Anesthetic Management for Implantation of the Jarvik 2000™ Left Ventricular Assist System Nancy A. Nussmeier, MD*, Charles B. Probert, MD*, Douglas Hirsch, MD*, John R. Cooper, Jr., MD*, Igor D. Gregoric, MD†, Timothy J. Myers, BS†, and O. H. Frazier, MD† From the *Department of Cardiovascular Anesthesiology and †The Cullen Cardiovascular Surgical Research Laboratories, Texas Heart Institute at St. Luke’s Episcopal Hospital, Houston, Texas

The Jarvik 2000 Heart™ is a left ventricular assist device that produces continuous nonpulsatile axial flow by means of a single, rotating, vaned impeller. Anesthetic and perioperative considerations of the Jarvik 2000 Heart™ differ from those of conventional assist devices. The Jarvik 2000 is implanted within the left ventricle through a left thoracotomy, which is aided by left lung isolation. A brief period of cardiopulmonary bypass and induced ventricular fibrillation facilitate implantation. Transesophageal echocardiography is essential to assure proper intraventricular positioning of the device and aortic outflow, confirmed by observation of aortic valve opening in the presence of adequate

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ardiac transplantation is the ultimate surgical treatment for end-stage heart failure, but the chronic shortage of donor hearts has necessitated clinical trials of other surgical options. Therefore, cardiovascular anesthesiologists are now confronted more frequently with the specialized needs of patients who receive left ventricular assist devices (LVADs) (1,2). Food and Drug Administration-approved LVADs in current clinical use are designed to use the entire venous return and can produce pulsatile blood flows of up to 12 L/min. These large, abdominally implanted devices are unsuitable for children and smaller adults because of their size. The Jarvik 2000 Heart™ (Jarvik Heart, New York, NY) is an implantable LVAD that produces continuous nonpulsatile axial flow by means of a single, rotating, vaned impeller (3– 6). Continuous-flow pump technology has allowed miniaturization and

Accepted for publication May 29, 2003. Address correspondence and reprint requests to Dr. Nussmeier, Department of Cardiovascular Anesthesiology, Texas Heart Institute at St. Luke’s Episcopal Hospital, PO Box 20345, MC1–226, Houston, TX 77030. Address email to [email protected]. DOI: 10.1213/01.ANE.0000081723.31144.D7

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left ventricular volume. Because continuous flow devices function best in the presence of lower systemic and pulmonary vascular resistance, milrinone was preferentially used as an inotropic drug. In the first group of 10 patients to receive the Jarvik 2000, the pump provided a cardiac output of up to 8 L/min, depending on preload, afterload, and pump speed. There were no early perioperative deaths. The average support duration was 81.2 days; the range was 13–214 days. Seven of the 10 patients survived to transplantation. Survivors underwent complete physical rehabilitation during pump support. (Anesth Analg 2003;97:964 –71)

use in smaller patients (Fig. 1) (6). The unique continuous flow and lack of stasis may minimize the chance of thrombus formation in the device (3– 6). Continuous flow also eliminates the need for valves, an internal compliance chamber, or an externalized vent, which are necessary components of previous LVAD designs. Furthermore, because of an adjustable output, this pump can be used as a true assist device, thereby theoretically maximizing the potential for ventricular recovery (4,7–11), whereas conventional LVADs perform functionally as left ventricular (LV) replacement devices. Finally, the Jarvik 2000 is usually implanted through a left thoracotomy, an approach that is potentially valuable in patients having prior median sternotomy. Presently, in the United States, the Jarvik 2000 clinical study involves only temporary use in heart transplant candidates. A multicenter trial is underway involving eight centers in the United States and five centers in Europe. Because the anesthetic considerations for patients undergoing insertion of the Jarvik 2000 differ from those of conventional LVAD recipients, we report the perioperative management of the 10 patients who participated in the initial feasibility study to evaluate the safety and utility of the Jarvik 2000 as a bridge to cardiac transplantation. ©2003 by the International Anesthesia Research Society 0003-2999/03

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Figure 1. The Jarvik 2000 Heart™ consists of an intraventricular blood pump, a 16-mm outflow graft, a percutaneous power cable, a speed controller, and a battery. The controller and battery are worn on a belt or are carried in a bag. Reprinted with permission from Circulation 2002;105:2855.

