Controlled Hypercapnia Enhances Cerebral Blood Flow and Brain Tissue Oxygenation After Aneurysmal Subarachnoid Hemorrhage: Results of a Phase 1 Study

Neurocrit Care. 2016 Oct;25(2):205-14. doi: 10.1007/s12028-016-0246-x.


Background: This study investigated if cerebral blood flow (CBF) regulation by changes of the arterial partial pressure of carbon dioxide (PaCO2) can be used therapeutically to increase CBF and improve neurological outcome after subarachnoid hemorrhage (SAH).

Methods: In 12 mechanically ventilated poor-grade SAH-patients, a daily trial intervention was performed between day 4 and 14. During this intervention, PaCO2 was decreased to 30 mmHg and then gradually increased to 40, 50, and 60 mmHg in 15-min intervals by modifications of the respiratory minute volume. CBF and brain tissue oxygen saturation (StiO2) were the primary and secondary endpoints. Intracranial pressure was controlled by an external ventricular drainage.

Results: CBF reproducibly decreased during hyperventilation and increased to a maximum of 141 ± 53 % of baseline during hypercapnia (PaCO2 60 mmHg) on all days between day 4 and 14 after SAH. Similarly, StiO2 increased during hypercapnia. CBF remained elevated within the first hour after resetting ventilation to baseline parameters and no rebound effect was observed within this time-span. PaCO2-reactivities of CBF and StiO2 were highest between 30 and 50 mmHg and slightly decreased at higher levels.

Conclusion: CBF and StiO2 reproducibly increased by controlled hypercapnia of up to 60 mmHg even during the period of the maximum expected vasospasm. The absence of a rebound effect within the first hour after hypercapnia indicates that an improvement of the protocol is possible. The intervention may yield a therapeutic potential to prevent ischemic deficits after aneurysmal SAH.

Keywords: CO2-reactivity; DCI; Delayed cerebral infarction; Hypercapnia; Ischemia; Subarachnoid hemorrhage; Vasospasm.

Publication types

  • Clinical Trial, Phase I

MeSH terms

  • Brain / metabolism*
  • Brain Ischemia / prevention & control*
  • Cerebrovascular Circulation / physiology*
  • Humans
  • Hypercapnia*
  • Intracranial Aneurysm / complications*
  • Outcome Assessment, Health Care*
  • Oxygen Consumption / physiology*
  • Subarachnoid Hemorrhage / etiology
  • Subarachnoid Hemorrhage / therapy*