CASE 6—1999 Off-pump coronary artery bypass graft surgery

CASE CONFERENCE Frederick A. Hensley, Jr, M D Solomon Aronson, MD, F A C C Section Editors

CASE 6--1999 Off-Pump CoronaryArtery Bypass Graft Surgery Andrew Maslow, MD, Solomon Aronson, MD, Eric Jacobsohn, MD, William E. Cohn, MD, and Robert G. Johnson, MD

Case Presentation*

The patient was a 69-year-old man with coronary artery disease and previous myocardial infarctions. He had presented to an outside hospital with unstable angina and was treated with coronary angioplasty and intracoronary stenting of the left anterior descending artery (LAD). The procedure was complicated by dissection of the LAD, severe ventricular dysfunction, and congestive heart failure requiring endotracheal intubation and mechanical ventilation. He was subsequently discharged home but then presented to this institution with unstable angina. Coronary angiography demonstrated 90% narrowing of the left main coronary artery as well as 90% narrowing of the proximal LAD, 70% narrowing of a large first diagonal artery, 90% narrowing of the ramus intermedius, total occlusion of the left circumflex artery, and total occlusion of the right coronary artery. There was an 80% in-stent stenosis of the middle portion of the LAD. Additional evaluation revealed a left ventricular ejection fraction of 20% to 30% with severe hypokinesis to akinesis of the inferior, posterior, anteroseptal, and anterior walls. There was apical wall dyskinesis. No intracardiac masses were seen. Right ventricular systolic function was normal. There was mild-to-moderate mitral regurgitation. Additional medical history included diabetes and peripheral vascular disease, for which the patient previously had an aorta-bifemoral bypass and right lower extremity femoralpopliteal bypass graft surgery. The preoperative hematocrit value was 36%. The patient was taken to the operating room for off-pump coronary artery bypass graft surgery (OP CABG) via a median sternotomy. After placement of two peripheral intravenous catheters, standard noninvasive monitoring, and an intraarterial catheter, a pulmonary artery catheter was placed. Baseline hemodynamics are shown in Table 1.

*S. Aronson,E. Jacobsohn, R.G. Johnson, and A. Maslow From the Department of Anesthesia, Rhode Island Hospital, Providence, RI; University of Chicago, Chicago, IL; Health Science Center, Winnepeg, Manitoba, Canada; and Department of Cardiothoracic Surgery, Beth Israel Deaconess Medical Center, Boston, MA. Address reprint requests to Andrew Maslow, MD, Department of Anesthesia, Rhode Island Hospital, Davol Building Room 129, 593 Eddy Street, Providence, R102903. Copyright © 1999 by W.B. Saunders Company 1053-0770/99/1306-0021510.00 Key Words: coronary artery bypass, stabilizer, anesthesia

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A general anesthetic was administered using thiopental, 150 rag; fentanyl, 500 lag, (7.0 lag&g); and pancuronium, 7 mg. After placement of an endotracheal tube, a 5.0-MHz transesophageal echocardiography probe (Hewlett Packard, Andover, MA) was placed. Maintenance of anesthesia was accomplished using isoflurane, 0.5% to 1.0%, and oxygen. Minute ventilation was kept constant at 4.5 L/rain. Baseline transesophageal echocardiography examination was consistent with the preoperative evaluation. There was mild nonmobile aortic atheromatous disease throughout. Magnesium sulfate, 10 g, was infused slowly after induction of general anesthesia and completed before manipulation of the native coronary arteries. Median sternotomy was performed, followed by dissection and preparation of the left internal mammary artery (LIMA). During this time, the left saphenous vein was harvested. Next, the pericardium was incised and retracted as is normally done for conventional bypass surgery. Additional deep pericardial sutures were placed posterior to the left phrenic nerve to facilitate exposure of the posterior and lateral myocardial walls. At this time, the operating room table was placed in steep Trendelenburg position and rotated to the right to facilitate mobilization of the heart and subsequent visualization, dissection, and grafting of the distal coronary arteries. Before manipulation of the heart, the systemic blood pressure was raised from 110/60 mmHg to 150/80 mmHg using a phenylephrine infusion. At this time, the heart was lifted and rotated to the right to visualize the circumflex artery and its branches. Tidal volumes were reduced while minute ventilation was maintained. Before placement of the coronary stabilizer (CS) (Genzyme, Cambridge, MA), heparin, 3 mg/kg, was given systemicallywith a goal of achieving an activated coagulation time (ACT) greater than or equal to 400 seconds. ACTs were subsequently assessed every 30 minutes, and additional heparin, 1 mg/kg, was given to maintain an ACT greater than or equal to 300 seconds.After this was done, the CS was placed using a seN-retainingsuspension apparatus and secured with silicone elastic tape placed in the myocardium and around the first obtuse marginal artery. This immobilized the planned site of anastomosis and provided a blood-free field. See Table 1 for hemodynamics. Vein grafts were constructed in the standard fashion. After each distal anastomosis was performed, the grafts were flushed with heparinized saline, 10 units/mL, demonstrating acceptable flow and surgical hemostasis. A sequential bypass was performed to the first obtuse marginal artery and to the first diagonal artery. Additional bypass was performed to the ramus intermedius.

Journal of Cardiothoracic and Vascular Anesthesia,

Vo113,No 6 (December),1999:pp 764-781

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Table 1. Hemodynamic Data During Off-Pump Coronary Artery Bypass Graft Surgery Baseline OM/Diag PDA

Heart rate (beats/min) Blood pressure (mmHg) Central venous pressure (mmHg) Pulmonary artery pressure (mmHg) Pulmonary capillary wedge pressure (mmHg) Cardiac output (L/min) Minute ventilation (L/rain) End-tidal carbon dioxide

75 130/60

LIMA

End

80 70 70 90 150/80 130~5 120/60 115/60

10

23

23

13

14

42/24

65/40

35~4

24/!2

30/20

20 4.5 4.5 40

35 3.0 4.5 35

20 2.0 4.5 32

10 3.2 4.5 38

15 4.3 5.0 40

respirations, and subsequently extubated within 10 minutes of arrival to the surgical ICU. The postoperative course was uuremarkable, and the patient was discharged from the surgical ICU on postoperative day 1 and from the hospital on postoperative day 4. DISCUSSlON1-

Evolution of Coronary Artery Bypass Graft Surgery

NOTE. Data include hemodynamic and pulmonary data before, during, and after cardiac manipulation. Of note is the elevation in central pressures and a decrease in cardiac output during cardiac manipulation. These changes returned toward baseline when the heart was returned to its normal position in the mediastinum. After the anastomosis of the left internal mammary artery (LIMAI to the left anterior descending artery, epinephrine was begun. Abbreviations: OM/Diag, obtuse marginal~diagonal arlery; PDA, posterior descending artery.

After these vessels were bypassed, the heart was rotated partially to the left and lifted further for subsequent bypass to the posterior descending artery (PDA). Vital signs during the procedure are shown in Table 1. After completion of the vein graft to the PDA, the heart was placed back in its normal position in the mediastinum. The LIMA was then anastomosed to the LAD using the CS. After completion of all distal anastomoses, the blood pressure was decreased to 85/50 mmHg before placement of tke partial occluder of the ascending aorta in preparation for proximal anastomoses. After completion of the proximal anastomoses and removal of the partial aortic cross-clamp, all grafts were deaired using a 30-gauge needle. After removal of the vascular clips, the grafts were perfused. All grafts were subjectively assessed using a 9.2-MHz pencil probe Doppler ultrasound (Ultrasonic Doppler flow detector 9.2 MHz; Parks Medical, Portland, Oregon). When graft flow was satisfactol?/ (phasic flow with dramatic augmentation and prolongation of the diastolic phase) and hemodynamics were stable, protamine was administered at a 1:1 ratio of heparin used. Echocardiographic examination showed similar wall motion abnormalities as before surgery. Given the amount of systolic dysfunction, an epinephrine infusion was started. After adequate hemostasis was obtained, the sternum was closed. Fluid administration consisted of 900 mL of cell-saved blood, 2 units of packed red blood cells, and 2 L of crystalloid. Urine output was 500 mL. Subsequent 100-pg doses of fentanyl were giwm when spontaneous respiration was present to keep respirator~ rate less than 15 breaths/min (total fentanyl, 800 lag or 11.4 pg/kg). At the completion of the surgery, pancuronium was reversed using neostigmine, 70 ~g/kg; glycopyrrolate was used to counteract unwanted side effects of the neostigmine. The patient was taken to the surgical intensive care unit (ICU), with spoataneous

CABG without cardiopulmonary bypass (CPB) was first reported in the mid to late 1960s and early 1970s. 14 One report of more than 200 patients undergoing bypasses to the LAD and fight coronary arteries demonstrated low mortality and comparable graft patency. 5 With the development and refinement of the CPB machine and cardioplegic techniques, off-pump (OP) myocardial revascularization fell out of favor for the preferred motionless, bloodless surgical field provided by CPB, aortic cross-clamp, and cardioplegic arrest. This field permitted the surgeon more time to bypass difficult vessels, such as intramyocardial, heavily calcified, or small arteries. Furthermore, the lateral walls of the heart (circumflex and obtuse marginal arteries) were considered inaccessible. Although OP CABG was not totally abandoned,6-8 only in the last decade has its popularity been renewed. 9-12 Several reasons that may have brought about the resurgence of OP CABG are (1) recognition of the multisystem adverse effects of CPB, (2) the drive toward less-invasive procedures, (3) shorter hospital stays, (4) reevaluation of hospital resources, and (5) the desire to decrease health care costs. 13-15 Although the performance of OP CABG by Buffolo et al6,9,13 may have been, in part, due to a decreased availability of resources, the avoidance of CPB and cardioplegia is also desirable. 1°-13,16 Although CPB bypass techniques have been refined, there are still significant associated adversities. This may be especially true in elderly patients, who may have a higher incidence of coexisting pathologies, especially relating to cerebrovascular disease. 17-19 If not clinically apparent, it is well known that elderly patients have less reserve function in systemic organ systems. 20 At this institution, OP CABG has been performed on patients with a wide spectrum of coronary artery disease and heart function (Table 2). Also, a large variety of coexisting diseases have been encountered (Table 3).