Methods Patients who had New York Heart Association (NYHA) functional class IV heart failure and a small body surface area (⬍2 m2) or those who had undergone a previous median sternotomy and had a body habitus unsuitable for a conventional LVAD were eligible for inclusion in the initial group of 10 patients to receive the Jarvik 2000 pump (Table 1). Inclusion and exclusion criteria for stable (Category I) or unstable (Category II) patients were similar to those for Phase 3 studies for all LVADs. All patients received care in compliance with institutional protocols approved by our hospital’s IRB. Written informed consent was obtained from all patients. Conventional monitors and a radial or brachial arterial catheter for blood pressure monitoring were applied while the patient was awake. Anesthetic induction was performed with fentanyl (5–10 ␮g/kg) and etomidate or thiopental. Small-dose isoflurane (0.4%–1.0%) was used for anesthetic maintenance and was supplemented by small doses of midazolam (5– 20 mg) and fentanyl (5–10 ␮g/kg). Other monitors were inserted after anesthetic induction, including a pulmonary arterial (PA) catheter (for monitoring pulmonary artery pressures, continuous cardiac output, and mixed venous oxygen saturation) and a transesophageal echocardiography (TEE) probe. Large bore

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IV access was secured via the right internal jugular vein or the right femoral vein for rapid administration of blood products. Patients were then turned 30°– 45° and secured in partial right lateral decubitus position. To minimize blood loss, all patients received either aminocaproic acid administered before, during, and after cardiopulmonary bypass (CPB) (for a total of 20 g) or aprotinin administered in a small-dose regimen (1,000,000 Kallikrein Inhibitor Units [KIU] administered before sternotomy and 1,000,000 KIU in the CPB circuit, followed by a continuous infusion of 250,000 KIU/hr for 5 h) (12). In addition, the CPB circuit was usually primed with fresh-frozen plasma instead of crystalloid because each of these patients was also receiving preoperative warfarin therapy. A TEE assessment was performed in all patients before initiation of CPB, although preoperative transthoracic echocardiography (TTE) had been performed a few days before surgery. Left and right ventricular function was evaluated, and the cardiac chambers were examined for thrombus, particularly at the apex of the left ventricle, which is the insertion site for the Jarvik 2000. Aortic valve function was assessed because the presence of moderate-to-severe insufficiency results in regurgitation of blood into the left ventricle when the device is activated. The atrial septum was inspected for a patent foramen ovale, which can lead to decreased systemic oxygenation as a result of rightto-left shunting with the lower left-sided pressure resulting from LVAD activation (13). The thoracic aorta was assessed for calcification, plaque, or dilation, although a computerized tomographic scan of the thoracic aorta was routinely obtained during the preoperative surgical workup. The heart and descending thoracic aorta were approached through a left lateral thoracotomy via the 6th intercostal space. A double-lumen or bronchialblocker tube facilitated exposure. Heparin (1 mg/kg) was administered. A portion of the descending aorta was partially excluded by a vascular clamp and the outflow graft of the pump was anastomosed to the aorta in an end-to-side fashion. Then, additional heparin (2 mg/kg) was administered to achieve full systemic heparinization. Throughout surgery, the adequacy of heparinization and later reversal was monitored with a hemostasis management system using heparin assays by protamine titration (Medtronic Hepcon™ HMS Plus, Medtronic, Minneapolis, MN). The left femoral artery and vein were cannulated for CPB. A large double-stage venous cannula, the Carpentier 30/33 French Bi-caval Femoral Cannula (Medtronic), was advanced into the right atrium, with TEE monitoring of placement. The device’s power cable was then brought through the abdominal wall. After initiation of femoral-femoral bypass, ventricular fibrillation was deliberately induced for ⬍1 min, with an alternating current ventricular fibrillator (A. C.

