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CASE REPORTS

The Anesthetic Management of a Patient with Paroxysmal Nocturnal Hemoglobinuria

Department of Anesthesiology and Intensive Care, Post Graduate Institute of Medical Education and Research, Chandigarh, India

Address correspondence and reprint requests to Subramaniam Kathirvel, MD, Department of Anesthesiology and Intensive Care, Postgraduate Institute of Medical Education and Research, Chandigarh-160012, India. Address e-mail to kathirvels{at}yahoo.com

	Abstract

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Implications: This case report describes the anesthetic considerations for a patient with paroxysmal nocturnal hemoglobinuria. Specific strategies to be applied in the perioperative period to prevent hemolytic episodes and venous thrombosis are also discussed.

	Introduction

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Paroxysmal nocturnal hemoglobinuria (PNH) is a disorder of stem cells resulting in complement-mediated red cell lysis (1). The literature search provided very scant information regarding the anesthetic management of these patients presenting for surgery (2). We describe the successful management of a patient with PNH with gall stones who underwent elective cholecystectomy under general anesthesia.

	Case Report

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A 55-yr-old woman, weighing 45 kg, had a 2-day history of fever, chills, right upper abdominal pain, jaundice, and dark colored urine. She was diagnosed to have PNH when she presented with similar symptoms 1.5 yr ago. At that time, she was managed conservatively and discharged. She was treated with prednisolone 30 mg once daily. On admission, she was febrile, toxic, dyspneic, and she complained of occipital headache. Her heart rate was 120 bpm, arterial blood pressure was 140/90 mm Hg, and respiratory rate was 32 breaths/min. Abdominal palpation revealed hepatosplenomegaly. Oxygen therapy and IV fluids were started immediately. Initial investigations showed severe anemia (hemoglobin [Hb], 4.2 g/dL), increased erythrocyte sedimentation rate (45 mm/h), and normal white blood cell and platelet counts. Serum bilirubin was 2.1 mg% (conjugated fraction, 1.4 mg%), but liver and renal function test results were within normal limits. Additional hematological investigations included a reticulocyte count of 15%, increased serum lactate dehydrogenase, reduced neutrophil alkaline phosphatase, urine Hb 2 mg% (normal, 0 mg%) and plasma Hb 6 mg% (normal, 0.6 mg/dL). Bone marrow showed hypercellularity. Red cell proteins, decay accelerating factor, and membrane inhibitor of reactive lysis were found to be deficient. Ultrasound analysis of the abdomen showed multiple gallbladder stones and dilated common bile duct. The common bile duct was stented. The bile culture showed Escherichia coli sensitive to cefotaxime and amikacin, which were immediately given to the patient. Initially, her condition improved, but deteriorated within a week. Serum bilirubin increased to 6.3 mg% (conjugated fraction, 2.1 mg%), and urine Hb increased to 6 mg%. Endoscopic retrograde cholangiopancreaticography was performed. The common bile duct stent was nonfunctional, and it was removed. A nasobiliary drainage was inserted. A bile culture at this time revealed enterococcus, sensitive to vancomycin, which was added to the treatment regimen. She also received iron and folate supplements along with six units of red cell transfusion over 20 days. Her symptoms improved, and she was referred for elective cholecystectomy. Her immediate preoperative investigations were as follows: Hb, 10.2 g%; urine and plasma Hb, negative; and serum bilirubin, 2.8 mg%. Informed consent was taken from the patient for the planned procedure. She was premedicated with diazepam 10 mg in the night and 5 mg in the morning along with morning dose of prednisolone 30 mg orally. She also received IV fluids 100 mL/h starting the night before surgery. Low molecular weight heparin 5000 IU subcutaneously once daily was started the day before surgery and continued until fifth postoperative day. Urinary catheterization was performed to monitor the adequacy of hydration and for detection of hemoglobinuria.

After the patient’s arrival in the operating room, anesthesia was induced with propofol 100 mg, and endotracheal intubation was facilitated with vecuronium 6 mg IV. Anesthesia was maintained with 50% nitrous oxide and 1 minimum alveolar anesthetic concentration halothane in oxygen. The usual monitoring was used. Intraoperative analgesia was provided with morphine 10 mg IV. After the cholecystectomy, peroperative cholangiography was performed with radio-contrast dye, iohexol. This was followed by common bile duct exploration and stone removal. The entire procedure lasted 2 h, and the blood loss was 500 mL. She was given 2.5 L of crystalloids, and urine output was 300 mL. There was no change in the color of the urine intraoperatively. The surgical wound was infiltrated with 0.25% bupivacaine for postoperative analgesia. Residual neuromuscular blockade was reversed with neostigmine 2.5 mg and glycopyrrolate 0.5 mg, and the trachea was extubated.

