Blood conservation strategies in Jehovah’s Witness patients undergoing complex aortic surgery: a report of three cases

CASE CONFERENCE Linda Shore-Lesserson, MD Mark A. Chaney, MD Section Editors

Blood Conservation Strategies in Jehovah’s Witness Patients Undergoing Complex Aortic Surgery: A Report of Three Cases Paul G. Loubser, MD, Steven M. Stoltz, BA,* Joseph D. Schmoker, MD, Frank Bonifacio, MD, Robert W. Battle, MD, Stephen Marcus, PA, Charles F. Krumholz, CCP,† David M. Moskowitz, MD, Aryeh Shander, MD,‡ and John H. Lemmer, Jr, MD§ Thoracic aortic surgery in Jehovah’s Witness (JW) patients presents a unique challenge to the surgeon and anesthesiologist because the patient’s religious-based objection to the use of allogeneic blood products impacts surgical technique and intraoperative fluid management methodology. Successful thoracic aortic repair without the transfusion of allogeneic blood products is especially difficult because the outcome of this type of surgery usually depends on the transfusion of relatively large amounts of allogeneic blood products.1 To maintain a treatment course congruent with the JW patient’s religious beliefs, alternative methods of blood conservation should be used by the anesthesiologist.2 Two cases are presented in which a JW patient underwent repair of a thoracoabdominal aneurysm (TAA), and a third case of a JW patient who underwent repair of an aortic root and arch aneurysm. All cases used acute normovolemic hemodilution (ANH) and underwent successful surgical repair without the use of allogeneic blood products. Case Presentations Case 1.* A 48-year old, 82-kg, hypertensive, nonsmoking JW man with an asymptomatic Crawford type II TAA was scheduled for elective surgical repair. Patient preparation for surgery included recombinant human erythropoietin, 300 U/kg/d, and oral iron supplements for 9 days. Pretreatment hemoglobin (Hb) was 10.8 g/dL and hematocrit (Hct) was 33%.

*P. Loubser and S. Stoltz From the *Department of Anesthesiology, McAllen Medical Center, McAllen, TX; Divisions of Cardiothoracic Surgery, Cardiology, and the Department of Anesthesiology, †Fletcher Allen Health Care and the University of Vermont, Burlington, VT; Divisions of Cardiothoracic Surgery and Cardiology, ‡Englewood Hospital and Medical Center, Englewood, NJ; and Department of Cardiothoracic Surgery, §University of Portland, Portland, OR. Address reprint requests to Paul G. Loubser, MD, 302 Lake Glen Court, Sugar Land, TX 77478. E-mail: [email protected] © 2003 Elsevier Inc. All rights reserved. 1053-0770/03/1704-0000$30.00/0 doi:10.1016/S1053-0770(03)00163-0 Key words: acute normovolemic hemodilution, blood conservation, Jehovah’s Witness, transesophageal echocardiography, thoracoabdominal aortic aneurysm, aortic arch, aortic root aneurysm 528

Preoperative echocardiography revealed normal right ventricular function, left ventricular hypertrophy, and left ventricular ejection fraction of 50%. Admission laboratory data were Hb ⫽ 12.9 g/dL, Hct ⫽ 37%, and platelet count ⫽ 209,000/␮L. Anesthetic management included induction with etomidate and maintenance with fentanyl, midazolam, pancuronium, and isoflurane. The trachea was intubated with a 39F left doublelumen endobronchial tube. A right radial artery catheter, right internal jugular introducer with oximetric pulmonary artery catheter (PAC), and transesophageal echocardiography (TEE) were used for hemodynamic monitoring. The patient was placed in the right lateral decubitus position, and ANH commenced via the PAC introducer side port. Autologous whole blood (AWB) was collected in collection bags containing citrate-phosphate-dextrose (CPD) using a gravitybased method. The ANH technique was modified so that the blood collection bags were kept connected to the patient’s side port at all times, to ensure continuity of the circuit tubing, and a continuous circuit between the patient’s circulation and the blood collection bags. The target Hb for blood sequestration was 9 g/dL and sequestered AWB was replaced with an equal volume of 6% hetastarch in lactated electrolyte solution (Hextend; Abbott Laboratories, Abbott Park, IL). The actual volume of blood to be sequestered was calculated using the standard equation: V ⫽ EBV ⫻ (Hbi-Hbf)/Hba, where V ⫽ volume of sequestered whole blood, EBV ⫽ the patient’s estimated blood volume (75 mL/kg), Hbi ⫽ the patient’s initial Hb, Hbf ⫽ the patient’s final or target Hb after hemodilution, and Hba ⫽ the average Hb (average of Hbi and Hbf).3 TEE was used during the blood collection process to monitor the volume status of the left ventricle and maintain normovolemia. One thousand five hundred milliliters of AWB were collected and were slowly continuously infused during the surgical procedure to mimic venous blood flow. An autotransfusion device was primed and connected to the patient before the commencement of any blood processing. After a test dose, 1 million kallikrein inhibiting units (KIU) of aprotinin were administered over 15 minutes followed by an infusion of 250,000 U/h. Using one-lung anesthesia, the TAA was resected and replaced with a 22-mm woven Dacron graft via a left thoracoabdominal approach. When the TAA was initially opened, blood within the aneurysm was transfused back to the patient via the autotransfusion device without processing to preserve

Journal of Cardiothoracic and Vascular Anesthesia, Vol 17, No 4 (August), 2003: pp 528-535