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Table 1. Criteria for Eligibility for Insertion of Jarvik 2000™ Inclusion Criteria Category I. NYHA class-IV status BSA ⬍2.0 m2 and ⬎1.2 m2 Approved for heart transplantation Pulmonary capillary wedge pressure of ⱖ18 mm Hg, with cardiac index ⱕ2.0 L/min/m2 or systolic blood pressure of ⱕ80 mm Hg Dependent on one or more IV inotropic drugs or an intraaortic balloon pump (inotropic drugs may include dopamine, dobutamine, milrinone, epinephrine, and digitalis) Category II. Approval for heart transplantation Hospitalized Receiving inotropic or intraaortic balloon pump support Having acute cardiac decompensation or cardiac arrest Exclusion Criteria Age ⬎75 yr Renal failure requiring hemodialysis for at least 7 of the preceding 30 days COPD, as documented by FEV1 ⬍35% of predicted Fixed pulmonary hypertension: pulmonary vascular resistance ⱖ6 Wood units with pulmonary vasodilator therapy Right-sided heart failure: RV ejection fraction ⬍10% with pulmonary vascular resistance ⬎8 Wood units Acute ventricular septal defect Sustained ventricular fibrillation or tachycardia, requiring ACLS, including cardiac massage for more than 1 h Artificial valves Severe aortic regurgitation (3⫹ to 4⫹) Liver cirrhosis, documented by liver biopsy Systemic infection Severe blood dyscrasia: PT ⬎16 s; PTT ⬎45 s, platelet count ⬍50, 000 mm3 without anticoagulant or antiplatelet therapy Peripheral vascular disease causing lower-extremity ischemic pain at rest, not treatable with surgery Malignancy not in remission Pregnancy Current participation in investigational trials with other devices, drugs, or biologic agents HIV-positive ACLS ⫽ advanced cardiac life support; BSA ⫽ body surface area; COPD ⫽ chronic obstructive pulmonary disease; FEV1 ⫽ forced expiratory volume in 1 second; HIV ⫽ human immunodeficiency virus; NYHA ⫽ New York Heart Association; PT ⫽ prothrombin time; PTT ⫽ partial prothrombin time; RV ⫽ right ventricular; HIV ⫽ human immunodeficiency virus.

Fibrillator Model #2039, Medtronic) preventing air from entering the left ventricle when it was incised to insert the device. Patient temperature on CPB was allowed to drift no lower than 34°C. A circular knife was then passed through the sewing cuff to incise the left ventricle. The pump was placed in the ventricle and secured. The heart was defibrillated, and air was removed from the apex of the left ventricle using a 19-gauge needle, with TEE assessment of adequacy of air removal. The outflow graft was then anastomosed to the previously placed aortic graft. Finally, the pump was activated and patients were weaned from CPB. During weaning from CPB, TEE was used to verify that the pump was correctly centered at the apex of the left ventricle, with the inlet positioned in axial alignment with the mitral valve opening (Fig. 2). This is best accomplished in the standard midesophageal 14-chamber (⬃0°) and 2-chamber (⬃90°) TEE views. Surgical repositioning of an incorrectly aligned device is possible, although this has not been necessary in our institution. After verification of satisfactory positioning and function of the device with TEE, heparin was reversed with protamine and adequacy of reversal was confirmed with the Hepcon™. A rapid infusion

Figure 2. Transesophageal midesophageal two-chamber echocardiographic view of the device in the left ventricle.

device and a fluid warmer were available because of potentially large postbypass blood losses associated with insertion of any LVAD. As the Jarvik 2000 can pump up to 8 L/min from the left ventricle, the main physiologic problem was maintenance of LV inflow. Therefore, pulmonary vasodilators

