Recent Trends in Hemodynamic Monitoring

As Published in Recent Trends in Hemodynamic Monitoring by Anne Staylor In critical care, the goal of hemodynamic monitoring is to provide data that guides treatment and prevents morbidity and mortality of critically ill patients. Clinicians use hemodynamic monitoring data to optimize the balance between tissue oxygen supply and demand and effectively combat global tissue hypoxia, shock, and multiorgan failure in critically ill patients. Market Outlook Within the market for hemodynamic monitoring products, there are two main segments: pulmonary artery catheters (PACs) and cardiac output (CO) monitoring systems, which include minimally invasive and noninvasive technologies. Over the past 10 years, the market for hemodynamic monitoring products has evolved, and growth in this market is being fueled by several factors, not the least of which is an aging population with an increasing number of cardiac disorders and other conditions that could benefit from hemodynamic monitoring. Growth is also being Exhibit 1 driven by the demand for less invasive and noninvasive technologies that measure CO, stroke volume, and other global parameters of oxygen delivery. Current technologies available for hemodynamic monitoring include products based on thermodilution, dye dilution, lithium dilution, those using the Fick principle, thoracic electrical bioimpedance, esophageal Doppler monitoring, pulse contour methods, ultrasonic CO monitoring, and transesophageal echocardiography. These technologies are increasingly being used in place of the more invasive PAC. The market for hemodynamic monitoring will also be driven by the increasing number of clinicians who can initiate and place these monitoring technologies. Previously, only a physician could initiate CO monitoring, as PAC catheters must be inserted by a physician. But with the advent of less invasive and noninvasive devices which can be used by any nurse, physician assistant, respiratory therapist, cardiovascular technologist, or anesthesia technician familiar with With the advent of less invasive and noninvasive devices, the base of clinicians that can initiate cardiac output monitoring has increased exponentially. Estimated Worldwide Sales of Hospital-Based Less Invasive Hemodynamic Monitoring Products $140 Sales ($millions) $120 $100 $80 $60 $40 $20 $0 All Others Note: Includes sales of disposables and monitors. SOURCE: Lifesciences 2010 Windhover Information, an Elsevier company. All rights reserved. 1

HEMODYNAMIC MONITORING Exhibit 2 Hemodynamic Monitoring Products, US Market Forecast, 2006-2012E Year Pulmonary Artery Catheter Sales ($M) basic invasive pressure monitoring the base of clinicians that can initiate CO monitoring has increased exponentially. In 2009, hospital-based sales of less invasive hemodynamic monitoring products was well over $120 million worldwide, according to Lifesciences Corp., an established leader in the hemodynamic monitoring market. (See Exhibit 1.) Clinicians in the US have been slower to adopt the less invasive and noninvasive hemodynamic Annual Change (%) Cardiac Output Monitoring System Sales ($M) Annual Change (%) Total Sales ($M) 2006 100.4 $22.5M 122.9 2007 98.1-2.3 31.5 40.0 129.6 2008 95.8-2.3 38.0 20.6 133.8 2009 93.7-2.2 45.0 18.4 138.7 2010 E 91.6-2.2 52.0 15.6 143.6 2011 E 89.0-2.8 60.0 15.4 149.0 2012 E 85.7-3.7 69.0 15.0 154.7 CAGR (2007-2012E) 3.6% Note: Figures for cardiac output monitoring systems include noninvasive and minimally invasive products. SOURCE: Medtech Insight Market Report #A346, US Markets for Patient Monitoring Products, published June 2008 monitoring products than those in Europe and other countries; however, US sales of these technologies have been steadily growing and are projected to reach $69.0 million by 2012. (See Exhibit 2.) And while the barriers to entry are high for this business, the prospect for future growth is significant, with the worldwide potential for hemodynamic monitoring estimated by at $540 million. Challenges Remain Noninvasive and minimally invasive hemodynamic monitoring devices have improved greatly over the last few years, and manufacturers have been developing devices that are more accurate, simpler to use, and allow for earlier diagnosis of sepsis and shock. But even with product improvements and increasing demand for these products, challenges remain. With the US hospital market for patient monitoring dominated by industry giants like Royal Philips Electronics NV s Philips Systems Inc., General Electric Co. s GE Healthcare and Draegerwerk AG s Draeger Inc., the biggest challenges for manufacturers of noninvasive and minimally invasive