Coronary Artery Bypass Graft Surgery Without Cardiopulmonary Bypass A variety of approaches to less invasive coronary artery bypass now exist. One procedure called minimally invasive direct CABG (MID CABG) or lateral anterior surgical thoracotomy avoids the traditional median sternotomy for a smaller anterior thoracotomy incision,n-2s The typical patient who benefits from this procedure is one in whom revascularization is of a single vessel, either the LAD (most) or the right coronary artery 26 is considered adequate. Coronary lesions are located in the proximal portion of the artery. Not only does this procedure avoid CPB, but also a median stemotomy, with its attendant

?A. Maslow, S. Aronson, E. Jacobsohn, W.E. Cohn, mad R.G. Johnson

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Table 2, Patient Demographics for the First 64 Patients Undergoing Off-Pump Coronary Artery BypassGraft Surgery Age (yr) Male/female (n) Coronary artery involvement (n) Left main 1-vessel disease 2-vessel disease 3-vessel disease Right coronary disease Previous procedure (n) CABG PTCA/DCA/stent Left ventricular ejection fraction Mean % (SD) Range % ->50% (n) 31%-49% (n) -<30% (n) Drugs (n) Beta-blocker Calcium channel blocker Aspirin ACE inhibitors Diuretic Antiplatelet Insulin/oral hypoglycemic Digoxin Nitroglycerin Heparin Warfarin (Coumadin) Antiarrhythmics Levothyroxine (Synthroid) Number of vessels bypassed (n) 1 2 3 4 5 Emergency (n) Incision (n) Median sternotomy Thoracotomy

65.1 (11.2) 41/23 25 (39%) 9 (14%) 15 (23%) 40 (63%) 46 (72%) 4 (6%) 16 (25%) 46 (13) 14-65 39 (61%) 19 (30%) 6 (9%) 61 26 38 16 13 4 14 5 29 23 6 6 4 10 (16%) 14 (22%) 28 (44%) 9 (14%) 3 (4%) 2 63 1

Abbreviations: CABG, coronary artery bypass graft; PTCA, percutaneous transluminal coronary angioplasty; DCA, directional coronary artherectomy; ACE, angiotensin-converting enzyme.

risks of sternal maiunion or infection. Although initially intended for patients needing only bypass of a single lesion, it has also been applied to patients with multivessel disease, in whom complete revascularization was not believed to be necessary at the time of surgery. In these cases, bypass grafting of the LAD or, less frequently, the right coronary artery would be adequate. 22,23,27,28This statement has been supported by long-term studies showing that 10- and 15-year survival after CABG was correlated to patency of the internal mammary artery, despite occlusion of vein grafts. 29,3° Other patient types in whom this procedure has been applied include redo CABG and patients with left main coronary artery diseaseY ,27,28In the latter group, once the LAD has been bypassed and protected, the invasive cardiologist can then perform a percutaneous procedure on either the left main coronary artery or in the circumflex territory.

Percutaneous procedures can be performed in the right coronary artery territory as well. These hybrid procedures are well suited for patients with coexisting pathologies that may preclude CPB. Several approaches to MID CABG have been described. The most popular is a simple direct anastomosis of the LIMA to the LAD. 21-27Another approach is called H-Graft, in which a vessel conduit, either a piece of vein or peripheral artery, is placed from the LIMA to the LAD. 28 This technique avoids extensive dissection and mobilization of the LIMA and saves the distal portion of the LIMA for possible future anastomosis. Finally, thoracoscopic techniques have been used to dissect the LIMA and anastomose it to the LAD. 26 The appeal of thoracoscopic techniques is the avoidance of a long incision. There is a significant learning curve with thoracoscopic techniques, however, and access to the heart is reduced compared with procedures performed through longer incisions. Furthermore, these techniques do not currently preclude CPB. Although MID CABG has become popular, there still remains the desire for complete revascularization. In addition, the amount of discomfort caused by MID CABG was underestimated, prompting clinicians to incorporate epidurai analgesia into the perioperative care of these patients. 31With the advent of newer surgical techniques, it is possible to perform one to five coronary bypasses, OP, using a variety of approaches to the heart, including median sternotomy, left thoracotomy, and epigastric incisions, with the first-mentioned being the most comnlon.13,16,32 This approach can be applied not only to elective surgical cases, but also high-risk emergency situations. Table 3. Coexisting Diseases of 64 Patients Undergoing Off-Pump Coronary Artery BypassGraft Surgery CoexistingDisease

n

Coronary artery disease alone Myocardial infarction Intra-aortic balloon pump Preoperative Intraoperative Congestive heart failure Valvular disease Mitral regurgitation (rood) Aortic insufficiency (mod) Hypertension Tobacco/COPD Intubated preoperative Diabetes mellitus Rhythm abnormalities Atrial tachyarrhythmias Ventricular tachyarrhythmias Pacemaker Stroke/TIA/ca rotid surgery Renal Chronic renal insufficiency (Cr >2.0 mg/dL) End-stage renal disease (hemodialysis) Hypothyroidism Peripheral vascular disease Other*

4 34 6 1 12 5 1 32 23 2 14 5 1 1 4 4 2 4 6 9

Abbreviations: COPD, chronic obstructive pulmonary disease; TIA, transient ischemic attack; Cr, creatinine. *Other includes chronic lymphocytic leukemia, pulmonary embolus, systemic lupus erythematosus; heparin-induced thrombocytopenia/thrombosis, idiopathic thrombocytopenia, and seizure.

CASE 6-1999

Buffolo et al 1~ reviewed more than 1,200 cases. Their data showed improved outcome, reduced hospital stay, and decreased costs compared with CABG with CPB. Surgical cases included all types of patients, including emergent patients with unstable angina. OP CABG will be applied with greater frequency as anesthetic mad surgical technologies and techniques improve. The surgical techniques of Buffolo et a113and Tasdemir et al ~6were similar. Through a median sternotomy, dissection and preparation of the internal mammary artery and saphenous vein and a pericardiotomy were performed. The heart was manipulated medially, laterally, or superiorly depending on the coronary vessel to be bypassed. Heparin, 2 mg/kg, was administered to minimize clot formation. 13 Once located, sutures were applied proximally and distally to the site selected for arteriotomy and anastomosis. ~3 The sutures were snared, effectively clamping those segments of the artery. Tasdemir et a116placed a bulldog clamp 1.5 cm proximal to the planned arteriotomy, then the adjacent epicardium was lifted using pickups to provide a motionless surgical field, while the heart continued to beat. In the Buffolo study, 13 verapamil was used to slow the heart rate, simulating a near-motionless site.

Coronm~ Artery Stabilizers CS have been introduced to facilitate distal anastomoses. 31-33 The CS is placed on the epicardium, over the planned site of arteriotomy, to provide regional immobilization. Although earlier reports described the use of pharmacologically induced hradycardia/asystole to slow or arrest the heart to simulate a motionless field, 6-s,21-28,31,34-36 the use of CS has eliminated the need for this technique. 31,32 The first CS to gain acceptance was the mechanical stabilizer by CardioThoracic Systems, or the CTS coronary stabil:,:zer)3A motionless field is obtained by placing the mechanical platform on the epicardium at the site of the arteriotomy. The platform is fixed in position using articulating arms. One of the earlier reports using this system during anastomosis of the LIMA to the LAD yielded 96% graft patency, similar to that of conwmtional bypass? 3 The Octopus stabilization system (Medtronic, Inc, Minneapolis, MN) consists of two paddles, with four to five suction domes, connected to mobile arms, which are, in turn, attached to the operating table) 2The suction domes are placed adjacent and parallel to the site of arteriotomy. Suction is applied, via the domes, to immobilize the surgical field. If needed, additional traction can be applied. Microvascular clamps are used. proximal and distal to the site of anastomosis, to provide a bloodless field. Four bypasses have been reported using this system through a variety of incisions.32 The Cohn Stabilizer (Genzyme, Cambridge, MA) consists of three pieces that are connected to either the sternal retractor (median sternotomy) or the rib retractor (thoracotomy approach). Two metal arms articulate and secure a plastic square plate to the site of arteriotomy. The square stabilizer is secured to the site via silicone elastic tapes that have been placed deep to the proximal and distal portions of the targeted coronary segment. After placement at the desired location, the two arms are cleated in place, providing a stable, motionless stlrgical field. To eliminate bleeding at the site, the two silicone elastic

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tapes are tightened, resulting in proximal and distal occlusion of the coronary artery. With this system, one to five distal anastomoses have been performed through a median stenotomy, lateral thoracotomy, or a lateral anterior thoracotomy incision° One potential benefit of the Octopus system is that it lifts the anastomotic site as compared to the CTS and Cohn/Genzyme stabilizers, which compress the site. The latter two systems may compress the myocardium and potentially impair ventricular filling. It is not clear how significant the impact of the individual stabilizers is on filling, especially when compared with the effects of cardiac manipulation. An additional surgical technique that may be used during the performance of the distal anastomosis is an intracoronary stent. This stent is placed via the arteriotomy and allows coronary blood flow to continue while the surgeon performs the anastomosis. The obvious benefit is that the vessel does not need to be occluded distally and proximally. There is a risk of intimal dissection during placement of the coronary stent.

