Resuscitation 83 (2012) 1425 1426
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Resuscitation
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Editorial
Optimizing oxygenation and ventilation after cardiac arrest in  little adults
In this issue of the journal, del Castillo et al.1 report the find- cardiopulmonary arrest in pediatrics to a level above that seen in
ings of the Iberoamerican Pediatric Cardiac Arrest Network on the adult resuscitation medicine. However, in children, we see from the
timely topic of oxygenation after cardiac arrest in children. Recent current report that hyperoxia was a fairly uncommon occurrence.
studies on the potential deleterious consequences of hyperoxia in This is likely in part due to the excellent treatment delivered by the
adults after cardiac arrest2,3 have brought considerable attention to caregivers of these patients. It could also result in part from the fact
this aspect of patient management and have created controversy.4,5 that over 35% of these children had lung disease as an underlying
In this exploratory study in 223 infants and children between 1 cause for the arrest, and the ability to generate arterial hyperoxia
month and 18 years of age, the authors once again demonstrate that may have been blunted, as reflected by the fact that many patients
pediatric patients are not little adults. Contrasting a recent report needed a high FiO2 to achieve normal arterial oxygenation. This is
in adults, they reported no association between hyperoxia (defined certainly not surprising, but highlights again the fact that asphyx-
as either a PaO2 > 300 mmHg, or a ratio of PaO2 to FiO2 > 300) after ial cardiopulmonary arrest is a unique form of cardiac arrest that
restoration of spontaneous circulation (ROSC) and mortality rate. has its own unique panoply of important associated factors. For
Acute and/or sub-acute (24 hour) hyperoxia (PaO2 > 300 mmHg) example, during the recent deliberations of the international com-
after ROSC were rarely seen and represented only 8.5% and 1.7% mittee addressing guidelines for the management of brain-directed
of cases, respectively. In contrast, hypercapnia or hypocapnea after therapy in the resuscitation of cardiopulmonary arrest in drown-
ROSC were common and both were significantly associated with ing victims, it was clear that approaches such as the use of room
mortality versus normocapnea. Finally, more than 66% of the chil- air in resuscitation could be deleterious to some patients given the
dren had a non-cardiac cause for their arrest, and more than 35% pulmonary morbidity commonly seen in drowning victims.14 How-
had a pre-existing respiratory illness as the arrest etiology. ever, it is important to recognize, that the question of potential
We have learned the lesson that children are not little adults deleterious effects of hyperoxia on mortality or reperfusion injury
on many occasions in medicine, and the field of resuscitation in brain or heart after ROSC in children was not really tested in this
medicine has produced some of the most striking examples in this study, given its rare occurrence in this dataset. Thus, the possibility
regard. For example, we know that after asphyxial cardiac arrest that pediatric patients could exhibit increased risk for reoxygena-
in children there is marked superiority of conventional cardiopul- tion injury in the setting of hyperoxia has not yet been adequately
monary resuscitation (CPR) when compared to compression only examined.
CPR6 importantly contrasting the adult findings.7 Well known to In contrast to hyperoxia, alterations in arterial PaCO2, defined as
most of the readership of this journal is the fact that pediatric <30 mmHg or >50 mmHg were common after asphyxial cardiopul-
cardiopulmonary arrest commonly results from non-cardiac eti- monary arrest in children, having been seen in 41% of the patients
ologies, specifically asphyxia contrasting the cardiac etiology in overall, and in over 13% and 27% of children, respectively. In addi-
adults.8,9 As mentioned above, that fact was again demonstrated in tion, both of these arterial blood gas abnormalities were associated
the current report of del Castillo et al.1 with mortality with odds ratios of 3.27 and 2.71, respectively.