hemodynamic monitoring devices will be establishing widespread distribution, gaining clinician trust and preference for the devices, and integrating these devices into proven treatment algorithms and goal-directed therapy that will ultimately demonstrate the data derived from these devices can be used to improve patient outcomes. Selected companies with less invasive and noninvasive hemodynamic monitoring devices include CardioDynamics International Corp. (acquired by SonoSite Inc. in August 2009), CAS Systems Inc. and newcomer Cheetah Inc., among others. (See Exhibit 3.) (See Sidebar, Cheetah : Advancing Noninvasive Hemodynamic Monitoring.) : A Case Study in Trends With its Swan-Ganz line of hemodynamic monitoring products, has long been an established leader in the worldwide hemodynamic monitoring market. Over the last five years, the company s product development strategies and sales of hemodynamic monitoring products have provided a real-world glimpse of the trends in the hemodynamic monitoring market. With increasing demand for less invasive technologies and with declining sales of the Swan-Ganz line, launched its own less invasive technology, the FloTrac System, in 2005. The FloTrac System, which includes the FloTrac Sensor and Vigileo Monitor, utilizes an existing arterial line and continuous self-calibration to provide key flow parameters, including CO, stroke volume, stroke volume variation, and systemic vascular resistance if central venous pressures are saved into the monitor. Since launching the 2 www.elsevierbi.com

HEMODYNAMIC MONITORING Exhibit 3 Selected Noninvasive and Minimally Invasive Hemodynamic Monitoring Systems Company Product Features Cardio- Dynamics International CAS Systems Cheetah Deltex Sciences Inc. Lifesciences Hemo Sapiens Inc. LiDCO Group PLC Noninvasive Technologies Inc. Pulsion Systems Respironics Inc./Philips Systems/Royal Philips Electronics BioZ Dx LIFEGARD II NICOM System CardioQ FloTrac Hemodynamic and Oxygen Transport & Management (HOTMAN) LiDCOplus IQ2 PiCCO 2 NICO Noninvasive impedance cardiography system that measures contractility, flow, fluid, and resistance parameters; Includes four dual sensors; Clinical indications include diagnosis of heart failure, dyspnea, and resistant hypertension Noninvasive hemodynamic monitor; Offers continuous CO and advanced hemodynamic parameters for immediate patient assessment; Monitor enables comparison of impedance cardiography and electrocardiogram waveforms, tabular trends, all data, and graphical trends (blood pressure, CO/ cardiac index, and heart rate viewable on all screens) Noninvasive hemodynamic monitor based on proprietary BIOREACTANCE technology that uses phase instead of amplitude to measure blood flow induced changes in electrical current as it goes through the chest; Offers continuous CO and advanced hemodynamic parameters for immediate patient assessment Includes a monitor and disposable probe; Monitor displays blood flow velocity profiles; The patented six-millimeter probe consists of two continuous-wave Doppler transducers that are inserted into the patient s esophagus near the descending aorta Arterial waveform analysis sensor system; The FloTrac sensor, which is connected to an arterial line, is used along with the company's Vigileo Monitoring System for monitoring continuous CO, stroke volume, stroke volume variation, and systemic vascular resistance; The FloTrac differs from other systems in that it does not require calibration with another method Impedance cardiography system for the noninvasive assessment, monitoring, management, and modeling of a patient s hemodynamics and oxygen transport dynamics; Different options are available for patient subgroups including adult males and postmenopausal females, neonatal and pediatric patients, pregnant women, and those in the childbearing age range Uses radial arterial pressure wave analysis to derive a real-time CO reading; Hemodynamic monitor analyzes the signal from a radial artery pressure sensor to derive CO and uses a lithium dilution technique to calibrate the system; Monitoring begins with a subtherapeutic dose of lithium chloride, which is injected in the venous circulation; An ion-selective electrode sensor in the arterial line is used to measure the dilution curve and calibrate the system; Calibration is maintained for eight to 12 hours Utilizes thoracic electrical bioimpedance technology to measure electrical impedance changes throughout the thorax as aortic blood volume increases and decreases in response to the beating heart; The company's patented technology plots power, time, and frequency of impedance changes to create a three-dimensional view of