PiCCO ... ...Simple – Safe – Speedy - Specific

1. PiCCOplusStandalone Monitor PiCCO-Technology PiCCO... ...Simple – Safe – Speedy - Specific

2. Contents • What is the PiCCO-Technology?.................................................................................... • What are the advantages of the PiCCO-Technology?.................................................... • How does the PiCCO-Technology work?....................................................................... • How to use the PiCCO-Technology?............................................................................. • Which disposables do I need for the PiCCO-Technology?............................................ • References…………………………………………………………………………………….. • 7. Where can I get what I need?.......................................................................................... 3 4 6 19 22 24 25

3. a. Transpulmonary thermodilution b. Arterial pulse contour analysis -∆T -∆T t t see also page 8 see also page 16 1. What is the PiCCO-Technology? • The PiCCO Technology is a combination of 2 techniques for advanced hemodynamic and volumetric management without the necessity of a pulmonary artery catheter in most patients:

4. 2. What are the advantages of the PiCCO-Technology? The PiCCO measures the following main parameters: • Thermodilution Parameters • Cardiac Output CO • Global Enddiastolic Volume GEDV • Intrathoracic Blood Volume ITBV • Extravascular Lung Water EVLW* • Pulse Contour Parameters • Pulse Continuous Cardiac Output PCCO • Systemic Vascular Resistance SVR • Stroke Volume Variation SVV * not available in USA

5. 2. What are the advantages of the PiCCO-Technology? • Less Invasiveness - Only central venous and arterial access required - No pulmonary artery catheter required - Applicable also in small children • Short Set-up Time - Can be installed within minutes • Dynamic, Continuous Measurement - Cardiac Output, Afterload and Volume Responsiveness are measured beat-by-beat • No Chest X-ray - To confirm correct catheter position no x-ray is necessary • Cost Effective -Less expensive than pulmonary artery catheter technique - Arterial PiCCO catheter can be in place for 10 days or more - Potential to reduce ICU stay and costs • More Specific Parameters - PiCCO parameters are easy to use and interpret even for less experienced clinical staff • Extravascular Lung Water* - Lung edema can be excluded or quantified at the bed-side * not available in USA

6. Central venous line (e.g. for vasoactive agents administration…) Arterial line (accurate monitoring of arterial pressure, blood samples…) 3. How does the PiCCO-Technology work? • Most of hemodynamic unstable and/or severely hypoxemic patients are instrumented with: • The PiCCO-Technology uses any standard CV-line and a thermistor-tipped arterial PiCCO-catheter instead of the standard arterial line.

7. Configuration CV • Central venous line(CV) • Thermodilution catheter with lumen for arterial pressure measurement • Axillary (A) • Brachial (B) • Femoral (F) • Radial (R), long catheter • Arterial pressure transducer A B R F

8. a. Transpulmonary Thermodilution • Transpulmonary thermodilution measurement simply requires the central venous injection of a cold (< 8°C) or room-tempered (< 24°C) saline bolus… CV Bolus Injection Lungs Right Heart Left Heart PiCCO Catheter e.g. in femoral artery

9. -Tb Injection t PiCCO Thermodilution Cardiac Output • After central venous injection of the indicator, the thermistor in the tip of the arterial catheter measures the downstream temperature changes • The cardiac output is calculated by analysis of the thermodilution curve using a modified Stewart-Hamilton algorithm:

10. Tb injection recirculation ln Tb -1 e At DSt MTt t PiCCO Volumetric Parameters • Global Enddiastolic Volume GEDV • Intrathoracic Blood Volume ITBV • Extravascular Lung Water EVLW* These volumetric parameters are obtained by advanced analysis of the thermodilution curve. (Detailed information and formulas available on request.) Advanced Thermodilution Curve Analysis * not available in USA

11. Global Enddiastolic Volume • Global Enddiastolic Volume (GEDV) is the volume of blood contained in the 4 chambers of the heart.

12. Intrathoracic Blood Volume • Intrathoracic Blood Volume (ITBV) is the volume of the 4 chambers of the heart + the blood volume in the pulmonary vessels.