CASE 4 —2003

platelets and other coagulation factors. In addition to standard monitoring methods, TEE was used to monitor biventricular function and preload continuously. Hemodynamic stability was facilitated by the judicious use of nicardipine (2.5-10 mg/h), nitroglycerin (0.8-1.5 ␮g/kg/min), norepinephrine (2-16 ␮g/ min), and epinephrine (0.03-0.1 ␮g/kg/min). The aortic crossclamp duration was 30 minutes during which 16 units of autologous salvaged centrifuged blood were transfused. AWB was transfused following protamine reversal of heparin. The patient was transferred to the intensive care unit (ICU) on completion of surgery, where initial laboratory data revealed Hb ⫽ 7.9 g/dL, Hct ⫽ 23%, platelet count ⫽ 98,000/␮L, prothrombin time (PT) ⫽ 15.4 seconds, and activated partial thromboplastin time (aPTT) ⫽ 39.3 seconds. The patient’s trachea was extubated 8 hours after ICU admission, and he was transferred from the ICU on the third postoperative day. No postoperative cardiac, renal, pulmonary, or neurologic complications occurred. At discharge on the 10th postoperative day, the Hb ⫽ 9.2 g/dL, Hct ⫽ 28%, and platelet count ⫽ 144,000/␮L. Case 2.* A 65-year-old, 89-kg, nonsmoking JW man, with a prior history of inferior wall myocardial infarction and a Crawford type I TAA was scheduled for elective surgical repair. The patient received a preoperative course of recombinant human erythropoietin (300 U/kg/d) and oral iron supplementation for 6 days. Pretreatment Hb was 12.1 g/dL and hematocrit was 36%, which increased to Hb ⫽ 14.3 g/dL and hematocrit ⫽ 44% on admission to the hospital. The preoperative platelet count was 171,000/␮L. Transthoracic echocardiography revealed basal, midinferior, and inferoseptal wall hypokinesis; mild mitral regurgitation; and a left ventricular ejection fraction of 35%. The anesthetic technique described for Case 1 was similarly applied to this patient, including aprotinin, ANH, TEE, pharmacologic support with nicardipine, nitroglycerin, epinephrine, and norepinephrine and in-line autotransfusion. The trachea was intubated with a 41F left double-lumen endobronchial tube. Two thousand milliliters of AWB were collected to a target Hb of 9 g/dL. Using one-lung anesthesia, the patient underwent resection and graft replacement of the TAA with a 24-mm woven Dacron graft via a left thoracoabdominal approach. With the initial incision into the aorta, blood within the aneurysm was similarly reinfused without processing. After aortic clamping, TEE showed marked left ventricular dilation and decreased global contractility, necessitating the initiation of left atrial to femoral arterial partial bypass. The duration of aortic clamping was 51 minutes, and a total of 7 units of salvaged processed autologous blood was reinfused. After 17 minutes of aortic clamping, the patient’s heart rate increased to 120 beats/min, Hb decreased to 7.3 g/dL, and a new wall motion abnormality (WMA) was detected in the midanterior left ventricular segment, suggesting myocardial ischemia secondary to anemia. However, after transfusion of 2 units of AWB, the WMA promptly resolved. The remaining 3 units of AWB were transfused after protamine administration.

*P. Loubser and S. Stoltz

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Fig 1. CT scan of the chest with intravenous contrast showing the aneurysmal ascending aorta.

The patient was transferred to the ICU at the completion of surgery, where initial laboratory data revealed Hb ⫽ 10.9 g/dL, Hct ⫽ 32%, platelet count ⫽ 74,000/␮L, PT ⫽ 14.4 seconds, and aPTT ⫽ 38.2 seconds. The patient’s trachea was extubated 10 hours after ICU admission, and he was transferred from the ICU on the fourth postoperative day. No postoperative cardiac, renal, pulmonary, or neurologic complications occurred. At discharge on the 12th postoperative day, Hb ⫽ 14.1g/dL, Hct ⫽ 40%, and platelet count ⫽ 102,000/␮L. Case 3.† A 38-year-old man presented with a 3-year history of intermittent chest pain. Cardiac catheterization one and one half years earlier revealed dilation of his aortic root, ascending aorta, and proximal aortic arch, with no significant coronary artery disease. The aortic arch measured 5 cm by magnetic resonance imaging. He was started on ␤-blocker therapy and followed clinically but developed recurrent chest pain. Computerized tomography revealed that the aneurysm had expanded to 5.8 cm (Fig 1). Echocardiography showed no evidence of aortic valvular insufficiency or stenosis. On presentation, he was normotensive, 175 cm in height, and 130 kg in weight, with a BSA ⫽ 2.47 m2. Hb concentration was 15.8 g/dL, and his Hct was 46%. The patient agreed to surgical correction, to the use of a blood cell–scavenging system (Haemonetics, Braintree, MA), and intraoperative AWB donation, provided that his blood remained in continuity with his body through intravenous tubing. At operation standard physiologic monitoring was performed and included a radial artery catheter, an internal jugular vein introducer with pulmonary artery catheter, upper-extremity venous and external jugular vein catheters, and TEE. A standard inhalation/sedative-hypnotic/narcotic anesthetic regimen was used. The patient’s Hct was 41% before CPB. Four units of

