Martin Grossherr

Protective ventilation using electrical impedance tomography

Dynamic thoracic EIT is capable of detecting changes of the ventilation distribution in the lung. Nevertheless, it has yet to become an established clinical tool. Therefore, it is necessary to consider application scenarios wherein fast and distinct changes of the tissue conductivities are to be found and also have a clear diagnostic significance. One such a scenario is the artificial ventilation of patients suffering from the acute respiratory distress syndrome (ARDS). New protective ventilation strategies involving recruitment manoeuvres are associated with noticeable shifts of body fluids and regional ventilation, which can quite easily be detected by EIT. The bedside assessment of these recruitment manoeuvres will help the attending physician to optimize treatment. Hence, we performed an animal study of lavage-induced lung failure and investigated if EIT is capable of qualitatively as well as quantitatively monitoring lung recruitment during a stepwise PEEP trial. Additionally, we integrated EIT into a fuzzy controller-based ventilation system which allows one to perform automated recruitment manoeuvres (open lung concept) based on online PaO2 measurements. We found that EIT is a useful tool to titrate the proper PEEP level after fully recruiting the lung. Furthermore, EIT seems to be able to determine the status of recruitment when combining it with other physiological parameters. These results suggest that EIT may play an important role in the individualization of protective ventilation strategies.

Discontinuous monitoring of propofol concentrations in expired alveolar gas and in arterial and venous plasma during artificial ventilation

Background: Analyzing propofol concentration in expired alveolar gas (cPA) may be considered as a convenient, noninvasive method to follow the propofol concentration in plasma (cPPL). In the current study, the authors established procedures to measure cPA and cPPL for the assessment of their relation in two animal models during anesthesia. Methods: Expired alveolar gas and mixed venous and arterial blood were simultaneously sampled during continuous application of propofol for general anesthesia to three goats and three pigs. Propofol infusion rates were varied to modify plasma concentrations. cPA, sampled cumulatively over several respiratory cycles, was quantified by thermal desorption gas chromatography–mass spectrometry. cPPL was determined using reversed phase high-performance liquid chromatography with fluorescence detection. Results: cPA ranged from 0 to 1.4 and from 0 to 22 parts per billion in goats and pigs, respectively, at cPPL of 0–8 &mgr;g/ml. The relation between cPA and cPPL was linear; however, the slopes of the regression lines varied between animals. Conclusion: Propofol can be quantified in expired alveolar gas. The results stress the role of marked species-specific variability.

Propofol concentration in exhaled air and arterial plasma in mechanically ventilated patients undergoing cardiac surgery

BACKGROUND Measuring propofol concentration in plasma (c(P)PL) and in exhaled alveolar gas (c(P)G) during constant infusion provides information about their respective time courses. In the present study, we compared these time courses in patients undergoing cardiac surgery from the beginning of propofol anaesthesia until eye opening upon awakening. METHODS The c(P)G was measured before, during, and after continuous infusion of propofol for general anaesthesia in 12 patients at two randomly allocated doses (3 or 6 mg kg(-1) h(-1)). Gas samples were collected on Tenax tubes. After thermodesorption, c(P)G was measured by gas chromatography mass spectrometry. Simultaneously with exhaled gas, arterial blood was sampled for measuring c(P)PL by reversed-phase high-performance liquid chromatography with fluorescence detection. In order to compare the time courses of c(P)PL and c(P)G as dimensionless values directly, each gas and plasma value was normalized by relating it to the corresponding value at the end of the initial infusion after 40 min. RESULTS The c(P)G ranged between 2.8 and 22.5 ppb, whereas the corresponding c(P)PL varied between 0.3 and 3.3 microg ml(-1). Normalized concentration values showed a delayed increase in c(P)G compared with c(P)PL under constant propofol infusion before the onset of cardiopulmonary bypass, and a delayed decrease after stopping the propofol at the end of anaesthesia. CONCLUSIONS Propofol can be measured in exhaled gas from the beginning until the end of propofol anaesthesia. The different time courses of c(P)PL and c(P)G have to be considered when interpreting c(P)G.

Effect of PEEP on regional ventilation during laparoscopic surgery monitored by electrical impedance tomography

Background: Anesthesia per se and pneumoperitoneum during laparoscopic surgery lead to atelectasis and impairment of oxygenation. We hypothesized that a ventilation with positive end‐expiratory pressure (PEEP) during general anesthesia and laparoscopic surgery leads to a more homogeneous ventilation distribution as determined by electrical impedance tomography (EIT). Furthermore, we supposed that PEEP ventilation in lung‐healthy patients would improve the parameters of oxygenation and respiratory compliance.

