Phaeochromocytoma in pregnancy is a rare but significant disorder because of the increased maternal and fetal mortality rates if it is not diagnosed during the antenatal period. Only 33% of such cases are diagnosed before delivery . However, the maternal mortality associated with phaeochromocytoma falls to 11% , and more recently, to 0%  when the diagnosis is made antepartum. The case report describes the present authors' experience of the management of a patient undergoing Caesarean section under epidural anaesthesia immediately followed by the removal of the tumour under general anaesthesia. The peri-operative management of this case, including the use of antihypertensive drugs without fetal crisis, is discussed.
The patient, a 32-year-old gravida 2, para 1, was admitted to the nearest hospital at 29 weeks' gestation with progressive hypertension. After 18 weeks of amenorrhoea, her blood pressure was 130/80 mmHg, at 28 weeks it was 150/90 mmHg and at 29 weeks it was 160/100 mmHg. The patient had no notable family history and no remarkable past medical history including hypertension until her second pregnancy. After admission, the diurnal variation of her blood pressure was unstable, ranging from 110/80 to 150/100 mmHg. A phaeochromocytoma was suspected and the diagnosis was confirmed by the finding of increased urinary vanyl mandelic acid (16.1 ng day−1) and plasma noradrenaline (4.40 mg mL−1) levels. An abdominal ultrasound revealed a 3.5-cm right adrenal mass. Another invasive investigation was not performed because of the side effects on the fetus. Treatment with labetalol (150 mg day−1) was commenced at once. The patient's blood pressure stabilized, ranging from 110/60 to 130/80 mmHg. She was referrred to hospital at 31 weeks of gestation for continuation of the pregnancy and pre-operative preparation for a tumour resection.
After entering hospital, the patient's urinary and plasma catecholamine levels were still high. The magnetic resonance imaging also showed a high-intensity area below the right adrenal gland. An ultrasound examination of the fetus was normal and no anomaly was detected. A case conference was held between the anaesthetists, surgeons and obstetricians. As a result, Caesarean section combined with tumour resection at 35 weeks' gestation was planned.
The day before surgery, the patient received two epidural catheters. One was inserted at the Th8-Th9 interspace for the resection of the tumour, and the other was inserted at the L2-L3 interspace for the Caesarean section. On the morning of surgery, she received ranitidine (50 mg) orally. After her entry to the operating room, a right radial arterial catheter and a pulmonary arterial catheter through the right internal jugular vein were inserted under local anaesthesia with 0.5% of lignocaine. Eight millilitres of 2% mepivacaine was injected through the epidural catheter. After confirming the analgesia, Caesarean section was commenced and 100% oxygen (3 L min−1) was administered via a face mask. The patient's blood pressure and heart rate increased gradually. Until delivery, 0.25 mg of nitroglycerine was administered intermittently to reduce blood pressure and heart rate, and to relax the uterine muscle . A male infant weighing 2894 g was delivered with a 5-min Apgar score of 9. After delivery, an infusion of 0.1 μg kg−1 min−1 prostaglandin E1 (PGE1) was begun in place of the nitroglycerine.
At the end of the skin closure, cricoid pressure was applied and general anaesthesia was induced with thiamyral (250 mg) plus suxamethonium (100 mg). After tracheal intubation, anaesthesia was maintained with 65% nitrous oxide, 35% oxygen and 0.5-1.0% sevoflurane combined with the epidural anaesthesia. Muscle relaxation was obtained with vecuronium bromide. The blood pressure increased to 180/130 mmHg during the manipulation of the tumour. The infusion rate of PGE1 was increased and phentolamine was administered intermittently until the blood pressure decreased to a normal level. After the resection of the tumour the blood pressure decreased rapidly to 80/40 mmHg. The infusion of PGE1 was stopped and 5 μg kg−1 min−1 of dopamine was infused to stabilize the blood pressure. At the end of surgery, the haemodynamic variables were stable and the patient was conscious. The trachea was extubated and the patient was transferred to the intensive care unit (ICU). The total blood loss was 1180 mL and the urine output was 600 mL. A total of 4800 mL of lactate Ringer solution and six units of red blood cells were given intraoperatively. The patient's stay in the ICU was essentially uneventful and she was discharged to the obstetrical ward the following morning. Both mother and baby had an uncomplicated post-operative course and were discharged after 2 weeks.
