Clinical application of high frequency jet ventilation in stereotactic liver ablations – a methodological study

Background: Computer-assisted navigation during thermal ablation of liver tumours, may help to correct needle placement and improve ablation efficacy in percutaneous, laparoscopic and open interventions. The potential advantage of using high frequency jet-ventilation technique (HFJV) during the procedure is by minimising the amplitude of respiration-related upper-abdominal organs movements. The aim of this clinical methodological trial was to establish whether HFJV would give less ventilatory induced liver movements than conventional ventilation, during stereotactic navigated ablation of liver metastases under open surgery. Methods: Five consecutive patients scheduled for elective, open liver ablation under general propofol and remifentanil anaesthesia were included in the study protocol. During the stereotactic targeting of the tumours, HFJV was chosen for intraoperative lung ventilation. For tracking of liver movement, a rigid marker shield was placed on the liver surface and tracked with an optical position measurement system. A 4D position of the marker shield was measured for HFJV and conventional tidal volume lung ventilation (TV). At each time point the magnitude of liver displacement was calculated as an Euclidean distance between translational component of the marker shield's 3D position and previously estimated centroid of the translational motion. Results: The mean Euclidean liver displacement was 0.80 (0.10) mm for HFJV and 2,90 (1.03) mm for TV with maximum displacement going as far as 12 mm on standard ventilation (p=0.0001). Conclusion: HFJV is a valuable lung ventilation method for patients undergoing stereotactic surgical procedures in general anaesthesia when reduction of organ displacement is crucial.


Introduction
Thermal ablation of primary and secondary liver tumours is a potentially curative treatment, and an alternative for patients not eligible for surgical resection due to severe comorbidity or underlying liver disease. Its efficacy has been proven for tumours smaller than 30mm in diameter, especially in treatment of hepatocellular carcinomas 1 . Adequate imaging of the tumour and precise guidance of the ablation device are crucial for accurate local ablative treatment. Accurate targeting is essential for an effective treatment, reducing the risk for local recurrence and need of retreatment 1,2 .
Recent developments in image guidance systems, with robotic and computer-assisted navigation, may help correct needle placement and improved ablation efficacy. Needle navigation and placement is based on pre-interventional imaging. Early phantom and clinical experiences with navigation systems suggest good procedural accuracy, reduced procedure time and reduced patient radiation exposure compared to freehand techniques 3 .
The high frequency jet-ventilation technique (HFJV) was developed in the seventies by Klain and Smith, and mostly applied in the field of ear-nose-and-throat (ENT) surgery. It does not rely on conventional tidal volumes but uses a high frequency forced gas move 4 . The potential advantage of using HFJV in abdominal surgery is to minimise the amplitude of respirationrelated upper-abdominal organs compared to conventional tidal volume lung ventilation (TV) 5-7 .
The aim of this clinical methodological trial was to measure the liver movements during open surgery under general anaesthesia and compare HFJV with conventional ventilation.

Methods
Five consecutive patients who were scheduled for elective, open liver ablations were included in the clinical protocol.

Lung ventilation and surgical precision evaluation
Endotracheal intubation with a conventional endotracheal (ET) tube was performed at the induction of anaesthesia, followed by the initiation of conventional lung ventilation with pressure control/volume guarantee ventilation (PCV/VG -Aisys Carestation, GE Healthcare, Helsinki, Finland) as well as a lungprotective regime to achieve normo-ventilatory status. Tidal volumes have been calculated after the reduced body weight with 6-7ml/kg target and fixed 5cmH20 positive end-expiratory pressure (PEEP). Laparotomy was performed with a right subcostal incision. A HFJV cannula (LaserJet Catheter, Acutronic Medical Systems AG, Hirzel, Switzerland) was inserted endotracheally with the tip at the end of the ET-tube. HFJV (Monsoon HFJV ventilator, Acutronic Medical Systems, AG, 8816 Hirzel, Switzerland) was then initiated and continued during the liver ablation procedure. HFJV driving pressure (DP) was adjusted downwards, beginning at 1.8 bar, until satisfactory operationfield conditions were reached in accordance with the operating surgeon's assessment.

