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Print version ISSN 0034-7094
Rev. Bras. Anestesiol. vol.55 no.3 Campinas May/June 2005
Anesthesia in obstetric patient with sickle cell anemia and thalassemic trait after plasmapheresis. Case report*
Anestesia en paciente obstétrica portadora de anemia falciforme y trazo talasémico después de plasmaféresis. Relato de caso
Eduardo Barbosa Leão, M.D.I; Guilherme A M de Barros, M.D.II; Laís H C Navarro, M.D.III; Yara Marcondes Machado Castiglia, TSA, M.D.IV
IME2 do CET/SBA do Departamento
de Anestesiologia da FMB-UNESP
IIDoutorando de Anestesiologia da FMB-UNESP, Médico da Disciplina de Terapia Antálgica e Cuidados Paliativos da FMB-UNESP
IIIMédica do Departamento de Anestesiologia da FMB-UNESP
IVProfessora Titular do Departamento de Anestesiologia da FMB-UNESP
BACKGROUND AND OBJECTIVES: Plasmapheresis
is the technique of choice for severe hemolytic anemia patients. A consequence
is plasma cholinesterase depletion, which interferes with metabolism of some
neuromuscular blockers currently used in anesthesiology.
CASE REPORT: Pregnant patient, 26 years old, physical status ASA IV, 30 weeks and 3 days gestational age, with sickle cell anemia, thalassemic trait and allo-immunization for high frequency antigens. Patient presented sickling crisis being transfused with incompatible blood. Patient evolved with massive hemolysis being admitted with 3 g/dL hemoglobin and 10% hematocrit, severe jaundice, tachycardia, apathic and pale. Hematological evaluation has concluded for the inexistence of compatible blood for transfusion. Patient was treated with steroids, immunoglobulins and plasmapheresis. In the second admission day patient evolved with acute renal failure and pulmonary edema, general state worsening and hemodynamic instability. Gestation resolution was indicated due to patient's clinical conditions and consequent acute fetal suffering. Patient was admitted to the operating room conscious, pale, with dyspnea, jaundice, 91% SpO2 in room air, heart rate of 110 bpm and blood pressure of 110 x 70 mmHg, under dopamine (1 µg.kg-1.min-1) and dobutamine (10 µg.kg-1.min-1). We decided for balanced general anesthesia with alfentanil (2.5 mg), etomidate (14 mg), atracurium (35 mg) and isoflurane. There were no anesthetic-surgical intercurrences. Patient was referred to ICU after surgery completion under tracheal intubation and vasoactive drugs, being extubated 3 hours later.
CONCLUSIONS: This case was a challenge for the team since patient was hemodynamically instable with coagulogram abnormalities counterindicating regional anesthesia. In addition, plasmapheresis potentially depletes plasma cholinesterase reserves, interfering with anesthesia. However, available drug armamentarium has allowed for the safe management of this situation.
Key words: ANESTHESIA, Obstetric: plasma cholinesterase; THERAPEUTIC: plasmapheresis
JUSTIFICATIVA Y OBJETIVOS: La plasmaféresis
es una técnica de tratamiento de elección para pacientes con anemia
hemolítica grave. Una de sus consecuencias es la depleción de
colinesterasa plasmática, lo que interfiere en la metabolización
de algunos bloqueadores neuromusculares de uso corriente en la práctica
RELATO DEL CASO: Paciente con 26 años, estado físico ASA IV, gestación de 30 semanas y 3 días, portadora de anemia falciforme, trazo talasémico y alo-inmunización para antígenos de alta frecuencia. Presentó crisis de falcización, siendo transfundida con derivado sanguíneo incompatible. Evolucionó con hemólisis maciza, siendo admitida con hemoglobina de 3 g/dL y hematócrito del 10%, ictericia intensa, taquicardia, apatía y con pérdida de color. En la evaluación hematológica se concluyó ser una situación de inexistencia de sangre compatible para transfusión. Fue tratada con corticoterapia, inmunoglobulinas y plasmaféresis. En el segundo día de internación, evolucionó con insuficiencia renal aguda y edema pulmonar agudo, empeoramiento del estado general e inestabilidad hemodinámica. Indicada la resolución de la gestación como resultado del cuadro clínico de la paciente y del sufrimiento fetal agudo que se sobrepuso. La paciente fue admitida en la sala de operaciones consciente, disneica, pálida, ictérica, SpO2 del 91% en aire ambiente, frecuencia cardiaca de 110 lpm y presión arterial de 110 x 70 mmHg, en uso de dopamina (1 µg.kg-1 min-1) y dobutamina (10 µg.kg-1.min-1). Se optó por anestesia general balanceada, con alfentanil (2,5 mg), etomidato (14 mg) y atracúrio (35 mg) e isoflurano. No se observó interocurrencias anestésico- quirúrgicas. Al final, la paciente fue encaminada a la UTI, bajo intubación orotraqueal, y en uso de drogas vasoactivas, habiendo sido extubada después de 3 horas.