In 2006, Vereczki et al.10 published an important pre-clinical The potential effects of hypocapnea in resuscitation are com-
report in an adult dog model of ventricular fibrillation (VF) car- plex; particularly so after asphyxial cardiopulmonary arrest. For
diac arrest showing that acute hyperoxia during resuscitation led example, overventilation has been shown to adversely impact car-
to increased neuronal death and poor outcomes. Mechanisms such diac output during CPR.15 Similarly hypocapnea has been suggested
as nitration of key mitochondrial enzymes like pyruvate dehydro- to produce cerebral vasoconstriction and exacerbate cerebral
genase or selective oxidation of mitochondrial caridolipin with hypoperfusion after ROSC. This phenomenon is well described in
subsequent triggering of apoptosis may be deleterious in this traumatic brain injury.16 Delayed hypoperfusion after ROSC may,
regard.11,12 There is a well known predisposition of the developing as first reported by Snyder et al.17 in classic studies, be important,
brain to injury from oxidative stress related in part to the age- and potentially exacerbated by hypocapnea. However, hypocap-
dependent relative lack of glutathione peroxidase.13 This creates nea could also confer potential benefit by normalizing arterial pH,
special vulnerability in infants to hydrogen peroxide when it is pro- a phenomenon that is seen with sodium bicarbonate in some, but
duced. These concerns have, for decades, been the basis of limiting not all studies.18 It is also possible that the association between
hyperoxia in the field of neonatology. One might, thus, anticipate hypocapnea and poor outcome could simply reflect overwhelming
that this biochemical risk factor would greatly increase the dele- injury with severe metabolic depression and resultant reduced CO2
terious consequences of exposure of the brain to hyperoxia after production, particularly in brain.
0300-9572/$  see front matter © 2012 Published by Elsevier Ireland Ltd.
http://dx.doi.org/10.1016/j.resuscitation.2012.09.004
1426 Editorial / Resuscitation 83 (2012) 1425 1426
The association between hypercapnea and mortality is also 9. Abend NS, Topjian AA, Kessler SK, et al. Outcome prediction by motor and pap-
illary responses in children treated with therapeutic hypothermia after cardiac
interesting and potentially complex in the setting of resuscitation
arrest. Pediatr Crit Care Med 2012;13:32 8.
after asphyxial cardiopulmonary arrest. Whether the hypercapnea
10. Vereczki V, Martin E, Rosenthal RE, Hof PR, Hoffman GE, Fiskum G. Nor-
has a cause and effect on mortality or whether the relationship rep- moxic resuscitation after cardiac arrest protects against hippocampal oxidative
stress, metabolic dysfunction, and neuronal death. J Cereb Blood Flow Metab
resents an epiphenomenon is unclear. Greater than 10% of patients
2006;26:821 35.
had both hypercapnea and hypoxemia, and thus could represent
11. Martin E, Rosenthal RE, Fiskum G. Pyruvate dehydrogenase complex: metabolic
a high risk subgroup with significant lung disease after ROSC.
link to ischemic brain injury and target of oxidative stress. J Neurosci Res
2005;79:240 7.
This may also be the case for the patients with isolated hyper-
12. Bay1
r H, Tyurin VA, Tyurina YY, et al. Selective early cardiolipin peroxida-
capnea, which has been shown to have adverse effects even on
tion after traumatic brain injury: an oxidative lipidomics analysis. Ann Neurol
resuscitation from experimental VF cardiac arrest.19 In addition to
2007;62:154 69.
13. Fan P, Yamauchi T, Noble LJ, Ferriero DM. Age-dependent differences in
simply reflecting lung disease or large functional dead space from
glutathione peroxidase activity after traumatic brain injury. J Neurotrauma
low cardiac output after ROSC, hypercapnea could potentially con-
2003;20:437 45.
tribute to acute post-resuscitation cerebral hyperemia, the impact
14. Topjian AA, Berg RA, Bierens JJ, et al. Brain resuscitation in the drowning victim.
of which has never been understood. Consistent with this possi- Neurocrit Care, 2012, [Epub ahead of print].
15. Aufderheide TP, Lurie KG. Death by hyperventilation: a common and life-
bility, although blood pressure autoregulation of cerebral blood
threatening problem during cardiopulmonary resuscitation. Crit Care Med
flow is likely disturbed after clinically relevant asphyxial cardiac
2004;32:S345 51.
arrest,20 it is likely that CO2 reactivity of the cerebral circulation 16. Kochanek PM, Carney N, Adelson PD, et al. Guidelines for the acute medical man-
agement of severe traumatic brain injury in infants, children, and adolescents,
is intact given that it is well known to be much more difficult
2nd edition. Pediatr Crit Care Med 2012;13:S1 82.
to attenuate.21 The status of blood pressure autoregulation of CBF
17. Snyder JV, Nemoto EM, Carroll RG, Safar P. Global ischemia in dogs: intracranial
and CO2 reactivity, and their impact on outcome inpatients merit pressures, brain blood flow and metabolism. Stroke 1975;6:21 7.