†J. Schmoker et al

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AWB were removed before CPB and placed in citrate-containing bags with additional heparin. These were placed on an agitator next to the patient and remained connected to him by intravenous tubing. Full-dose aprotinin, heparinization without heparin-bonded circuits (ACT ⬎700 seconds), and CPB with roller pumps were used. The CPB prime was 1,400 mL of lactated Ringer’s solution. After cannulation of the distal aortic arch, CPB was instituted and systemic cooling ensued. The aorta was clamped, and the heart was arrested and cooled with blood cardioplegia and a cooling jacket (Daily Medical Products Inc., San Diego, CA). The aortic valve was found to be bicuspid, noncalcified, and freely mobile. The aortic annulus measured 25 mm, and the right coronary ostium was displaced 2 cm. The aortic root was replaced with a composite valve graft (CVG; St. Jude Medical, Inc, St. Paul, MN) with mobilization and direct reimplantation of the coronary buttons. After root replacement, deep hypothermic circulatory arrest (DHCA) was instituted at a nasopharyngeal temperature of 18°C and a bladder temperature of 19°C after completion of at least 30 minutes of cooling. The dilated proximal aortic arch and lesser curve were excised. The end of the CVG was tailored to the remaining aorta, and an end-to-end anastomosis was performed using a Teflon (Impra, Inc., Tempe, AZ) felt strip to bolster the posterior suture line. Retrograde cerebral perfusion was used during construction of the anterior suture line. Perfusion was reinstituted with controlled warming. The CPB, aortic cross-clamp, and DHCA times were 174, 106, and 28 minutes, respectively. During CPB, Hct values ranged from 28% to 33%. The patient was weaned from CPB in normal sinus rhythm with an Hct ⫽ 26%. The 4 units of AWB were reinfused after administration of protamine, and the final Hct recorded in the operating room was 31%. The salvaged blood volume was 150 mL and was not reinfused. The patient received a total of 4,100 mL of lactated Ringer’s during the case and had adequate urine output. Postoperatively, the patient had no significant bleeding. His ICU admission Hb concentration was 11.6 g/dL. He was discharged home on the fourth postoperative day on warfarin. At discharge, his Hb concentration was 12.0 g/dL, his Hct was 33%, and his international normalized ratio was 2.0. Erythropoietin and iron supplements were not used. The patient is doing well after 1 year of follow-up. DISCUSSION*†

Use of ANH to facilitate complete avoidance of allogeneic blood transfusion in JW patients undergoing TAA repair has not been previously described. ANH exerts its blood conservation action by reducing the quantity of red blood cells lost via surgical hemorrhage and by providing an intraoperative source of platelets and coagulation factors in fresh, sequestered AWB.3 A recent meta-analysis by Bryson et al4 questioned the efficacy of ANH in reducing allogeneic blood exposure, citing flawed experimental design in published studies. However, recent controlled studies by Cina et al5,6 examined the effect of ANH on coagulation parameters and blood transfusion in pa-

*P. Loubser and S. Stoltz †J. Schmoker et al

tients undergoing surgery of the thoracic aorta, reporting that patients undergoing ANH showed lower total allogeneic blood donor exposures and higher platelet counts postoperatively. Although JW patients uniformly refuse transfusion of all allogeneic blood products in accord with their religious beliefs,2 considerable variance may be encountered with respect to specific pharmacologic agents and/or blood conservation techniques. Therefore, the preanesthesia assessment and informed consent process should delineate the specific blood conservation paradigm for each JW patient. During the conduct of ANH, JW patients require that blood collection bags remain connected to their central catheter via a series of stopcocks, with a slow, continuous reinfusion of AWB blood to mimic venous blood flow.7 Choice of ANH replacement fluid should be discussed with the patient preoperatively. Albumin was refused by patients in this report because it was regarded as a product derived from blood. Six percent hetastarch in lactated electrolyte solution is preferable to 6% hetastarch in normal saline because the latter is limited by a dosage of 20 mL/kg and has the potential to produce coagulopathy.8 Rosengart et al9 have shown that ANH efficacy is dependent on collecting the “maximal” volume of AWB. Recombinant human erythropoietin stimulates red blood cell production and is particularly useful in preparing patients for TAA surgery. The rate and amount of Hb increase with erythropoietin are subject to individual patient variation and average 1.44 g/dL of Hb per week.10 Erythropoietin is more effective when preoperative Hb is ⱕ13 g/dL, having little effect when Hb is ⬎13 g/dL. Because Hb levels are increased preoperatively, the potential volume of intraoperative sequestered AWB also increases. However, delaying surgery to achieve higher Hb levels should be carefully weighed against the risks of TAA rupture. Although use of aprotinin for patients undergoing cardiothoracic surgery with cardiopulmonary bypass (CPB) is well established, recent evidence suggests that it may also reduce surgical bleeding and allogeneic blood transfusion for patients undergoing aortic aneurysm surgery.11,12 However, use of aprotinin for TAA surgery may be associated with increased renal morbidity. After intravenous administration, aprotinin is filtered by glomeruli, reabsorbed by proximal renal tubule and stored in phagolysosomes.13 The subsequent degradation of aprotinin by lysosomes is slow and similar to that of other small proteins (eg, insulin).13 Cross-clamping the thoracoabdominal aorta is associated with severe (90%) decreases of renal blood flow, glomerular filtration rate, and urine output.14 Furthermore, the incidence of postoperative renal failure in patients undergoing TAA surgery ranges from 25% to 50%.15,16 In addition, because aprotinin has “prothrombotic properties,” caution has been expressed about its usage for surgical procedures in which CPB is not used.17-19 A modified low-dose regimen of aprotinin was therefore selected for the above patients. In Case 2, because the priming volume of the left atriofemoral circuit and pump approximated only 250 mL, the addition of aprotinin to this circuit was not deemed necessary. Blood within the TAA itself may approximate 400 mL and should be immediately reinfused after surgical entry into the aneurysm. If a patient’s hemodynamic status permits, the reinfusion of sequestered AWB should be carefully coordinated with the surgeon’s efforts and, if possible, delayed until surgi-