13. Extravascular Lung Water* • Extravascular Lung Water (EVLW)* is the amount of water content in the lungs. It allows bedside quantification of the degree of pulmonary edema. * not available in USA

14. PiCCO Preload Indicators • Intrathoracic Blood Volume, ITBV and Global Enddiastolic Volume, GEDV have shown to be far more sensitive and specific to cardiac preload than the standard cardiac filling pressures CVP + PCWP but also than right ventricular enddiastolic volume. 2,3,5,6,8,9,12,13,22 • The striking advantage of ITBV and GEDV is that they are not wrongly influenced by mechanical ventilation and give correct information on the preload status under any condition. 2,3,6,7,8,9,12,13, 22

15. Extravascular Lung Water* • Extravascular Lung Water, EVLW* assessment by transpulmonary thermodilution has been validated against dye dilution and the reference gravimetric method.11,16,21,23 • Extravascular Lung Water, EVLW* has shown to have a clear correlation to severity of ARDS, length of ventilation days, ICU-Stay and Mortality and to be superior toassessment of lung edema by chest x-ray.7,8,15,20,23,24 * not available in USA

16. -∆T -∆T t t b. Arterial Pulse Contour Analysis • Arterial pulse contour analysis provides continuous beat-by-beat parameters obtained from the shape of the arterial pressure wave. • The algorithm is capable of computing each single strokevolume (SV) after being calibrated by an initial transpulmonary thermodilution. Calibration SV P [mm Hg] t [s]

17. Cardiac Output and Systemic Vascular Resistances As pulse contour analysis continuously measures stroke volume and arterial pressure, cardiac output (CO) and systemic vascular resistance (SVR) are computed as follows: • CO is calculated as stroke volume x heart rate • SVR is calculated as (mean arterial pressure - central venous pressure) / CO

18. Stroke Volume Variation (SVV) In mechanically ventilated patients without arrhythmia, • SVV reflects the sensitivity of the heart to the cyclic changes in cardiac preload induced by mechanical ventilation.1,14,17,18,19 • SVV can predict whether stroke volume will increase with volume expansion.1,14,17,18,19

19. 4. How to use the PiCCO-Technology? • Connect the injectate-temperature sensor housing to the CV line already in place. • Insert a PiCCO arterial thermistor catheter into a large artery, preferable femoral artery, but also brachial / axillary artery and radial artery (with long catheter). • Connect the injectate sensor, the arterial catheter’s thermistor and pressure line to your PiCCO monitor. • For blood pressure transfer to any bedside monitoring system, connect the cable at the back side of the PiCCO monitor. • Now the system is ready to work. • For information how to handle your PiCCO monitor, please refer to your accompanying PiCCO Operator’s Manual.

20. How to manage my patient with the PiCCO-Technology? • Management of a patients hemodynamic situation is easily possible by following the therapeutic guideline shown below.+ • It was developed out of daily clinical practice, has shown to be successful in over a hundred thousand patients and refers to below listed normal values of indices: Cardiac Index CI 3.0 – 5.0 l/min/m2 Global Enddiastolic Blood Volume Index GEDI 680 – 800 ml/m2 Intrathoracic Blood Volume Index ITBI 850 – 1000 ml/m2 Stroke Volume Variation SVV 10 % Extravascular Lung Water Index* ELWI* 3.0 – 7.0 ml/kg +without guarantee * not available in USA

21. Decision tree for hemodynamic / volumetric monitoring** CI (l/min/m ) <3.0 >3.0 2 R 2 E <700 <700 >700 >700 GEDI (ml/m ) S 2 <850 >850 <850 >850 ITBI ( ml/m ) or U L T ELWI (ml/kg) <10 >10 <10 >10 <10 >10 <10 >10 S V+ V - V+ V+! Cat Cat V+! Cat V - T 700 - 800 700 - 800 700 - 800 2 >700 700 - 800 >700 GEDI (ml/m ) >700 1. H 2 >850 850 - 1000 >850 850 - 1000 ITBI (ml/m ) 850 - 1000 850 - 1000 >850 or E + T R 2. Optimise to <10 <10 <10 <10 <10 <10 <10 <10 SVV (%) A A R P G Y >5.5 >4.5 >5.5 CFI (1/min) >4.5 E >30 >25 >30 GEF (%) >25 OK! T or * ELWI (ml/kg) £ £ £ £ 10 10 10 10 (slowly responding) + - Cat = catecholamine / cardiovascular agents V = volume loading (! = cautiously) V = volume contraction + SVV only applicable in ventilated patients without cardiac arrh ythmia **without guarantee *not available in USA

22. 5. Which disposables do I need with the PiCCO-Technology? • PULSIOCATH arterial thermodilution catheter • Injectate temperature sensor housing • Any standard central venous catheter • Specifically designed for less invasive volumetric, hemodynamic monitoring • To be placed with Seldinger Technique • Several sizes available for pediatric and adult patients • Can remain within the patient up to 10 days or longer

23. PULSIOCATH arterial thermodilution catheters product range PULSIOCATH arterial thermodilution catheters are specifically designed for less invasive volumetric hemodynamic monitoring with the PiCCO Technology. The catheters are placed with Seldinger Technique. Several versions and sizes are available. They can remain within the patient up to 10 days or even longer. Technical specifications are subject to change without further notice The catheters are also available as complete kits (e.g. PVPK2015L20-46), including a disposable pressure transducer and the injectate temperature sensor housing. These kits can optionally be ordered with an additional pressure line for intermittent central venous pressure monitoring. Catheters have to be selected depending on patient size, weight and insertion site.

