Cerebrovascular physiology – article alert #33

COPD and the brain

142- Decreased cerebrovascular response to CO2 in post-menopausal females with COPD: role of oxidative stress – Hartmann et al.

Stroke and the brain

143- The relationship of flow velocities to vessel diameters differs between extracranial carotid and vertebral arteries of stroke patients – Owolabi et al.

Positioning and the brain

144- Effects of positioning on cerebral oxygenation – Soeding

Exercise and the brain

145- The influence of exercise on cognitive abilities – Gomez-Pinilla and Hillman


Phenylephrine and cerebral oxygenation in anesthetized patients: influence of carbon dioxide

Our research group, as well as others, have reported a reduction in cerebral oxygenation with administration of phenylephrine in healthy volunteers and anesthetized patients. You can read other posts related to this topic for further details (here, here, here and here).

Since carbon dioxide is a powerful modulator of cerebrovascular tone, Meng et al. were interested in determining whether the reduction in cerebral oxygenation (measured by near-infrared spectroscopy or NIRS) following administration of phenylephrine, was dissimilar at different arterial carbon dioxide tension (PaCO2) in healthy anesthetized patients undergoing surgery (14 patients [11 males, three females, age 44 (15) yr old, height 175 (10) cm, and weight 80 (14) kg].

Phenylephrine boluses were administered (to increase mean arterial pressure by 20-30% from baseline) during steady state normocapnia (normal PaCO2) and then during steaty state hypocapnia (reduced PaCO2) or hypercapnia (increased PaCO2) by manipulating minute ventilation. Of note, the same dose of vasopressor was administered at all CO2 levels, but doses varied between patients because of differences in body weight. Cerebral oxygenation, cerebral blood volume, systemic hemodynamics and arterial blood oxygen saturation were monitored during the protocol.

Reductions in cerebral oxygenation following phenylephrine boluses were observed during hypocapnia, normocapnia and hypercapnia. However, changes in cerebral oxygenation were significantly different between the three experimental conditions. More specifically,  the reduction is cerebral oxygenation was more important during hypocapnia and blunted during hypercapnia in these patients. Still, changes in mean arterial pressure, cardiac output, heart rate, arterial blood oxygen saturation and depth of anesthesia, were similar between different CO2 levels. Thus, results from this study suggest that the CO2 level could influence the extent of the reduction in cerebral oxygenation following administration of phenylephrine in anesthetized patients.

An important section of the discussion is dedicated to how phenylephrine could influence the NIRS signal. The signal monitored by NIRS represents a mix of arterial and venous blood per unit of cerebral tissue and changes in the cerebral arterial to venous blood volume ratio is known to modify the NIRS signal.

The authors suggest that phenylephrine could influence the arterial/venous blood volume ratio.

They propose that:

(…) the flow velocity in cerebral arterial bed (mainly arterioles) is increased by a phenylephrine-induced increase in perfusion pressure. At the same time, cerebral blood flow (CBF)-regulating vessels (mainly arterioles) constrict due to stretch or increased transmural pressure-mediated vasoconstriction. In accordance with autoregulation, CBF (velocity multiplied by cross-sectional area) is maintained because the increase in velocity is offset by the decrease in cross-sectional area. Cerebral vasoconstriction is an indirect autoregulation-mediated consequence, because phenylephrine does not cross the blood – brain barrier and it cannot constrict cerebral vessels directly.

This study also supports the notion that cardiac output is involved in these changes in cerebral oxygenation, since reductions in cardiac output were observed in the three CO2 conditions. However, since these changes in cardiac output following phenylephrine were similar between CO2 conditions, other mechanisms have to play a significant role in the reduction in cerebral oxygenation following phenylephrine administration.

An important issue is also addressed by the authors:

Even though phenylephrine causes a consistent decrease in SctO2 (cerebral oxygenation), the magnitude of the decrease is very small (1.5–3.5% absolute change depending on CO2 level) and seems unlikely to be clinically significant. Al-Rawi and colleagues found that a relative 13% decrease from baseline, which is approximately twice as great as that seen here, correlates with cerebral ischaemia in patients undergoing carotid artery procedures.

I agree that such a small reduction (and for a short amount of time) may be trivial for the brain. However, some studies have reported greater reductions in cerebral oxygenation following administration of this vasopressor. In addition, we still don’t know what is the impact of a reduction of, let’s say 10%, over longer periods of time (2 hours during cardiopulmonary bypass for example) vs. a few minutes during a controlled study in a laboratory. The latter could have a potentially negative impact on the brain…

Meng L, Gelb AW, Alexander BS, Cerussi AE, Tromberg BJ, Yu Z, Mantulin WW. Impact of phenylephrine administration on cerebral tissue oxygen saturation and blood volume is modulated by carbon dioxide in anaesthetized patients. Br J Anaesth 108 (5): 815–22 (2012). doi:10.1093/bja/aes023

Cerebrovascular physiology – article alert #32

Brain autoregulation

133- Dynamic cerebral autoregulation in subjects with Alzheimer’s disease, mild cognitive imparment, and controls: evidence for increased peripheral vascular resistance with possible predictive value – Gommer et al.

134- The frequency response of cerebral autoregulation – Fraser et al.

Lower body positive pressure and the brain

135- Middle cerebral artery blood flow velocity in response to lower body positive pressure – Perry et al.

Hypothermia after cardiac arrest and the brain

136-  Mild therapeutic hypothermia is superior to controlled normothermia for the maintenance of blood pressure and cerebral oxygenation, prevention of organ damage and suppression of oxidative stress after cardiac arrest in a porcine model – Ostadal et al.

Orthostatic tolerance and the brain

137- Slow breathing as a means to improve orthostatic tolerance: a randomized sham-controlled trial – Lucas et al.

Vasopressors and the brain

138- Haemodynamic effects of glycopyrrolate pre-treatment before phenylephrine infusion during spinal anaesthesia for caesarean delivery – Ngan Kee et al.

139- Cerebral effects of commonly used-vasopressor-inotropes: A study in newborn piglets – Hahn et al.

Obstructive sleep apnea and the brain

140- Cerebral oxygenation during sleep in patients with obstructive sleep apnea: A near-infrared spectroscopy study – Akhan et al.

Heart failure and the brain

141- Can early changes in cerebral oxygenation during submaximal exercise predict outcomes in heart failure patients ? – Rafai et al.

Cerebrovascular physiology – article alert #31

Exercise training and the brain

129- Relationship between aerobic endurance training and dynamic cerebral blood flow regulation in humans – Ichikawa et al.

Acute exercise and the brain

130- Dynamic exercise improves cognitive function in association with increased prefrontal oxygenation – Endo et al.

Aging, cognitive load and the brain

131-Very-low-frequency oscillations of cerebral hemodynamics and blood pressure are affected by aging and cognitive load – Vermeij et al.

Sex-related differences in the brain

132- Male-female differences in upregulation of vasoconstrictor responses in human cerebral arteries – Ahnstedt et al.

Cerebrovascular physiology – article alert #29

Treatment of blood pressure and the brain

124- Treatment of presumed hypotension in very low birthweight neonates: effects on regional cerebral oxygenation – Garner and Burchfield

Brain autoregulation

125- Regional differences in dynamic cerebral autoregulation in the healthy brain assessed by magnetic resonance imaging – Horsfield et al.

Primary intracerebral hemorrhage and the brain

126- Autoregulation of cerebral blood flow is preserved in primary intracerebral hemorrhage – Gould et al.