Anesthesia for Pheochromocytoma in a Surgically Anephric Child

Pheochromocytoma is a rare tumor in children arising from the chromaffin tissue of the adrenal medulla and sympathetic ganglia [1,2]. Early diagnosis [3,4] is important not only because hypertension can be cured [5] but also because unrecognized pheochromocytoma is a potentially lethal risk in patients undergoing surgery for other conditions [6,7]. End-stage renal disease is also a rare condition in childhood with an incidence of 0.5 to 5.5 per million [8]. The association between pheochromocytoma and terminal renal failure seems uncommon, and no case of such association in children has been previously reported in the English literature. Case Report A 13-yr-old boy weighing 24 kg was diagnosed as having an adrenal pheochromocytoma and was prepared for its surgical removal. He had undergone right adrenonephrectomy, followed by postoperative radiation therapy and chemotherapy at the age of 13 mo because of a Wilms' tumor, which was found as part of a Drash syndrome [pseudohermaphroditism, Wilms' tumor, hypertension, and degenerative disease [9]]. At 5 yr of age, conservative management of his nephropathy no longer sufficed and dialysis was required. A renal transplantation was performed when the patient was 6 yr of age. Hypertension (170-160/110-100 mm Hg) resistant to treatment with vasodilators and alpha-adrenergic and beta-adrenergic blockers (doxazosina 0.1 mg/kg, hydralazine 0.25 mg [center dot] kg-1 [center dot] 6 h-1, and atenolol 2 mg [center dot] kg-1 [center dot] 12 h-1) persisted during the posttransplant period, and at the age of 12 years, a left nephrectomy was performed. Dialysis was necessary because of chronic rejection. His arterial blood pressure remained increased and the graft was finally removed. Hypertension persisted, with occasional episodes of headache and sweating. Biochemical screening revealed plasma epinephrine 96 pg/mL (normal 20-60 pg/mL), norepinephrine 580 pg/mL (normal 135-300 pg/mL), and aldosterone 237 pg/mL (normal 17-130 pg/mL). A focal uptake in left adrenal gland was shown by computed tomography (CT) with131 I-labeled meta-iodobenzylguanidine after a normal CT scan. Histopathology confirmed the diagnosis of pheochromocytoma. The patient was placed on daily hemodialysis until 2 days before surgery (type of dialysis: filter NT 0908, blood flow 200 mL/min, dialysis fluid flow 500 mL/min, and ultrafiltration of 200 mL/h). Erythropoietin 50 mg/kg was given intravenously (IV) at the and of each 3-h session. Sixteen hours after the last hemodialysis, results of laboratory tests were as follows: white blood cell count 4300/mm (3), red blood cell count 3650 x 104 mm (3), hemoglobin 11 g/dL, hematocrit 32%, serum levels of sodium 135 mmol/L, potassium 3.8 mmol/L, chloride 102 mmol/L, calcium 8.7 mg/dL, phosphorus 7.1 mg/dL, blood urea nitrogen 125 mg/dL, serum creatinine 5 mg/dL, and blood glucose 85 mg/dL. Arterial blood gas analysis revealed pH 7.44, PaO2 87 mm Hg, Paco2 45.5 mm Hg, and bicarbonate 23.7 mmol/L. The anesthetic technique consisted of thoracic epidural anesthesia with a superimposed general anesthesia. Diazepam 5 mg was given sublingually the night before surgery and repeated 1 h before operation. The patient's monitoring consisted of a continuous electrocardiogram, end-tidal CO2 and Spo2 monitoring, radial artery catheter for direct pressure measurement and blood sampling, urinary catheter, temperature probe, and central venous pressure line. Anesthesia was induced with IV diazepam 0.1 mg/kg, fentanyl 2 micro g/kg, propofol 2 mg/kg, and atracurium 0.5 mg/kg. The trachea was intubated, and anesthesia was maintained with nitrous oxide 50% in oxygen and atracurium 0.5 mg [center dot] kg-1 [center dot] h-1 and propofol 6 mg [center dot] kg-1 [center dot] h-1 using an infusion pump. The patient was placed in the left lateral position. A median approach at T9-10 epidural interspace was used, and correct positioning of the needle was ascertained by using the loss of resistance method with a normal saline-filled syringe. A bolus of 0.5 mL/kg of 0.25% bupivacaine mixed with 50 micro g/kg of morphine was injected using a Tuohy 18-gauge needle. The end of the epidural catheter was placed at T6. Thirty minutes after the initial dose and after a pinprick test, a supra-infraumbilical laparotomy incision was made. During operation, isotonic saline solution 20 mL [center dot] kg-1 [center dot] h-1 was infused during the first hour, and 10 mL [center dot] kg-1 [center dot] h-1 was infused until the end of the surgical procedure. Hemodynamic and biochemical variables were measured (Table 1) after the induction of anesthesia (C1), 15 min after initiation of surgery (C2), during maximal tumor handling (C3), 15 min after tumor removal (C4), and 12 h after surgery (C5).Table 1: Controls of Hemodynamic Parameters and Plasma Concentrations of Catecholamines, Cortisol, Growth Hormone, Glucose, and Insulin at Different Perioperative IntervalsThere were no cardiac dysrhythmias during the operation. Arterial blood pressure changed from 145/85 mm Hg to 100/65 mm Hg, and heart rate changed from 73 bpm to 132 bpm. Replacement therapy with IV hydrocortisone 0.5 mg [center