated with cardiac arrest is due to post cardiac arrest syndrome which involves global ischemia reperfusion injury, myocardial stunning and anoxic brain injury. During CPR and prior to ROSC the bodies ability to deliver oxygen is severely limited. However, with the return of circulation, the myocardial blood flow increases and the amount of blood passing though the pulmonary vasculature increases, making a hyperemic response of available blood to oxygenate (Vincent et al. 2017). The overall effect can be a rapid re-oxygenation of the ischemic myocardial tissue leading to a burst of reactive oxygen species (ROS) generation and redox stress which ties into the research performed by Helmerhorst et al. (2015). These studies by Helmerhorst et al. (2015) and Vincent et al. (2017) have shown the oxidative stress from ROS produced by excessive oxygenation after reperfusion may lead to increased cellular death by diminishing mitochondrial function, blocking normal enzymatic activities, and damaging membrane lipids causing additional severe pathologic changes to the brain and worsened neurological deficits.

Kilganon et al. (2010) conducted a study with the primary objective of testing the hypothesis that exposure to hyperoxia after resuscitation is associated with increased mortality. This was a muticenter cohurt study using the critical care database of intensive care units at 120 US hospitals over the course of 4 years. In this study they found that adult patient exposure to Hyperoxia (PaO2 >300 mmHg) following ROSC was a common occurrence based upon the first ABG results obtained upon ICU arrival. The analysis had three groups from the 6326 patients included in the study. 1156 had hyperoxia which was categorized by a PaO2 of greater that 300 mmHg, 3999 had hypoxia categorized as a PaO2 less than 60 mmHg and 1171 had normoxic with a PaO2 that falls in between the two values. These values were based on arterial blood gas analysis performed within 24 hours following resuscitation from cardiac arrest. The results showed that among the patients admitted to the ICU following resuscitation from cardiac arrest, arterial hyperoxia had a significantly higher in-hospital mortality rate compared to the normoxia and even hypoxemia group. This study additionally found that among hospital survivors, hyperoxia was associated with a lower likelihood of independent functional status after hospital discharge. The downfall of this study is that hyperoxia was defined as a PaO2 of greater than 300 mmHg, but the precise PaO2 level associated with maximal risk is unknown.

A year later, Kilgannon et al 2011, wanted to conduct a second more focused study using the Project IMPACT database which covered 4459 patients in intensive care units in 120 US hospitals. The inclusion criteria was; older that 17 years of age, nontrauma, received CPR less than 24 hours prior to admission to ICU, and arterial blood gasses (ABG) performed within 24 hours of ICU arrival. Patients with hypoxemia (PaO2 less than 60 mmHg) were excluded from this trial as apposed to his former study. This study grouped the in-hospital mortality rates by ranges of oxygen tension; PaO2 60 to 90, 100 to 199, 200 to 299, 300 to 399, and 400 or greater. This study also included a comparison of the patients discharged alive and functionally independent across the groups. The data analysis of this study took into account patient race, preadmission functional status, comorbitities, site of origin prior to ICU admission, time of admission, treatment with vassopressor or inotropic agents, hospital size and many other variables that could have played an affect on the patient outcome.

The average post-resuscitation PaO2 levels among all the patients was 231 mmHg, and 2399 of the 4459 patients suffered the outcome of in-hospital death. 41% of the in-hospital deaths were patients in the oxygen tension range of 60-99 mmHg, and rose to 65% for patients with PaO2 greater than 400 mmHg. The study also found that there was a decline in patients discharged with independent function in relation to ascending PaO2 levels, 23% with a PaO2 level of 60-99 and only 9% of the patients who survived with a PaO2 greater than 400 mmHg were discharged with independent function. The results revealed that the association between supernormal oxygen tension and in-hospital mortality were not limited to only the extreme oxygen tension levels, but a minimal increase of 25 mmHg in PaO2 level was associated with a 6% increase in the risk of death. Patients resuscitated from cardiac arrest are exposed to global ischemia reperfusion injury with potential neurological consequences based upon the study by Helmerhorst et al. (2015), but there are limitations to the control of human studies in regards to levels of oxygen administration during cardiac arrest. Therefore there have been additional controlled animal studies to gain more evidence of the effects of excessive supplemental oxygen during and after cardiac arrest.