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(e.g., inhaled nitric oxide [20 – 80 parts per million] and either IV prostaglandin E1 [0.025– 0.05 ␮g/kg] or nesiritide [2 ␮g/kg followed by 0.01 ␮g · kg⫺1 · min⫺1]) were used to decrease right ventricular afterload, as guided by PA pressures. Fresh gas flows of at least 10 L/min were required during administration of inhaled nitric oxide to avoid buildup of nitrogen dioxide. PA pressures were maintained as low as possible, although all patients had preexisting pulmonary hypertension. Inotropic drugs were used as necessary to support right-sided cardiac function. Because axial flow devices function best in the presence of lower systemic and pulmonary vascular resistance, drugs such as milrinone (50 ␮g/kg followed by 0.25– 0.5 ␮ g · kg ⫺1 · min ⫺1 ), dobutamine (5–20 ␮g · kg⫺1 · min⫺1), or isoproterenol (0.025– 0.5 ␮ g/min), were preferentially used. Fenoldopam (0.05– 0.1 ␮g · kg⫺1 · min⫺1) was used in all patients to potentially increase renal blood flow, with larger doses to further decrease systemic vascular resistance, if needed. Conversely, some patients required an increase in systemic vascular resistance; if so, vasopressin (1– 4 U/h), epinephrine (1–20 ␮g/min) or, rarely, norepinephrine (1–20 ␮g/kg) was used. Jarvik 2000 pump speeds may be varied between 8000 rotations per minute (rpm) and 12,000 rpm. Cardiac output was adequate with or without pulsatile flow (Fig. 3). At rapid flow rates, sufficient blood is shunted through the pump to prevent the aortic valve from opening. To avoid stasis in the aortic root and subsequent decreased coronary flow, pump speed was adjusted to allow the aortic valve to open (6,14). Intraoperatively, the pump speed was increased by 1000-rpm increments throughout the entire operating range until aortic valve opening could be verified with TEE and observed on the arterial pressure wave form. If the pump speed was too fast, the arterial pressure wave form decreased and the dicrotic notch was absent (indicating a closed aortic valve). The presence of a pulsatile wave form with a dicrotic notch indicated some aortic outflow and was verified with TEE (Fig. 3). Aortic valve opening was dependent on left atrial and ventricular volume as well as pump speed, with volume status guided by TEE. An ultrasonic flowprobe was placed on the pump’s outflow graft to verify flow rates against varying mean arterial pressure (7); this probe was removed before thoracotomy closure. Patients were sedated with a propofol infusion (33–50 ␮g · kg⫺1 · min⫺1) and transferred to the intensive care unit. Hemodynamic stability was maintained with inotropic drugs and pulmonary vasodilators, as required (Table 2). Preload was maintained according to central venous pressure measurements individualized in each patient, as well as the desired presence of a pulsatile wave form. Residual paralysis was allowed to dissipate and propofol was discontinued when patients achieved hemodynamic stability. Weaning from

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Figure 3. Arterial pressure wave form observed in a single patient when the pump speed was increased by 1000-rpm increments over the entire operating range (8000 –12,000 rpm). The dicrotic notch is present at 8000 and 9000 rpm, but is absent at 10,000 rpm. In this case, the pump speed was set at 9000 rpm, so there was some aortic outflow. BP ⫽ blood pressure. Reprinted with permission from Circulation 2002;105:2855.

mechanical ventilation was accomplished according to institutional protocol, with incremental decreases in intermittent mandatory ventilation rate from 10 to 4 bpm, then to zero (with 5 cm H2O of continuous positive airway pressure). Patients were then tracheally extubated if criteria were met (negative inspiratory force of ⬎ ⫺25 cm H2O and vital capacity of at least 12–15 mL/kg). Small doses of morphine (2–5 mg increments) were administered as needed for analgesia before and after extubation. In the early postoperative period, hemodynamic assessment was performed at least daily using the intraarterial pressure line, PA pressures, thermodilution cardiac outputs, and TTE. After all monitoring lines were removed, hemodynamic assessment was based on TTE and vital signs.

Results In its first year of clinical use (April 2000 to March 2001), the Jarvik 2000 was implanted in 10 patients (seven men and three women) who had been approved for heart transplantation. There were six patients diagnosed with idiopathic cardiomyopathy and four patients with ischemic cardiomyopathy. Demographic characteristics and perioperative data are shown in Table 2. Duration of CPB was 62.4 ⫾ 21.3 min. Mean intraoperative blood loss was 2930 ⫾ 2775 mL. There were no early perioperative deaths. Seven of the 10 patients survived to transplantation. Hemodynamic function improved in all patients when compared with preoperative values. Forty-eight

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Table 2. Demographic and Perioperative Patient Characteristics Age (yr) Weight (kg) BSA (m2) Gender (% male) Duration of cardiomyopathy (yr) Duration of CPB (min) Duration of procedure (h) Intraoperative PRBC (units) Intraoperative FFP (units) Intraoperative platelets (units) EBL (ml) Vasoactive drugs at ICU admission Patient 1 Patient 2 Patient 3 Patient 4 Patient 5 Patient 6 Patient 7 Patient 8 Patient 9 Patient 10

51.3 ⫾ 9.2 73.0 ⫾ 12.4 1.9 ⫾ 0.2 70 12.2 ⫾ 7.8 62.4 ⫾ 21.3 6.5 ⫾ 1.0 4.6 ⫾ 4.5 8.6 ⫾ 6.6 7.8 ⫾ 6.4 2930 ⫾ 2775 Nitric oxide, fenoldopam, PGE1, milrinone Nitric oxide, PGE1, fenoldopam, milrinone, dopamine Nitric oxide, PGE1, fenoldopam, milrinone, epinephrine, norepinephrine Nitric oxide, fenoldopam Nitric oxide, fenoldopam, milrinone Nitric oxide, PGE1, fenoldopam, milrinone, dobutamine, epinephrine, norepinephrine Nitric oxide, PGE1, fenoldopam, milrinone, epinephrine Nitric oxide, PGE1, fenoldopam, milrinone, dobutamine, epinephrine, nitroglycerin Nitric oxide, fenoldopam, milrinone, epinephrine Nitric oxide, fenoldopam, milrinone, dopamine