Surgical Procedure The surgery begins similarly to conventional bypass surgery. While the LIMA is dissected and prepared, saphenous vein is harvested from the lower extremity. If desired, other vascular conduits can be used (radial artery, gastroepiploic artery, right internal mammary artery). The initial bypasses are performed along the lateral walls of the heart supplied by the circumflex artery, its branches, and branches of the LAD. After these anastomoses, attention is directed to the posterior and right side of the heart, which is supplied by the posterior descending artery and the right coronary artery. After this, the LIMA is anastomosed to the LAD. The order of grafting can be changed to suit coronary dominance and areas of higher risk. Preparation for the periods of local ischemia include raising the blood pressure to offset the hemodynamic perturbations during cardiac manipulation. In addition, this action may help maintain or perhaps improve collateral coronary blood flow. 37-39 This is usually accomplished using a phenylephrine infusion. The blood pressure is raised as high as 160/95 mmHg before cardiac manipulation.Also the operating room table is placed in steep Trendelenburgposition and rotated to the right to facilitate mobilization of the heart as well as visualization, dissection, and grafting of the distal coronary arteries. Placing the bed in Trendelenburgposition may increase blood pressure by increasing cardiac preload. The heart is intermittently lifted to allow placement of deep pericardial sutures. These are placed posterior to the left phrenic nerve. When tension is placed on the sutures, the heart is lifted slightly upward, facilitating exposure of the posterior and lateral myocardial walls. The heart is further lifted, then rotated to the right to better visualize proposed targets and to prepare for placement of the CS. Before placement of the CS (Genzyme, Cambridge, MA), heparin, 3 mg/kg, is given systemically with a goal of achieving an ACT greater than or equal to 400 seconds. ACTs are assessed every 30 minutes, and additional heparin, 1 mg/kg, is given to maintain an ACT greater than or equal to 400 seconds. This maintenance is done to prevent thrombus formation in native arteries and bypass grafts and to allow emergent institution of CPB if needed. Silicone elastic tapes are placed in the myocardium, deep to the native artery, proximal and distal

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to the site of anastomosis. The CS is then placed using a self-retaining suspension apparatus and secured using silicone elastic tapes. After arteriotomy and assessment of the native coronary artery, the silicone elastic tapes are pulled tighter to provide a blood-free field. This would be considered ischemic time. Compared with conventional CABG with CPB and cardioplegic arrest, the iscbemia is regionalized. In addition to immobilizing the site, the CS has successfully provided a surgical field comparable to that seen when CPB and cardioplegic arrest are used. During the cardiac manipulation, placement of the stabilizer, and performance of the distal anastomoses, a combination of vasopressor (inotrope if needed depending on the patient's preoperative cardiac function) and fluid is used to maintain blood pressure. The patient's ability to tolerate the procedure is continuously assessed. If the patient is unable to tolerate the placement of the stabilizer or cardiac manipulation (refractory hypotension, arrhythmias, or increasing ST-segment changes), conventional CPB can be instituted. After each distal anastomosis is performed, it is hemostatically assessed and flushed with heparin, 10 ~/mL, and clamped. When all distal vein graft anastomoses are completed, attention is turned toward the LAD. The heart is placed in its normal position in the mediastinum. Either the LIMA or a vein graft is anastomosed in similar fashion. Before placing the proximal anastomoses, the blood pressure is lowered to 100/60 mmHg or lower. If a transesophageal echocardiogram probe were in place, the ascending aorta would have been assessed for presence of atheroma.4°,41 If need be, an epiaortic echocardiography probe (7.5 MHz) may be used to better assess the site of aortic manipulation.42 At this time, a partial cross-clamp is placed on the proximal ascending aorta to allow the performance of proximal anastomoses and maintenance of systemic perfusion. When all anastomoses are completed, all surgical sites along the heart and the aorta are hemostatically assessed. The grafts are then subjectively assessed by Doppler ultrasound. Adequate blood flow is described as phasic flow with dramatic augmentation and prolongation of the diastolic phase. Protamine is given at a 1:1 ratio to the dose of heparin used during the case, and ACT is obtained. Graft flow and hemostasis are then reassessed. If the patient is stable, the pericardium and sternum are closed, as would be done in conventional bypass surgery.

Patient Selection Patient selection for OP CABG has not been defined. Two large studies have demonstrated that OP CABG can be performed in a variety of patients with acceptable morbidity, including patients with stable and unstable angina or hemodynamics, single-vessel or multivessel disease, and a variety of coexisting pathologies. 13,16 Relative contraindications to OP CABG include patients in whom coronary artery visualization, dissection, and bypass may be difficult.43 This might include patients with intramyocardial, heavily calcified, long coronary lesions or small-caliber coronary arteries. Visualization of the target lesion may be more feasible during conventional CPB.43 Patients with large hearts (atria or ventricles) may present difficulties in visualization of the lateral and posterior aspects of the heart because there may be greater difficulty in manipulating

MASLOW ET AL

the heart owing to its size. Cardiopulmonary bypass with cardioplegic arrest empties the heart and allows more time for dissection and manipulation of the coronary artery and bypass graft. With improved technique and technologies, however, it is plausible to consider that all coronary lesions may be amenable to OP CABG. At this time, there are few, if any, data regarding patient selection for OP CABG. With adequate immobilization of the arteriotomy site and proximal and distal occlusion of the targeted coronary artery (or placement of a coronary stent), clinicians should be able to reproduce the conditions present during CPB, aortic cross-clamp, and cardioplegic arrest. As this technology improves, OP CABG will be applicable to a greater spectrum of patients.

Early Results Early results are positive in that a variety of patients have undergone OP CABG with comparable or lower morbidity (Table 4).44 Extubation times, intensive care unit stays, and hospital stays are favorable with a low cardiac mortality. In the first 64 patients, 2 patients died. One died of bypass graft failure. The second died 2 days after surgery. At autopsy, all bypass grafts were patent. Despite these new procedures, neurologic injury occurs at a similar frequency as with conventional bypass surgery.44 Type 1 neurologic injury (frank focal deficits) occurred in 3% of patients, which is consistent with data from conventional bypass surgery.44 One of the two patients had a history of stroke before surgery. Type 2 neurologic injury (seizures, intellectual or emotional changes) did not occur in the OP CABG. Depending on the testing, neuropsychiattic changes have been reported as high as 60%. 45 It is possible that type 2 injury may be decreased when CPB is avoided. Maintaining pulsatile flow and avoiding the inflammatory response and cerebral edema associated with CPB may minimize the incidence of neurologic injury. Type 1 injury, however, which may be due to microemboli or macroemboli, persists and may be related to ascending aortic manipulation. Ultrasound imaging of the ascending aorta may help decrease neurologic

Table 4. Perioperative Complications in the First 64 Patients Undergoing Off-Pump Coronary Artery Bypass Graft Surgery Complication

No. (%)

Myocardial infarction Atrial arrhythmias (new) Ventricular arrhythmias (new) Respiratory failure (ETT >48 hr) Stroke Pulmonary embolus Blood products during hospitalization Conversion to cardiopulmonary bypass Death

2 (3) 11 (17) 3 (5) 3 (5)* 2 (3)t 1 (1.5) 24 (37) 2 (3) 2 (3)¢

Abbreviation: E'I-F, Endotracheal tube. *Two patients were mechanically ventilated before surgery (one with a tracheostomy tube). The third patient suffered a stroke. tOne patient had a history of stroke. ~:One patient died immediately after surgery as a result of coronary bypass graft failure. A second patient had ventricular fibrillation on the 2rid day after surgery. At autopsy, this latter patient was shown to have widely patent coronary bypasses.

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injury by identifying significant atheromatous disease in the ascending aorta.4! Atrial arrhythmias occurred in 17% of OP CABG procedures (Tables 4 and 5), which is probably not significantly different from conventional bypass surgeries. Because atrial cannulation and resultant trauma are avoided, the cause of atrial alTbythmias is still not clear. There is a suggestion that magnesium may decrease the incidence of atrial arrhythmias in this population as it has in conventional bypass surgeries (Table 5).

