Clinical and Economic Benefits of ImaCor TEE Monitoring

White Paper 2010-03*

Harold M. Hastings, Ph.D. Scott L. Roth, M.D.
Executive summary TEE monitoring in cardiac and general ICU populations with the ImaCor TEE monitoring system led to significant changes in hemodynamic management in over half of the patients studied, with economic benefits significantly exceeding the cost of probes used. 1. Cardiac surgery. In a series of 46 patients at two institutions, surgical re-exploration was avoided in five patients (11%), reducing hospital charges by $ 150,000 (extrapolated from Speir, 2009), and fluid and pressor administration was changed in 23 patients (50%), reducing hospital charges by at least $414,000 (based on literature review below, especially Hravnak et al., 2010), for a total reduction of at least $564,000. Cost of 49 ImaCor ClariTEE probes (some patients used more than one probe): $49,000. Not included: economic benefits of TEE detection of tamponade and rapid surgical intervention, TEE-guided VAD adjustment, likely reduction in acute kidney injury (AKI, a common, major and expensive complication of cardiac surgery) due to reduced pressor usage. In conclusion, gross savings of at least $564,000 were 11 times the cost of probes; on a per patient basis gross savings averaged at least $12,260; twelve times the cost of a probe. 2. Non-cardiac ICU. In a series of 68 patients, hemodynamic management was changed in 28 (41%), reducing hospital charges by at least $504,000. Cost of 68 probes: $68,000. Not included: likely reduction in AKI due to reduced pressor usage. In conclusion, gross savings of at least $504,000 were over seven times the cost of probes; on a per patient basis gross savings averaged at least $6,400; again over seven times the cost of a probe. Conclusions. As described above, studies to date have shown significant clinical and economic impact by demonstrating the potential to reduce cardiac surgery costs by at least $12,000 per patient and general ICU costs by at least $6,400 per patient in study populations. Figure 1. Economic Impact of ImaCor TEE monitoring in the cardiac ICU and general ICU, per patient. Savings from avoided re-explorations are shown in red; savings from hemodynamic management are shown in plum. Savings far exceed the $1,000 cost of the ImaCor ClariTEE probe.
ImaCor saves $11,260 per pt. in the CARDIAC ICU: from a 46 patient study*

11 the cost of a probe

Avoiding re-op: $3,260

Preventing and treating shock: $9,000

ImaCor saves $6,410 per pt. GENERAL ICU: from a 68 patient study** 6.4 the cost of a probe
Preventing and treating shock: $7,410
Probe cost

$2000

$4000

$6000

$8000

$10,000

$12,000

*see FACTS-Care 2010 abstract

**see SCCM 2010 abstract

* Notes on ImaCor White Papers follow on page 2.

Notes on ImaCor White Papers. The purpose of ImaCor White papers is to provide background for understanding the role of the ImaCor TEE system in addressing major areas of clinical concern. ImaCor White Paper 2009-01 addressed Hemodynamic Monitoring. ImaCor White Paper 2009-02 addressed ImaCor TEE for Sepsis Monitoring ImaCor White Paper 2010-01 addressed the role of ImaCor TEE in avoiding and guiding re-exploration post cardiac surgery. ImaCor White Paper 2010-02 is an updated version of White Paper 2009-02, addressing ImaCor TEE for Sepsis Monitoring. White Papers and Case Studies are available upon request: please email jkujawski@imacormonitoring.com.

Outline. We describe the clinical and especially economic impact of hemodynamic monitoring with the ImaCor TEE monitoring system in cardiac ICU and general ICU populations. In particular, ImaCor TEE monitoring is shown to save an average of over $12,000 per patient, twelve times the cost of a probe, in cardiac ICU patients; over $ 6,400 per patient, 6.4 times the cost of a probe in general ICU patients. This paper is organized as follows: 1. Background a. Tissue and organ perfusion the challenge in critical care b. Detecting hemodynamic instability: From TEE hemodynamic assessment to TEE hemodynamic monitoring c. Complications and cost of hemodynamic instability 2. Cardiac ICU case series 3. General ICU case series 4. Conclusions Appendices 1. Illustrative cases 2. Supporting economic data References

