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On-line version ISSN 1806-907X
Rev. Bras. Anestesiol. vol.57 no.6 Campinas Nov./Dec. 2007
Anesthesia for treatment of cardiac aspergillosis in a patient with thrombocytopenia and the judicious use of aprotinin*
Anestesia para tratamiento de aspergilosis cardiaca en paciente con trombocitopenia: el uso con criterio de la aprotinina
Raquel Reis Soares, TSAI; Viviane Ferreira Albergaria, TSAII; Michelle Nacur Lorentz, TSAI; Friederike W.ValadaresI
do Biocor Instituto
IIAnestesiologista do Biocor Instituto; Anestesiologista e Co-Responsável pelo CET do Hospital das Clínicas da UFMG
OBJECTIVES: Aprotinin has been widely used in cardiac surgeries as a therapeutic
resource for reducing the effects of cardiopulmonary bypass (CPB) on coagulation
and fibrinolysis. Recovery of adequate hemostasia at the end of the procedure
is one of the objectives of the anesthesiologist. However, aprotinin has specific
indications. The objective of this report was to present the case of a patient
with severe thrombocytopenia undergoing cardiac surgery in which consultation
with Hematology and adequate planning were responsible for the success of the
CASE REPORT: An 18-year old male patient, weighing 64 kg, physical status ASA IV, with a diagnosis of bone marrow aplasia, was being investigated to undergo bone marrow transplantation. He had persistent fever for a month, which did not improve with antibiotics. During the investigation with imaging exams, a left atrial mass was discovered. Laboratory exams revealed hemoglobin 9 g.dL-1 and thrombocytopenia with 6,000 platelets.mm3. He underwent a sternotomy with CPB to remove the intracavitary thrombus. In order to control intraoperative bleeding, the following was administered: plateletpheresis, hydrocortisone, and aprotinin. Increased bleeding and hemodynamic instability did not develop during the surgery, and the patient was transferred to the Intensive Care Unit (ICU) without intercurrences. The anatomo-pathologic exam revealed the thrombus to be filled with Aspergillus (fungal mass). On the seventh postoperative day the patient developed respiratory failure and cardiorespiratory arrest that did not respond to resuscitation maneuvers.
CONCLUSIONS: Despite the increased risk of bleeding in this patient, cardiac surgery with CPB was performed without intercurrences due to the use of aprotinin and plateletpheresis.
Key Words: ANESTHESIA, Cardiac, general; DISEASES: aspergillosis, bone marrow aplasia, thrombocytopenia; DRUGS: aprotinin; SURGERY, Cardiac: cardiopulmonary bypass, left atrial mass.
Y OBJETIVOS: La aprotinina ha sido muy utilizada en intervenciones quirúrgicas
cardiacas como recurso terapéutico para la reducción de los efectos
de la circulación extracorpórea (CEC) sobre la coagulación
y la fibrinólisis. La recuperación de la hemostasia adecuada al
final del procedimiento es uno de los objetivos del anestesiólogo. Sin
embargo, el uso de la aprotinina tiene una indicación específica.
El objetivo de este trabajo fue presentar el caso de un paciente con plaquetopenia
intensa sometido a la intervención quirúrgica cardiaca en el cual
la interconsulta con hematología y la planificación adecuada permitieron
el éxito del procedimiento.
RELATO DEL CASO: Paciente del sexo masculino, 18 años, 64 kg, estado físico ASA IV, portador de aplasia de medula, en investigación para ser sometido al transplante de médula. Presentaba fiebre persistente, de un mes de evolución, sin mejoría con antibioticoterapia. En la investigación con métodos de imagen, se diagnosticó masa intra atrial izquierda. En el examen de laboratorio presentaba hemoglobina de 9 g.dL-1 y trombocitopenia 6.000 plaquetas mm-3. Se sometió a la esternotomía con CEC para retirada de trombo intracavitario. Con el objetivo de controlar el sangramiento intraoperatorio fueron administrados: plaqueto-aferesis, hidrocortisona y aprotinina. Durante la intervención quirúrgica no hubo aumento del sangramiento ni inestabilidad hemodinámica y el paciente fue llevado a la Unidad de Terapia Intensiva (UTI) sin intercurrencias. El examen anátomo patológico reveló trombo repleto de Aspergilus (masa fúngica). Al sétimo día del postoperatorio el paciente evolucionó con insuficiencia respiratoria y parada cardiorrespiratoria sin respuesta a las maniobras de reanimación.