When a diagnosis of phaeochromocytoma is made during pregnancy, the drug therapy requires careful considerations to avoid maternal and fetal mortality. Phenoxybenzamine, an irreversible alpha-adrenoreceptor antagonist, has been widely used during pregnancy around the world . However, this drug is clinically contraindicated in Japan because of its teratogenic and carcinogenic effects. Prazosin (a postsynaptic alpha-adrenoreceptor antagonist)  and labetalol (an alpha- and beta-adrenoreceptor antagonist)  are recommended during pregnancy. These drugs have no harmful effects on the fetus. The beta-adrenoreceptor antagonist should not be used independently until adequate alpha-blockade is established . In the patient in the present study, labetalol was effective for the control of her blood pressure. No other adrenoreceptor blockade agent was required.
The timing of such a tumour resection and the delivery have aroused much controversy. When the diagnosis is made before 23 weeks' gestation, the tumour should be removed after an adrenergic blockade has been established . After 24 weeks' gestation, an elective Caesarean section combined with tumour removal under adrenergic blockade is often recommended [8,9]. In the past, vaginal delivery was carried out and resulted in a higher mortality (31%) than Caesarean section (19%) . If such a pregnancy has proceeded without the diagnosis of phaeochromocytoma, the outcome can be hazardous. Therefore, the preoperative diagnosis of phaeochromocytoma and the early medication of alpha-blockade are considered to be vital to save maternal and fetal lives. The present patient was diagnosed as having a phaeochromocytoma at 29 weeks' gestation with progressive hypertension. The present authors chose elective Caesarean section, followed immediately by exploration for the tumour.
The difficulty in anaesthetic management of a patient undergoing Caesarean section with phaeochromocytoma is decreasing the risk of hypertension without decreasing uterine blood flow. General anaesthesia with volatile agents and opioids should be avoided if possible because of the hypnotic effects of these drugs on the fetus. Continuous epidural anaesthesia can be employed without major disadvantages . This technique provides pain-free labour, and theoretically reduces the catecholamine response. However, the severe hypertension could not be blocked with epidural anaesthesia during Caesarean section in the present case. Nitroglycerin was administered to control blood pressure, and to maintain uterine blood flow and prevent uterine muscle contraction . After delivery, general anaesthesia was induced, and the nitroglycerine was replaced by PGE1 because of the risk of uterine atony and bleeding. PGE1 has a strong vasodilating effect and contributes to cardiovascular stability. In addition, this drug contracts uterine smooth muscle. In several studies, PGE1 decreased blood pressure by a direct action on the vascular beds  and by inhibiting the catecholamine release from the terminals of sympathetic nerves and the adrenal medulla [12,13]. During the handling of the present tumour, excessive hypertension was controlled by infusing PGE1 (0.1-0.2 μg kg−1 min−1). The total systemic vascular resistance also decreased depending on the dose of PGE1, but levels of plasma catecholamines remained high. These results suggest that the principal mechanism underlying the suppression of hypertension by PGE1 is the dilation of vascular smooth muscle, not a blockade of the sympathetic nervous system.
In summary, a case of phaeochromocytoma removal and Caesarean section with a successful outcome is presented. The patient had pre-operative antihypertensive therapy with an adrenergic blocker. During the surgery, antihypertensive drugs were administered depending on their effects on the uterine blood flow. The anaesthetic methods also varied to avoid fetal crisis. Thus, adequate pre-operative preparation and peri-operative management should reduce maternal and fetal mortality rates in such cases.
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