1. Background a. Tissue and organ perfusion the challenge in critical care One major challenge in critical care is providing and maintaining adequate tissue and organ perfusion. Hemodynamic stability is one key component of tissue and organ perfusion. The central role of hemodynamic stability in maintaining adequate tissue and organ perfusion has led to a wide variety of clinical interventions (fluids, pressors, inotropes, etc.), clinical protocols and hemodynamic monitors. On the other hand, organ failure may have many causes, as illustrated by acute kidney injury (AKI), a common and expensive complication of cardiac surgery (Hein, 2006a,b,c; Rosner and Okusa, 2006; Rosner, Portilla and Okusa, 2008; Elahi et al., 2009; STS risk calculator). In particular, Rosner and Okusa (2006) cite systemic inflammation, reduced LV function, vasoactive agents, and hemodynamic instability [in general] as postoperative pathophysiological factors in AKI. b. Detecting hemodynamic instability: Development of the ImaCor TEE hemodynamic monitoring system In order to better understand the clinical and economic impact of the ImaCor TEE hemodynamic monitoring system, we begin with a brief review of the unique advantages of TEE for hemodynamic assessment. Trans-esophageal echocardiography (TEE) has long been accepted as the gold standard in the cardiac operating room because TEE allows direct visualization of cardiac filling and function, and has

the unique ability to identify specific causes of hemodynamic instability. These advantages have led Vieillard-Baron et al. (2003, 2006), and Poelaert and Schpfer (2005) to call for more widespread use of TEE for hemodynamic assessment in intensive care. Dr. Frances Colreavy eloquently expressed the potential of TEE in a post-graduate lecture at the 2010 Barcelona meeting of the European Society for Intensive Care Medicine in an acronym for rapid echocardiographic assessment of hemodynamic problems: V: ventricles (left and right ventricles) O: obstructions T: tamponade (see ImaCor case cited below) E: effusion (see ImaCor case cited below) D: dissection It is especially important to properly assess fluid responsiveness to properly guide hemodynamic stabilization. For example, Gordon and Russell (2005) observed that the treatment group in a variety of goal-directed therapies consistently received more fluid early than controls, and this may be the reason for their success. Indirect methods for assessing fluid responsiveness such as the PA catheter rely on assumed pressure-volume relations, and are thus limited at best (Marik, Baram and Vahid, 2008); in contrast, TEE can be used to directly assess fluid responsiveness (Charron et al., 2006).

c. Complications and cost of hemodynamic instability Major complications of hemodynamic instability following cardiac surgery include (1) surgical re-exploration, (2) increased resource utilization and length of stay, and (3) AKI, among others. The latter two factors, increased resource utilization and length of stay, and AKI are also major complications in general ICU patients. This section presents detailed analyses behind our cost data for re-exploration ($30,000 can be saved by avoiding one re-exploration) and hemodynamic instability ($18,000 per patient can be saved by improving hemodynamic management). There are several large studies, mostly focusing on complication rates, length of stay and other clinical impact. Hein et al. (2006 a, b, c) reported complication rates and length of stay data on all cardiac surgery patients [2,683 patients] admitted postoperatively to the cardiothoracic ICU at the Hospital Charit-University Medicine Berlin, for a period of two years from August 1, 2001 to August 31, 2003. The STS-CAPS Care study reported complication rates on 2,390 high risk CABG patients. Hravnak et al. (2010 presentation) reported hemodynamic instability and hospital charge data on 622 patients in a step down unit. These data, cost data from Speir (2009) and data from several smaller studies yield consistent estimates of the likelihood and costs associated with three main complications of hemodynamic instability: (1) surgical re-exploration, (2) increased resource utilization and length of stay, and (3) AKI. The main results are summarized below; details are presented in appendix 1. (1) Surgical re-exploration Likelihood: Surgical re-exploration may occur in 7-12% of typical patients. Hein et al. (2006 a, b, c) cited re-exploration in 7.2% of all cardiac surgery patients [2,683 patients] admitted postoperatively to the cardiothoracic ICU at the Hospital Charit-University Medicine Berlin, for a period of two years from August 1, 2001 to August 31, 2003. 78.2 % of patients with re-exploration had an ICU stay > 3 days; compared with 19.2 % of patients with no reexploration. Even though CABG has become relatively routine, Ranucci et al. (2008) cite a reexploration rate of 2-6%, with re-exploration resulting in much higher mortality: 14.2% versus 3.4%. For comparison, the STS CAPS-Care study of 2,390 high risk CABG patients (reported by J Williams at FACTS-Care 2010) cites a re-exploration rate of 9-10%. In fact, we have seen a significant increase in operative risk in CABG because Patients are sicker today (Biancari et al., 2009). We found a risk of 12.1% for MVR+CABG in a patient with a few other risk factors using the STS calculator available on the web. Cost: $ 30,000 in 2010 based upon Speir (2009).