CPB, cardiopulmonary bypass; PRBC, packed red blood cells; FFP, fresh frozen plasma; ICU, intensive care unit; BSA ⫽ body surface area; EBL ⫽ estimated blood loss; PGE ⫽ prostaglandin E. Data presented as mean ⫾ sd. Duration of cardiac failure, onset of symptoms until LVAD insertion, rounded off to the nearest year.

hours after device implantation, the average cardiac index, measured by thermodilution technique via the PA catheter, increased by 43% and the pulmonary capillary wedge pressure decreased by 52% (Table 3). Organ function was maintained, as indicated by renal and hepatic laboratory values (Table 3). Inotropic support was gradually reduced, and patients were completely weaned from inotropes by 3–5 days postoperatively. Five patients were tracheally extubated within ⬍24 h, 2 patients within 48 h, and 1 patient on the fourth postoperative day. One of these patients required reintubation after an episode of ventricular tachycardia with resultant hypotension, occurring on the 20th postoperative day. He was tracheally extubated after 1 wk, then remained extubated until induction of anesthesia for heart transplantation. The remaining 2 patients were ventilated for the entire duration of support until death. In this group, the Jarvik 2000 provided a cardiac output of up to 8 L/min, depending on preload, afterload, and pump speed. Optimal flow and cardiac output were achieved when the mean arterial blood pressure was in the range of 65–75 mm Hg. At the standard speed setting (9000 rpm), the mean cardiac index was 3.2 L/min/m2. However, in individual patients, pump flow and the corresponding cardiac index were primarily determined by differential pressure across the pump (LV pressure versus aortic pressure), as estimated by systemic vascular resistance, rather than by rpm (Fig. 4). Average pulse pressure varied between 13 mm Hg at 12,000 rpm and

42 mm Hg with the pump off. At 11,000 rpm and 12,000 rpm, flow through the LV outflow tract was minimal as monitored by echocardiography, indicating that the pump was capturing nearly all of the cardiac output (6). Partial aortic outflow with some pulsatile pressure occurred with pump speeds of 9000 –10,000 rpm. As pump flow was decreased by decreasing the RPM, the cardiac output (representing the sum of pump function plus native heart function) remained relatively constant in most patients. Although regurgitant flow back through the pump from aorta to LV cavity is theoretically possible when the pump is completely turned off, such regurgitant flow was documented to be minimal by TEE or TTE. In brief (5-min) device-off studies, the mean regurgitant flow was 0.35 L/min/m2, and the mean regurgitant fraction was 11% (6). Three patients died despite proper functioning of the Jarvik 2000. Two of the deaths were from ventricular arrhythmias unresponsive to therapy. Because the right heart does not pump effectively in the presence of ventricular arrhythmia, flow is inadequate, particularly with a true assist device such as the Jarvik 2000. One death was attributable to adult respiratory distress syndrome thought to be secondary to coagulopathy that required significant blood transfusion. In nine patients, anticoagulation therapy was administered to maintain the international normalized ratio (INR) between 1.5 and 2.0. Anticoagulation was individualized to each patient’s overall clinical condition, according to protocol. Heparin was initiated at 12

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Table 3. Baseline and 48-Hour Postimplant Mean Hemodynamic Data; Laboratory Values at Baseline and Mean Values During Entire Support

Cardiac Output (L/min) Cardiac Index (L/min/m2) Heart rate (bpm) Systemic systolic BP (mm Hg) Systemic diastolic BP (mm Hg) Systemic mean BP (mm Hg) SVR (dynes) PA systolic BP (mm Hg) PA diastolic BP (mm Hg) PA mean BP (mm Hg) PVR (Wood Units) PCWP (mm Hg) CVP (mm Hg) BUN (mg/dL)* Cr (mg/dL)* Total bilirubin (mg/dL)* SGOT (U/L)* SGPT (U/L)* LDH (U/L)*

