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* From the Departments of Anesthesia and
Surgery, Royal Victoria Hospital and McGill University, 687 Pine Ave. W., Montreal, QC, H3A 1A1 Canada.
Address correspondence to: Dr. S.B. Backman. Phone: 514-842-1231, local 4880; Fax: 514-843-1723; E-mail: mdba{at}musica.mcgill.ca
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Abstract |
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Clinical features: A 49-yr-old Jehovah's Witness with ankylosing spondylitis and end stage liver disease secondary to sclerosing cholangitis underwent orthotopic liver transplantation. Recombinant human erythropoietin (4,000 IU sc every two days for four weeks, then 4,000 IU sc every week) established a normal hemoglobin concentration preoperatively (>140 g•L–1 compared with 120 g•L–1 baseline). Intraoperatively, strategies for reducing risk of blood product transfusion included avoidance of hypothermia (T>35°C), minimal blood sampling (four 1 ml samples), normovolemic hemodilution (two units), administration of Aprotinin (2 million units bolus dose followed by infusion of 500,000 u•hr–1), and return of blood (1,500 ml) scavenged from the operative field. Estimated blood loss was 2,200 ml. The preoperative and postoperative hemoglobin concentration was 147 g•L–1 (hematocrit 0.45) and 123 g•L–1 (hematocrit 0.37), respectively. No blood products were required and he was discharged three weeks postoperatively without complication.
Conclusion: Technological and pharmacological advances allow patients to undergo surgery traditionally associated with large volume blood loss with reduced risk of blood product administration.
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Case report |
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After routine initial pre-transplant investigations were completed, the patient was placed on 300 mg FeSO4 TID po and 4,000 IU recombinant human erythropoietin sc every two days and was listed for liver transplant. His initial hemoglobin concentration was 120 g•L–1. Once a target hemoglobin of 135 g•L–1 was achieved after four weeks, he was maintained on 4,000 IU erythropoietin sc every week. His hemoglobin peaked at 154 g•L–1 and remained above 140 g•L–1 until the time of transplantation. Other medications included sulfasalazine, indomethacin, misoprostol, enalapril, and lansoprazole.
A suitable donor became available seven months after enlistment. On the day of transplant, his hemoglobin was 147 g•L–1 (hematocrit 0.45) with a platelet count of 270 x 109•L–1. He had a prothrombin time (PT) of 11.4 sec, partial thromboplastin time (PTT) of 31.5 sec, International Normalised Ratio (INR) of 0.928, and fibrinogen concentration of 3.63 g•L–1. Factors II, V, VII, VIII, IX, X, XI and XII levels were within the normal range. Blood electrolyte values were normal as was the BUN (7.2 mMol•L–1) and creatinine (65 mMol•L–1)
Because of the airway difficulties associated with the ankylosing spondylitis, after careful positioning of the head the trachea was intubated with a fibreoptic bronchoscope following adequate sedation (3.0 mg midazolam and 5 µg sufentanil) and airway topicalization (bilateral superior laryngeal nerve block and inhalation of aerosolised lidocaine 4%). General anesthesia was induced with 25 µg sufentanil and 60mg propofol and muscle paralysis was achieved with 10 mg pancuronium. Anesthesia was maintained with isoflurane in an O2 / air (50%:50%) mixture, and an infusion of 1 mg•hr–1 midazolam and 25 µg•hr–1 sufentanil. Neuromuscular relaxation was maintained with periodic doses of pancuronium. Monitoring consisted of ECG (leads II & V), pulse oximetry, capnography, nasopharyngeal T°, and a nerve stimulator. Invasive systemic blood pressure was recorded via a catheter inserted into a radial artery, and pulmonary artery and central venous pressures via a catheter inserted into an internal jugular vein. The patient's temperature was maintained > 35°C using a water-heated mattress and warmed air delivered to the upper and lower body. All fluids administered through intravenous catheters in the upper extremities (#14 & #16 gauge) were warmed using a Hot LineTM.
After induction of anesthesia, the patient was given a bolus of 2 million units Aprotinin followed by an infusion of 500,000 units•hr–1 in anticipation of primary fibrinolysis that may arise during the anhepatic and reperfusion phases of liver transplantation.