Cardiac Protection: CardiopIegia The idea of cardiac protection dates back to the i[950s.46 Initial cardiac procedures were performed using cav~ inflow occlusion techniques to allow repair of simple congenital lesions. The heart was able to tolerate these brief period~ of low flow. The introduction of hypothermia allowed the myocardium to tolerate these brief periods of ischemia and permitted repair of more complicated cardiac lesions.47 Initial attempts at a chemical arrest were performed using a high-potassium ~olution infused through the coronary arteries.48 Although, in theory, arrest during diastole using high potassium seemed to be ideal, the high-potassium cardioplegic solution caused a primary injury to the heart. Subsequently, chemical arrest was made safer by lowering the potassium concentration in the caxdioplegic solution and adding several standard components. 49 These additional components of the cardioplegic solution include hypothermia (although this may not be as crucial), citrate to prevent accumulation of cellular calcium, acid buffel, :;odium and mannitol to prevent cellular edema, high-energy phosphate, dextrose, and more recently a mixture of blood and crystalloid to allow carrying and delivery of oxygen to the myocardium.5° Although there are many variations, the basic features of cardiac protection are consistent. One of the controversies surrounding CABG without CPB and cardioplegic arrest is the ability to protect the myoc~trdium during periods of ischemia. Supporters of cardioplegic arrest argue that cardioplegia attenuates myocardial injury during an ischemic period (aortic cross-clamp).5°,51 In comparison to OP CABG, cardioplegic arrest and aortic cross-clamp result in a prolonged period of global ischemia; whereas during OP CABG, ischemia is relatively brief (10 to 15 minute's) and regionalized to the area in which the graft is being placed. After placement of the distal anastomosis, the graft is flushed with heparin, and the proximal and distal silicone elastic tapes are removed (ie, coronary perfusion is restored). In cases in which a

Table 5. Data Regarding the Use of Magnesium and Its Relation to New Postoperative Atrial and Ventricular Arrhythmias for the First 64 Cases

Magnesium (n) Yes/no New postoperative atrial tachyarrhythmias All patients No magnesium Magnesium New postoperative ventricutar arrhythmias No magnesium Magnesium

23/41 (56%)

8/37 (22%) 3/22 (13%)

coronary" stent is used, coronary flow is not interrupted at any time. Two additional techniques include warm cardioplegia and the use of retrograde cardioplegia.5245 One relatively recent advance is the change from crystalloid cardioplegia to blood cardioplegia.56 This now widely accepted technique minimizes hemodilution from crystalloid cardioplegia while, perhaps, increasing oxygen delivery to the myocardium.56 Warm cardioplegia may allow enhanced delivery of oxygen to the cells and with hopes of minimizing ventricular dysfunction that may be caused by hypothermiaF ,Ss It is not clear, however, that warm cardioplegia is superior to hypothermic blood cardioplegia. 59 Retrograde cardioplegia allows delivery of cardioplegia to the myocardium via the venous system, which characteristically has no obstructions compared with diseased arteries.6°,6~ Although retrograde cardioplegia has advantages for delivery of cardioplegia to the left ventricle, delivery to the right ventricle may not be as uniform and may even place the fight ventricle at risk for injnry.53,55,62-65 The presumed advantage of cardioplegia is the reduction of myocardial metabolism during a period of reduced oxygen delivery. While metabolism is significantly reduced, it is not eliminated. Although cardioplegia does provide a significant degree of protection, it does not eliminate myocardial injury during the ischemic period. 5°,51 Furthermore, the duration of CPB and cardioplegia arrest is correlated with ventricular dysfunction seen on reperfusion of the myocardium.5°,5~

Closed-Chest Cardiopulmonary Bypass Another technologic development is closed-chest CPB with cardioplegic arrest.66-68 The central feature of this approach is the Heart Port Cardiopulmonary bypass system (Heartport, Inc, Redwood City, CA). This system has been described elsewhere and is not the focus of this report. Although the system has been shown to provide adequate cardiac protection during cardiac surgery, its role in CABG is yet to be determined. The idea of closed-chest CPB is to provide less-invasive cardiac protection. It does not, however, avoid adverse systemic effects of CPB (pulmonary, hematologic, cardiac, neurologic, renal, hepatic). 69 There appears to be a significant learning curve for the placement of the endovascular system. Direct and indirect costs may make it a less desirable option in various regionalized health care economies 69.70Early reports have shown reductions in intubation time and hospital stay when compared with each institution's historical data. There are no randomized, prospective controlled studies confirming these data available at this time. Finally, the use of the Heart Port system may be relatively contraindicated in patients with significant aortoiliac atheromatous disease, because it involves the passage of a long aortic cannula via the femoral artery into the ascending aorta. Aside from the potential for aortic injury, there may be significant risk for dislodgment of atheromatous debris. Technical difficulties may also be encountered if the aorta is tortuous.

Noncardioplegic Cardiac Protection 3/41 (7%) 0/22

One development that is applicable for CABG without CPB and cardioplegic arrest is ischemic preconditioning. For 10 to

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20 minutes, during the distal anastomosis, there is no flow through the coronary artery, and there is no protection. During conventional CPB, the delivery of cardioplegia is thought to minimize myocardial injury during the ischemic period.7],72 This protective effect is not present during OP CABG. Although the mechanism of ischemic preconditioning is unknown, it has been shown to decrease the amount of injury from subsequent ischemic periods. Although much of the literature has involved animals, there have been several reports in humans suggesting that ischemic preconditioning may be beneficial. Ischemic preconditioning is performed by occluding the coronary artery for a period of time followed by a period of reperfusion. There is significant species variation regarding the ideal time of occlusion, repeffusion, and number of times ischemic preconditioning should be performed. Evidence of ischemia as measured by ST-segment depression and elevation or transesophageal echocardiography evidence of systolic wall motion abnormalities during ischemic preconditioning have been seen infrequently. Diastolic function, as an early sign of ischemia, was not actively assessed. Because of the lack of ischemia, the benefits of ischemic preconditioning in this setting are uncertain. Potential benefits of the ischemic preconditioning maneuver may also be reduced by presence of chronic coronary artery narrowing, collateral vessels, and the confounding influences of anesthesia. It is possible that the presence of chronic narrowing with or without collateral vessels may present a natural form of low-flow conditioning. This possibility may explain why patients often do not complain of angina during percutaneous coronary angioplasty, stenting, or atherectomy. Also, under anesthesia, myocardial oxygen consumption may be reduced via changes in preload, afterload, and contractility. Finally, there are several pharmacologic agents that may provide preconditioning when administered before an ischemia period. Inhalation anesthetic agents, such as isoflurane, have been shown to have a protective effect on the myocardium during ischemia.73 Magnesium has also been shown to exert a protective effect when given before an ischemic period.74 For these reasons, the regular use of ischemic preconditioning has been abandoned. Buffolo et al6,933 and Tasdemir et a116 have described more than 3,000 cases of CABG without CPB. Neither group reports the use of ischemic preconditioning. In the former, the perioperative myocardial infarction rate was the same as in those patients in whom CPB and cardioplegia were employedY In the latter group, the perioperative myocardial infarction rate was 2.9%, and nonfatal low cardiac output state occurred in 2.8%.]6

Why Avoid Cardiopulmonary Bypass? The primary role of CPB is to divert blood away from the cardiopulmonary system and return it to the systemic arterial circulation. The use of CPB with cardioplegic arrest has allowed complex cardiac surgical procedures to be performed in a motionless, bloodless rid& Most patients who undergo surgery requiring CPB experience few identifiable adverse sequelae and subsequently convalesce normally. Nearly all patients experience an alteration in physiology in response to CPB which can, occasionally, result in a clinically apparent complication. The severe deleterious effects may manifest as the postperfusion syndrome, which may include one or multiple

