Elsevier

Resuscitation

Volume 135, February 2019, Pages 110-117
Resuscitation

Experimental paper
Effect of mild hypercapnia on outcome and histological injury in a porcine post cardiac arrest model

https://doi.org/10.1016/j.resuscitation.2018.10.024Get rights and content

Abstract

Aim of the study

To evaluate in an established porcine post cardiac arrest model the effect of a mild hypercapnic ventilatory strategy on outcome.

Methods

The left anterior descending coronary artery was occluded in 14 pigs and ventricular fibrillation induced and left untreated for 12 min. Cardiopulmonary resuscitation was performed for 5 min prior to defibrillation. After resuscitation, pigs were assigned to either normocapnic (end-tidal carbon dioxide (EtCO2) target: 35–40 mmHg) or hypercapnic ventilation (EtCO2 45–50 mmHg). Hemodynamics was invasively measured and EtCO2 was monitored with an infrared capnometer. Blood gas analysis, serum neuron-specific enolase (NSE) and high sensitive cardiac troponin T (hs-cTnT) were assessed. Survival and functional recovery were evaluated up to 96 h.

Results

Twelve pigs were successfully resuscitated and eight survived up to 96 h, with animals in the hypercapnic group showing trend towards a longer survival. EtCO2 and arterial partial pressure of CO2 were higher in the hypercapnic group compared to the normocapnic one (p < 0.01), during the 4-hour intervention. Hypercapnia was associated with higher mean arterial pressure compared to normocapnia (p < 0.05). No significant differences were observed in hs-cTnT and in NSE between groups, although the values tended to be lower in the hypercapnic one. Neuronal degeneration was lesser in the frontal cortex of hypercapnic animals compared to the normocapnic ones (p < 0.05). Neurological recovery was equivalent in the two groups.

Conclusion

Mild hypercapnia after resuscitation was associated with better arterial pressure and lesser neuronal degeneration in this model. Nevertheless, no corresponding improvements in neurological recovery were observed.

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.

References (40)

  • D.G. Kiely et al.

    Effects of hypercapnia on hemodynamic, inotropic, lusitropic, and electrophysiologic indices in humans

    Chest

    (1996)
  • L. Pynnönen et al.

    Therapeutic hypothermia after cardiac arrest–cerebral perfusion and metabolism during upper and lower threshold normocapnia

    Resuscitation

    (2011)
  • R.L. Parke et al.

    Co-enrolment for the TAME and TTM-2 trials: the cerebral option

    Crit Care Resusc

    (2017)
  • H.V. Ganga et al.

    The impact of severe acidemia on neurologic outcome of cardiac arrest survivors undergoing therapeutic hypothermia

    Resuscitation

    (2013)
  • N. Nielsen et al.

    Targeted temperature management at 33°C versus 36°C after cardiac arrest

    N Engl J Med

    (2013)
  • G. Ristagno et al.

    Postresuscitation treatment with argon improves early neurological recovery in a porcine model of cardiac arrest

    Shock

    (2014)
  • G.M. Eastwood et al.

    The impact of oxygen and carbon dioxide management on outcome after cardiac arrest

    Curr Opin Crit Care

    (2014)
  • J. Vaahersalo et al.

    Arterial blood gas tensions after resuscitation from out-of-Hospital cardiac arrest

    Crit Care Med

    (2014)
  • Q. Zhou et al.

    Effects of permissive hypercapnia on transient global cerebral ischemia-reperfusion injury in rats

    Anesthesiology

    (2010)
  • G. Curley et al.

    Bench-to-bedside review: carbon dioxide

    Crit Care

    (2010)
  • Cited by (0)

    View full text