How much oxygen in adult cardiac arrest?
Critical Care
How much oxygen in adult cardiac arrest?
Antonio Maria Dell'Anna 0
Irene Lamanna 0
Jean-Louis Vincent 0
Fabio Silvio Taccone 0
0 Department of Intensive Care, Erasme Hospital, Université Libre de Bruxelles , Belgium, Route de Lennik 808, 1070 Brussels , Belgium
Although experimental studies have suggested that a high arterial oxygen pressure (PaO2) might aggravate post-anoxic brain injury, clinical studies in patients resuscitated from cardiac arrest (CA) have given conflicting results. Some studies found that a PaO2 of more than 300 mm Hg (hyperoxemia) was an independent predictor of poor outcome, but others reported no association between blood oxygenation and neurological recovery in this setting. In this article, we review the potential mechanisms of oxygen toxicity after CA, animal data available in this field, and key human studies dealing with the impact of oxygen management in CA patients, highlighting some potential confounders and limitations and indicating future areas of research in this field. From the currently available literature, high oxygen concentrations during cardiopulmonary resuscitation seem preferable, whereas hyperoxemia should be avoided in the post-CA care. A specific threshold for oxygen toxicity has not yet been identified. The mechanisms of oxygen toxicity after CA, such as seizure development, reactive oxygen species production, and the development of organ dysfunction, need to be further evaluated in prospective studies.
Introduction
Sudden cardiac arrest (CA) is the leading cause of death
among adults worldwide [
1,2
]. In most patients, attempts
at cardiopulmonary resuscitation (CPR) remain ineffective
and spontaneous cardiac activity cannot be restored [3].
Among those patients who do achieve return of
spontaneous circulation (ROSC), there are two key periods when
death may occur: early (during the first three days), usually
because of recurrent CA or severe cardiovascular failure
resulting in multiple organ failure (MOF), and late (beyond
day 3), usually secondary to withdrawal of life-sustaining
therapies in the absence of neurological recovery [
4
].
Although several interventions, including target temperature
management (TTM), have been introduced into the
postCA care of these patients [
5,6
], conflicting results have been
obtained [7], and these approaches are not sufficient to
prevent the deleterious consequences of brain ischemia in all
patients. During the post-CA care, secondary brain insult
must be avoided [
8
] and optimization of brain oxygenation
is likely to be an important component of brain recovery.
The restoration of adequate systemic hemodynamics is a
prerequisite to provide adequate cerebral blood flow in CA
patients [
9,10
], but brain oxygenation is also determined by
the arterial oxygen content. Arterial oxygen pressure
(PaO2) itself may influence brain cellular oxygen supply;
if hypoxemia (that is, PaO2 of less than 60 mm Hg) is
associated with poor outcomes after CA [11], a high PaO2 may
also be detrimental in a vulnerable brain, as suggested in
patients with traumatic brain injury or stroke [
12,13
]. The
aims of this article are to review the potential mechanisms
of oxygen toxicity after CA and to discuss the clinical
impact of oxygen management on post-CA care.
Post-cardiac arrest syndrome: the role of oxygen
Post-cardiac arrest syndrome (PCAS) is a complex
phenomenon, which shares several features with septic
shock [
7,14
]. In particular, PCAS includes a systemic
inflammatory response that can be triggered by the
ischemia-reperfusion injury and also specific precipitating
events, such as concomitant infections or heart disease.
Moreover, PCAS can contribute to brain injury and
myocardial dysfunction and can rapidly lead to MOF.
The primary ischemia-reperfusion injury [15] activates
various intracellular pathways, promoting ion
concentration disequilibrium with increased intracellular levels of
inorganic phosphate, lactate, and H+, and resulting in an
influx of calcium into the cell [
16
], which aggravates
mitochondrial dysfunction and eventually leads to
programmed cellular death (apoptosis). After reperfusion has
occurred, other mediators, including superoxide (O2−),
peroxynitrite (NO2−), hydrogen peroxide (H2O2), and
hydroxyl radicals (OH−), contribute to worsen cellular function
by oxidizing and damaging numerous cellular components
[
17
] (Figure 1). These reactive oxygen species (ROS)
then have a central role in initiating and enhancing the
post-ischemic damage [
15
]. Indeed, supra-normal oxygen
concentrations in this context may further stimulate ROS
production and contribute to worsen cellular function in a
setting of impaired mitochondrial function and impaired
oxygen utilization. Moreover, some other systemic
detrimental effects of hyperoxemia have been known for many
years [
18-20
]. Hyperoxemia causes systemic and coronary
vasoconstriction, which can decrease cardiac output and
induce m (...truncated)