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clinical signs, such as pulmonary dysfunction, renal impairment, neurologic dysfunction, Needing diathesis, increased susceptibility to infection, accumulation of interstitial fluid, leukocytosis, fever, or hemolysis.75-77 Despite major advancement of this technology, CPB is inherently a pathologic condition in which blood is continuously exposed to nonendothelial surfaces of the pump oxygenator circuit.78 This exposure activates a generalized inflammatory response resulting in alterations in the complement, coagulation, and fibrinolytic systems.7a,79 These responses vary from individual to individual. Although conventional bypass and blood cardioplegia both reduce myocardial oxygen consumption and provide dextrose, high-energy phosphate, and oxygen for basal metabolic function, they do not replace the patient's own pulsatile blood flow. It has been shown that the amount of time on CPB with cardioplegic arrest correlates with cardiac dysfunction.~1Whether this dysfunction is due to ischemia, myocardial edema, inflammation, or depression of beta-adrenergic pathway is not clear.5°,51,s°-s2 In addition to the heart, postoperative lung function is compromised as evidenced by increased alveolararterial oxygen tension gradients,a3-a7A variety of causes have been proposed, including atelectasis, pulmonary edema, inflammation, capillary permeability, and pleural effusions, s3-87 Although the effects of CPB on renal function have been debated,as the importance of maintaining adequate renal perfusion during heart surgery is highlighted by the significant mortality associated with new perioperative renal failure,as-9° Neurologic dysfunction has long been recognized as a major contributor to morbidity.19,45,91 Cerebral swelling has been reported in both hypothermic and normothermic bypass, with neither being more beneficial.92,93Other causes include coexisting cerebrovascular disease; carotid artery disease; and manipulation of the ascending aorta, during aortic cannulation or cross-clamping, which may create atheromatous embolization to the cerebral circulation.94 Aortic manipulation is not prevented by the use of a partial aortic clamp during OP CABG. Two of the first 64 patients undergoing OP CABG suffered neurologic complications. These injuries resulted in focal deficits and were classified as a type 1 neurologic injnry.44 As stated earlier, no type Ii dysfunction was reported. Although this type of injury may be due to emboli, neuropsychiatric changes may be due to a more generalized process, such as hypothermia, inflammation, or both. Hypothermia and inflammation are avoided, or at least minimized, by not instituting CPB. Derangements in the coagulation system are well known. 95,96 Both coagulation factors and platelets are affected by the extracorporeal circuit and hypothermia.97,98 There has been great interest in reducing the impact on the coagulation system by the administration of antifibrinolytic agents.99-1°] Much interest has been directed toward the systemic inflammatory response to CPB. se,m2-1°6 It has been thought that this response may contribute to reduced systemic vascular resistance, changes in pulmonary function, and other organ function. w2,]°3 The inflammatory response is equally present with both normothermic and hypothermic CPB. ]°4 Furthermore, the severity of the response is related to the duration of CPB. 1°7 Although there has been no documentation of changes in the inflammatory system with OP CABG, the inflammatory re-

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Table 6. Intraoperative Anesthetic Management of the First 64 Cases

Anesthetic technique (n) Induction agent (TP/Etom/Prop/Mid) Narcotic (fenta nyl/sufenta nil) Muscle relaxant (pancuronium/vecuronium Inhalation agent (isoflurane [forane]/other) Reversal (yes/no) Epidural Monitoring (n) Arterial line Central venous pressure alone Pulmonary artery catheter Transesophageal echocardiography Vasoactive agents (n) Phenylephrine Norepinephrine (Levophed) Epinephrine Dobutamine Calcium chloride Nitroglycerin Convert to cardiopulmonary bypass (n)

43/7/1/13 60/4 5,3/6 "34 32/32 1 64 27 37 55

64 "~3

4 1 4 37 2

NOTE. Data include anesthetic agents, monitoring, use of vasoactive medicines, and intraoperative intra-aortic balloon counterpulsation. Abbreviations: TP, thiopental; Etom, etomidate; Prop, propofol; Mid, midazolam.

sponse is suspected to be reduced. Although all organs may be affected by inflammation, it is possible that neurologic and pulmonary function are significantly affected, s2,91,1°2 Furthermore, proinflammatory cytokines have been considered significant contributors to postoperative myocardial ischer~Ja and cardiac dysfunction in otherwise uncomplicated coronary surgical procedures. ~°s Research on the anti-inflammatory effects of aprotonin and glucocorticoids has shown that both may reduce the amount of inflammation.82,~°2Advances in CPB technologies have been introduced to decrease or minimize the interaction of the bypass circuit and blood cellular componenti~.1°9-112 Heparin-bonded or heparin-coated bypass circuits have demonstrated reductions in contact activation, cytokine relea,ze, and generalized blood activation. 1°9m2 Despite all the advances in bypass technologies and knowledge of the pathophysiologic response to CPB, most clinicians believe that shorter bypass times result in less inflammation, cellular activation, and systemic organ dysfunction.

trending is used to monitor heart rate and for ischemia. If access to the heart is going to be limited (MID CABG) or potentially not easily accomplished (redo sternotomy), external defibrillator and pacing pads are placed. A transesophageal echocardiography probe is used to monitor cardiac function and for ischemia. Although ischemia monitoring is important throughout, it is most important during cardiac manipulation, placement of the coronary stabilizer, and performance of distal anastomosis. However, when the heart is lifted and rotated, it is difficult to assess left ventricular function. Echocardiographic imaging of the ventricle from gastric or esophageal views is difficult. In addition, tile pulmonary artery catheter and electrocardiogram data are also affected by cardiac manipulation. The policy at this institution is to reestablish a new baseline after the heart is in position for each anastomosis. During this time, cardiac function is visualized and subjectively assessed. If needed, epicardial echocardiography can be performed to assess ventricnlar function. The use of pulmonary artery catheters is a controversial topic. Previous reports have shown both safety and improved costs when pulmonary artery catheters were not used routinely. ~13,1~4 Initially the authors were selective in the use of pulmonary artery catheters. Currently, however, pulmonary artery catheters are placed in all patients undergoing OP CABG to monitor hemodynamic changes and guide therapy. Furthermore, pulmonary artery catheters are placed to obtain further information on the hemodynamic changes during cardiac manipulation. The future use of pulmonary artery catheters in OP CABG is likely to be reduced as it has in MID CABG patients. 31 Data suggest that the end-tidal carbon dioxide (ETCO2) monitor may be used to grossly assess blood flow returning to the central circulation. 115-~7In the case presented, there was a direct relationship between cardiac output and ETCO2. ETCO2, in arrest situations, has been shown to predict outcome. ~15It can also monitor changes in blood flow as long as temperature and minute ventilation are held constant.~17 Maintenance of stable blood pressure during OP CABG may pose greater challenges for the anesthesiologist than conventional CABG with CPB. Hemodynamic changes seen during heart manipulation include elevations in pulmonary artery pressure, pulmonary capillary wedge pressure, and central venous pressure, and a decrease in cardiac output. Hemodynamically, these changes may be suggestive of left ventricular systolic failure with right ventricular failure (Table 7). Subjective visual inspection of the heart shows preserved left and right

Anesthetic Management Anesthetic management has been described for MID CABG.31,34-36Evolution of both surgical and anesthetic management of MID CABG has been described. 31 In general, the concerns during OP CABG through a median stemotomy or thoracotomy are the same as those of conventional CABG with CPB. These include monitoring for and prevention of coronary ischemia, maintaininganesthetic depth and hemodynamic stability, and plans for postoperative care. Monitoring has included standard noninvasive techniques, an intra-arterial line (radial artery), and central cardiac catheter to monitor pressure and blood flow (Table 6). In addit, on, a five-lead electrocardiogram is placed with continuous threelead monitoring and continuous ST-segment analysis, and

Table 7. Hemodynamic Data Before, During, and After Cardiac Manipulation During Off-Pump Coronary Artery Bypass Graft Surgery for the First 64 Cases Premanipulation

CVP (mmHg) Mean PAP (mmHg) CO (L/min)

Manipulation

Postma nipulation

10.1 (2,9)

21,6 (5.9)

11,2 (3.6)

21.9 (6.3) 5.26 (0.8)

33.2 (10.2) 3.28 (0.8)

22.2 (4.8) 4.35 (0.9)

NOTE. Manipulation refers to superior and rightward displacement of the heart to visualize the posterior and lateral myocardial walls. Data are presented as mean SD. Abbreviations: CVP' central nervous pressure; PAP, pulmonary artery pressure; CO, cardiac output.

772

ventricular systolic function without enlargement of the cavities. Using intraoperative transgastric, esophageal, and epicardial echocardiography, changes have been seen in ventricular and atrial inflow patterns that are consistent with impaired diastolic filling of the left ventricle. In a different patient from that presented, transmitral flow patterns showed a reduction in the early velocity compared with that during atrial contraction (low transmitral E/A wave ratio). Pulmonary venous flow pattern demonstrates a blunted diastolic component. During this time, epicardial echocardiography showed stable ventricular systolic function and a reduction in the left ventricular cavity size. These changes are consistent with impaired diastolic function of the left ventricle. 118-121Changes in transmitral and pulmonary venous flow patterns are also affected by changes in loading conditions in addition to changes in myocardial relaxation, us,119,122 Regardless of the cause, it is apparent that the manipulation of the heart and placement of the CS result in some alteration in diastolic filling, whether it be mechanical or physiologic. As stated earlier, heparin is used to obtain an ACT equal to or greater than 400 seconds before manipulation of the coronary arteries. When all anastomoses are satisfactorily completed, protamine is administered to reverse the effects of heparin anticoagulation. Hemostasis is managed in similar fashion as during conventional bypass surgery. It would be expected that there would be less alteration in the clotting system because CPB is avoided. It has not been the authors' practice to administer antiflbrinolyticagents during OP CABG. After the distal anastomoses are completed, the heart is placed in its normal position in the mediastinum. At this time, the LIMA is anastomosed to the LAD. The hemodynamic profile returns to its baseline, provided that no injury has occurred. Doppler analyses also return to baseline. Blood pressure is decreased to 80 to 100/40 to 60 mmHg in preparation for partial cross-clamp of the ascending aorta and performance of the proximal anastomoses. If thought necessary, epiaortic echocardiography is performed to assess the extent of aortic atheromatous disease and to locate areas of minimal or no disease for the placement of the partial aortic cross-clamp and proximal anastomoses. Fluid management is based on ongoing assessment of the patient. During the time of cardiac manipulation, filling of the ventricular cavity may be difficult. Ventricular filling is not impaired when the heart is returned to its normal mediastinal position, and therefore fluid resuscitation is easier to perform. Cell saver is important for fluid management. Cell saver volumes range from 500 to 2,000 mL. Unless the procedure was performed through a lateral thoractomy, a single-lumen endotracheal tube is used. When a lateral thoracotomy is performed, a double-lumen endotracheal tube is used and single-lung ventilation employed. Other options include the univent tube or bronchial blockers. These latter options have been described for MID CABG. 36 In these cases, the dissection of the LIMA was facilitated when the left lung was deflated. This facilitation was especially important when thoracoscopic techniques were used. Reports of CABG without CPB and cardioplegic arrest described the use of pharmacologically induced bradycardia/ asystole to facilitate performance of distal anastomoses. 31,35,36