(2) Hemodynamic instability (in general). Likelihood: Hravnak et al. reported on a large (622 patient) inclusive study at the 23rd ESICM Annual Congress in Barcelona, October 2010: 34% of patients in a step-down unit displayed at least some mild hemodynamic instability, 18% at least some major hemodynamic instability. Hemodynamic instability may be much more common in the ICU, especially following cardiac or serious general surgery. Cost: Our analysis of Hravnaks data found that the presence of any hemodynamic instability increased length of stay by at least 1.3 days, and hospital charges by at least $18,000 per patient; see Appendix 2. These data are consistent with an example from sepsis protocols: Trzeciak et al. (2006) found that the use of sepsis protocols reduced median hospital facility charges $53,000 per patient. Shorr et al. (2007) found that LOS was reduced by five days. When all costs of a prolonged LOS were included, 1 day LOS corresponded to $ 11,000 in cost throughout the stay in 2007. We shall make a conservative estimate that an increased length of stay by one day due to hemodynamic instability costs at least $18,000. Note on vasoactive agents. The use of vasoactive agents was also associated with longer LOS (Hein, 2006 a, b, c): 46.0 % of patients receiving Dopamine/dobutamine > 5 g kg1 min1 had an ICU stay > 3 days; compared with 25.3 % of patients receiving Dopamine/dobutamine 5 g kg1 min1 . (3) Acute kidney injury. Likelihood. The announcement of an upcoming SCCM clinical focus session (SCCM Clinical Focus 2011, http://www.sccm.org/Conferences/Topics/Clinical-FocusRenal/Pages/default.aspx) cites that AKI occurs in approximately 67% of intensive care unit (ICU) patients annually and is associated with increased hospital mortality rates. Generally defined as an abrupt and sustained decrease in kidney function, treatment of AKI is complex. Rosner, Portilla and Okusa (2008) reported that Acute renal failure (ARF) occurs in up to 30% of patients who undergo cardiac surgery, with dialysis being required in approximately 1% of all patients. The development of ARF is associated with substantial morbidity and mortality independent of all other factors. Heins (2006 a, b, c) large study reported a rate of renal failure involving dialysis of 9.5%; the recent STS CAPS-Care study (reported at FACTS-Care, Washington, DC, October 2010) reported a rate of 2-4% in high risk CABG patients. The STS calculator projected AKI in 7.7% of patients receiving MVR and CABG with a few other risk factors. Shaw et al. (2008) and Elahi et al. (2009) report a rate of 5%. Hein (2006 a, b, c) showed that AKI with dialysis (Called ARF-D in Heins work) is a significant risk factor for prolonged length of stay: odds ratio 6.83. 86.2 % of patients with ARFD had an ICU stay > 3 days; compared with 19.2 % of patients with no ARF-D. Cost. $ 60,000, extrapolated from Speir (2009). We now apply the above economic analysis to two case series of patients monitored by the ImaCor hemodynamic monitoring system: (i) 46 cardiac surgery patients at UAB and Vanderbilt, and (ii) 68 other ICU patients at eight institutions. 2. Cardiac surgery case series. In a series of 46 patients at two institutions, surgical re-exploration was avoided in five patients (11%), reducing hospital charges by $ 150,000 (extrapolated from Speir, 2009), and fluid and pressor administration was changed in 23 patients (50%), reducing hospital charges by at least $414,000 (based on literature review below, especially Hravnak et al., 2010), for a total reduction of at least $564,000. Cost of 49 ImaCor ClariTEE probes (some patients used more than one probe): $49,000. We have not included economic benefits of TEE detection of tamponade and rapid surgical intervention, TEE-guided VAD adjustment, likely reduction in AKI, (a common, major and expensive complication of cardiac surgery) due to reduced pressor usage, all due to insufficient specific data.