The patient remained conscious and pain free with stable vital signs in the postoperative period. There was mild discoloration of urine in the first hour of recovery room stay, which cleared without any active intervention. Hydrocortisone 25 mg IV 6 hourly was given until she started taking oral prednisolone. On the third postoperative day, Hb was 9.8 g%, urine Hb was 2 mg%, plasma Hb was 4 mg%, and serum bilirubin was 1.4 mg%. The postoperative hospital stay was uneventful, and she was discharged on seventh postoperative day and advised to continue steroids.

	Discussion

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PNH is a distinctive hemolytic disorder resulting from an intracorpuscular defect acquired at the stem cell level. The lack of two proteins, decay accelerating factor and membrane inhibitor of reactive lysis, make the red cells more sensitive to the lytic effect of complement. The disorder is characterized by attacks of intravascular hemolysis and hemoglobinuria that occur chiefly when the patient is asleep. The patient recognizes hemoglobinuria by the abnormal appearance of first voided urine in the morning. However, in most cases the classic pattern is not observed, and the patients manifest a chronic low-grade hemolysis punctuated by occasional episode of hemoglobinuria (1).

Anesthesia by itself should be a risk factor for an episode of hemoglobinuria by inducing sleep. Nocturnal exacerbation of hemoglobinuria was attributed to carbon dioxide retention and acidosis of the blood leading to activation of complement systems (3). Mild acidosis associated with strenuous exercise was also associated with the exacerbation of hemolysis (4). Factors predisposing to acidosis and subsequent activation of a complement, such as hypoxemia, hypoperfusion, and hypercarbia, should be avoided in these patients. In this case we maintained oxygen saturation, end tidal carbon dioxide, noninvasive blood pressure, and urine output within normal limits throughout the procedure.

The mode of action of steroids in PNH is speculative. The use of steroids is based on clinical reports showing significant improvement in patients with PNH and prominent hemolytic symptoms (5). We have given supplemental steroids in the perioperative period to avoid both hemolytic exacerbation and addisonian crisis because the patient was receiving long-term steroid therapy.

Hemolytic episodes in PNH can be precipitated by minor infections (6). Biliary sepsis caused by gall stone disease precipitated exacerbation of hemolysis (increase in unconjugated bilirubin and urine hemoglobin) in our patient. Bile duct drainage along with appropriate antibiotics helped optimize the patient’s condition before surgery.

Patients with PNH can be divided into two groups, those without a history of aplasia (primary PNH) and those with a history of aplastic anemia who subsequently develop PNH (1). Taylor et al. (2) suggested that nitrous oxide is better avoided in patients of PNH with hypoplastic anemia, especially if liver function is deranged. Fifty percent nitrous oxide administered for <8–12 hours caused no significant changes in bone marrow. The bone marrow changes induced by nitrous oxide administration for a longer period could be prevented by pretreatment with folinic acid (7). In this patient, there was evidence of bone marrow hyperplasia in bone marrow aspiration and reticulocytosis in peripheral blood smear. The surgical procedure lasted only 2 hours. The patient was receiving folate treatment in the preoperative period. The liver function tests were normal. So, we continued nitrous oxide 50% for maintenance of anesthesia with halothane. Taylor et al. (2) used isoflurane in their case because of deranged liver function.

Taylor et al. (2) advised that induction with volatile anesthetics is preferable to IV anesthetics because of their association with a high frequency of anaphylactoid reactions, some of which involve complement activation. Drugs formulated in Cremophor EL were cited as classical examples of causing complement mediated reactions (8). Watkins (9) found that 10% of thiopental-induced anaphylactic reactions may be associated with altered complement levels, and 4% of thiopental reactions were mediated by an alternate complement pathway. Doenicke et al. (10) studied propofol in healthy volunteers and concluded that no change consistent with a propensity to produce anaphylactoid reactions could be seen from the measurement of immunoglobulin levels, complement levels, or plasma histamine concentration in propofol-treated patients. In our case, we used propofol, morphine, and vecuronium. Although there was mild hemoglobinuria in the recovery room, we cannot attribute this to any specific drug, because classic complement activation can occur after the induction of anesthesia in 30% of patients (11).

PNH is associated with a striking predisposition to thrombosis within the venous circulation and usually involves portal, renal, and cerebral circulation (1). This could be caused by an increase in acute phase complement proteins, which reaches the maximum on the fourth postoperative day (12). Maintenance of adequate hydration is of paramount importance in preventing this complication. Central venous pressure monitoring may be needed for more invasive surgical procedures in which blood loss is anticipated. The role of prophylactic heparin is not clear because large, randomized trials are not possible to evaluate its role considering the small prevalence of this condition. We did not anticipate a major blood loss unlike the surgical procedure in Taylor et al.’s (2) case. We administered low molecular weight heparin up to the fifth postoperative day. Androgens are used in PNH patients with prominent marrow hypoplasia. Some investigators suggest that androgens might predispose a patient to an insidious form of hepatic vein thrombosis (5).