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Pharmacologically induced bradycardia/asystole would provide a relatively quiet surgical field, thus simulating the conditions of CPB with cardioplegic arrest. This practice raised concerns of hemodynamically significant bradycardia, especially because access to the heart was limited. Previous reports described the use of pacing pulmonary artery catheters and later percutaneous pacing/defibrillator pads (Zoll Pads, Biodetec Providence, RI). During OP CABG, performed through either a median sternotomy or a lateral thoracotomy, the access to the heart is not an issue. In addition, since the introduction of the CS, pharmacologically induced bradycardia/asystole is no longer used. Currently, pacing pulmonary artery catheters are placed only when there is a clinical indication for temporary pacing specific to the patient. At all times, the means to temporarily pace the heart and control heart rate must be available. This ability is more important during manipulation of the right coronary artery, especially if there is right coronary dominance. Pacing can be accomplished using a pulmonary artery catheter with pacing capabilities or simply by the placement of alligator clips or pacing wires by the surgeon. Regardless, a pacemaker should always be available for such an event. After bypasses are performed, ventricular pacing wires with or without atrial epicardial pacing wires are placed before closure of the sternotomy. Temperature control is achieved using a variety of methods, including low gas flows, passive humidifiers, fluid warmers, warming blankets (Bear Hugger [Augustine Medical, Wakefield, UK] a lower body blanket placed on the head and shoulders), and maintaining the operating room temperature at 70°E Temperature is monitored from the thermistor of the pulmonary artery catheter. If needed, a sterile Bear Hugger blanket is available to be placed on the lower extremities after the saphenous vein has been harvested. The cardiac anesthesia division at this institution has not routinely administered magnesium during these cases. There has been a suggestion that intraoperative magnesium has a role in patients undergoing CABG without CPB. Retrospectively, it was noted that there may be a reduction in new postoperative atrial and ventricular arrhythmias in patients who received intraoperative magnesium (Table 5). It is difficult to perform a statistical analysis on these data because they are not controlled or retrospective, and the dose of magnesium was variable. A similar reduction in postoperative arrhythmias was seen in a report on MID CABG patients. 31There are, however, other data to suggest that the routine use of intraoperative magnesium may be beneficial. 123,124 The anesthetic technique for OP CABG and median sternotomy is balanced anesthetic with the same goals as conventional CABG with CPB (Table 6). The intraoperative management is also geared toward early extubation, unless there was a perioperative event that dictated otherwise (eg, preoperative intubation, excess bleeding, hemodynamic instability, pulmonary dysfunction). A variety of induction agents have been used, including thiopental, propofol, and etomidate. Fentanyl has been the primary narcotic used at doses ranging from 5 to 20 gg/kg depending on age and stability of the patient. Muscle relaxation is generally achieved with pancuronium. Other agents, such as vecuronium, have been used depending on baseline heart rate (>---90beats/rain) and renal function. Isoftu-

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773

rane is used to supplement the anesthetic and to provide amnesia. With the exception of one patient undergoing OP CABG, postoperative pain management was treated with systemic narcotics with or without ketorolac tromethamine (Toradol), In one patient who underwent OP CABG via a left lateral thoracotomy, a thoracic epidural (T56) was used (0.1 cA bupivacaine [Marcaine] and 4 pg/mL of fentanyl). At the conclusion of the surgical procedure, patients who are to be extubated early are given neostigmine to reverse muscle relaxation. These patients are either extubated in the operating room or la~:erin the ICU (Table 8). The use of vasoactive agents is determined in similar fashion to that of conventional CABG. Preoperative cardiopulmonary function and intraoperative events determine the use of inotropes, vasopressors, and vasodilators. The use of vasoactive agents, especially inotropes, is not considered a contraindication to early extubation. Given that change from positivepressure ventilation to spontaneous (negative-pressure) ventilaTable 8. Times to Extubation, Intensive Care Unit Discharge, and Hospital Discharge of First 64 Patients Undergoing Off-Pump Coronary Artery BypassGraft Surgery Extubation Mean (days; SD) Operating room (n) Same day ICU (n) Postop day 1 (n) Other (n) ICU Mean (days; SD) Postop day 1 (n) Postop day 2 (n) Other (n) Hospital Mean (days; SD) Postop day 3 (n) Postop day 4 (n) Postop day 5 (n) Postop day 6 (n) Others (n) Deaths (n)

0.3 (0.5)* 6 36 19 3 (2 went to rehab with trach) 1.1 (0.4)t 57 3 4 5.8 (4.4)~ 12 19 11 10 10 2

Abbreviations: ICU, intensive care unit; Postop, postoperative. *Extubation: Does not include one patient who had been intubated and ventilated before surgery, who required intubation until the 8th day after surgery, and two patients who went to rehabilitation with a tracheostomy and assisted ventilation (one patient had tracheostomy before surgery, and the second had a major stroke in the perioperative period). tlCU discharge: Does not include two patients who were intubated and mechanically ventilated before surgery (10, 12 days) one patient who had an uncomplicated operative procedure but had a perioperative stroke (21 days), SHospital discharge: Includes one patient who had end-stage renal disease and was mechanically ventilated before surgery (12 days), a patient who was mechanically ventilated for pneumonia before surgery (19 days), a patient who suffered a large perioperative stroke (21 days), and a patient who presented with an infected hip prosthesis with sepsis and diffuse electrocardiogram changes consistent with ischemia (28 days). This last patient underwent off-pump coronary artery bypass graft surgery followed by a bipolar hip surgery. During the hip surgery, the patient suffered a cardiac arrest during the placement of cement and prosthesis.

tion can place a significant stress on the heart and increased workload on the diaphragm, the use of cardioactive drugs to help support cardiac function may help facilitate successful weaning from positive-pressure ventilation.~a5 COMMENTARY~:

Early Extubation and New Paradigms of Postoperative Care After Less Invasive Cardiac Surgery Most physicians agree that there is an urgent need to examine the current use of hospital resources; physicians have to increase efficiency and produce cost savings but at the same time improve the quality of care provided. Less invasive cardiac surgery techniques, among other advantages discussed earliel, attempt to do this. As the surgical techniques are becoming less invasive, it follows that the anesthetic and postoperative care of these patients should also become less invasive. An integrated, multidisciplinary fast-track pathway can do this. The fast-track program at this institution is called facilitated recovely pathway because the term fast-track has developed pejorative connotations to some patients. The cost of cardiovascular care in the United States, including hospitals, physicians, nurses, and drugs, was estimated to be about $260 billion in 1996 (Fact Book Fiscal Year 1996. National Heart, Lung and Blood Institute, 1997). Facilities that provide cardiovascular services experience increased demand at a time when total health care costs are increasing, and payers and governments are demanding lower costs. One estimate of the cost of 300,000 CABG procedures performed at approximately $40,000.00 per case is $12 billion, or 2% of all health care costs in the United States. a26 A significant anaount of this money is spent in the postoperative and ICU care of these patients. To continue to provide these services to all patients who need them, physicians have to become more cost-effective. This increased cost-effectiveness involves careful scrutiny of current practice and using evidence-based medicine wherever possible. Current paradigms of care have to be challenged; this clearly applies to the current way in which high-risk patients are managed in the postoperative period. How are cardiac surgical patients ventilated and routinely managed in an ICU in the postoperative period? The first report of ventilation of patients after high-risk surgery came from Bjork and Engstrom 127 from Stockholm in 1955. They described the use of the volume ventilator for the treatment of respiratory failure after pulmonary resection. In 1956, Bjork and Engstrom 1% described the use of mechanical ventilation in 61 thoracic surgical cases. An addendum to the article is the first report of postoperative artificial ventilation for patients who had undergone cardiac surgery. In 1959, Spencer et a1129 from the Department of Anesthesiology at John Hopkins University reported on the use of mechanical ventilation for patients after cardiac surgery. Of the 10 patients they described, 7 had cardiac surgical procedures (congenital heart surgery and valvular surgery). They concluded that mechanical ventilation was an effective form of management of people at high risk for respiratory complications after cardiac surgery. In 1962, Dammann et aF 3° from the University of Virginia School of