24. 6. References • 1. Berkenstadt H et al., Anesth Analg, 2001 • 2. Bindels A et al., Crit Care 4, 2000 • 3. Boussat S et al., Int Care Med 2002 • 4. Brock H et al., Eur J Anaesth 19 (4), 2002 • 5. Della Rocca G et al., Eur J Anaesth 19, 2002 • 6. Della Rocca G et al., Anesth Analg 95, 2002 • 7. Eisenberg PR et al., Am Rev Respir Dis 136 (3), 1987 • 8. Gödje O et al., Chest 118, 2000 • 9. Gödje O et al., Eur J of Cardio-thoracic Surgery 13, 1998 • 10. Haperlin et al., Chest, 1985 • 11. Katzenelson et al., SCCM 2001, San Diego • 12. Lichtwarck-Aschoff M et al., Journal of Critical Care 11 (4), 1996 • 13. Lichtwarck-Aschoff M et al., Intensive Care Med 18, 1992 • 14. Michard F et al., Yearbook of Intensive Care Med, 2002 • 15. Mitchell JP et al., Am Rev Respir Dis 145 (5), 1992 • 16. Neumann et al., Intensive Care Med 1999 • 17. Reuter DA et al., Crit Care Med, 2003 • 18. Reuter DA et al., Intensive Care Med, 2002 • 19. Reuter DA et al., Brit J Anaesth, 2002 • 20. Sakka SG et al., Chest 122, 2002 • 21. Sakka S et al., Intensive Care Med 2000 • 22. Sakka S et al., Journal of Critical Care 14 (2), 1999 • 23. Sturm JA, Practical Applications of Fiberoptics in Critical Care Monitoring, 1990 • 24. Takeda A et al., J Vet Med Sci 57, 1995

25. 7. Where can I get what I need? For further information or ordering, please contact your local PULSION Office: PULSION Medical Systems AG Stahlgruberring 28 D- 81829 München Germany Tel.: +49 (0)1805 PULSION +49 (0)89 4599140 Fax: +49 (0)89 45991418 info@pulsion.com PULSION Medical U.K., Ltd. P.O. Box 315 Arundel Road Uxbridge, Middlesex GB- UB8 2US, England Great Britain Tel.: +44 (0) 1895 455255 Fax: +44 (0) 1895 274035 info@pulsionmedical.co.uk PULSION France sarl 6, Place Jeanne d´Arc F- 13100 Aix en Provence France Tél. : +33 (0)4 42 27 67 19 Fax : +33 (0)4 42 27 44 90 info@pulsion.fr PULSION Medical Systems Ibérica S.L. Pol. Ind. Las Nieves, C/ Puerto Canencia 21 E- 28935 Móstoles, Madrid Spain Tel.: +34 91 665 73 12 Fax: +34 91 616 94 27 info@pulsioniberica.com Seda S.p.A. Via Tolstoi, 7/B I- 20090 Trezzano sul Naviglio (MI) Italy Tel.: +39 02 48424219 Fax: +39 02 48424290 sd@sedaitaly.it If your country is not listed above, please contact PULSION Germany PULSION Benelux nv/sa Maaltecenter, Blok G Derbystraat 341 B- 9051 Gent (SDW) Belgium Tel. : +32 (0)9 242 99 10 Fax : +32 (0)9 242 99 11 info@pulsion.be PULSION Pacific Pty. Ltd. P.O. Box 823 AUS- Randwick, NSW Australia, 2031 Australia Tel.: +61 (0) 2 9340 5525 Fax: +61 (0) 2 9340 5515 info@pulsionpacific.com.au

26. The PiCCO-Technology is also available as a module for Philips IntelliVue / CMS patient monitoring systems. For more information please refer to your local PULSION representative (page 25) or visit www.pulsion.com

27. For further information, please visit • www.pulsion.com • There you will find also information on other revolutionary PULSION products: • LiMON - noninvasive bedside liver function monitor • ICG-PULSION - indocyanine green dye for diagnostics • VoLEF - PiCCOplus add-on monitor for cardiac sub-volumes and RVEF • IC-VIEW - laser fluorescence makes tissue perfusion visible @ PULSION 07/2003 MPI812205