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From the Department of Anesthesiology, American University of Beirut-Medical Center, Beirut, Lebanon.
Address correspondence to: Dr. Anis Baraka, Professor and Chairman, American University of Beirut, Department of Anesthesiology, P.O. Box 11 0236, Beirut, Lebanon. Phone: 961 1 350000; Fax: 961 1 744464; E-mail: abaraka{at}aub.edu.lb
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Clinical findings: A 28-yr-old man who had undergone at age 12 a laparotomy for excision of an extraadrenal pheochromocytoma complained of paroxysmal headache, occasional sweating and palpitations. The arterial blood pressure (BP) was 200/100 mmHg. A 24-hr-urine collection showed catecholamines 5076 µg•24 hr-1 (normal < 25 µg•24 hr-1). Computed tomography of the abdomen revealed two retroperitoneal masses, one adjacent to the lower pole of the right kidney and a second larger mass located at the aortic bifurcation in the region of the organ of Zuckerkandl. The patient was scheduled for excision of multiple extraadrenal pheochromocytomas. He was prepared preoperatively for two weeks with prazosin 1 mg po q six hours and propranolol 10 mg tid. Manipulation of the infrarenal tumour was uneventful but manipulation of the Zuckerkandl tumour resulted in severe hypertensive episodes with BP ranging from 200/100 to 320/120 mmHg. Surgery was interrupted temporarily; the hypertensive crisis was controlled by the infusion of sodium nitroprusside and by iv phentolamine and esmolol.
Conclusion: In a patient undergoing resection of recurrent multicentric extraadrenal pheochromoctyomas, severe hypertensive episodes occurred during manipulation of one tumour but not during manipulation of the other. This may be attributed to inadequate preparation of the patient, difficult surgical dissection of the large Zuckerkandl pheochromocytoma, and/or secondary to an excessive and different pattern of release of catecholamines during manipulation of the Zuckerkandl tumour.
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The present report describes the perioperative anesthetic management and the serious hemodynamic fluctuations observed in a patient undergoing resection of recurrent retroperitoneal multicentric extraadrenal pheochromocytomas. The report also shows that variable hemodynamic responses may occur during surgical excision of multicentric pheochromocytomas, suggesting that these tumours may be quite different functionally even if they grow concomitantly in the same patient.
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The patient was prepared preoperatively for two weeks with prazosin 1 mg po q six hours (because of the unavailability of phenoxybenzamine in our hospital), and propranolol 10 mg tid. The BP stabilized at 120/90 mmHg supine and standing, with a regular heart rate (HR) of 68 beats•min-1. Electrocardiogram (ECG) showed normal sinus rhythm, with non-specific T wave changes in V1–V4 leads. Hematocrit (Hct) was 43% and blood sugar level was normal.
The patient was premedicated with diazepam 5 mg po. In the operating room, he was monitored continuously with a 5-lead ECG, pulse oximetry, capnography, intraarterial BP measurement, and pulmonary artery (PA) catheter. Prior to induction of anesthesia, BP was 145/90 mmHg and HR was 75 beats•min-1. General anesthesia was induced with iv lidocaine 1 mg•kg-1, propofol 3 mg•kg-1, fentanyl 2 µg•kg-1 and rocuronium 1 mg•kg-1. The patient was ventilated with 4% sevoflurane in 100% O2 prior to proceeding with laryngoscopy and tracheal intubation. Anesthesia was then maintained with 4–8% sevoflurane in 100% O2, and by incremental doses of fentanyl and rocuronium, as needed. Blood volume was expanded throughout the procedure by lactated Ringer’s solution and by Haemaccel® (Hoechst Marion Roussel, Frankfurt am Main, Germany) to maintain adequate central venous pressure and urine output.
Through a midline abdominal incision, the right kidney was exposed and a mass was visualized, medial to the lower pole of the kidney, inferior to the renal hilum and lateral to the vena cava. Dissection of the tumour from its surrounding structures was performed easily. Minimal hemodynamic changes occurred and responded to increasing concentrations of sevoflurane.