cardiac function; The 11-parameter system provides real-time cardiac, hemodynamic, and pulmonary data and has emergency department, hospital, nursing home, and outpatient applications Minimally invasive hemodynamic monitoring system; Access via femoral, brachial, or axillary artery; Performs pulse contour analysis on thermodilution waveforms to generate CO; Requires bolus injection for calibration; Provides long-term monitoring capabilities and continuous, real-time monitoring; Suitable for pediatric care The monitor measures CO based on changes in respiratory carbon dioxide concentration, which is caused by a brief period of rebreathing; The measurement of CO is accomplished by interpreting data collected by proprietary sensors that measure flow, airway pressure, and carbon dioxide concentration; These signals are then combined to calculate carbon dioxide elimination; Using these variables, a technique known as Fick partial rebreathing is applied to calculate CO; Monitor may be used only with mechanically ventilated patients and requires artificial respiration; Not suitable for pediatric patients or those with lung disease; Does not provide long-term or real-time monitoring Väsamed AcQtrac System The noninvasive system uses thoracic impedance cardiography to present a unique cardiovasculogram waveform that illustrates the mechanical function of the cardiovascular system; Uses four pre-gelled electrodes; Monitors 12 cardiac parameters Notes: The BioZ Dx product is the result of a codevelopment partnership and original equipment manufacturer agreement with Philips Systems/Royal Philips Electronics. In May 2007, Analogic Corp. and CAS Systems announced a cobranding agreement, giving CAS Systems worldwide exclusive rights to market and sell Analogic s LIFEGARD family of noninvasive patient monitors. In March 2001, Medis GMBH entered into a technology licensing relationship with Analogic. Under the agreement, Medis licensed its impedance cardiography circuit board and software design to Analogic as a key component to the LIFEGARD Monitor. (In June 2004, CardioDynamics International acquired Medis; the company receives a licensing fee each time an Analogic impedance cardiography device is sold. SonoSite acquired Cardiodynamices in August 2009.) In March 2008, Royal Philips Electronics completed the acquisition of Respironics, which acquired Novametrix Systems Inc. developer of the NICO System in 2002. SOURCE: Medtech Insight Report #A346 2010 Windhover Information, an Elsevier company. All rights reserved. 3

HEMODYNAMIC MONITORING Exhibit 4 Estimated Worldwide Market Share of Hospital-Based Less Invasive Hemodynamic Monitoring Products Pulsion PiCCO 2 Others 30% 16% 54% Note: Includes sales of disposables and monitors. SOURCE: Lifesciences Exhibit 5 FloTrac Estimated Worldwide Shares of Addressable Market for Hospital- Based Less Invasive Monitoring Products All Others Unreached ICU Note: Includes sales of disposables and monitors. SOURCE: Lifesciences Lifesciences Unreached High-risk Surgery FloTrac System, the company has capitalized on its reputation and leadership position established with the Swan-Ganz Catheter and has captured 54% of the global market share for less invasive hemodynamic monitoring products, according to company estimates. (See Exhibit 4.) At the same time, growth opportunities remain in the intensive care unit (ICU) and high-risk surgery markets. (See Exhibit 5.) Like other manufacturers of noninvasive and less invasive hemodynamic monitoring devices, has been developing product enhancements to the FloTrac System to address the evolving needs of critical care professionals working in an increasingly understaffed, complex, and demanding environment. Since 2005, has added more user-friendly patient trending and analysis to the FloTrac System and launched a third-generation algorithm that enhanced the FloTrac System s accuracy when used in patients with sepsis and other critical illnesses. In the second quarter of 2010, is planning to launch a new integrated hardware platform, the EV1000, which will ultimately consolidate all the company s parameters, including the FloTrac Sensor and the PreSep and PediaSat Oximetry Catheters, into a simpler, more intuitive informational display. According to the company, the EV1000 will have an Applelike interface, and a user-friendly touch screen that dynamically integrates several hemodynamic parameters into different color zones, which will allow clinicians to quickly view the overall hemodynamic status of a patient from across a room. The company is also planning to launch the VolumeView Catheter in 2010, a technology that allows bedside assessment of