Carbon dioxide control
In the first phase, after the induction of anaesthesia, end-tidal carbon dioxide tension (EtCO2) was continuously monitored through the use of classical side-stream capnography towards the normocapnic state. During the HFJV phase, sequential measurements were taken with 10 minute intervals (Integrated Monsoon ventilator etCO2 module). After the termination of the last tumour ablation and the completion of liver movement measurement, the conventional lung ventilation was restored. Lastly, the etCO2 measurement was repeated following the same method as the one used at the start of the procedure. Cut-off values for discontinuation of HFJV was either etCO2 rise over 10 kPa, or oxygen de-saturation under 90%. With etCO2 exceeding 8 kPa, the DP down-regulation has been stopped and instead increased by 0.1 bar increments every 5 minutes until the target etCO2 was reached.

Surgical imaging and liver motion measurements
Patients were selected at the regional liver multidisciplinary team conference and were regarded as unresectable due to multiple metastases involving too many liver segments, but numbered less than twenty and none larger than thirty millimeters in diameter 8 . Multiple ablations were then performed using an intraoperative ultrasound and a stereotactic targeting device, CAS-one (Cascination AG, Bern, Switzerland) where a previously acquired computed tomography scan was merged with previous scans in cases of vanished lesions, and a 3D model of the liver reconstructed by MeVIS medical solutions AG (Bremen, Germany) was used as a surgical map with optical navigation of ablation antennae, as previously described 8 . For tracking of liver movement, a rigid marker shield with a set of retroreflective marker spheres was placed on the liver surface in the vicinity of the lower border of segment 4b and tracked with an optical position measurement system (Polaris Vicra, NDI, Canada) incorporated into the CAS-One system which was positioned in the vicinity of the operative field thus providing a constant line of sight. A 4D position of the marker shield was measured for approximately 2-3 minutes for HFJV and conventional ventilation.
At each time point t, the magnitude of liver displacement d, was calculated as an Euclidean distance between translational component p  of the marker shield's 3D position, and previously estimated centroid of the translational motion c , i.e. an average translational position of the marker, as listed in the equation below: All displacement errors d were described quantitatively using mean (µ) and standard deviation (σ) as well as a maximum error value. Statistically significant differences were tested with the two-tailed, nonparametric, unpaired t-test, where p < 0.05 was defined as statistically significant.

Results
Patient demographics, medical status and extent of surgery is presented in Table 1.
Ventilator settings and readings are shown in in Table 2. The following parameters have been registered: end tidal CO 2 concentrations before and after HFJV phase, respiratory pressures on conventional tidal volume ventilation before and after HFJV, peak inspiratory pressure and mean airway before and after HFJV, mean airway pressure, dynamic lung compliance both before and after HFJV phase as well as tidal volumes on conventional lung ventilation, at liver displacement measurement point. HFJV ventilator settings: respiratory frequency and target driving pressure as well as the measured respiratory  parameters: peak inspiratory pressure and mean airway pressure as well as maximum end tidal carbon dioxide tension on HFJV.
In one case (patient number 2) an increase in DP was needed, because the etCO2 rose to 8.3 kPa and the optimal value was set on to 1.5 bar where in other four cases it was set to 1.1-1.2 bar. One patient (number 5) turned out to have more than 20 metastases at time of surgery, but not on the imageing where the treatment was allocated. Rather than to close up, a new evaluation was done during surgery using intraoperative ultrasound and it was found that ablations could be done leaving an adequate volume of functioning liver parenchyma, why this was the course taken.
The mean Euclidean liver displacement was 0.80 (0.10 SD) mm and 2.90 (1.03 SD) mm for HFJV and TV respectively with maximum displacement going as far as 12 mm on standard ventilation (p=0.0001). Data shown in Figure 1.

