Abstract

Pheochromocytoma is a catecholamine-producing tumor but rarely delayingly diagnosed until during pregnancy. We reported a pregnant woman who underwent emergent cesarean section because of intrauterine growth retardation, oligohydramnios, and hypertension. The existence of an undiagnosed pheochromocytoma was suspected by the unusual hemodynamic response to spinal anesthesia, abdominal compressions, and operative stimulus. Hypertensive crisis occurred during the operation and she was sent to the intensive care unit for postoperative care. In the intensive care unit, cardiovascular collapse occurred after nonselective β-adrenergic blockade. Unexpected hypertensive crisis during the perioperative period should alert clinicians to the possibility of a pheochromocytoma. For the treatment of choice, nonselective β-adrenergic blockade should not be used before the α-blockade.

Keywords

heart arrest; hypertension; labetalol; malignant; pheochromocytoma;

1. Introduction

Anesthetic management of pregnant women with an undiagnosed pheochromocytoma is an awful and challenging sweat. Its symptoms may be confused with those of preeclampsia. Furthermore, anesthetic drugs, operation, or any stimulus may precipitate a hypertensive crisis and the mother and fetus may be exposed to a significant risk of death. In the cases reported between 1980 and 1987, the maternal and fetal mortality rates were 33% and 39%, respectively, when the diagnosis was not made before labor.¹ Prompt recognition of the presence of pheochromocytoma is important so that the proper treatment can be arranged. We report a pregnant woman with suspected pheochromocytoma because of her unusual hemodynamic response to spinal anesthesia, abdominal compressions, operative stimulus, and cardiovascular system collapse after nonselective β-adrenergic blockade at the intensive care unit (ICU). We also discuss the diagnosis of pheochromocytoma during pregnancy, the mechanism of nonselective β-adrenergic blockade-induced cardiovascular system collapse, anesthesia for pheochromocytoma in pregnancy, and the proper treatment of hypertensive crisis.

2. Case report

A 35-year-old, Gravida 6, Para 3, 65 kg woman underwent emergent cesarean section (C/S) at 34 3/7 weeks of gestation because of oligohydramnios, intrauterine growth retardation, and hypertension. She had history of hypertension for about 10 years and was under regular follow-up at our cardiology clinic. Her current medications included acebutolol 800 mg twice daily and methyldopa 500 mg thrice daily. In addition, she sustained four miscarriages because of hypertension-related complications. During this pregnancy, her blood pressure was supervised regularly by her cardiologist and it ranged from 130/80 mmHg to 160/100 mmHg. Her last cardiology visit was 1 week before the delivery. During her obstetric visits at 34 3/7 weeks of gestation, her blood pressure rose somewhere about 245/134 mmHg, whereas her heart rate was 62 beats per minute (bpm). Moreover, poor fetal movement was noted. Because antihypertensive therapy was ineffective, in considering the risk of persistent hypertension, emergent C/S was arranged.

At the operating room, her blood pressure was 236/137 mmHg and her heart rate was 70 bpm. On physical examination, there was no evidence of peripheral edema or other abnormality. Spinal anesthesia was performed with 11 mg bupivacaine. The sensory block as checked was up to T5–T6. Surprisingly, 5 minutes after spinal anesthesia, her blood pressure did not drop. Instead, it increased to 260/145 mmHg and her heart rate remained at 75 bpm. Nicardipine 1 mg was administered intravenously and her blood pressure decreased to 170/100 mmHg, whereas her heart rate was 80 bpm. However, after the abdominal compression for delivery of a 1.426 kg male baby, her blood pressure and heart rate abruptly rose to 260/140 mmHg and 110 bpm, respectively. Nicardipine 2 mg and apresoline 5 mg were administered incrementally, but her blood pressure remained at 220/130 mmHg and her heart rate increased to 130 bpm by the end of surgery. Although severe hypertension and tachycardia were noted, the mother did not complain of any discomfort.