CONCLUSIONES: A pesar del gran riesgo de sangramiento en el paciente descrito, se logró realizar la intervención quirúrgica cardiaca con CEC sin intercurrencias gracias al uso de aprotinina y plaquetoaféresis.
Cardiopulmonary bypass leads to the consumption of coagulation factors and change platelet function by the contact between the blood and the non-endothelial surfaces of the circuit, mechanical stress, and hemodilution. However, the treatment of coagulopathies associated with cardiac surgeries should be guided by laboratorial evaluation. Prophylactic administration of coagulation factors should not be encouraged. This report presents the case of a patient with preoperative thrombocytopenia secondary to bone marrow aplasia who needed surgery for removal of a mass in the left atrium. Orientation from Hematology, that was responsible for the patient, was extremely important to reduce intraoperative bleeding. Aprotinin offers clinical benefits by inhibiting the excessive activation of coagulation and fibrinolysis, and it is indicated in cases of altered hemostasia, risk of increased bleeding, need to protect the platelets, and it also has anti-inflammatory properties. Its use has been indicated in expected cases of thrombocytopenia: liver transplant surgeries 1 and cardiac surgeries with hematologic disturbances 2.
An 18-year old male patient, physical status ASA IV, body mass index 25.8 kg.m-2, with a diagnosis of bone marrow aplasia for 10 years, was admitted to the hospital with persistent fever for one month, which did not improve with antibiotics.
Laboratory exams revealed anemia, with hemoglobin 9 g.dL-1; thrombocytopenia, with 6,000 platelets.mm-3; and leukopenia with 1,000 leukocytes.mm-3. The patient was investigated to locate a probable infection. Chest X-rays revealed an image suggestive of pneumonia in the right upper lobe, and CT scan of the chest showed a mass in the left atrium. Echocardiogram diagnosed a large mass in the left atrium compatible with a tumor, raising the suspicion of a left atrial myxoma or vegetation. Biventricular systolic function was preserved, but there was a 21 mmHg pressure gradient in the left atrium.
The patient was being treated with antibiotics (vancomycin, cephepime, and amphotericin B) for three weeks. During the treatment, BUN increased to 57 mg.dL-1 and creatinine to 1.9 mg.dL-1 and, therefore, vancomycin was discontinued. He was also on pulse hydrocortisone prescribed by Hematology. Blood cultures were negative.
Surgery for removal of the left atrial mass was indicated with plateletpheresis every 12 hours, hydrocortisone, and aprotinin to control bleeding.
The patient received 10 mg of oral diazepam the night before the procedure. Upon admission to the operating room, he was calm and hemodynamically stable. After institution of monitoring with cardioscope, pulse oximetry, and non-invasive blood pressure, venopuncture was performed with a 20G catheter, followed by sedation with 3 mg of midazolam. Afterwards, a 20G catheter was introduced in the left radial artery. Mean arterial pressure was 70 mmHg, heart rate 100 bpm, and SpO2 96%. Anesthesia was induced with fractionated doses of fentanyl (for a total of 15 µg.kg-1), midazolam (up to a total of 7 mg), and atracurium (0.5 mg.kg-1) for the neuromuscular blockade and endotracheal intubation. Hemodynamic changes were not observed during induction. Blood gas analyzer, esophageal temperature, and serial laboratorial tests were added to the monitoring. A long-standing 16G catheter was introduced in the right subclavian vein without intercurrences, and venous central pressure was monitored; initially, it was 16 mmHg. Inhalational anesthesia was maintained with isoflurane, varying from 0.5 to 1 MAC, according to the needs of the patient.
Following the recommendations of the manufacturer, a test dose of 1 mL of aprotinin (10,000 KIU kallikrein inhibitor unit) was administered. After the test dose of aprotinin, which did not cause any reaction, the drug was administered as follows: 2,000,000 KIU over 40 minutes after anesthetic induction, followed by 2,000,000 KIU in the priming of the cardiopulmonary bypass, and 500,000 KIU during the remainder of the surgery. Aprotinin was administered through the central venous access without hemodynamic repercussions. Surgical access was through a thoracic incision and sternotomy.
Heparin, 4 mg.kg-1, was administered in order to maintain the activated coagulation time (ACT) above 600 seconds during cardiopulmonary bypass. After CPB was initiated, the left atrium was opened, revealing a large thrombus extending into the right pulmonary vein. Additional doses of fentanyl (10 µg.kg-1), midazolam (5 mg), and atracurium (0.4 mg.kg-1) were administered during CPB. The patient tolerated well the removal of the CPB, which lasted for 60 minutes. After administration of protamine, plateletpheresis was initiated. During revision of hemostasia, there was no evidence of increased bleeding. The activated coagulation time at the end of the surgery was 120 seconds. The patient was transferred to the ICU hemodynamically stable, without inotropic support or significant bleeding. He was extubated 4 hours after the procedure, and was discharged to the regular ward after 48 hours.