Discussion
One of the most important challenges the anaesthesiologist faces perioperatively is the maintaining of the patient's homeostasis and the facilitating of the course of surgery. In certain clinical situations, such as in stereotactic ablative procedures, it can be difficult to establish since there is a demand for keeping respiratory organ displacement to a minimum.
The recent investigation provides evidence for the claim that respiration induced liver motion during intervention can be reduced by more than two thirds when using HFJV instead of TV. This is the only study measuring this effect dynamically. This can have a decisive bearing on the risk of local recurrence rates and risk for collateral damage after image guided stereotactic treatment of liver tumours. The benefits in terms of radiation dose and respiratory organ shifting, when using HFJV in interventional radiology has previously been reported from several groups 5,6,9 , but these were all conducted in the setting of a CT-guided ablation with non-dynamic measurements of target organ displacement.
Stereotactic navigation is often performed on rigid registration between the intraoperative target organ with the images obtained before the surgery. With this setting, soft tissue deformation and patient motion will affect the navigation system and can cause significant inaccuracy 10 . The minimization of deformation-induced errors can be done in several ways. From experimental research point of view, the position of the moving target can be measured by implanted navigation aids or by using electromagnetic tracking devices 10,11 . Implantation of invasive needles is however not prudent in a clinical setting due to high risk of haemorrhage, tumour seeding, and long-term risks with leaving foreign bodies in situ.
Another approach is the mathematical modelling of mechanical tissue properties and organ motion in order to predict the target location based on a statistical model derived from preoperative 4D CT. This approach is frequently used in intensity modulated radiation therapies (IMRT) 12 . The relationship between the respiratory cycle and the movement of a target is however complex to predict and not possible in real time due to highly intensive computational requirements and obvious risks of differences in outcome during the acquisition of preoperative images and a situation with artificial respiration and an open or laparoscopically affected abdomen.
Therefore, respiratory gating methods that reliably reproduce a known breathing stage (temporarily disconnecting endotracheal tube in anaesthetized patients) seem to be a more reliable approach 12,13 . An overall internal target movement of 1.41 ± 0.75 mm was reported. However, periods of apnea are usually limited to 1-2 minutes depending on the health condition of the patient. HFJV overcomes these restrictions.
Use of HFJV outside the ENT and Thorax suites have been the subject of several, but rather anecdotal reports. In minimally invasive oncological procedures HFJV have been used in percutaneous, laparoscopic as well as in open approaches 3,5,6,14 .
In cardiology it has been beneficial in catheter ablations 15 . In urology it can be helpful to minimize the numbers of shocks needed during ESWL-treatment 15,16 .
The present study is small and though the liver displacement data is solid, further studies on the physiological effects of HFJV is needed to elucidate the limitations. Carbon dioxide control is one of the important aspects of perioperative management. In the treatment protocol established during the study, it remained even more challenging because of the "less is better" strategy, favouring relatively low respiratory driving pressures.
Introducing HFJV in the management of computer-assisted abdominal surgery to a wider extent remains promising. The wider use of this method is, however, limited by the equipment availability and staff experience. Nevertheless, in the scale of a highly specialized centre, the acceptable skill level can easily be achieved, and the overall cost of the equipment as well as materials and utilities remains reasonable. HFJV is a promising lung ventilation modality for patients undergoing stereotactic surgical procedures in general anaesthesia when reduction of target organ displacement is crucial.

Ethical considerations
All procedures performed were in accordance with the ethical standards of the institution at which the studies were conducted. Since this was a retrospective analysis of the clinical material collected before, the written consent has been obtained only from two patients still alive at the time when the decision of data analysis and publication have been made. Other three patients have already died.

Grant information
The author(s) declared that no grants were involved in supporting this work.

If applicable, is the statistical analysis and its interpretation appropriate? Yes
Are all the source data underlying the results available to ensure full reproducibility? Yes

Are the conclusions drawn adequately supported by the results? Yes
No competing interests were disclosed.

Competing Interests:
We have read this submission. We believe that we have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. We would like to thank professor Trzebicki for his positiv input. The suggested terminological changes in definition of conventional lung ventilation will be done in the manuscript soon. We choose the TV abbreviation for tidal volume ventilation. The second comment concerning the number of metastases in case 5 was the same as professor Sandströms and the appopriate explanation will be done in Discussion chapter.
There is no competing interests. have written an important paper comparing liver movement during computer-assisted liver et al thermal ablation using high frequency jet-ventilation (HFJV) compared to conventional ventilation. The study includes 5 patients treated with open liver tumor ablations and both methods are used in each patient showing a significant and clinically relevant reduced liver movement with HFJV. As pointed out by the authors, liver displacement must be as small as possible when performing liver ablations, to reduce the risk of missing the lesion.
A few minor comments 1,2 1 2 during surgery using intraoperative ultrasound and it was found that ablations could be done leaving an adequate volume of functioning liver parenchyma, why this was the course taken.
2. Open surgery was used because at this time the hardware and software used for lesion tracking was only adapted for open surgery. We now use a laparoscopic approach instead and have done for a few years.
3. ENT is of course ear, nose and throat. This should have been spelled out in the text. 4. A dynamic study of liver motion with respiration could indeed be studied using flouroscopy or even better, tracking an electromagnetic intravascular probe introduced as far peripherally as possible in the liver. We have not done this but the suggestion is very good since this is an obvious problem during CT-guided interventions.

no competing interests Competing Interests:
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