If the patient with PNH needs a blood transfusion, saline-washed red blood cells can be given to reduce the risk of leukocyte sensitization, antibody production against human leukocyte antigens, and reactions which may activate complement (13). Brecher and Taswell (14) reviewed the transfusion reactions for 38 years in patients with PNH and concluded that the use of washed red cells is not necessary. Patients with PNH should be transfused with group-specific and fresh blood and blood products. During blood transfusion, the complement can be activated by the interaction of transfused antibodies with susceptible cells, the reaction between the patient’s antibodies and transfused red cells, or by the prolonged storage of blood. These can be avoided by transfusing group specific and fresh red cells. If such precautions are taken, washing of red cells is unnecessary in PNH patients. If these precautions cannot be taken, the reactions can still be avoided by using washed red cell transfusion (15). Preoperatively, this patient received only unwashed red cells (6 units over 20 days) without significant exacerbation of hemolysis during transfusions. However, if the patient needs large volumes of blood over a short period of time, such as with massive blood loss, the role of washed red cells to avoid the reactions needs to be considered.

In conclusion, the anesthetic management of patients with PNH should be aimed at preoperative treatment of precipitating factors, such as sepsis, avoidance of drugs and techniques activating the complement, and prevention of thrombotic episodes.

	References

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1. Parker CJ, Lee GR. Paroxysmal nocturnal hemoglobinuria. In: Lee GR, Foerster J, Lukens J, et al., eds. Wintrobe’s clinical hematology. Baltimore: Williams & Wilkins, 1999: 1264–88.
2. Taylor MB, Whitwam JG, Worsley A. Paroxysmal nocturnal haemoglobinuria: perioerative management of a patient with Budd-Chiari syndrome. Anaesthesia 1987; 42: 639–42.[Web of Science][Medline]
3. Ham TH. Chronic hemolytic anemia with paroxysmal nocturnal hemoglobinuria. N Engl J Med 1937; 217: 915.[Web of Science]
4. Blum SF, Sullivan JM, Gardner FH. The exacerbation of hemolysis in paroxysmal nocturnal hemoglobinuria by strenuous exercise. Blood 1967; 30: 513–7.[Abstract/Free Full Text]
5. Rosse WF. Treatment of paroxysmal nocturnal hemoglobinuria. Blood 1982; 60: 20–3.[Abstract/Free Full Text]
6. Nakakuma H, Hidaka M, Nagakura S, et al. Expression of cryptantigen Th on paroxysmal nocturnal hemoglobinuria erythrocytes in association with a hemolytic exacerbation. J Clin Invest 1995; 96: 201–6.
7. O’Sullivan H, Jannings F, Ward K, et al. Human bone marrow biochemical functions and megaloblastic hematopoiesis after nitrous oxide anesthesia. Anesthesiology 1981; 55: 645–9.[Web of Science][Medline]
8. Mckinnon RP, Wildsmith JA. Histaminoid reactions under anaesthesia. Br J Anaesth 1995; 74: 217–28.[Free Full Text]
9. Watkins J. Allergic and pseudo allergic mechanisms in anesthesia. In: Sage DJ, ed. International anesthesiology clinics. Boston: Little, Brown and Company, 1985: 17–40.
10. Doenicke A, Lorenz W, Stanworth D, et al. Effects of propofol on histamine release, immunoglobulin levels and activation of complement in healthy volunteers. Postgrad Med J 1985; 61 (Suppl 3): 15–20.[Abstract/Free Full Text]
11. Lewis RE Jr, Curse JM, Richey JV. Effects of anesthesia and operations on the classical pathway of complement activation. Clin Immunol Immunopathol 1982; 23: 666–71.[Web of Science][Medline]
12. Schutte M, Dicamelli R, Murphy P, et al. Effects of anesthesia, surgery and inflammation upon host defense mechanisms. 1. Effects upon the complement system. Int Arch Allergy Immunol 1975; 48: 706–20.
13. Dacie JV. Transfusion of saline-washed red cells in paroxysmal nocturnal hemoglobinuria. Clin Sci 1948; 7: 65.
14. Brecher E, Taswell HF. Paroxysmal nocturnal hemoglobinuria and the transfusion of washed red cells: a myth revisited. Transfusion 1989; 29: 683–5.
15. Rosse WF. Transfusion in paroxysmal nocturnal hemoglobinuria: to wash or not to wash. Transfusion 1989; 29: 663–4.[Web of Science][Medline]

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Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999