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BJA Advance Access originally published online on June 27, 2007
British Journal of Anaesthesia 2007 99(3):349-352; doi:10.1093/bja/aem170
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© The Board of Management and Trustees of the British Journal of Anaesthesia 2007. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

Perioperative management of four anaemic female Jehovah’s Witnesses undergoing urgent complex cardiac surgery

V. Casati1,*, A. D'Angelo4, L. Barbato2, D. Turolla2, F. Villa2, M. A. Grasso1, A. Porta3 and F. Guerra2

1 Division of Cardiovascular Anaesthesia and Intensive Care
2 Division of Cardiovascular Surgery
3 Division of Medicine, Policlinico di Monza, Monza, Italy
4 Coagulation Service and Thrombosis Research Unit, Scientific Institute H.S. Raffaele, Milan, Italy

* Corresponding author: Division of Cardiovascular Anaesthesia and Intensive Care Policlinico di Monza via Amati 111, Monza 20052, Italy. E-mail: valter.casati{at}policlinicodimonza.it


    Abstract
 Top
 Abstract
 Introduction
 Methods
 Discussion
 References
 
Previous studies have demonstrated that preoperative haemoglobin concentration and female gender are related to an increased need for perioperative allogeneic transfusions in cardiac surgery. Hence, urgent cardiac surgery presents a dilemma for female patients who are Jehovah’s Witnesses, because of their refusal of allogeneic transfusion. This report describes the management of four high-risk anaemic female patients undergoing urgent complex cardiac surgery. In these Jehovah’s Witness patients, strict application of a comprehensive blood-sparing protocol permitted safe avoidance of allogeneic transfusions. The protocol involved intraoperative acute normovolaemic haemodilution, intraoperative administration of tranexamic acid, intra- and postoperative use of a cell-saver system, postoperative administration of erythropoietin, iron and folic acid, and a careful surgical technique to avoid perioperative bleeding.

Keywords: blood, haemodilution; blood, salvage; complications, Jehovah’s Witness; surgery, cardiovascular; tranexamic acid


    Introduction
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 Abstract
 Introduction
 Methods
 Discussion
 References
 
Excessive bleeding, with the resulting need for allogenic transfusion, remains a common event in complex cardiac surgery involving cardiopulmonary bypass (CPB), such as re-operation, combined interventions and thoracic aortic surgery. Preoperative characteristics associated with an increased need for perioperative allogeneic transfusions include low haemoglobin values and female gender.1 Therefore, urgent complex cardiac surgery presents a high risk for female Jehovah’s Witness anaemic women, because their religion prohibits the use of blood transfusion.

This report describes the management of four anaemic female Jehovah’s Witnesses requiring urgent complex cardiac surgery, operated on by the same surgeon (F.G.) at our centre between 2003 and 2005. In these patients, the use of a comprehensive blood-sparing anaesthetic and surgical protocol permitted safe avoidance of allogenic transfusion.


    Methods
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 Abstract
 Introduction
 Methods
 Discussion
 References
 
Jehovah’s Witness patients refuse preoperative donated autologous transfusions. However, acute normovolaemic haemodilution (ANH) is generally accepted if the maintenance of the continuity of the blood with the patients is guaranteed until re-infusion. The technique we used has been described previously in detail.2 In brief, after the induction of anaesthesia and before systemic heparinization, blood was drawn by gravity through a large bore catheter (8 F) placed into the right internal jugular vein and collected into a single sterile bag containing a dose of citrate phosphate dextrose calculated on the basis of the amount of autologous whole blood (AWB) to withdraw. The amount of AWB was calculated3 to achieve a haematocrit of 20% at the start of CPB. During blood withdrawal, 4% succinylated gelatin in 0.9% NaCl was infused at a ratio of 1:1. The AWB obtained was kept in the operating theatre and gently agitated at room temperature through a blood mixer and balance system (Easymix V3, Baxter Healthcare Corporation, Irvine, CA, USA). Continuity between the AWB and the patient’s blood was guaranteed by circuit tubing, until re-infusion. In all patients, AWB re-infusion was started at the end of surgery, and completed during the first two postoperative hours in the intensive care unit (ICU).

The standard protocol in our institution4 includes administration of tranexamic acid, 1 g as a bolus dose, 20 min before skin incision, followed by a continuous infusion of 400 mg h–1 until the end of surgery, with the addition of 0.5 g at the start of CPB.