.~E. Jacobsohn, University of Chicago

774

Medicine described the perioperative management of patients after cardiac surgery. They proposed that all patients having cardiac surgery were at high risk for developing respiratory and cardiovascular complications and should remain deeply anesthetized and be returned to the recovery room or ICU and be mechanically ventilated. In another case series in 1963, the same group of investigators studied the work of breathing in 12 patients undergoing cardiac surgery. 13x They found that the work of breathing was increased in most patients after cardiac surgery; they believed they now had objective support for the prophylactic use of mechanical ventilation in patients after cardiac surgery. They also suggested that a similar application of mechanical ventilation be used in all other debilitated surgical patients or patients having major surgical procedures. Several more reports on the use of mechanical ventilation after cardiac surgery appeared after 1965-1966. All these reports proposed that patients having cardiac surgery should be routinely ventilated.~32,1~2a,~33Similar to many studies at this time, however, these were not prospective, randomized controlled trials. In one of these studies, Lefemine et a1133 compared the use of routine mechanical ventilation with a group of patients who did not have routine mechanical ventilation in previous years (control group). They found that patients having routine mechanical ventilation had better outcomes and lower morbidity, including less emergency tracheal intubation, less vasopressor use, and improved perioperative PaO2/PaCO2 and better acid-base status. The patients in the control ventilation group also had a lower incidence of atelectasis. Although the authors acknowledged that routine ventilation was not required in all patients, they thought that it was difficult to predict which patients would get into trouble and therefore proposed that all patients should be ventilated for at least 6 hours in the postoperative period. They described the best form of sedation for these patients as intermittent doses of morphine as well as continuous nitrous oxide administration. Patients having cardiac surgery in the 1950s and 1960s were generally very sick and had congenital heart disease or valvular heart disease, and the surgical, anesthesia, and CPB techniques were relatively "undeveloped" compared with today. This is particularly true if these patients are compared with patients undergoing less invasive surgical procedures. In 1970, Sykes et al134 from London reported on the effect of mechanical ventilation after open heart surgery. Although they supported the concept of mechanical ventilation postoperatively, they were the first to highlight that mechanical ventilation in itself has serious disadvantages and has in itself an associated morbidity and mortality. They proposed that patients be weaned to spontaneous ventilation as soon as possible and that extubation be performed as soon as stable blood gases are demonstrated on spontaneous ventilation. Just as it appeared as though the concept of routine postoperative mechanical ventilation was to be challenged, however, the development of narcotic-based anesthesia changed the face of postoperative care of high-risk patients. In 1969, Lowenstein et al x35reported on the use of high doses of intravenous morphine, 0.5 to 3 mg/kg, in patients undergoing cardiac surgery. They concluded that morphine stood in striking contrast to other anesthetic agents of the time, which uniformly had cardiac depressant effects. They proposed that morphine be used as an anesthetic agent in patients with

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minimal circulatory reserve undergoing major surgery. In 1972, Arens et al136 reported on high-dose morphine in 200 patients undergoing CABG procedures. They concluded from this study that analgesia and anesthesia were excellent and that high-dose narcotic anesthesia should be adopted in all patients undergoing cardiac revascularization procedures. This pattern of practice quickly became well established, and with the first description of high-dose fentanyl anesthesia for cardiac surgery by Stanley et al~38in 1978, the technique of high-dose narcotic anesthesia became standard practice in cardiac and other high-risk surgical procedures. In 1974, Midell et al ~39at the University of Chicago Pritzker School of Medicine published the first report of early extubation in patients having cardiac valve operations. In their report, only 10 of 100 consecutive patients having valve surgery required postoperative mechanical ventilation. These patients had anesthesia maintained with halothane; narcotics were used only sparingly in the postoperative period for pain. Their strict protocol for postoperative mechanical ventilation, combined with intraoperative inhalation anesthesia, showed that routine use of postoperative controlled ventilation for cardiac surgery was unnecessary. They concluded that not using mechanical ventilation simplified the postoperative care and avoided the complications associated with mechanical ventilation. In the next 2 decades, multiple studies comparing early versus late extubation after cardiac surgery were published. These studies resulted from economic pressures and evidence that anesthetic agents per se do not affect outcome after cardiac surgery. The first prospective, controlled trial of early extubation was performed by Quasha et 13_1140 at the University of California, San Francisco, and published in 1980; they showed that the practice was safe and saved money and that patients had a decrease in cardiopulmonary morbidity. Although many of the subsequent studies differed in design, most of them concluded that early extubation is safe and generally cost-effective. In only two of the studies is the issue of bypassing the intensive care unit addressed. In 1992, Chong et al141 in Oxford reported that more than 90% of 245 patients undergoing cardiac surgery were safely treated in a more economical area than the ICU. They based their management on an anesthetic technique that allowed early extubation in a designated cardiac recovery area. The level of care was rapidly deintensified. Patients were transferred to a general medical ward within 24 hours, often within hours of surgery. Chong et a1141 proposed that advances in the anesthetic, surgical, and perfusion techniques allowed this protocol to be safely instituted. In Chong's series, 85% of operations were completed within 90 minutes from incision to closure. In 1993, the same group 142 reported on 1,000 consecutive patients having cardiac surgery between 1990 and 1991; most of these patients were not admitted to ICU. They recovered in the special cardiac recovery area under the care of nurse-practitioners following a clinical pathway. Of the 1,000 patients, 45 were admitted directly to the ICU from the operating room based on preoperative or intraoperative risk factors. Anesthesia consisted of low-dose fentanyl and halothane-nitrous oxide. All patients were thoroughly rewarmed after the procedure. Of the remaining 955 patients, 10 failed to do well in the cardiac recovery area and had to be transferred to the ICU. After a few hours of recovery in the cardiac recovery area, patients had their arterial

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775

lines removed and were then managed on a general surgical ward. The cardiac recovery beds could therefore be reused several times a day. The overall mortality rate for the patients recovered in the cardiac recovery area was 1.4%, and the authors reported no adverse clinical sequelae that could be attributed to the area of recovery or that would have been prevented by routine admission to an ICU. They reported cost savings of about $1,000 in ICU nursing costs alone; they did not calculate cost savings for physicians, technicians, and ventilators. Attitudes toward postoperative care of cardiac surgical patients have not kept pace with the general improvements in cardiac surgery, cardiac anesthesia, and CPB techniques. Although Chong et al t41 and Westaby et a1142have shown that it is possible to have a rapid reduction in intensity of care and not use conventional ICUs, the standard approach has been to extubate patients earlier (but probably not early enough) and still manage them in an ICU for 24 hours. There appears to be a reluctance to accept that deintensification of therapy in the postoperative period is safe. In particular, most patients having OP procedures are suited to having a deintensified postoperative management plan. From 1995 to 1997, Jacobsohn et al143 developed a facilitated recovery protocol to expand the cardiac surgery program at their center. This facilitated recovery program is a multidisciplinary pathway that includes low-dose narcotic anesthesia, ( < 1 gg/kg sufentanil for entire case; maintenance of anesthesia with isoflurane; and minimal benzodiazepine use, maintaining normothermia), an initial 4- to 6-hour postanesthesia care unit-based recovery directed by both the anesthesiologist and the cardiac surgeon, elimination of routine ICU admission, and further recovery in a cardiac surgery stepdown unit for 24 hours.

The cardiac stepdown unit has no facilities for intravenous vasodilators, vasopressors, mechanical ventilation, pulmonary artery catheters, or maximum nurse-to-patient ratio 1:2; it is n o t an ICU referred to by another name. For this paradigm of care to become accepted by all caregivers, it was gradually introduced. In 1996, one patient per week was initially selected; by January 1997, most patients were being considered for this program. Pain is treated aggressively with a multimodal method, including intrathecal narcotics when not contraindicated, and nonsteroidal anti-inflammatory drugs. 144 Low-dose intrathecal morphine has been particularly successful; results show it is possible to obtain good analgesia with much smaller doses of intrathecal morphine (5 ~g/kg). Extubation was not delayed, and postoperative pulmonary function was improved, t45 Patients are mobilized within several hours of surgery; chest tubes (if present) are removed on the first postoperative day; and all intravenous fluids, catheters, and tubes are removed as soon as possible to enhance earlier patient mobilization and to create a mindset for a rapid recovery and mobilization. All patients having cardiac surgery at this institution are now considered for facilitated recovery without routine ICU admission. Final determination of recovery site is made when the surgery is completed and, in some cases, after initial admission to the postanesthesia care unit. If intraoperative and early postoperative events ( < 4 hours) have developed that would make facilitated recovery unlikely, transfer to the ICU is arranged. If the patient is not able to be transferred out of the postanesthesia care unit after 4 hours, a consultation is requested from the surgical ICU to assume ongoing management. Operating room records, ICU, and cardiac anesthesia databases were reviewed for the years 1994-1997 for pertinent data with respect to ICU use.143 As shown in Table 9, most patients are extubated within

Table 9. Results Showing Intensive Care Unit Use After Introducing the Facilitated Recovery Pathway

Total cases* ICU admissions (total/%) ICU bed days/100 cases/yr Day 1 APACHE II (mean _+ SD) In-hospital mortality (%) ICU LOS (days; median and range) Readmission to ICU from stepdown Time to extubation (hr) In OR 0-2 2-4 4-6 >6 Other Patients reintubatedl" In OR 0-2 2-4 4-6 >6 Other

1994

1995

1996

1997

212 212 (100) 224 14.9 ~ 5.9 5.7 1.0 (0.1-23,6) NA NA

289 289 (100) 185 13.9 +- 5,0 4.6 1.0 (0.1-27.5) NA NA

370 235 (63.5) 123 14.3 -+ 5,0 2.5 0.9 (0.3-67.5) NA NA

410 71 (17.3) 40.5 16,6 + 5.9 3.5 1.2 (0.2-40.5) 1 78 166 59 16 64 27

NA

NA

NA 1/78 2/166 0/59 2/16 6/64 n/a

Abbreviations: ICU, intensive care unit; APACHE, Acute Physiology and Chronic Health Evaluation; LOS, length of stay; OR, operating room; NA, not available. *All cardiac surgical procedures including thoracic aneurysm. ?lncluding cases complicated by bleeding.

