Standard Protocol Approvals, Registrations, and Patient Consents
This is a retrospective cohort study of patients treated at the University Hospital of Bern. We obtained approval from the local ethics committee (Kantonale Ethikkommission Bern, Switzerland) for this study (Project ID 2019-00921), which, because of the retrospective analysis of routine data, waived the need for individual informed consent for the study and allowed the further use of health care data if the patient or next-of-kin had followed the general consent procedure.
Patient Population
We included all patients, who had a ptO2 probe inserted between January 2010 and April 2019. Inclusion criteria for the study population were insertion of a ptO2 probe by CT-guidance, which was routinely performed between October 2017 and April 2019, and age ≥ 18 years. For the historical control group, inclusion criteria were conventional, free-hand insertion of a ptO2 probe, which was routine before October 2017, and age ≥ 18 years. Inclusion was irrespective of the underlying pathology, but most patients suffered either from TBI or SAH.
Intervention
The indications for placement of a ptO2 probe were:
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Risk of evolving ischemia because of cerebral vasospasms and inability to monitor clinically in patients suffering from aneurysmal SAH.
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Critical ICP elevation despite maximal conservative therapy and potential need for intermittent moderate hyperventilation in patients suffering from traumatic brain injury or intracerebral hemorrhage.
We determined for each patient individually an area of interest for ptO2 measurements based on clinical grounds as well as radiological signs of hypoperfusion on CT-perfusion imaging, vasospasm of the basal cerebral arteries on angiography, or perifocal edema of mass occupying lesions. Generally, we aimed at placing the ptO2 probe in an area at risk for hypoxic brain injury. In patients with vasospasms in the territories of the anterior cerebral artery (ACA) and the middle cerebral artery (MCA), we aimed for the watershed zone between these two supply areas. Contrary, in patients with vasospasms in only one of these vessels, we aimed for the specific supply area. If the patient had a preexisting intraparenchymal hematoma, contusion, or infarction, that area was avoided. In patients with traumatic brain injury, we aimed for the frontal lobe on the side, which was more affected by intracranial injuries or for the right frontal lobe, if both sides were equally affected. A target area was chosen at a safe distance from hemorrhagic contusions and preexisting external ventricular drains. Anatomically, the probes were aimed for the watershed zone between the ACA and MCA supply area or in the anterior MCA territory if access to the watershed zone was restricted by a preexisting external ventricular drain.
The technique of CT-guided ptO2 probe insertion was modified and derived from our recent description of CT-guided insertion of external ventricular drains [30]. The exclusive use of single lumen bolts allowed insertion of ptO2 probes irrespective of the location other neuro-monitoring devices. Because the commercially available bolt-kit ptO2 probe (LICOX, Integra LifeSciences, Plainsboro, NJ) has to be inserted at a fixed depth of 30 mm from the inner table or 35 mm from the outer table of the skull bone into the brain, we projected a sphere with a radius of 35 mm with the area of interest in the center of the sphere onto the patient’s CT scan. We then selected a point on the intersection line with the outer table of the skull, which was suitable for burr hole placement and probe insertion. The distance to well-defined craniometrics landmarks (midline, nasion, bregma, coronal suture, or an existing external ventricular drain) was measured on the CT scan. We transferred these measurements onto the patient’s skull and placed the burr hole accordingly. Burr hole placement and bolt insertion were performed in a standard manner in the CT or angiography suite. We use povidone-iodine (Betadine; Mundipharma, Basel, Switzerland) or chlorhexidine (chlorhexidine 2% alcoholic uncolored, B. Braun Medical, Melsungen, Germany) and surgical drapes for skin preparation. The surgeon incised the skin over approximately 5 mm at the site of the planned burr hole. The burr hole was drilled with a manually operated twist drill. After the dura was perforated, we screwed the bolt of the ptO2 probe (LICOX, Integra LifeSciences, Plainsboro, NJ) superficially into the skull in the approximate angle necessary to reach the area of interest. We then performed an immediate bolt CT scan to verify the trajectory of the bolt. In order to reduce the radiation dose, the scan covered only the supraorbital part of the skull including the bolt end down to roof of the third ventricle. The CT data set was immediately reconstructed along the trajectory of the bolt. If necessary, we adjusted the trajectory by adapting the angulation of the bolt. In this case, a second bolt CT was performed to confirm the correct trajectory. This procedure was repeated until the correct bolt angulation was found. Then, the surgeon screwed the bolt firmly into the skull and inserted the sheath of the ptO2 probe. Another CT scan was acquired to confirm the correct location of the sheath. After insertion of the ptO2 probe, a final postoperative CT scan was performed to assess the correct location of the tip of the ptO2 probe in the area of interest.
If duration of ptO2 monitoring exceeded one week, we routinely exchanged probes.
