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

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.

Effects of Fluid Treatment With Hydroxyethyl Starch on Renal Function in Patients With Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Recent reports have doubted the efficacy and safety of hydroxyethyl starch (HES) for volume resuscitation. HES has been reported to promote renal insufficiency particularly in sepsis and trauma patients. This analysis investigated the effects of HES 6% 130/0.4 for fluid therapy in patients with intact renal function who suffered aneurysmal subarachnoid hemorrhage (SAH). METHODS: This retrospective analysis included 107 patients and was conducted in the framework of a clinical trial assessing the efficacy of magnesium sulfate in SAH. Because magnesium is renally eliminated, patients with renal insufficiency had been excluded. Standard therapy after aneurysm occlusion included the daily administration of HES 6% 130/0.4. Serum and urine creatinine and fluid balance were measured daily. RESULTS: Patients received a daily mean of 1101±524 mL HES and 3353±1396 mL Ringer's solution. The highest creatinine values were recorded on day 3 after admission (0.88±0.25 mg/100 mL) and continuously decreased thereafter. In 6 patients, creatinine values temporarily increased by >0.3 mg/100 mL but recovered to admission values at the end of the observation period. CONCLUSIONS: Concerning renal function, the first days after SAH seem to be a vulnerable phase in which a variety of interventions are performed, including contrast-enhanced neuroradiologic procedures. In this period, HES 6% 130/0.4 should be administered with caution. However, no patient suffered from renal failure and required temporary or permanent renal replacement therapy. These results suggest that the administration of HES 6% 130/0.4 is safe in SAH patients without preexisting renal insufficiency.

Cerebral tissue oxygenation during the initiation of venovenous ECMO.

UNLABELLED: In an acute respiratory distress syndrome, venovenous extracorporeal membrane oxygenation (vvECMO) can rapidly normalize arterial hypoxemia and carbon dioxide tension (PaCO2). Considering the positive relationship between PaCO2 and cerebral blood flow, the aim of the current study was to evaluate cerebral regional tissue oxygen saturation (rSO2) during the implementation of vvECMO. Fifteen acute respiratory distress syndrome patients with recordings of cerebral rSO2 by near-infrared spectroscopy before vvECMO implementation until the optimization of the ECMO/ventilator settings were retrospectively studied. RESULTS: median (interquartile range). The cerebral rSO2 increased significantly (p < 0.05) from 69(61-74) to 75(60-80)% after ECMO was started, concomitant to the arterial oxygenation. Until the end of the observation period after 83(44-132) minutes, cerebral rSO2 decreased significantly to 61(52-71)%. PaCO2 decreased from 70(61-87) to 43(38-54) mm Hg and the pH increased from 7.23(7.14-7.29) to 7.39(7.34-7.43). The baseline arterial oxygen saturation and tension as well as the actual bicarbonate concentration were negatively correlated with the absolute change in cerebral rSO2 (ΔrSO2). In the 11 nonhypoxemic patients (arterial oxygen saturation ≥90%) ΔPaCO2 was significantly correlated with ΔrSO2. Patients receiving vvECMO treatment are at risk for a decrease in cerebral rSO2. This decrease is more distinct in patients with normal baseline arterial oxygenation and high actual bicarbonate.

Controlled transient hypercapnia: a novel approach for the treatment of delayed cerebral ischemia after subarachnoid hemorrhage?

OBJECT: 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 ).