A study performed by Brucken et al. (2010), was performed to determine the influence of different time intervals of pure oxygen ventilation after experimental cardiac arrest on histopathological changes of the brain and actual functional neurologic outcome. The study was conducted by inducing cardiac arrest in 15 pigs, then performing CPR, ventilation, and administering epinephrine in a synchronized fashion to each pig with no variables in the delivery of resuscitation, times and medications administered. The animals successfully resuscitated were then divided into two groups, the hyperoxia group, where they were ventilated with 100% oxygen for 1 hour, and the normoxia group, ventilated for only 10 min. The ABG values were obtained at baseline then at 10, 60, and 240 minutes after resuscitation. The functional performance was measured by an established neurocognitive test and deficit score. The brains of the subjects were then harvested five days later for histopathological analyses. The conclusion to this study is that prolonged ventilation with 100% oxygen after successful resuscitation from cardiac arrest caused significant alterations in the brains of the pig subjects as evidence by a marked increases in the number of necrotic neurons and greater extent of inflammation in brain structures. A similar study was performed by Angelos et al. (2011) on rats with a focus on the effects on heart mitochondrial function. The test was performed with 60 min of either 100% or 40% oxygen administered. Group one had 100% oxygen administered with continuous pulse oximetry at 100%. Group two had only 40% oxygen delivered and it was titrated to keep the pulse oximetry between 92% and 96%. ABG values were also measured periodically during the 60 min ROSC period. The results of this study showed the PaO2 levels of the 40% group to remain at 105 mmHg, and the 100% oxygen group had an average PaO2 level of 280 mmHg. The heart mitochondria were then isolated at the end of the study and showed that there was increased injury and ischemia caused to the rats exposed to hyperoxia with an increase in ROS formation.

A study by Wang 2017, placed their research on non traumatic out of hospital cardiac arrest with return of spontaneous circulation surviving more than one hour after being brought into the emergency department. This analysis was based on patients first and last ABG values within the first 24 hours of admission. This study involved 9176 patients that fit the criteria and a total of 35,576 AGB measurements were taken. There was an average of 3 ABG measurements per patient. With the first measurement obtained within 2 hours after ED arrival. The ABG measurements frequently exhibited hyperoxemia. The results of this study additionally showed that the presence of initial and continued hyperoxemia was associated with increased hospital mortality.

Cardiac arrest, either out-of-hospital or in-hospital, is a common and lethal emergency condition. Even if return of spontaneous circulation (ROSC) is achieved, most patients do not survive to hospital discharge. According to Zima (2015) the high post-ROSC mortality may be attributed to post-cardiac arrest syndrome, which includes anoxic brain injury, heart muscle deterioration, and a systemic ischemic/reperfusion response. The Review by Wang 2014 analyzed 14 different observational studies and then compared different levels of partial pressure of arterial oxygen (PaO2) in post-ROSC patients with mortality and neurological status at hospital discharge. The result of the study was that hyperoxia appears to have a linear correlation with increased in-hospital mortality of post-ROSC patients. In the search for other modifiable post-ROSC factors that can improve outcomes, the role of oxygen in the cardiac arrest situation has gained increasing attention recently.

The issue lies with the amount of uncontrollable variables such as patient comorbidities, inability to measure exact oxygen supplied to patient while manually ventilating and timeframes for resuscitation.

These studies tie in the role of the RN while working bedside with a patient during cardiac arrest and through transfer of care following. The study by Helmerhorst et al. (2015) shows that post-ischemic re-oxygenation is necessary to minimize ongoing ischemic injury, but excess oxygenation after circulation is restored causes further injury by the release of ROS. According to a survey by Burls et al. (2010), 98% of clinicians reported that they always or usually use oxygen, and only 1.3% thought it could increase mortality. There has been many different forms of research showing the negative effects of supplying excess oxygenation, yet the debate continues. However, because exposure to hyperoxia shows no obvious benefits, clinicians and nursing staff need to administer oxygen cautiously. The error begins at the supplemental oxygen received through a bag-walve-mask (BVM), and continues in negligence of hyper-oxygenating patients who are not hypoxemic following cardiac arrest. The average adult BVM has a volume of 1.0-1.2 liters, and the average tidal volume needed for an adult patient is about half of that (Merelman, 2016), thus it is imperative to correctly manually ventilate a patient.

According to Interstate Nursing Practice and Regulation: Ethical Issues for the 21st Century written by Silva & Ludwick written in 1999 and updated in 2019, the first principle of nursing practice still remains as nonmaleficence, or do no harm, which is directly tied to the nurse's duty to protect the patient's safety. It is a nurses duty to stay up to date with evidenced based practice and remain a patient advocate and dependent of the physician on call, a nurse may also be responsible for leading a code, or RN will likely be responsible for the providing manual ventilation with a BVM. In these critical situations it is important that a nurse is educated with correct research in order to provide the safest care to their patients. The nurse is required to deliver a calm and focused performance and assist his/her team to deliver the best life support to a patient in cardiac arrest, while not supplying the patient with too large of a tidal volume, or too quick of breath. Although there is still additional research to investigate the exact clinical outcome and therapeutic amount of oxygen during CA, there is enough supplemental research showing that there is an effect on patient survival based on the amount of oxygen provided, thus careful oxygen administration is warranted in order to ensure adequate tissue oxygenation while preventing hyperoxemic harm.

In conclusion, the purpose of this paper was to improve nursing practice by reviewing research studies regarding hyperoxygenation in regards to resuscitation from cardiac arrest. This paper has discussed studies regarding hyperoxemia and showed a high portion of adult patients are exposed to hyperoxemia following ROSC. The research also highlighted the deleterious effects of hyperoxemia and outcome in regards to in-hospital mortality, neurological status, and cellular damage through human and animal studies. There are multiple challenges in solidifying the optimal therapeutic oxygenation during CPR and immediately after ROSC, but it is imperative to provide safe controlled supplemental oxygenation.