To limit the degree of haemodilution during CPB, we used a modified circuit consisting of a roller-pump, a small-volume oxygenator with integral hard-shell phosphorilcoline-coated reservoir (D905 EOS, Dideco, Mirandola, Italy), and small-diameter tubing, which permitted the reduction of the priming volume to 750 ml (Ringer lactate 500 ml, 250 ml of mannitol 18%). In addition, ultrafiltration and administration of diuretic drugs were liberally applied to avoid excessive haemodilution as a result of the addition of cardioplegia solution during CPB. Extra-corporeal circulation was performed with moderate hypothermia (30°C), maintaining the pump flow between 2.6 and 3.0 litre min–1 m–2. Arterial and venous samples for blood gas analysis and calculation of oxygen delivery, and for evaluation of mixed venous oxygen saturation and lactate plasma concentrations, were obtained every 15 min during CPB. During surgery, the surgeon used meticulous haemostasis, limiting the use of laparotomy swabs. After protamine reversal of heparin (1.3:1 ratio of the total dose of heparin administered), blood shed from the surgical field and collected in a cardiotomy, and blood remaining in the CPB circuit were washed and concentrated in a cell salvage circuit (Compact Advanced, Dideco, Mirandola, Italy), and re-infused through a circuit which guarantees the continuity of the system.5 The same circuit and procedures were maintained in the ICU for the reinfusion of the blood shed during the first 12 h after operation. In the postoperative period, each patient received iron (300 mg) and folic acid (5 mg) orally daily, and s.c. recombinant human erythropoietin (rh-EPO, 150 U kg–1 three times a week for 3 weeks with haematocrit values <25% and haemoglobin values <8.5 g dl–1; or 120 U kg–1 with haematocrit values between 25 and 30% and haemoglobin values between 8.5 and 10 g dl–1).

All four patients gave written informed consent for all the procedures described.

Patient 1
A 67-yr-old, 65-kg female Jehovah's Witness had mitral and aortic valve replacement in 1988 at another centre, and urgent re-operation after 2 months for partial mitral valve prosthesis detachment because of Streptococcus epidermidis endocarditis. In September 2003, she presented with fever and dyspnoea. Laboratory analysis revealed a haemoglobin of 8.8 g dl–1 and a haematocrit of 26.2%. Urine bacterial analysis showed Escherichia coli. Transoesophageal echocardiography demonstrated a leaking mitral valve prosthesis. Therapy with oral iron and erythropoietin was started (150 U kg–1 by s.c. injection three times a week for 3 weeks). In spite of a relative improvement in haemoglobin (10.7 g dl–1, haematocrit 32%), the general condition of the patient worsened during this period, and she was referred to our centre for urgent surgery.

After the induction of anaesthesia, 700 ml of AWB were withdrawn. During CPB, ultrafiltration removed 1000 ml of excess fluid. The mitral and aortic prosthetic valves were replaced. Total CPB time was 223 min and aortic clamp time was 206 min. Minimum mixed oxygen venous saturation and maximum lactate levels recorded during CPB were, respectively, 73% and 2.1 mmol litre–1. Postoperative blood loss was 750 ml, and 500 ml of washed blood was re-infused. The postoperative course was uneventful, and the patient was transferred to our rehabilitation unit on postoperative day 7 with a haemoglobin of 9.4 g dl–1.

Patient 2
A 68-yr-old, 53-kg female who had mitral valve replacement with a mechanical prosthetic valve in another centre in 1985 was referred to our centre with ecocardiographic diagnosis of partial prosthesis detachment, severe pulmonary hypertension, and mildly reduced left ventricular function. The patient presented with jaundice, and the laboratory analysis showed marked haemolysis with relative anaemia (haemoglobin 10.2 g dl–1, haematocrit 30.5%). She presented with dyspnoea and peripheral oedema. Aggressive diuretic therapy was started, and rh-EPO was started at a dose of 100 UI kg–1, three times a week. After 2 weeks of therapy, no significant increase in haemoglobin was observed (11 g dl–1, haematocrit 31.5%) with a worsening of haemolysis. The patient had undergone urgent mitral prosthesis valve replacement. During surgery, before systemic heparinization, 500 ml of AWB were withdrawn. Ultrafiltration was initiated after the start of CPB, and 550 ml of excess fluid was removed. Total CPB time was 66 min and aortic clamp time was 54 min. Minimum mixed oxygen venous saturation and maximum lactate levels recorded during CPB were, respectively, 78% and 1.7 mmol litre–1. Postoperative blood loss was 450 ml, and 250 ml of shed blood was re-infused. The postoperative course was uneventful, and the patient was transferred to our rehabilitation unit on postoperative day 8 with a haemoglobin of 8.5 g dl–1.