CASE 4 —2003

cal hemorrhage is controlled. Postheparin reversal with protamine represents an optimal stage to reinfuse any remaining AWB because the transfusion of coagulation factors and platelets in fresh, whole blood would augment surgical hemostasis. The hematocrit in sequestered AWB is highest in the first unit collected, which should be reinfused first to augment oxygen delivery. On completion of the procedure, any remaining AWB should be transfused before patient transfer to the ICU. Although some TEE views are limited in the lateral decubitus position, TEE is a particularly sensitive monitor of ventricular function, preload, and myocardial ischemia.20-22 In these patients, a target Hb of 9 g/dL was selected as the endpoint for whole-blood sequestration. Bak et al22 examined TEE during ANH to a Hb of 8 g/dL in 8 anesthetized patients without heart disease. Systolic and diastolic ventricular function were not compromised, although cardiac output increased secondary to decreased systemic vascular resistance. The prompt detection of acute left ventricular failure after aortic clamping in case 2, using TEE, facilitated the immediate implementation of left atriofemoral bypass. In both patients, reliance was placed on autologous cell-saver blood to maintain oxygen-carrying capacity during the period of aortic crossclamping. However, development of a new WMA during aortic clamping strongly suggests myocardial ischemia secondary to anemia and should be promptly treated with nitroglycerin and transfusion of AWB.23 There are few published reports on the surgical correction of complex aortic disease in adult JW patients. These reports describe heroic operations in patients with life-threatening catastrophes.24,25 Elective complex aortic operations have not been routinely performed in these patients because of the usual need for blood product administration. Case 3 describes a strategy for the elective replacement of the aortic root, ascending aorta, and proximal aortic arch in a JW patient using DHCA. Decision making before operation in this patient included whether to preserve the patient’s functionally normal aortic valve or to use a valve substitute. The latter was chosen given that a bicuspid aortic valve was found at the time of operation. All potentially diseased tissue should be removed from these patients because repeat sternotomy is associated with high mortality.26 To decrease the risk for reoperation, a mechanical valve conduit was used in this patient for long-term durability, despite the requirement for life-long anticoagulation. The intraoperative use of cell-scavenging systems and intraoperative autologous blood donation can be life saving. Patients may agree to these modalities if a circuit is maintained in continuity with their bodies. In case 3, the authors did not reinfuse the patient’s scavenged blood because their system was not equipped to wash the low volume that was collected. To reinfuse low shed volumes, a pediatric collection bowl or a continuous autotransfusion device27 is recommended. If intraoperative blood donation is used, aggressive steps should be taken to prevent clotting. In case 3, heparin was placed in the CPD bags, and they were placed on a platelet agitator to prevent aggregation. Because of this patient’s large size, a large quantity of blood was removed before cardiopulmonary bypass (CPB) with standard pump priming. These authors have used retrograde autologous priming9 in other JW patients with suc-

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cess, but it was not necessary in this patient. Finally, although controversial in regard to decreasing blood loss associated with DHCA,28 these authors believe that full-dose aprotinin is safe and should be used as an adjunct to diminish bleeding. The operative technique in case 3 was modified to prevent blood loss. A cooling jacket was used in place of topical cold saline so that all shed blood could be directed back to the CPB pump. The authors also modified their cannulation technique. The usual method is to perform right axillary artery cannulation, with innominate artery clamping during DHCA, for delivery of antegrade cerebral perfusion. Instead, in this patient they cannulated the distal aortic arch to avoid a separate incision, so that all shed blood would be kept in 1 field for scavenging. It could be argued, however, that using continuous antegrade cerebral perfusion via the axillary artery in conjunction with moderate hypothermia (at 24°-28°C)29 could decrease total CPB time. This could potentially decrease coagulation abnormalities compared with those known to occur during longer bypass runs and deep hypothermia. When replacing both the aortic root and aortic arch, the authors’ standard technique is to first replace the arch with a separate graft, perform the root replacement while rewarming, and then perform a graft-graft anastomosis after the root replacement is completed. Instead, the root replacement was performed first and the end of the CVG was brought up for direct anastomosis to the arch. This eliminates a suture line but also makes it more difficult to access bleeding along the posterior part of the anastomosis. Therefore, a Teflon strip was incorporated into the posterior suture line as a bolster. Biologic glue was not used. Pacing wires were not placed in this patient because sinus rhythm was restored after CPB, there was no evidence of a bundle-branch block pattern on telemetry, and there was a small but real risk of bleeding with their removal. If pacing is required, a less morbid option would be the insertion of a temporary transvenous ventricular pacing wire through an introducer in the jugular vein. Temporary epicardial pacing wires could be inserted and then simply cut at skin level after use to avoid potential problems with bleeding. This latter option may expose the patient to an increased risk of mediastinal infection. Autotransfusion of mediastinal blood from the chest tube canister was not necessary given insignificant postoperative bleeding. COMMENTARY 1‡

These case reports show the ability to successfully perform complex thoracoabdominal aortic surgery, which is usually associated with major blood loss, without the use of allogeneic blood products (ABPs). Because of the risks associated with allogeneic blood transfusion, blood conservation and the tolerance of acute anemia have become increasingly important.9,30-33 Lessons from the coordinated care that was applied in these cases can be applied to all patients. JW patients refuse transfusion of whole blood, red blood cells, white cells, and platelets. Products containing plasma fractions (eg, immunoglobulins, albumin) are a matter for personal decision. JW patients believe that blood removed from

‡A. Shander and D. Moskowitz

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Table 1. Surgical and Anesthetic Principles of Blood Conservation with Bloodless Management 1. Preoperative assessment planning: management of anemia, management of anticoagulation and congenital and drug-induced coagulopathies, prophylactic interventional radiology/embolization, prescribing/scheduling of cell salvage apparatus, restricted diagnostic phlebotomy. 2. Intraoperative blood conservation: meticulous surgical hemostasis, blood salvage, hemodilution, pharmaceutical enhancement of hemostasis, maintenance of normothermia, surgical positioning to minimize blood loss and hypertension. 3. Postoperative blood conservation: blood salvage, tolerance of anemia, optimum fluid and volume management, restricted diagnostic phlebotomy, adequate analgesia, maintenance of normothermia. 4. Maintain appropriate fluid resuscitation. Significant normovolemic anemia is well tolerated in hemodynamically stable patients. 5. In actively bleeding patients, the first management priority must be to stop the bleeding. Avoid attempts to normalize blood pressure until hemorrhage is controlled. 6. Prevent or treat coagulation disorders promptly. 7. Oral or parenteral iron may be used to improve iron stores. Recombinant (synthetic) human erythropoietin (rHuEPO) effectively increases red cell mass. 8. Hematology/oncology: aggressive rHuEPO and iron therapy for prophylaxis of anemia, individualized chemotherapy protocols to minimize hematologic toxicity, pharmacologic prophylaxis and treatment of bleeding, tolerance of anemia, and restricted diagnostic phlebotomy.