Dose-Escalation Study for Cardiac Radiosurgery in a Porcine Model

PURPOSE To perform a proof-of-principle dose-escalation study to radiosurgically induce scarring in cardiac muscle tissue to block veno-atrial electrical connections at the pulmonary vein antrum, similar to catheter ablation. METHODS AND MATERIALS Nine mini-pigs underwent pretreatment magnetic resonance imaging (MRI) evaluation of heart function and electrophysiology assessment by catheter measurements in the right superior pulmonary vein (RSPV). Immediately after examination, radiosurgery with randomized single-fraction doses of 0 and 17.5-35 Gy in 2.5-Gy steps were delivered to the RSPV antrum (target volume 5-8 cm(3)). MRI and electrophysiology were repeated 6 months after therapy, followed by histopathologic examination. RESULTS Transmural scarring of cardiac muscle tissue was noted with doses ≥32.5 Gy. However, complete circumferential scarring of the RSPV was not achieved. Logistic regressions showed that extent and intensity of fibrosis significantly increased with dose. The 50% effective dose for intense fibrosis was 31.3 Gy (odds ratio 2.47/Gy, P<.01). Heart function was not affected, as verified by MRI and electrocardiogram evaluation. Adjacent critical structures were not damaged, as verified by pathology, demonstrating the short-term safety of small-volume cardiac radiosurgery with doses up to 35 Gy. CONCLUSIONS Radiosurgery with doses >32.5 Gy in the healthy pig heart can induce circumscribed scars at the RSPV antrum noninvasively, mimicking the effect of catheter ablation. In our study we established a significant dose-response relationship for cardiac radiosurgery. The long-term effects and toxicity of such high radiation doses need further investigation in the pursuit of cardiac radiosurgery for noninvasive treatment of atrial fibrillation.

Electrical impedance tomography: changes in distribution of pulmonary ventilation during laparoscopic surgery in a porcine model

BackgroundBecause of the creation of a pneumoperitoneum, impairment of ventilation is a common side-effect during laparoscopic surgery. Electrical impedance tomography (EIT) is a method with the potential for becoming a tool to quantify these alterations during surgery. We have studied the change of regional ventilation during and after laparoscopic surgery with EIT and compared the diagnostic findings with computed tomography (CT) scans in a porcine study.Materials and methodsAfter approval by the local animal ethics committee, six pigs were included in the study. Two laparoscopic operations were performed [colon resection (n=3) and fundoplicatio (n=3)]. The EIT measurements (6th parasternal intercostal space) were continuously recorded by an EIT prototype (EIT Evaluation Kit, Dräger Medical, Lübeck, Germany). To verify ventilatory alterations detected by EIT, a CT scan was performed postoperatively.ResultsVentilation with defined tidal volumes was significantly correlated to EIT measurements (r2=0.99). After creation of the pneumoperitoneum, lung compliance typically decreased, which agreed well with an alteration of the distribution of pulmonary ventilation measured by EIT. Elevation of positive end-inspiratory pressure reopened non-aerated lung areas and showed a recovery of the regional ventilation measured by EIT. Additionally, we could detect pulmonary complications by EIT monitoring as verified by CT scans postoperatively.ConclusionEIT monitoring can be used as a continuous non-invasive intraoperative monitor of ventilation to detect regional changes of ventilation and pulmonary complications during laparoscopic surgery. These EIT findings indicate that surgeons and anesthetists may eventually be able to optimize ventilation directly in the operating theatre.

Pulmonary vein isolation by radiosurgery: implications for non-invasive treatment of atrial fibrillation

AIMS Electrical isolation of the pulmonary veins (PVs) has been established in clinical routine as a curative treatment for atrial fibrillation (AF). While catheter ablation carries procedural risks, radiosurgery might be able to non-invasively induce lesions at the PV ostia to block veno-atrial electrical conduction. This porcine feasibility and dose escalation study determined the effect of radiosurgery on electrophysiologic properties of the left atrial-PV junction. METHODS AND RESULTS Eight adult Goettingen mini-pigs underwent electrophysiological voltage mapping in the left atrium and the upper right PV. Radiation was delivered with a conventional linear accelerator. A single homogeneous dose ranging from 22.5 to 40 Gy was applied circumferentially to the target vein antrum. Six months after radiosurgery, electrophysiological mapping was repeated and a histological examination performed. Voltage mapping consistently showed electrical potentials in the upper right PV at baseline. Pacing the target vein prompted atrial excitation, thus proving veno-atrial electrical conduction. After 6 months, radiation had reduced PV electrogram amplitudes. This was dose dependent with a mean interaction effect of -5.8%/Gy. Complete block of atrio-venous electrical conduction occurred after 40 Gy dose application. Histology revealed transmural scarring of the targeted PV musculature with doses >30 Gy. After 40 Gy, it spanned the entire circumference in accordance with pulmonary vein isolation. CONCLUSION Pulmonary vein isolation to treat AF can be achieved by radiosurgery with a conventional linear accelerator. Yet, it requires a high radiation dose which might limit clinical applicability.