CONCLUSIONES: Este caso se mostró un desafío para el equipo, ya que la paciente presentaba inestabilidad hemodinámica y alteración del coagulograma, condiciones que contraindican la anestesia regional, además de esto, la plasmaféresis potencialmente depleta las existencias de colinesterasas plasmáticas, lo que interfiere en la anestesia. Mientras, el arsenal medicamentoso disponible, permitió el manoseo seguro de esta situación.
Plasmapheresis is the technique of choice for severe hemolytic anemia patients. A consequence of this procedure is depletion of plasma cholinesterase, enzyme responsible for acetylcholine hydrolysis 1-4, which interferes with the metabolism of some neuromuscular blockers currently used in anesthesia 5,6.
Pregnant patient, 26 years old, 72 kg, 1.66 m, fourth gestation, second labor, one abortion and one previous C-section, physical status ASA IV, 30 weeks and 3 days gestational age, no spleen, with sickle cell anemia, thalassemic trait and allo-immunization for high frequency antigens.
Patient presented viral respiratory infection in her home city evolving with sickling crisis and was transfused with red cells concentrate from the same isogroup, since her pre-transfusion hemoglobin was 6 g/dL. After transfusion, patient evolved with massive hemolysis being then urgently transferred to Hospital das Clínicas Botucatu - UNESP. At admission, parturient was in bad general state, apathic and asthenic. At physical evaluation she was extremely pale, with jaundice, fine pulses, tachycardia, systolic murmur 3+/6+, normal pulmonary auscultation, normotensive and anuric.
Overt hemolytic crisis (hemoglobin 2.4 g/dL and hematocrit 6%) and compensated disseminated intravascular coagulation were diagnosed, that is, with normal platelet count. Hematological evaluation has concluded that this is was situation in which there was no compatible blood to be transfused, reason why patient developed hemolytic reaction after red cells concentrate administered in her home city. So, patient was allo-immunized for erythrocyte antigens (anti-Kell, anti-E, anti-Duffyª, anti-S), in addition to presenting allo-antibody directed against a highly frequent antigen among population - VEL. Therapy consisted of: 1) 2.5 volume plasmapheresis; 2) intravenous 1 g.kg-1/day human immunoglobulin for two days; 3) washed, irradiated, without leucocytes, phenotyped red cells concentrate compatible with Kell, E, Duffyª and S systems, however incompatible with VEL system; 4) erythropoietin. Important clinical improvement was observed after this therapy.
In the second admission day, patient evolved with acute renal failure (ARF) due to hemoglobin breakdown products deposition in renal tubules. Patient also presented acute pulmonary edema with consequent volume overload determined by transfused human immunoglobulin and worsened by coexisting ARF. Patient evolved with general state worsening and hemodynamic instability. Heart failure as consequence of severe anemia - cor-anemic was characterized.
Faced to the severity of conditions, multidisciplinary team was involved in the treatment of this patient got together: Hematology, Anesthesiology and Obstetrics agreed with immediate gestation resolution due to patient's progressive and unstable clinical condition and consequent acute fetal suffering.
Patient was urgently referred to the obstetric center where she was admitted conscious, dyspneic, with increased respiratory rate, pale, with jaundice, 91% SpO2 in room air and bilateral clicking rales in 2/3 lower lungs. Heart rate was 110 bpm and blood pressure 110 x 70 mmHg, under dopamine (1 µg.kg-1.min-1) and dobutamine (10 µg.kg-1.min-1). Monitoring consisted of stethoscope, noninvasive blood pressure, cardioscopy, capnography with capnometry, pulse oximetry, blood gases analyzer and vesical catheter. Preoperative lab tests are shown in table I.
We decided for balanced general anesthesia after clinical and lab evaluation. Anesthesia was induced with tracheal intubation in rapid sequence with Sellick's maneuver. Drugs were alfentanil (35 mg.kg-1), etomidate (0.2 mg.kg-1) and atracurium (0.5 mg.kg-1). Anesthesia was maintained with isoflurane in variable concentrations, as needed.
Intraoperative metabolic acidosis was treated with sodium bicarbonate (100 mEq) and adequate mechanical ventilation. Acute pulmonary edema was treated with 40 mg furosemide and 100 g mannitol. One unit of phenotyped red cells compatible with the four systems already described, however incompatible with VEL system was transfused. There were no anesthetic-surgical intercurrences.
Patient was referred to ICU after surgical completion intubated, sedated with midazolam and under vasoactive drugs, being extubated 3 hours later. Hemodialysis sessions were performed with satisfactory clinical evolution. Patient was discharged 4 weeks later with her baby with no sequelae.
Current anesthesiologists are faced with extremely severe situations. In these cases, they need the cooperation of other specialists, as in our case. This interaction is extremely beneficial for patients' evolution, in addition to being an opportunity to share experiences and knowledge from different medical areas.