the body should be discarded and therefore will not accept transfusions of stored autologous blood components such as preoperative autologous donated blood products. They will, however, accept autologous blood obtained intraoperatively. Thus, intraoperative and postoperative cell salvage, ANH, plasma sequestration, and CPB can all be used for the consenting JW patient, providing a circuit is established with the patient’s own circulation. It is the JW community that has led medicine to increasingly adopt measures for blood conservation. The informed medical community now considers a blood transfusion akin to an organ transplant. Many articles have identified a significant association between allogeneic blood transfusion and recurrence of cancer and increased rates of postoperative infection.34-40 Infectious complications, immune modulation, and a shortage of blood products are bringing blood conservation strategies to the forefront for all patients. It is difficult to conduct prospective, randomized, and blinded clinical trials comparing groups who do or do not receive ABP because of logistic and ethical considerations. A review of 16 reports of the surgical outcome in JW patients who were not given ABP during major surgical procedures resulted in a mortality rate of 0.5% to 1.5% because of anemia.41 Nonetheless, the hematopoietic reserve is substantial. One recent landmark article supporting tolerance of anemia was a randomized, controlled trial involving 838 euvolemic critically ill patients. A restrictive RBC transfusion strategy (hemoglobin level between 7 and 9 g/dL) was associated with significantly lower mortality rates and was at least as safe and probably superior to a liberal transfusion strategy (hemoglobin level between 10 and 12 g/dL).42 In studies involving patients with cardiovascular disease undergoing CPB, a lower hemoglobin threshold was not associated with any increase in morbidity or mortality.43,44 In fact, higher hematocrit on admission to the intensive care unit was a multivariate risk factor for postoperative myocardial infarction.44 Recent confirmatory data from 2 studies totaling 4,670 patients indicated that transfusions themselves are independently associated with both increased multiorgan failure and mortality.45

The current case reports add significantly to a sparse literature regarding transfusion-free complex cardiothoracic surgery. Rosengart et al9 successfully applied a blood conservation strategy for operating without ABT in 50 consecutive adult JW patients undergoing cardiac operations at a single institution. Successful management of individual JW patients undergoing complex cardiac and aortic surgery with CPB and/or DHCA has been described.24,25,31,46 Taken together with the current reports, exposure of patients to ABT can be minimized or avoided by the systematic use of multiple blood conservation techniques. Strategies for perioperative blood conservation are well described and use appropriate combinations of hematopoietic and hemostatic drugs, technological devices to reduce blood loss or recover shed blood, and surgical techniques.30,47,48 The importance of surgical technique and meticulous hemostasis cannot be overemphasized. Every attempt must be made to avoid unnecessary bleeding because all of the appropriate blood conservation techniques are only effective when used in concert with meticulous surgical hemostasis. Table 1 gives an overview of blood conservation strategies in the perioperative period. Blood conservation programs demand an interdisciplinary team approach, combining medical, surgical, and other specialists who share a commitment to avoiding the use of allogeneic blood transfusion. Experience and commitment to blood conservation are necessary to create a successful program. These reports nicely convey the extent of presurgical planning that is necessary for a successful outcome. They reiterate that with proper care, most of the cases can be performed successfully without the use of ABP. A team approach involves thorough careful preoperative evaluation and prophylaxis (eg, erythropoietin therapy, screening for underlying coagulopathies), a dedication to “every drop of blood counts,” meticulous surgical technique and hemostasis, aggressive cell recovery within accepted guidelines, the use of hemodilution as a standard practice in high blood-loss surgeries, accurate volume assessment and fluid replacement, and the use of appropriate point-of-care testing to facilitate rational clinical care. When carried out cooperatively, the result is particularly rewarding as the efforts presented here show.

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COMMENTARY 2§

The challenge of performing cardiac or thoracic aortic procedures on patients who categorically refuse blood product transfusions arises infrequently but not rarely. In the authors’ practice, JW patients accounted for approximately 1% (137 of 12,560) of such procedures performed over the recent 10-year period. Thus, it is useful to have a management plan (“Bloodless Surgery Program” [BSP]) for these special patients. It is also useful for the participating doctors to have some understanding of this religion-based proscription, although agreeing with it is not a prerequisite to treating the JW patient.49 The magnitude of the challenge of the JW patient depends not only on the usual risk factors such as age and ventricular function but also on additional factors that impact the potential need for blood product transfusions. These factors include the patient’s preoperative red cell mass (a function of patient size, sex, and hematocrit), the presence of drugs that may contribute to bleeding (eg, antiplatelet agents, low–molecular-weight heparin), the complexity of the planned surgery, and the primary or reoperative nature of the surgery. Clearly, “big” operations in JW patients, such as those described in these reports, warrant special considerations that impact all phases of the surgical experience. Preoperative Considerations An important aspect of the preoperative preparation for BSP cardiac surgery is the preoperative meeting with the patient, his/her family, and (if possible) a representative of the JW church. At major BSP programs, JW representatives may have an office in the hospital, are available for consultation, and often have a very active role in outlining the patient’s transfusion restrictions. Not all JW patients follow the exact same restrictions, with some decisions being matters of individual conscience. For example, some JW patients will accept transfusion of cryoprecipitate because this is a highly purified product; others will not. For many JW patients, the use of coagulant adjuncts such as BioGlue Surgical Adhesive (CryoLife International Inc, Kennesaw, GA) and FloSeal Matrix (Fusion Medical Technologies, Inc., Mountain View, CA) are acceptable as these products contain bovine, but not human, components.50,51 Similarly, many JW patients will accept purified products such as antithrombin III concentrate (Thrombate III威; Bayer Corporation, Elkhart, IN), which may be necessary for the heparinresistant patient requiring CPB because fresh frozen plasma would not be permitted. For most JW patients, the intraoperative use of the blood salvage device (eg, cell saver) is acceptable as long as there is uninterrupted flow from the device bowl to the patient. Similarly, most patients will accept the use of ANH, also known as intraoperative autologous donation, as long as the removed blood is kept in continuous contact with the patient. Clearly, it is best for these decisions to be made and documented before undertaking surgery. Before elective surgery, it is important to raise the patient’s red blood cell volume to a high normal level. In practice, this is accomplished with erythropoietin and iron administration.52 The aim is for a hematocrit level of approximately 45%. If the