At the recovery room, her blood pressure was 223/145 mmHg and her heart rate was 125 bpm. Apresoline 10 mg was administered intravenously again, but blood pressure did not drop. Furthermore, her heart rate increased to 160 bpm. Persistent severe hypertension and marked tachycardia progressively existed despite the antihypertensive therapy. At this time, her unusual hemodynamics led us to suspect the presence of a pheochromocytoma. We consulted the cardiologist and sent her to the ICU for postoperative care.

At the ICU, her blood pressure was 249/160 mmHg and her heart rate was 138 bpm. The on duty cardiology resident considered that she was a case of essential hypertension with acute crisis. Continuous labetalol infusion was administered under intra-arterial blood pressure monitoring. The patient’s blood pressure slowly decreased to 198/145 mmHg and her heart rate lingered about at 136 bpm after 2 hours of treatment. By the 3^rd hour after labetalol 35 mg was used, her heart rate and blood pressure dropped to 128 bpm and 90/84 mmHg, respectively. Her pulse pressure became severely narrowed. Labetalol infusion was discontinued and dopamine was administered immediately. However, her cardiovascular function suddenly collapsed 10 minutes later. She lost consciousness and her electrocardiogram showed ventricular fibrillation. Cardiovascular resuscitation was performed; however, the patient died 48 hours later. Computed tomography performed after resuscitation showed a 3 cm × 4.5 cm × 6 cm retroperitoneal enhancing mass located between the pancreatic head and inferior vena cava (Fig. 1). Post mortem histolopathological examination confirmed the mass to be a pheochromocytoma.

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Fig. 1. Computed tomography scan shows a 3 cm × 4.5 cm × 6 cm retroperitoneal enhancing mass (arrow) located between the pancreatic head and inferior vena cava.

3. Discussion

Pheochromocytoma is a rare catecholamine-producing tumor with an estimated annual incidence of 2–8 per million population. The prevalence in hypertensive patients is 0.2–0.4%.² Pheochromocytoma arises from chromaffin cells of adrenal and extra-adrenal sites. It can secrete endogenous catecholamines, such as norepinephrine, epinephrine, and dopamine or their metabolites (metanephrine and vanillyl mandelic acid), which create hemodynamic instability and hypertensive crises. These hormones are released intermittently and not continuously in most cases and the typical symptoms are headache, sweating, and palpitation during the attack. Seventy-five percent of affected patients suffer from attacks weekly, others several times per day or just once every few months.³ However, the classic triad of headache, palpitations, and sweating in the presence of hypertension has high specificity (93.8%) and sensitivity (90.9%) for the diagnosis of pheochromocytoma.⁴

Antenatal recognition of pheochromocytoma and subsequent pharmacological or surgical therapy are important because they may improve maternal and fetal outcomes. The maternal and fetal mortality rates decreased to 17% and 26%, respectively when the diagnosis was made before labor.¹ Pheochromocytoma can mimic the symptoms and signs of preeclampsia and therefore the diagnosis is often missed. However, preeclampsia is usually accompanied by proteinuria, sudden weight gain, and edema, as well as liver and coagulation abnormalities. In hypertension associated with pheochromocytoma, excessive urinary protein excretion and liver or coagulation abnormalities occur rarely, and sudden weight gain and edema are unusual.⁵ Screening should be undertaken in those with accelerated or progressive hypertension; hypertension occurring at a young age or not responding to conventional treatment; and those with pressor responses to induction of anesthesia, intravenous contrast media, or labor.⁶ Unexplained severe hypertension and tachycardia after induction of general anesthesia must raise the suspicion of undiagnosed pheochromocytoma.⁷ And in a case of sustained, paroxysmal hypertension or paradoxical hypertension despite antihypertensive therapy, especially during therapy with β-blockers, the diagnosis of pheochromocytoma has to be kept in mind and ruled out.² If an undiagnosed pheochromocytoma is suspected, urine total metanephrines, serum total catecholamines, and urine vanillylmandelic acid should be checked. Magnetic resonance imaging is suggested as the initial imaging technique for diagnosis and localization diagnosis and has a sensitivity ranging from 90% to 100%.⁸ Magnetic resonance imaging and ultrasound are the preferable methods for localization of tumor in pregnant patients to avoid exposing the fetus to ionizing radiation.