18. Bar-Joseph G, Abramson NS, Kelsey SF, et al. Acta Anaesthesiol Scand
additional study in the field of resuscitation. Delayed hypercap-
2005;49:6 15.
nea at 24 h after ROSC was seen in <"10% of children and whether
19. Idris AH, Wenzel V, Becker LB, Banner MJ, Orban DJ. Does hypoxia or hyper-
this contributed to deleterious mechanisms such as intracranial
carbia independently affect resuscitation from cardiac arrest? Chest 1995;108:
522 8.
hypertension, brain swelling, or herniation is unclear. Similarly,
20. Manole MD, Foley LM, Hitchens TK, et al. Magnetic resonance imaging assess-
hypercapnea after ROSC could also exacerbate pulmonary hyper-
ment of regional cerebral blood flow after asphyxial cardiac arrest in immature
tension in some infants and children and reduce cardiac output.
rats. J Cereb Blood Flow Metab 2009;29:197 205.
21. Bouma GJ, Muizelaar JP. Cerebral blood flow, cerebral blood volume, and
Information on parameters such as cardiac output and mixed
cerebrovascular reactivity after severe head injury. J Neurotrauma 1991;9:
venous saturation might have been further informative.The con-
S333 48.
trasting findings of del Castillo et al.1 and the aforementioned prior
reports in adults may not simply reflect differences between cardiac
a,b,"
Patrick M. Kochanek
arrest in children and adults. They may reflect important differ-
a
Safar Center for Resuscitation Research, University
ences between cardiopulmonary arrests of asphyxial vs. cardiac
of Pittsburgh School of Medicine, Pittsburgh, PA,
origins, whether in children or adults. However, the key clinical
United States
studies published to date in adults have not specifically addressed
b
Department of Critical Care Medicine, University of
the impact of hyperoxia (or alterations in PaCO2) in adults in
Pittsburgh School of Medicine, Pittsburgh, PA, United
asphyxial cardiac arrest victims.2 4
States
In any case, del Castillo et al.1 once again demonstrate that
cardiac arrest in infants and children represents a unique entity a,b,c,d
Hülya Bay1
r
and that the impact of various therapeutic interventions must be a
Safar Center for Resuscitation Research, University
specifically examined in that setting.
of Pittsburgh School of Medicine, Pittsburgh, PA,
United States
References b
Department of Critical Care Medicine, University of
Pittsburgh School of Medicine, Pittsburgh, PA, United
1. Del Castillo J, López-Herce J, Matamoros M, et al. Hyperoxia, hypocapnia, and
States
hypercapnia as outcome factors after cardiac arrest in children. Resuscita-
c
tion, 2012; http://dx.doi.org/10.1016/j.resuscitation.2012.07.019, [Epub ahead Department of Environmental and Occupational
of print].
Health, University of Pittsburgh School of Medicine,
2. Kilgannon JH, Jones AE, Shapiro NI, et al. Association between arterial hyperoxia
Pittsburgh, PA, United States
following resuscitation from cardiac arrest and in-hospital mortality. J Am Med
d
Pittsburgh Center for Free Radical and Antioxidant
Assoc 2010;303:2165 71.
3. Kilgannon JH, Jones AE, Parrillo JE, et al. Relationship between supranormal oxy-
Health, University of Pittsburgh School of Medicine,
gen tension and outcome after resuscitation from cardiac arrest. Circulation
Pittsburgh, PA, United States
2011;123:2717 22.
4. Bellomo R, Bailey M, Eastwood GM, et al. Arterial hyperoxia and in-hospital
"
mortality after resuscitation from cardiac arrest. Crit Care 2011;15:R90.
Corresponding author at: Safar Center for
5. Kochanek PM, Bay1
r H. Titrating oxygen during and after cardiopulmonary resus-
Resuscitation Research, University of Pittsburgh
citation. J Am Med Assoc 2001;303:2190 1.
School of Medicine, 3434 Fifth Avenue, Pittsburgh,
6. Kitamura T, Iwami T, Kawamura T, et al. Conventional and chest-compression-
only cardiopulmonary resuscitation by bystanders for children who have out-
PA 15260, United States. Tel.: [phone];
of-hospital cardiac arrests: a prospective, nationwide, population-based cohort
fax: [phone].
study. Lancet 2010;375:1347 54.
E-mail address: [e-mail] (P.M.
7. Iwami T, Kawamura T, Hiraide A, et al. Effectiveness of bystander-initiated
cardiac-only resuscitation for patients with out-of-hospital cardiac arrest. Cir- Kochanek)
culation 2007;116:2900 7.
8. Fink EL, Clark RSB, Kochanek PM, Bell MJ, Watson RS. A tertiary care center s
5 September 2012
experience with therapeutic hypothermia after pediatric cardiac arrest. Pediatr
Crit Care Med 2010;11:66 74.