§John H. Lemmer Jr.

procedure is urgent, a preoperative dose of erythropoietin is given with the expectation that this will stimulate postoperative hematopoiesis and thus improve recovery. All drugs that may contribute to bleeding are stopped before surgery, with the exception of unfractionated heparin that may be required to treat unstable angina or endocarditis. For the patient with unstable angina who has received aspirin, intravenous heparin may be continued for 3 to 5 days while the aspirin effect is allowed to wear off. After 4 days of not receiving aspirin, about 50% of the patient’s circulating platelets should be unimpaired. Likewise, clopidogrel’s irreversible platelet effect should be reduced after 4 to 5 days of abstinence. Low–molecular-weight heparin, when given within about 24 hours of cardiac surgery, increases perioperative bleeding and the need to return the patient to the operating room for postoperative bleeding.53,54 Thus, if preoperative anticoagulation of the patient is required, it is preferred to switch the patient from low–molecular-weight heparin to unfractionated heparin for at least 24 hours before surgery. The patients described in these reports were all men with body weights above 80 kg. Preoperative hematocrit levels were 37%, 44%, and 47%. Consideration of preoperative erythropoietin treatment might have been given to the patient with the lower red cell mass, assuming the operation was elective, allowing time for hematopoiesis to occur. Intraoperative Considerations The reports detailed in this case conference describe a number of intraoperative techniques to reduce bleeding and the need for blood product transfusion. Clearly, meticulous technique with a clear-cut operative plan that minimizes aortic cross-clamp, CPB, and total surgical times are of prime importance. The surgical times for the complex procedures described in these reports are very commendable and clearly were important contributors to the successful outcomes described. Central to these case reports is the use of ANH. With this technique, whole blood is withdrawn from the patient and stored in anticoagulant-containing bags that are kept in continuity with the patient (with the blood being continuously transfused back to the patient at a very low rate). After the administration of protamine, the remaining blood is given back to the patient. ANH clearly reduces the need for red blood cell transfusion. Because the sequestered blood is protected from the detrimental effects of CPB, this technique may preserve coagulation factors and platelet function resulting in reduced postoperative bleeding, although evidence in this regard is not entirely conclusive.55,56 In any event, ANH is safe and effective and should be strongly considered for all JW patients and for appropriate non-JW patients undergoing surgery using CPB. One note of caution, however; it is possible to overfill the anticoagulant-containing collection bag and thus exceed the capacity of the bag to keep the blood anticoagulated. This can lead to clotting of the withdrawn blood. This intraoperative bloodletting would, of course, be very counterproductive. The patients described in these reports received aprotinin. This drug, an inhibitor of the serine proteases, reduces bleeding and the need for blood product transfusions in patients undergoing cardiac surgery using CPB.57,58 Aprotinin has a very favorable safety profile, including use in patients undergoing DHCA so long as adequate anticoagulation with appropriate

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monitoring is used.28 Experience in using aprotinin for patients undergoing ascending, arch, descending, and TAAs has been described.25,59 Aprotinin is clearly indicated for all JW patients undergoing CPB operations and those undergoing major thoracic aorta operations such as those described in this case conference. The full dose regimen (2 million KIU load, 2 million KIU in the pump prime solution, and continuous intraoperative infusion at 500,000 KIU per hour) is recommended. Interesting technical considerations are described in the patient undergoing ascending aorta and arch replacement. In this patient, only the proximal arch was aneurysmal, and it was possible to cannulate the aorta distally through the sternotomy incision. Performance of the root replacement first followed by direct anastomoses of the distal end of the graft to the arch is a bit unconventional but did eliminate a suture line and save time, both important factors for reducing bleeding. The authors also did not place a pacing wire to reduce the chance of bleeding. Many surgeons would place a single bipolar ventricular wire. Before the patient’s discharge from the hospital, the wire can be placed on tension and cut at skin level; the end will then retract into the subcutaneous tissue and not be a problem. Unexpected complete heart block can occasionally occur after operations on the aortic valve and epicardial pacing capability would avert a potential problem.

Postoperative Considerations As described in the report, postoperative autotransfusion of shed mediastinal blood is usually acceptable to the JW patient, as long as the circuit (from the patient to the collection device and back to the patient) remains uninterrupted. This can be easily achieved with intravenous tubing and a pump. Postoperative autotransfusion is frequently not needed, as the volume of shed blood is so small as to be inconsequential. If the amount of postoperative bleeding is not small, a low threshold for returning the patient to the operating room must be maintained. It is not possible to tide the bleeding JW patient over with red cell transfusions or make efforts to improve abnormal coagulation parameters with fresh frozen plasma and platelets. If the patient is bleeding significantly after surgery, early exploration is the best course of action. The successful management of JW patients undergoing complex high-risk operations described in these reports reflects perioperative considerations that should be applied to all patients, JW or not. These considerations include thoughtful preoperative preparation, communication between the participating anesthesiologists and surgeons, the appropriate application of contemporary blood conservation measures, and the willingness to take on challenging clinical problems.

