Cerebral energy metabolism during haemorrhagic shock and the concept of permissive hypotension

Research output: ThesisPh.D. thesis

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Haemorrhagic shock continues to be the leading cause of preventable deaths from trauma. Trauma results in both tissue damage and haemorrhage, and if severe enough – haemorrhagic shock. Throughout recent years, Damage Control Resuscitation has become widely accepted as the primary strategy in treating haemorrhagic shock. Damage Control Resuscitation incorporates a wide range of techniques, including permissive hypotension. The clinician allows the systemic blood pressure to decrease to below normal limits in permissive hypotension to minimise the bleeding. However, the apparent danger of permissive hypotension is that blood supply to the organs, and especially the brain, is at risk of being compromised. The use of norepinephrine in the case of life-threatening haemorrhagic shock is still controversial and not widely accepted. No clear evidence exists whether the use of norepinephrine results in a survival benefit nor if norepinephrine results in cerebral vasoconstriction and compromised cerebral metabolism. With the use of the in-vivo technique of microdialysis, it is possible to examine the metabolic redox state of the brain via the changes in the relationship between lactate and pyruvate. The thesis aims at defining the concept of permissive hypotension based on the variables related to cerebral energy metabolism obtained by microdialysis and routine biochemical analyses (lactate, pyruvate, glucose, glutamate, glycerol):

To answer the research questions, we conducted three exploratory animal studies. The first describing the biochemical pattern when the decrease in MAP causes pronounced ischemia (depletion of oxygen and substrate) resulting in irreversible cell damage. The second study describing the biochemical pattern when the decrease in MAP causes a moderate reduction of CBF (pronounced decrease in oxygen at continued supply of substrate) compatible with a normalization at re-transfusion. And the third the biochemical pattern when pronounced hypotension due to haemorrhagic shock is treated with norepinephrine to normalize MAP. Lastly, we examined if it is possible to use microdialysis of the draining venous cerebral blood to evaluate perturbation of global cerebral energy metabolism during haemorrhagic shock.

In summary, the thesis demonstrates that the level of MAP and the duration of arterial hypotension during haemorrhagic shock are not sufficient criteria to determine whether irreversible brain damage will occur or not. From a clinical perspective, group data from large studies a used to establish general recommendations. These recommendations are not necessarily adequate for the individual patient and recent guidelines emphasize that individual considerations should be taken. However, there is presently no clinical routine technique available to determine the individual limits.

We have shown that intracerebral microdialysis may be used to determine the biochemical pattern when haemorrhagic shock will cause irreversible tissue damage. The pattern is different from that obtained during a moderate reduction in cerebral blood flow compatible with a normalization of energy metabolism after re-transfusion. Further, we have shown that early treatment with norepinephrine (i.e., before the biochemical variables indicate pronounced ischemia with depletion of oxygen and substrate) may normalize energy metabolism before re-transfusion. As intracerebral microdialysis will hardly be an option during severe haemorrhagic shock under clinical conditions, we have examined whether microdialysis of the draining venous blood may be used as a surrogate marker during a dangerous deterioration of cerebral energy metabolism. 
Translated title of the contributionCerebral energimetabolisme under hæmoragisk shock og begrebet permissiv hypotension
Original languageEnglish
Awarding Institution
  • University of Southern Denmark
  • Toft, Palle, Principal supervisor
  • Nielsen, Troels Halfeld, Co-supervisor
Publication statusPublished - 21. Apr 2022


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