Experimental paperEffect of mild hypercapnia on outcome and histological injury in a porcine post cardiac arrest model
Introduction
Despite of continuous improvements in post-resuscitation (PR) care, outcome of cardiac arrest (CA) remains poor. Indeed, more than half of resuscitated patients die early after hospital admission,1, 2 such that the final survival ranges from 0.5 to 20% in Europe, with great differences among countries.3, 4 For this reason, one of the main objective of resuscitation science is investigating novel therapeutic strategies that may improve survival with good neurological recovery.5, 6 For example, the optimal respiratory targets, i.e. ideal blood partial pressure (Pa) of oxygen (O2) and carbon dioxide (CO2) are currently unknown and several specific trials have been undertaken.7, 8, 9
Recently, the role of PaCO2 became of particular interest after the publication of a series of experimental and observational studies anticipating potential benefits on CA outcome from a ventilation pattern set to maintain a mild hypercapnia.8, 10, 11 In a rodent model of global cerebral ischemia but without cardiac arrest, mild to moderate hypercapnia (PaCO2 60–100 mmHg) was associated with lesser histological brain damage and lesser apoptosis compared to normocapnia or severe hypercapnia after cerebral ischemia.12 Pathophysiologically, hypercapnia holds interesting properties that might be beneficial for CA patients such as an increase in cerebral blood flow, an increase in arterial blood pressure due to endogenous catecholamine release, and an attenuation of ischemia-reperfusion injury due to mitigation of oxidative stress.13, 14, 15
This study aimed to investigate the effects of PR mild hypercapnia on survival and functional recovery in a porcine post-CA model. We hypothesized that a period of hypercapnia after resuscitation might ameliorate cardiac and neurological dysfunction and survival compared to normocapnia.
Section snippets
Material and methods
All procedures involving animals and their care were in conformity with national and international laws and policies. Approval of the study was obtained by the governmental review board, within a wider protocol on inhalatory strategies to improve CA outcome (N.84/2014-PR).
Results
No significant differences in body weight, hemodynamics, myocardial function, and blood gas analyses were observed between groups at baseline (Table 1). All the animals, except 2 in the hypercapnia group, were successfully resuscitated. The duration of CPR and the total number of defibrillation delivered were similar in both groups (Table 1). Eighty percent of the animals resuscitated from CA and treated with hypercapnia survived till 96 h compared to 57% in the normocapnia group (Fig. 2).
After
Discussion
The present study investigated the effect of post resuscitation mild hypercapnia, obtained by reducing minute ventilation, as a potential treatment to improve outcome of CA. Indeed, in our model, a 4-h period of mild hypercapnia was associated with a better mean arterial pressure and a decrease in neuronal degeneration in the frontal cortex; nevertheless, no corresponding functional improvements in neurological recovery were observed.
CO2 is the major determinant of cerebral blood flow, with
Conclusions
Our study partially confirmed the hypothesis of a beneficial effects of mild hypercapnia on CA outcome with better mean arterial pressure and a lesser neuronal degeneration in the frontal cortex. However, no corresponding improvements in neurological recovery or survival was observed. A greater acidotic status and a lower PaO2 observed during hypercapnia might have blunted its cardio- and neuroprotective effects.
Conflicts of interest
All authors declare no conflicts.
For comparisons of resuscitation and survival outcomes, including OPC, χ2 test was used. One-way ANOVA was used for comparisons of number of defibrillation, duration of survival, and LV infarct size. For comparisons of all other time-based variables, repeated measures ANOVA with Holm-Sidak’s multiple comparison was used.
Acknowledgments
The study was supported by Laerdal Foundation for Acute Medicine.
The authors thanks: Physio-Control for the LUCAS 2 compressor and Philips Medical Systems for the MRx defibrillator.
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