Sickle cell anemia incidence is expressive in Brazilian population, especially among Afro-American people. Sickling crises are triggered by multiple factors such as infection, dehydration and hypothermia, among others, and may lead to blood transfusions. When sickling crises are recurrent or there are other hematological diseases with periods of acute anemia, there is the need for repeated blood transfusions and the consequence may be sensitization to blood antigens frequent among general population.
This becomes a very delicate situation and depends on the number and the antigens against which patients develop specific antibodies. If VEL antigen, extremely frequent among general population, is among those against which patients' are sensitized, there will be huge difficulties to find compatible blood to be transfused 7.
This case was a challenge for the team. It was a patient with hemodynamic instability, acute pulmonary edema, acute renal failure, coagulopathy secondary to acute transfusion hemolytic reaction and liver overload with splenectomy.
Due to described clinical condition, it was difficult to choose the most adequate anesthetic technique. Coagulopathy and hemodynamic instability are conditions counterindicating neuraxial anesthetic block 8,9. In addition, pregnancy and plasmapheresis potentially deplete more than 80% of plasma cholinesterase reserves 10-13, which interferes with anesthetic agents depending on this enzyme for metabolism, such as succinylcholine, and with some nondepolarizing neuromuscular blockers, such as mivacurium 14-18.
Because blockades were counterindicated, we decided for balanced general anesthesia with controlled ventilation. Choice of perianesthetic drugs was based not only on gestational physiological changes but also on pathological conditions adding to severity.
So, anesthesia was induced with etomidate, which is a hypnotic providing satisfactory hemodynamic stability 19-23, being useful in situations of maternal hypovolemia and hemorrhage, as well as for cardiac parturients and those not tolerating decreased peripheral vascular resistance 24. Alfentanil was the opioid of choice for having low pKa, fast onset, short duration and high protein binding, which decreases placental crossing 25-28. Although potentially inducing transient respiratory depression in the neonate when used in doses above 10 µg.kg-1 24, alfentanil for anesthetic induction attenuates maternal response to intubation stress and surgical nociceptive stimulations 29.
At the end of gestation, uterine vascular bed is in its highest vasodilation level 30. So, increased maternal catecholamine concentration caused by tracheal intubation 31,32 decreases uterine blood flow 33,34 in up to 35% 35, compromising fetal vitality 36. This way, 15 to 30 µg.kg-1 alfentanil is an effective measure to attenuate adrenergic response to tracheal intubation 37.
Atracurium and cisatracurium are nondepolarizing neuromuscular blockers metabolized by Hoffmann's reaction 38,39 and independent of plasma acetylcholinesterase activity and renal and liver functions 40-43. Both drugs could have been used in our case, however atracurium was chosen due to lower cost and the lack of specific indications for cisatracurium.
All inhalational anesthetics cross the placental barrier 44. Fetal effects are minor when birth occurs in less than 10 minutes after anesthetic induction. However, with prolonged maternal administration, fetal blood anesthetic concentration is close to mother's, inducing fetal sedation 24. Isoflurane for Cesarean section is well documented in the literature.
In a study by Tunstall et al. 45 and Piggott et al. 46, 1.25% to 1.8% isoflurane concentrations have not caused maternal awareness and neonate depression, thus being well tolerated by both 47,48. Low fetal blood isoflurane solubility as compared to maternal solubility, assures its fast fetal excretion 24,49. In some situations in which regional anesthesia is counterindicated, 0.5% to 1.5% isoflurane may be used to maintain anesthesia for Cesarean section 50. Clinically, isoflurane and sevoflurane are similar when administered for general anesthetic maintenance during elective Cesarean section in terms of maternal-fetal effects 50,51 ,and in all parameters used to evaluate fetal evolution, such as CSF gases analysis, Apgar score and neurological adaptative capacity score 50. Drugs used allowed for adequate and safe management of this situation with satisfactory outcome.
01. Wood L, Jacobs P, Dubovsky DW et al -The role of continuous-flow blood fraction separators in clinical practice. S Afr Med J, 1981;59:99-104. [ Links ]
02. Menges T, Wagner RM, Welters I et al - The role of the protein C-thrombomodulin system and fibrinolysis during cardiovascular surgery: influence of acute preoperative plasmapheresis. J Cardiothorac Vasc Anesth, 1996;10:482-489. [ Links ]
03. von Bormann B, Boldt J, Schleinzer W et al - Hemodynamics in donor plasmapheresis. Anaesthesist, 1988;37:316-320. [ Links ]
Dr. Eduardo Barbosa Leão
Address: Av. Caetité 175, Centro
ZIP: 46190-000 City: Paramirim, Brazil
Submitted for publication July 12, 2004
Accepted for publication January 20, 2005
* Received from Departamento de Anestesiologia da Faculdade de Medicina de Botucatu (FMB-UNESP), Botucatu, SP