Spinal anesthesia-induced hypotension is usually observed in the ordinary pregnant woman. However, our patient’s blood pressure contrarily increased up to 260/145 mmHg after spinal anesthesia. Although her blood pressure slightly decreased after nicardipine therapy, it elevated abruptly again after the abdominal compressions during delivery. Pheochromocytoma with ongoing hypertensive crisis was then suspected. Hypertensive crises can be precipitated by straining, pressure on the abdomen, and drugs, such as anesthetics.⁷ Patients with pheochromocytoma crisis may present with clinical features of profound sweating, marked tachycardia, pallor, numbness, tingling, and coldness of hands and feet.⁹ If pheochromocytoma is suspected as the underlying cause of the hypertensive crisis, the treatment of choice should be intravenous α blockers, such as phentolamine (1–5 mg repeated every 15 minutes as required) or phenoxybenzamine (1 mg/kg infused over at least 2 hours). An alternative treatment would be sodium nitroprusside.

Nonselective β-blockade, with agents, such as labetalol, is considered dangerous in pheochromocytoma patients. Labetalol blocks α1-, β1-, and β2-adrenoreceptors, but it has predominantly β-adrenoreceptor blocking activity and has only weak α-blocking activity. The ratio of α-blockade to β-blockade has been estimated to be approximately 1:7 following intravenous administration.¹⁰ There have been several reports of worsening of hypertension, hypertensive crises, or pulmonary edema in pheochromocytoma patients treated with labetalol and propranolol before α-blockade.11, 12, 13, 14 Initiation of nonselective β-blocker therapy without preceding α-blockade in a patient with pheochromocytoma may precipitate a crisis with hemodynamic collapse. Nonselective β-blockade leads to loss of β-2 receptor-mediated vasodilatation and the unopposed effects of α-receptors cause vasoconstriction, resulting in arterial hypertension and increased afterload, causing myocardial dysfunction, pulmonary edema, and death.2, 5, 7, 15 Nonselective β-blockers should be avoided in any patient who could conceivably have a pheochromocytoma.

Stonham and Wakefield¹⁶ reported two cases for C/S in whom epidural anesthesia was successfully performed with the pheochromocytoma having been antenatally diagnosed. These patients were invasively monitored throughout and received preoperative phenoxybenzamine, which produced cardiovascular stability and led to the delivery of healthy infants. The adrenal glands are innervated by sympathetic nerves from T5 to T12, thus epidural sympathetic blockade across these levels would obtund the neurogenic stimulation of a possible adrenal tumor. An epidural anesthesia would also provide optimal analgesia, thus reducing catecholamine concentration further.¹⁷ Magnesium sulphate infusions could also be used as the main antiadrenergic agent during the surgical management of pheochromocytoma in pregnant women. The rationale for using magnesium infusions is based on the ability of magnesium to inhibit the release of catecholamines from the adrenal medulla, reduce the sensitivity of the α-adrenergic receptors to catecholamines, and to exert a direct vasodilator effect.18, 19

In conclusion, the identification of the parturient with hypertension secondary to pheochromocytoma is difficult. We should always keep in mind the possibility of pheochromocytoma when unexplained cardiopulmonary dysfunction occurs during the perioperative period or after the institution of β-blockade. If pheochromocytoma is suspected, nonselective β-adrenergic blockers should not be used before α-blockers because they can increase the systemic vascular resistance, causing myocardial dysfunction, pulmonary edema, and death.