In conclusion, gross savings of at least $564,000 were 11 times the cost of probes; on a per patient basis gross savings averaged at least $12,260; twelve times the cost of a probe. We conclude that the ImaCor TEE system offers significant economic benefits in post cardiac surgery patients. Some of these results were presented at the cardio-thoracic surgery conference FACTSCare, Washington DC, October 2010. 3. General ICU case series. In a series of 68 patients, hemodynamic management was changed in 28 (41%), reducing hospital charges by at least $504,000. Cost of 68 probes: $68,000. We have not included likely reduction in AKI due to reduced pressor usage. In conclusion, gross savings of at least $504,000 were over seven times the cost of probes; on a per patient basis gross savings averaged at least $6,400; again over seven times the cost of a probe. We conclude that the ImaCor TEE system offers significant economic benefits in post cardiac surgery patients. Some of these results were presented at the critical care conference SCCM, Miami, FL, January 2010. We also reported there that the overall impact of the ImaCor Zura imaging system with the miniaturized ClariTEE probe was equivalent to the impact reported by Httemann's (2006) large review of studies with conventional TEE probes. The ImaCor system influenced clinical management in 40% of patients; this compared well with Httemann's reported 36% (range 10% - 69%). We conclude that monitoring cardiac function via direct visualization with a miniaturized TEE probe has significant clinical utility. Figure 2. Clinical impact of the ImaCor TEE system in an early study (Hastings et al., SCCM 2010 presentation)
Clinical impact of the ImaCor system
50

Number of patients

40 30 20 10 0 Patient population New information Influenced mamagement

4. Conclusions. As described in our application for a Qualifying Therapeutic Discovery Project grant, ImaCor developed a TEE monitoring system to improve critical care and peri-operative management by diagnosing a common problem, hemodynamic instability, and its underlying causes moved TEE, the gold standard for diagnosing and monitoring cardiac filling and function, key determinants of hemodynamic instability out of the operating room, and beyond on-demand assessment to an episodic monitoring tool, using a miniaturized (5.5 vs. 10-14 mm) probe. ImaCor TEE monitoring allows intensivists to diagnose underlying causes of hemodynamic instability through ongoing direct visualization, and thus guide therapeutic management. The QTDP program funded projects with a significant potential for reducing health care costs, and ImaCor was pleased to have received the endorsement of QTDP support.

As described above, studies to date have shown significant clinical and economic impact by demonstrating the potential to reduce cardiac surgery costs by over $7,200 per patient and general ICU costs by $3,100 per patient in study populations.

Figure 3. Economic Impact of ImaCor TEE monitoring in the cardiac ICU and general ICU, per patient. Savings from avoided re-explorations are shown in red; savings from hemodynamic management are shown in plum. Savings far exceed the $1,000 cost of the ImaCor ClariTEE probe.

ImaCor saves $11,260 per pt. in the CARDIAC ICU: from a 46 patient study*

11 the cost of a probe

Avoiding re-op: $3,260

Preventing and treating shock: $9,000

ImaCor saves $6,410 per pt. GENERAL ICU: from a 68 patient study** 6.4 the cost of a probe
Preventing and treating shock: $7,410
Probe cost

$2000

$4000

$6000

$8000

$10,000

$12,000

*see FACTS-Care 2010 abstract

**see SCCM 2010 abstract

Appendix 1. Illustrative cases. Here are four cases and one additional case series which illustrate the role of the ImaCor system in TEE monitoring. Case 1. Hemodynamics fluids can be tricky Assessing volume status with the ImaCor TEE monitoring system. Hemodynamic instability in a 77 year-old, 48 kg female post spinal surgery was due to volume deficiency despite receiving 4.5 L of fluids. Patient with Hypotension in PACU Following Spinal Fusion (http://www.imacormonitoring.com/case_deta.php?id=9) Jesse Marymont, MD, Cardiac Anesthesia Evanston Hospital, Evanston, IL Background: A 77 year-old, 48 kg female with multiple myeloma presented with a collapsed T12 vertebrae. On admission her hemoglobin was 9.7. Additional medical history included hypertension, a prior coronary angioplasty, and a prior carotid endarterectomy. During the operation the patient sustained a blood loss of 1700 mL with a urine output of 400 mL. During the procedure, the patient received 4500 mL of IV fluids, 4 units of PRBC, and 250 mL Hespan. In the PACU the patient was still found to be hypotensive (70-80 mm Hg systolic) after 750 mL of IV fluid and neosynepherine were administered. Methods: The attending physician ordered a bedside TEE using the ClariTEE probe. The probe was successfully placed, and the transgastric short-axis view (TGSAV) of the left ventricle (LV) was obtained. Qualitative and quantitative analysis of the left ventricular size and function revealed hypovolemia, ventricular hypertrophy, and abnormal wall motion. With this information, additional fluids were aggressively administered and pressors were titrated and subsequently discontinued upon achieving normotensive blood pressure. The ClariTEE probe remained indwelling in the patient to enable further assessments. Results: Patient was normotensive (140 mm Hg) in the intensive care unit the next morning. Conclusions: Postoperative hemodynamic stability is a common complication following noncardiac surgery. Empiric administration of IV fluids and plasma expanders is inadequate and may contribute to new problems. The ClariTEE probe is an effective tool for diagnosing causes of hemodynamic instability in the PACU environment due to the immediacy of the imaging and the actionable data provided to the intensivists.