Baseline Values

Mean Values at 48 Hours

3.3 ⫾ 0.5 1.8 ⫾ 0.2 93.1 ⫾ 16.3 103.9 ⫾ 11.3 59.2 ⫾ 10.1 78.4 ⫾ 11.0 1702 ⫾ 297 43.9 ⫾ 11.0 22.2 ⫾ 5.0 30.0 ⫾ 7.0 2.6 ⫾ 1.7 21.7 ⫾ 4.0 9.8 ⫾ 3.3 23.1 ⫾ 10.4 1.2 ⫾ 0.4 1.5 ⫾ 1.3 70.2 ⫾ 109.2 82.8 ⫾ 181.0 411.3 ⫾ 551.5

6.1 ⫾ 0.5 3.5 ⫾ 0.4 109.2 ⫾ 9.3 94.8 ⫾ 11.9 70.2 ⫾ 9.0 78.4 ⫾ 7.5 886 ⫾ 100 40.4 ⫾ 8.6 20.6 ⫾ 3.5 28.3 ⫾ 5.8 3.3 ⫾ 1.4 10.3 ⫾ 3.8 10.6 ⫾ 6.4 22.8 ⫾ 3.9 1.2 ⫾ 0.3 4.0 ⫾ 3.7 95.7 ⫾ 39.1 60.4 ⫾ 49.5 634.0 ⫾ 279.8

BP, blood pressure; SVR, systemic vascular resistance; PA, pulmonary artery; PVR, pulmonary vascular resistance; PCWP, pulmonary capillary wedge pressure; CVP, central venous pressure. BUN, blood urea nitrogen; Cr, creatinine; SGOT, serum glutamateoxoacetic transaminase; SGPT, serum glutamate pyruvate transaminase; LDH, lactate dehydrogenase. Mean Valves at 48 h or * during entire support. Data presented as mean ⫾ sd.

Figure 4. Effect of systemic vascular resistance on cardiac index at various settings of the Jarvik 2000, an “afterload dependent” pump. Cardiac index increases as systemic vascular resistance decreases below 1000 dynes.

U · kg⫺1 · h⫺1 to maintain a target INR of 1.3–1.6, with warfarin simultaneously initiated at 5 mg IV or PO each day. Warfarin dosing was then adjusted to achieve an INR of 1.5–2.5. Antiplatelet therapy was added with dipyridamole (75 mg every 8 h PO) and aspirin (81 mg PO each day). Efficacy of antiplatelet therapy was monitored with a platelet aggregation study on the seventh day. However, one patient had

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chronic bleeding from a gastric ulcer and was supported for 244 days without anticoagulation (6). The average support duration was 81.2 ⫾ 57.9 days; the range was 13 to 214 days. In survivors, the average duration was 82.9 ⫾ 62.7 days, whereas in the 3 nonsurvivors, the average duration was 77.3 ⫾ 57.1 days. Two patients had superficial infections at the exit site of the power cable that did not alter the clinical course. With the small pump, ambulation was relatively easy and recovery relatively rapid. In fact, all survivors underwent complete physical rehabilitation during LVAD support and achieved NYHA class I cardiac status before reoperation for transplantation (6). Although the survivors could have gone home while awaiting transplantation, hospital discharge was not allowed (per protocol) in this initial feasibility study.

Discussion Anesthetic management of patients undergoing Jarvik 2000 insertion differs from that of other LVADs in several important respects. The physiology is unique in that flow is nonpulsatile and continuous. The left ventricle is offloaded and blood flow is provided throughout the cardiac cycle (6,7). Ideally, this pump acts as a true LVAD, functioning synergistically with the native pulsatility of the heart. However, if necessary, end-organ perfusion can be completely supported. Because the pump provides positive continuous pressure and flow during systole and diastole, end-organ perfusion is further augmented. The primary variables that determine blood flow through the Jarvik 2000 are the impeller speed and the mean arterial pressure (resistance) (6). Therefore, a unique anesthetic goal is to maintain relatively low mean arterial pressure (60 –75 mm Hg) and an accompanying low systemic vascular resistance, to optimize blood flow and organ perfusion. Anesthetic management for the Jarvik 2000 also differs in that a left thoracotomy approach is used. Hence, a repeat sternotomy is avoided in patients who have already undergone cardiac surgery. In patients who have not undergone prior surgery and who are receiving the pump as a bridge to transplantation, a left thoracotomy preserves the transsternal approach for the transplant procedure. This approach is greatly aided by left lung isolation, which may be accomplished with conventional endobronchial tubes or bronchial blockade. Not only does lung collapse improve surgical exposure, it also reduces the risk of trauma to the left lung, especially as patients must receive heparin. A brief period of anticoagulation for bypass minimizes the hypoxemia that can occur as a result of manipulation of the left lung after heparinization and the consequent intrapulmonary bleeding. Although the left thoracotomy approach (as opposed to a median sternotomy) does not allow the