REFERENCES 1. Svensson LG, Crawford ES, Hess KR, et al: Experience with 1509 patients undergoing thoracoabdominal aortic operations. J Vasc Surg 17:357-368, 1993 2. Dupuis JF, Nguyen DT: Anesthetic management of the patient who refuses blood transfusions. Int Anesthesiol Clin 36:117-131, 1998 3. Zauder HL, Stehling L: Acute normovolemic hemodilution. J Clin Anesth 12:31-35, 2000 4. Bryson GL, Laupacis A, Wells GA: Does acute normovolemic hemodilution reduce perioperative allogeneic transfusion? A metaanalysis. The International Study of Perioperative Transfusion. Anesth Analg 86:9-15, 1998 5. Cina CS, Bruin G: Acute normovolemic hemodilution (ANH) in surgery of the thoracoabdominal aorta. A cohort study to evaluate coagulation parameters and blood products utilization. J Cardiovasc Surg (Torino) 40:37-43, 1999 6. Cina CS, It SC, Clase CM, et al: A cohort study of coagulation parameters and the use of blood products in surgery of the thoracic and thoracoabdominal aorta. J Vasc Surg 233:462-468, 2001 7. Clinical strategies for avoiding and controlling hemorrhage and anemia without blood transfusion in surgical patients, Hospital Information Services for Jehovah Witnesses, Watch Tower Bible and Tract Society of New York, Inc., Brooklyn, NY,2001pp 2–5. 8. Gan TJ, Bennett-Guerrero E, Phillips-Bute B, et al: Hextend, a physiologically balanced plasma expander for large volume use in major surgery: A randomized phase III clinical trial. Hextend Study Group. Anesth Analg 88:992-998, 1999 9. Rosengart TK, Helm RE, DeBois WJ, et al: Open heart operations without transfusion using a multimodality blood conservation strategy in 50 Jehovah’s Witness patients: Implications for a “bloodless” surgical technique. J Am Coll Surg 184:618-629, 1997 10. De Andrade JR, Jove M, Landon G, et al: Baseline hemoglobin as a predictor of risk of transfusion and response to epoietin alfa in orthopedic surgery patients. Am J Orthop 25:533-542, 1996 11. Vorweg M, Hartmann B, Knuttgen D, et al: Management of fulminant fibrinolysis during abdominal aortic surgery. J Cardiothorac Vasc Anesth 15:764-767, 2001

12. Robinson J, Nawaz S, Beard JD: Randomized, multicentre, double-blind, placebo-controlled trial of the use of aprotinin in the repair of ruptured abdominal aortic aneurysm. On behalf of the Joint Vascular Research Group. Br J Surg 87:754-757, 2000 13. Trasylol Prescribing Information, PZ500190, Clinical Pharmacology, Bayer Corporation, West Haven, CT, 2001, pp 1–2 14. Gelman S: The pathophysiology of aortic cross-clamping and unclamping. Anesthesiology 82:1026-1060, 1995 15. Godet G, Fleron MH, Vicaut E, et al: Risk factors for acute postoperative renal failure in thoracic or thoracoabdominal aortic surgery: A prospective study. Anesth Analg 85:1227-1232, 1997 16. Hollier LH, Moore WM: Avoidance of renal and neurologic complications following thoracoabdominal aortic aneurysm repair. Acta Chir Scan Suppl 555:129-135, 1990 17. Donias HW, Karamanoukian RL, Karamanoukian HL: Antifibrinolytic therapy during OPCAB surgery: A word of caution. J Cardiothor Vasc Anesth 16:391-392, 2002 18. Mariani MA, Gu YJ, Boonstra PW, et al: Procoagulant activity after off-pump coronary operations: Is the current anticoagulation adequate. Ann Thor Surg 67:1370-1375, 1999 19. Fitzsimons MG, Peterfreund RA, Raines DE: Aprotinin administration and pulmonary thromboembolism during orthotopic liver transplantation: Report of two cases. Anesth Analg 92:1418-1421, 2001 20. Smith JS, Cahalan MK, Benefiel DJ, et al: Intraoperative detection of myocardial ischemia in high-risk patients: Electrocardiography versus two-dimensional transesophageal echocardiography. Circulation 72:1015-1021, 1985 21. Sutton DC, Cahalan ML: Intraoperative assessment of left ventricular function with transesophageal echocardiography. Cardiol Clin 11:389-398, 1993 22. Scmidlin D, Bettex D, Bernard E, et al: Transesophageal echocardiography in cardiac and vascular surgery: Implications and observer reliability. Br J Aneasth 86:497-505, 2001 23. Bak Z, Abildgard L, Lisander B, et al: Transesophageal echocardiographic hemodynamic monitoring during acute normovolemic hemodilution. Anesthesiology 92:1250-1256, 2000