Blood gas partition coefficient and pulmonary extraction ratio for propofol in goats and pigs.

The interpretation of continuously measured propofol concentration in respiratory gas demands knowledge about the blood gas partition coefficient and pulmonary extraction ratio for propofol. In the present investigation we compared both variables for propofol between goats and pigs during a propofol anaesthesia. In ten goats and ten pigs, expired alveolar gas and arterial and mixed venous blood samples were simultaneously drawn during total intravenous anaesthesia with propofol. The blood gas partition coefficient and pulmonary extraction ratio were calculated for both species. Non-parametric methods were used for statistical inference. The blood gas partition coefficient ranged between 7000 and 646 000 for goats and between 17 000 and 267 000 for pigs. The pulmonary extraction ratio ranged between 32.9% and 98.1% for goats and was higher for pigs, which ranged between −106.0% and 39.0%. The blood gas partition coefficient for propofol exceeded those for other known anaesthetic compounds so that it takes longer to develop a steady-state. The different pulmonary extraction rates in two species suggest that there are different ways to distribute propofol during the lung passage on its way from the blood to breathing gas. This species-specific difference has to be considered for methods using the alveolar gas for monitoring the propofol concentration in plasma.

Pharmacokinetic modeling of the transition of propofol from blood plasma to breathing gas

The anesthetic agent propofol is applied intravenously and different groups demonstrated that it is detectable in breathing gas. To quantify the propofol concentration in breathing gas (cbreath) might be a promising feedback for anesthesiologist and for potential closed loop control, yet there is no online measurement in standard clinical practice. Since the physiological relevance of the propofol concentration in breath is not entirely known it may be adverse to control the infusion with cbreath as target variable. In order to control the concentration at the plasma site (cplasma) or even at the effect site (ceffect) in the brain mathematical models can be used to describe the dependencies between cbreath and cplasma or ceffect. This contribution presents the pharmacokinetic modeling of the transition from blood to alveolar gas concentration of propofol. For characterization a model described by a gas blood partition coefficient and one time constant or an equivalent one compartment system, respectively, is taken into account. Clinical data obtained in a study with 17 patients are used for fitting. During anesthesia breathing gas was monitored continuously with an electrochemical sensor and venous blood samples were taken at given times. The use of the mentioned model structure leads to a simple and adequate characterization. A data conditioning in form of a model based interpolation was performed prior to the identification process. The identified parameters are comparable to results of other research works.

Propofol in bronchoalveolar lavage during anaesthesia.

BACKGROUND The lung protecting effect of propofol requires methods to measure the propofol concentration of the epithelial line fluid covering the alveolar surface. We hypothesized that (1) propofol can be determined in bronchoalveolar lavage (BAL) by reversed phase high performance liquid chromatography with fluorescence detection. (2) Positive end-expiratory pressure (PEEP) ventilation may have an effect on propofol concentration in BAL (cpB). METHODS 76 surgical patients were investigated after institutional review board approval. After criteria-based exclusion 45 samples were included. For group I (n=15) BAL was performed directly after induction, for group Z (n=15, PEEP=0 cm H₂O) and P (n=15, PEEP=10 cm H₂O) at the end of anaesthesia. BAL and plasma samples were analysed for propofol by reversed phase high performance liquid chromatography with fluorescence detection. Data from all groups were compared by non-parametric Mann-Whitney U-test. RESULTS Propofol can be detected in BAL. CpB varied between 23 and 167 μg l⁻¹ in all groups. Patients ventilated with PEEP (group P) showed significantly higher cpB (median 74.5 μg l⁻¹) compared to those immediately after induction of anaesthesia (median 42.0 μg l⁻¹) (group I), but not to those ventilated without PEEP in group Z (median 52.5 μg l⁻¹). CONCLUSION Epithelial line fluid, sampled by BAL, can be used to determine cpB by reversed phase high performance liquid chromatography with fluorescence detection. Continuous propofol infusion and PEEP ventilation may have an effect on cpB.