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anesthesiologist direct visualization of the heart, TEE can be used for this purpose. The TEE examination is uniquely and critically important during and after implantation of the Jarvik 2000 to document correct intraventricular placement of the pump, centered at the apex of the left ventricle, with the inlet positioned in axial alignment with the mitral valve opening. Furthermore, it is desirable to verify the point at which the aortic valve opens as pump speed is decreased by 1000-rpm increments throughout the entire operating range. As the pump speed decreases, the pulse pressure increases. However, aortic valve opening is dependent not only on pump speed but also on left heart volume, which is monitored with TEE. Although pulsatile pumps markedly reduce left atrial pressure, continuous flow pumps ideally leave some residual volume in the left atrium (6). Unlike pulsatile pumps that work by completely unloading the left ventricle at flow rates of up to 12 L/min, the goal with the Jarvik 2000 is to assist rather than replace LV function. Therefore, it is necessary to maintain some residual volume in the left atrium and ventricle. Partial unloading can result in normalization of cardiac index by improving native ventricular function (3,11). By reducing LV volume and end-diastolic pressure, chronic partial unloading of the failed heart may eventually result in myocyte recovery (4,7–10). Maintenance of flow through the LV outflow tract and aortic valve is important after implantation of an axial flow device, not only to maximize the potential for eventual improvement of native ventricular function but also to minimize the risk of supraaortic valve stasis and thrombus formation (14). After CPB, right ventricular function and LV volume are continuously monitored using TEE. In particular, TEE is used to detect right heart failure, which can occasionally occur if LV volume is severely reduced in the setting of hypovolemia or high pump speeds. A centrifugal pump such as the Jarvik 2000 can create high flow, causing collapse of the left ventricle, with shift of the ventricular septum to the left side, possibly contributing to right ventricular dysfunction. Inotropic support of the right ventricle and reduction of pulmonary vascular resistance are important during any type of LVAD implantation because without a functioning right ventricle (or at least a right ventricle and pulmonary circuit that do not obstruct flow), the LVAD will not receive the preload required to provide adequate cardiac output. The achievement of both goals may be aided by the use of inotropes such as milrinone, dobutamine, or isoproterenol, which may have PA dilatory effects, or with drugs such as nitric oxide, prostaglandin E1, or nesiritide, which have a more direct effect on the pulmonary circuit. Because the Jarvik 2000 is “afterload dependent” and cannot pump as effectively against a high

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systemic vascular resistance, the use of inotropic drugs that also have systemic vasodilatory effects actually improves pump performance. Some patients, however, manifest very low systemic vascular resistance, either as an unwanted result of drugs used for right ventricular support or as a syndrome associated with severe heart failure (15). Vasopressin, which has systemic effects but relatively little effect on pulmonary vasculature, has proved useful in small doses (1– 4 U/h) (15,16). Some may consider epidural techniques to manage the postoperative pain associated with a left lateral thoracotomy approach, but because of the coagulopathy in severe heart failure patients preoperatively, the systemic anticoagulation intraoperatively, and the high risk of coagulopathy postoperatively, we have not used an epidural technique, nor do we recommend its use with this type of procedure. Surgical implantation of the Jarvik 2000 is markedly simplified compared with conventional LVADs (3,6). The Jarvik 2000 device is much smaller than the HeartMate and there is no intraabdominal surgery; hence, there is less bleeding (Table 2). Intraventricular placement obviates the need for an inlet cannula, thereby eliminating a source of stasis and later thrombotic complications. The continuous blood flow through the pump also eliminates the need for valves, an internal compliance chamber, or an externalized vent, which are necessary components of previous LVAD designs. The less extensive implant surgery shortens the duration of CPB and decreases surgical complications. With respect to long-term circulatory support with minimal pulse pressure, it is encouraging to note that end-organ structure and function are well maintained in both humans and animal models using the Jarvik 2000 (14,17,18).