Case 2. Pressers are often needed, but can be dangerous TEE-guided rapid weaning from pressors. The following case illustrates the role of the ImaCor TEE monitoring system in rapid weaning from pressors in a post cardiac surgery patient with an ischemic gut (SCCM 2011, Poster # 936). TEE-guided rapid weaning from pressors in a post cardiac surgery patient with an ischemic gut Jiri Horak, Hospital of the University of Pennsylvania, Philadelphia, PA Frans van Wegenberg, University of Pennsylvania School of Medicine, Philadelphia, PA Scott Roth, Harold Hastings, ImaCor Inc A 37-year-old man with a history of hypertension initially presented with a ruptured type A dissection. He underwent aortic valve resuspension, total arch replacement, and replacement of the ascending aorta. Echo on postop day 5 showed normal biventricular function. The patient did well but complained of severe abdominal pain and increasing distress on day 7. Lab work revealed new onset coagulopathy, acute renal failure, hyperkalemia, increased white blood cell count and rising lactate levels. The patient became progressively hypotensive requiring phenylephrine

support at 150mg/min and ICU admission. Bedside transthoracic echo (TTE) showed normal biventricular function. CT angiography revealed a flap compromising the superior mesenteric artery and celiac artery origins. Emergent thoracic endovascular aortic repair and exploratory laparotomy were performed. The patient required CPR following cardiac arrest in the OR. Exploratory laparotomy revealed only dusky gall bladder and gut. The patient was left open. The patient was hemodynamically unstable at high levels of pressor support. A ClariTEE probe revealed adequate systolic function, leading the physician to conclude that diastolic dysfunction was the cause of hemodynamic instability. (Cardiac dysfunction after intestinal reperfusion has been described in rats, Horton and White, 1991). Pressors were rapidly weaned and fluid administered under TEE monitoring. Figure 4. Rapid Weaning from Pressors under TEE Monitoring. Pressors were rapidly weaned and fluid administered under TEE monitoring. Hemodynamics remained stable throughout the process. At the end of the 7 hour process: Epinephrine was off, Phenylephrine was down 50% and Vasopressin was down 50%.

Epinephrine reduced from 2 mcg/ min to 0

Phenylephrine reduced from 200 to 100 mcg/ min

Vasopressin reduced from 0.08 to 0.04 unit/ min

We were able to confidently wean down pressors because TEE monitoring revealed satisfactory systolic function throughout the process. This was particularly important as excessive pressors in this patient could have caused further gut ischemia, inflammatory mediator release, and further diastolic dysfunction. TEE monitoring in the ICU with a miniaturized probe is a valuable addition for assessing cardiac function. Further studies to evaluate its impact on efficacy and clinical outcomes are warranted.

