Endotoxemia, PaCO2 and dynamic cerebral autoregulation

During my postdoc in Copenhagen, I had access to a human model of endotoxemia (for more information, you can read this article). In this model, variables of interest are monitored for 3 hours after an endotoxin bolus (2 ng/kg; Escherichia coli) in healthy volunteers. It represents a model to evaluate the systemic inflammatory response with vasodilatation associated with sepsis but without the associated altered microcirculation

As you may guess, I was really interested in the impact of endotoxemia on the cerebrovascular physiology. Endotoxemia/sepsis is usually associated with reduced cerebral blood flow. Static cerebral autoregulation can be altered or can be intact in septic patients. However, at the moment of the study, the influence of endotoxemia/sepsis on dynamic cerebral autoregulation remained unknown (since then, another paper reported data on dynamic cerebral autoregulation). Our group of research considered that a reduction in PaCO2 (induced by hyperventilation associated with endotoxemia/sepsis) would attenuate cerebral blood flow/cerebral blood flow velocity and improve dynamic cerebral autoregulation in these subjects following the administration of endotoxin.

So, we studied systemic hemodynamics, cerebral blood flow velocity, and dynamic cerebral autoregulation (by transfer function analysis) in healthy volunteers before and after an endotoxin bolus.

In these healthy volunteers, in whom cerebrovascular reactivity to CO2 seemed intact, endotoxemia was associated with reduced PaCO2 and cerebral blood flow velocity and with improved dynamic cerebral autoregulation. This “improvement” in dynamic cerebral autoregulation, that is the capacity to restore cerebral blood flow within seconds following acute changes in arterial pressure that are transmitted to the cerebral circulation, is really important for patients with sepsis, especially within a context of low mean arterial pressure.

Our manuscript was accompanied by an editorial that had the perfect title:

How to regulate brain perfusion during sepsis? Breathe rapidly…

 

Reference

Brassard P, Kim YS, van Lieshout J, Secher NH, Rosenmeier JB. Endotoxemia reduces cerebral perfusion but enhances dynamic cerebrovascular autoregulation at reduced arterial carbon dioxide tension. Crit Care Med 2012; 40(6):1873-8

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4 thoughts on “Endotoxemia, PaCO2 and dynamic cerebral autoregulation

  1. Interesting. Do you think if you had them breathe more slowly or done rebreathing and increased their PCO2 levels back to their pre-endotoxemia levels that the differences would have been abolished?

    Yes, studying on a Friday night – my comprehensive exams are coming up shortly!

  2. Ahh… comprehensive exams… I remember those days 🙂

    Excellent question! We discussed that specific issue in our paper…Although our results suggest that a lowering of PaCO2 is associated with improvement in dynamic cerebral autoregulation, PaCO2 would have needed to be returned to baseline after endotoxemia to confirm that hypothesis !

    A recent study (you can have access to the paper here: http://ccforum.com/content/16/5/R181, since it’s open access) reported altered dynamic cerebral autoregulation (measured by the index of cerebrovascular autoregulation (Mx)) in patients with sepsis. Interestingly, PaCO2 levels were at the upper normal range in these patients. These high PaCO2 levels could have impaired dynamic cerebral autoregulation in these sepsis patients. You can have access to our online comment here: http://ccforum.com/content/16/5/R181/comments

  3. Are you specifically studying cerebrovascular physiology for your comprehensive exams ? What will be your main interests during your PhD studies ?

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