Supplemental text
Autoregulation of ventilation with neurally adjusted ventilatory assist on extracorporeal lung support
Christian Karagiannidis1*, Matthias Lubnow1, Alois Philipp2, Guenter AJ Riegger1, Christof Schmid2, Michael Pfeifer1 and Thomas Mueller1
1Department of Internal Medicine II, 2Department of Cardiothoracic Surgery, University Hospital of Regensburg, Germany
Methods
Study population
Six adult patients with severe respiratory failure due to bilateral pneumonia treated with veno-venous ECMO and NAVA were included in this study. All patients had been transferred from external hospitals, because severe ARDS, defined according to the criteria of the American – European Conference on ARDS (1) had not been stabilized on conventional ventilation. In two patients too instable for transfer, ECMO was started by our mobile team before transport. In the other extracorporeal veno-venous lung support was initiated, because despite continuing efforts in our centre to improve gas exchange with optimised protective ventilation and prone positioning the paO2/FiO2 ratio remained < 100 mmHg and/or severe respiratory acidosis could not be controlled. After implementation of ECMO invasiveness of mechanical ventilation was reduced to avoid further ventilator–induced lung injury. Preset goals for oxygenation were a PaO2 of > 65 mmHg and PaCO2 was adjusted to achieve a normal arterial pH level. Patients´ characteristics before and after one day on ECMO are summarized in Table 1. Individual diagnoses and base line characteristics are documented in Supplemental Table 1 in the online data supplement. After stabilization sedation was reduced to encourage spontaneous breathing even on high PEEP levels. Assisted ventilation was established in the NAVA mode, which is described in more detail later. All patients had a favourable outcome, five survived to discharge, the sixth was transferred for successful lung transplant.
Technique of extracorporeal lung support
The extracorporeal system consists of two venous cannulae, a centrifugal pump and a membrane oxygenator (Maquet Cardiopulmonary AG, Hirrlingen, Germany). Cannulae were implanted in Seldinger technique. For outflow the right femoral vein was cannulated with a long 21 – 23 Fr cannula (Sorin Group Deutschland GmbH, Munich, Germany), which was advanced into the inferior caval vein. For reinfusion a short 17 Fr cannula (NovaLung GmbH, Talheim, Germany) was used that was implanted in the right internal jugular vein. Blood flow was generated by a centrifugal pump (Rotaflow Centrifugal Pump, Maquet Cardiopulmonary AG); the membrane oxygenator (PLS QuadroxD, Maquet Cardiopulmonary AG) is made of polymethylpentene, which avoids plasma leakage. It has a total gas exchange surface of 1.8 m² with a very low inherent resistance to blood flow and an incorporated heat exchanger. As the whole system is coated with heparin, a pronounced systemic anticoagulation is not necessary and an activated partial thromboplastin time (aPTT) of 1.5 normal is sufficient. Oxygen was used as sweep gas with a flow between a maximum of 8 L/min and a minimum of 1 L/min. The oxygen transfer capacity of the ECMO was calculated by multiplying the difference of oxygen content pre and post ECMO with the blood flow. The approximated carbon dioxide content was estimated in the same way. Carbon dioxide content of blood pre and post ECMO was calculated by the blood gas analyser with consideration of the Henderson–Hasselbalch equation, plasma-PCO2 and pH, as CO2 measurement in exhaust-gas, the preferable and precise method, was not available. Blood gas analysis was done with Radiometer 700 (Radiometer, Copenhagen, Denmark).
Neurally adjusted ventilatory assist (NAVA)
All patients were ventilated with the Servo-I ventilator including the NAVA option (Maquet Critical Care, Rastatt, Germany). During NAVA the EAdi signal is processed as described previously (2, 3), and pressure support is applied proportionally to the EAdi signal. The EAdi signal in µV is multiplied with a gain factor called NAVA level and thereby transposed into pressure support. The NAVA level was individually titrated. In short, NAVA ventilation was initiated with a NAVA level, which resulted in a protective, low-tidal volume ventilation. Patients were given enough time to adapt to this NAVA level. Subsequently, the level was individually titrated until a physiological breathing pattern with protective peak pressure and tidal volumes was achieved. ECMO and NAVA was established for several days in the early course of the disease. Only after improvement of the reason for lung failure and a stable fraction of inspired oxygen at or below 0.5 patients were enrolled in the current study. This ECMO weaning time point was chosen for measurement as otherwise turning off the ECMO at earlier time points could have had serious and probably life threatening consequences. Patients were sedated solely with short acting agents (propofol and remifentanil or sufentanil) with an intended RASS score of –3 to -1 (4). During the measuring period patients were not actively moved into another position, a calm environment was established to avoid arousals, and no change in sedation was allowed.
Data acquisition and analysis
Data were collected prospectively. After several hours in stable condition on a preset NAVA-level, blood gas analysis and ventilatory parameters were documented at five consecutive times, each data set for a period of 30 minutes: at base line, after reduction of ECMO sweep gas flow to 50%, again after temporarily pausing sweep gas flow, after increase of FiO2 to achieve a normal-high saturation and finally again at base line settings. All respirator parameters were obtained with a high resolution once per breath, except for minute ventilation, which was measured once per minute. At the end of each 30 min. period blood gas analysis was performed. In patient E the period without ECMO was shortened due to rapidly developing respiratory acidosis and inability to compensate.
Approval for this study was gained from the Ethics Committee of the University of Regensburg. Informed consent was obtained from the legal representatives of the patients, and agreement with publication of data from the patients. All patients were under constant supervision of an experienced intensivist, no relevant side-effects did occur.
Variables are reported as mean with a 95% confidence interval. Non-parametric ANOVA test was used for statistical analysis. A p-value of less than 0.05 was considered statistically significant. For statistical analysis, we used GraphPad Prism 4 for Macintosh computer (La Jolla, CA 92037 USA). Data were acquired with the Ventilation-Record-Card SERVO-i Vers. 1.3 and in parallel with SERVO-i-RCR Version 2.3 (Maquet, Critical Care, Rastatt, Germany).
Figure Legend
Supplemental Figure 1
Proportional to the EAdi (electrical activity of the diaphragm) peak signal PIP (peak inspiratory pressure) ranged in mean from 19 to 29 cmH2O with active ECMO and from 21 to 45 cmH2O with inactivated ECMO (p < 0.05). In parallel to the EAdi peak-data PIP stepwise increased with reduced sweep gas flow. With a preset PEEP level of 10 cmH2O or more most patients did not increase the mean PIP above 30 cmH2O.
Supplemental Figure 2
Minute ventilation (VE) increased rapidly in all patients after reducing and turning off the sweep gas flow (p < 0.05). The rise in VE was partly a result of increased VT, but mainly caused by a steep increase in breathing frequency.
Supplemental Figure 3
Breathing frequency with different ECMO/ NAVA settings (patient A-F).
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