pulmonary edema. The VolumeView Catheter measures extravascular lung water and displays it on the monitor using a graphic representation of the lungs. Pulsion Systems AG, a market leader in hemodynamic monitoring in Europe, also offers a display that features a type of dynamic status indicator as part of its PiCCO2 Monitor. The technology, called Spidervision, enables clinicians to simultaneously view different hemodynamic parameters to see if they are outside the target range. The PiCCO2 also features a measure of extravascular lung water. (See Hemodynamic Monitoring Enters a New Era, Medtech Insight, April 2008.) In January 2010, announced that it signed a licensing agreement with Philips 4 www.elsevierbi.com

HEMODYNAMIC MONITORING Systems to integrate its oximetry technology into Philips IntelliVue Patient Monitors. This is the first modular agreement for, which has previously only offered its monitoring technology for use with its own proprietary stand-alone monitors. In the future, says it plans to make its critical care parameters more widely accessible through licensing in an effort to drive more sales of its disposable catheters. The company also has plans to launch a new continuous glucose monitoring system on the US market in 2010. has been codeveloping the device with DexCom Inc. for use in critically ill adults in the hospital environment. (See Lifesciences and DexCom Join Forces in New Critical Care Growth Market, IN VIVO, December 2008.) The device performs one reading every 7.5 minutes and is indicated for automatic, real-time monitoring and trending of blood glucose concentration. CHEETAH MEDICAL: ADVANCING NONINVASIVE HEMODYNAMIC MONITORING In an ideal world, hemodynamic monitoring technology would be completely noninvasive, continuous, affordable, easy to use and understand, and as accurate as the gold-standard pulmonary artery catheter. One company that believes it has achieved this ideal is Tel Aviv, Israel-based Cheetah. The company s NICOM System is a noninvasive hemodynamic monitoring device based on Cheetah s proprietary BIOREAC- TANCE technology. At first glance, BIOREACTANCE looks very similar to thoracic bioimpedance, as both technologies use electrodes placed on the patient s chest to deliver an electrical current across the thorax. However, the comparison stops there, according to Cheetah s CEO, Yoav Avidor, MD. BIOREACTANCE primarily differs from bioimpedance technology in that it uses phase instead of amplitude to measure blood flow-induced changes in electrical current as it goes through the chest, says Dr. Avidor. If you correlate the change in phase and the degree of the change to flow, there s actually a very accurate, consistent relationship. Although accuracy has been an issue for some noninvasive devices, the company says the NICOM System has been validated in several clinical studies and is the only noninvasive product that was US Food & Drug Administration (FDA) cleared using the pulmonary artery catheter (Swan- Ganz) as a predicate device. Some have likened BIOREAC- TANCE technology to the frequency modulation (FM) used in radio transmissions, since the phase modulation used in NICOM and FM are closely related. By detecting changes in signal frequency (FM) rather than changes in signal amplitude (AM), FM radio allows greater signal fidelity. According to Dr. Avidor, phase (as frequency) provides physical advantages that can then be translated into monitoring advantages, accuracy advantages, and a different type of care. For example, phase is not impacted by the location of electrodes on the body, which can be a big advantage in the operating room and ICU where patients can have limited areas available for electrode placement. Also, certain physical conditions such as obesity and pleural effusion do not impact phase, but can be a problem for bioimpedance because they modify the amplitude that is reported. As far as motion, Avidor says the NICOM System is highly motion tolerant, allowing clinicians to conduct continuous hemodynamic monitoring and stress testing or monitor patients that are awake or who are moving continuously. And although things like dialysis machines, monitors, and pacemakers can induce voltage and be a problem for bioimpedance, Avidor says this is not a problem with BIOREACTANCE. Phase is filterable while amplitude is not, so you can filter out the electrical noise from interfering technologies because they re not in the same frequency domain, according to Avidor. The company is initially targeting the ICU and anesthesia markets, but Avidor believes the technology also addresses several significant unmet needs in stepdown units and emergency