Case 3. Surgical re-exploration: avoid it if you can Use of the ImaCor TEE monitoring system to avoid surgical re-exploration for hemodynamic instability post cardiac surgery. Effusion, a common complication of cardiac surgery, was managed medically under the guidance of the ImaCor TEE monitoring system. TEE Monitoring Guides Medical Management of Cardiac Effusion Benjamin H Webster, MD Chad E Wagner, MD Vanderbilt University Hospital, Nashville, TN A 66-yr-old male with a history of two-vessel coronary artery bypass (CAB) and aortic valve (AV) stenosis with valve area of 0.8cm2 presented with exertional chest pain, shortness of breath, and lightheadedness. After evaluation by left and right heart catheterization the patient was scheduled for urgent re-do sternotomy, aortic valve replacement, and repeat coronary artery bypass (CAB) surgery. After induction of anesthesia, intraoperative transesophageal echocardiography (TEE) examination revealed severe aortic stenosis, left ventricular hypertrophy, and normal wall motion with an EF of 50%. He underwent CAB x 2 with left internal mammary artery to left anterior descending artery, saphenous vein to first obtuse marginal, and AV replacement with a 25mm bioprosthetic valve. Dobutamine and norepinephrine infusions were required for separation from cardiopulmonary bypass (CPB) and initial TEE demonstrated a well placed bioprosthetic AV and absence of regional wall motion abnormalities (RWMA). Significant bleeding and hemodynamic instability required administration of multiple blood products, initiation of a vasopressin infusion, and recombinant factor VIIa. The patient was stabilized and transported to the cardiovascular intensive care unit (CVICU). Initial hemodynamic assessment in the CVICU showed a cardiac index (CI) of 1.5, arterial blood pressure (ABP) 81/45, pulmonary artery catheter (PAC) pressure of 40/23, central venous pressure (CVP) of 14, systemic vascular resistance (SVR) of 898, mixed venous oxygen saturation (MVO2) of 46%, low urine output, and mildly elevated chest tube output. Over the next hour the MVO2 remained low with an increasing CVP (20mmHg) and decreasing urine output. A miniaturized disposable TEE monitoring probe (ImaCor) was placed, which demonstrated a posterior and lateral pericardial effusion with inadequate left ventricular end diastolic area (LVEDA) despite high filling pressures (image 1/video1). Based on the TEE findings we continued volume resuscitation despite elevated measured PAC filling pressures. LV volume increased despite a small increase in pericardial fluid and the patients hemodynamic status began to stabilize (image 2/video2). The CVICU team and cardiac surgeon decided to continue to monitor the pericardial effusion and LV volume with the ImaCor TEE probe rather than returning to the operating room for re-exploration. Over the subsequent ten hours episodic assessment using the ImaCor probe demonstrated continued resolution of the pericardial fluid collection with increased LVEDA (image 3). Hemodynamics concomitantly improved to: ABP 115/65, CI of 2.6, PAP 40/22, CVP 14, SVR 735, and MVO2 of 60%. Vasoactive infusions were able to be weaned and the patient was extubated and transferred to intermediate care.

Case 4. Surgical re-exploration intervene rapidly under guidance, if you must. Detection of tamponade as the cause of hemodynamic instability with the ImaCor TEE monitoring system. When surgical re-exploration is necessary, rapid, guided re-exploration can reduce both mortality and morbidity (c.f. Ranucci, 2008). This case also demonstrates the advantages of TEE over TTE in diagnosing the cause of hemodynamic instability. (http://www.imacormonitoring.com/case_deta.php?id=11) Tamponade Diagnosed Post CABG Michael Wall, MD, Cardiac Anesthesia Barnes-Jewish Hospital, St. Louis, MO Background: 86 year-old male with extensive medical history who had undergone elective CABG several hours earlier. In the CTICU, the patient was tachycardic and hypotensive (80110 mm Hg) while on Levophed. SVO2 was 32% and CVP was 25 mm Hg. TEE examinations: Attending ICU physician ordered a transthoracic echo (TTE) and a transesophageal echo (TEE) with the ClariTEE probe. Both studies were performed at the bedside simultaneously in the ICU. Results: An echo technologist performed the TTE from the patients left side and was unable to assess the right atrium. The attending ICU physician, performing the TEE exam from the right side of the bed easily placed the probe without complication and was quickly able to obtain a four-chamber view of the heart. From this view, the physician noticed a large blood clot pressing on the right atrium and concluded that localized tamponade was the cause of the patients deterioration. Based on this new information, the patient was taken directly back to the operating room for an immediate reoperation and the clot was removed. The patients status immediately stabilized, and he returned to the ICU. Shortly after the patients return, the physician performed a second assessment with the ClariTEE probe and determined that the right atrium was filling normally. The patients blood pressure was no longer labile (140-150 mm Hg), Levophed was discontinued, and the patient was hemodynamically stable (HR: 70 beats/minute and CVP: 8 mm Hg). Discussion: The published incidence of tamponade following cardiac surgeries is 0.5%-5.8% (Russo et al., 1993), and re-operation due to tamponade is costly and associated with increased mortality and prolonged hospital stay. While the use of TEE is well documented as an effective tool in the cardiac O.R. for monitoring patients, there is currently no effective method of monitoring these patients outside the O.R. where serious complications often occurs. In this specific case, as often occurs in the ICU, the TTE was unable to provide the critical information required to make this diagnosis. Conclusion: The ClariTEE probe can be an effective and useful tool in diagnosing tamponade in postcardiac surgery cases. Moreover, the ClariTEE probe allows physicians to establish a continuity of care in the ICU that heretofore has not been available.