The tumour of Zuckerkandl was overlying and adherent to the bifurcation of the aorta. Surgical dissection of the tumour was difficult and associated with excessive blood loss. Manipulation of the tumour resulted in severe hypertensive episodes with BP ranging from 200/100 to 320/120 mmHg. Systemic hypertension was associated with elevation of PA pressure. Surgery was interrupted temporarily; sodium nitroprusside was infused in increasing doses up to 2 µg•kg-1•min-1, and two doses of iv phentolamine 5 mg were administered. Hypertension also necessitated the bolus administration of esmolol 0.5 mg•kg-1 iv to be followed by an iv infusion of 30 mg esmolol over 20 min.
Ligation of the efferent vein of the tumour immediately resulted in a fall in BP which reached 70/50 mmHg. This hypotension was treated by decreasing the concentration of sevoflurane, as well as by rapid iv infusion of lactated Ringer’s solution and 2 U of blood. In addition, a norepinephrine infusion (0.05 µg•kg-1•min-1) was required for 20 min. Thereafter, BP returned to normal without further treatment. The patient was kept sedated, intubated and transferred to the intensive care unit with a BP of 130/75 mmHg and a HR of 85 beats•min-1. His postoperative course was smooth and uneventful.
The hemodynamic variables immediately after induction, during manipulation and after resection of the tumours are shown in the Table
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It is rare for functional and nonfunctional pheochromocytoma/paragangliomas to coexist.2 When multicentric, it is more common to find tumours at multiple extraadrenal sites rather than adrenal and extraadrenal sites.2 Our patient had recurrent multicentric extraadrenal pheochromocytomas; one was found at the lower pole of the right kidney and the second overlying the bifurcation of the aorta, in the region of the organ of Zuckerkandl.
Most extraadrenal pheochromocytomas secrete norepinephrine exclusively.1 If both norepinephrine and epinephrine are secreted, then the pheochromocytoma is very likely to be adrenal or Zuckerkandl in origin.9 The main findings of the present report relate to the different hemodynamic responses noted during surgical manipulations of the two tumours. Manipulation of the upper tumour resulted in a moderate increase of BP associated with an increase of systemic vascular resistance (SVR) and a decrease of cardiac output (CO), suggesting a norepinephrine-secreting tumour.10 In contrast, manipulation of the Zuckerkandl tumour caused a dramatic increase of BP associated with a significant increase of CO and a moderate increase in SVR, suggesting the release of both epinephrine and norepinephrine.10
In a retrospective study, Kinney et al. found that preoperative factors univariately associated with adverse perioperative events included larger tumour size, prolonged duration of anesthesia and increased levels of preoperative urinary catecholamines and catecholamine metabolites.11 In our patient, BP fluctuations were most severe during manipulation of the tumour of the organ of Zuckerkandl, which may be attributed to excessive catecholamine release secondary to its larger size and its more difficult resection and extensive manipulation.
A reduction in perioperative mortality associated with excision of pheochromocytoma from 45% down to between 0 and 3% followed the introduction of 
-adrenergic antagonists for preoperative preparation of patients.12 Preparation will not only control hypertension, but can also expand the intravascular fluid compartment. Perioperative BP fluctuation, myocardial infarction, congestive heart failure, cardiac dysrythmia, and cerebral hemorrhage all appear to be reduced in frequency when the patient has been prepared with -adrenergic blockers.12
Despite preoperative pharmacologic preparation of our patient with -adrenergic blockers, serious intraoperative hemodynamic liability occurred. Roizen et al. have suggested the following criteria as indicative of the adequacy of preoperative preparation of pheochromocytoma patients: 1) no BP reading > 165/90 mmHg for 48 hr, 2) presence of orthostatic hypotension, 3) absence of segment-T wave changes, 4) absence of other signs of catecholamine excess.13 In our patient, hypertension was well controlled and the ECG was free of PVC. However, no orthostatic variation in BP was noted. In addition, the ECG showed non-specific T wave changes, and the Hct was 43%. This might suggest that the preoperative preparation of our patient was suboptimal.
