title: Controlled transient hypercapnia: a novel approach for the treatment of delayed cerebral ischemia after subarachnoid hemorrhage?
abstract: OBJECTIVE
  The authors undertook this study to investigate whether the physiological mechanism of cerebral blood flow (CBF) regulation by alteration of the arterial partial pressure of carbon dioxide (PaCO₂) can be used to increase CBF after aneurysmal subarachnoid hemorrhage (aSAH).
  
  
  METHODS
  In 6 mechanically ventilated patients with poor-grade aSAH, the PaCO₂ was first decreased to 30 mm Hg by modification of the respiratory rate, then gradually increased to 40, 50 and 60 mm Hg for 15 minutes each setting. Thereafter, the respirator settings were returned to baseline parameters. Intracerebral CBF measurement and brain tissue oxygen saturation (StiO₂), measured by near-infrared spectroscopy (NIRS), were the primary and secondary end points. Intracranial pressure (ICP) was controlled by external ventricular drainage.
  
  
  RESULTS
  A total of 60 interventions were performed in 6 patients. CBF decreased to 77% of baseline at a PaCO₂ of 30 mm Hg and increased to 98%, 124%, and 143% at PaCO₂ values of 40, 50, and 60 mm Hg, respectively. Simultaneously, StiO₂ decreased to 94%, then increased to 99%, 105%, and 111% of baseline. A slightly elevated delivery rate of cerebrospinal fluid was noticed under continuous drainage. ICP remained constant. After returning to baseline respirator settings, both CBF and StiO₂ remained elevated and only gradually returned to pre-hypercapnia values without a rebound effect. None of the patients developed secondary cerebral infarction.
  
  
  CONCLUSIONS
  Gradual hypercapnia was well tolerated by poor-grade SAH patients. Both CBF and StiO₂ reacted with a sustained elevation upon hypercapnia; this elevation outlasted the period of hypercapnia and only slowly returned to normal without a rebound effect. Elevations of ICP were well compensated by continuous CSF drainage. Hypercapnia may yield a therapeutic potential in this state of critical brain perfusion. Clinical trial registration no.: NCT01799525 ( ClinicalTrials.gov ).
authors.affiliation: Departments of Neurosurgery and.
authors.forename: Thomas
authors.initials: T
authors.lastname: Westermaier
authors.forename: Christian
authors.initials: C
authors.lastname: Stetter
authors.forename: Ekkehard
authors.initials: E
authors.lastname: Kunze
authors.forename: Nadine
authors.initials: N
authors.lastname: Willner
authors.forename: Judith
authors.initials: J
authors.lastname: Holzmeier
authors.forename: Christian
authors.initials: C
authors.lastname: Kilgenstein
authors.forename: Jin-Yul
authors.initials: JY
authors.lastname: Lee
authors.forename: Ralf-Ingo
authors.initials: RI
authors.lastname: Ernestus
authors.forename: Norbert
authors.initials: N
authors.lastname: Roewer
authors.forename: Ralf Michael
authors.initials: RM
authors.lastname: Muellenbach
mesh_terms: D000328:Adult; D000368:Aged; D001784:Blood Gas Analysis; D002545:Brain Ischemia / Q000209:etiology* / Q000628:therapy*; D002245:Carbon Dioxide / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D002533:Cerebral Angiography; D002544:Cerebral Infarction / Q000503:physiopathology; D002560:Cerebrovascular Circulation; D005260:Female; D006439:Hemodynamics / Q000502:physiology; D006801:Humans; D006935:Hypercapnia / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D012121:Respiration, Artificial; D013345:Subarachnoid Hemorrhage / Q000150:complications*; D020301:Vasospasm, Intracranial / Q000503:physiopathology
chemical_list: D002245:Carbon Dioxide
keywords: CBF; CBF = cerebral blood flow; DCI = delayed cerebral ischemia; ICP = intracranial pressure; NIRS = near-infrared spectroscopy; PaCO2 = arterial partial pressure of carbon dioxide; PaO2 = arterial partial pressure of oxygen; SAH = subarachnoid hemorrhage; StiO2 = brain tissue oxygen saturation; TCD = transcranial Doppler sonography; aSAH = aneurysmal SAH; delayed cerebral ischemia; hypercapnia; neuroprotection; subarachnoid hemorrhage; vascular disorders; vasospasm