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24. Bricker DL, Parker TM, Mistrot JJ, et al: Repair of acute dissection of the ascending aorta, associated with coarctation of the thoracic aorta in a Jehovah’s Witness. J Cardiovasc Surg (Torino) 21:374-378, 1980 25. Coselli JS, Buket S, Van Cleve GD: Successful reoperation for ascending aorta and arch aneurysm in a Jehovah’s Witness. Ann Thorac Surg 58:871-873, 1994 26. Lewis CT, Murphy MC, Cooly DA: Risk factors for cardiac operations in adult Jehovah’s Witnesses. Ann Thorac Surg 51:448-450, 1991 27. Brooke M, Schmidt C, Van Aken H, et al: Continuous autotransfusion in a Jehovah’s Witness undergoing coronary artery bypass grafting. Anesth Analg 89:262, 1999 28. Smith CR, Spanier TB: Aprotinin in deep hypothermic circulatory arrest. Ann Thorac Surg 68:278-286, 1999 29. Wozniak G, Dapper F, Zickmann B, et al: Selective cerebral perfusion via innominate artery in aortic arch replacement without deep hypothermic circulatory arrest. Int J Angiology 8:50-56, 1999 30. Helm RE, Rosengart TK, Gomez M, et al: Comprehensive multimodality blood conservation: 100 consecutive CABG operations without transfusion. Ann Thorac Surg 65:125-136, 1998 31. Moskowitz DM, Perelman SI, Cousineau KM, et al: Multidisciplinary management of a Jehovah’s Witness patient for the removal of a renal cell carcinoma extending into the right atrium: [La prise en charge multidisciplinaire d’un patient Temoin de Jehovah pour le retrait d’un hypernephrome s’etendant dans l’oreillette droite]. Can J Anaesth 49:402-408, 2002 32. Weiskopf RB, Viele MK, Feiner J, et al: Human cardiovascular and metabolic response to acute, severe isovolemic anemia [published erratum appears in JAMA 1998 Oct 28;280(16):1404] [see comments]. JAMA 279:217-221, 1998 33. Lieberman JA, Weiskopf RB, Kelley SD, et al: Critical oxygen delivery in conscious humans is less than 7.3 mL O2/kg/min. Anesthesiology 92:407-413, 2000 34. Tung-Ping Poon R, Fan ST, Wong J: Risk factors, prevention, and management of postoperative recurrence after resection of hepatocellular carcinoma. Ann Surg 232:10-24, 2000 35. Vamvakas EC: Transfusion-associated cancer recurrence and postoperative infection: meta-analysis of randomized, controlled clinical trials. Transfusion 36:175-186, 1996 36. Agarwal N, Murphy JG, Cayten CG, et al: Blood transfusion increases the risk of infection after trauma. Arch Surg 128:171-176, discussion 6-7, 1993 37. Carson JL, Altman DG, Duff A, et al: Risk of bacterial infection associated with allogeneic blood transfusion among patients undergoing hip fracture repair. Transfusion 39:694-700, 1999 38. Blumberg N, Heal JM: Blood transfusion immunomodulation: the silent epidemic. Arch Pathol Lab Med 122:117-119, 1998 39. Goodnough LT, Brecher ME, Kanter MH, et al: Transfusion medicine. First of two parts—Blood transfusion. N Engl J Med 340: 438-447, 1999 40. Klein HG: Immunomodulatory aspects of transfusion: A once and future risk? Anesthesiology 91:861-865, 1999 41. Kitchens CS: Are transfusions overrated? Surgical outcome of Jehovah’s Witnesses. Am J Med 94:117-119, 1993 42. Hebert PC, Wells G, Blajchman MA, et al: A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care. Transfusion Requirements in Critical Care Investigators,

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Canadian Critical Care Trials Group [see comments] [published erratum appears in N Engl J Med 1999 Apr 1;340(13):1056]. N Engl J Med 340:409-417, 1999 43. Bracey AW, Radovancevic R, Riggs SA, et al: Lowering the hemoglobin threshold for transfusion in coronary artery bypass procedures: Effect on patient outcome. Transfusion 39:1070-1077, 1999 44. Spiess BD, Ley C, Body SC, et al: Hematocrit value on intensive care unit entry influences the frequency of Q-wave myocardial infarction after coronary artery bypass grafting. The Institutions of the Multicenter Study of Perioperative Ischemia (McSPI) Research Group. J Thorac Cardiovasc Surg 116:460-467, 1998 45. Vincent JL, Baron JF, Reinhart K, et al: Anemia and blood transfusion in critically ill patients. JAMA 288:1499-1507, 2002 46. Aldea GS, Shapira OM, Treanor PR, et al: Effective use of heparin-bonded circuits and lower anticoagulation for coronary artery bypass grafting in Jehovah’s Witnesses. J Card Surg 11:12-17, 1996 47. Ozawa S, Shander A, Ochani TD: A practical approach to achieving bloodless surgery. AORN J 74:34-40, 2001 48. Baele P, Van der Linden P: Developing a blood conservation strategy in the surgical setting. Acta Anaesthesiol Belg 53:129-136, 2002 49. Singelenberg R: The blood transfusion taboo of Jehovah’s Witnesses: Origin, development and function of a controversial doctrine. Soc Sci Med 31:515-523, 1990 50. Passage J, Jalali H, Tam RKW, et al: BioGlue Surgical Adhesive—An appraisal of its indications in cardiac surgery. Ann Thorac Surg 74:432-437, 2002 51. Oz MC, Cosgrove DM III, Badduke BR, et al: Controlled clinical trial of a novel hemostatic agent in cardiac surgery. Ann Thorac Surg 69:1376-1382, 2000 52. Rosengart TK, Helm RE, Klemperer K, et al: Combined aprotinin and erythropoietin use for blood conservation: Results with Jehovah’s Witnesses. Ann Thorac Surg 58:1397-1403, 1994 53. Clark SC, Vitale N, Zacharias J, et al: Effect of low-molecularweight heparin (fragmin) on bleeding after cardiac surgery. Ann Thorac Surg 69:762-765, 2000 54. Jones HU, Muhlestain JB, Jones KW, et al: Preoperative use of enoxaparin compared with unfractionated heparin increases the incidence of re-exploration for postoperative bleeding after open-heart surgery in patients who present with an acute coronary syndrome. Circulation 106:I19-I22, 2002 (suppl I) 55. Schonbereger JPAM, Bredee JJ, Tjian D, et al: Intraoperative predonation contributes to blood saving. Ann Thorac Surg 56:893-898, 1993 56. Helm RE, Klemperer JD, Rosengart TK, et al: Intraoperative autologous blood donation preserves red cell mass but does not decrease postoperative bleeding. Ann Thorac Surg 62:1431-1441, 1996 57. Levi M, Cromheecke ME, de Jonge E, et al: Pharmacological strategies to decrease excessive blood loss in cardiac surgery: A metaanalysis of clinically relevant endpoints. Lancet 354:1940-1947, 1999 58. Peters DC, Noble S: Aprotinin: An update of its pharmacology and therapeutic use in open heart surgery and coronary artery bypass surgery. Drugs 57:233-260, 1999 59. Godet G, Bertrand M, Samama C-M, et al: Aprotinin to decrease bleeding and intraoperative blood transfusion during descending thoracic and thoracoabdominal aortic aneurysmectomy using cardiopulmonary bypass. Ann Thorac Surg 8:452-456, 1994