Case series. Liver transplants. Dr. Luc Frenette (UAB) used the ImaCor system to monitor a case series of 23 consecutive liver transplant patients to date. Maintaining hemodynamic stability in these patients is especially challenging because of conflicting demands of transplant surgery and post-surgical recovery. Dr. Frenette found reduced pressor usage with expected significant economic benefits. Details will be reported elsewhere, later.

10

Appendix 2. More detailed clinical and economic analysis. (1) Surgical re-exploration Likelihood: Surgical re-exploration may occur in 7-12% of typical patients. Hein et al. (2006 a,b,c) cited re-exploration in 7.2% of all cardiac surgery patients [2,683 patients] admitted postoperatively to the cardiothoracic ICU at the Hospital Charit-University Medicine Berlin, for a period of two years from August 1, 2001 to August 31, 2003. 78.2 % of patients with re-exploration had an ICU stay > 3 days; compared with 19.2 % of patients with no re-exploration. Even though CABG has become relatively routine, Ranucci et al. (2008) cite a re-exploration rate of 2-6%, with re-exploration resulting in much higher mortality: 14.2% versus 3.4%. For comparison, the STS CAPS-Care study of 2,390 high risk CABG patients (reported by J Williams at FACTS-Care 2010) cites a re-exploration rate of 9-10%. In fact, we have seen a significant increase in operative risk in CABG because Patients are sicker today (Biancari et al., 2009). We found a risk of 12.1% for MVR+CABG in a patient with a few other risk factors using the STS calculator available on the web. Cost: $ 30,000 in 2010 based upon Speir (2009). Effects on length of stay: Re-exploration is associated with increased length of stay (Hein, 2006 a, b, c).

Table 1. Re-exploration is associated with longer ICU stay. Re-explorPatients with an ICU Patients with an ICU ation stay > 3 days stay 3 days Yes re151 42 exploration No 534 1,956 Totals

Totals 193 (7.2 % of total 2,683) 2,490 (92.8% of total 2,683) 2,683 total patients

685 (26% of total 1,998 (74% of total 2,683) 2,683) 78.2 % of patients with re-exploration had an ICU stay > 3 days; compared with 19.2 % of patients with no re-exploration.

(2) Hemodynamic instability (in general). Likelihood: Hravnak et al. reported on a large (622 patient) inclusive study at the 23rd ESICM Annual Congress in Barcelona, October 2010: 34% of patients in a step-down unit displayed at least some mild hemodynamic instability, 18% at least some major hemodynamic instability. Hemodynamic instability may be much more common in the ICU, especially following cardiac or serious general surgery. Cost: Our analysis of Hravnaks data found than the presence of any hemodynamic instability increased length of stay by at least 1.3 days, and hospital charges by at least $18,000 per patient. These data are consistent with an example from sepsis protocols: Trzeciak et al. (2006) found that the use of sepsis protocols reduced median hospital facility charges $53,000 per patient. Shorr et al. (2007) found that LOS was reduced by five days. When all costs of a prolonged LOS were included, 1 day LOS corresponded to $ 11,000 in cost throughout the stay in 2007. We shall make a conservative estimate that an increased length of stay by one day due to hemodynamic instability costs at least $10,000. Details follow.

11

Table 2. Likelihood of hemodynamic instability (from Hravnak et al., 2010) Type of hemodynamic instability Duration of hemodynamic instability none 1-30 min 31-90 min >90 min

mild 66% 19% 7% 8%

major 82% 9% 5% 4%

Table 3. Effects of mild hemodynamic instability upon length of stay (LOS) and hospital charges, analysis based on Hravnak et al. (2010). Hospital charges Duration of hemodynamic instability none 1-30 min 31-90 min >90 min Length of stay 4.6 days 5.9 days 6.6 days 7.0 days Increased due to Total for Daily hemodynamic stay average instability $104,500 $22,700 none $122,500 $20,700 $18,000 $145,500 $22,000 $41,000 $152,200 $21,800 $47,700

Figure 5. Increased costs due to hemodynamic instability reflect both increased resource use in early days, and increased length of stay.