Whereas norepinephrine released from sympathetic nerve fibres activates the junctional 1-receptor, it is thought that postsynaptic 2-receptors are extrajunctional, and are preferentially stimulated by circulating catecholamine.14 Despite its selective 1-receptor antagonist effect, prazosin has little or no 2-receptor blocking effect at concentrations achieved clinically.14 Nicholson and colleagues found that pheochromocytoma patients pretreated with prazosin exhibited marked hypertensive responses to tumour handling requiring phentolamine.15 In another study by Russel and colleagues, phenoxybenzamine pretreatment provided superior intraoperative stability compared to prazosin.16
In contrast to phenoxybenzamine, prazosin has a short elimination half-life (two to three hours); therefore prazosin blood concentration may decrease to ineffective levels at the time of surgery.17 In our patient, it seems likely that large catecholamine surges of both norepinephrine and epinephrine occurred during manipulation of the tumour arising from the organ of Zuckerkandl. These were enough to overcome the competitive -1 blockade induced by prazosin on the blood vessels with a consequent increase of SVR, and to produce a significant increase of CO by their ß-adrenergic action on the heart.
In conclusion, the present report shows, in a patient undergoing resection of recurrent multicentric extraadrenal pheochromocytomas, the occurrence of variable hemodynamic responses during surgery. Manipulations of one tumour was associated with minor hemodynamic fluctuations suggesting the release of norepinephrine, while manipulation of the tumour arising from the organ of Zuckerkandl was associated with major hemodynamic fluctuations suggesting the release of both epinephrine and norepinephrine. The hemodynamic differences during resection of the two tumours suggest that multicentric pheochromocytomas may be functionally quite different even if they grow concomitantly in the same patient.
Revision received May 27, 2002. Accepted for publication February 26, 2002.
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2 Avila NA, Doppman JL, Walther MM, Keiser HR. Synchronous multicentric extraadrenal phaeochromocytoma: implications for management. Clin Radiol 1999; 54: 772–80.[Medline]
3 Stoelting RK, Dierdorf SF. Anesthesia and Co-Exisiting Disease, 3rd ed. New York: Churchill Livingstone, 1993: 363–7.
4 Whalen RK, Althausen AF, Daniels GH. Extra-adrenal pheochromocytoma. J Urol 1992; 147: 1–10.[Medline]
5 Goldstein RE, O’Neill JA, Holcomb GW III, et al. Clinical experience over 48 years with pheochromocytoma. Ann Surg 1999; 229: 755–66.[Medline]
6 Goldfarb DA, Novick AC, Bravo EL, Straffon RA, Montie JE, Kay R. Experience with extra-adrenal pheochromoctyoma. J Urol 1989; 142: 931–6.[Medline]
7 Melicow MM. One hundred cases of pheochromocytoma (107 tumors) at the Columbia-Presbyterian Medical Center, 1926–1976: a clinicopathological analysis. Cancer 1977; 40: 1987–2004.[Medline]
8 Kaufman BH, Telander RL, van Heerden JA, Zimmerman D, Sheps SG, Dawson B. Pheochromocytoma in the pediatric age group: current status. J Pediatr Surg 1983; 18: 879–84.[Medline]
9 Page LB, Raker JW, Berberich FR. Pheochromocytoma with predominant epinephrine secretion. Am J Med 1969; 47: 648–52.[Medline]
10 Baraka A, Haroun S, Baroody MA, et al. The hemodynamic effects of intravenous norepinephrine versus epinephrine and phenylephrine in patients with ischemic heart disease. Middle East J Anesthesiol 1991; 11: 53–62.[Medline]
11 Kinney MAO, Warner ME, vanHeerden JA, et al. Perianesthetic risks and outcomes of pheochromocytoma and paraganglioma resection. Anesth Analg 2000; 91: 1118–23.
12 Barash PG, Cullen BF, Stoelting RK. Clinical Anesthesia, 3rd ed. Philadelphia: Lipincott-Raven Publishers, 1997: 1050–3.
13 Roizen MF, Fleisher LA. Essence of Anesthesia Practice, 2nd ed. W.B. Saunders Company, 2002: 258.
14 Hardman JG, Limbird LE. Goodman and Gilman’s The Pharmacological Basis of Therapeutics, 9th ed. New York: McGraw-Hill publishers, 1996: 227–9.
15 Nicholson JP Jr, Vaughn ED Jr, Pickering TG, et al. Pheochromocytoma and prazosin. Ann Int Med 1983; 99: 477–9.
16 Russell WJ, Metcalfe IR, Tonkin AL, Frewin DB. The preoperative management of phaeochromocytoma. Anaesth Intensive Care 1998; 26: 196–200.[Medline]
17 Prys-Roberts C. Phaeochromocytoma–recent progress in its management. Br J Anaesth 2000; 85: 44–57.
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