Anatomo-pathological examination revealed the thrombus to be filled with Aspergillus, which also occluded the upper pulmonary veins.
After the surgery, the patient continued to be followed by Hematology, and he needed several transfusions of red blood cell concentrates and plateletpheresis due to the bone marrow aplasia.
One week after the surgery, the patient developed respiratory failure, which did not respond to therapeutic measures. He was transferred to the ICU where a new echocardiogram revealed another mass in the left atrium invading the pulmonary veins. The patient evolved with cardiorespiratory arrest and did not respond to the resuscitation procedures.
Cardiac aspergillosis in its different forms, such as endocarditis, myocarditis, or fungal mass, is an opportunistic infection affecting immunocompromised patients 3. The prognosis of fungal masses is related to their risk of embolization, which indicates the need of immediate surgery 4.
In the case of a patient with bone marrow aplasia with severe thrombocytopenia, it was necessary to discuss with the Hematology service of the hospital in order to prepare the surgery with cardiopulmonary bypass.
Thrombocytopenia and coagulation deficits should always be investigated by the medical team before major surgeries. Only 30,000 to 50,000 platelets.mm-3 with normal function are necessary to form a blood clot. The half-life of a platelet is approximately 8 hours, and the bone marrow usually produces 70,000 platelets.mm-3 a day. One unit of platelets increases the platelet count in 4,000 to 20,000 mL-1 5,6. Cases like the one presented here demand special arrangements for the anesthetic-surgical procedure. It was decided to use preoperative corticotherapy to increase the number of platelets, plateletpheresis every 12 hours pre-, intra-, and postoperatively, and full doses of aprotinin. Plateletpheresis is a specific collection of platelets in which a volume corresponding to 8 to 10 units of platelets are extracted from one donor. It is the best option for patients on chronic transfusion of blood products.
Aprotinin is a polypeptide derived from bovine lung, which has plasmin, trypsin, and kallikrein inhibitor activity in humans, forming reversible enzyme-inhibitor complexes. These enzymes are involved in coagulation, fibrinolysis, and in the inflammatory cascade, demonstrating the capacity of aprotinin to modulate several systemic processes 7. This drug has been extensively used in the last 10 years in cardiac interventions due to its capacity to decrease intraoperative bleeding, the need of blood products, and systemic inflammatory response to cardiopulmonary bypass. Despite the known risks to kidney function, tendency for thromboembolic events, and anaphylaxis, aprotinin has been approved by the Food and Drug Administration. In a recent study, Mangano et al. reported that cardiac, brain, and renal complications are twice as often in patients treated with aprotinin when compared with patients without anti-fibrinolytics 8. Until that report, all studies presented by different groups had not shown similar results 7,9,11. The work of Mangano was criticized for using two very different groups of patients. The aprotinin group had greater incidence of lung, liver, and renal disorders, diabetes mellitus, hypertension, angina, and increased frequency of repeated surgeries and vascular procedures 12. It is believed that aprotinin is a drug with adequate risk/benefit ratio, and it should be reserved for cases with a need to reduce blood loss 13.
Judicious use of aprotinin, respecting its indications and limitations, decreases intraoperative bleeding, which is extremely important in some situations, including the case described here. Antifibrinolytic treatment is routine in pediatric cardiac surgeries with extensive suturing, repeated surgeries, and surgeries with circulatory arrest and profound hypothermia. It is also used in patients with bleeding disorders. It has been reported the successful use of aprotinin in a cardiac surgery in a patient with Jacobsen syndrome, a rare autosomal dominant disorder that manifests with delayed neuropsychomotor development, cardiac abnormalities, and thrombocytopenia 2. Surgeries in patients with hematologic disorders represent a great challenge due to the risk of bleeding, infection, and delayed healing 14. Special cases should be discussed with the Hematology Department in order to program measures to reduce intraoperative bleeding. Although the death of this patient was secondary to its baseline disease, the surgery evolved without intercurrences, with adequate control of intraoperative bleeding, the greatest risk in this case.
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Dra. Raquel Reis Soares
Rua Groelândia, 375/704 Sion
30320-060 Belo Horizonte, MG
Submitted em 23
de outubro de 2006
Accepted para publicação em 21 de agosto de 2007
* Received from Hospital Biocor, Nova Lima, MG