dot] kg (-1) [center dot] 4 h-1 was administered. The operation lasted 140 min. A bolus of 8 mL of 0.1% bupivacaine was given through the epidural catheter 30 min before the end of surgery. No neuromuscular blockade was administered. The trachea was extubated in the operating room, and the patient-who was conscious, quiet, breathing spontaneously, and free of pain-was taken to the postoperative care unit. During the postoperative period, hypertension was controlled with nitroprusside 1.2 micro g [center dot] kg-1 [center dot] min-1 and doxazosina 0.1 mg [center dot] kg-1 [center dot] 8 h-1. Treatment with fludocortisone 0.05 mg/d was begun. During the first 72 h postoperatively, a bolus of 8 mL of 0.05% bupivacaine with morphine 30 micro g [center dot] kg-1 [center dot] 12 h-1 was administered through the epidural catheter, and the patient remained sedated and free of pain during this period. Forty-eight hours after surgery, hemodialysis was initiated. Two months after surgery, he had normal blood pressure without antihypertensive drugs, was dialyzed three times a week, and was treated with fludocortisone 0.05 mg/d in the reduction phase to 0.025 mg/d. Discussion Patients on regular hemodialysis often have renal hypertension. In preoperative management, it is very important to control hypertension and to correct the circulating blood volume. It is very difficult to determine the adequate degree of correction with respect to circulating blood volume. Hemodynamic alterations are frequent and may have severe consequences in patients with chronic renal failure who also have a poor cardiovascular reserve, usually associated with anemia, azotemia, and electrolyte imbalance [4]. A precipitous decrease in blood pressure may occur after removal of the tumor because of a decrease in cardiac output [7]. Volume reposition should be carried out according to results of blood pressure, central venous pressure, and heart rate to avoid compensatory overload. In the case of cardiovascular failure, treatment with adrenergic inotropic agents, such as dobutamine or dopamine, or drugs with selective inotropic properties, such as amrinone, is indicated to achieve the desired hemodynamic action. Despite the progress made in perioperative management, the resection of pheochromocytoma is still a high-risk operation. The anesthetic management of the surgical resection of a pheochromocytoma requires preoperative preparation, good communication with the surgical team, and anesthetist familiarity with the pathophysiology of the pheochromocytoma patient [4,10]. Any anesthetic, surgical, or pharmacological stimulus to catecholamine release must be avoided [3,4]. Very large doses of general anesthetics can attenuate these responses, but unfortunately, effective ablation of the stress response to major surgery requires doses of opioids far larger than those required to provide analgesia, and necessitates postoperative ventilation [11]. Sympathetic blockade up to T4 by epidural anesthesia has been shown to inhibit sympathetic innervation in the adrenal medulla [12,13], although the release of catecholamines in response to tumor handling is not prevented [4]. In our case, although there were no serious dysrhythmias, the heart rate and blood pressure during handling of the tumor were higher that it had been at baseline. The increased epinephrine and norepinephrine levels at this time suggests that the administration of a beta-blocker with short half-life, such as esmolol, and a vasodilator, such as nitroprusside or adenosine, or an alpha-blocker, such as phentolamine, might have been useful during manipulation of the tumor if hemodynamic alterations would have been significant and persistent. Epidural administration of local anesthetics are increasingly used in modern pediatric anesthesia to relieve pain intra- and postoperatively [4]. In the presence of normal blood volume, epidural anesthesia is accompanied by excellent hemodynamic stability [14]. Epidural morphine produces long-lasting analgesia, and although it is not an ideal drug for epidural administration because of the well recognized risk of delayed respiratory depression, if the dose is minimized, good quality analgesia is obtained with a lower incidence of respiratory depression [15]. In conclusion, the risk in the surgical resection of pheochromocytoma in children with terminal renal failure is minimized when a partial blockade has been established, electrolyte and blood volume have been corrected, monitoring to assess perioperative hemodynamic parameters is available, response to surgical stress is blocked or inhibited, and therapeutic protocols to treat possible hemodynamic alterations can be used. Although a consensus on the most suitable anesthetic technique has not been reached, we believe that the association of general anesthesia and thoracic extradural analgesia does not completely protect against the major problem of catecholamine release derived from tumor handling. However, when extubation at the end of the surgical procedure is anticipated, epidural postoperative analgesia could be the technique of choice for patients in whom management of postoperative analgesia by other routes may be more complex and difficult.