Normovolemic hemodilution was achieved by removing two units of whole blood (each unit approx 500 ml) from the patient prior to commencement of surgery and storing them into transfusion bags, while infusing a volume of crystalloid in a 3:1 ratio to that removed. The transfusion bags were maintained connected to the patient via Continu-Flo® Solution Set tubing connected to the iv catheters, in accordance with the wishes of the patient. In keeping with a strategy of blood conservation, minimal blood tests were drawn intraoperatively. Four 1 ml samples of arterial blood were sent for blood gas, hematocrit and electrolyte (calcium & potassium) determination. A baseline hematocrit of 0.45 was recorded shortly after induction of anesthesia. The hematocrit was 0.34 after removal of the first unit and 0.28 after removal of the second unit (approximately 30 and 60 min following induction, respectively). A hematocrit of 0.25 was determined at the end of the anhepatic phase after four hours following induction. The two units of autologous blood were transfused during the last 60 min of surgery. Blood was scavenged from the operative field, washed and immediately re-transfused using a COBE® BRAT 2 cell saver. In this case, 2,800 ml were scavenged from the surgical field and 1,500 ml of hemoconcentrated blood were returned to the patient. The estimated blood loss combining weight of sponges and cell saver loss was 2,200 ml. A total of 12,000 ml crystalloid (8,000 ml normal saline, 4,000 ml lactated Ringer's) and 500 ml PENTASPAN® were administered intraoperatively, and urine output was approximately 5,000 ml.
Due to size differences between the patient and the transplanted liver as well as intestinal edema, fascial closure was not possible at the end of the operation. A cutaneous closure was completed after six hours of operating time and the patient was brought to the intensive care unit. The immediate postoperative laboratory results were hemoglobin 123 g•L–1 (hematocrit 0.37), platelet count 175 x 109•L–1, PT 15.3 sec, PTT 67.7 sec, INR 1.702. Postoperative use of blood products was not required. Although the patient's mental and physiological status would have permitted extubation in the immediate postoperative period, owing to the potential difficulties in re-establishing tracheal intubation in the case of deterioration, the trachea was extubated the next day, approximately 20 hr after the operation. He returned to the operating room four days later for fascial closure of the abdominal wall. During the postoperative period, the patient's coagulation parameters rapidly returned to normal and he was discharged from hospital three weeks after transplantation.
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In a case series of four patients with religious objection to blood transfusion who underwent liver transplantation, Ramos and colleagues1 outlined six criteria that would disqualify patients from a bloodless surgery protocol (Table
). The patient in this report would not have been disqualified using these criteria. Such criteria are useful in determining which patients are acceptable risks for surgery assuming that modern techniques of perioperative blood conservation are implemented.
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The use of intraoperative and postoperative blood scavenging systems has reduced the amount of allogeneic blood transfusions required by patients. These techniques are, however, expensive and require relatively sophisticated equipment and trained personnel. While a few case reports suggest that DIC, ARDS and renal failure can arise from the reintroduction of fat microemboli, denatured protein, free hemoglobin, cell fragments, and platelet-leukocyte microaggregates into the blood stream,12,13 more carefully designed studies have failed to show a significant increase in these complications. The washing phase after centrifugation eliminates these products as well as heparin, plasma elastases and soluble cytokines such as TNF-alpha.13 While coagulation disorders associated with transfusion of a large volume of blood products are well described, it is not clear to what extent retransfusion of scavenged blood per se contributes to a coagulopathy. Traditionally, patients undergoing bowel surgery and cancer resection are not considered as suitable candidates for the use of intraoperative blood scavenging because of the fear of retransfusing bowel flora and exfoliated cancer cells. However, the recent use of blood scavenging techniques in trauma cases with intestinal perforation did not yield more patients with positive blood cultures or wound infections, even though the washing phase does not eliminate all bacteria. Processing of scavenged blood does not eliminate tumour cells thus mandating the use of a special filter if this strategy is to be employed during cancer surgery.13
Acute normovolemic hemodilution (ANH) has been advocated as a safe, easy and inexpensive way to avoid exposure to allogeneic blood.6,12,13 There are several theoretical advantages to this technique:
Aprotinin has been demonstrated to decrease the risk of allogenic blood transfusion in a recent meta-analysis of prospective, randomised, controlled studies of pharmacological strategies to decrease bleeding associated with cardiac surgery.16 A similar analysis has not been done with patients who have undergone liver transplantation. Although there is evidence to support the use of aprotinin in this type of patient,17 the usefulness of this approach has been challenged.18 Interestingly, the benefits conferred by aprotinin using high doses, as employed in this case, may also be achieved with somewhat lower doses.19
Repeated blood sampling for laboratory analysis should not be underestimated as a source of blood loss, and such analysis was kept to a minimum in this case. The avoidance of severe hypothermia prevented temperature-related coagulopathy. Although veno-venous bypass has been suggested to decrease blood product requirements3 this technique is almost never used at our institution during liver transplantation and we elected not to use it in this patient, particularly since he had a normally functioning heart. Often left unreported in discussions of perioperative blood conservation is meticulous surgical technique. Dissection was done almost exclusively with electrocautery, as emphasised in previous reports.3 There are new surgical devices to minimise blood loss which are described in a recent review.20
A most important contributor to the successful clinical outcome in this case is that the patient received his liver transplant before he demonstrated severe liver failure. Thus, the patient's liver was able to maintain normal blood concentrations of factors necessary for hemostasis. Patients that require bloodless liver transplantation have to be listed for surgery early before their coagulation profile is severely affected.