Patient 3
A 72-yr-old, 55-kg female woman was referred to our centre with the diagnosis of unstable angina and refractory to infusion therapy of unfractionated heparin and nitrates. Coronary angiography showed three-vessel pathology; trans-thoracic echocardiography demonstrated moderate ischaemic mitral valve insufficiency and an ejection fraction of 25%. She had undergone urgent myocardial revascularization and mitral valve repair. Her preoperative haemoglobin was 11.6 g dl–1. After the induction of anaesthesia, 650 ml of AWB was withdrawn. Furosemide (20 mg) was administered and no ultrafiltration was performed because of limited return in the cardiotomy of the CPB circuit. The surgeon performed three bypass grafts (left mammary artery on descending coronary artery and saphenous vein on right and circumflex coronaries) and mitral valve repair. Total CPB time was 93 min and aortic clamp time was 67 min. Minimum mixed oxygen venous saturation and maximum lactate levels recorded during CPB were, respectively, 78% and 2.2 mmol litre–1. Postoperative blood loss was 550 ml, and 300 ml of shed blood were reinfused. The postoperative course was uneventful, with the exception of atrial fibrillation treated with amiodarone, and the patient was transferred to rehabilitation on postoperative day 9 with a haemoglobin of 9.2 g dl–1.

Patient 4
A 65-yr-old, 73-kg female, previously operated on at our centre in September 2004 for severe aortic insufficiency and ascending aortic dilatation with the implantation of a stentless aortic root, underwent a computed tomography scan control in May 2005. The radiologist diagnosed an aortic pseudoaneurysm close to the proximal suture of the aortic prosthesis requiring urgent intervention. She had undergone a Bentall procedure. Her preoperative haemoglobin was 11.2 g dl–1. After the induction of anaesthesia, 850 ml of AWB was withdrawn. Ultrafiltration was initiated after the start of CPB, and 850 ml of excess fluid removed. Total CPB time was 262 min and aortic clamp time was 167 min. Minimum mixed oxygen venous saturation and maximum lactate levels recorded during CPB were, respectively, 74% and 2.4 mmol litre–1. Postoperative total blood loss was 900 ml, and 650 ml of shed blood was re-infused. No major complications occurred in the postoperative period, with the exception of atrial fibrillation treated with amiodarone. The patient was transferred to rehabilitation on postoperative day 9 with a haemoglobin of 8.7 g dl–1.

The perioperative haematocrit changes observed in the four patients are shown in Figure 1.


Figure 1
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Fig 1 Changes in haematocrit values from baseline to discharge from the hospital in all patients. Times shown are during cardiopulmonary bypass after ANH (CPB 15 min) and after initiation of ultrafiltration and administration of diuretics (CPB 30–210 min), at arrival in the ICU (after the start of autologous blood reinfusion), on postoperative days 1–4 (P.d. 1–4), and at discharge from the hospital.

 

    Discussion
 Top
 Abstract
 Introduction
 Methods
 Discussion
 References
 
Previously published reports of the management of cardiac surgery in Jehovah’s Witness patients focused on patients with normal preoperative haemoglobin values.6 7 This is the first description of the management of Jehovah’s Witnesses requiring urgent cardiac surgery and with preoperative haemoglobin levels presenting a high risk of perioperative anaemia. The importance of using a comprehensive blood-sparing protocol to reduce the need for allogeneic transfusions has previously been highlighted.8 In our patients, the combination of perioperative blood conservation, haemostatic and haematopoietic drugs, re-infusion of shed blood, and a careful surgical technique resulted in safe avoidance of allogeneic transfusion.

Although its use is still debated,9 10 the real efficacy of ANH in reducing the need for allogeneic transfusions appears to be related to the maximal allowable volume of AWB withdrawn and to the blood volume lost.2 3 11 Preoperative anaemia limits the volume of AWB, especially in patients undergoing surgery with CPB. Miniaturization of the CPB circuit, resulting in reduced haemodilution as a result of the priming, will allow the ‘maximal’ volume of intraoperative autologous blood donation,3 and the use of ultrafiltration and diuretics will limit haemodilution during CPB.

Careful control of oxygen delivery and moderate hypothermia allowed the patients to tolerate haematocrit levels lower than those reported as associated with an increased risk for postoperative morbidity and mortality.12 During CPB, normal mixed venous oxygen saturation and lactate levels were recorded, indicating good peripheral perfusion. Aprotinin has been suggested as the antifibrinolytic drug of choice to prevent bleeding excess in Jehovah's Witnesses undergoing cardiac surgery,7 8 but it is no longer available in Italy. We routinely use tranexamic acid at our centre, as it has similar haemostatic effects.13 Accurate surgical haemostasis and limited use of laparotomy swabs are important in avoiding excessive intraoperative bleeding, and the effectiveness of a cell-saver circuit for intra- and postoperative reinfusion of the blood loss to preserve red cell mass has previously been demonstrated.11 14

Treatment with rh-EPO has a major role in the management of anaemic cardiac surgical patients.6 7 15 16 In two of our patients, rh-EPO therapy was ineffective, because of worsening of the clinical condition (patient 1), and because of severe haemolysis resulting from partial detachment of the prosthetic mitral valve (patient 2). In the other two cases, the urgency of the surgery precluded starting rh-EPO treatment. The cost-effectiveness of rh-EPO has been criticized,17 but our decision to use rh-EPO after operation was based on evidence of the efficacy of high-dose rh-EPO to stimulate erythropoiesis in critically ill patients.18 19

In conclusion, our series suggests that close adherence to a well-defined perioperative strategy permits successful treatment of high-risk, anaemic Jehovah’s Witnesses requiring urgent cardiac surgery.