Charges each day ($)

Increased use of resources to treat hemodynamic instability increases cost Increased LOS due to hemodynamic instability also increases cost

Hemodynamics stable Length of stay (days)

Note on vasoactive agents. The use of vasoactive agents was also associated with longer LOS (Hein, 2006 a, b, c): 46.0 % of patients receiving Dopamine/dobutamine > 5 g kg1 min1 had an ICU stay > 3 days; compared with 25.3 % of patients receiving Dopamine/dobutamine 5 g kg1 min1.

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Additional notes on protocolized fluid administration. Sepsis patients: the major difference between treatment and control groups was increased fluid over the first 6 hours (Rivers, 2001): 5 L vs. 3.5 L. Mortality was sharply reduced. As stated above, Trzeciak et al. (2006) found that the use of sepsis protocols reduced median hospital facility charges $53,000 per patient. Shorr et al. (2007) found that LOS was reduced by five days. Cardiac surgery patients: similarly, the treatment group received 3.2L of fluid in the first postoperative night, ws. 2 L for controls (Plnen et al., 2000) and had a significantly shorter hospital stay. General major surgery patients: Pearse et al. (2005) reported fewer complications after increased early fluid administration (treatment group: 1.9 L vs. 1.2 L for controls). In summary, Gordon and Russell (2005) reported that the treatment group has consistently received more fluid in prior studies and this may well be the major contributor to success. Additional notes on vasoactive agents and length of stay. The use of vasoactive agents was also associated with longer LOS (Hein, 2006 a, b, c): 46.0 % of patients receiving Dopamine/dobutamine > 5 g kg1 min1 had an ICU stay > 3 days; compared with 25.3 % of patients receiving Dopamine/dobutamine 5 g kg1 min1. Table 4. Dopamine/dobutamine administration is associated with prolonged stay Catecholamine therapy on Patients with an Patients with Totals admission to the ICU ICU an ICU stay > 3 days stay 3 days 1,493 1,747 None/dopamine/dobutamine 254 5 g kg1 min1 Dopamine/dobutamine > 5 g 431 505 936 (34.9 % of total 2,683 kg1 min1 Totals 685 (26% of 1,998 (74% of 2,683 total total 2,683) total 2,683) patients 1 1 46.0 % of patients receiving Dopamine/dobutamine > 5 g kg min had an ICU stay > 3 days; compared with 25.3 % of patients receiving Dopamine/dobutamine 5 g kg1 min1 Conclusions. Hemodynamic stabilization brings significant clinical and economic benefits; these benefits are increased when patient status allows increases in fluid administration and decreases in vasoactive agents. See, for example, Appendix 1, Case 1 and Case 4. Increased in fluid administration and decreased vasoactive agents were common management changes when ImaCor TEE monitoring was used. A detailed discussion will appear elsewhere. (3) Acute kidney injury. Likelihood. Rosner, Portilla and Okusa (2008) reported that Acute renal failure (ARF) occurs in up to 30% of patients who undergo cardiac surgery, with dialysis being required in approximately 1% of all patients. The development of ARF is associated with substantial morbidity and mortality independent of all other factors. Heins (2006 a, b,c) large study reported a rate of renal failure involving dialysis of 9.5%; the recent STS CAPS-Care study (reported at FACTS-Care, Washington, DC, October 2010) reported a rate of 2-4% in high risk CABG patients. The STS calculator projected AKI in 7.7% of patients receiving MVR and CABG with a few other risk factors. Shaw et al. (2008) and Elahi et al. (2009) report a rate of 5%. Cost. $ 60,000, extrapolated from Speir (2009). Effects on length of stay. Hein (2006 a, b, c) showed that AKI with dialysis is a significant risk factor for prolonged length of stay: odds ratio 6.83. Here is a summary of his data.

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Table 5. AKI (here called ARF) with dialysis is associated with longer ICU stay (univariate analysis from Hein (2006 a, b, c). ARF-D Patients with an Patients with an ICU Totals ICU stay 3 days stay > 3 days Yes - ARF-D 219 35 254 (9.5 % of total 2,683) No 466 1,963 2,429 (90.5% of total 2,683) Totals 685 (26% of total 1,998 (74% of total 2,683 total patients 2,683) 2,683) 86.2 % of patients with ARF-D had an ICU stay > 3 days; compared with 19.2 % of patients with no ARF-D

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