Conclusions Anesthetic management of patients receiving a Jarvik 2000 implant is unique because of 1) the physiology of nonpulsatile continuous flow, with optimal pump function in the presence of relatively low mean arterial pressure and systemic vascular resistance; 2) implantation using a left thoracotomy approach, necessitating left lung isolation; and 3) unique use of TEE to document correct intraventricular placement of the pump and to demonstrate that the native heart is only partially assisted, whereby flow maintained through the LV outflow tract is adequate to cause aortic valve opening. The small size and ease of implantation and operation have otherwise simplified anesthetic management compared with conventional LVADs. Some of the patients who have received the Jarvik 2000 have

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CARDIOVASCULAR ANESTHESIA NUSSMEIER ET AL. ANESTHETIC MANAGEMENT OF THE JARVIK LEFT VENTRICULAR ASSIST DEVICE

had a body surface area of ⬍2 m2; thus, this technology is potentially lifesaving for smaller patients, especially women and children. Although further shortterm and long-term support studies are necessary, the initial positive anesthetic and surgical experience is promising.

References 1. Mets B. Anesthesia for left ventricular assist device placement. J Cardiothorac Vasc Anesth 2000;14:316 –26. 2. Nicolosi AC, Pagel PS. Perioperative considerations in the patients with a left ventricular assist device. Anesthesiology 2003; 98:565–70. 3. Frazier OH, Myers TJ, Jarvik RK, et al. Research and development of an implantable axial-flow left ventricular assist device: the Jarvik 2000 heart. Ann Thorac Surg 2001;71:S125–32. 4. Westaby S, Takahiro K, Houel R, et al. Jarvik 2000 heart: potential for bridge to myocyte recovery. Circulation 1998;98:1568 –74. 5. Westaby S, Banning AP, Jarvik R, et al. First permanent implant of the Jarvik 2000 heart. Lancet 2000;356:900 –3. 6. Frazier OH, Myers TJ, Gregoric ID, et al. Initial clinical experience with the Jarvik 2000 implantable axial-flow left ventricular assist system. Circulation 2002;105:2855– 60. 7. Macris MP, Myers TJ, Jarvik R, et al. In vivo evaluation of an electric intraventricular axial flow pump assist device. ASAIO J 1994;40:M719 –22. 8. Frazier OH, Benedict CR, Radovancevic B, et al. Improved left ventricular function after chronic left ventricular offloading. Ann Thorac Surg 1996;62:675– 82.

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9. Levin HR, Oz MC, Chen JM, et al. Reversal of chronic ventricular dilation in patients with end stage cardiomyopathy by prolonged mechanical offloading. Circulation 1995;91:2717–20. 10. Muller J, Wallukat G, Weng Y, et al. Weaning from mechanical cardiac support in patients with idiopathic dilated cardiomyopathy. Circulation 1997;96:542–9. 11. Frazier OH, Gregoric ID, Delgado RM, et al. Initial experience with the Jarvik 2000 left ventricular assist system as a bridge to transplantation: report of 4 cases. J Heart Lung Transplant 2001; 20:201. 12. Levy JH, Pifarre R, Schaff HV, et al. A multicenter, double-blind, placebo-controlled trial of aprotinin for reducing blood loss and the requirement for donor-blood transfusion in patients undergoing repeat coronary artery bypass grafting. Circulation 1995; 92:2236 – 44. 13. Baldwin RT, Duncan MJ, Frazier OH, et al. Patent foramen ovale: a cause of hypoxemia in patients on left ventricular support. Ann Thorac Surg 1991;52:865–7. 14. Siegenthaler MP, Martin J, van de Loo A, et al. Implantation of the permanent Jarvik-2000 left ventricular assist device. J Am Coll Cardiol 2002;39:1764 –72. 15. Gold J, Cullinane S, Chen J, et al. Vasopressin in the treatment of milrinone-induced hypotension in severe heart failure. Am J Cardiol 2000;85:506 – 8. 16. Morales DLS, Gregg D, Helman DN, et al. Arginine vasopressin in the treatment of 50 patients with postcardiotomy vasodilatory shock. Ann Thorac Surg 2000;69:102– 6. 17. Saito S, Westaby S, Piggot D, et al. End-organ function during chronic nonpulsatile circulation. Ann Thorac Surg 2002;74: 1080 –5. 18. Westaby S, Banning AP, Saito S, et al. Circulatory support for long-term treatment of heart failure: experience with an intraventricular continuous flow pump. Circulation 2002;105: 2588 –9.