    References
 Top
 Abstract
 Introduction
 Methods
 Discussion
 References
 
1 Magovern JA, Sakert T, Benckart DH, et al. A model for predicting transfusion after coronary artery bypass grafting. Ann Thorac Surg (1996) 61:27–32.[Abstract/Free Full Text]

2 Casati V, Speziali G, D'Alessandro C, et al. Intraoperative low-volume acute normovolemic hemodilution in adult open-heart surgery. Anesthesiology (2002) 97:367–73.[CrossRef][Web of Science][Medline]

3 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 (1996) 62:1431–41.[Abstract/Free Full Text]

4 Casati V, Della Valle P, Benussi S, et al. Effects of tranexamic acid on postoperative bleeding and related hematochemical variables in coronary surgery: comparison between on-pump and off-pump techniques. J Thorac Cardiovasc Surg (2004) 128:83–91.[Abstract/Free Full Text]

5 Waters JH, Potter PS. Cell salvage in the Jehovah's Witness patient. Anesth Analg (2000) 90:229–30.[Free Full Text]

6 Holt RL, Martin TD, Hess PJ, Beaver TM, Klodell CT. Jehovah's Witnesses requiring complex urgent cardiothoracic surgery. Ann Thorac Surg (2004) 78:695–7.[Abstract/Free Full Text]

7 Loubser PG, Stoltz SM, Schmoker JD, et al. Blood conservation strategies in Jehovah's Witness patients undergoing complex aortic surgery: a report of three cases. J Cardiothorac Vasc Anesth (2003) 17:528–35.[CrossRef][Web of Science][Medline]

8 Madjdpour C, Spahn DR. Allogeneic red blood cell transfusion: efficacy, risks, alternatives and indications. Br J Anaesth (2005) 95:33–42.[Abstract/Free Full Text]

9 Second Consensus Conference on Autologous Transfusion. Autologous transfusion 3 yr on—what is new? Br J Anaesth (1999) 82:783–4.[Free Full Text]

10 Segal JB, Blasco-Colmenares E, Norris EJ, Guallar E. Preoperative acute normovolemic haemodilution: a meta-analysis. Transfusion (2004) 44:632–44.[CrossRef][Web of Science][Medline]

11 Napier JA, Bruce M, Chapman J, et al. Guidelines for autologous transfusion. II. Perioperative haemodilution and cell salvage. Br J Anaesth (1997) 78:768–71.[Free Full Text]

12 Habib RH, Zacharias A, Schwann TA, et al. Role of hemodilutional anemia and transfusion during cardiopulmonary bypass in renal injury after coronary revascularization: implications on postoperative outcome. Crit Care Med (2005) 33:1749–56.[CrossRef][Web of Science][Medline]

13 Casati V, Guzzon D, Oppizzi M, et al. Tranexamic acid compared with high-dose aprotinin in primary elective heart operations: effects on perioperative bleeding and allogeneic transfusions. J Thorac Cardiovasc Surg (2000) 120:520–7.[Abstract/Free Full Text]

14 McGill N, O'Shaughnessy D, Pickering R, Herbertson M, Gill R. Mechanical methods of reducing blood transfusion in cardiac surgery: randomised controlled trial. Br Med J (2002) 324:1299–305.[Abstract/Free Full Text]

15 Konishi T, Ohbayashi T, Kaneko T, Ohki T, Saitou Y, Yamato Y. Preoperative use of erythropoietin for cardiovascular operations in anemia. Ann Thorac Surg (1993) 56:101–3.[Abstract]

16 Sowade O, Warnke H, Scigall P, et al. Avoidance of allogeneic blood transfusions by treatment with epoietin beta (recombinant human erythropoietin) in patients undergoing open-heart surgery. Blood (1997) 89:411–8.[Abstract/Free Full Text]

17 Neff TA, Stocker R, Wight E, Spahn DR. Extreme intraoperative blood loss and haemodilution in a Jehovah's Witness: new aspects in postoperative management. Anesthesiology (1999) 91:1949–51.[CrossRef][Web of Science][Medline]

18 Price S, Pepper JR, Jaggar SI. Recombinant human erythropoietin use in a critically ill Jehovah's witness after cardiac surgery. Anesth Analg (2005) 101:325–7.[Abstract/Free Full Text]

19 Walsh TS, Saleh EE. Anaemia during critical illness. Br J Anaesth (2006) 97:278–91.[Free Full Text]


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