Our threshold for the initiation of diagnostic or therapeutic measures is a ptO2 measurement ≤ 15 mmHg for ≥ 10 min. In cases with an evident reason for ptO2 decline, e.g., documented vasospasms after SAH, no further diagnostic studies were initiated, but therapeutic measures were taken directly. These consisted of medical measures first (e.g., adjustment of mean arterial pressure in case of vasospasm related misery perfusion or medical therapy for increased ICP) and in refractory cases, interventional measures such as local spasmolysis or angioplasty, or surgical interventions (e.g., hemicraniectomy). A detailed description of the therapeutic algorithm is given in Fig. 1. The algorithm is consistent with the BONANZA algorithm and in large parts with the BOOST-II algorithm, although inspiratory oxygen fraction was not increased to correct ptO2 values [16].
Data Analysis
The primary endpoint was the successful CT-guided positioning of the ptO2 probe inside the area of interest in the study group. The correct location was evaluated by two raters (L. H. and M. D. R.). Based on the target area specified in the operation report, as well as the consideration of clinical and imaging characteristics of each individual patient, each rater retrospectively placed a sphere with a radius of 1 cm (volume of 4.2 ml) with the point of major interest in the center onto the preinterventional CT scan. Overlap with preexisting infarcts, hematomas, and contusions was avoided. These spheres represented the target location. We fused the pre- and postinterventional images then and evaluated the location of the probe with respect to the sphere. If the tip of the probe was inside the sphere, we considered the placement correct. Conversely, if the tip of the probe was located outside the sphere, we considered the placement incorrect. If both raters agreed on the correct placement of the probe, the primary endpoint was reached and the positioning successful. If one of the raters considered the tip inside the target location, while the other rater did not, or if both raters agreed on the incorrect placement, we considered the placement unsuccessful and the primary endpoint was not reached. For image manipulation and fusion, the software Elements (Brainlab, Munich, Germany) was used.
Secondary endpoints included radiological and clinical parameters. We evaluated for the study and the historical control group complications from probe insertion, clinical consequences from ptO2 measurements, as well as clinical outcome according to the modified Rankin Scale (mRS) after 6 months. A good outcome was considered a mRS score of ≤ 3.
Radiological outcome was assessed by a board-certified, senior neuroradiologist (F. W.) and included complications from probe insertion, determination of the vascular territory of the probe, and assessment of vasospasm, hypoperfusion, or ischemia over the course of ptO2 monitoring until 7 days thereafter inside or outside the target area of the probe. Furthermore, we recorded the appearance of any new parenchymal lesions or ischemia on the latest imaging study available from each patient.
Clinical data and ptO2 values were extracted from the institutional electronic Patient Data Management System (Centricity™ Critical Care, General Electric Company, GE Healthcare, USA). The system automatically documents all ptO2 and ICP values, hemodynamic, and respiratory variables in intervals of 2 min. Further clinical data such as GCS score, fluid balances, and administered drugs are entered manually by the bedside team.
Additionally, for the study group only, the total number of CT scans for probe insertion as well as the cumulative radiation exposure was documented for each patient. The cumulative radiation dose was calculated as the sum of the dose-length product (DLP) of each CT scan:
$$ {\text{DLP }} = {\text{ CTDI}}_{{{\text{Vol}}}} {\text{x nT}}, $$
where CTDI = computed tomography dose index and nT = product of the number of slices and slice thickness. To calculate the effective dose (E), a conversion factor of 0.0021 was applied:[31]
$$ {\text{E }} = {\text{ DLP x }}0.00{21}. $$
The duration of the intervention was derivated from the acquisition time of imaging data. The total duration was defined as the time interval between the last diagnostic scan, i.e., before insertion of the bolt, and the final confirmatory scan. Thus, the total duration includes the time for diagnostic imaging analysis, target selection, entry point calculation, bolt insertion, analysis and correction of the trajectory, any additional scans, and insertion of the probe. The extra duration of using CT-guidance was defined as the time interval between the first scan with the bolt in situ and the final confirmatory scan. The extra duration represents the time for the analysis and correction of the trajectory, any additional scans, and insertion of the probe.
Based on the three vascular territories available (ACA, watershed zone, and anterior MCA), we grouped the correctly placed probes together and measured the location of the cranial entry points and trajectories of the ptO2 probes. The location of the entry point as distance from the midline in the coronal plane and as distance from the coronal suture in the sagittal plane was measured. Furthermore, the probe trajectory was assessed in degrees angulation in a sagittal projection with reference to the Frankfurt horizontal plane as well as in a coronal projection with reference to the midline.
Statistics
We will report results of the primary outcome descriptively. In case a patient had bilateral probes placed, we evaluated both sides independently.
For comparison of entry sites and trajectories between groups of different vascular territories, a Kruskal–Wallis test was applied. Continuous variables are reported as mean and standard deviation. We compared the study group and the control group using a Mann–Whitney U test for continuous variables and Chi-Square or Fisher’s exact test for nominal variables. Statistical analysis was performed using the statistical software SPSS (IBM, Version 25).
We addressed missing values first by re-analyzing the source data or, in case no value was retrievable, pairwise deletion.