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2 hours; the reintubation rate is low. There is a large reduction in ICU use, shown as the percent admissions and ICU days/100 cases/yr (p < 0.001, 1997 v all previous years and trend). The chance of ICU admission from stepdown is low. As expected, ICU length of stay in 1997 was longer than in 1996 (p < 0.01); this reflects the fact that patients who are admitted to the ICU are sicker. The Acute Physiology and Chronic Health Evaluation II scores increase would be expected (p < 0.01, 1997 v all previous years as well as trend). There has been no significant change in mortality. It is clear from the literature that the current style of patient care after cardiac surgery has to be reassessed. There is little or no evidence to support many of the common paradigms of care. This lack of support is even more evident when examined in terms of less invasive cardiac surgery. A multidisciplinary program for cardiac surgery based on early extubation and postanesthesia care unit/stepdown-based recovery can dramatically and safely reduce ICU use and lead to a less invasive postoperative course. This program is particularly suited for less invasive cardiac surgical procedures. There may be large potential cost savings with this model of care; the impetus against the introduction of such a model in most of North America has possibly been the fear of medicolegal repercussions; however, this fear appears unfounded. Clearly, the cost benefit in the U.S. model of care would be enormous. Much of what is done in the perioperative course is rooted in tradition and in uncontrolled studies; caregivers must challenge current paradigms of care and establish care plans based on evidence wherever possible. COMMENTARY§

The regional changes in myocardial flow subtended by each coronary artery into the various myocardial segments of the left ventricle are reflected by a flow-function relationship in each segment. The functional component of this assessment is easily derived with the use of intraoperative transesophageal echocardiography. Often the transesophageal echocardiography image is left in the short-axis midpapillary muscle plane (transgastric short axis) of the ventricles and is used for quick reference. It is important to ascertain whether this plane can be used as an easily reproducible image to monitor changes in regional wall motion. Smith et al146 have found that repositioning the transesophageal echocardiography probe at this level after inserting or withdrawing it by 2 cm yielded the same enddiastolic area and systolic area and no greater than one grade of regional wall motion abnormality difference. Rouine-Rapp et al147 reported that the midpapillary short-axis view detected only 17% of the regional wall motion abnormality episodes associated with intraoperative ischemia. Furthermore, they also found that single-planetransesophageal echocardiography imaging might miss 35% of all episodes of regional wall motion abnormalities and ischemia as compared with biplane transesophageal echocardiography imaging. The relationship between functional changes and flow has been adapted to evaluation of MID CABG. Aronson and

§S. Aronson,Universityof Chicago

Albertucci148 adapted the principle originally described by Allen for detecting ischemia distal to the wrist to a flow and function relationship of the myocardium. They describe the following technique: During observation (with intraoperative echocardiography) of the normal contraction and relaxation cycle of the heart, the surgeon simultaneously occludes the native LAD circulation and the LIMA-to-LAD anastomosis for 10 to 15 seconds, thus occluding blood flow to the myocardial regional subtended by the LAD. Evaluation of regional wall motion continues throughout occlusion of the native and graft LAD flow. The appearance of a new regional wall motion abnormality implies ischemically induced changes. In patients with extensive collateral circulation beyond the contribution of the LAD vascular bed, new acute regional wall motion abnormalities would not be expected. If adequate collateral flow to the region supplied by the LAD does not exist, persistent regional wall motion abnormalities are observed because of obstruction to the two main channels (native LAD and graft LAD) supplying the myocardial region of interest. On release of the LIMA-LAD graft, if regional wall motion returns to normal, adequate flow thorough the graft can be presumed. If on release of the graft, regional wall motion abnormalities persist, inadequate graft flow is suspected. 148 Occasionally the accuracy of regional ventricular function assessment is affected by the anestbesiologist's inability to grade regional wall motion abnormality subjectively or to adequately image portions of the left ventricle. To improve accuracy, several approaches have been developed to aid the detection of endocardial border and to quantify ventricular wall motion.149 The use of ultrasound contrast agents to improve detection of the endocardial border15°-152has been introduced by two independent investigators. Erb et a115° and Kim et a1152 demonstrated that the intravenous injection of an ultrasound contrast agent (Optison; MBI, San Diego) improved endocardial visualization and enabled novice echocardiographers to interpret regional wall motion and ventricular function with greater accuracy when compared with an expert. This simple maneuver (eg, intravenous injection of a contrast agent) allows rapid, accurate, and reliable interpretation of intraoperative echocardiography changes at a time when multiple tasks prohibit prolonged devoted attention to the echocardiography screen. The direct assessment of the myocardial flow component of the flow-function dynamic is under investigation. Performing surgery on a beating heart raises the concerns that the graft quality may be compromised. A convenient method for documenting intraoperative graft patency is desirable. Methods used for assessing the patency of the LIMA-LAD graft include visual examination and palpation of the graft, direct Doppler and electromagnetic flow probe measurements, coronary sinus thermodilution, and newer techniques such as thermal angiography and intraoperative selective internal mammary artery catheterization.153 Other options include postoperative angiography, but this has its obvious limitations. A novel intraoperative catheterization technique of catheterizing the LIMA via the radial artery has been described. 154,157Most of these methods, however, rely on new and expensive technologies and are not practical in most centers. Because transesophageal echocardiog-

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raphy is now routinely available in most cardiac surgery suites, using this technology to assess myocardial perfusion and graft patency is comparatively easy. The technique requires little training beyond the usual skills of intraoperative transesophageal echocardiography, and the incremental expense is small. Echocardiographic contrast agents have been used 10 assess cardiovascular function during cardiac surgery. 155a56The microbubbles reflect ultrasound and are excellent contrast agents. Sonicated albumin is isomolar, is nondiffusible, and has rheologic properties similar to that of erythrocytes. It has no significant effects on systemic, pulmonary, or coronary hemodynamics, and it is safe for intravenous and direct intracoronary injection. Jacobsohn et al ~57 described the use of contrast echocardiography during minimally invasive coronary artery bypass procedures. Just before completing the last two sutures in the LIMA-to-LAD anastomosis, the LIMA was retrogradely filled with a sonicated albumin ultrasound contrast medium. The contrast medium was kept in the vessel by means of a temporary occluding device on the LIMA that was placed as close to the anastomosis as possible. After the last few sutures were placed in the anastomosis (a step that usually requires <1 minute), the temporary clip was released, and the images were obtained. The contrast material that was contained in the vessel was then delivered to the area subtended by the LIMA-LAD graft. Although the volume of contrast medium injected into the vessel was small (1 to 2 mL), this was enough to allow the investigators to determine patency and to document the region perfused by the graft. The investigators commented that it would be easier to inject contrast agent proximally into the LIMA graft, but they were reluctant to do so because of fear of

damaging the graft. Intravenous contrast agents such as Optison (MBI, San Diego) provide a better signal-to-noise contrast effect observed in the myocardium than the older agent used in the study. Among the echocardiographic techniques employed to directly or indirectly assess the flow-function relationship of the heart, there remain limitations. These limitations include the fact that image acquisition may be hindered by surgical rotation of the heart to access coronary arteries. Furthermore, newly introduced devices designed to immobilize the anastomosis site may lift the heart away from the mediastinum, thereby reduciug the echocardiographic window. Also, the problem with poor visualization of certain ventricular segments may hinder the assessment of regional wall motion abnormalities. CONCLUSION

There is a trend toward reducing invasiveness and health care costs. Avoidance of CPB during CABG is becoming popular. Elimination of CPB and cardioplegia would not only decrease costs, but would also eliminate systemic organ effects that are a result of extracorporeal circulation. In addition, cardiac function may be better preserved if cardioplegia is not needed. A randomized, controlled study is yet to be performed. Several reports, however, demonstrate the safety and perhaps reduction in patient morbidity when compared with data from each institution using CPB. Although much skepticism may still exist regarding OP CABG, the further improvement in both anesthetic and surgical techniques will make OP CABG applicable to an even greater spectrum of coronary artery disease. OP CABG may eliminate the need for CPB in most patients, stable or otherwise.

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