Experimental paperCerebral energy failure following experimental cardiac arrest: Hypothermia treatment reduces secondary lactate/pyruvate-ratio increase*
Introduction
During the last years mild hypothermia (33 ± 1 °C) following cardiac arrest (CA) has gained clinical acceptance as a method to improve neurological outcome and reduce mortality.1, 2
The explanation for the neuroprotective effects of hypothermia is not entirely known. It is believed to comprise several factors3 for example reduced cerebral metabolism4 and slowing down the excitotoxic cascade.5, 6 When using hypothermia in the clinical setting, there are several unanswered questions about how to best perform the therapy. There is still need to further explore the cerebral effects of hypothermia and different modalities of hypothermia treatment, as for example induction methods, treatment time and temperature range. In addition, little is known about the effects of rewarming. One could speculate that harmful processes are inhibited by hypothermia only to result in a rebound phenomenon during restoration of normal body temperature.7, 8
Induction of hypothermia by means of infusion of ice-cold fluid has been described in both experimental9 and clinical settings10, 11 and is now an established method.
In this study we hypothesized that mild hypothermia, induced by cold infusion, after resuscitation from CA reduces cerebral energy failure due to cerebral ischaemia but that harmful effects emerge during rewarming. Cerebral ischaemia was examined by cerebral microdialysis, and oxygen extraction together with intracranial pressure (ICP) monitoring. The methods used for examining cerebral injury were chosen in order to be feasible in the clinical setting.
Section snippets
Methods
The care and handling of the animals involved were reviewed and approved by the Institutional Review Board for Animal Experimentation in Uppsala, Sweden.
Results
Sixteen animals followed the entire protocol. One animal in the hypothermic group was excluded due to technical problems with the microdialysis catheter and one animal in the normothermic group was excluded because of technical problems with the infusion pump. There were no significant differences in baseline physiological variables.
All pigs achieved ROSC after the initial defibrillatory shock, and survived during the entire observation period.
Discussion
After CA, 60% of the animals developed a secondary increase in L/P-ratio indicating secondary energy failure. The incidence of secondary energy failure was lower in the hypothermic group. To our knowledge, these results are the first suggesting that hypothermia treatment diminishes secondary energy failure following resuscitation after CA.
The mechanisms for secondary energy failure, and why some pigs were more prone to develop it, are unclear. The fact that there was no correlation between
Conclusions
In conclusion, there is a risk of secondary energy failure following successful resuscitation after CA, expressed by a secondary increase in L/P-ratio. Hypothermia treatment seems to reduce the occurrence. There were no indications that rewarming by 0.5–1.0 °C/h could induce cerebral ischaemia, secondary energy failure or excitotoxicity in this model set up. Hypothermia treatment increases jugular bulb venous oxygen content probably due to decreased cerebral metabolism.
Conflict of interest statement
None of the authors had any personal financial interest that could bias this work.
Acknowledgements
The authors wish to express their gratitude to research assistants Anders Nordgren, Elisabeth Pettersson and Monika Hall for their excellent technical assistance, to Inger Ståhl Myllyaho for help with microdialysate analysis and to biostatistician Niclas Eriksson at Uppsala Clinical Research Centre for help with statistic evaluations.
This study was supported by grants from the Swedish Heart and Lung Association and from the Swedish Research Council (Grant number 2002/A0799).
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A Spanish translated version of the summary of this article appears as Appendix in the final online version at doi:10.1016/j.resuscitation.2009.02.003.