TY  - JOUR
A1  - Stetter, Christian
A1  - Weidner, Franziska
A1  - Lilla, Nadine
A1  - Weiland, Judith
A1  - Kunze, Ekkehard
A1  - Ernestus, Ralf-Ingo
A1  - Muellenbach, Ralf Michael
A1  - Westermaier, Thomas
T1  - Therapeutic hypercapnia for prevention of secondary ischemia after severe subarachnoid hemorrhage: physiological responses to continuous hypercapnia
JF  - Scientific Reports
N2  - Temporary hypercapnia has been shown to increase cerebral blood flow (CBF) and might be used as a therapeutical tool in patients with severe subarachnoid hemorrhage (SAH). It was the aim of this study was to investigate the optimum duration of hypercapnia. This point is assumed to be the time at which buffer systems become active, cause an adaptation to changes of the arterial partial pressure of carbon dioxide (PaCO2) and annihilate a possible therapeutic effect. In this prospective interventional study in a neurosurgical ICU the arterial partial pressure of carbon dioxide (PaCO\(_2\)) was increased to a target range of 55 mmHg for 120 min by modification of the respiratory minute volume (RMV) one time a day between day 4 and 14 in 12 mechanically ventilated poor-grade SAH-patients. Arterial blood gases were measured every 15 min. CBF and brain tissue oxygen saturation (StiO\(_2\)) were the primary and secondary end points. Intracranial pressure (ICP) was controlled by an external ventricular drainage. Under continuous hypercapnia (PaCO\(_2\) of 53.17 ± 5.07), CBF was significantly elevated between 15 and 120 min after the start of hypercapnia. During the course of the trial intervention, cardiac output also increased significantly. To assess the direct effect of hypercapnia on brain perfusion, the increase of CBF was corrected by the parallel increase of cardiac output. The maximum direct CBF enhancing effect of hypercapnia of 32% was noted at 45 min after the start of hypercapnia. Thereafter, the CBF enhancing slowly declined. No relevant adverse effects were observed. CBF and StiO\(_2\) reproducibly increased by controlled hypercapnia in all patients. After 45 min, the curve of CBF enhancement showed an inflection point when corrected by cardiac output. It is concluded that 45 min might be the optimum duration for a therapeutic use and may provide an optimal balance between the benefits of hypercapnia and risks of a negative rebound effect after return to normal ventilation parameters.
KW  - cerebrovascular disorders
KW  - clinical trials
KW  - neurology
KW  - neurovascular disorders
KW  - Phase II trials
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-260779
VL  - 11
IS  - 1
ER  - 
TY  - THES
A1  - Weidner, Franziska
T1  - Therapeutische Hyperkapnie bei aneurysmatischer Subarachnoidalblutung (SAB) : Evaluation der optimalen Hyperkapniedauer
T1  - Dose Optimization Study of Therapeutic Hypercapnia for Prevention of Secondary Ischemia After Severe Subarachnoid Hemorrhage
N2  - In einer vorangegangenen Phase-1-Studie wurde beobachtet, dass bei Patienten mit schwerer aneurysmatischer SAB, die CBF durch intermittierende kontrollierte Hyperkapnie erhöht werden kann. Zudem zeigte sich in dieser vorherigen Studie nach dem Zurücksetzen der mechanischen Beatmung auf die Ausgangsparameter eine langsame und asymptotische Rückkehr der CBF zu den Ausgangsniveaus ohne einen negativen Rebound-Effekt. Diese Beobachtung legte nahe, dass eine längere Dauer der Hyperkapnie den CBF-erhöhenden Effekt verlängern kann. 
Die vorliegende Studie wurde als Dosisoptimierungsstudie geplant, um den Zeitpunkt zu bestimmen, zu dem der CBF ein Maximum erreicht, und unter der Annahme, dass nach diesem Maximum Puffermechanismen in Blut und Liquor zu Anpassungsmechanismen führen können, die nach dem Abbruch zu einem negativen Rebound-Effekt führen. 
Es ergab sich eine "Netto" - Optimaldauer der Hyperkapnieintervention von 45 Minuten.
N2  - In a previous phase 1 study, it was observed that CBF can be increased by intermittent controlled hypercapnia in the days after aneurysm rupture in patients with poor to very poor SAB. After resetting mechanical ventilation to baseline parameters, CBF showed a slow and asymptotic return to baseline values without a negative rebound effect. This observation suggests that a longer duration of hypercapnia may prolong the CBF-increasing effect. 
 This study was designed as a dose-optimization study to identify the time point at which CBF reaches a maximum and under the assumption that after this maximum, buffering mechanisms in blood and CSF could lead to adaptation mechanisms that result in a negative rebound effect after cessation of the hypercapnic challenge. An optimal duration of hypercapnia of 45 minutes was noted.
KW  - Hyperkapnie
KW  - Subarachnoidalblutung
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-238696
ER  -