medicine. BIOREACTANCE is also being used in outpatient cardiology for heart failure patients to determine cardiac response to stress testing and for optimization of biventricular pacemakers. The NICOM System has been commercially available in Europe for 18 months and received clearance for use in Canada in November 2009. The device received FDA clearance in the US in January 2008 and is being used by several leading US hospitals, including Ohio State University, Memorial Sloan-Kettering Cancer Center, Weill Cornell Center, and Dartmouth- Hitchcock Center. Avidor says the company opened its first commercial account in the US in January 2009. Cheetah plans to use recent financing to expand distribution for the device and carry out various large-scale clinical studies to demonstrate the value of continuous hemodynamic monitoring in large, less traditional sites of care. 2010 Windhover Information, an Elsevier company. All rights reserved. 5

HEMODYNAMIC MONITORING Exhibit 6 Lifesciences: Revenue Model for Hemodynamic Monitoring, 2006 2011E Hemodynamic Monitoring Studies have shown that hospitalized patients can be at a higher risk of infection and other complications if their blood glucose level is elevated for prolonged periods. Currently, clinicians manage patients glucose levels by manually obtaining intermittent samples over various periods of time, typically every one to four hours. According to the company, the trending provided by 2006 2007 2008 2009E 2010E 2011E $175M $199M $230M $225M $247M $272M Year/Year Growth 14% 14% -2% 10% 10% FloTrac $15M $34M $44M $58M $66M $74M Year/Year Growth 127% 29% 32% 14% 13% Notes: Revenue for hemodynamic monitoring includes FloTrac. SOURCE: Morgan Stanley Research, July 21, 2009 products are projected to increase by 10% in 2010. (See Exhibit 6.) Assessing the Future Growth in the market for hemodynamic monitoring products will continue as manufacturers develop new parameters and product enhancements that make noninvasive and less invasive hemodynamic monitors more accurate, simpler to use, easier to understand and interpret, and more available to a wider base of clinicians. Looking to the future, critical care monitoring will go beyond hemodynamic monitors that measure global parameters of oxygen delivery as manufacturers and researchers develop new technologies that allow for earlier diagnosis of sepsis and shock. continuous glucose monitoring may reduce nursing time and provide a new level of insight into serum glucose variability that enables clinicians to more effectively implement glycemic control in critically ill and hospitalized patients. Edward s continuous glucose monitoring system received CE Mark in November 2009 and is commercially available in the European Union. The company is currently conducting market evaluations and implementing a controlled roll out at a limited number of European sites to make sure clinicians are educated appropriately and are using it correctly in high-risk patients. According to an spokesperson, the company is hoping to receive US regulatory clearance for the glucose monitoring system sometime in mid-2010. With the addition of continuous glucose monitoring, gains a potentially high-growth product for its hospital monitoring business. According to the company, the worldwide market for continuous glucose monitoring of critically ill patients was an estimated $200 million in 2009. Overall, with new product introductions and continued growth in its disposables business, sales of Edward s hemodynamic monitoring There is burgeoning interest in emerging technologies that monitor changes in microcirculatory flow and more downstream markers of effective resuscitation, including regional tissue oxygenation, organ perfusion, lactic acid, and biomarkers. As this field matures, researchers will continue to add to their knowledge of the physiology of critical illness, an area where much remains unknown. What s clear at the moment is that current monitoring technologies provide only one piece of the patient puzzle. Future advances will be driven by an expanded understanding of critical illness at the molecular level and new technologies will evolve accordingly. [A#2010400014] Anne Staylor is Senior Editor for Medtech Insight (E-mail: A.Staylor@Elsevier.com) RELATED READING Device Opportunities in the Diabetes Treatment Market, Medtech Insight, October 2009 [A#2009400080] Lifesciences and DexCom Join Forces in New Critical Care Growth Market, IN VIVO, December 2008 [A#2008800196] Hemodynamic Monitoring Enters a New Era, Medtech Insight, April, 2008 [A#2008400027] ACCESS THESE ARTICLES AT OUR ONLINE STORE: www.windhover.com/article 6 www.elsevierbi.com