Finally, the value of discussion and preoperative involvement of a multidisciplinary team cannot be overstated. Clarification of the patient's wishes, concerns and beliefs concerning transfusion of blood products is critical. In this particular case, the potential legal, ethical and medical complications of performing a liver transplant in a patient refusing transfusion of blood products were discussed at many multidisciplinary rounds involving anesthesia, surgery, hematology and intensive care personnel. Specific consultation was obtained with the hospital medical ethicist and lawyer and from the Canadian Medical Protective Association (CMPA). Following several frank discussions with the patient and his family, the patient's decision concerning the potential use of blood products in the face of a life-threatening situation was carefully documented.
In conclusion, we describe a Jehovah's Witness patient with ankylosing spondylitis who underwent liver transplantation without requiring transfusion of blood products during the perioperative period. The pharmacological and technological strategies employed to help conserve blood in the perioperative period, as described in this report, may help to reduce the necessity for the transfusion of blood.
Accepted for publication April 1, 2000.
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References |
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2 Seu P, Neelankanta G, Csete M, et al. Liver transplantation for fulminant hepatic failure in a Jehovah's Witness. Clin Transplant 1996; 10: 404–7.[Medline]
3
Snook NJ, O'Beirne HA, Enright S, Young Y, Bellamy MC. Use of recombinant human erythropoietin to facilitate liver transplantation in a Jehovah's Witness. Br J Anaesth 1996; 76: 740–3.
4 Detry O, Honoré P, Delwaide J, Dondelinger RF, Meurisse M, Jacquet N. Liver transplantation in a Jehovah's witness. (Letter) Lancet 1999; 353: 1680.
5 Kettelhack C, Hönes C, Messinger D, Schlag PM. Randomized multicentre trial of the influence of recombinant human erythropoietin on intraoperative and postoperative transfusion need in anaemic patients undergoing right hemicolectomy for carcinoma. Br J Surg 1998; 85: 63–7.[Medline]
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Goodnough LT, Monk TG, Andriole GL. Erythropoietin therapy. N Eng J Med 1997; 336: 933–8.
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Milbrink J, Birgegård G, Danersund A, Helmers C, Nordström L, Sandhagen B. Preoperative autologous donation of 6 units of blood during rh-EPO treatment. Can J Anaesth 1997; 44: 1315–8.
8
Mann JFE. What are the short-term and long-term consequences of anaemia in CRF patients? Nephrol Dial Transplant 1999; 14: 29–36.
9 Tang WW, Stead RA, Goodkin DA. Effects of epoetin alfa on hemostasis in chronic renal failure. Am J Nephrol 1998; 18: 263–73.[Medline]
10 Goldberg MA. Perioperative epoetin alfa increases red blood cell mass and reduces exposure to transfusions: results of randomized clinical trials. Semin Hematol 1997; 34: 41–7.[Medline]
11 Tryba M. Epoetin alfa plus autologous blood donation in patients with a low hematocrit scheduled to undergo orthopedic surgery. Semin Hematol 1996; 33: 22–6.[Medline]
12
Hardy J-F, Bélisle S, Janvier G, Samama M. Reduction in requirements for allogeneic blood products: nonpharmacologic measures. Ann Thorac Surg 1996; 62: 1935–43.
13 Stehling L. Autologous transfusion. In: Miller RD (Ed.) Anesthesia, 4th ed. New York: Churchill Livingstone Inc., 1994: 1647–60.
14 Weiskopf RB. Mathematical analysis of isovolemic hemodilution indicates that it can decrease the need for allogeneic blood transfusion. Transfusion 1995; 35: 37–41.[Medline]
15 Bryson GL, Laupacis A, Wells GA. Does acute normovolemic hemodilution reduce perioperative allogenic transfusion? A meta-analysis. Anesth Analg 1998; 86: 9–15.[Abstract]
16 Levi M, Cromheecke ME, de Jonge E, et al. Pharmacological strategies to decrease excessive blood loss in cardiac surgery: a meta-analysis of clinically relevant endpoints. Lancet 1999; 354: 1940–7.[Medline]
17
Llamas P, Cabrera R, Gómez-Arnau J, Fernandez MN. Hemostasis and blood requirements in orthotopic liver transplantation with and without high-dose aprotinin. Haematologica 1998; 83: 338–46.
18 Garcia-Huete L, Domenech P, Sabaté A, Martinez-Brotons F, Jaurrieta E, Figueras J. The prophylactic effect of aprotinin on intraoperative bleeding in liver transplantation: a randomized clinical study. Hepatology 1997; 26: 1143–8.[Medline]
19 Marcel RJ, Stegall WC, Suit CT, et al. Continuous small-dose aprotinin controls fibrinolysis during orthotopic liver transplantation. Anesth Analg 1996; 82: 1122–5.[Abstract]
20 Spence RK. Emerging trends in surgical blood transfusion. Semin Hematol 1997; 34: 48–53.[Medline]
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